TBI-ROC Part Nine: Diagnosing TBI and Psychiatric Disorders

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Elias, Eileen; Weider, Katie; Mustafa, Ruman

2011-01-01

This article is the ninth of a multi-part series on traumatic brain injury (TBI). It focuses on the process of diagnosing TBI and psychiatric disorders. Diagnosing traumatic brain injury can be challenging. It can be difficult differentiating TBI and psychiatric symptoms, as both have similar symptoms (e.g., memory problems, emotional outbursts,…

Hyperfractionation as an altered fractionation regimen in primary radiotherapy for squamous cell carcinoma of the larynx

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Krstevska, V.; Smichkoska, S.

2006-01-01

The aim of the study was to investigate the efficacy of hyperfractionation as altered fractionation treatment schedule in comparison with conventional fractionation in primary definitive radiotherapy for laryngeal squamous cell carcinoma. From March 1999 to December 2000, a group of 28 patients with previously untreated squamous cell carcinoma of the larynx were irradiated with conventional fractionation to to total doses of 66 to 70 Gy in 33 to 35 fraction/6.5 to 7 weeks, 2 Gy/fraction/day, 5 days/week. From January 2001 to June 2004, the other 27 patients with the same diagnosis, were treated prospectively with hyperfractionation receiving radiotherapy delivered at 1.2 Gy/fraction, twice daily, 5 days/week to 74.4 to 79.2 Gy/62 to fractions/6.2 to 7 weeks. Complete response rates after two mounts of radiotherapy completion were 78.6% (22 of 28) and 66.7% (18 of 27) in the conventional fractionation and hyperfractionation group, respectively (Fisher exact test; P=0.246). The two year loco-regional control rates were 61 .0%±18.1 (95% CI) in the conventional fractionation group and 45.0%±18.8 (95% CI) in the hyperfractionation group (long-rank test; P=0.075). Overall survival rate at two years was 71.0%±16.8 (95% CI) for the conventional group and 43.0%±18.7 (95% CI) for the hyperfractionation group (long- rank test; P=0.071). The absence of statistically significant differences either in loco-regional control or overall survival observed between the two treatment modalities suggested that hyperfractionation regimen was not more efficacious than conventionally fractionated radiotherapy for previously untreated carcinoma of the larynx.

Serial histopathological changes in irradiated guinea pig lung receiving conventional fractionated and hyperfractionated irradiation

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Itoh, Satoshi; Inomata, Taisuke; Ogawa, Yasuhiro; Yoshida, Shoji; Sonobe, Hiroshi; Ohtsuki, Yuji

1999-01-01

The purpose of this study is to determine serial histopathological differences in guinea pig lungs receiving the same total dose as clinically used between conventional fractionated and hyperfractionated irradiation. The guinea pigs received 80 Gy in 40 daily fractions of 2 Gy each (conventional fractionation), 80 Gy in 80 fractions of 1 Gy each twice a day (hyperfractionation), 81 Gy in 27 daily fractions of 3 Gy each (conventional fractionation), or 81 Gy in 54 fractions of 1.5 Gy each twice a day (hyperfractionation). We evaluated the histopathological changes of irradiated guinea pig lungs at 1, 2, 3, 6, 9, and 12 months after irradiation. The guinea pig lungs that received 81 Gy in 27 daily fractions showed histopathological changes of inflammation including formation of lymph follicles after 6 months. The lungs which received 81 Gy in 54 fractions showed similar but slightly less pronounced changes than those that received 81 Gy in 27 daily fractions. The guinea pig lungs of other groups showed no histopathological changes during the observation period. In hyperfractionated irradiation the damage to the guinea pig lung is quantitatively less than that occurring as a result of conventional fractionated irradiation of the same total dose. (author)

Serial histopathological changes in irradiated guinea pig lung receiving conventional fractionated and hyperfractionated irradiation

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Itoh, Satoshi; Inomata, Taisuke; Ogawa, Yasuhiro; Yoshida, Shoji; Sonobe, Hiroshi; Ohtsuki, Yuji [Kochi Medical School, Nankoku (Japan)

1999-05-01

The purpose of this study is to determine serial histopathological differences in guinea pig lungs receiving the same total dose as clinically used between conventional fractionated and hyperfractionated irradiation. The guinea pigs received 80 Gy in 40 daily fractions of 2 Gy each (conventional fractionation), 80 Gy in 80 fractions of 1 Gy each twice a day (hyperfractionation), 81 Gy in 27 daily fractions of 3 Gy each (conventional fractionation), or 81 Gy in 54 fractions of 1.5 Gy each twice a day (hyperfractionation). We evaluated the histopathological changes of irradiated guinea pig lungs at 1, 2, 3, 6, 9, and 12 months after irradiation. The guinea pig lungs that received 81 Gy in 27 daily fractions showed histopathological changes of inflammation including formation of lymph follicles after 6 months. The lungs which received 81 Gy in 54 fractions showed similar but slightly less pronounced changes than those that received 81 Gy in 27 daily fractions. The guinea pig lungs of other groups showed no histopathological changes during the observation period. In hyperfractionated irradiation the damage to the guinea pig lung is quantitatively less than that occurring as a result of conventional fractionated irradiation of the same total dose. (author)

Acute central nervous system (CNS) toxicity of total body irradiation (TBI) measured using neuropsychological testing of attention functions

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Wenz, Frederik; Steinvorth, Sarah; Lohr, Frank; Hacke, Werner; Wannenmacher, Michael

1999-01-01

Purpose: The purpose of this study was to investigate acute normal tissue damage of low irradiation doses to the healthy, adult central nervous system (CNS) using neuropsychological testing of attention functions. Methods and Materials: Neuropsychological testing (IQ, attention [modified Trail-Making Test A, Digit Symbol Test, D2 Test, Wiener Determination Machine]) was used to examine 40 patients (43 ± 10 years) before and immediately after the first fraction (1.2 Gy) of hyperfractionated total body irradiation (TBI) at the University of Heidelberg. The patients received antiemetic premedication. Test results are given as mean percentiles ± standard deviation, with 50 ± 34 being normal. Thirty-eight control patients (53 ± 15 years) were studied to quantify the influence of hospitalization, stress, and repeated testing. Results: The patients showed normal baseline test results (IQ = 101 ± 14, attention = 54 ± 28) and no decrease in test results after 1.2 Gy TBI. Attention functions improved (66 ± 25) corresponding to a practice effect of repeated testing that was seen in the control group, although alternate versions of the tests were used (IQ = 104 ± 10, attention before = 42 ± 29, attention after = 52 ± 31). Conclusion: Our data show no deterioration of neuropsychologic test results acutely after 1.2 Gy whole body exposure in adult patients without CNS disease receiving antiemetic medication

Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer

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Jeremic, Branislav; Shibamoto, Yuta; Acimovic, Ljubisa; Milisavljevic, Slobodan

1997-01-01

Purpose: Among patients with Stage I nonsmall cell lung cancer (NSCLC), those treated with conventional radiotherapy show poorer prognosis than those treated by surgery. To improve the prognosis of such patients, we have used hyperfractionated radiation therapy. Methods and Materials: Between 1988 and 1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 29 had medical problems and 20 refused surgery. The median age and Karnofsky Performance Status was 63 years and 90, respectively. No patient received chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not given. Results: The median survival time was 33 months, and the 5-year survival rate was 30%. The rate at 5 years for freedom from each of relapse, local recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%, 55%, 89%, and 75%, respectively. Univariate analysis revealed that higher Karnofsky Performance Status score, absence of weight loss before treatment, and T1 stage were associated with better survival, although the T stage became insignificant on multivariate analysis. There were two Grade 3 acute toxicities and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity. Conclusion: The results of this study compare favorably with those of most previous studies employing conventional fractionation. Further studies on hyperfractionation seem to be warranted for Stage I NSCLC

Assessment of long-term quality of life of esophageal carcinoma patients treated with continuous accelerated hyperfractionated and late-course accelerated hyperfractionated radiotherapy

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Wang Yang; He Shaoqin; Shi Xuehui; Jiang Kaida; Yao Weiqiang; Wang Ying

2002-01-01

Objective: To compare the long-term quality of life in esophageal carcinoma patients treated with continuous accelerated hyperfractionated (CAHF) and late-course accelerated hyperfractionated (LCAF) radiotherapy. Methods: Subjective and Objective Management Analysis (SOMA) scale, Symptom Checklist 90 (SCL-90) and Life Satisfaction Index A (LSIA) questionnaire were mailed to the long survivors in both CAHF and LCAF groups to assess the long-term quality of life including symptoms, psychological status and life satisfaction. Results: There was no significant difference between the two groups in the score of quality of life such as late radiation reaction, SCL-90 and LSI-A. Conclusions: 1. It is reasonable to assess the quality of life with these scales for esophageal carcinoma patients treated with radiotherapy, 2. Preliminary results demonstrate that there is no significant difference in long-term quality of life between the CAHF and LCAF radiotherapy groups, 3. Methods of evaluating the long-term quality of life for esophageal carcinoma patients treated with radiotherapy needs further investigation, preferably involving more patients and setting on control arm

Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies

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Girinsky, T.; Benhamou, E.; Bourhis, J.H.; Dhermain, F.; Guillot-Valls, D.; Ganansia, V.; Luboinski, M.; Perez, A.; Cosset, J.M.; Socie, G.; Baume, D.; Bouaouina, N.; Briot, E.; Baudre, A.; Bridier, A.; Pico, J.L.

2001-01-01

The efficiency of the two irradiation modes are similar, but the hyperfractionated irradiation seems superior in term of global and specific survival. The incidence rates of pneumopathies are not different between the two groups but the incidence rate of the liver vein-occlusive illness is superior in the group treated by non fractionated whole body irradiation. The cost of the hyperfractionated whole body irradiation is superior to this one of the non fractionated whole body irradiation around a thousand dollars. (N.C.)

The prognostic values of CYP2B6 genetic polymorphisms and metastatic sites for advanced breast cancer patients treated with docetaxel and thiotepa.

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Song, Qingkun; Zhou, Xinna; Yu, Jing; Dong, Ningning; Wang, Xiaoli; Yang, Huabing; Ren, Jun; Lyerly, H Kim

2015-11-25

This study investigated interactive effects of CYP2B6 genotypes and liver metastasis on the prognosis of metastatic breast cancer patients who received combined chemotherapy of docetaxel and thiotepa. Totally 153 patients were retrospectively genotyped rs8192719 (c.1294 + 53C > T) and rs2279343 (c.785A > G). Kaplan-Meier method and Cox Proportional Hazard Regression model were used to estimate the survival. Patients with liver metastasis had worsen prognosis, conferring a 2.26-fold high risk of progression and 1.93-fold high risk of death (p T) and AG genotype of rs2279343 (c.785A > G) prolonged survival (p G) was associated with a 47% reduced risk of death and a 6-month-longer overall survival (p T) were 0.45 for progression and 0.40 for death; and the corresponding survival was improved by 6 months and 16 months, respectively (p < 0.05). Genotypes of CYP2B6 had an interaction with clinical efficacy of docetaxel and thiotepa on metastatic breast cancer patients; and metastatic sites also affected clinical responses. Further therapies should take into account of chemotherapy regimen, genotypes of metabolizing enzymes and metastatic sites for the particular subpopulation.

Second Study of Hyper-Fractionated Radiotherapy

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R. Jacob

1999-01-01

Full Text Available Purpose and Method. Hyper-fractionated radiotherapy for treatment of soft tissue sarcomas is designed to deliver a higher total dose of radiation without an increase in late normal tissue damage. In a previous study at the Royal Marsden Hospital, a total dose of 75 Gy using twice daily 1.25 Gy fractions resulted in a higher incidence of late damage than conventional radiotherapy using 2 Gy daily fractions treating to a total of 60 Gy. The current trial therefore used a lower dose per fraction of 1.2 Gy and lower total dose of 72 Gy, with 60 fractions given over a period of 6 weeks.

Traumatic Brain Injury (TBI) in Kids

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... Information Share Facebook Twitter Pinterest Email Print Traumatic Brain Injury (TBI): Condition Information What is TBI? TBI ... external force that affects the functioning of the brain. It can be caused by a bump or ...

Hyperfractionated abdominal radiotherapy in children. Efficacy and tolerance in 13 cases

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Lagrange, J.L.; Roullet, B.; Cosset, J.M.; Sarrazin, D.; Lemerle, J.

1984-01-01

The experience at IGR has shown that hyperfractionation, especially abdominal has been well tolerated in adult patients. This finding led to employ this technic in the pediatric population who had failed standard treatment. An experience with hyperfractionated radiotherapy of the abdomen and liver in children, is reported. The children were treated 4 days per week, receiving 5 fractions daily of 0.7 Gy, with a 2 hours interval between each treatment. A total dose of 28 Gy was delivered in 40 fractions over 12 days. A second course of irradiation was delivered in 5 patients, 3 with abdominal treatment and 2 with liver irradiation. The vital organs were shielded with blocks at normal dose tolerance levels. The results are encouraging since an immediate efficacy was observed in 8 of 13 patients. Long term survivals were observed in 4 patients with nephroblastomas and 1 patient with a hepatoblastoma. On the other hand acute gastrointestinal tolerance seemed less good in the children than previously observed in the adults. Five radiation hepatitis appeared, immediately after the irradiation, whom four children irradiated to the entire abdomen [fr

Hyperfractionated conformal radiotherapy in locally advanced prostate cancer: results of a dose escalation study

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Forman, Jeffrey D.; Duclos, Marie; Shamsa, Falah; Porter, Arthur T.; Orton, Colin

1996-01-01

Purpose: This study was initiated to assess the incidence of chronic complications and histologic and biochemical control following hyperfractionated conformal radiotherapy in patients with locally advanced prostate cancer. Methods and Materials: Between October 1991 and October 1994, 49 patients with locally advanced prostate cancer were entered on the first two dose levels of a prospective dose-escalation study using hyperfractionated three dimensional conformal radiotherapy. The first 25 patients received a minimum tumor dose of 78 Gy to the prostate and seminal vesicles in 6 weeks at 1.3 Gy, b.i.d. No increase in chronic toxicity compared with conventional radiotherapy was noted; therefore, an additional 24 patients were treated to a minimum tumor dose of 82.8 Gy to the prostate and seminal vesicles in 7 weeks at 1.15 Gy, b.i.d. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. Efficacy was assessed through scheduled postradiation prostate specific antigen values and ultrasound-guided biopsies. The median follow-up for the entire group was 20 months. Results: The hyperfractionated external radiation was well tolerated with minimal acute morbidity. At 30 months, the actuarial probability of Grade 2 gastrointestinal toxicity was 17%. At 30 months, the actuarial probability of Grade 2 genitourinary toxicity was 16%. There was no statistically significant difference between the two dose levels. No Grade 3 or 4 gastrointestinal or genitourinary toxicity was noted. At 12 months, 84% of patients had a prostate specific antigen ≤ 4; and 53%; ≤ 1 ng/ml. At 12 months, 71% of patients had post radiation biopsies that were either negative (55%) or showed a marked therapeutic effect (16%). Conclusion: The use of hyperfractionated conformal radiotherapy facilitated dose escalation with no increase in chronic toxicity compared to standard doses. The initial tumor response based on prostate specific antigen measurements and

Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

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Mikell, John L., E-mail: jmikell@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waller, Edmund K. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hall, William A. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Langston, Amelia A. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khoury, H. Jean [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

2014-06-01

Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

Preoperative concurrent CBDCA chemotherapy and accelerated hyperfractionated radiotherapy for squamous cell carcinoma of the maxillary region

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Omura, Ken; Harada, Hiroyuki; Suzuki, Haruhiko; Takeuchi, Yosuke; Hatano, Kazuo; Togawa, Takashi

2001-01-01

Between 1994 and 2000, 28 patients with T3/T4 squamus cell carcinoma of the maxillary region (maxillary sinus, 22; maxillary gingiva, 4; maxillary bone, 1; buccal mucosa, 1) had accelerated hyperfractionated radiotherapy combined with simultaneous CBDCA chemotherapy preoperatively, at Chiba Cancer Center Hospital. The protocol consisted of combined therapy with accelerated hyperfractionated irradiation of 1.6 Gy, twice a day, to a total dose of 32.0-51.2 Gy and concurrent intra-arterial or intravenous infusion of CBDCA 20-30 mg/body/day for a cumulative total dose of 270-480 mg. After completion of the preoperative combined therapy, the clinical CR rate was 17.9%, and the good PR·CR rate was 32.1%. According to the initial findings and response to the combined therapy, all patients had maxillectomy (subtotal, 3; total, 16; extended, 9) 4 weeks after completion of the preoperative combined therapy. Postoperatively, the complete pathologic response (Ohboshi and Shimozato's classification, grade III and IV) rate was 28.6%. And the actuarial local control rate was 85.7%, with a mean follow-up of 46.2 months. Based on these results, we believe this preoperative therapy with CBDCA chemotherapy and accelerated hyperfractionated radiation is a significant choice as treatment for squamous cell cancer of the maxillary region. (author)

Traumatic Brain Injury (TBI) Data and Statistics

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... TBI Online Concussion Training Press Room Guide to Writing about TBI in News and Social Media Living with TBI HEADS UP to Brain Injury Awareness Get Email Updates To receive email updates about this topic, ...

Hyperfractionated external radiation therapy in stage IIIB carcinoma of uterine cervix: a prospective pilot study

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Faria, Sergio L.; Ferrigno, Robson

1997-01-01

Purpose: Brazil has one of the highest incidence of carcinoma of the cervix in the world. Half of the patients have advanced stages at the diagnosis. Due to this large number of patients we decided to conduct a prospective pilot study to investigate the tolerance to and survival rate with hyperfractionated external radiotherapy only in patients with Stage IIIB carcinoma of the uterine cervix. Methods and Materials: Between January 1991 and December 1993, 23 patients underwent hyperfractionated external beam radiotherapy without brachytherapy. All cases were biopsy proven squamous cell carcinoma of cervix clinically Staged as IIIB (FIGO). Hyperfractionation (HFX) was given with 1.2 Gy doses, twice daily at 6-h interval, 5 days/week, to the whole pelvis up to 72 Gy within 30 working days. Complications were evaluated by an adaptation of the RTOG Radiation Morbidity Scoring Table graded as 1 = none/mild; 2 = moderate, and 3 = severe. Results: Follow-up ranged from 27 to 50 months (median 40 months) on the 9 to 23 living patients at the time of the analysis in December 1995. There was no severe acute toxicity, but moderate acute reaction was high: 74%. The commonest site of complication was the intestine where severe late toxicity occurred in 2 of 23 (9%). Overall survival rate at 27 months was 48% and at 40 months was 43%. Discussion: There is little information in literature about HFX in carcinoma of the cervix. This is the third published study about it and the one that gave the highest total dose with external HFX of 60 x 1.2 Gy = 72 Gy. Theoretically, through the linear quadratic formula this schedule of HFX would be equivalent to 30 x 2 Gy = 60 Gy of standard fractionation, both treatments given in 30 working days. HFX schedules must be tested to establish their safety. Present results suggest being possible to further increase the total dose in the pelvis with hyperfractionated irradiation

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

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Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S

2013-10-01

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral

Early termination of prostate cancer hyperfractionated dose escalation study

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Forman, Jeffrey D; Porter, Arthur T; Kocheril, Paul; Grignon, David; Orton, Colin

1996-01-01

Purpose: This study was initiated to determine the maximum tolerable dose of hyperfractionated radiation in patients with locally advanced prostate cancer. Materials and Methods: Forty-nine patients with locally advanced prostate cancer (T3-T4 Nx, 0, 1 M0 and/or Gleason Score ≥ 8) were treated on the first two steps of a prospective dose-escalation study using hyperfractionated conformal radiotherapy. The first 25 patients received a minimum dose of 78Gy to the clinical tumor volume (CTV) including the prostate, seminal vesicle and a 5mm margin at 1.3Gy b.i.d. The second group (24 patients) received a minimum dose to the CTV of 82.8Gy at 1.15Gy b.i.d. Twenty eight patients received neo-adjuvant hormonal therapy in conjunction with their radiation (8 of 25 patients at 78Gy and 20 of 24 patients at 82.8Gy). Toxicity was scored according to the RTOG grading scale. Efficacy was evaluated by PSA levels and ultrasound guided biopsies. Median follow up was 36 and 18 months for the 78Gy and 82.8Gy dose levels, respectively. Results: No grade 3 or 4 gastrointestinal (GI) or genitourinary (GU) toxicity was noted. At 36 months, the actuarial probability of Grade 2 GI and GU toxicity were 16 and 20%, respectively. Twelve to 18 months following radiation, 41 patients (86%) underwent ultrasound guided biopsy. At 78Gy, 60% of 20 patients had a biopsy which was negative or showed a marked therapeutic effect. At 82.8Gy, these combined rates were 95% in the 21 patients who had biopsies. Nine patients (50%) who did not receive neo-adjuvant hormones had positive biopsies. No patient who received neo-adjuvant hormones plus 78Gy (5 patients) or 82.8Gy (18 patients) had a positive biopsy. Conclusion: Proceeding to the next dose level (87.4Gy) was justified by the lack of severe chronic toxicity. However, in view of the high rate of histologic sterilization when hyperfractionated irradiation was given in conjunction with neo-adjuvant hormonal therapy, it was felt to be unethical to

Validating Multidimensional Outcome Assessment Using the TBI Common Data Elements: An Analysis of the TRACK-TBI Pilot Sample.

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Nelson, Lindsay D; Ranson, Jana; Ferguson, Adam R; Giacino, Joseph; Okonkwo, David O; Valadka, Alex; Manley, Geoffrey; McCrea, Michael

2017-06-08

The Glasgow Outcome Scale-Extended (GOSE) is often the primary outcome measure in clinical trials for traumatic brain injury (TBI). Although the GOSE's capture of global function outcome has several strengths, concerns have been raised about its limited ability to identify mild disability and failure to capture the full scope of problems patients exhibit after TBI. This analysis examined the convergence of disability ratings across a multidimensional set of outcome domains in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot study. The study collected measures recommended by the TBI Common Data Elements (CDE) Workgroup. Patients presenting to 3 emergency departments with a TBI of any severity enrolled in TRACK-TBI prospectively after injury; outcome measures were collected at 3 and six months postinjury. Analyses examined frequency of impairment and overlap between impairment status across the CDE outcome domains of Global Level of Functioning (GOSE), Neuropsychological (cognitive) Impairment, Psychological Status, TBI Symptoms, and Quality of Life. GOSE score correlated in the expected direction with other outcomes (M Spearman's rho = .21 and .49 with neurocognitive and self-report outcomes, respectively). The subsample in the Upper Good Recovery (GOSE 8) category appeared quite healthy across most other outcomes, although 19.0% had impaired executive functioning (Trail Making Test Part B). A significant minority of participants in the Lower Good Recovery subgroup (GOSE 7) met criteria for impairment across numerous other outcome measures. The findings highlight the multidimensional nature of TBI recovery and the limitations of applying only a single outcome measure.

Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

International Nuclear Information System (INIS)

Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

1985-01-01

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

Preoperative concurrent CBDCA chemotherapy and accelerated hyperfractionated radiotherapy for squamous cell carcinoma of the maxillary region

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Omura, Ken; Harada, Hiroyuki [Tokyo Medical and Dental Univ. (Japan). Graduate School; Suzuki, Haruhiko; Takeuchi, Yosuke; Hatano, Kazuo; Togawa, Takashi

2001-11-01

Between 1994 and 2000, 28 patients with T3/T4 squamus cell carcinoma of the maxillary region (maxillary sinus, 22; maxillary gingiva, 4; maxillary bone, 1; buccal mucosa, 1) had accelerated hyperfractionated radiotherapy combined with simultaneous CBDCA chemotherapy preoperatively, at Chiba Cancer Center Hospital. The protocol consisted of combined therapy with accelerated hyperfractionated irradiation of 1.6 Gy, twice a day, to a total dose of 32.0-51.2 Gy and concurrent intra-arterial or intravenous infusion of CBDCA 20-30 mg/body/day for a cumulative total dose of 270-480 mg. After completion of the preoperative combined therapy, the clinical CR rate was 17.9%, and the good PR{center_dot}CR rate was 32.1%. According to the initial findings and response to the combined therapy, all patients had maxillectomy (subtotal, 3; total, 16; extended, 9) 4 weeks after completion of the preoperative combined therapy. Postoperatively, the complete pathologic response (Ohboshi and Shimozato's classification, grade III and IV) rate was 28.6%. And the actuarial local control rate was 85.7%, with a mean follow-up of 46.2 months. Based on these results, we believe this preoperative therapy with CBDCA chemotherapy and accelerated hyperfractionated radiation is a significant choice as treatment for squamous cell cancer of the maxillary region. (author)

Mild TBI Diagnosis and Management Strategies

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Department of Veterans Affairs — The Mild Traumatic Brain Injury (TBI) Diagnosis and Management Strategies will assist in the study of TBI issues, such as the Influence of Concussion on Persistent...

Hyperfractionation radiation therapy in advanced head and neck cancer

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Kim, Jin Hee; Ye, Ji Won

2003-01-01

The effects of hyperfractionation radiation therapy, such as the failure pattern and survival, on the treatment results in advanced stage head and neck cancer were studied. Between September 1990 and October 1998, 24 patients with advanced stage (III, IV) head and neck cancers, were treated using hyperfractionation radiation therapy in the Department at Radiation Oncology at the Keimyung University Dongsan Medical Center. The male to female ratio was 7 ; 1, and the age range from 38 to 71 years with the median of 56 years. With regard to the TNM stage, 11 patients were stage III and 13 were stage IV. The sites of primary cancer were the nasopharynx in six, the hypopharynx in 6, the larynx in five, the oropharynx in three, the maxillary sinus in three, and the oral cavity in one patient. The radiotherapy was delivered by 6 MV X-ray, with a fraction size of 1.2 Gy at two fractions a day, with at least 6 hours inter-fractional interval. The mean total radiation doses was 72 Gy, (ranging from 64.4 to 76.8 Gy). Fallow-up periods ranged between 3 and 136 months, with the median of 52 months. The overall survival rates at 3 and 5 years in all patients were 66.7% and 52.4%. The disease-free survival rates at 3 and 5 years (3YDFS, 5YDFS) in all patients Were 66.7% and 47.6%. The 3YDFS and 5YDFS in stage III patients were 81.8% and 63.6%, and those in stage IV patients were 53.8% and 32.3%. Ten patients were alive with no local nor distant failures at the time of analyses. Six patients (25%) died due to distant metastasis and 12.5% died due to local failure. Distant metastasis was the major cause of failure, but 2 patients died due to unknown failures and 3 of other diseases. The distant metastasis sites were the lung (3 patients), the bone (1 patient), and the liver (2 patients). One patient died of second esophageal cancer. There were no severe late complications, with the exception of 1 osteoradionecrosis of the mandible 58 months after treatment. Although this study was

TBI parameters and relapse of acute leukemia

International Nuclear Information System (INIS)

Sugawara, Tadashi; Inoue, Toshihiko; Mori, Tomoyuki.

1994-01-01

The purpose of this study, which involved 240 acute leukemia patients (ALL: 115, ANL: 125) who received an allogeneic bone marrow transplantation (BMT) with preconditioning by total body irradiation (TBI) and chemotherapy, was to examine retrospectively the TBI factors that may have influenced a leukemic relapse. The patients were divided into two groups: 124 patients who had received their BMT within a diagnosis-transplantation period of 9 months or less (DTP9 group), and 116 patients who had received their BMT within a diagnosis-transplantation period of 10 months or more (DTP10 group). It was concluded that: (1) the higher the TBI dose, the fewer the relapse rates in DTP9 group; (2) the longer the TBI period, the greater the increase in the relapse rate in DTP10 group. It was thus speculated that an effective TBI regimen for acute leukemia patients may vary depending on the length of time that has elapsed from the diagnosis of leukemia to the BMT. (author)

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

Science.gov (United States)

2015-10-01

injury (TBI) and posttraumatic stress disorder ( PTSD ) benefit fully from interventions for both conditions. PTSD and TBI occur together frequently in...veterans with comorbid traumatic brain injury and posttraumatic stress disorder : study protocol for a randomized controlled trial. CONCLUSION: In...moderate TBI (mTBI) and PTSD . Emotional symptoms are likely a main cause of the persistence of post -concussive symptoms while thinking problems

Classical spreading-fractionation, hyperfractionation, hypofractionation: let us attempt to be practical

International Nuclear Information System (INIS)

Cosset, J.M.; Baillet, F.

1986-01-01

The so-called classical spreading-fractionation (5 sessions of 2 Gy per week) was elaborated originally by the first generation of radiotherapists at the beginning of the century. It is a remarkable fact that even today the most up-to-date radiobiologists are in agreement that this regimen usually represents the best possible compromise between antitumoral efficacy and toxicity to healthy tissue. Hyperfractionation is still in the clinical trial stage with the aim of defining its precise place in clinical practice. At the present there is only one formal indication apart from within this framework: tumors with very rapid times for doubling in size, since hyperfractionation alone can deliver a high dose in a short period of time (accelerated treatment). Hypofractionation can be highly recommended for palliative treatment, because of its simplicity and efficacy. In contrast, when large size tumours (particularly digestive) are treated in patients with an elevated expected rate of recovery, this technique may provoke late complications and should, a priori, be avoided. For small size tumours however (ENT, breast) it would appear possible to elaborate hypofractio - nation protocols allowing local control to a similar degree to that obtained with the classical regimen, without significantly increasing late complications, on the condition that radiation parameters (dose, spread, fractionation) be cho - sen with the greatest care [fr

Neutrophils in traumatic brain injury (TBI): friend or foe?

Science.gov (United States)

Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

2018-05-17

Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: 10-Year Follow-Up of a Randomized Phase III Trial (SAKK 10/94)

International Nuclear Information System (INIS)

Ghadjar, Pirus; Simcock, Mathew; Studer, Gabriela; Allal, Abdelkarim S.; Ozsahin, Mahmut; Bernier, Jacques; Töpfer, Michael; Zimmermann, Frank; Betz, Michael; Glanzmann, Christoph; Aebersold, Daniel M.

2012-01-01

Purpose: To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer. Methods and Materials: From July 1994 to July 2000, a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to receive either hyperfractionated radiotherapy alone (median total dose, 74.4 Gy; 1.2 Gy twice daily; 5 days per week) or the same radiotherapy combined with two cycles of cisplatin (20 mg/m 2 for 5 consecutive days during weeks 1 and 5). The primary endpoint was the time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to Radiation Therapy Oncology Group criteria. Results: Median follow-up was 9.5 years (range, 0.1–15.4 years). Median time to any treatment failure was not significantly different between treatment arms (hazard ratio [HR], 1.2 [95% confidence interval {CI}, 0.9–1.7; p = 0.17]). Rates of locoregional failure-free survival (HR, 1.5 [95% CI, 1.1–2.1; p = 0.02]), distant metastasis-free survival (HR, 1.6 [95% CI, 1.1–2.5; p = 0.02]), and cancer-specific survival (HR, 1.6 [95% CI, 1.0–2.5; p = 0.03]) were significantly improved in the combined-treatment arm, with no difference in major late toxicity between treatment arms. However, overall survival was not significantly different (HR, 1.3 [95% CI, 0.9–1.8; p = 0.11]). Conclusions: After long-term follow-up, combined-treatment with cisplatin and hyperfractionated radiotherapy maintained improved rates of locoregional control, distant metastasis-free survival, and cancer-specific survival compared to that of hyperfractionated radiotherapy alone, with no difference in major late toxicity.

Altered Mitochondrial Dynamics and TBI Pathophysiology

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Tara Diane Fischer

2016-03-01

Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved

Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer

International Nuclear Information System (INIS)

Kim, Jong H.; Choi, Eun K.; Kim, Sung B.; Park, Seung I.; Kim, Dong K.; Song, Ho Y.; Jung, Hwoon Y.; Min, Young I.

2001-01-01

Purpose: To evaluate the local control rates, survival rates, and patterns of failure for esophageal cancer patients receiving preoperative concurrent chemotherapy and hyperfractionated radiotherapy followed by esophagectomy. Methods and Materials: From May 1993 through January 1997, 94 patients with resectable esophageal cancers received continuous hyperfractionated radiation (4,800 cGy/40 fx/4 weeks), with concurrent FP chemotherapy (5-FU 1 g/m 2 /day, days 2-6, 30-34, CDDP 60 mg/m 2 /day, days 1, 29) followed by esophagectomy 3-4 weeks later. If there was evidence of disease progression on preoperative re-evaluation work-up, or if the patient refused surgery, definitive chemoradiotherapy was delivered. Minimum follow-up time was 2 years. Results: All patients successfully completed preoperative treatment and were then followed until death. Fifty-three patients received surgical resection, and another 30 were treated with definitive chemoradiotherapy. Eleven patients did not receive further treatment. Among 91 patients who received clinical reevaluation, we observed 35 having clinical complete response (CR) (38.5%). Pathologic CR rate was 49% (26 patients). Overall survival rate was 59.8% at 2 years and 40.3% at 5 years. Median survival time was 32 months. In 83 patients who were treated with surgery or definitive chemoradiotherapy, the esophagectomy group showed significantly higher survival, disease-free survival, and local disease-free survival rates than those in the definitive chemoradiation group. Conclusion: Preoperative chemoradiotherapy in this trial showed improved clinical and pathologic tumor response and survival when compared to historical results. Patients who underwent esophagectomy following chemoradiation showed decreased local recurrence and improved survival and disease-free survival rates compared to the definitive chemoradiation group

Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using Diffuse and Mechanical TBI Animal Models

Science.gov (United States)

2016-05-01

Award Number: PT075653 (grant) W81XWH-08-2-0153 (contract) TITLE: Treatment of TBI with Hormonal and Pharmacological Support, Preclinical...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-08-2-0153 Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using...rats. Our in vivo tests also included MRI imaging, focusing on edema resolution and reduction of diffuse axonal damage (fractional anisotropy

Autobiographical memory and structural brain changes in chronic phase TBI.

Science.gov (United States)

Esopenko, Carrie; Levine, Brian

2017-04-01

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of metabolomics in TBI research

Science.gov (United States)

Wolahan, Stephanie M.; Hirt, Daniel; Braas, Daniel; Glenn, Thomas C.

2016-01-01

Synopsis Metabolomics is an important member of the omics community in that it defines which small molecules may be responsible for disease states. This article reviews the essential principles of metabolomics from specimen preparation, chemical analysis, and advanced statistical methods. Metabolomics in TBI has so far been underutilized. Future metabolomics based studies focused on the diagnoses, prognoses, and treatment effects, need to be conducted across all types of TBI. PMID:27637396

Effect of single dose, fractionated, and hyperfractionated trunk irradiation on weight gain, respiration frequency, and survival in rats

International Nuclear Information System (INIS)

Kimler, B.F.; Giri, P.G.S.; Giri, U.P.; Cox, G.G.

1986-01-01

It is concluded that, in this rat trunk irradiation model, fractionation of a single dose into two equal doses separated by 4-6 h produced a sparing effect of approx. 5Gy as measured by delay in weight gain; approx. 4Gy as measured by increased respiration frequency; and approx. 6Gy as measured by survival. Fractionation into daily doses or hyperfractionation into twice-daily doses permitted an approximate doubling of the dose required for the same suppression of weight gain. For the respiration rates and survival endpoints, fractionation or hyperfractionation produced an even greater sparing effect since there was no increase in the respiration frequency at twice the doses that would produce changes if delivered within a few hours; and since essentially no lethality was observed at twice the doses that would kill 70%-100% of animals if delivered in one day. (UK)

Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy

International Nuclear Information System (INIS)

Ricardi, Umberto; Corrias, Andrea; Einaudi, Silvia; Genitori, Lorenzo; Sandri, Alessandro; Cordero Di Montezemolo, Luca; Besenzon, Luigi; Madon, Enrico; Urgesi, Alessandro

2001-01-01

Purpose: Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of childhood medulloblastoma. Due to the strong radiobiologic rationale, hyperfractionation can reduce the delayed effects of radiation injury. Methods and Materials: The authors compared the incidence of thyroid dysfunction after conventionally fractionated radiotherapy (Group A, n=20 patients) vs. hyperfractionated radiotherapy (Group B, n=12 patients) in a group of pediatric patients with posterior fossa primitive neuroectodermal tumor (PNET). Results: The mean age at the time of tumor diagnosis was 7.4 years in Group A and 8.4 years in Group B. Thyroid function was evaluated yearly, with ultrasonographic examination every 2 years. The patients were followed after diagnosis for a mean of 10.8 years for Group A and 6.0 years for Group B. Approximately 80% of the Group A (16/20) and 33.3% of the Group B (4/12) patients developed primary hypothyroidism within a similar period after irradiation (4.2 vs. 3.5 years, respectively). Analysis by cumulative incidence function demonstrated a significant difference in the risk of developing thyroid dysfunction between these two groups of patients (p<0.05). Ultrasonography showed reduced thyroid volume in 7 Group A patients and structural changes in 21 patients (17 Group A, 4 Group B cases); a thyroid benign nodule was detected in 2 Group A patients. Conclusions: The current study findings suggest that the use of hyperfractionated craniospinal radiotherapy in the treatment of childhood medulloblastoma is associated with a lower risk of these patients' developing late thyroid dysfunction

Clinical evaluation of bone marrow transplantation using total body irradiation and induction chemotherapy. Treatment results during twelve years at our hospital and some problems on the therapy

International Nuclear Information System (INIS)

Kawamura, Toshiki; Koga, Sukehiko; Kikukawa, Kaoru; Okamoto, Masataka; Miyazaki, Hitoshi; Kojima, Hiroshi; Esaki, Kohji

2000-01-01

We performed sixty patients with hematological malignancies the total body irradiation prior to bone marrow transplantation (TBI-BMT) from 1988 to 2000. We delivered our each patient hyperfractionated TBI consisting of 2 fractions of 3 Gy per day for 2 consecutive days following induction chemotherapy. It proved that TBI-BMT was a valuable treatment method for hematological malignancies which have poor prognosis. About the cumulative survival rate, patients of first remission were better outcome than patients beyond second remission. However, the therapy remained some problems which were the prophylaxis of GVHD for HLA-matched unrelated recipients. And we have to consider a new maintenance procedure to prevent relapse from transplanted donor cell. (author)

Total body irradiation (TBI) of chronic lymphocytic leukemia (CLL)

Energy Technology Data Exchange (ETDEWEB)

Ruehl, U; Johnson, R E

1975-01-01

80 patients with previously untreated CLL have been admitted to the Radiation Oncology Branch of the NCI. Fourteen of these patients have remained classified as 'indolent' until the present time and have not received any treatment. 48 patients with 'active' CLL were treated with TBI and were compared with 18 patients treated with chemotherapy and/or local irradiation. Our series of patients primarily treated with TBI have twice the median survival (57 months) measured from first therapy of the concurrent chemotherapy series (27 months). One third of the TBI group have experienced a complete or nearly complete remission and these patients showed a definite longer survival, with a median survival well in excess of five years until now. However, patients with a less complete remission failed to demonstrate a prolonged survival time with TBI in comparison to other modes of treatment. These results indicate that TBI can induce complete remissions which improve the prognosis in patients with active CLL.

Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-2-0026 TITLE: Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium PRINCIPAL...2017 4. TITLE AND SUBTITLE Legacy Clinical Data from the Mission Connect Mild TBI Translational Research 5a. CONTRACT NUMBER Consortium 5b. GRANT...mTBI) Translational Research Consortium was to improve the diagnosis and treatment of mTBI. We enrolled a total of 88 mTBI patients and 73 orthopedic

TBI Assessment of Readiness Using a Gait Evaluation Test (TARGET): Development of a Portable mTBI Screening Device

Science.gov (United States)

2016-05-01

determine the validity and reliability of an Android device-based mTBI (mild traumatic brain injury) screening test app for assessing motor function. The...individuals and those with clinically confirmed mTBI in both a civilian and military population. 15. SUBJECT TERMS- 16. SECURITY CLASSIFICATION OF: 17...8 5. Changes/ Problems 9 6. Products 11 7. Participants & Other Collaborating Organizations 14 8. Special Reporting Requirements 16 9. Appendices

Quality of Survival and Growth in Children and Young Adults in the PNET4 European Controlled Trial of Hyperfractionated Versus Conventional Radiation Therapy for Standard-Risk Medulloblastoma

Energy Technology Data Exchange (ETDEWEB)

Kennedy, Colin, E-mail: crk1@soton.ac.uk [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Bull, Kim [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Chevignard, Mathilde [Hôpitaux de Saint Maurice, Saint Maurice (France); Neurophysiology, University of Pierre et Marie-Curie Paris 6, Paris (France); Culliford, David [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Dörr, Helmuth G. [Kinder- und Jugendklinik der Universität Erlangen, Erlangen (Germany); Doz, François [Institut Curie and University Paris Descartes, Sorbonne Paris Cité (France); Kortmann, Rolf-Dieter [Department of Radiation Therapy, University of Leipzig, Leipzig (Germany); Lannering, Birgitta [Department of Pediatrics, The Sahlgren Academy, University of Gothenburg, Gothenburg (Sweden); Massimino, Maura [Fondazione Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Navajas Gutiérrez, Aurora [Hospital Universitario Cruces, Baracaldo-Vizcaya (Spain); Rutkowski, Stefan [University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Spoudeas, Helen A. [Center for Pediatric Endocrinology, University College London, London (United Kingdom); Calaminus, Gabriele [Pediatric Oncology, University of Muenster, Muenster (Germany)

2014-02-01

Purpose: To compare quality of survival in “standard-risk” medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Methods and Materials: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Results: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Conclusions: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life.

Quality of Survival and Growth in Children and Young Adults in the PNET4 European Controlled Trial of Hyperfractionated Versus Conventional Radiation Therapy for Standard-Risk Medulloblastoma

International Nuclear Information System (INIS)

Kennedy, Colin; Bull, Kim; Chevignard, Mathilde; Culliford, David; Dörr, Helmuth G.; Doz, François; Kortmann, Rolf-Dieter; Lannering, Birgitta; Massimino, Maura; Navajas Gutiérrez, Aurora; Rutkowski, Stefan; Spoudeas, Helen A.; Calaminus, Gabriele

2014-01-01

Purpose: To compare quality of survival in “standard-risk” medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Methods and Materials: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Results: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Conclusions: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life

Quality of survival and growth in children and young adults in the PNET4 European controlled trial of hyperfractionated versus conventional radiation therapy for standard-risk medulloblastoma.

Science.gov (United States)

Kennedy, Colin; Bull, Kim; Chevignard, Mathilde; Culliford, David; Dörr, Helmuth G; Doz, François; Kortmann, Rolf-Dieter; Lannering, Birgitta; Massimino, Maura; Navajas Gutiérrez, Aurora; Rutkowski, Stefan; Spoudeas, Helen A; Calaminus, Gabriele

2014-02-01

To compare quality of survival in "standard-risk" medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life. Copyright © 2014 Elsevier Inc. All rights reserved.

Phase I Trial of Gross Total Resection, Permanent Iodine-125 Brachytherapy, and Hyperfractionated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme

International Nuclear Information System (INIS)

Chen, Allen M.; Chang, Susan; Pouliot, Jean; Sneed, Penny K.; Prados, Michael D.; Lamborn, Kathleen R.; Malec, Mary K.; McDermott, Michael W.; Berger, Mitchell S.; Larson, David A.

2007-01-01

Purpose: To evaluate the feasibility of gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy for patients with newly diagnosed glioblastoma. Methods and Materials: From April 1999 to May 2002, 21 patients with glioblastoma multiforme were enrolled on a Phase I protocol investigating planned gross total resection and immediate placement of permanent I-125 seeds, followed by postoperative hyperfractionated radiotherapy to a dose of 60 Gy at 100 cGy b.i.d., 5 days per week. Median age and Karnofsky performance status were 50 years (range, 32-65 years) and 90 (range, 70-100), respectively. Toxicity was assessed according to Radiation Therapy Oncology Group criteria. Results: Eighteen patients completed treatment according to protocol. The median preoperative tumor volume on magnetic resonance imaging was 18.6 cm 3 (range, 4.4-41.2 cm 3 ). The median brachytherapy dose measured 5 mm radially outward from the resection cavity was 400 Gy (range, 200-600 Gy). Ten patients underwent 12 reoperations, with 11 of 12 reoperations demonstrating necrosis without evidence of tumor. Because of high toxicity, the study was terminated early. Median progression-free survival and overall survival were 57 and 114 weeks, respectively, but not significantly improved compared with historical patients treated at University of California, San Francisco, with gross total resection and radiotherapy without brachytherapy. Conclusions: Treatment with gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy as performed in this study results in high toxicity and reoperation rates, without demonstrated improvement in survival

TBI Endpoints Development

Science.gov (United States)

2015-10-01

therapy , and early mild physical activity, which result in fewer symptoms, lower mean severity of symptoms, less social disability, and fewer days off work...developing more precise TBI diagnostic tools, clinical endpoints, and effective therapies . We designed and executed an interactive program that combined...surgery, neuropsychology, neuroradiology, psychiatry, neurology, sports medicine, pediatrics, geriatrics , health economics, biostatistics, and informatics

Malignant astrocytoma: hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial

International Nuclear Information System (INIS)

Payne, D.G.; Simpson, W.J.; Keen, C.; Platts, M.E.

1982-01-01

A prospective randomized trial of 157 patients with malignant astrocytomas (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m 2 ) six weekly and hydroxyurea (HU, 3.5 gm/m 2 over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600-4000 rad in 36-40 fr of 100 rad each, given 4 fr per day at 3-hour intervals over two weeks). Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P<0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow-up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimes had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease

EYE-TRAC: monitoring attention and utility for mTBI

Science.gov (United States)

Maruta, Jun; Tong, Jianliang; Lee, Stephanie W.; Iqbal, Zarah; Schonberger, Alison; Ghajar, Jamshid

2012-06-01

Attention is a core function in cognition and also the most prevalent cognitive deficit in mild traumatic brain injury (mTBI). Predictive timing is an essential element of attention functioning because sensory processing and execution of goal-oriented behavior are facilitated by temporally accurate prediction. It is hypothesized that impaired synchronization between prediction and external events accounts for the attention deficit in mTBI. Other cognitive and somatic or affective symptoms associated with mTBI may be explained as secondary consequences of impaired predictive timing. Eye-Tracking Rapid Attention Computation (EYE-TRAC) is the quantification of predictive timing with indices of dynamic visuo-motor synchronization (DVS) between the gaze and the target during continuous predictive visual tracking. Such quantification allows for cognitive performance monitoring in comparison to the overall population as well as within individuals over time. We report preliminary results of normative data and data collected from subjects with a history of mTBI within 2 weeks of injury and post-concussive symptoms at the time of recruitment. A substantial proportion of mTBI subjects demonstrated DVS scores worse than 95% of normal subjects. In addition, longitudinal monitoring of acute mTBI subjects showed that initially abnormal DVS scores were followed by improvement toward the normal range. In summary, EYE-TRAC provides fast and objective indices of DVS that allow comparison of attention performance to a normative standard and monitoring of within-individual changes.

Mission Connect Mild TBI Translational Research Consortium

Science.gov (United States)

2010-08-31

using magneto - Investigators A. Papanicolaou, PhD – PI J. Breier, PhD E. Castillo, PhD T. Kent, MD Project Summary Introduction: The aim of this...secondary insults such as hemorrhagic hypotension. Antioxidant therapies have had limited success in treating mTBI. We identified carbon nanomaterials... therapies for TBI using nanomaterials that are capable of addressing, for the first time, key components of the “neurovascular unit”. If the PEG-HCCs

Targeting Epigenetic Mechanisms in Pain due to Trauma and TBI

Science.gov (United States)

2017-10-01

disability after trauma, particularly in the setting of TBI. This objective is closely in alignment with the pain management focus area of the CRMRP... management of acute and chronic pain under the care of a clinician in non-deployed settings (specifically in patients with TBI), and 3) research...distant from the head after TBI. This constitutes a fundamental contribution to the discipline. What was the impact on other disciplines? The field

Angiosarcoma after breast-conserving therapy: long-term outcomes with hyperfractionated radiotherapy.

Science.gov (United States)

Palta, Manisha; Morris, Christopher G; Grobmyer, Stephen R; Copeland, Edward M; Mendenhall, Nancy P

2010-04-15

With breast-conserving therapy (BCT) as the standard of care for patients with noninvasive and early stage invasive breast cancer, a small incidence of post-BCT angiosarcoma has emerged. The majority of therapeutic interventions have been unsuccessful. To the authors' knowledge, there is no consensus in the medical literature to date regarding the treatment of this malignancy. The current study was conducted to report the long-term outcomes of a novel approach using hyperfractionated and accelerated radiotherapy (HART) for angiosarcoma developing after BCT. The authors retrospectively reviewed the outcomes of 14 patients treated with HART with or without surgery at the University of Florida between November 1997 and March 2006 for angiosarcoma that developed after BCT. At the time of last follow-up, 9 patients had remained continuously without evidence of disease for a median of 61 months after HART (range, 36-127 months). Five patients had further manifestations of angiosarcoma after HART at a median of 1 month (range, 1-28 months): 3 with progressive pulmonary and/or mediastinal disease that was likely present before HART and 2 with local or regional disease extension. Progression-free survival rates for the 14 patients at 2 years and 5 years were 71% and 64%, respectively. The overall and cause-specific survival rates were both 86% at 2 years and 5 years. To the best of the authors' knowledge, HART with or without subsequent surgery, as documented in the current series, is the first approach to provide a high rate of local control, disease-free survival, and overall survival after the development of post-BCT angiosarcoma. The authors believe the success noted with this approach is related to both the hyperfractionation and acceleration of the RT. (c) 2010 American Cancer Society.

Leveraging Game Consoles for the Delivery of TBI Rehabilitation

Science.gov (United States)

Super, Taryn; Mastaglio, Thomas; Shen, Yuzhong; Walker, Robert

2011-01-01

Military personnel are at a greater risk for traumatic brain injury (TBI) than the civilian population. In addition, the increase in exposure to explosives, i.e. , improvised explosive devices, in the Afghanistan and Iraq wars, along with more effective body armor, has resulted in far more surviving casualties suffering from TBI than in previous wars. This effort presents the results of a feasibility study and early prototype of a brain injury rehabilitation delivery system (BIRDS). BIRDS is designed to provide medical personnel treating TBI with a capability to prescribe game activities for patients to execute using a commercially available game console, either in a clinical setting or in their homes. These therapeutic activities will contribute to recovery or remediation of the patients' cognitive dysfunctions. Solutions such as this that provide new applications for existing platforms have significant potential to address the growing incidence of TBI today.

Traumatic Brain Injury Registry (TBI)

Data.gov (United States)

Department of Veterans Affairs — As the number of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Traumatic Brain Injury (TBI) patients has grown, so has the need to track and monitor...

Caregiver functioning following early childhood TBI: do moms and dads respond differently?

Science.gov (United States)

Wade, Shari L; Walz, Nicolay C; Cassedy, Amy; Taylor, H Gerry; Stancin, Terry; Yeates, Keith Owen

2010-01-01

Research suggests that pediatric TBI results in injury-related stress and burden and psychological distress for parents. However, existing studies have focused almost exclusively on mothers, so that we know relatively little about the impact of childhood TBI on fathers. The aims were to prospectively examine differences in maternal and paternal response to early childhood TBI over time relative to a comparison cohort of mothers and fathers of children with orthopedic injuries (OI). The concurrent cohort/prospective research design involved repeated assessments of children aged 3-6 years with TBI or OI requiring hospitalization and their families. Shortly after injury and at 6, 12, and 18 months post injury, parents of 48 children with TBI (11 severe and 37 moderate) and 89 with OI completed standardized assessments of injury-related stress and burden, parental distress, and coping strategies. Mixed models analyses and Generalized Estimating Equations examined differences in maternal versus paternal burden, distress, and coping over time. The analyses included interactions of parent sex with group (severe TBI, moderate TBI, OI) and time since injury, to examine the moderating effects of injury severity on parental response to injury over time. Fathers were more likely than mothers to use denial to cope following moderate and severe TBI, but not OI. Conversely, mothers were more likely to prefer acceptance and emotion-focused strategies than fathers regardless of the type of injury. The use of active coping strategies varied as a function of injury type, parent sex, and time since injury. Fathers reported greater injury-related stress and distress than mothers over time, with pronounced differences in the severe TBI and OI groups. Mothers and fathers appear to respond differently following TBI. The different types of responses may serve to exacerbate emerging family dysfunction.

Indicators of complicated mild TBI predict MMPI-2 scores after 23 years.

Science.gov (United States)

Hessen, Erik; Nestvold, Knut

2009-03-01

Research suggests that post-concussive syndrome may become persistent after mild traumatic brain injury (mTBI). The aim of this study was to investigate determinants of subjective complaints, characteristic for post-concussive syndrome, 23 years after mTBI. The study was a follow-up after a prospective head injury study at a general hospital in Norway. Ninety-seven patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining primarily mTBI. A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the patients that sustained complicated mTBI showed somewhat more pathological scores, well-matched with mild post-concussive syndrome. The most important predictors of poor outcome were a combination of post-traumatic amnesia >30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was found. The results are in line with previous research findings and support the notion of potentially differential impact of uncomplicated vs. complicated mTBI. The findings suggest that complicated mTBI may cause subtle chronic symptoms typical of post-concussive syndrome.

Safety and adverse events of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) for rectal cancer

International Nuclear Information System (INIS)

Doi, Hiroshi; Kamikonya, Norihiko; Hirota, Shozo; Beppu, Naohito; Yanagi, Hidenori

2014-01-01

We presented good tolerability and short-term outcomes of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART; 25 Gy in 10 fractions for 5 days) combined with chemotherapy in a total of 73 patients with lower rectal cancer. Age, gender, tumor differentiation, and the type of surgery seemed to have no apparent effects on toxicity of SC-HART. SC-HART appeared to have a good feasibility for use in further clinical trials. (author)

Hyperfractionated 3D conformal radiotherapy and concurrent chemotherapy for unresectable stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Choi, E.K.; Ahn, S.D.; Yi, B.Y.; Chang, H.S.; Lee, J.H.; Suh, C.W.; Lee, J.S.; Kim, S.H.; Koh, Y.S.; Kim, W.S.; Kim, D.S.; Kim, W.D.; Sohn, K.H.

1997-01-01

Purpose/Objective: This phase II study has been conducted to determine the feasibility, toxicity, response rate, local control, distant metastasis, and survival of hyperfractionated 3D conformal radiotherapy and concurrent chemotherapy with mitomycin C, vinblastine, and cisplatin in unresectable stage III non-small cell lung cancer (NSCLC), and also to find the most ideal 3D conformal radiotherapy technique. Materials and Methods: From Aug 1993, 173 patients with unresectable stage III NSCLC were entered into this trial and 146 (84%) completed the treatment. Hyperfractionated radiotherapy was given to a total dose of 65-70 Gy (120 cGy/fx, bid) with concurrent 2 cycles of MVP chemotherapy (Mitomycin C 6 mg/m 2 d2 and d29, Vinblastine 6 mg/m 2 d2 and d29, Cisplatin 60 mg/m 2 d1 and d28). Of these 146 patients who completed the treatment, 78 received noncoplanar 3D conformal radiotherapy using 4-6 fields and 17 received coplanar segmented conformal radiotherapy. Clinical tumor response was assessed one month after the completion of radiotherapy by computerized tomography (CT) scan. Toxicity was graded by RTOG and SWOG criteria. Normal tissue complication probability (NTCP) for lung was calculated to find the correlation with radiation pneumonitis. Results: Nineteen (13%) had stage IIIa and 127 (87%) had IIIb disease including 16 with pleural effusion and 20 with supraclavicular lymph node metastases. Response rate was 74%, including 20% complete response and 54% partial response. With a minimum follow up of 12 months, overall survival was 60% at 1 year, 30% at 2 years and median survival was 15 months. Patients achieving a complete response (n=29) had a 2-year overall survival of 46.5% compared to 28.7% for partial responders (n=79) (p=.001). Actuarial local control was 66.7% at 1 year and 43.7% at 2 years. Actuarial distant free survival was 52.3% at 1 year and 39.8% at 2 years. Major hematologic toxicity (Gr 3-4) occurred in 33% of the patients but treatment delay

Automated Comprehensive Evaluation of mTBI Visual Dysfunction

Science.gov (United States)

2017-04-01

of the NODe . Subtask 1: Statistical analysis of NODe data from controls and mTBI patients: COMPLETED Data Processing : Automated data analyses are...order visual processing dysfunctions on a large population of Warfighters with acute mTBI as compared to healthy age-matched controls . This study also... controls ) military personnel will be recruited from the patient population at Womack Army Medical Center (WAMC). The central hypothesis is that a NODe test

Sleep Disturbances, TBI and PTSD: Implications for Treatment and Recovery

Science.gov (United States)

Gilbert, Karina Stavitsky; Kark, Sarah M.; Gehrman, Philip; Bogdanova, Yelena

2015-01-01

Post-Traumatic Stress Disorder (PTSD), traumatic brain injury (TBI), and sleep problems significantly affect recovery and functional status in military personnel and Veterans returning from combat. Despite recent attention, sleep is understudied in the Veteran population. Few treatments and rehabilitation protocols target sleep, although poor sleep remains at clinical levels and continues to adversely impact functioning even after the resolution of PTSD or mild TBI symptoms. Recent developments in non-pharmacologic sleep treatments have proven efficacious as stand-alone interventions and have potential to improve treatment outcomes by augmenting traditional behavioral and cognitive therapies. This review discusses the extensive scope of work in the area of sleep as it relates to TBI and PTSD, including pathophysiology and neurobiology of sleep; existing and emerging treatment options; as well as methodological issues in sleep measurements for TBI and PTSD. Understanding sleep problems and their role in the development and maintenance of PTSD and TBI symptoms may lead to improvement in overall treatment outcomes while offering a non-stigmatizing entry in mental health services and make current treatments more comprehensive by helping to address a broader spectrum of difficulties. PMID:26164549

Sexual Functioning, Desire, and Satisfaction in Women with TBI and Healthy Controls

Directory of Open Access Journals (Sweden)

Jenna Strizzi

2015-01-01

Full Text Available Traumatic brain injury (TBI can substantially alter many areas of a person’s life and there has been little research published regarding sexual functioning in women with TBI. Methods. A total of 58 women (29 with TBI and 29 healthy controls from Neiva, Colombia, participated. There were no statistically significant differences between groups in sociodemographic characteristics. All 58 women completed the Sexual Quality of Life Questionnaire (SQoL, Female Sexual Functioning Index (FSFI, Sexual Desire Inventory (SDI, and the Sexual Satisfaction Index (ISS. Results. Women with TBI scored statistically significantly lower on the SQoL (p<0.001, FSFI subscales of desire (p<0.05, arousal (p<0.05, lubrication (p<0.05, orgasm (p<0.05, and satisfaction (p<0.05, and the ISS (p<0.001 than healthy controls. Multiple linear regressions revealed that age was negatively associated with some sexuality measures, while months since the TBI incident were positively associated with these variables. Conclusion. These results disclose that women with TBI do not fare as well as controls in these measures of sexual functioning and were less sexually satisfied. Future research is required to further understand the impact of TBI on sexual function and satisfaction to inform for rehabilitation programs.

Head injuries (TBI) to adults and children in motor vehicle crashes.

Science.gov (United States)

Viano, David C; Parenteau, Chantal S; Xu, Likang; Faul, Mark

2017-08-18

This is a descriptive study. It determined the annual, national incidence of head injuries (traumatic brain injury, TBI) to adults and children in motor vehicle crashes. It evaluated NASS-CDS for exposure and incidence of various head injuries in towaway crashes. It evaluated 3 health databases for emergency department (ED) visits, hospitalizations, and deaths due to TBI in motor vehicle occupants. Four databases were evaluated using 1997-2010 data on adult (15+ years old) and child (0-14 years old) occupants in motor vehicle crashes: (1) NASS-CDS estimated the annual incidence of various head injuries and outcomes in towaway crashes, (2) National Hospital Ambulatory Medical Care Survey (NHAMCS)-estimated ED visits for TBI, (3) National Hospital Discharge Survey (NHDS) estimated hospitalizations for TBI, and (4) National Vital Statistics System (NVSS) estimated TBI deaths. The 4 databases provide annual national totals for TBI related injury and death in motor vehicle crashes based on differing definitions with TBI coded by the Abbreviated Injury Scale (AIS) in NASS-CDS and by International Classification of Diseases (ICD) in the health data. Adults: NASS-CDS had 16,980 ± 2,411 (risk = 0.43 ± 0.06%) with severe head injury (AIS 4+) out of 3,930,543 exposed adults in towaway crashes annually. There were 49,881 ± 9,729 (risk = 1.27 ± 0.25%) hospitalized with AIS 2+ head injury, without death. There were 6,753 ± 882 (risk = 0.17 ± 0.02%) fatalities with a head injury cause. The public health data had 89,331 ± 6,870 ED visits, 33,598 ± 1,052 hospitalizations, and 6,682 ± 22 deaths with TBI. NASS-CDS estimated 48% more hospitalized with AIS 2+ head injury without death than NHDS occupants hospitalized with TBI. NASS-CDS estimated 29% more deaths with AIS 3+ head injury than NVSS occupant TBI deaths but only 1% more deaths with a head injury cause. Children: NASS-CDS had 1,453 ± 318 (risk = 0.32 ± 0.07%) with severe head injury (AIS 4+) out of 454,973 exposed

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism.

Science.gov (United States)

Pierce, Janet D; Gupte, Raeesa; Thimmesch, Amanda; Shen, Qiuhua; Hiebert, John B; Brooks, William M; Clancy, Richard L; Diaz, Francisco J; Harris, Janna L

2018-06-01

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI. © 2018 Wiley Periodicals, Inc.

Pilot production of the wedge filter for the TBI (total body irradiation)

International Nuclear Information System (INIS)

Ikezaki, Hiromi; Ikeda, Ikuo; Maruyama, Yasushi; Nako, Yasunobu; Tonari, Ayako; Kusuda, Junko; Takayama, Makoto

2007-01-01

Total body irradiation (TBI) is performed by various methods, such as a long SSD method and a translational couch method. For patient safety in carrying out TBI, the patient should be placed on the supine position and prone position near the floor. TBI is performed from 2 opposite ports (AP/PA) with a linear accelerator (10 MV X-ray). We experimented with a wedge filter for TBI created by us, which makes dose distribution to a floor uniform. The wedge filter, made of iron alloy, was attached to the linear accelerator. In designing the wedge filter, thickness of the lead-made wedge filter can be calculated numerically from the ratio of linear attenuation coefficient of iron alloy and lead. In measuring the dose profile for a phantom of 20 cm thick, dose homogeneity less than 10% was proved by the wedge filter for TBI. (author)

The indication and the point at issue in total body irradiation (TBI)

International Nuclear Information System (INIS)

Kikuchi, Yuzo; Nishino, Shigeo.

1992-01-01

The role of radiation in the cause of interstitial pneumonitis (IP) was analysed here. Also optimal dose fractionation was discussed about total absorbed lung dose, dose rate and fractionation in spect of IP. After all optimal time schedule was recommended 3, 4 and 6 fraction of ≤ 4 Gy of fraction size using conventional and hyperfractionated irradiation. In the end the present condition and the point at issue in the irradiation of blood for prevention GVHD were discussed. (author)

Delivery of mental health treatment to combat veterans with psychiatric diagnoses and TBI histories.

Directory of Open Access Journals (Sweden)

Shannon R Miles

Full Text Available Traumatic brain injury (TBI and mental health (MH disorders are prevalent in combat veterans returning from Afghanistan and/or Iraq (hereafter referred to as returning veterans. Accurate estimates of service utilization for veterans with and without TBI exposure (referred to as TBI history are imperative in order to provide high quality healthcare to returning veterans. We examined associations between TBI history and MH service utilization in a subsample of returning veterans who were newly diagnosed with posttraumatic stress disorder (PTSD, depression, and/or anxiety in the 2010 fiscal year (N = 55,458. Data were extracted from the Veterans Health Administration (VHA National Patient Care Database. Veterans with MH diagnoses and TBI histories attended significantly more psychotherapy visits, (M = 8.32 visits, SD = 17.15 and were more likely to attend at least 8 psychotherapy visits, (15.7% than veterans with MH diagnoses but no TBI history (M = 6.48 visits, SD = 12.12; 10.1% attended at least 8 sessions. PTSD and TBI history, but not depression or anxiety, were associated with a greater number of psychotherapy visits when controlling for demographic and clinical variables. PTSD, anxiety, depression, and TBI history were associated with number of psychotropic medication-management visits. TBI history was related to greater MH service utilization, independent of MH diagnoses. Future research should examine what MH services are being utilized and if these services are helping veterans recover from their disorders.

Electropalatographic (EPG) assessment of tongue-to-palate contacts in dysarthric speakers following TBI.

Science.gov (United States)

Kuruvilla, Mili S; Murdoch, Bruce E; Goozee, Justine V

2008-09-01

The aim of the investigation was to compare EPG-derived spatial and timing measures between a group of 11 dysarthric individuals post-severe TBI and 10 age- and sex-matched neurologically non-impaired individuals. Participants of the TBI group were diagnosed with dysarthria ranging from mild-to-moderate-severe dysarthria. Each participant from the TBI and comparison group was fitted with a custom-made artificial acrylic palate that recorded lingual palatal contact during target consonant production in sentence- and syllable-repetition tasks at a habitual rate and loudness level. Analysis of temporal parameters between the comparison and TBI groups revealed prolonged durations of the various phases of consonant production, which were attributed to articulatory slowness, impaired speech motor control, impaired accuracy, and impaired coordination of articulatory movements in the dysarthric speakers post-TBI. For the spatial measurements, quantitative analysis, as well as visual inspection of the tongue-to-palate contact diagrams, indicated spatial aberrations in dysarthric speech post-TBI. Both the spatial and temporal aberrations may have at least partially caused the perceptual judgement of articulatory impairments in the dysarthric speakers.

Factors modifying the toxicity of total body irradiation (TBI) with bone marrow transplant

International Nuclear Information System (INIS)

Fish, B.L.; Moulder, J.E.

1987-01-01

In defined-flora, barrier-maintained rats, radiation nephritis is the principle late toxicity seen after single dose, high dose rate TBI with bone marrow transplant. Shielding the kidneys eliminates this late toxicity. If rats are exposed to a conventional microbiological environment during and after TBI and bone marrow transplant, the principle late toxicity is pneumonitis. Low dose rate TBI gives similar renal toxicity but at doses twice as large. Clinically, TBI and bone marrow transplant is preceded by intensive drug treatment, typically with cyclophosphamide (Cytoxan) and cytosine arabinoside (ara-C). Pretreatment with a standard cytoxan/ara-C regimen, has no effect on the gastrointestinal toxicity of TBI, but results in a decrease in marrow toxicity. Late renal toxicity still occurs when bone marrow transplants are given, but it is to early to determine whether drug treatment has affected late renal tolerance. Experiments are also underway to determine the effects of fractionated TBI (3, 6 and 9 fractions in 60 hours) on acute tolerance and on late tolerance after bone marrow transplantation

Role of Sertraline in insomnia associated with post traumatic brain injury (TBI depression

Directory of Open Access Journals (Sweden)

Ansari Ahmed

2016-09-01

Full Text Available Traumatic brain injury (TBI is a major cause of disability (1, 2. Sleep disturbances, such as insomnia, are very common following traumatic brain injury and have been reported in frequencies from 40% (3 to as high as 84% (4. Sleep disruption can be related to the TBI itself but may also be secondary to neuropsychiatric (e.g., depression or neuromuscular (e.g., pain conditions associated with TBI or to the pharmacological management of the injury and its consequences. Post-TBI insomnia has been associated with numerous negative outcomes including daytime fatigue, tiredness, difficulty functioning: impaired performance at work, memory problems, mood problems, greater functional disability, reduced participation in activities of daily living, less social and recreational activity, less employment potential, increased caregiver burden, greater sexual dysfunction, and also lower ratings of health, poor subjective wellbeing. These negative consequences can hamper the person’s reintegration into the community, adjustment after injury, and overall QOL. (5 The connection between depression and insomnia has not been investigated within the post TBI population to a great extent. For the general population, clinically significant insomnia is often associated with the presence of an emotional disorder (6. Fichtenberg et al. (2002 (7, in his study established that the strongest relationship with the diagnosis of insomnia belonged to depression. Given the high prevalence of depression during the first 2 years following TBI (8, a link between depression and insomnia among TBI patients makes innate sense. The present study aims at assessing role of sertralline in post TBI insomnia associated with depression.

Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

International Nuclear Information System (INIS)

Yumura-Yagi, Keiko; Inoue, Masami; Okamura, Takayuki

1997-01-01

Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin±methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus±prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

When Injury Clouds Understanding of Others: Theory of Mind after Mild TBI in Preschool Children.

Science.gov (United States)

Bellerose, Jenny; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H

2015-08-01

There is evidence to suggest that social skills, such as the ability to understand the perspective of others (theory of mind), may be affected by childhood traumatic brain injuries; however, studies to date have only considered moderate and severe traumatic brain injury (TBI). This study aimed to assess theory of mind after early, mild TBI (mTBI). Fifty-one children who sustained mTBI between 18 and 60 months were evaluated 6 months post-injury on emotion and desires reasoning and false-belief understanding tasks. Their results were compared to that of 50 typically developing children. The two groups did not differ on baseline characteristics, except for pre- and post-injury externalizing behavior. The mTBI group obtained poorer scores relative to controls on both the emotion and desires task and the false-belief understanding task, even after controlling for pre-injury externalizing behavior. No correlations were found between TBI injury characteristics and theory of mind. This is the first evidence that mTBI in preschool children is associated with theory of mind difficulties. Reduced perspective taking abilities could be linked with the social impairments that have been shown to arise following TBI.

Individual neuropsychological support and group sessions for relatives to TBI patients

DEFF Research Database (Denmark)

Siert, Lars

TITLE: Individual neuropsychological support and group sessions for relatives to TBI patients. OBJECTIVE: To describe how the neuropsychologist work with early and ongoing individual support and group sessions for relatives to adult TBI patients in the acute and sub acute phase and after discharge...

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

Science.gov (United States)

Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

Towards systemic sustainable performance of TBI care systems: emergency leadership frontiers.

Science.gov (United States)

Caro, Denis H J

2010-11-10

Traumatic brain injuries (TBIs) continue as a twenty-first century subterranean and almost invisible scourge internationally. TBI care systems provide a safety net for survival, recovery, and reintegration into social communities from this scourge, particularly in Canada, the European Union, and the USA. This paper examines the underlying issues of systemic performance and sustainability of TBI care systems, in the light of decreasing care resources and increasing demands for services. This paper reviews the extant literature on TBI care systems, systems reengineering, and emergency leadership literature. This paper presents a seven care layer paradigm, which forms the essence of systemic performance in the care of patients with TBIs. It also identifies five key strategic drivers that hold promise for the future systemic sustainability of TBI care systems. Transformational leadership and engagement from the international emergency medical community is the key to generating positive change. The sustainability/performance care framework is relevant and pertinent for consideration internationally and in the context of other emergency medical populations.

Alterations of total non stimulated salivary flow in patients with squamous cell carcinoma of the mouth and oropharynx submitted to hyperfractionated radiation therapy

International Nuclear Information System (INIS)

Guebur, Maria Isabela; Rapoport, Abrao; Sassi, Laurindo Moacir; Oliveira, Benedito Valdecir de; Ramos, Gyl Henrique Albrecht; Pereira, Jose Carlos Gasparin

2004-01-01

Prevention and early diagnosis are actually the most effective measures that we dispose to improve the prognostic of the malignant tumors. The mouth and oropharynx tumors are treated with success, when early diagnosed. The radiotherapy is almost always one of the selected treatments for these tumors. When cancer is diagnosed in advanced stages, many a time the treatment needs to be carried out swiftly to be efficient, and consequently the radio therapist use the hyperfractionated therapy, with the patient receiving two lower doses of radiation in two sessions daily, amounting to a higher daily dosage, of about 160 cGy/2x/day. When the major salivary glands are present in the radiated field, the xerostomia appears by the second week of treatment (1500 to 2000 cGy), changing the patient's health, and causing difficulties for him to eat, speak and sleep. The objective of this study was to evaluate the quantitative alterations of the total non stimulated salivate flow of patients who underwent hyperfractionated therapy for the treatment of squamous cell carcinoma of mouth and oropharynx. Samples of twelve male patients saliva from Erasto Gaertner Hospital in Curitiba, PR, Brazil, were examined. Two samples of saliva were collected from each patient, the first one before the beginning of the radiotherapy, and the second at the end of the treatment. As a result, we obtained salivary loss in 91.7% of the patients, with a percentage of total salivary flow loss of 62.9%, registered in the second collection. We concluded that the hyperfractionated therapy causes a marked xerostomia when the major salivary glands are in the radiated field. (author)

Hyperfractionated radiotherapy (2100 cGY) for stage 4 neuroblastoma as part of intensive multimodality therapy

International Nuclear Information System (INIS)

Gollamudi, S.V.; Kushner, B.H.; Merchant, T.E.; LaQuaglia, M.; Lindsley, K.; Rosenfield, N.; Abramson, S.; Kramer, K.; Cheung, N.K.V.

1997-01-01

PURPOSE: To retrospectively evaluate the role of hyperfractionated radiotherapy to the primary site following induction chemotherapy and aggressive surgical resection in patients (pts) with stage 4 neuroblastoma. MATERIALS AND METHODS: 48 previously untreated children (median age at diagnosis 3 yo, range 1-10 yo) with stage 4 neuroblastoma achieved a complete-, near-complete-, or partial-remission after multimodality therapy (protocol N4: 6 pts, N5: 7 pts, N6: 27 pts, or N7: 8 pts). All protocols included a regimen consisting of dose-intensive multiagent chemotherapy, maximal surgical debulking, followed by hyperfractionated radiotherapy. Most pts then underwent consolidation with either autologous marrow transplantation (N4 and N5), or immunotherapy (N6 and N7) with radioimmunotherapy (N7). Of 48 pts, 46 had microscopic disease at the primary site prior to beginning radiotherapy (45 underwent gross total resection of the primary, and one had no residual primary disease after chemotherapy alone). One pt had a partial resection, and one remained unresectable after mutimodality therapy. The pre-chemotherapy volume of the primary tumor and regional lymph nodes were irradiated to a total dose of 2100cGy delivered twice-daily in 150 cGy fractions over 7 treatment days. RESULTS: With a median follow-up of 32.5 months (range= 8-145 months), local-regional control was achieved in 44 of the 48 pts. Of the pts who are progression-free, median follow-up was 53.5 months. Overall, 24 of 48 pts progressed, three with local-regional recurrence as the first site of relapse, one with distant failure first and subsequent local-regional recurrence, and 21 with distant failure only. The probability of local-regional control at 32 months was 83%. One of the four pts with local-regional relapse never achieved a complete remission with either systemic therapy, surgical resection or radiotherapy. The progression-free survival at 32 months was 46%. Median time to overall progression was 16

Rates of TBI-related Deaths by Age Group - United States, 2001 - 2010

Data.gov (United States)

U.S. Department of Health & Human Services — Changes in the rates of TBI-related deaths vary depending on age. For persons 44 years of age and younger, TBI-related deaths decreased between the periods of...

Preoperative hyperfractionated accelerated radiotherapy and radical surgery in advanced head and neck cancer: A prospective phase II study

International Nuclear Information System (INIS)

Lindholm, Paula; Valavaara, Ritva; Aitasalo, Kalle; Kulmala, Jarmo; Laine, Juhani; Elomaa, Liisa; Sillanmaeki, Lauri; Minn, Heikki; Grenman, Reidar

2006-01-01

Background and purpose: To evaluate whether preoperative hyperfractionated accelerated radiotherapy (RT) combined with major radical surgery is feasible and successful in the treatment of advanced primary head and neck cancer. Patients and methods: Ninety four patients with histologically confirmed head and neck squamous cell cancer (HNSCC) in the oral cavity (41/96; 43%), supraglottis (14/96; 15%), glottis (5/96; 5%), oropharynx (16/96; 17%), nasal cavity/paranasal sinuses (8/96; 8%), nasopharynx (3/96; 3%), hypopharynx (7/96; 7%) and two (2%) with unknown primary tumour and large cervical lymph nodes entered into the study. 21/96 patients (22%) had stage II, 17/96 (18%) stage III and 58/96 patients (60%) stage IV disease. The patients received preoperative hyperfractionated RT 1.6 Gy twice a day, 5 days a week to a median tumour dose of 63 Gy with a planned break for 11 days (median) after the median dose of 37 Gy. Then, after a median of 27 days the patients underwent major radical surgery of the primary tumour and metastatic lymph nodes including reconstructions with pedicled or microvascular free flaps when indicated as a part of the scheduled therapy. 12/96 patients had only ipsilateral or bilateral neck dissections. Results: After a median follow-up time of 37.2 mos 77/96 (80.2%) patients had complete locoregional control. All but 2 patients had complete histological remission after surgery. 40/96 pts were alive without disease, two of them after salvage surgery. 32/96 patients had relapsed; 15 had locoregional and 13 distant relapses, 4 patients relapsed both locoregionally and distantly. Fifty patients have died; 29 with locoregional and/or distant relapse, eight patients died of second malignancy, and 19 had intercurrent diseases. Disease-specific and overall survival at 3 years was 67.7 and 51%, respectively. Acute grade three mucosal reactions were common, but transient and tolerable. Late grade 3-4 adverse effects were few. Conclusions: Preoperative

Preventing Older Adult Falls and TBI

Centers for Disease Control (CDC) Podcasts

2008-03-05

This podcast provides tips on how older adults can prevent falls and related injuries, such as traumatic brain injuries (TBI).  Created: 3/5/2008 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 3/7/2008.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

Science.gov (United States)

Prodam, F; Gasco, V; Caputo, M; Zavattaro, M; Pagano, L; Marzullo, P; Belcastro, S; Busti, A; Perino, C; Grottoli, S; Ghigo, E; Aimaretti, G

2013-08-01

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (phypopituitaric patients. In particular, triglycerides (phypopituitaric TBI patients. We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD

Science.gov (United States)

2016-10-01

1 Award Number: W81XWH-11-1-0796 TITLE: Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD PRINCIPAL...30Sept2015 - 29Sept2016 4. TITLE AND SUBTITLE: Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD 5a. CONTRACT... met criteria for TBI during military service, 48.8% of whom reported multiple head injuries. The most common mechanisms of injury included blast

An audit of traumatic brain injury (TBI) in a busy developing-world ...

African Journals Online (AJOL)

Committee in Neurotraumatology.[7] Four years later, at the ... the resources necessary to manage severe TBI according to interna- ... An audit of traumatic brain injury (TBI) in a busy .... The danger with this approach is that it risks becoming a.

rTMS: A Treatment to Restore Function After Severe TBI

Science.gov (United States)

2017-10-01

Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for...magnetic stimulation (rTMS), which is a non-invasive technique to stimulate the brain. The evidence of therapeutic efficacy from the literature in non-TBI...Transcranial Magnetic Stimulation (rTMS), Traumatic Brain Injury (TBI), Vegetative (VS), Minimally Conscious (MCS) 16. SECURITY CLASSIFICATION OF

Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

Science.gov (United States)

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

Phase I/II Trial of Hyperfractionated Concomitant Boost Proton Radiotherapy for Supratentorial Glioblastoma Multiforme

International Nuclear Information System (INIS)

Mizumoto, Masashi; Tsuboi, Koji; Igaki, Hiroshi; Yamamoto, Tetsuya; Takano, Shingo; Oshiro, Yoshiko; Hayashi, Yasutaka; Hashii, Haruko; Kanemoto, Ayae; Nakayama, Hidetsugu; Sugahara, Shinji; Sakurai, Hideyuki; Matsumura, Akira; Tokuuye, Koichi

2010-01-01

Purpose: To evaluate the safety and efficacy of postoperative hyperfractionated concomitant boost proton radiotherapy with nimustine hydrochloride for supratentorial glioblastoma multiforme (GBM). Methods and Materials: Twenty patients with histologically confirmed supratentorial GBM met the following criteria: (1) a Karnofsky performance status of ≥60; (2) the diameter of the enhanced area before radiotherapy was ≤40 cm; and (3) the enhanced area did not extend to the brain stem, hypothalamus, or thalamus. Magnetic resonance imaging (MRI) T 2 -weighted high area (clinical tumor volume 3 [CTV3]) was treated by x-ray radiotherapy in the morning (50.4 Gy in 28 fractions). More than 6 hours later, 250 MeV proton beams were delivered to the enhanced area plus a 10-mm margin (CTV2) in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume (CTV1) in the latter half (23.1 GyE in 14 fraction). The total dose to the CTV1 was 96.6 GyE. Nimustine hydrochloride (80 mg/m2) was administered during the first and fourth weeks. Results: Acute toxicity was mainly hematologic and was controllable. Late radiation necrosis and leukoencephalopathy were each seen in one patient. The overall survival rates after 1 and 2 years were 71.1% and 45.3%, respectively. The median survival period was 21.6 months. The 1- and 2-year progression-free survival rates were 45.0% and 15.5%, respectively. The median MRI change-free survival was 11.2 months. Conclusions: Hyperfractionated concomitant boost proton radiotherapy (96.6 GyE in 56 fractions) for GBM was tolerable and beneficial if the target size was well considered. Further studies are warranted to pursue the possibility of controlling border region recurrences.

Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

Energy Technology Data Exchange (ETDEWEB)

Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

1985-04-01

The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body.

Hyperfractionated Radiotherapy with Concomitant Boost Technique for Unresectable Non-Small Cell Carcinoma of the Lung

International Nuclear Information System (INIS)

Chun, Ha Chung; Lee, Myung Za

1991-01-01

Twenty five patients with unresectable non-small cell carcinoma of the lung have been treated with hyperfractionated radiotherapy with concomitant boost technique since September, 1989. Those patients with history of previous surgery or chemotherapy, pleural effusion or significant weight loss (greater than 10% of body weight) were excluded from the study. Initially, 27 Gy were delivered in 15 fractions in 3 weeks to the large field. Thereafter, large field received 1.8 Gy and cone down boost field received 1.4Gy with twice a day fractinations up to 49.4Gy. After 49.4Gy, only boost field was treated twice a day with 1.8 and 1.4 Gy. Total tumor doses were 62.2Gy for 12 patients and 65.4Gy for remaining 13 patients. Follow up period was ranged from 6 to 24 month. Actuarial survival rates at 6, 12, and 18 month were 88%, 62%, and 38%, respectively. Corresponding disease free survival rates were 88%, 41%, and 21%, respectively. Actuarial cumulative local failure rates at 9,12 and 15 month were 36%, 42%, and 59%, respectively. No significant increase of acute or late complications including radiation pneumonitis was noted with maximum follow up of 24 month. Although the longer follow up is needed, it is worthwhile to try the prospective randomized study to evaluate the efficacy of hyperfractionated radiotherapy with concomitant boost technique for unresectable non-small cell lung cancers in view of excellent tolerance of this treatment. In the future, further increase of total radiation dose might be necessary to improve local control for non-small cell lung cancer

Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

International Nuclear Information System (INIS)

Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

1985-01-01

The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body

Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer. A pilot study

International Nuclear Information System (INIS)

Jereczek-Fossa, B.; Medical Univ. Gdansk; De Braud, F.; Gasparetto, M.; De Pas, T.; Tradati, N.; Leonardi, M.C.; Marsiglia, H.R.; Orecchia, R.; Milan Univ.

1998-01-01

Purpose: To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer. Methods: A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m 2 , day 1) and 5-fluorouracil (1000 mg/m 2 in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m 2 ). Results: Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed. Conclusions: High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer. (orig.) [de

Effects of categorization training in patients with TBI during postacute rehabilitation: preliminary findings.

Science.gov (United States)

Constantinidou, Fofi; Thomas, Robin D; Scharp, Victoria L; Laske, Kate M; Hammerly, Mark D; Guitonde, Suchita

2005-01-01

Previous research suggests that traumatic brain injury (TBI) interferes with the ability to extract and use attributes to describe objects. This study explored the effects of a systematic Categorization Program (CP) in participants with TBI and noninjured controls. Ten persons with moderate to severe TBI who received comprehensive postacute rehabilitation services and 13 matched noninjured controls participated in the study. All participants received CP training for 3 to 5 hours per week for 10 to 12 weeks that consisted of 8 levels and targeted concept formation, object categorization, and decision-making abilities. The Mayo-Portland Adaptability Inventory-3 (MPAI-3) and the Community Integration Questionnaire (CIQ). Two Categorization Tests (administered pretraining and posttraining) and 3 Probe Tasks (administered at specified intervals during training) assessed skills relating to categorization. Both groups showed significant improvement in categorization performance after the CP training on the 2 Categorization Tests related to the CP. They also were able to generalize and apply categorization and sorting skills in new situations (as measured by the Probe Tasks). Participants with TBI had improved functional outcome performance measured by the MPAI-3 and the CIQ. The systematic and hierarchical structure of the CP is beneficial to participants with TBI during postacute rehabilitation. This study contributes to the growing body of evidence supporting cognitive rehabilitation after moderate to severe TBI.

Toward Development of a Field-Deployable Imaging Device for TBI

Science.gov (United States)

2015-06-01

5] J.M. Seelig, D.P. Becker, J.D. Miller, R.P. Greenberg, J.D. Ward, S.C. Choi, Traumatic acute subdural hematoma : major mortality reduction in...the field. This results in a delay in quantifi- cation of the type and extent of TBI – epidural, subdural , versus intra-parenchymal bleeds; diffuse...example, surgical evacuation of epidural and subdural bleeds within hours of TBI immediately reduces the chance of exposure of brain to blood products

Investigating social functioning after early mild TBI: the quality of parent-child interactions.

Science.gov (United States)

Lalonde, Gabrielle; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H

2018-03-01

The young brain is particularly vulnerable to injury due to inherent physiological and developmental factors, and even mild forms of traumatic brain injury (mTBI) can sometimes result in cognitive and behavioural difficulties. Despite the high prevalence of paediatric mTBI, little is known of its impact on children's social functioning. Parent-child relationships represent the centre of young children's social environments and are therefore ideal contexts for studying the potential effects of mTBI on children's social functioning. The aim of this study was to assess the quality of parent-child interactions after mTBI using observational assessment methods and parental report. The sample included 130 children (18-60 months at recruitment) divided into three groups: children with uncomplicated mTBI (n = 47), children with orthopaedic injury (OI, n = 27), and non-injured children (NI, n = 56). The quality of parent-child interactions was assessed 6 months post-injury using the Mutually Responsive Orientation (MRO) scale, an observational measure which focuses on the dyadic nature of parent-child exchanges, and the Parental Stress Index questionnaire (Parent-Child Dysfunctional Interaction (PCDI) domain). Significant differences with medium effect sizes were found between the mTBI group and the NI group on the MRO, but not between the OI group and the other two groups. PCDI scores did not differ across groups, suggesting that observational measures may be more sensitive to changes in parent-child interactions after TBI. The current findings have implications for children's post-injury social development and highlight the importance of monitoring social outcomes even after minor head injuries. © 2016 The British Psychological Society.

Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Heaton, D.; Yordan, E.; Reddy, S.; Bonomi, P.; Lee, M.S.; Lincoln, S.; Graham, J.; Dolan, T.; Miller, A.; Phillips, A. (Rush Presbyterian-St. Lukes Hospital, Chicago, IL (USA))

1990-09-01

Attempting to improve local disease control in bulky primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.

Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck: a phase I-II study

International Nuclear Information System (INIS)

Amichetti, Maurizio; Romano, Mario; Busana, Lucia; Bolner, Andrea; Fellin, Gianni; Pani, Giuseppe; Tomio, Luigi; Valdagni, Riccardo

1997-01-01

Twenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60-76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity was mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 ± 19% and 5-year actuarial survival was 24 ± 10%. The treatment of nodal metastases from head and neck tumours with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile

Concurrent platinum-based chemotherapy and hyperfractionated radiotherapy with late intensification in advanced head and neck cancer

International Nuclear Information System (INIS)

Glicksman, Arvin S.; Wanebo, Harold J.; Slotman, Gus; Liu Li; Landmann, Christine; Clark, Jeffrey; Zhu, Timothy C.; Lohri, Andreas; Probst, Rudolf

1997-01-01

Purpose: To determine whether a course of hyperfractionated radiation therapy concomitant with escalated radiosensitizing platinum compounds can be administered with acceptable morbidity and achieve a high rate of loco-regional control for Stage III and IV head and neck cancer and whether the patients can be tumor free at the primary site after initial therapy and cured by the additional chemoradiation without radical resection of the primary tumor. Methods and Materials: Patients with Stage III/IV head and neck cancer were treated in this multicenter Phase II Study with 1.8 Gy fraction radiotherapy for 2 weeks, with escalation to 1.2 Gy b.i.d. hyperfractionation to 46.8 Gy. Concomitant continuous infusion cisplatinum (CDDP) 20 mg per meter square on day 1 to 4 and 22 to 25 was given. Reassessment by biopsy of primary and nodes was done. Patients with a complete response continued with hyperfractionated radiotherapy to 75.6 Gy with simultaneous carboplatinum (Carbo), 25 mg per meter square b.i.d. for 12 consecutive treatment days. Patients with residual disease at 46.8 Gy required curative surgery. Seventy-four patients were treated at the three institutions; 20 were Stage III and 54 were Stage IV. All patients had daily mouth care, nutritional, and psychosocial support. Results: This regime was well tolerated. Eighty-five percent of toxicities were Grade 1 or 2 and there was only one Grade 4 hematologic toxicity. Late toxicities included xerostomia in 25 patients, dysplasia in 18, and mild speech impediment in 11. Biopsies of primary site were done after the first course of treatment in 59 patients. Neck dissections were performed in 35 patients. Forty-four of 59 (75%) primary sites and 16 of 35 (46%) lymph nodes had pathologically complete response (CR). Of the 74 patients, only 12 required surgical resection of the primary site. Thirty-five of the 50 node positive patients had neck dissections, 16 of these were CRs at surgery. At 4 years (median follow-up of 26

Advanced MRI in Acute Military TBI

Science.gov (United States)

2013-09-01

having high levels of clustering and a short path length for efficient global and local communications (Latora and Marchiori, 2001; Watts and Strogatz ...Warden, D.L., 2006. Military TBI during the Iraq and Afghanistan wars. J. Head Trauma Rehabil. 21, 398–402. Watts, D.J., Strogatz , S.H., 1998. Collective

The impact of pediatric traumatic brain injury (TBI) on family functioning: a systematic review.

Science.gov (United States)

Rashid, Marghalara; Goez, Helly R; Mabood, Neelam; Damanhoury, Samah; Yager, Jerome Y; Joyce, Anthony S; Newton, Amanda S

2014-01-01

To explore the impact moderate to severe traumatic brain injury (TBI) in a child has on family functioning. The search was conducted using 9 bibliographic databases for articles published between 1980 and 2013. Two reviewers independently screened for inclusion and assessed study quality. Two reviewers extracted study data and a third checked for completeness and accuracy. Findings are presented by three domains: injury-related burden and stress, family adaptability, and family cohesion. Nine observational studies were included. Across the studies, differences between study groups for family functioning varied, but there was a trend for more dysfunction in families whose child had a severe TBI as compared to families whose child had a moderate TBI or orthopedic injury. In three studies, injury-associated burden was persistent post-injury and was highest in families whose child had a severe TBI followed by families with a child who had a moderate TBI. One study found fathers reported more family dysfunction caused by their child's injury compared to mothers. Two studies found that mothers' adaptability depended on social support and stress levels while fathers' adaptability was independent of these factors and injury severity. Moderate to severe TBI has a significant, long-standing impact on family functioning. Factors associated with family adaptability vary by parental role.

Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population

OpenAIRE

Raji, Cyrus A.; Willeumier, Kristen; Taylor, Derek; Tarzwell, Robert; Newberg, Andrew; Henderson, Theodore A.; Amen, Daniel G.

2015-01-01

PTSD and TBI are two common conditions in veteran populations that can be difficult to distinguish clinically. The default mode network (DMN) is abnormal in a multitude of neurological and psychiatric disorders. We hypothesize that brain perfusion SPECT can be applied to diagnostically separate PTSD from TBI reliably in a veteran cohort using DMN regions. A group of 196 veterans (36 with PTSD, 115 with TBI, 45 with PTSD/TBI) were selected from a large multi-site population cohort of individua...

A phase ii study of concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide for elderly patients with stage iii non-small-cell lung cancer

International Nuclear Information System (INIS)

Jeremic, Branislav; Shibamoto, Yuta; Milicic, Biljana; Milisavljevic, Slobodan; Nikolic, Nebojsa; Dagovic, Aleksandar; Aleksandrovic, Jasna; Radosavljevic-Asic, Gordana

1999-01-01

Purpose: To investigate feasibility, toxicity, and efficacy of accelerated hyperfractionated radiation therapy and concurrent carboplatin/oral etoposide in elderly (> 70 years) patients with stage III non-small-cell lung cancer. Methods and Materials: Between January 1988 and June 1993, a total of 58 patients entered a phase II study. Carboplatin (400 mg/m 2 ) was given intravenously on days 1 and 29, and etoposide (50 mg/m 2 ) was given orally on days 1-21 and 29-42. Accelerated hyperfractionated radiotherapy was administered starting on day 1, with a total dose of 51 Gy in 34 fractions over 3.5 weeks. Results: In 55 evaluable patients, the complete response rate was 27% and the overall response rate was 65%. For the 55 patients, the median survival time was 10 months, and the 1-, 2-, and 5-year survival rates were 45%, 24%, and 9.1%, respectively. The median time until relapse was 8 months and the 1-, 2-, and 5-year relapse-free survival rates were 45%, 20%, and 9.1%, respectively. The median time to local recurrence was 14 months and the 5-year local control rate was 13%; the median time to distant metastasis was 18 months and the 5-year distant metastasis-free rate was 15%. Hematological, esophageal, and bronchopulmonary acute grade 3 or 4 toxicities were observed in 22%, 7%, and 4% of the patients, respectively. There was no grade 5 toxicity or late grade ≥ 3 toxicity. Conclusion: Concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide produced relatively low and acceptable toxicity. The survival results appeared to be comparable to those obtained in nonelderly patients with stage III non-small-cell lung cancer treated by full-dose radiation

Hyperfractionated-accelerated radiotherapy followed by radical surgery in locally advanced tumors of the oral cavity

International Nuclear Information System (INIS)

Hoeller, U.; Biertz, I.; Tribius, S.; Alberti, W.; Flinzberg, S.; Schmelzle, R.

2006-01-01

Purpose: to evaluate the outcome of hyperfractionated-accelerated radiotherapy and subsequent planned primary tumor resection and radical neck dissection in locally advanced tumors of the oral cavity. Patients and Methods: this retrospective analysis evaluates 126 subsequent patients who were treated between 1988 and 1997 for locally advanced tumors of the oral cavity (with extension into the oropharynx in 17 patients), 34 (27%) AJCC stage III and 92 (73%) stage IV. Primary tumor and nodal metastases were irradiated with 1.4 Gy bid to a median total dose of 72.8 Gy (range 58.8-75.6 Gy). Then, planned radical surgery of the primary site according to the initial tumor extent and cervical nodes was performed. Median follow-up of living patients was 6 years (range 1-11 years). Results: 4 weeks after radiotherapy, 14 patients (11%) had complete tumor remission, 92 (73%) partial remission, 15 (12%) no change, and five (4%) progressive disease. Complete resection was achieved in 117 (93%) patients (nine incomplete resections). 5-year locoregional control rate was 62 ± 9%, overall survival 36 ± 9%. Surgery-related morbidity occurred in 42 patients (33%; mainly delayed wound healing and fistulae), overall severe treatment-related morbidity in 46 patients (36%). 24/84 relapse-free patients (29%) required a percutaneous gastrostomy or nasal tube ≥ 1 year after therapy. Conclusion: in this study, the outcome of combined curative radiotherapy and planned surgery of the primary tumor and neck nodes was comparable to reported results of hyperfractionated radiotherapy with or without salvage surgery of the neck nodes with respect to locoregional control and overall survival. Planned surgery carries a substantial risk of morbidity and seems to offer no benefit in comparison to salvage surgery of the neck nodes only. Therefore, salvage surgery is preferred. (orig.)

Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population.

Science.gov (United States)

Raji, Cyrus A; Willeumier, Kristen; Taylor, Derek; Tarzwell, Robert; Newberg, Andrew; Henderson, Theodore A; Amen, Daniel G

2015-09-01

PTSD and TBI are two common conditions in veteran populations that can be difficult to distinguish clinically. The default mode network (DMN) is abnormal in a multitude of neurological and psychiatric disorders. We hypothesize that brain perfusion SPECT can be applied to diagnostically separate PTSD from TBI reliably in a veteran cohort using DMN regions. A group of 196 veterans (36 with PTSD, 115 with TBI, 45 with PTSD/TBI) were selected from a large multi-site population cohort of individuals with psychiatric disease. Inclusion criteria were peacetime or wartime veterans regardless of branch of service and included those for whom the traumatic brain injury was not service related. SPECT imaging was performed on this group both at rest and during a concentration task. These measures, as well as the baseline-concentration difference, were then inputted from DMN regions into separate binary logistic regression models controlling for age, gender, race, clinic site, co-morbid psychiatric diseases, TBI severity, whether or not the TBI was service related, and branch of armed service. Predicted probabilities were then inputted into a receiver operating characteristic analysis to compute sensitivity, specificity, and accuracy. Compared to PSTD, persons with TBI were older, male, and had higher rates of bipolar and major depressive disorder (p SPECT separated PTSD from TBI in the veterans with 92 % sensitivity, 85 % specificity, and 94 % accuracy. With concentration scans, there was 85 % sensitivity, 83 % specificity and 89 % accuracy. Baseline-concentration (the difference metric between the two scans) scans were 85 % sensitivity, 80 % specificity, and 87 % accuracy. In separating TBI from PTSD/TBI visual readings of baseline scans had 85 % sensitivity, 81 % specificity, and 83 % accuracy. Concentration scans had 80 % sensitivity, 65 % specificity, and 79 % accuracy. Baseline-concentration scans had 82 % sensitivity, 69 % specificity, and 81�

Can Post mTBI Neurological Soft Signs Predict Postconcussive and PTSD Symptoms : A Pilot Study

Science.gov (United States)

2014-02-01

disorders , including post - traumatic stress disorder ( PTSD ), but they have scarcely been studied in TBI. The present study measured NSS in the...including post - traumatic stress disorder ( PTSD ), but they have scarcely been studied in TBI. The present study measured NSS in the acute aftermath of...Can Post mTBI Neurological Soft Signs Predict Postconcussive and PTSD Symptoms?: A Pilot Study 5a. CONTRACT NUMBER E-Mail:

Neurologic Functional and Quality of Life Outcomes after TBI: Clinic Attendees versus Non-Attendees.

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Patel, Mayur B; Wilson, Laura D; Bregman, Jana A; Leath, Taylor C; Humble, Stephen S; Davidson, Mario A; de Riesthal, Michael R; Guillamondegui, Oscar D

2015-07-01

This investigation describes the relationship between TBI patient demographics, quality of life outcome, and functional status outcome among clinic attendees and non-attendees. Of adult TBI survivors with intracranial hemorrhage, 63 attended our TBI clinic and 167 did not attend. All were telephone surveyed using the Extended-Glasgow Outcome Scale (GOSE), the Quality of Life after Brain Injury (QOLIBRI) scale, and a post-discharge therapy questionnaire. To determine risk factors for GOSE and QOLIBRI outcomes, we created multivariable regression models employing covariates of age, injury characteristics, clinic attendance, insurance status, post-discharge rehabilitation, and time from injury. Compared with those with severe TBI, higher GOSE scores were identified in individuals with both mild (odds ratio [OR]=2.0; 95% confidence interval [CI]: 1.1-3.6) and moderate (OR=4.7; 95% CI: 1.6-14.1) TBIs. In addition, survivors with private insurance had higher GOSE scores, compared with those with public insurance (OR=2.0; 95% CI: 1.1-3.6), workers' compensation (OR=8.4; 95% CI: 2.6-26.9), and no insurance (OR=3.1; 95% CI: 1.6-6.2). Compared with those with severe TBI, QOLIBRI scores were 11.7 points (95% CI: 3.7-19.7) higher in survivors with mild TBI and 17.3 points (95% CI: 3.2-31.5) higher in survivors with moderate TBI. In addition, survivors who received post-discharge rehabilitation had higher QOLIBRI scores by 11.4 points (95% CI: 3.7-19.1) than those who did not. Survivors with private insurance had QOLIBRI scores that were 25.5 points higher (95% CI: 11.3-39.7) than those with workers' compensation and 16.8 points higher (95% CI: 7.4-26.2) than those without insurance. Because neurologic injury severity, insurance status, and receipt of rehabilitation or therapy are independent risk factors for functional and quality of life outcomes, future directions will include improving earlier access to post-TBI rehabilitation, social work services, affordable insurance

Acute tolerance of hyperfractionated accelerated total body irradiation

International Nuclear Information System (INIS)

Latz, D.; Schraube, P.; Wannenmacher, M.

1996-01-01

Background: Acute side effects of total body irradiation lead to intense molestations of the patients. Therefore, it is desirable to take measures to reduce these side effects. In a retrospective study the frequency on acute side effects of a hyperfractionated accelerated total body irradiation was assessed and compared to frequencies of other exposure schedules published in the literature. Additionally the influence of ondansetron on the frequency of nausea and vormiting was investigated. Patients and Method: From 1989 to 1992, 76 patients (47 male, 29 female; median age 38 years) underwent total body irradiation before autologeous bone marrow transplantation. They received 3 daily doses of 1.20 Gy each every 4 h on 4 successive days to a total dose of 14,40 Gy. Thirty-nine patients received 3x8 mg (daily, intravenous or per os) ondansetron during the whole course of irradiation. Results: The most relevant side effects were nausea and vomiting. Patients, who did not receive ondansetron (n=37) showed a nausea and emesis rate of 73%. With ondansetron (n=39) nausea and emesis were reduced to 38%. Also the grade of severity of these side effects was reduced. Conclusions: Ondansetron proved to be an effective medicament for relieving nausea and vormiting during total body irradiation. The results obtained are in concordance with those published in the literature. (orig.) [de

Brain-Derived Neurotrophic Factor in TBI-related mortality: Interrelationships between Genetics and Acute Systemic and CNS BDNF Profiles

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Failla, Michelle D.; Conley, Yvette P.; Wagner, Amy K.

2015-01-01

Background Older adults have higher mortality rates after severe traumatic brain injury (TBI) compared to younger adults. Brain derived neurotrophic factor (BDNF) signaling is altered in aging and is important to TBI given its role in neuronal survival/plasticity and autonomic function. Following experimental TBI, acute BDNF administration has not been efficacious. Clinically, genetic variation in BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) were protective in acute mortality. Post-acutely, these genotypes carried lower mortality risk in older adults, and greater mortality risk among younger adults. Objective Investigate BDNF levels in mortality/outcome following severe TBI in the context of age and genetic risk. Methods CSF and serum BDNF were assessed prospectively during the first week following severe TBI (n=203), and in controls (n=10). Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors. Results CSF BDNF levels tended to be higher post-TBI (p=0.061) versus controls and were associated with time until death (p=0.042). In contrast, serum BDNF levels were reduced post-TBI versus controls (pBDNF serum and gene*age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI (p=0.07). Conclusions BDNF levels predicted mortality, in addition to gene*age interactions, suggesting levels capture additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to injury and age-related increases in pro-apoptotic BDNF target receptors. Negative CSF and serum BDNF correlations post-TBI suggest blood-brain barrier transit alterations. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment. PMID:25979196

Social reintegration of TBI patients: a solution to provide long-term support.

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Bulinski, Leszek

2010-01-01

This article evaluates the effectiveness of a workable long-term program to provide social support for TBI patients, based on the "Academy of Life" concept. Disability after TBI causes numerous disruptions of normal life, which affect the patient, the family, and society. The patient needs the particular kind of support the program was designed to provide. The study involved 200 married couples with a TBI spouse previously enrolled in the "Academy of Life." The methods included documentation analysis, clinical interviews, the Family Bonds Scale, the Social Isolation Scale, and the Social Functions subscale from a battery used to evaluate QOL after TBI. The subjects were examined before and after completing the program. In the first examination all types of family bonds were found to be severely weakened; there was deep social isolation, loneliness, sadness, a feeling of being surrounded by hostility, and no purposeful social activity. The most common form of support from significant others was pity and unwanted interference, accompanied by lack of understanding and social ostracism. In the second examination there was selective improvement of all parameters, significantly greater in patients without PTSD symptoms. The best effects were achieved in the reduction of social dysfunctions, the growth of purposeful social activity, and improvement in the type of support received, and a reduction of selected parameters of social isolation. The program here described is selectively effective for the social reintegration of TBI-patients, especially those without PTSD symptoms.

Contemporary imaging of mild TBI: the journey toward diffusion tensor imaging to assess neuronal damage.

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Fox, W Christopher; Park, Min S; Belverud, Shawn; Klugh, Arnett; Rivet, Dennis; Tomlin, Jeffrey M

2013-04-01

To follow the progression of neuroimaging as a means of non-invasive evaluation of mild traumatic brain injury (mTBI) in order to provide recommendations based on reproducible, defined imaging findings. A comprehensive literature review and analysis of contemporary published articles was performed to study the progression of neuroimaging findings as a non-invasive 'biomarker' for mTBI. Multiple imaging modalities exist to support the evaluation of patients with mTBI, including ultrasound (US), computed tomography (CT), single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI). These techniques continue to evolve with the development of fractional anisotropy (FA), fiber tractography (FT), and diffusion tensor imaging (DTI). Modern imaging techniques, when applied in the appropriate clinical setting, may serve as a valuable tool for diagnosis and management of patients with mTBI. An understanding of modern neuroanatomical imaging will enhance our ability to analyse injury and recognize the manifestations of mTBI.

Alpha desynchronization/synchronization during working memory testing is compromised in acute mild traumatic brain injury (mTBI).

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Arakaki, Xianghong; Shoga, Michael; Li, Lianyang; Zouridakis, George; Tran, Thao; Fonteh, Alfred N; Dawlaty, Jessica; Goldweber, Robert; Pogoda, Janice M; Harrington, Michael G

2018-01-01

Diagnosing and monitoring recovery of patients with mild traumatic brain injury (mTBI) is challenging because of the lack of objective, quantitative measures. Diagnosis is based on description of injuries often not witnessed, subtle neurocognitive symptoms, and neuropsychological testing. Since working memory (WM) is at the center of cognitive functions impaired in mTBI, this study was designed to define objective quantitative electroencephalographic (qEEG) measures of WM processing that may correlate with cognitive changes associated with acute mTBI. First-time mTBI patients and mild peripheral (limb) trauma controls without head injury were recruited from the emergency department. WM was assessed by a continuous performance task (N-back). EEG recordings were obtained during N-back testing on three occasions: within five days, two weeks, and one month after injury. Compared with controls, mTBI patients showed abnormal induced and evoked alpha activity including event-related desynchronization (ERD) and synchronization (ERS). For induced alpha power, TBI patients had excessive frontal ERD on their first and third visit. For evoked alpha, mTBI patients had lower parietal ERD/ERS at the second and third visits. These exploratory qEEG findings offer new and non-invasive candidate measures to characterize the evolution of injury over the first month, with potential to provide much-needed objective measures of brain dysfunction to diagnose and monitor the consequences of mTBI.

Selling the story: narratives and charisma in adults with TBI.

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Jones, Corinne A; Turkstra, Lyn S

2011-01-01

To examine storytelling performance behaviours in adults with traumatic brain injury (TBI) and relate these behaviours to perceived charisma and desirability as a conversation partner. Seven adult males with traumatic brain injury (TBI) told their accident narratives to a male confederate. Ten male undergraduate students rated 1-minute video clips from the beginning of each narrative using the Charismatic Leadership Communication Scale (CLCS). Raters also indicated whether or not they would like to engage in conversation with each participant. Of the performative behaviours analysed, gestures alone significantly influenced CLCS ratings and reported likelihood of engaging in future conversation with the participant. Post-hoc analysis revealed that speech rate was significantly correlated with all of the preceding measures. There was a significant correlation between self- and other-ratings of charisma. The findings suggest that aspects of non-verbal performance, namely gesture use and speech rate, influence how charismatic an individual is perceived to be and how likely someone is to engage in conversation with that person. Variability in these performance behaviours may contribute to the variation in social outcomes seen in the TBI population.

TBI-ROC Part Seven: Traumatic Brain Injury--Technologies to Support Memory and Cognition

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Scherer, Marcia; Elias, Eileen; Weider, Katie

2010-01-01

This article is the seventh of a multi-part series on traumatic brain injury (TBI). The six earlier articles in this series have discussed the individualized nature of TBI and its consequences, the rehabilitation continuum, and interventions at various points along the continuum. As noted throughout the articles, many individuals with TBI…

Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

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2013-07-22

and Post-TBI Psychiatric Disorders 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK...in (282–285)]. Based on a review of the literature, Graham and Cardon reported that substance abuse rates decline following TBI, including mild TBI...preva- lence and outcomes research (1994-2004). Neuropsychol Rehabil (2006) 16(5):537–60. doi:10.1080/09602010500231875 285. Graham DP, Cardon AL. An

Balancing act: the influence of adaptability and cohesion on satisfaction and communication in families facing TBI in Mexico.

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Lehan, Tara J; Stevens, Lillian Flores; Arango-Lasprilla, Juan Carlos; Díaz Sosa, Dulce María; Espinosa Jove, Irma Guadalupe

2012-01-01

Much of what is known about family functioning in the face of traumatic brain injury (TBI) is based on research conducted in the United States. The purpose of this study was to (1) describe the levels of family adaptability, cohesion, communication, and satisfaction as reported by Mexican TBI survivors and their family caregivers, (2) test the hypothesis of the Circumplex Model that balanced families would exhibit better communication and greater satisfaction, and (3) explore how TBI survivors' and their family caregivers' perceptions of family adaptability and cohesion influenced their own and the other's perceptions of family communication and satisfaction. In the majority of dyads, both the TBI survivor and the family caregiver endorsed balanced family adaptability and cohesion. Both TBI survivors and their family caregivers reported a relatively high level of family communication and satisfaction. TBI survivors and family caregivers who reported greater levels of family adaptability and cohesion also endorsed better family communication and greater family satisfaction. In addition, individuals with TBI whose family caregiver endorsed balanced family adaptability and cohesion reported better family communication. Further, family caregivers of TBI survivors who reported balanced family adaptability and cohesion reported better family communication. Implications for research and practice are discussed.

Reliability of a computer and Internet survey (Computer User Profile) used by adults with and without traumatic brain injury (TBI).

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Kilov, Andrea M; Togher, Leanne; Power, Emma

2015-01-01

To determine test-re-test reliability of the 'Computer User Profile' (CUP) in people with and without TBI. The CUP was administered on two occasions to people with and without TBI. The CUP investigated the nature and frequency of participants' computer and Internet use. Intra-class correlation coefficients and kappa coefficients were conducted to measure reliability of individual CUP items. Descriptive statistics were used to summarize content of responses. Sixteen adults with TBI and 40 adults without TBI were included in the study. All participants were reliable in reporting demographic information, frequency of social communication and leisure activities and computer/Internet habits and usage. Adults with TBI were reliable in 77% of their responses to survey items. Adults without TBI were reliable in 88% of their responses to survey items. The CUP was practical and valuable in capturing information about social, leisure, communication and computer/Internet habits of people with and without TBI. Adults without TBI scored more items with satisfactory reliability overall in their surveys. Future studies may include larger samples and could also include an exploration of how people with/without TBI use other digital communication technologies. This may provide further information on determining technology readiness for people with TBI in therapy programmes.

Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) clinical interview and the VA TBI screen.

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Fortier, Catherine Brawn; Amick, Melissa M; Kenna, Alexandra; Milberg, William P; McGlinchey, Regina E

2015-01-01

Mild traumatic brain injury is the signature injury of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND), yet its identification and diagnosis is controversial and fraught with challenges. In 2007, the Department of Veterans Affairs (VA) implemented a policy requiring traumatic brain injury (TBI) screening on all individuals returning from deployment in the OEF/OIF/OND theaters of operation that lead to the rapid and widespread use of the VA TBI screen. The Boston Assessment of TBI-Lifetime (BAT-L) is the first validated, postcombat semistructured clinical interview to characterize head injuries and diagnose TBIs throughout the life span, including prior to, during, and post-military service. Community-dwelling convenience sample of 179 OEF/OIF/OND veterans. BAT-L, VA TBI screen. Based on BAT-L diagnosis of military TBI, the VA TBI screen demonstrated similar sensitivity (0.85) and specificity (0.82) when administered by research staff. When BAT-L diagnosis was compared with historical clinician-administered VA TBI screen in a subset of participants, sensitivity was reduced. The specificity of the research-administered VA TBI screen was more than adequate. The sensitivity of the VA TBI screen, although relatively high, suggests that it does not oversample or "catch all" possible military TBIs. Traumatic brain injuries identified by the BAT-L, but not identified by the VA TBI screen, were predominantly noncombat military injuries. There is potential concern regarding the validity and reliability of the clinician administered VA TBI screen, as we found poor correspondence between it and the BAT-L, as well as low interrater reliability between the clinician-administered and research-administered screen.

Predictive factors for 1-year outcome of a cohort of patients with severe traumatic brain injury (TBI): results from the PariS-TBI study.

Science.gov (United States)

Jourdan, C; Bosserelle, V; Azerad, S; Ghout, I; Bayen, E; Aegerter, P; Weiss, J J; Mateo, J; Lescot, T; Vigué, B; Tazarourte, K; Pradat-Diehl, P; Azouvi, P

2013-01-01

To assess outcome and predicting factors 1 year after a severe traumatic brain injury (TBI). Multi-centre prospective inception cohort study of patients aged 15 or older with a severe TBI in the Parisian area, France. Data were collected prospectively starting the day of injury. One-year evaluation included the relatives-rating of the Dysexecutive Questionnaire (DEX-R), the Glasgow Outcome Scale-Extended (GOSE) and employment. Univariate and multivariate tests were computed. Among 257 survivors, 134 were included (mean age 36 years, 84% men). Good recovery concerned 19%, moderate disability 43% and severe disability 38%. Among patients employed pre-injury, 42% were working, 28% with no job change. DEX-R score was significantly associated with length of education only. Among initial severity measures, only the IMPACT prognostic score was significantly related to GOSE in univariate analyses, while measures relating to early evolution were more significant predictors. In multivariate analyses, independent predictors of GOSE were length of stay in intensive care (LOS), age and education. Independent predictors of employment were LOS and age. Age, education and injury severity are independent predictors of global disability and return to work 1 year after a severe TBI.

The incidence of ARDS and associated mortality in severe TBI using the Berlin definition.

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Aisiku, Imoigele P; Yamal, Jose-Miguel; Doshi, Pratik; Rubin, Maria Laura; Benoit, Julia S; Hannay, Julia; Tilley, Barbara C; Gopinath, Shankar; Robertson, Claudia S

2016-02-01

The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients. The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score. Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01). Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings. Epidemiologic study, level II.

Clinical Utility and Psychometric Properties of the Traumatic Brain Injury Quality of Life Scale (TBI-QOL) in US Military Service Members.

Science.gov (United States)

Lange, Rael T; Brickell, Tracey A; Bailie, Jason M; Tulsky, David S; French, Louis M

2016-01-01

To examine the clinical utility and psychometric properties of the Traumatic Brain Injury Quality of Life (TBI-QOL) scale in a US military population. One hundred fifty-two US military service members (age: M = 34.3, SD = 9.4; 89.5% men) prospectively enrolled from the Walter Reed National Military Medical Center and other nationwide community outreach initiatives. Participants included 99 service members who had sustained a mild traumatic brain injury (TBI) and 53 injured or noninjured controls without TBI (n = 29 and n = 24, respectively). Participants completed the TBI-QOL scale and 5 other behavioral measures, on average, 33.8 months postinjury (SD = 37.9). Fourteen TBI-QOL subscales; Neurobehavioral Symptom Inventory; Posttraumatic Stress Disorder Checklist-Civilian version; Alcohol Use Disorders Identification Test; Combat Exposure Scale. The internal consistency reliability of the TBI-QOL scales ranged from α = .91 to α = .98. The convergent and discriminant validity of the 14 TBI-QOL subscales was high. The mild TBI group had significantly worse scores on 10 of the 14 TBI-QOL subscales than the control group (range, P quality of life in a mild TBI military sample. Additional research is recommended to further evaluate the clinical utility of the TBI-QOL scale in both military and civilian settings.

Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial

International Nuclear Information System (INIS)

Allal, Abdelkarim S.; Bieri, Sabine; Bruendler, Marie-Anne; Soravia, Claudio; Gertsch, Philippe; Bernier, Jacques; Morel, Philippe; Roth, Arnaud D.

2002-01-01

Purpose: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. Methods and Materials: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. Results: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located ≤6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). Conclusion: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

Directory of Open Access Journals (Sweden)

Veronica eSebastian

2013-05-01

Full Text Available Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within in a single task. Thus we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM with a sequence of 4 baited and 4 unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test two weeks after training. Multiple training trials not only provide robust training, but also test the subjects’ ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing two weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze.

Science.gov (United States)

Sebastian, Veronica; Diallo, Aissatou; Ling, Douglas S F; Serrano, Peter A

2013-01-01

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

What Are Common Traumatic Brain Injury (TBI) Symptoms?

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... sleep habits Behavior or mood changes Trouble with memory, concentration, attention, or thinking Loss of consciousness lasting a few ... may have caused a TBI should seek medical attention. 4 ... Traumatic brain injury information page . Retrieved May 4, 2018, from https://www. ...

Cognitive ability predicts motor learning on a virtual reality game in patients with TBI.

Science.gov (United States)

O'Neil, Rochelle L; Skeel, Reid L; Ustinova, Ksenia I

2013-01-01

Virtual reality games and simulations have been utilized successfully for motor rehabilitation of individuals with traumatic brain injury (TBI). Little is known, however, how TBI-related cognitive decline affects learning of motor tasks in virtual environments. To fill this gap, we examined learning within a virtual reality game involving various reaching motions in 14 patients with TBI and 15 healthy individuals with different cognitive abilities. All participants practiced ten 90-second gaming trials to assess various aspects of motor learning. Cognitive abilities were assessed with a battery of tests including measures of memory, executive functioning, and visuospatial ability. Overall, participants with TBI showed both reduced performance and a slower learning rate in the virtual reality game compared to healthy individuals. Numerous correlations between overall performance and several of the cognitive ability domains were revealed for both the patient and control groups, with the best predictor being overall cognitive ability. The results may provide a starting point for rehabilitation programs regarding which cognitive domains interact with motor learning.

Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

Science.gov (United States)

Barrett, K F; Masel, B; Patterson, J; Scheibel, R S; Corson, K P; Mader, J T

2004-01-01

To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

Backscatter Correction Algorithm for TBI Treatment Conditions

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Sanchez-Nieto, B.; Sanchez-Doblado, F.; Arrans, R.; Terron, J.A. [Dpto. Fisiología Médica y Biofísica, Universidad de Sevilla, Avda. Sánchez Pizjuán, 4. E-41009, Sevilla (Spain); Errazquin, L. [Servicio Oncología Radioterápica, Hospital Univ.V. Macarena. Dr. Fedriani, s/n. E-41009, Sevilla (Spain)

2015-01-15

The accuracy requirements in target dose delivery is, according to ICRU, ±5%. This is so not only in standard radiotherapy but also in total body irradiation (TBI). Physical dosimetry plays an important role in achieving this recommended level. The semi-infinite phantoms, customarily used for dosimetry purposes, give scatter conditions different to those of the finite thickness of the patient. So dose calculated in patient’s points close to beam exit surface may be overestimated. It is then necessary to quantify the backscatter factor in order to decrease the uncertainty in this dose calculation. The backward scatter has been well studied at standard distances. The present work intends to evaluate the backscatter phenomenon under our particular TBI treatment conditions. As a consequence of this study, a semi-empirical expression has been derived to calculate (within 0.3% uncertainty) the backscatter factor. This factor depends lineally on the depth and exponentially on the underlying tissue. Differences found in the qualitative behavior with respect to standard distances are due to scatter in the bunker wall close to the measurement point.

Analysis of late complications after rapid hyperfractionated radiotherapy in advanced head and neck cancers

International Nuclear Information System (INIS)

Nguyen, T.D.; Panis, X.; Froissart, D.; Legros, M.; Coninx, P.; Loirette, M.

1988-01-01

Late effects were analyzed in a series of 39 patients with a 2-year minimal follow-up who were treated by rapid hyperfractionated radiotherapy. The total dose was 66-72 Gy delivered in two series of 33-36 Gy separated by a 2-4 week rest interval. The number of daily fractions ranged from 8 to 6 and the interval between each fraction was 2 hr. Late complications consisted of cervical fibrosis, mucosal necrosis, bone necrosis, trismus, and laryngeal edema. Seventy percent of patients experienced late complications, and in 54% of cases, these reactions were considered severe, causing death in 13% of patients. No relationship was found between field sizes, dosimetric data and type and frequency of late effects. It is therefore suggested that the interval between two daily sessions in any multifractionated protocol may be of critical importance

Modeling, planning and XiO R CMS validation of TBI treatment (extended SSD 400 cm); Modelacion, planificacion y validacion del XiO CMS para tratamientos TBI (SSD extendida de 400 cm)

Energy Technology Data Exchange (ETDEWEB)

Teijeiro, A.; Pereira, L.; Moral, F. del; Vazquez, J.; Lopez Medina, A.; Meal, A.; Andrade Alvarez, B.; Salgado Fernandez, M.; Munoz, V.

2011-07-01

The whole body irradiation (TBI) is a radiotherapy technique previously used a bone marrow transplant and for certain blood diseases, in which a patient is irradiated to extended distance (SSD from 350 to 400). The aim of the TBI is to kill tumor cells in the receiver and prevent rejection of transplanted bone marrow. The dose is prescribed at the midpoint of the abdomen around the navel wing. The most planners not permit the treatment of patients with a much higher SSD to 100 cm, also using the table TBI with spoiler to increase skin dose should be taken into account This requires measurements and checks ad hoc if you use a planner, because modeling is not optimized a priori for an SSD of 400 cm.

Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

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Hao Yan

2016-01-01

Full Text Available Traumatic brain injuries (TBIs are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub, left hippocampus (the personal experience binding hub, and left parahippocampal gyrus (the contextual association hub were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory and the right medial frontal gyrus (MeFG in the anterior prefrontal cortex (PFC. We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging.

Review of the literature on the use of social media by people with traumatic brain injury (TBI).

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Brunner, Melissa; Hemsley, Bronwyn; Palmer, Stuart; Dann, Stephen; Togher, Leanne

2015-01-01

To review the literature relating to use of social media by people with a traumatic brain injury (TBI), specifically its use for social engagement, information exchange or rehabilitation. A systematic review with a qualitative meta-synthesis of content themes was conducted. In June 2014, 10 databases were searched for relevant, peer-reviewed research studies in English that related to both TBI and social media. Sixteen studies met the inclusion criteria, with Facebook™ and Twitter™ being the most common social media represented in the included studies. Content analysis identified three major categories of meaning in relation to social media and TBI: (1) risks and benefits; (2) barriers and facilitators; and (3) purposes of use of social media. A greater emphasis was evident regarding potential risks and apparent barriers to social media use, with little focus on facilitators of successful use by people with TBI. Research to date reveals a range of benefits to the use of social media by people with TBI however there is little empirical research investigating its use. Further research focusing on ways to remove the barriers and increase facilitators for the use of social media by people with TBI is needed.

Home-based, Online Mindfulness and Cognitive Training for Soldiers and Veterans with TBI

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2017-10-01

AWARD NUMBER: W81XWH-16-1-0685 TITLE: Home-based, Online Mindfulness and Cognitive Training for Soldiers and Veterans with TBI PRINCIPAL...TITLE AND SUBTITLE Home-based, Online Mindfulness and Cognitive Training for Soldiers and Veterans with TBI 5a. CONTRACT NUMBER 5b. GRANT NUMBER...individuated brain training program (cognitive training + mindfulness /stress- reduction training) with caregiver support portal and lifestyle monitor is

Histopathological changes in the irradiated normal organs of guinea pigs with conventional fractionation and hyperfractionation

International Nuclear Information System (INIS)

Inomata, Taisuke; Itoh, Satoshi; Tsuboi, Nobuaki

1998-01-01

Guinea pigs were divided into groups according to four irradiation schedules : 2 Gy/3 Gy x 1/day, five fractions/week, total 80 Gy/81 Gy (A/C group) and 1.0 Gy/1.5 Gy x 2/day, ten fractions/week, total 80 Gy/81 Gy (B/D group). The A group and the C group pathologically caused severe damage in the kidney six and three months after irradiation, respectively. In the B group pathological analysis suggested that only slight-to-moderate changes were occurred in the Bowman's capsule. The D group caused slight damage in the kidney six months after irradiation. Hyperfractionation (B/D group) used in this protocol can clearly reduce radiation damage in the kidney of guinea pigs as compared with conventional fractionation (A/C group). (author)

Trajectories of life satisfaction after TBI: Influence of life roles, age, cognitive disability, and depressive symptoms

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Juengst, Shannon B.; Adams, Leah M.; Bogner, Jennifer A.; Arenth, Patricia M.; O’Neil-Pirozzi, Therese M.; Dreer, Laura E.; Hart, Tessa; Bergquist, Thomas F.; Bombardier, Charles H.; Dijkers, Marcel P.; Wagner, Amy K.

2015-01-01

Objectives 1) Identify life satisfaction trajectories after moderate to severe traumatic brain injury (TBI), 2) establish a predictive model for these trajectories across the first 5 years post-injury, and 3) describe differences in these life satisfaction trajectory groups, focusing on age, depressive symptoms, disability, and participation in specific life roles,. Research Method Analysis of the longitudinal TBI Model Systems National Database was performed on data collected prospectively at 1, 2, and 5 years post-TBI. Participants (n=3,012) had a moderate to severe TBI and were 16 years old and older. Results Four life satisfaction trajectories were identified across the first 5 years post-injury, including: Stable Satisfaction, Initial Satisfaction Declining, Initial Dissatisfaction Improving, and Stable Dissatisfaction. Age, depressive symptoms, cognitive disability, and life role participation as a worker, leisure participant, and/ or religious participant at one year post-injury significantly predicted trajectory group membership. Life role participation and depressive symptoms were strong predictors of life satisfaction trajectories across the first 5 years post TBI. Conclusions The previously documented loss of life roles and prevalence of depression after a moderate to severe TBI make this a vulnerable population for whom low or declining life satisfaction is a particularly high risk. Examining individual life role participation may help to identify relevant foci for community-based rehabilitation interventions or supports. PMID:26618215

Psychological and marital adjustment in couples following a traumatic brain injury (TBI): a critical review.

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Blais, Marie Claude; Boisvert, Jean-Marie

2005-12-20

The first part of this paper examines current data describing the psychological and marital adjustment of couples following a traumatic brain injury (TBI). Although these findings reveal some discrepancies, they highlight that adjustment following a TBI represents a genuine challenge for those involved in the process. The second part moves toward the examination of factors associated with psychological and marital adjustment in both couple partners. Here again, there exists a large diversity in empirical data and theoretical models informing this emerging area of interest. Nevertheless, cognitive variables such as coping skills are commonly seen as critical variables to explain the adjustment level in people with TBI and their spouse/caregivers. Concurrently with the discussion of the methodological issues and pitfalls encountered in this area of research, the conclusion provides suggestions of further steps to undertake in this endeavour toward a better understanding of the adjustment process following TBI.

Linac-based total body irradiation (TBI) with volumetric modulated arc therapy (VMAT)

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Tas, B.; Durmus, I. F.; Okumus, A.; Uzel, O. E.

2017-02-01

To evaluate dose distribution of Volumetric modulated arc therapy (VMAT) planning tecnique using Versa HD® lineer accelerator to deliver Total Body Irradiation (TBI) on the coach. Eight TBI patient's Treatment Planning System (TPS) were performed with dual arc VMAT for each patient. The VMAT-TBI consisted of three isocentres and three dual overlapping arcs. The prescribed dose was 12 Gy. Mean dose to lung and kidney were restricted less than 10 Gy and max. dose to lens were restricted less than 6 Gy. The plans were verified using 2D array and ion chamber. The comparison between calculation and measurement were made by γ-index analysis and absolute dose. An average total delivery time was determined 923±34 seconds and an average MU was determined 2614±228 MUs for dual arc VMAT. Mean dose to lungs was 9.7±0.2 Gy, mean dose to kidneys was 8.8±0.3 Gy, max. dose to lens was 5.5±0.3 Gy and max. dose was 14.6±0.3 Gy, HI of PTV was 1.13±0.2, mean dose to PTV was 12.6±1.5 Gy and mean γ-index pass rate was %97.1±1.9. The results show that the tecnique for TBI using VMAT on the treatment coach is feasible.

Growth impairment after TBI of leukemia survivors children: a model- based investigation.

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Galletto, Chiara; Gliozzi, Antonio; Nucera, Daniele; Bertorello, Nicoletta; Biasin, Eleonora; Corrias, Andrea; Chiabotto, Patrizia; Fagioli, Franca; Guiot, Caterina

2014-10-13

Children receiving Total Body Irradiation (TBI) in preparation for Hematopoietic Stem Cell Transplantation (HSCT) are at risk for Growth Hormone Deficiency (GHD), which sometimes severely compromises their Final Height (FH). To better represent the impact of such therapies on growth we apply a mathematical model, which accounts both for the gompertzian-like growth trend and the hormone-related 'spurts', and evaluate how the parameter values estimated on the children undergoing TBI differ from those of the matched normal population. 25 patients long-term childhood lymphoblastic and myeloid acute leukaemia survivors followed at Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital (Turin, Italy) were retrospectively analysed for assessing the influence of TBI on their longitudinal growth and for validating a new method to estimate the GH therapy effects. Six were treated with GH therapy after a GHD diagnosis. We show that when TBI was performed before puberty overall growth and pubertal duration were significantly impaired, but such growth limitations were completely reverted in the small sample (6 over 25) of children who underwent GH replacement therapies. Since in principle the model could account for any additional growth 'spurt' induced by therapy, it may become a useful 'simulation' tool for paediatricians for comparing the predicted therapy effectiveness depending on its timing and dosage.

Concussion in the Military: an Evidence-Base Review of mTBI in US Military Personnel Focused on Posttraumatic Headache.

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Holtkamp, Matthew D; Grimes, Jamie; Ling, Geoffrey

2016-06-01

Traumatic brain injury (TBI) is defined as an alteration in brain function caused by an external force. Mild TBI or concussion is now well recognized to be a risk of military service as well as participation in athletic sports such as football. Posttraumatic headache (PTH) is the most common symptom after mTBI in US service members. PTH most commonly presents with migraine-like headache features. The following is an overview of the epidemiology, pathophysiology, clinical course, prognosis, complications, and treatment of mTBI and associated comorbidities with a focus on PTH. There is a particular emphasis on emerging evidence-based clinical practice. One important medical consequence of the recognition that mTBI is a highly prevalent among military service members is that the Department of Defense (DoD) is dedicating significant financial and intellectual resources to better understanding and developing treatments for TBI. The identification of the importance of TBI among the US military population has had the added benefit of increasing awareness of this condition among civilian populations, particularly those engaged in both professional and youth sports. The NIH and NSF are also supporting important TBI research. President Obama's Brain Initiative is also providing additional impetus for these efforts. Unfortunately, the understanding of the acute and chronic effects of mTBI on the brain remains limited. Gratefully, there is hope that through innovative research, there will be advances in elucidating the underlying pathophysiology, which will lead to clinical and prognostic indicators, ultimately resulting in new treatment options for this very complicated set of disorders.

Survival and Injury Outcome After TBI: Influence of Pre- and Post-Exposure to Caffeine

Science.gov (United States)

2012-10-01

10-1-0757 TITLE: Survival and Injury Outcome After TBI: Influence of Pre- and Post- Exposure to Caffeine PRINCIPAL INVESTIGATOR...Lusardi, Ph.D. Survival and Injury Outcome After TBI: Influence of Pre- and Post- Exposure to Caffeine 33 Legacy Emanual Hospital & Health Center...Phase 1: Study the prophylactic effects of caffeine exposure prior to FPI

COMPARISON OF CONVENTIONAL RADIATIOTHERAPY AND ACCELERATED HYPERFRACTIONATED RADIATIOTHERAPY IN CHEMORADIATION TREATMENT FOR SMALL CELL LUNG CANCER

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I. A. Gulidov

2013-01-01

Full Text Available The 5-year treatment outcomes of 69 patients with stage IIA–IIIA locally advanced small cell lung cancer have been presented. Accelerated hyperfractionated radiotherapy was administered in the uneven daily dose fractionation (single dose of 1 + 1,5 Gy with a 5–6hour interval to a total dose of 60–70 Gy depending on the health status and lung function. The complete response was achieved in 13 (42 % patients, the median survival was 28 months and the 5-year survival rate was 26,2 %. Grade III lung and pericardium toxicities (according to RTOG toxicity scale were observed in 3,2 % and 6,5 % of patients, respectively. No grade III–IV radiation-induced blood and esophageal damages were found.

Deep pockets or blueprint for change: traumatic brain injury (TBI) proactive strategy.

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Wood, D W; Pohl, S; Lawler, S; Okamoto, G

1998-09-01

The Pacific Conference scheduled for October 1-3, 1988, is a critical event in the development of an integrated community-based plan for a comprehensive continuum of services to address the "silent epidemic," Traumatic Brain Injured (TBI). This paper provides insights of the complex nature and the special problems faced by the TBI survivors; their families, natural supports and caregivers, as well as the health, social and educational care providers in Hawaii. Process for the development of the community plan is presented.

There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a pediatric oncology group phase III trial comparing conventional vs. hyperfractionated radiotherapy

International Nuclear Information System (INIS)

Mandell, Lynda R.; Kadota, Richard; Freeman, Carolyn; Douglass, Edwin C.; Fontanesi, James; Cohen, Michael E.; Kovnar, Edward; Burger, Peter; Sanford, Robert A.; Kepner, James; Friedman, Henry; Kun, Larry E.

1999-01-01

Purpose: In June 1992, POG began accrual to a phase III study, POG-9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem tumor treated with 100 mg/m 2 of infusional cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. Methods and Materials: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for a diffusely infiltrating pontine lesion. Treatment consisted of a six-week course of local field radiotherapy with either once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG-8495) (arm 2). Because of previously reported poor results with conventional radiotherapy alone, cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the phase I cisplatin dose escalation trial, POG-9139, 100 mg/m 2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during weeks 3 and 5. One hundred thirty eligible patients were treated on protocol, 66 on arm 1 and 64 on arm 2. Results: The results we report are from time of diagnosis through October 1997. For patients treated on arm 1, the median time to disease progression (defined as time to off study) was 6 months (range 2-15 months) and the median time to death 8.5 months (range 3-24 months); survival at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the corresponding values were 5 months (range 1-12 months) and 8 months (range 1-23 months), with 1- and 2-year

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

OpenAIRE

Sebastian, Veronica; Diallo, Aissatou; Ling, Douglas S. F.; Serrano, Peter A.

2013-01-01

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either r...

High-dose, hyperfractionated, accelerated radiotherapy using a concurrent boost for the treatment of nonsmall cell lung cancer: unusual toxicity and promising early results

International Nuclear Information System (INIS)

King, Stephen C.; Acker, Jeffrey C.; Kussin, Peter S.; Marks, Lawrence B.; Weeks, Kenneth J.; Leopold, Kenneth A.

1996-01-01

Purpose: The treatment of nonsmall cell lung cancer (NSCLC) with conventional radiotherapy (RT) results in inadequate local tumor control and survival. We report results of a Phase II trial designed to treat patients with a significantly increased total dose administered in a reduced overall treatment time using a hyperfractionated, accelerated treatment schedule with a concurrent boost technique. Methods and Materials: A total of 49 patients with unresectable Stage IIIA/IIIB (38 patients) or medically inoperable Stage I/II (11 patients) NSCLC were prospectively enrolled in this protocol. Radiation therapy was administered twice daily, 5 days/week with > 6 h between each treatment. The primary tumor and adjacent enlarged lymph nodes were treated to a total dose of 73.6 Gy in 46 fractions of 1.6 Gy each. Using a concurrent boost technique, electively irradiated nodal regions were simultaneously treated with a dose of 1.25 Gy/fraction for the first 36 fractions to a total dose of 45 Gy. Results: Median survival for the entire group of 49 patients is 15.3 months. Actuarial survival at 2 years is 46%: 60% for 11 Stage I/II patients, 55% for 21 Stage IIIA patients, and 26% for 17 Stage IIIB patients. The actuarial rate of freedom from local progression at 2 years is 64% for the entire group of 49 patients: 62% for Stage I/II patients, 70% for Stage IIIA patients, and 55% for Stage IIIB patients. Patients who underwent serial bronchoscopic reevaluation (4 Stage I/II, 8 Stage IIIA, and 6 Stage IIIB) have an actuarial rate of local control of 71% at 2 years. The median total treatment time was 32 days. Nine of 49 patients (18%) experienced Grade III acute esophageal toxicity. The 2-year actuarial risk of Grade III or greater late toxicity is 30%. The 2-year actuarial rate of severe-late pulmonary and skin-subcutaneous toxicity is 20% and 15%, respectively. Conclusion: This treatment regimen administers a substantially higher biologically effective dose compared with

The consequence of spatial visual processing dysfunction caused by traumatic brain injury (TBI).

Science.gov (United States)

Padula, William V; Capo-Aponte, Jose E; Padula, William V; Singman, Eric L; Jenness, Jonathan

2017-01-01

A bi-modal visual processing model is supported by research to affect dysfunction following a traumatic brain injury (TBI). TBI causes dysfunction of visual processing affecting binocularity, spatial orientation, posture and balance. Research demonstrates that prescription of prisms influence the plasticity between spatial visual processing and motor-sensory systems improving visual processing and reducing symptoms following a TBI. The rationale demonstrates that visual processing underlies the functional aspects of binocularity, balance and posture. The bi-modal visual process maintains plasticity for efficiency. Compromise causes Post Trauma Vision Syndrome (PTVS) and Visual Midline Shift Syndrome (VMSS). Rehabilitation through use of lenses, prisms and sectoral occlusion has inter-professional implications in rehabilitation affecting the plasticity of the bi-modal visual process, thereby improving binocularity, spatial orientation, posture and balance Main outcomes: This review provides an opportunity to create a new perspective of the consequences of TBI on visual processing and the symptoms that are often caused by trauma. It also serves to provide a perspective of visual processing dysfunction that has potential for developing new approaches of rehabilitation. Understanding vision as a bi-modal process facilitates a new perspective of visual processing and the potentials for rehabilitation following a concussion, brain injury or other neurological events.

Technology and its role in rehabilitation for people with cognitive-communication disability following a traumatic brain injury (TBI).

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Brunner, Melissa; Hemsley, Bronwyn; Togher, Leanne; Palmer, Stuart

2017-01-01

To review the literature on communication technologies in rehabilitation for people with a traumatic brain injury (TBI), and: (a) determine its application to cognitive-communicative rehabilitation, and b) develop a model to guide communication technology use with people after TBI. This integrative literature review of communication technology in TBI rehabilitation and cognitive-communication involved searching nine scientific databases and included 95 studies. Three major types of communication technologies (assistive technology, augmentative and alternative communication technology, and information communication technology) and multiple factors relating to use of technology by or with people after TBI were categorized according to: (i) individual needs, motivations and goals; (ii) individual impairments, activities, participation and environmental factors; and (iii) technologies. While there is substantial research relating to communication technologies and cognitive rehabilitation after TBI, little relates specifically to cognitive-communication rehabilitation. Further investigation is needed into the experiences and views of people with TBI who use communication technologies, to provide the 'user' perspective and influence user-centred design. Research is necessary to investigate the training interventions that address factors fundamental for success, and any impact on communication. The proposed model provides an evidence-based framework for incorporating technology into speech pathology clinical practice and research.

TBI server: a web server for predicting ion effects in RNA folding.

Science.gov (United States)

Zhu, Yuhong; He, Zhaojian; Chen, Shi-Jie

2015-01-01

Metal ions play a critical role in the stabilization of RNA structures. Therefore, accurate prediction of the ion effects in RNA folding can have a far-reaching impact on our understanding of RNA structure and function. Multivalent ions, especially Mg²⁺, are essential for RNA tertiary structure formation. These ions can possibly become strongly correlated in the close vicinity of RNA surface. Most of the currently available software packages, which have widespread success in predicting ion effects in biomolecular systems, however, do not explicitly account for the ion correlation effect. Therefore, it is important to develop a software package/web server for the prediction of ion electrostatics in RNA folding by including ion correlation effects. The TBI web server http://rna.physics.missouri.edu/tbi_index.html provides predictions for the total electrostatic free energy, the different free energy components, and the mean number and the most probable distributions of the bound ions. A novel feature of the TBI server is its ability to account for ion correlation and ion distribution fluctuation effects. By accounting for the ion correlation and fluctuation effects, the TBI server is a unique online tool for computing ion-mediated electrostatic properties for given RNA structures. The results can provide important data for in-depth analysis for ion effects in RNA folding including the ion-dependence of folding stability, ion uptake in the folding process, and the interplay between the different energetic components.

TBI server: a web server for predicting ion effects in RNA folding.

Directory of Open Access Journals (Sweden)

Yuhong Zhu

Full Text Available Metal ions play a critical role in the stabilization of RNA structures. Therefore, accurate prediction of the ion effects in RNA folding can have a far-reaching impact on our understanding of RNA structure and function. Multivalent ions, especially Mg²⁺, are essential for RNA tertiary structure formation. These ions can possibly become strongly correlated in the close vicinity of RNA surface. Most of the currently available software packages, which have widespread success in predicting ion effects in biomolecular systems, however, do not explicitly account for the ion correlation effect. Therefore, it is important to develop a software package/web server for the prediction of ion electrostatics in RNA folding by including ion correlation effects.The TBI web server http://rna.physics.missouri.edu/tbi_index.html provides predictions for the total electrostatic free energy, the different free energy components, and the mean number and the most probable distributions of the bound ions. A novel feature of the TBI server is its ability to account for ion correlation and ion distribution fluctuation effects.By accounting for the ion correlation and fluctuation effects, the TBI server is a unique online tool for computing ion-mediated electrostatic properties for given RNA structures. The results can provide important data for in-depth analysis for ion effects in RNA folding including the ion-dependence of folding stability, ion uptake in the folding process, and the interplay between the different energetic components.

Mathematical models of blast induced TBI: current status, challenges and prospects

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Raj K Gupta

2013-05-01

Full Text Available Blast induced traumatic brain injury (TBI has become a signature wound of recent military activities and is the leading cause of death and long-term disability among U.S. soldiers. The current limited understanding of brain injury mechanisms impedes the development of protection, diagnostic and treatment strategies. We believe mathematical models of blast wave brain injury biomechanics and neurobiology, complemented with in vitro and in vivo experimental studies, will enable a better understanding of injury mechanisms and accelerate the development of both protective and treatment strategies. The goal of this paper is to review the current state of the art in mathematical and computational modeling of blast induced TBI, identify research gaps and recommend future developments. A brief overview of blast wave physics, injury biomechanics and the neurobiology of brain injury is used as a foundation for a more detailed discussion of multiscale mathematical models of primary biomechanics and secondary injury and repair mechanisms. The paper also presents a discussion of model development strategies, experimental approaches to generate benchmark data for model validation and potential applications of the model for prevention and protection against blast wave TBI.

Improving Balance in TBI Using a Low-Cost Customized Virtual Reality Rehabilitation Tool

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2016-10-01

quality of life , and cognitive function. This design will allow us to assess the efficacy of IQ as a customizable balance treatment in TBI, and to...VANJHCS.  As  such,  we  have   explored  additional  avenues  and  are   working  closely  with  the  dedicated...AWARD NUMBER: W81XWH-14-2-0150 TITLE: Improving Balance in TBI Using a Low-Cost Customized Virtual Reality Rehabilitation Tool PRINCIPAL

A Randomized Controlled Trial of the Group-Based Modified Story Memory Technique in TBI

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2017-10-01

major task was to coordinate the study staff for the clinical trial. This is also a time- consuming processing that involves hiring the appropriate...for improving NLM in individuals with Multiple Sclerosis (MS) and TBI across three realms of functioning, objective behavior , brain functioning and...improving new learning and memory in individuals with Multiple Sclerosis (MS) and TBI across three realms of functioning, objective behavior , brain

Mission Connect Mild TBI Translational Research Consortium

Science.gov (United States)

2013-08-01

global volumetry using tensor-based morphometry, tissue microstructural integrity using diffusion tensor imaging (DTI), and T2-weighted images for...GM and CSF volumetry were not different between controls and mTBI. Consistent with a previous report (3), subtle changes in WM microstructure due...function is warranted. Figure 1. Representative scatter plots of global volumetry of (A) sulcal CSF, (B) neocortical GM and bar graphs of regional coronal

Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer

International Nuclear Information System (INIS)

Movsas, Benjamin; Hanlon, Alexandra L.; Lanciano, Rachelle; Scher, Richard M.; Weiner, Louis M.; Sigurdson, Elin R.; Hoffman, John P.; Eisenberg, Burton L.; Cooper, Harry S.; Provins, Susan; Coia, Lawrence R.

1998-01-01

Purpose: To determine the acute toxicity, post-operative complications, pathologic response and extent of downstaging to high dose pre-operative radiation using a hyperfractionated radiation boost and concurrent chemotherapy in a prospective Phase I trial. Materials and Methods: To be eligible for this study, patients had to have adenocarcinoma of the rectum less than 12 cm from the anal verge with either Stage T4 or T3 but greater than 4 cm or greater than 40% of the bowel circumference. All patients received 45 Gy pelvic radiation (1.8 Gy per fraction). Subsequent radiation was given to the region of the gross tumor with a 2 cm margin. This 'boost' treatment was given at 1.2 Gy twice daily to a total dose of 54.6 Gy for Level I, 57 Gy for Level II, and 61.8 Gy for Level III. 5-FU was given at 1g/m 2 over 24 hours for a four day infusion during the first and sixth weeks of radiation, with the second course concurrent with the hyperfractionated radiation. Surgical resection was carried out 4-6 weeks following completion of chemoradiation (in curative cases) and additional adjuvant chemotherapy consisting of 5-FU and Leucovorin was given for an additional 4 monthly cycles Days 1 through 5 beginning four weeks post surgery. Results: Twenty-seven patients, age 40-82 (median 61), completed the initial course of chemoradiation and are included in the analysis of toxicity. The median follow-up is 27 months (range 8-68). Eleven patients were treated to a dose of 54.6 Gy, nine patients to 57 Gy, and seven patients to 61.8 Gy. Twenty-one patients had T3 tumors, and six patients T4 tumors. Grade III acute toxicity from chemoradiation included proctitis (5 patients), dermatitis (9), diarrhea (five), leukopenia (1), cardiac (1). Grade IV toxicities included one patient with diarrhea (on dose Level I) and one patient (on dose Level III) with cardiac toxicity (unrelated to radiation). Surgical resection consisted of abdominal perineal resection in 16 and low anterior resection

MVP Chemotherapy and Hyperfractionated Radiotherapy for Stage III Unresectable Non-Small Cell Lung Cancer - Randomized for maintenance Chemotherapy vs. Observation; Preliminary Report-

International Nuclear Information System (INIS)

Choi, Euk Kyung; Chang, Hye Sook; Suh, Cheol Won

1991-01-01

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991. Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGY following 3 cycles of induction MVP (Mitomycin C 6 mg/m 2 , vinblastine 6 mg/m 2 , Cisplatin 60 mg/m 2 ) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 16 were analyzed for this preliminary report. The response rate of induction chemotherapy was 62.5%; partial response, 50% and minimal response, 12.5%. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue

Rates of TBI-related Emergency Department Visits, Hospitalizations, and Deaths by Sex - United States, 2001 – 2010

Data.gov (United States)

U.S. Department of Health & Human Services — Overall rates of TBI climbed slowly from 2001 through 2007, then spiked sharply in 2008 and continued to climb through 2010. The increase in TBI rates in 2008 was...

Hyperfractionated stereotactic reirradiation for recurrent head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Cvek, Jakub; Knybel, Lukas; Skacelikova, Eva; Otahal, Bretislav; Molenda, Lukas; Feltl, David [University Hospital Ostrava, Department of Oncology, Ostrava (Czech Republic); Stransky, Jiri; Res, Oldrich [University Hospital Ostrava, Department of Maxilofacial Surgery, Ostrava (Czech Republic); Matousek, Petr; Zelenik, Karol [University Hospital Ostrava, Department of Otolaryngology, Ostrava (Czech Republic)

2016-01-15

The goal of this work was to evaluate the efficacy and toxicity of hyperfractionated stereotactic reirradiation (re-RT) as a treatment for inoperable, recurrent, or second primary head and neck squamous cell cancer (HNSCC) that is not suitable for systemic treatment. Forty patients with recurrent or second primary HNSCC were included in this study. The patients had a median gross tumor volume of 76 ml (range 14-193 ml) and a previous radiotherapy dose greater than 60 Gy. Treatment was designed to cover 95 % of the planning target volume (PTV, defined as gross tumor volume [GTV] + 3 mm to account for microscopic spreading, with no additional set-up margin) with the prescribed dose (48 Gy in 16 fractions b.i.d.). Treatment was administered twice daily with a minimum 6 h gap. Uninvolved lymph nodes were not irradiated. Treatment was completed as planned for all patients (with median duration of 11 days, range 9-14 days). Acute toxicity was evaluated using the RTOG/EORTC scale. A 37 % incidence of grade 3 mucositis was observed, with recovery time of ≤ 4 weeks for all of these patients. Acute skin toxicity was never observed to be higher than grade 2. Late toxicity was also evaluated according to the RTOG/EORTC scale. Mandible radionecrosis was seen in 4 cases (10 %); however, neither carotid blowout syndrome nor other grade 4 late toxicity occurred. One-year overall survival (OS) and local progression-free survival (L-PFS) were found to be 33 and 44 %, respectively. Performance status and GTV proved to be significant prognostic factors regarding local control and survival. Hyperfractionated stereotactic re-RT is a reasonable treatment option for patients with recurrent/second primary HNSCC who were previously exposed to high-dose irradiation and who are not candidates for systemic treatment or hypofractionation. (orig.) [German] Ziel der Studie war es, die Effektivitaet und Toxizitaet der hyperfraktionierten akzelerierten stereotaktischen Wiederbestrahlung (re

An examination of the Wechsler Adult Intelligence Scales, Fourth Edition (WAIS-IV) in individuals with complicated mild, moderate and Severe traumatic brain injury (TBI).

Science.gov (United States)

Carlozzi, Noelle E; Kirsch, Ned L; Kisala, Pamela A; Tulsky, David S

2015-01-01

This study examined the clinical utility of the Wechsler Adult Intelligence Scales-Fourth Edition (WAIS-IV) in individuals with complicated mild, moderate or severe TBI. One hundred individuals with TBI (n = 35 complicated mild or moderate TBI; n = 65 severe TBI) and 100 control participants matched on key demographic variables from the WAIS-IV normative dataset completed the WAIS-IV. Univariate analyses indicated that participants with severe TBI had poorer performance than matched controls on all index scores and subtests (except Matrix Reasoning). Individuals with complicated mild/moderate TBI performed more poorly than controls on the Working Memory Index (WMI), Processing Speed Index (PSI), and Full Scale IQ (FSIQ), and on four subtests: the two processing speed subtests (SS, CD), two working memory subtests (AR, LN), and a perceptual reasoning subtest (BD). Participants with severe TBI had significantly lower scores than the complicated mild/moderate TBI on PSI, and on three subtests: the two processing speed subtests (SS and CD), and the new visual puzzles test. Effect sizes for index and subtest scores were generally small-to-moderate for the group with complicated mild/moderate and moderate-to-large for the group with severe TBI. PSI also showed good sensitivity and specificity for classifying individuals with severe TBI versus controls. Findings provide support for the clinical utility of the WAIS-IV in individuals with complicated mild, moderate, and severe TBI.

Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.

Science.gov (United States)

Storb, R; Raff, R F; Graham, T; Appelbaum, F R; Deeg, H J; Schuening, F G; Sale, G; Seidel, K

1999-01-01

We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. TBI doses studied were just below the dose at which all dogs die despite optimal support. Specifically, 18 dogs were given single doses of 200 cGy TBI, delivered at either 10 (n=13) or 60 (n=5) cGy/min. Thirty-one dogs received 300 cGy TBI at 10 cGy/min, delivered as either single doses (n=21) or three fractions of 100 cGy each (n=10). Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.

Influence of Mild Traumatic Brain Injury (TBI) and Posttraumatic Stress Disorder (PTSD) on Pain Intensity Levels in OEF/OIF/OND Veterans.

Science.gov (United States)

Stojanovic, Milan P; Fonda, Jennifer; Fortier, Catherine Brawn; Higgins, Diana M; Rudolph, James L; Milberg, William P; McGlinchey, Regina E

2016-11-01

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common among US veterans of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND). We postulated that these injuries may modulate pain processing in these individuals and affect their subjective pain levels. Cross-sectional. 310 deployed service members of OEF/OIF/OND without a lifetime history of moderate or severe TBI were included in this study. All participants completed a comprehensive evaluation for Blast Exposure, mTBI, PTSD, and Pain Levels. The Boston Assessment of TBI-Lifetime Version (BAT-L) was used to assess blast exposure and potential brain injury during military service. The Clinician-Administered PTSD Scale (CAPS) characterized presence and severity of PTSD. The Visual Analog Scale (VAS) was used to assess pain intensity over the previous month before the interview, with higher scores indicative of worse pain. Statistical analysis was performed by ANOVA and results were adjusted for co-morbidities, clinical characteristics and demographic data. In comparison to control participants (veterans without mTBI or current PTSD), veterans with both current PTSD and mTBI reported the highest pain intensity levels, followed by veterans with PTSD only (P Pain levels in veterans with mTBI only were comparable to control participants. Comorbid PTSD and mTBI is associated with increased self-reported pain intensity. mTBI alone was not associated with increased pain. Published by Oxford University Press on behalf of the American Academy of Pain Medicine 2016. This work is written by US Government employees and is in the public domain in the US.

Fracture of a HTR-PMI cranioplastic implant after severe TBI.

Science.gov (United States)

López González, Antonio; Pérez Borredá, Pedro; Conde Sardón, Rebeca

2015-02-01

A 13-year-old girl with a large left fronto-parietal hard-tissue replacement patient-matched implant (HTR®-PMI) cranioplasty-since she suffered from a traumatic brain injury (TBI) 6 years ago-had a new severe TBI that detached and fractured the implant as well as caused a left subdural hematoma and a large frontal contusion. The hematoma and contusion were removed and the implant was substituted by a provisional titanium mesh. To the best of our knowledge, this is the first case reported about an HTR®-PMI fracture. It is theorized that the bone ingrowth into the macroporous implants, like those of hydroxyapatite, gives strength and resistance to the implant. But in the case we describe, no macroscopic bone ingrowth was detected 6 years after implantation and the traumatic force that impacted over the cranioplasty exceeded its properties.

Reliability of the NINDS common data elements cranial tomography (CT) rating variables for traumatic brain injury (TBI)

NARCIS (Netherlands)

Harburg, Leah; McCormack, Erin; Kenney, Kimbra; Moore, Carol; Yang, Kelly; Vos, Pieter; Jacobs, Bram; Madden, Christopher J; Diaz-Arrastia, Ramon R; Bogoslovsky, Tanya

2017-01-01

Background: Non-contrast head computer tomography (CT) is widely used to evaluate eligibility of patients after acute traumatic brain injury (TBI) for clinical trials. The NINDS Common Data Elements (CDEs) TBI were developed to standardize collection of CT variables. The objectives of this study

TH-EF-BRB-09: Total Body Irradiation with Uniform MU and Modulated Arc Segments, UMMS-TBI

Energy Technology Data Exchange (ETDEWEB)

Yi, B; Chung, H; Mutaf, Y; Prado, K [University of Maryland School of Medicine, Baltimore, MD (United States)

2016-06-15

Purpose: To test a novel total body irradiation (TBI) system using conformal partial arc with patient lying on the stationary couch which is biologically equivalent to a moving couch TBI. This improves the scanning field TBI, which is previously presented. Methods: The Uniform MU Modulated arc Segments TBI or UMMS-TBI scans the treatment plane with a constant machine dose rate and a constant gantry rotation speed. A dynamic MLC pattern which moves while gantry rotates has been designed so that the treatment field moves same distance at the treatment plane per each gantry angle, while maintaining same treatment field size (34cm) at the plane. Dose across the plane varies due to the geometric differences including the distance from the source to a point of interest and the different attenuation from the slanted depth which changes the effective depth. Beam intensity is modulated to correct the dose variation across the plane by assigning the number of gantry angles inversely proportional to the uncorrected dose. Results: Measured dose and calculated dose matched within 1 % for central axis and 3% for off axis for various patient scenarios. Dose from different distance does not follow the inverse square relation as it is predicted from calculation. Dose uniformity better than 5% across 180 cm at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 200 MU/min. Conclusion: This novel technique, yet accurate but easy to implement enables TBI treatment in a small treatment room with less program development preparation than other techniques. The VMAT function of treatment delivery is not required to modulate beams. One delivery pattern can be used for different patients by changing the monitor units.

Immunosuppression prior to marrow transplantation for sensitized aplastic anemia patients: comparison of TLI with TBI

International Nuclear Information System (INIS)

Shank, B.; Brochstein, J.A.; Castro-Malaspina, H.; Yahalom, J.; Bonfiglio, P.; O'Reilly, R.J.

1988-01-01

From May 1980 through July 1986, 26 patients with severe aplastic anemia, sensitized with multiple transfusions of blood products, were treated on either of two immunosuppressive regimens in preparation for bone marrow transplantation from a matched donor. There were 10 patients treated with total body irradiation (TBI), 200 cGy/fraction X 4 daily fractions (800 cGy total dose), followed by cyclophosphamide, 60 mg/kg/d X 2 d. An additional 16 patients were treated with total lymphoid irradiation (TLI) [or, if they were infants, a modified TLI or thoracoabdominal irradiation (TAI)], 100 cGy/fraction, 3 fractions/d X 2 d (600 cGy total dose), followed by cyclophosphamide, 40 mg/kg/d X 4 d. The extent of immunosuppression was similar in both groups as measured by peripheral blood lymphocyte depression at the completion of the course of irradiation (5% of initial concentration for TBI and 24% for TLI), neutrophil engraftment (10/10 for TBI and 15/16 for TLI), and time to neutrophil engraftment (median of 22 d for TBI and 17 d for TLI). Marrow and peripheral blood cytogenetic analysis for assessment of percent donor cells was also compared in those patients in whom it was available. 2/2 patients studied with TBI had 100% donor cells, whereas 6/11 with TLI had 100% donor cells. Of the five who did not, three were stable mixed chimeras with greater than or equal to 70% donor cells, one became a mixed chimera with about 50% donor cells, but became aplastic again after Cyclosporine A cessation 5 mo post-transplant, and the fifth reverted to all host cells by d. 18 post-transplant. Overall actuarial survival at 2 years was 56% in the TLI group compared with 30% in the TBI group although this was not statistically significant. No survival decrement has been seen after 2 years in either group

Sleep quality affects cognitive functioning in returning combat veterans beyond combat exposure, PTSD, and mild TBI history.

Science.gov (United States)

Martindale, Sarah L; Morissette, Sandra B; Rowland, Jared A; Dolan, Sara L

2017-01-01

The purpose of this study was to determine how sleep quality affects cognitive functioning in returning combat veterans after accounting for effects of combat exposure, posttraumatic stress disorder (PTSD), and mild traumatic brain injury (mTBI) history. This was a cross-sectional assessment study evaluating combat exposure, PTSD, mTBI history, sleep quality, and neuropsychological functioning. One hundred and nine eligible male Iraq/Afghanistan combat veterans completed an assessment consisting of a structured clinical interview, neuropsychological battery, and self-report measures. Using partial least squares structural equation modeling, combat experiences and mTBI history were not directly associated with sleep quality. PTSD was directly associated with sleep quality, which contributed to deficits in neuropsychological functioning independently of and in addition to combat experiences, PTSD, and mTBI history. Combat experiences and PTSD were differentially associated with motor speed. Sleep affected cognitive function independently of combat experiences, PTSD, and mTBI history. Sleep quality also contributed to cognitive deficits beyond effects of PTSD. An evaluation of sleep quality may be a useful point of clinical intervention in combat veterans with cognitive complaints. Improving sleep quality could alleviate cognitive complaints, improving veterans' ability to engage in treatment. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Fifteen-year results of a randomized prospective trial of hyperfractionated chest wall irradiation versus once-daily chest wall irradiation after chemotherapy and mastectomy for patients with locally advanced noninflammatory breast cancer

International Nuclear Information System (INIS)

Buchholz, Thomas A.; Strom, Eric A.; Oswald, Mary Jane; Perkins, George H.; Oh, Julia; Domain, Delora; Yu, Tse-Kuan; Woodward, Wendy A.; Tereffe, Welela; Singletary, S. Eva; Thomas, Eva; Buzdar, Aman U.; Hortobagyi, Gabriel N.; McNeese, Marsha D.

2006-01-01

Purpose: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. Methods and Materials: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. Results: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p = 0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p = 0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p = 0.54). Conclusion: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients

Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

OpenAIRE

Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

2006-01-01

Abstract Background The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. Methods From 1997 to 2004, 64 patients suffering from advanced head and neck ca...

Neurobehavioral toxicity of total body irradiation: a follow-up in long-term survivors

International Nuclear Information System (INIS)

Peper, Martin; Steinvorth, Sarah; Schraube, Peter; Fruehauf, Stefan; Haas, Rainer; Kimmig, Bernhard N.; Lohr, Frank; Wenz, Frederik; Wannenmacher, Michael

2000-01-01

Purpose: Total body irradiation (TBI) in preparation for bone marrow transplantation (BMT) is a routine treatment of hematological malignancy. A retrospective and a prospective group study of long-term cerebral side effects was performed, with a special emphasis on neurobehavioral toxicity effects. Methods and Materials: Twenty disease-free patients treated with hyperfractionated TBI (14.4 Gy, 12 x 1.2 Gy, 4 days), 50 mg/kg cyclophosphamide, and autologous BMT (mean age 38 years, range 17-52 years; age at TBI 35 years, 16-50 years; follow-up time 32 months, 9-65 months) participated in a neuropsychological, neuroradiological, and neurological examination. Data were compared to 14 patients who were investigated prior to TBI. Eleven patients with renal insufficiencies matched for sex and age (38 years, 20-52 years) served as controls. In a longitudinal approach, neuropsychological follow-up data were assessed in 12 long-term survivors (45 years, 23-59 years; follow-up time 8.8 years, 7-10.8 years; time since diagnosis 10.1 years, 7.5-14.2 years). Results: No evidence of neurological deficits was found in post-TBI patients except one case of peripheral movement disorder of unknown origin. Some patients showed moderate brain atrophy. Neuropsychological assessment showed a subtle reduction of memory performance of about one standard deviation. Cognitive decline in individual patients appeared to be associated with pretreatment (brain irradiation, intrathecal methotrexate). Ten-years post disease onset, survivors without pretreatment showed behavioral improvement up to the premorbid level. Conclusion: The incidence of long-term neurobehavioral toxicity was very low for the present TBI/BMT regimen

A phase II study of hyperfractionated accelerated radiotherapy (HART) after induction cisplatin (CDDP) and vinorelbine (VNR) for stage III Non-small-cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Ishikura, Satoshi; Ohe, Yuichiro; Nihei, Keiji; Kubota, Kaoru; Kakinuma, Ryutaro; Ohmatsu, Hironobu; Goto, Koichi; Niho, Seiji; Nishiwaki, Yutaka; Ogino, Takashi

2005-01-01

Purpose: The purpose was to assess the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HART) after induction chemotherapy for Stage III non-small-cell lung cancer. Methods and materials: Treatment consisted of 2 cycles of cisplatin 80 mg/m 2 on Day 1 and vinorelbine 25 mg/m 2 on Days 1 and 8 every 3 weeks followed by HART, 3 times a day (1.5, 1.8, 1.5 Gy, 4-h interval) for a total dose of 57.6 Gy. Results: Thirty patients were eligible. Their median age was 64 years (range, 46-73 years), 24 were male, 6 were female, 8 had performance status (PS) 0, 22 had PS 1, 9 had Stage IIIA, and 21 had Stage IIIB. All but 1 patient completed the treatment. Common grade ≥3 toxicities during the treatment included neutropenia, 25; infection, 5; esophagitis, 5; and radiation pneumonitis, 3. The overall response rate was 83%. The median survival was 24 months (95% confidence interval [CI], 13-34 months), and the 2-year overall survival was 50% (95% CI, 32-68%). The median progression-free survival was 10 months (95% CI, 8-20 months). Conclusion: Hyperfractionated accelerated radiotherapy after induction of cisplatin and vinorelbine was feasible and promising. Future investigation employing dose-intensified radiotherapy in combination with chemotherapy is needed

Hydrocephalus during rehabilitation following severe TBI. Relation to recovery, outcome, and length of stay

DEFF Research Database (Denmark)

Linnemann, Mia; Tibæk, Maiken; Kammersgaard, Lars Peter

2014-01-01

BACKGROUND: Post traumatic hydrocephalus (PTH) is a frequent complication during rehabilitation following severe TBI. However, the diagnosis of PTH is not straightforward and despite shunting recovery may be delayed. OBJECTIVE: To study the influence of PTH on recovery and outcome during rehabili......BACKGROUND: Post traumatic hydrocephalus (PTH) is a frequent complication during rehabilitation following severe TBI. However, the diagnosis of PTH is not straightforward and despite shunting recovery may be delayed. OBJECTIVE: To study the influence of PTH on recovery and outcome during...

Defining the Pathophysiological Role of Tau in Experimental TBI

Science.gov (United States)

2017-10-01

neurodegenerative disorder ; and (iii) novel biomarkers for neurodegeneration are non-invasive blood measures of brain dysfunction valuable for the...dissociated from microtubules, aggregated, and mislocalized within cell bodies and proximal dendrites instead of axonal processes, abnormalities that... disorder , and TBI induced by inertial forces, concussive blows, or blast will sometimes lead to chronic, progressive brain atrophy and cognitive

The role of accelerated hyperfractionated radiotherapy in the treatment of inoperable non-small cell lung cancer: a controlled clinical trial

International Nuclear Information System (INIS)

Reinfuss, M.; Kowalska, T.; Glinski, C.

2000-01-01

Radiotherapy remains the basic form of treatment in cases of non-small cell lung cancer (NSCLC) but there still exist controversies concerning optimal radiotherapy regimen and in particular, the total dose and fractionation schedules. To prove whether the question: if using an unconventional dose fractionation regimen (accelerated hyperfractionation) could improve the results of palliative teleradiotherapy patients with NSCLC. Between 1997 and 2000 in the Cancer Centre in Cracow (COOK) a controlled clinical trial was conducted in a group of 150 patients with locally advanced (III Deg) inoperable and unsuitable for radical radiotherapy NSCLC, with no major symptoms of the disease. In 76 patients conventionally fractionated radiotherapy was performed - 50 Gy in 25 fractions during 5 weeks (CF). 74 patients were irradiated twice a day (AHF); the dose per fraction was 1.25 Gy and the minimum interval between fractions - 6 hours. The total dose was 50 Gy in 40 fractions during 26 days. The probability of 12 months survival was 47.4% in the CF arm and 45.9% in the AHF arm; the probability of 24 months survival was 16.2% and 15.8%, respectively. In all 76 patients in CF arm the treatment was carried out in prescribed time without breaks. Out of 74 patients in the A HF group 8 (10,8%) did not complete the treatment and 2 of then died in 3rd and 4th week of treatment. The use of accelerated hyperfractionation does not improve the results of palliative teleradiotherapy in patients with locally advanced NSCLC without severe symptoms related to intrathoracic tumor. The treatment of choice in this group of patients os conventionally fractionated radiotherapy with a total dose of 50 Gy in 25 fractions in 5 week of treatment. (author)

Is it time to rethink the role of hyperfractionated radiotherapy in the management of children with newly-diagnosed brainstem glioma?: Results of a Pediatric Oncology Group Phase III trial comparing conventional VS. hyperfractionated radiotherapy

International Nuclear Information System (INIS)

Mandell, L.; Kadota, R.; Douglass, E.C.; Fontanesi, J.; Freeman, C.; Cohen, M.; Kovnar, E.; Burger, P.; Sanford, R.A.; Kepner, J.; Friedman, H.; Kun, L.

1997-01-01

Purposes/Objective: In June 1992, POG began accrual to a Phase III study, POG 9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem glioma treated with 100 mg/m 2 of infusional Cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. The trial was closed in March 1996, having achieved its accrual goal. Materials and Methods: Patients (pts) eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for diffusely infiltrating pontine glioma. Treatment (Rx) consisted of a six-week course of local field radiotherapy with either once a day treatment (Rx 1) of 180 cGy per fraction to a total dose of 5400 cGy or a twice a day regimen (Rx 2) of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG 8495). Because of previously reported poor results with conventional radiotherapy alone, Cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the Phase I Cisplatin dose escalation trial, POG 9139, 100 mg/m 2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during Weeks 3 and 5. Of the 132 pts accrued to the study, 94 are eligible for review based upon time since entry, 47 in each Rx arm. In Rx 1, there were 23 males and 24 females, ranging in age from 40 to 161 mo (median, 77 mo); in Rx 2, there were 20 males and 27 females, ranging in age from 41 to 212 mo (median, 77 mo). As of 4/18/96, the study coordinator had not yet verified eligibility and assessed the evaluability of the remaining pts. Results: All results are from time of diagnosis

Effect of binasal occlusion (BNO) on the visual-evoked potential (VEP) in mild traumatic brain injury (mTBI).

Science.gov (United States)

Ciuffreda, Kenneth J; Yadav, Naveen K; Ludlam, Diana P

2013-01-01

The purpose of the experiment was to assess the effect of binasal occlusion (BNO) on the visually-evoked potential (VEP) in visually-normal (VN) individuals and in those with mild traumatic brain injury (mTBI) for whom BNO frequently reduces their primary symptoms related to abnormally-increased visual motion sensitivity (VMS). Subjects were comprised of asymptomatic VN adults (n = 10) and individuals with mTBI (n = 10) having the symptom of VMS. Conventional full-field VEP testing was employed under two conditions: without BNO and with opaque BNO which blocked regions on either side of the VEP test stimulus. Subjective impressions were also assessed. In VN, the mean VEP amplitude decreased significantly with BNO in all subjects. In contrast, in mTBI, the mean VEP amplitude increased significantly with BNO in all subjects. Latency was normal and unaffected in all cases. Repeat VEP testing in three subjects from each group revealed similar test-re-test findings. Visuomotor activities improved, with reduced symptoms, with BNO in the mTBI group. It is speculated that individuals with mTBI habitually attempt to suppress visual information in the near retinal periphery to reduce their abnormal VMS, with addition of the BNO negating the suppressive influence and thus producing a widespread disinhibition effect and resultant increase in VEP amplitude.

Efficacy and acceptability of a home-based, family-inclusive intervention for veterans with TBI: A randomized controlled trial.

Science.gov (United States)

Winter, Laraine; Moriarty, Helene J; Robinson, Keith; Piersol, Catherine V; Vause-Earland, Tracey; Newhart, Brian; Iacovone, Delores Blazer; Hodgson, Nancy; Gitlin, Laura N

2016-01-01

Traumatic brain injury (TBI) often undermines community re-integration, impairs functioning and produces other symptoms. This study tested an innovative programme for veterans with TBI, the Veterans' In-home Programme (VIP), delivered in veterans' homes, involving a family member and targeting the environment (social and physical) to promote community re-integration, mitigate difficulty with the most troubling TBI symptoms and facilitate daily functioning. Interviews and intervention sessions were conducted in homes or by telephone. Eighty-one veterans with TBI at a VA polytrauma programme and a key family member. This was a 2-group randomized controlled trial. Control-group participants received usual-care enhanced by two attention-control telephone calls. Follow-up interviews occurred up to 4 months after baseline interview. VIP's efficacy was evaluated using measures of community re-integration, target outcomes reflecting veterans' self-identified problems and self-rated functional competence. At follow-up, VIP participants had significantly higher community re-integration scores and less difficulty managing targeted outcomes, compared to controls. Self-rated functional competence did not differ between groups. In addition, VIP's acceptability was high. A home-based, family-inclusive service for veterans with TBI shows promise for improving meaningful outcomes and warrants further research and clinical application.

A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

Directory of Open Access Journals (Sweden)

Budach V

2006-01-01

Full Text Available Abstract Background Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX to radiotherapy (RT and to some extent also for the use of hyperfractionated radiation therapy (HFRT and accelerated radiation therapy (AFRT in locally advanced squamous cell carcinoma (SCC of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Methods Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in Results Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p Conclusion RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival.

Neuro-, Trauma -, or Med/Surg-ICU: Does it matter where polytrauma patients with TBI are admitted? Secondary analysis of AAST-MITC decompressive craniectomy study

Science.gov (United States)

Scalea, Tom; Sperry, Jason; Coimbra, Raul; Vercruysse, Gary; Jurkovich, Gregory J; Nirula, Ram

2016-01-01

Introduction Patients with non-traumatic acute intracranial pathology benefit from neurointensivist care. Similarly, trauma patients with and without TBI fare better when treated by a dedicated trauma team. No study has yet evaluated the role of specialized neurocritical (NICU) and trauma intensive care units (TICU) in the management of TBI patients, and it remains unclear which TBI patients are best served in NICU, TICU, or general (Med/Surg) ICU. Methods This study is a secondary analysis of The American Association for the Surgery of Trauma Multi-Institutional Trials Committee (AAST-MITC) decompressive craniectomy study. Twelve Level 1 trauma centers provided clinical data and head CT scans of patients with Glasgow Coma Scale (GCS) ≤13 and CT evidence of TBI. Non-ICU admissions were excluded. Multivariate logistic regression was performed to measure the association between ICU-type and survival and calculate the probability of death for increasing ISS. Polytrauma patients (ISS > 15) with TBI and isolated TBI patients (other AIS polytrauma patients admitted to a TICU had improved survival across increasing ISS (Fig1). Survival for isolated TBI patients was similar between TICU and NICU. Med/Surg ICU carried the greatest probability of death. Conclusion Polytrauma patients with TBI have lower mortality risk when admitted to a Trauma ICU. This survival benefit increases with increasing injury severity. Isolated TBI patients have similar mortality risk when admitted to a Neuro ICU compared to a Trauma ICU. Med/Surg ICU admission carries the highest mortality risk. PMID:28225527

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

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Flandin, Isabelle; Hartmann, Olivier; Michon, Jean; Pinkerton, Ross; Coze, Carole; Stephan, Jean Louis; Fourquet, Bernard; Valteau-Couanet, Dominique; Bergeron, Christophe; Philip, Thierry; Carrie, Christian

2006-01-01

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver, kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma

Advancing Clinical Outcomes, Biomarkers and Treatments for Severe TBI

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2017-08-01

including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this...determining the neurobehavioral and neural effects of repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive technique to stimulate the...TERMS Disability Rating Scale (DRS), Neurobehavioral, Repetitive Transcranial Magnetic Stimulation (rTMS), Traumatic Brain Injury (TBI), Vegetative

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

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2017-12-01

PTSD in which CPT is interwoven with compensatory cognitive rehabilitation principles (CogSMART) to create a hybrid treatment, SMART-CPT. The...symptoms resulting from mild to moderate TBI. These practice standards have been organized into a manualized treatment, Cognitive Symptom Management ...tested a modification of CPT in which CPT was enhanced with compensatory cognitive rehabilitation principles detailed in CogSMART. The enhanced CPT

Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation

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Linsenmeier, Claudia; Thoennessen, Daniel; Negretti, Laura; Streller, Tino; Luetolf, Urs Martin [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Bourquin, Jean-Pierre [University Children' s Hospital Zurich (Switzerland). Dept. of Hemato-Oncology; Oertel, Susanne [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Heidelberg Univ. (Germany). Dept. of Radiation Oncology

2010-11-15

To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG {>=}3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated

Phase II Trial of Hyperfractionated Intensity-Modulated Radiation Therapy and Concurrent Weekly Cisplatin for Stage III and IVa Head-and-Neck Cancer

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Maguire, Patrick D.; Papagikos, Michael; Hamann, Sue; Neal, Charles; Meyerson, Martin; Hayes, Neil; Ungaro, Peter; Kotz, Kenneth; Couch, Marion; Pollock, Hoke; Tepper, Joel

2011-01-01

Purpose: To investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25-Gy fractions b.i.d. to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07, and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m 2 /week was started Week 1. Patients completed the Quality of Life Radiation Therapy Instrument pretreatment (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12 months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed. Results: Of 39 patients, 30 (77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51%): mean 7.8 PRE vs. 3.9 EOT. By month 1, H and N QOL returned near baseline (mean 6.2, SD = 1.7). The most common acute Grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%), and leukopenia (26%). Conclusions: Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol.

Effect of chromatic filters on visual performance in individuals with mild traumatic brain injury (mTBI): A pilot study.

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Fimreite, Vanessa; Willeford, Kevin T; Ciuffreda, Kenneth J

2016-01-01

Spectral filters have been used clinically in patients with mild traumatic brain injury (mTBI). However, they have not been formally assessed using objective techniques in this population. Thus, the aim of the present pilot study was to determine the effect of spectral filters on reading performance and visuo-cortical responsivity in adults with mTBI. 12 adults with mTBI/concussion were tested. All reported photosensitivity and reading problems. They were compared to 12 visually-normal, asymptomatic adults. There were several test conditions: three luminance-matched control filters (gray neutral density, blue, and red), the patient-selected 'precision tint lens' that provided the most comfort and clarity of text using the Intuitive Colorimeter System, and baseline without any filters. The Visagraph was used to assess reading eye movements and reading speed objectively with each filter. In addition, both the amplitude and latency of the visual-evoked potential (VEP) were assessed with the same filters. There were few significant group differences in either the reading-related parameters or VEP latency for any of the test filter conditions. Subjective improvements were noted in most with mTBI (11/12). The majority of patients with mTBI chose a tinted filter that resulted in increased visual comfort. While significant findings based on the objective testing were found for some conditions, the subjective results suggest that precision tints should be considered as an adjunctive treatment in patients with mTBI and photosensitivity. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Results of Hematopoietic Stem Cell Transplantation After Treatment With Different High-Dose Total-Body Irradiation Regimens in Five Dutch Centers

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Loes van Kempen-Harteveld, M.; Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; Maazen, Richard W. van der; Cornelissen, Jan J.; Eijkenboom, Wil M.H.; Lelie, Johannes P. van der; Oldenburger, Foppe; Barge, Renee M.; Biezen, Anja van; Vossen, Jaak M.J.J.; Noordijk, Evert M.; Struikmans, Henk

2008-01-01

Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. Results: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. Conclusions: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced

Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy.

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Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P; Zhang, Zheng Gang; Lehman, Norman L; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease.

Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

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Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P.; Zhang, Zheng Gang; Lehman, Norman L.; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

Background To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Methods Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Results Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Conclusions Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease

DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of U.S. veterans.

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Main, Keith L; Soman, Salil; Pestilli, Franco; Furst, Ansgar; Noda, Art; Hernandez, Beatriz; Kong, Jennifer; Cheng, Jauhtai; Fairchild, Jennifer K; Taylor, Joy; Yesavage, Jerome; Wesson Ashford, J; Kraemer, Helena; Adamson, Maheen M

2017-01-01

Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n  = 109; Age: M  = 47.2, SD  = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.

Comparative Effectiveness of Family Problem-Solving Therapy (F-PST) for Adolescent TBI

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2018-01-25

Tbi; Intracranial Edema; Brain Edema; Craniocerebral Trauma; Head Injury; Brain Hemorrhage, Traumatic; Subdural Hematoma; Brain Concussion; Head Injuries, Closed; Epidural Hematoma; Cortical Contusion; Wounds and Injuries; Disorders of Environmental Origin; Trauma, Nervous System; Brain Injuries

Accelerated Hyperfractionated Radiotherapy for Locally Advanced Uterine Cervix Cancers

International Nuclear Information System (INIS)

Seo, Young Seok; Cho, Chul Koo; Yoo, Seong Yul

2008-01-01

To assess the efficacy of the use of accelerated hyperfractionated radiotherapy (AHRT) for locally advanced uterine cervix cancers. Between May 2000 and September 2002, 179 patients were identified with FIGO stage IIB, IIIB, and IVA cancers. Of the 179 patients, 45 patients were treated with AHRT (AHRT group) and 134 patients were treated with conventional radiotherapy (CRT group), respectively. Patients undergoing the AHRT regimen received a dose of 30 Gy in 20 fractions (1.5 Gyx2 fractions/day) to the whole pelvis. Subsequently, with a midline block, we administered a parametrial boost with a dose of 20 Gy using 2 Gy fractions. Patients also received two courses of low-dose-rate brachytherapy, up to a total dose of 85∼90 Gy to point A. In the CRT group of patients, the total dose to point A was 85∼90 Gy. The overall treatment duration was a median of 37 and 66 days for patients that received AHRT and CRT, respectively. Statistical analysis was calculated by use of the Kaplan-Meier method, the log-rank test, and Chi-squared test. For patients that received cisplatin-based concurrent chemotherapy and radiotherapy, the local control rate at 5 years was 100% and 79.2% for the AHRT and CRT group of patients, respectively (p=0.028). The 5-year survival rate for patients with a stage IIB bulky tumor was 82.6% and 62.1% for the AHRT group and CRT group, respectively (p=0.040). There was no statistically significant difference for severe late toxicity between the two groups (p=0.561). In this study, we observed that treatment with AHRT with concurrent chemotherapy allows a significant advantage of local control and survival for locally advanced uterine cervix cancers

Pupillometry and Saccades as Objective mTBI Biomarker

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2016-10-01

football , hockey, soccer, and rugby [5,6,12,13]. All of 306 D.V. Walsh et al. / Journal of the Neurological Sciences 370 (2016) 305–309these studies have...and multiple sclero- sis [16], not acutemTBI as seen in the present study. But a recent KD test study on subjects recruited from an emergency ...Silverberg, T.M. Luoto, J. Ohman, G.L. Iverson, Assessment of mild traumatic brain injury with the King-Devick Test in an emergency department sample

The Community Balance and Mobility Scale: A Pilot Study Detecting Impairments in Military Service Members With Comorbid Mild TBI and Psychological Health Conditions.

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Pape, Marcy M; Williams, Kathy; Kodosky, Paula N; Dretsch, Michael

2016-01-01

To compare the capacity of the Community Balance and Mobility Scale (CB&M) to identify balance and mobility deficits in Service Members (SMs) with mild traumatic brain injury and comorbid psychological health conditions (mTBI/PH) to other commonly used balance assessments. A clinical research institute that provides a 4-week, outpatient, interdisciplinary program for active-duty SMs with mTBI/PH. A nonrandomized, cross-sectional design that compared multiple measures between 2 groups-active duty SMs with (n = 8) and without (n = 8) the dual diagnosis of mTBI/PH. Gait speed, Activities-specific Balance Confidence scale (ABC), Functional Gait Assessment (FGA), and CB&M to assess functional balance among the community-dwelling, TBI population. Across all measures, the mTBI/PH group performed significantly worse (P ≤ .01) with the exception of the FGA. The abilities of all objective measures to distinguish participants with mTBI/PH from healthy controls ranged from fair to excellent (area under the curve [AUC] = 0.66-0.94). However, the CB&M showed the largest group differences in effect size (d = 2.6) and had the highest discriminate ability (AUC = 0.98; sensitivity 100%; specificity 88%). The CB&M appears to have higher sensitivity and specificity than other measures of balance in SMs with mTBI/PH. A higher cut score for the CB&M is needed for this population.

A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice.

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Edut, S; Rubovitch, V; Rehavi, M; Schreiber, S; Pick, C G

2014-12-01

Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.

Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

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2014-01-01

Andersson G (2009) The role of anxiety sensitivity and behavioral avoidance in tinnitus disability. IntJAudiol 48:295-299. Hiller W, Goebel G (1999...Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI) PRINCIPAL INVESTIGATOR...Induced Tinnitus and Related Traumatic Brain Injury (TBI) 5b. GRANT NUMBER W81XWH-11-2-0031 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

Allogeneic marrow transplantation following cyclophosphamide and escalating doses of hyperfractionated total body irradiation in patients with advanced lymphoid malignancies: a phase I/II trial

International Nuclear Information System (INIS)

Demirer, Taner; Petersen, Finn B.; Appelbaum, Frederick R.; Barnett, Todd A.; Sanders, Jean; Deeg, H. Joachim; Storb, Rainer; Doney, Kristine; Bensinger, William I.; Shannon-Dorcy, Kathleen; Buckner, C. Dean

1995-01-01

Purpose: To define the maximum tolerated dose (MTD) of unshielded total body irradiation (TBI) delivered from dual 60 C sources at an exposure rate of 0.08 Gy/min and given in thrice daily fractions of 1.2 Gy in patients with advanced lymphoid malignancies. Methods and Materials: Forty-four patients with a median age of 28 (range 6-48) years were entered into a Phase I/II study. All patients received cyclophosphamide (CY), 120 mg/kg administered over 2 days before TBI. Marrow from human leukocyte antigen (HLA) identical siblings was infused following the last dose of TBI. An escalation-deescalation schema designed to not exceed an incidence of 25% of Grade 3-4 regimen-related toxicities (RRTs) was used. The first dose level tested was 13.2 Gy followed by 14.4 Gy. Results: None of the four patients at the dose level of 13.2 Gy developed Grade 3-4 RRT. Two of the first eight patients receiving 14.4 Gy developed Grade 3-4 RRT, establishing this as the MTD. An additional 32 patients were evaluated at the 14.4 Gy level to confirm these initial observations. Of 40 patients receiving 14.4 Gy, 13 (32.5%) developed Grade 3-4 RRTs; 46% in adults and 12% in children. The primary dose limiting toxicity was Grade 3-4 hepatic toxicity, which occurred in 12.5% of patients. Noninfectious Grade 3-4 interstitial pneumonia syndrome occurred in 5% of patients. The actuarial probabilities of event-free survival, relapse, and nonrelapse mortality at 2 years were 0.10, 0.81, and 0.47, respectively, for patients who received 14.4 Gy of TBI. Conclusions: The outcome for patients receiving 14.4 Gy of TBI was not different from previous studies of other CY and TBI regimens in patients with advanced lymphoid malignancies. These data showed that the incidence of Grade 3-4 RRTs in adults was greater than the 25% maximum set as the goal of this study, suggesting that 13.2 Gy is a more appropriate dose of TBI for adults, while 14.4 Gy is an appropriate dose for children

Diffusion tensor imaging (DTI) findings in adult civilian, military, and sport-related mild traumatic brain injury (mTBI): a systematic critical review.

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Asken, Breton Michael; DeKosky, Steven T; Clugston, James R; Jaffee, Michael S; Bauer, Russell M

2018-04-01

This review seeks to summarize diffusion tensor imaging (DTI) studies that have evaluated structural changes attributed to the mechanisms of mild traumatic brain injury (mTBI) in adult civilian, military, and athlete populations. Articles from 2002 to 2016 were retrieved from PubMed/MEDLINE, EBSCOhost, and Google Scholar, using a Boolean search string containing the following terms: "diffusion tensor imaging", "diffusion imaging", "DTI", "white matter", "concussion", "mild traumatic brain injury", "mTBI", "traumatic brain injury", and "TBI". We added studies not identified by this method that were found via manually-searched reference lists. We identified 86 eligible studies from English-language journals using, adult, human samples. Studies were evaluated based on duration between injury and DTI assessment, categorized as acute, subacute/chronic, remote mTBI, and repetitive brain trauma considerations. Since changes in brain structure after mTBI can also be affected by other co-occurring medical and demographic factors, we also briefly review DTI studies that have addressed socioeconomic status factors (SES), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD). The review describes population-specific risks and the complications of clinical versus pathophysiological outcomes of mTBI. We had anticipated that the distinct population groups (civilian, military, and athlete) would require separate consideration, and various aspects of the study characteristics supported this. In general, study results suggested widespread but inconsistent differences in white matter diffusion metrics (primarily fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) following mTBI/concussion. Inspection of study designs and results revealed potential explanations for discrepant DTI findings, such as control group variability, analytic techniques, the manner in which regional differences were reported, and

Reintegrating Troops with Mild Traumatic Brain Injury (mTBI) into their Communities: Understanding the Scope and Timeline of Post-Deployment Driving Problems

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2015-10-01

AWARD NUMBER: W81XWH-08-2-0196 TITLE: Reintegrating Troops with Mild Traumatic Brain Injury (mTBI) into Their Communities: Understanding the...REPORT TYPE Final 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Reintegrating troops with mild traumatic brain injury...n=6), TBI (n=12), PTSD (n=7), and dual diagnosis (TBI/PTSD) n=19. Additional comparisons were made between 28 Family /Friends matched to their SMs

Facial emotion recognition deficits following moderate-severe Traumatic Brain Injury (TBI): re-examining the valence effect and the role of emotion intensity.

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Rosenberg, Hannah; McDonald, Skye; Dethier, Marie; Kessels, Roy P C; Westbrook, R Frederick

2014-11-01

Many individuals who sustain moderate-severe traumatic brain injuries (TBI) are poor at recognizing emotional expressions, with a greater impairment in recognizing negative (e.g., fear, disgust, sadness, and anger) than positive emotions (e.g., happiness and surprise). It has been questioned whether this "valence effect" might be an artifact of the wide use of static facial emotion stimuli (usually full-blown expressions) which differ in difficulty rather than a real consequence of brain impairment. This study aimed to investigate the valence effect in TBI, while examining emotion recognition across different intensities (low, medium, and high). Twenty-seven individuals with TBI and 28 matched control participants were tested on the Emotion Recognition Task (ERT). The TBI group was more impaired in overall emotion recognition, and less accurate recognizing negative emotions. However, examining the performance across the different intensities indicated that this difference was driven by some emotions (e.g., happiness) being much easier to recognize than others (e.g., fear and surprise). Our findings indicate that individuals with TBI have an overall deficit in facial emotion recognition, and that both people with TBI and control participants found some emotions more difficult than others. These results suggest that conventional measures of facial affect recognition that do not examine variance in the difficulty of emotions may produce erroneous conclusions about differential impairment. They also cast doubt on the notion that dissociable neural pathways underlie the recognition of positive and negative emotions, which are differentially affected by TBI and potentially other neurological or psychiatric disorders.

The effects of single dose TBI on hepatic and renal function in non-human primates and patients

International Nuclear Information System (INIS)

Broerse, J.J.; Bakker, B.; Davelaar, J.; Leer, J.W.H.; Niemer-Tucker, M.M.B.; Noordijk, E.M.

1996-01-01

Total body irradiation (TBI) and bone marrow transplantation (BMT) are common procedures in the treatment of severe combined immune deficiency syndromes, leukemia, non-Hodgkin lymphoma and other hematological disorders. Improved results following TBI and BMT have increased the number of patients in long term follow up. Late detrimental effects of TBI have been investigated in non-human primates and patients with emphasis on vital organs like liver and kidney. The response of monkeys to radiation is not significantly different from that in man. Long term effects of TBI could be studied by keeping 84 monkeys of different ages under continuous observation for a period up to 25 years. Effects on hepatic and renal function were demonstrated using serological and histological parameters. The values of the liver function parameters such as alkaline phosphatase and gamma glutamyl transferase in the irradiated group are significantly increased after TBI. Also the parameters of kidney dysfunction, e.g., Ht and urea show a significant change in the irradiated old aged cohort with respect to the controls. Between 1967 and 1993, 336 bone marrow transplantations were performed at the University Hospital Leiden. The present Study was restricted to those patients who survived at least 18 months after transplantation. This retrospective analysis consequently amounts to 120 patients. The monkey data indicated subclinical organ damage for postirradiation intervals exceeding 15 years. However, up to the present time, the human data do not support these findings since the follow up time is still restricted to a median survival of 4,5 years. Detrimental effects in liver and kidney function at a later stage can not be excluded yet, and careful examinations of the patients remain indicated

Counselor-Assisted Problem Solving (CAPS) Improves Behavioral Outcomes in Older Adolescents with Complicated Mild to Severe TBI

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Wade, Shari L.; Stancin, Terry; Kirkwood, Michael; Brown, Tanya Maines; Rochester, Mayo Clinic; McMullen, Kendra M.; Taylor, H. Gerry

2013-01-01

Objective To test the efficacy of Counselor-Assisted Problem Solving (CAPS) versus an internet resources comparison (IRC) condition in reducing behavior problems in adolescents following traumatic brain injury (TBI). Design Randomized clinical trial with interviewers naïve to treatment condition. Setting Three large tertiary children's hospitals and two general hospitals with pediatric commitment. Participants 132 children ages 12-17 years hospitalized during the previous 6 months for moderate to severe TBI. Interventions Participants in CAPS (n = 65) completed 8-12 online modules providing training in problem solving, communication skills, and self-regulation and subsequent synchronous videoconferences with a therapist. Participants in the IRC group (n = 67) received links to internet resources about pediatric TBI. Main Outcome Measures Child Behavior Checklist (CBCL) administered before and after completion of treatment (i.e., approximately six months after treatment initiation). Results Post hoc analysis of covariance (ANCOVA), controlling for pre-treatment scores, was used to examine group differences in behavior problems in the entire sample and among older (n=59) and younger adolescents (n=53). Among older but not younger adolescents, CAPS resulted in greater improvements on multiple dimensions of externalizing behavior problems than did IRC. Conclusion Online problem-solving therapy may be effective in reducing behavior problems in older adolescent survivors of moderate-severe TBI. PMID:23640543

Effect of chromatic filters on visual performance in individuals with mild traumatic brain injury (mTBI: A pilot study

Directory of Open Access Journals (Sweden)

Vanessa Fimreite

2016-10-01

Conclusions: The majority of patients with mTBI chose a tinted filter that resulted in increased visual comfort. While significant findings based on the objective testing were found for some conditions, the subjective results suggest that precision tints should be considered as an adjunctive treatment in patients with mTBI and photosensitivity.

Imaging response is highly predictive of survival of malignant glioma patients treated with standard or hyperfractionated RT and carmustine in RTOG 9006

International Nuclear Information System (INIS)

Curran, Walter J.; Scott, Charles B.; Yung, W.K. Alfred; Scarantino, Charles; Urtasun, Raul; Movsas, Benjamin; Jones, Christopher; Simpson, Joseph; Fischbach, A. Jennifer; Petito, Carol; Nelson, James

1996-01-01

Objectives: Limited information is available correlating response to initial therapy and survival outcome among malignant glioma patients. This analysis was conducted to determine the response rate of malignant glioma patients to either standard (STN) or hyperfractionated (HFX) RT and carmustine and to correlate the tumor response status with survival. Patients and Methods: From (11(90)) to (3(94)), 712 newly diagnosed malignant glioma patients were registered on RTOG 9006 and randomized between hyperfractionated RT of 72.0 Gy in 1.2 Gy twice-daily fractions and 60.0 Gy in 2.0 Gy daily fractions. All patients received 80 mg/m-2 of carmustine D 1-3 q 8 wks. As reported in the 1996 Proceedings of the Amer Soc Clin Oncol (Abstr no. 280), there was no survival benefit observed for the HFX regimen. 529 of the 686 eligible patients had pre-operative, post-operative, and post-RT contrast-enhanced MR and/or CT scans available for central review of tumor and peritumoral edema measurements. Response status was judged by applying standard response criteria to a comparison of tumor measurements on follow-up and post-operative films. Results: Of the 529 patients evaluated for imaging response, the complete and partial response rates were 14% and 20%, respectively. A significant correlation between response and survival was observed (P<0.0001). Variables which predicted for a better tumor response were anaplastic astrocytoma vs glioblastoma multiforme histology, better performance status, more extensive resection, and a more favorable Recursive Partitioning and Amalgamation class assignment (JNCI 85:704-710, 1993). Conclusion: The objective response rate for malignant glioma patients to RTOG 9006 therapy was 34%, and survival outcome is strongly correlated with tumor response status. These observations justify the testing of aggressive salvage strategies for patients without imaging evidence of response following initial therapy

Pupillometry and Saccades as Objective mTBI Biomark

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2017-06-01

Parkinson’s disease , Parkinsonism Relat. Disord. 20 (2) (2014) 226–229, http://dx.doi.org/10.1016/j.parkreldis.2013.10.009 (PubMed PMID: 24269283...The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an official Department of the...Saccades as Objective mTBI Biomark 5a. CONTRACT NUMBER W81XWH-14-C-0048 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) LTC Jose E

[Sensitivity of BALB/c and WR strain mice to the immunodepressive action of cyclophosphamide and thiophosphamide].

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Ir, K N; Telegin, L Iu; Pevnitskiĭ, L A; Malashenko, A M

1984-05-01

Experiments were made on BALB/cJ YSto and WR/Y mice to study the immunosuppressant action of cyclophosphamide (CP) and thiophosphamide (thiotepa) in vivo. WR mice were found to be significantly more sensitive to the immunosuppressant action of thiotepa than BALB/c mice and to have similar sensitivity to the action of CP. BALB/c mice appeared highly resistant to the action of both the drugs. Based on the data obtained and those reported in the literature a possible parallelism is suggested between the mutagenic and immunosuppressant action of CP and thiotepa.

Neuropsychological recovery and quality-of-life in children and adolescents with growth hormone deficiency following TBI: a preliminary study.

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Wamstad, Julia B; Norwood, Kenneth W; Rogol, Alan D; Gurka, Matthew J; Deboer, Mark D; Blackman, James A; Buck, Marcia L; Kuperminc, Michelle N; Darring, Jodi G; Patrick, Peter D

2013-01-01

To compare neurocognition and quality-of-life (QoL) in a group of children and adolescents with or without growth hormone deficiency (GHD) following moderate-to-severe traumatic brain injury (TBI). Thirty-two children and adolescents were recruited from the TBI clinic at a children's hospital. Growth hormone (GH) was measured by both spontaneous overnight testing and following arginine/glucagon stimulation administration. Twenty-nine subjects participated in extensive neuropsychological assessment. GHD as measured on overnight testing was significantly associated with a variety of neurocognitive and QoL measures. Specifically, subjects with GHD had significantly (p  0.05). GHD noted in response to provocative testing was not associated with any neurocognitive or QoL measures. GHD following TBI is common in children and adolescents. Deficits in neurocognition and QoL impact recovery after TBI. It is important to assess potential neurocognitive and QoL changes that may occur as a result of GHD. It is also important to consider the potential added benefit of overnight GH testing as compared to stimulation testing in predicting changes in neurocognition or QoL.

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

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2017-12-01

S) Amy Jak 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: ajak@ucsd.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...points during the study. The investigation sought to improve treatment outcomes for combat- related psychological health and develop an evidence-based...focused on helping Iraq and Afghanistan Veterans who have a history of mild to moderate traumatic brain injury (TBI) and posttraumatic stress

Hyperfractionated Radiotherapy and Concurrent Chemotherapy for Stage III Unascertainable Non Small Cell Lung Cancer : Preliminary Report for Response and Toxicity

International Nuclear Information System (INIS)

Choi, Eun Kyung; Kim, Jong Hoon; Chang, Hye Sook

1995-01-01

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy( 120 cGy/fx BID, 6480 cGY/54fx) and concurrent 2 cycles of MVP(Motomycin C 6 mg/m 2 , d2 and d29, Vinblastin 6 mg/m 2 , d2 and d29, Cisplatin 6 mg/m 2 , d1 and d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study ; 6(10%) had advanced stage IIIa and 56(90%) had IIIb disease including 1 with pleural effusion and 10 with supraclavicular metastases. Among 62 Patients, 48(77%) completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, 34(74%) showed major response including 10(22%) with complete and 24(52%) with partial responses. Of 48 patients evaluable for toxicity, 13(27%) showed grade IV hematologic toxicity but treatment delay did not exceed 5 days. Two patients died of sepsis during chemoradiotherapy. Server weight(more than 10%) occurred in 9 patients(19%) during treatment. Nine patients(19%) developed radiation pneumonitis. Six of these patients had grad I(mild) pneumonitis with radiographic changes within the treatment fields. Three other patients had grade II pneumonitis, but none of theses patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance rate(7%) in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary, supportive care will given as in patients. Longer follow-up and larger sample size is needed to

Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI) in adolescent rats.

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Yamakawa, Glenn R; Lengkeek, Connor; Salberg, Sabrina; Spanswick, Simon C; Mychasiuk, Richelle

2017-01-01

Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI), we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours). In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau), in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored.

Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI in adolescent rats.

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Glenn R Yamakawa

Full Text Available Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI, we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours. In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau, in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored.

Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis.

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Harris, N G; Verley, D R; Gutman, B A; Thompson, P M; Yeh, H J; Brown, J A

2016-03-01

While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity

Fatigue - but not mTBI history, PTSD, or sleep quality - directly contributes to reduced prospective memory performance in Iraq and Afghanistan era Veterans.

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Rau, Holly K; Hendrickson, Rebecca; Roggenkamp, Hannah C; Peterson, Sarah; Parmenter, Brett; Cook, David G; Peskind, Elaine; Pagulayan, Kathleen F

2017-10-13

Memory problems that affect daily functioning are a frequent complaint among Veterans reporting a history of repetitive mild traumatic brain injury (mTBI), especially in cohorts with comorbid PTSD. Here, we test the degree to which subjective sleep impairment and daytime fatigue account for the association of PTSD and self-reported mTBI history with prospective memory. 82 Veterans with and without personal history of repeated blast-related mTBI during deployment were administered the Clinician Administered PTSD Scale (CAPS), Memory for Intentions Test (MIST), Patient Health Questionnaire-9 (PHQ-9), Neurobehavioral Symptom Inventory (NSI), and the Pittsburgh Sleep Quality Index (PSQI). Relationships between self-reported mTBI, PTSD, self-reported poor sleep and daytime fatigue, and MIST performance were modeled using partial least squares structural equation modeling (PLS-SEM). Reported daytime fatigue was strongly associated with poorer prospective memory performance. Poor subjective sleep quality was strongly and positively associated with reported daytime fatigue, but had no significant direct effect on prospective memory performance. PTSD diagnosis and self-reported mTBI history were only associated with prospective memory via their impact on subjective sleep quality and daytime fatigue. Results suggest that daytime fatigue may be a mediating factor by which both mTBI and PTSD can interfere with prospective memory. Additional attention should be given to complaints of daytime fatigue, independent of subjective sleep quality, in the clinical care of those with a self-reported history of mTBI, and/or PTSD. Further research into whether interventions that decrease daytime fatigue lead to improvement in prospective memory and subjective cognitive functioning is warranted.

Novel Treatment for Patients with Traumatic Brain Injury (TBI)

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2016-06-01

equieffectiv e dose of phenylephri ne (PE)? 18 Does AVP maintain brain and muscle tissue 02 during CPP managemen t after TBI relative to an... Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any...discuss the meeting dates. I can be reached by telephone or email as listed below. K nnet 1·0 t ,. ti .. P ofessor of Surgery Leonard M. Miller

Continuous hyperfractionated accelerated radiotherapy (chart) in localized cancer of the esophagus

International Nuclear Information System (INIS)

Powell, Melanie E.B.; Hoskin, Peter J.; Saunders, Michele I.; Foy, Christopher J.W.; Dische, Stanley

1997-01-01

Purpose: To assess the efficacy and toxicity of continuous hyperfractionated accelerated radiotherapy (CHART) in locoregional control compared with a historical group of patients treated with conventionally fractionated radical radiotherapy. Methods and Materials: Between 1985 and 1994, 54 patients with localized esophageal cancer were treated with CHART. Twenty-eight patients received CHART alone (54 Gy in 36 fractions over 12 consecutive days) and 15 were given intravenous mitomycin C and cisplatin on days 10 and 13, respectively. Eleven patients received 40.5 Gy in 27 fractions over 9 days, followed by a single high-dose-rate intraluminal brachytherapy insertion of 15 Gy at 1 cm. Results: Acute toxicity was well tolerated and dysphagia was improved in 35 patients (65%), with 28 (52%) eating a normal diet by week 12. This compares with an improvement in dysphagia score in 72% of the conventionally treated group. The median duration of relief of dysphagia was 7.8 months (range 0-41.4) in the CHART group compared with 5.5 months (range 0-48) in the controls. Strictures developed in 29 patients (61%) and 18 were confirmed on biopsy to be due to recurrent disease. Median survival was 12 months (range 0.5-112) in the CHART group and 15 months (range 3.6-56) in the control patients. Conclusion: CHART is well tolerated and achieves a high rate of local control. Palliation in the short overall treatment time of esophageal cancer is an advantage in these patients whose median survival is only 12 months

Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI

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2017-06-01

working memory load effects after mild traumatic brain injury. Neuroimage, 2001. 14(5): p. 1004-12. 2. Chen, J.K., et al., Functional abnormalities in...report. 10 Supporting Data None. Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI Psychological Health

Mild-moderate TBI: clinical recommendations to optimize neurobehavioral functioning, learning, and adaptation.

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Chen, Anthony J-W; Loya, Fred

2014-11-01

Traumatic brain injury (TBI) can result in functional deficits that persist long after acute injury. The authors present a case study of an individual who experienced some of the most common debilitating problems that characterize the chronic phase of mild-to-moderate TBI-difficulties with neurobehavioral functions that manifest via complaints of distractibility, poor memory, disorganization, poor frustration tolerance, and feeling easily overwhelmed. They present a rational strategy for management that addresses important domain-general targets likely to have far-ranging benefits. This integrated, longitudinal, and multifaceted approach first addresses approachable targets and provides an important foundation to enhance the success of other, more specific interventions requiring specialty intervention. The overall approach places an emphasis on accomplishing two major categories of clinical objectives: optimizing current functioning and enhancing learning and adaptation to support improvement of functioning in the long-term for individuals living with brain injury. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the radiation therapy oncology group (RTOG) 9104

International Nuclear Information System (INIS)

Murray, Kevin J.; Scott, Charles; Greenberg, Harvey M.; Emami, Bahman; Seider, Michael; Vora, Nayana L.; Olson, Craig; Whitton, Anthony; Movsas, Benjamin; Curran, Walter

1997-01-01

Purpose: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. Methods and Materials: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. Results: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary

Late course accelerated hyperfractionated radiotherapy of nasopharyngeal carcinoma (LCAF)

International Nuclear Information System (INIS)

He Xiayun; Liu Taifu; He Shaoqin; Huan Sulan; Pan Ziqiang

2007-01-01

Background and purpose: To study the efficacy of late course accelerated fractionated (LCAF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). The end-points were local control, radiation-induced complications, and factors influencing survival. Patients and methods: Between December 1995 and April 1998, 178 consecutive NPC patients were admitted for radiation treatment. The radiation beam used was 60 Co γ or 6 MV X rays. For the first two-thirds of the treatment, two daily fractions of 1.2 Gy were given to the primary lesion, with an interval of ≥6 h, 5 days per week to a total dose of 48 Gy/40 fractions, over a period of 4 weeks. For the last third of the treatment, i.e., beginning the 5th week of treatment, an accelerated hyperfractionated schedule was carried out. The dose per fraction was increased to 1.5 Gy, 2 fractions per day with an interval of ≥6 h, the total dose for this part of the protocol was 30 Gy/20 fractions over 2 weeks. Thus the total dose was 78 Gy in 60 fractions in 6 weeks. Results: All patients completed the treatment. Acute mucositis: none in 2 cases, Grade 1 in 43 cases, Grade 2 in 78 cases, Grade 3 in 52 cases, and Grade 4 in 3 cases. Local control rate: the 5 year nasopharyngeal local control rate was 87.7%, and the cervical lymph nodes local control rate was 85.7%. The 5-year distant metastasis rate was 26.1%, and 5 year survivals were 67.9%, 16 (9%) patients had radiation-induced cranial nerve palsy, 7(4%) patients had temporal lobe or brainstem damage. Conclusions: With this treatment schedule, patients' tolerance was good, local control and 5 year survivals were better than conventional fractionation schedules, and radiation-related late complications did not increase, as 5-year survival rates of conventional fractionation radiotherapy were only 58%. Randomized clinical trials are being carried out to further confirm the efficacy of LCAF for nasopharyngeal carcinoma

SU-E-T-485: In Vivo Dosimetry with EBT3 Radiochromic Films for TBI Treatments

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Lozares, S; Gracia, M; Olasolo, J; Gallardo, N; Fuentemilla, N; Pellejero, S; Miquelez, S; Maneru, F; Martin, M; Bragado, L; Rubio, A [Complejo Hospitalario de Navarra, Pamplona, Navarra (Spain)

2015-06-15

Purpose: Total body irradiation (TBI) is a technique that requires special equipment to control “in vivo” the dose to the patient because it is a complex technique performed in extraordinary conditions. There are several devices to perform this task (diodes, TLDs, ionization chambers, MOSFET). In this paper we study the possibility of performing these measurements with radiochromic films EBT3 properly calibrated. This method has been compared to the PTW diodes system for TBI. Methods: Once made the TC to the patients, we measured different thicknesses of the relevant areas of the body (head, neck, chest with or without arms, umbilicus area, knees and ankles); for each of these thicknesses we measured dose rate (cGy / UM) in RW3 phantom, in TBI conditions, with ionization chamber in the center; in turn, the input diode and the output of each configuration is placed to assign dose to each set of diodes. Movie calibration is performed according to manufacturer’s recommendations but TBI conditions. The dose at the center of each thickness compared to a linear interpolation of the dose at the entrance and exit, resulting in an adequate approximation. Finally in each session for each patient put a piece of film (2×2 cm2) at the entrance and another at the exit in each area, obtaining these readings and interpolating the estimated center dose, as with the diodes. Results: These results show a greater homogeneity in the distribution for use with film and validate the use of the same for this task and, if necessary, to avoid purchasing diode group if they have not. Conclusion: By using radiochromic films for this technique gives us a proper calculation of the dose received by the patient in the absence of other methods, or gives us a second additional track that already used normally.

A study on dose attenuation in bone density when TBI using diode detector and TLD

International Nuclear Information System (INIS)

Im, Hyun Sil; Lee, Jung Jin; Jang, Ahn Ki; KIm, Wan Sun

2003-01-01

Uniform dose distribution of the whole body is essential factor for the total body irradiation(TBI). In order to achieved this goal, we used to compensation filter to compensate body contour irregularity and thickness differences. But we can not compensate components of body, namely lung or bone. The purpose of this study is evaluation of dose attenuation in bone tissue when TBI using diode detectors and TLD system. The object of this study were 5 patients who undergo TBI at our hospital. Dosimetry system were diode detectors and TLD system. Treatment method was bilateral and delivered 10 MV X-ray from linear accelerator. Measurement points were head, neck, pelvis, knees and ankles. TLD used two patients and diode detectors used three patients. Results are as followed. All measured dose value were normalized skin dose. TLD dosimetry : Measured skin dose of head, neck, pelvis, knees and ankles were 92.78±3.3, 104.34±2.3, 98.03±1.4, 99.9±2.53, 98.17±0.56 respectably. Measured mid-depth dose of pelvis, knees and ankles were 86±1.82, 93.24±2.53, 91.50±2.84 respectably. There were 6.67%-11.65% dose attenuation at mid-depth in pelvis, knees and ankles. Diode detector : Measured skin dose of head, neck, pelvis, knees and ankles were 95.23±1.18, 98.33±0.6, 93.5±1.5, 87.3±1.5, 86.90±1.16 respectably. There were 4.53%-12.6% dose attenuation at mid-depth in pelvis, knees and ankles. We concluded that dose measurement with TLD or diode detector was inevitable when TBI treatment. Considered dose attenuation in bone tissue, We must have adequately deduction of compensator thickness that body portion involved bone tissue.

SU-E-T-485: In Vivo Dosimetry with EBT3 Radiochromic Films for TBI Treatments

International Nuclear Information System (INIS)

Lozares, S; Gracia, M; Olasolo, J; Gallardo, N; Fuentemilla, N; Pellejero, S; Miquelez, S; Maneru, F; Martin, M; Bragado, L; Rubio, A

2015-01-01

Purpose: Total body irradiation (TBI) is a technique that requires special equipment to control “in vivo” the dose to the patient because it is a complex technique performed in extraordinary conditions. There are several devices to perform this task (diodes, TLDs, ionization chambers, MOSFET). In this paper we study the possibility of performing these measurements with radiochromic films EBT3 properly calibrated. This method has been compared to the PTW diodes system for TBI. Methods: Once made the TC to the patients, we measured different thicknesses of the relevant areas of the body (head, neck, chest with or without arms, umbilicus area, knees and ankles); for each of these thicknesses we measured dose rate (cGy / UM) in RW3 phantom, in TBI conditions, with ionization chamber in the center; in turn, the input diode and the output of each configuration is placed to assign dose to each set of diodes. Movie calibration is performed according to manufacturer’s recommendations but TBI conditions. The dose at the center of each thickness compared to a linear interpolation of the dose at the entrance and exit, resulting in an adequate approximation. Finally in each session for each patient put a piece of film (2×2 cm2) at the entrance and another at the exit in each area, obtaining these readings and interpolating the estimated center dose, as with the diodes. Results: These results show a greater homogeneity in the distribution for use with film and validate the use of the same for this task and, if necessary, to avoid purchasing diode group if they have not. Conclusion: By using radiochromic films for this technique gives us a proper calculation of the dose received by the patient in the absence of other methods, or gives us a second additional track that already used normally

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

Directory of Open Access Journals (Sweden)

Maryse C Cnossen

Full Text Available The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI is low. Comparative effectiveness research (CER has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI study.We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions.All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%, designated as a level I trauma center (n = 48, 68% and situated in an urban location (n = 70, 99%. The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57% had a dedicated neuro-intensive care unit (ICU, 36 (51% had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45 of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers.Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches.

Amelioration of rCBF and PbtO2 following TBI at high altitude by hyperbaric oxygen pre-conditioning.

Science.gov (United States)

Hu, Shengli; Li, Fei; Luo, Haishui; Xia, Yongzhi; Zhang, Jiuquan; Hu, Rong; Cui, Gaoyu; Meng, Hui; Feng, Hua

2010-03-01

Hypobaric hypoxia at high altitude can lead to brain damage and pre-conditioning with hyperbaric oxygen (HBO) can reduce ischemic/hypoxic brain injury. This study investigates the effects of high altitude on traumatic brain injury (TBI) and examines the neuroprotection provided by HBO preconditioning against TBI. Rats were randomly divided into four groups: HBO pre-conditioning group (HBOP, n=10), high altitude group (HA, n=10), plain control group (PC, n=10) and plain sham operation group (sham, n=10). All groups were subjected to head trauma by weight drop device except for the sham group. Rats from each group were examined for neurological function, regional cerebral blood flow (rCBF) and brain tissue oxygen pressure (PbtO(2)) and were killed for analysis by transmission electron microscope. The score of neurological deficits in the HA group was highest, followed by the HBOP group and the PC group, respectively. Both rCBF and PbtO(2) were the lowest in the HA group. Brain morphology and structure seen via the transmission electron microscope was diminished in the HA group, while fewer pathological injuries occurred in the HBOP and PC groups. High altitude aggravates TBI significantly and HBO pre-conditioning can attenuate TBI in rats at high altitude by improvement of rCBF and PbtO(2). Pre-treatment with HBO might be beneficial for people traveling to high altitude locations.

Comparative binding characteristics of Tc-CPI, Tc-TBI, and Tc-MIBI in cultured heart cells: Correlation with biochemical analysis and animal images

International Nuclear Information System (INIS)

Piwnica-Worms, D.; Kronauge, J.F.; Holman, B.L.; Davison, A.; Jones, A.G.

1987-01-01

Hexakis (isonitrile)technetium (I) complexes are a new class of cationic, lipophilic myocaridal perfusion imaging agents. To better understand their cellular mechanisms of uptake and washout, chick heart cells grown in culture were used as a model myocardial system. Tc-MIBI showed uptake to a plateau at a rate similar to Tc-CPI (t1/2 = 4.1 +- 0.7 minutes); however, the plateau was 63% greater. Tc-TBI uptake approached a plateau 900% greater than Tc-CPI binding. Heart cell studies showed washout of Tc-CPI>Tc-TBI>Tc-MIBI, which correlated with kinetic analysis of rabbit myocardial images. Biochemical in vitro analysis in human plasma demonstrated 75% enzymatic ester hydrolysis of Tc-CPI by 3 minutes, but no hydrolysis of Tc-TBI and Tc-MIBI. The results suggest that metabolism of the ester function of Tc-CPI following myocardial uptake may in part account for the more rapid cellular washout rates of Tc-CPI compared with Tc-TBI and Tc-MIBI

The ties that bind: the relationship between caregiver burden and the neuropsychological functioning of TBI survivors.

Science.gov (United States)

Lehan, Tara; Arango-Lasprilla, Juan Carlos; de los Reyes, Carlos José; Quijano, María Cristina

2012-01-01

Advances in medical and assistive technology have increased the likelihood of survival following a traumatic brain injury (TBI). Consequently, families frequently must provide care to individuals with TBI. Because they are rarely prepared for the associated demanding medical needs and financial burden, family caregivers are at risk for physical and emotional problems, which can negatively influence their individual and family functioning. Whereas scholars have examined the influence of survivor functioning on caregiver burden, few have explicitly recognized that caregiver burden also influences survivor functioning. Results of a multivariate linear regression suggest that, in a sample of 51 pairs of TBI survivors and their caregivers living in Colombia, survivors receiving care from a family member who reported a higher level of burden had poorer objective neuropsychological functioning than those receiving care from a family member who reported a lower level of burden, after controlling for survivor education and history of occupational therapy. Therefore, a family-focused approach might maximize intervention effectiveness, especially for Latin American and Hispanic families, which tend to be characterized by a strong sense of familism. The emphasis on family can create problems in a healthcare system that views the individual as the primary unit.

To Fear Is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls.

Science.gov (United States)

Visser-Keizer, Annemarie C; Westerhof-Evers, Herma J; Gerritsen, Marleen J J; van der Naalt, Joukje; Spikman, Jacoba M

2016-01-01

Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has not been investigated how recognition of fear influences risk behavior in healthy subjects and TBI patients. The ability to recognize fear is thought to be related to the ability to experience fear and to use it as a warning signal to guide decision making. We hypothesized that a better ability to recognize fear would be related to a better regulation of risk behavior, with healthy controls outperforming TBI patients. To investigate this, 59 healthy subjects and 49 TBI patients were assessed with a test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests) and a gambling task (Iowa Gambling Task (IGT)). The results showed that, regardless of post traumatic amnesia duration or the presence of frontal lesions, patients were more impaired than healthy controls on both fear recognition and decision making. In both groups, a significant relationship was found between better fear recognition, the development of an advantageous strategy across the IGT and less risk behavior in the last blocks of the IGT. Educational level moderated this relationship in the final block of the IGT. This study has important clinical implications, indicating that impaired decision making and risk behavior after TBI can be preceded by deficits in the processing of fear.

To Fear Is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls.

Directory of Open Access Journals (Sweden)

Annemarie C Visser-Keizer

Full Text Available Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI, in particular when the frontal lobe is damaged. So far, it has not been investigated how recognition of fear influences risk behavior in healthy subjects and TBI patients. The ability to recognize fear is thought to be related to the ability to experience fear and to use it as a warning signal to guide decision making. We hypothesized that a better ability to recognize fear would be related to a better regulation of risk behavior, with healthy controls outperforming TBI patients. To investigate this, 59 healthy subjects and 49 TBI patients were assessed with a test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests and a gambling task (Iowa Gambling Task (IGT. The results showed that, regardless of post traumatic amnesia duration or the presence of frontal lesions, patients were more impaired than healthy controls on both fear recognition and decision making. In both groups, a significant relationship was found between better fear recognition, the development of an advantageous strategy across the IGT and less risk behavior in the last blocks of the IGT. Educational level moderated this relationship in the final block of the IGT. This study has important clinical implications, indicating that impaired decision making and risk behavior after TBI can be preceded by deficits in the processing of fear.

Blood Biomarker Profile of TBI-Associated Cognitive Impairment Among Old and Young Veterans

Science.gov (United States)

2017-10-01

Unclassified c. THIS PAGE Unclassified Unclassified 9 19b. TELEPHONE NUMBER (include area code) Email : cgawards@ncire.org Table of Contents...analyze and interpret the results, comparing the biomarker profiles of veterans with TBI, controls, and veterans with mild AD, and write them up for

Tribes and tribulations: interdisciplinary eHealth in providing services for people with a traumatic brain injury (TBI).

Science.gov (United States)

Hines, M; Brunner, M; Poon, S; Lam, M; Tran, V; Yu, D; Togher, L; Shaw, T; Power, E

2017-11-21

eHealth has potential for supporting interdisciplinary care in contemporary traumatic brain injury (TBI) rehabilitation practice, yet little is known about whether this potential is being realised, or what needs to be done to further support its implementation. The purpose of this study was to explore health professionals' experiences of, and attitudes towards eHealth technologies to support interdisciplinary practice within rehabilitation for people after TBI. A qualitative study using narrative analysis was conducted. One individual interview and three focus groups were conducted with health professionals (n = 17) working in TBI rehabilitation in public and private healthcare settings across regional and metropolitan New South Wales, Australia. Narrative analysis revealed that participants held largely favourable views about eHealth and its potential to support interdisciplinary practice in TBI rehabilitation. However, participants encountered various issues related to (a) the design of, and access to electronic medical records, (b) technology, (c) eHealth implementation, and (d) information and communication technology processes that disconnected them from the work they needed to accomplish. In response, health professionals attempted to make the most of unsatisfactory eHealth systems and processes, but were still mostly unsuccessful in optimising the quality, efficiency, and client-centredness of their work. Attention to sources of disconnection experienced by health professionals, specifically design of, and access to electronic health records, eHealth resourcing, and policies and procedures related to eHealth and interdisciplinary practice are required if the potential of eHealth for supporting interdisciplinary practice is to be realised.

Toward Development of a Field-Deployable Imaging Device for TBI

Science.gov (United States)

2014-03-01

of the head then application of a lotion hair remover. Prior to surgery, lidocaine (1 mg/kg) was injected subcutaneously to the surgery site. For...resonance imaging (MRI) are capable of identifying TBI, their logistics make them ineffective diagnostic tools in the field, where rapid triage can...Dwight Co, INC., Princeton, NJ, USA). Following epilation, subcutaneous lidocaine (0.08 mL, 20 mg/mL) and bupivicaine (0.08 mL, 0.32 mg/mL) were

Modeling, planning and XiO R CMS validation of TBI treatment (extended SSD 400 cm)

International Nuclear Information System (INIS)

Teijeiro, A.; Pereira, L.; Moral, F. del; Vazquez, J.; Lopez Medina, A.; Meal, A.; Andrade Alvarez, B.; Salgado Fernandez, M.; Munoz, V.

2011-01-01

The whole body irradiation (TBI) is a radiotherapy technique previously used a bone marrow transplant and for certain blood diseases, in which a patient is irradiated to extended distance (SSD from 350 to 400). The aim of the TBI is to kill tumor cells in the receiver and prevent rejection of transplanted bone marrow. The dose is prescribed at the midpoint of the abdomen around the navel wing. The most planners not permit the treatment of patients with a much higher SSD to 100 cm, also using the table LUT with spoiler to increase skin dose should be taken into account This requires measurements and checks ad hoc if you use a planner, because modeling is not optimized a priori for an SSD of 400 cm.

Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

Energy Technology Data Exchange (ETDEWEB)

Dandekar, Prasad [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Harmer, Clive; Barbachano, Yolanda [Department of Clinical Research and Development, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher [Head and Neck-Thyroid Unit, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom); Newbold, Kate [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Consultant Clinical Oncologist, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom)

2009-06-01

Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

Effect of binasal occlusion (BNO) and base-in prisms on the visual-evoked potential (VEP) in mild traumatic brain injury (mTBI).

Science.gov (United States)

Yadav, Naveen K; Ciuffreda, Kenneth J

2014-01-01

To assess quantitatively the effect and relative contribution of binasal occlusion (BNO) and base-in prisms (BI) on visually-evoked potential (VEP) responsivity in persons with mild traumatic brain injury (mTBI) and the symptom of visual motion sensitivity (VMS), as well as in visually-normal (VN) individuals. Subjects were comprised of 20 VN adults and 15 adults with mTBI and VMS. There were four test conditions: (1) conventional pattern VEP, which served as the baseline comparison condition; (2) VEP with BNO alone; (3) VEP with 2 pd BI prisms before each eye; and (4) VEP with the above BNO and BI prism combination. In mTBI, the mean VEP amplitude increased significantly in nearly all subjects (∼90%) with BNO alone. In contrast, in VN, it decreased significantly with BNO alone in all subjects (100%), as compared to the other test conditions. These objective findings were consistent with improvements in visual impressions and sensorimotor tasks in the group with mTBI. Latency remained within normal limits under all test conditions in both groups. Only the BNO condition demonstrated significant, but opposite and consistent, directional effects on the VEP amplitude in both groups. The BNO-VEP test condition may be used clinically for the objectively-based, differential diagnosis of persons suspected of having mTBI and VMS from the VNs.

Variation in structure and process of care in traumatic brain injury: Provider profiles of European Neurotrauma Centers participating in the CENTER-TBI study

NARCIS (Netherlands)

M.C. Cnossen (Maryse); S. Polinder (Suzanne); Lingsma, H.F. (Hester F.); A.I.R. Maas (Andrew); D.K. Menon (David ); E.W. Steyerberg (Ewout); Adams, H. (Hadie); Alessandro, M. (Masala); J.E. Allanson (Judith); Amrein, K. (Krisztina); Andaluz, N. (Norberto); N. Andelic (Nada); Andrea, N. (Nanni); L. Andreassen (Lasse); Anke, A. (Audny); Antoni, A. (Anna); Ardon, H. (Hilko); G. Audibert (Gérard); Auslands, K. (Kaspars); Azouvi, P. (Philippe); Baciu, C. (Camelia); Bacon, A. (Andrew); Badenes, R. (Rafael); Baglin, T. (Trevor); Bartels, R. (Ronald); Barzó, P. (Pál); Bauerfeind, U. (Ursula); R. Beer (Ronny); Belda, F.J. (Francisco Javier); B.-M. Bellander (Bo-Michael); A. Belli (Antonio); Bellier, R. (Rémy); H. Benali (Habib); Benard, T. (Thierry); M. Berardino (Maurizio); Beretta, L. (Luigi); Beynon, C. (Christopher); Bilotta, F. (Federico); H. Binder (Harald); Biqiri, E. (Erta); Blaabjerg, M. (Morten); Borgen, L.S. (Lund Stine); Bouzat, P. (Pierre); Bragge, P. (Peter); A. Brazinova (Alexandra); F. Brehar (Felix); Brorsson, C. (Camilla); Buki, A. (Andras); M. Bullinger (Monika); Bučková, V. (Veronika); Calappi, E. (Emiliana); P. Cameron (Peter); Carbayo, L.G. (Lozano Guillermo); Carise, E. (Elsa); Carpenter, C.; Castaño-León, A.M. (Ana M.); Causin, F. (Francesco); Chevallard, G. (Giorgio); A. Chieregato (Arturo); G. Citerio (Giuseppe); M. Coburn (Mark); J.P. Coles (Jonathan P.); Cooper, J.D. (Jamie D.); Correia, M. (Marta); A. Covic (Amra); N. Curry (Nicola); E. Czeiter (Endre); M. Czosnyka (Marek); Dahyot-Fizelier, C. (Claire); F. Damas (François); P. Damas (Pierre); H. Dawes (Helen); De Keyser, V. (Véronique); F. Della Corte (Francesco); B. Depreitere (Bart); Ding, S. (Shenghao); D.W.J. Dippel (Diederik); K. Dizdarevic (Kemal); Dulière, G.-L. (Guy-Loup); Dzeko, A. (Adelaida); G. Eapen (George); Engemann, H. (Heiko); A. Ercole (Ari); P. Esser (Patrick); Ezer, E. (Erzsébet); M. Fabricius (Martin); V.L. Feigin (V.); Feng, J. (Junfeng); Foks, K. (Kelly); F. Fossi (Francesca); Francony, G. (Gilles); J. Frantzén (Janek); Freo, U. (Ulderico); S.K. Frisvold (Shirin Kordasti); Furmanov, A. (Alex); P. Gagliardo (Pablo); D. Galanaud (Damien); G. Gao (Guoyi); K. Geleijns (Karin); A. Ghuysen (Alexandre); Giraud, B. (Benoit); Glocker, B. (Ben); Gomez, P.A. (Pedro A.); Grossi, F. (Francesca); R.L. Gruen (Russell); Gupta, D. (Deepak); J.A. Haagsma (Juanita); E. Hadzic (Ermin); I. Haitsma (Iain); J.A. Hartings (Jed); R. Helbok (Raimund); E. Helseth (Eirik); Hertle, D. (Daniel); S. Hill (Sean); Hoedemaekers, A. (Astrid); S. Hoefer (Stefan); P.J. Hutchinson (Peter J.); Håberg, A.K. (Asta Kristine); B.C. Jacobs (Bart); Janciak, I. (Ivan); K. Janssens (Koen); J.-Y. Jiang (Ji-Yao); Jones, K. (Kelly); Kalala, J.-P. (Jean-Pierre); Kamnitsas, K. (Konstantinos); Karan, M. (Mladen); Karau, J. (Jana); A. Katila (Ari); M. Kaukonen (Maija); Keeling, D. (David); Kerforne, T. (Thomas); N. Ketharanathan (Naomi); J. Kettunen (Johannes); Kivisaari, R. (Riku); A.G. Kolias (Angelos G.); Kolumbán, B. (Bálint); E.J.O. Kompanje (Erwin); D. Kondziella (Daniel); L.-O. Koskinen (Lars-Owe); Kovács, N. (Noémi); F. Kalovits (Ferenc); A. Lagares (Alfonso); L. Lanyon (Linda); S. Laureys (Steven); Lauritzen, M. (Martin); F.E. Lecky (Fiona); C. Ledig (Christian); R. Lefering; V. Legrand (Valerie); Lei, J. (Jin); L. Levi (Leon); R. Lightfoot (Roger); H.F. Lingsma (Hester); D. Loeckx (Dirk); Lozano, A. (Angels); Luddington, R. (Roger); Luijten-Arts, C. (Chantal); A.I.R. Maas (Andrew I.R.); MacDonald, S. (Stephen); MacFayden, C. (Charles); M. Maegele (Marc); M. Majdan (Marek); Major, S. (Sebastian); A. Manara (Alex); Manhes, P. (Pauline); G. Manley (Geoffrey); Martin, D. (Didier); C. Martino (Costanza); Maruenda, A. (Armando); H. Maréchal (Hugues); Mastelova, D. (Dagmara); Mattern, J. (Julia); C. McMahon (Catherine); Melegh, B. (Béla); T. Menovsky (Tomas); C. Morganti-Kossmann (Cristina); Mulazzi, D. (Davide); Mutschler, M. (Manuel); H. Mühlan (Holger); Negru, A. (Ancuta); D. Nelson (David); E. Neugebauer (Eddy); V.F. Newcombe (Virginia F.); Noirhomme, Q. (Quentin); Nyirádi, J. (József); M. Oddo (Mauro); Oldenbeuving, A. (Annemarie); M. Oresic (Matej); Ortolano, F. (Fabrizio); A. Palotie (Aarno); P.M. Parizel; Patruno, A. (Adriana); J.-F. Payen (Jean-François); Perera, N. (Natascha); V. Perlbarg (Vincent); Persona, P. (Paolo); W.C. Peul (Wilco); N. Pichon (Nicolas); Piilgaard, H. (Henning); A. Piippo (Anna); Pili, F.S. (Floury Sébastien); M. Pirinen (Matti); H. Ples (Horia); Pomposo, I. (Inigo); M. Psota (Marek); P. Pullens (Pim); L. Puybasset (Louis); A. Ragauskas (Arminas); Raj, R. (Rahul); Rambadagalla, M. (Malinka); Rehorčíková, V. (Veronika); J.K.J. Rhodes (Jonathan K.J.); S. Richardson (Sylvia); S. Ripatti (Samuli); S. Rocka (Saulius); Rodier, N. (Nicolas); Roe, C. (Cecilie); Roise, O. (Olav); Roks, G. (Gerwin); Romegoux, P. (Pauline); J. Rosand (Jonathan); Rosenfeld, J. (Jeffrey); C. Rosenlund (Christina); G. Rosenthal (Guy); R. Rossaint (Rolf); S. Rossi (Sandra); Rostalski, T. (Tim); Rueckert, D.L. (Danie L.); Ruiz De Arcaute, F. (Felix); M. Rusnák (Martin); Sacchi, M. (Marco); Sahakian, B. (Barbara); J. Sahuquillo (Juan); O. Sakowitz (Oliver); Sala, F. (Francesca); Sanchez-Pena, P. (Paola); Sanchez-Porras, R. (Renan); Sandor, J. (Janos); Santos, E. (Edgar); N. Sasse (Nadine); Sasu, L. (Luminita); Savo, D. (Davide); I.B. Schipper (Inger); Schlößer, B. (Barbara); S. Schmidt (Silke); Schneider, A. (Annette); H. Schoechl (Herbert); G.G. Schoonman; R. Schou (Rico); E. Schwendenwein (Elisabeth); Schöll, M. (Michael); Sir, O. (Özcan); T. Skandsen (Toril); Smakman, L. (Lidwien); D. Smeets (Dirk); Smielewski, P. (Peter); Sorinola, A. (Abayomi); Stamatakis, E.L. (Emmanue L.); S. Stanworth (Simon); Stegemann, K. (Katrin); Steinbüchel, N. (Nicole); R. Stevens (Robert); W. Stewart (William); N. Stocchetti (Nino); Sundström, N. (Nina); Synnot, A. (Anneliese); J. Szabó (József); J. Söderberg (Jeannette); F.S. Taccone (Fabio); Tamás, V. (Viktória); Tanskanen, P. (Päivi); A. Tascu (Alexandru); Taylor, M.S. (Mark Steven); Te Ao, B. (Braden); O. Tenovuo (Olli); Teodorani, G. (Guido); A. Theadom (Alice); Thomas, M. (Matt); D. Tibboel (Dick); C.M. Tolias (Christos M.); Tshibanda, J.-F.L. (Jean-Flory Luaba); Tudora, C.M. (Cristina Maria); P. Vajkoczy (Peter); Valeinis, E. (Egils); W. van Hecke (Wim); D. Van Praag (Dominique); D. Van Roost (Dirk); Van Vlierberghe, E. (Eline); Vande Vyvere, T. (Thijs); Vanhaudenhuyse, A. (Audrey); A. Vargiolu (Alessia); E. Vega (Emmanuel); J. Verheyden (Jan); P.M. Vespa (Paul M.); A. Vik (Anne); R. Vilcinis (Rimantas); Vizzino, G. (Giacinta); C.L.A.M. Vleggeert-Lankamp (Carmen); V. Volovici (Victor); P. Vulekovic (Peter); Vámos, Z. (Zoltán); Wade, D. (Derick); Wang, K.K.W. (Kevin K.W.); Wang, L. (Lei); Wildschut, E. (Eno); G. Williams (Guy); Willumsen, L. (Lisette); Wilson, A. (Adam); L. Wilson (Lindsay); Winkler, M.K.L. (Maren K. L.); P. Ylén (Peter); Younsi, A. (Alexander); M. Zaaroor (Menashe); Zhang, Z. (Zhiqun); Zheng, Z. (Zelong); Zumbo, F. (Fabrizio); De Lange, S. (Stefanie); G.C.W. De Ruiter (Godard C.W.); Den Boogert, H. (Hugo); Van Dijck, J. (Jeroen); T.A. van Essen (T.); C.M. van Heugten (Caroline M.); M. van der Jagt (Mathieu); J. van der Naalt (Joukje)

2016-01-01

textabstractIntroduction: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map

Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI) in adolescent rats

OpenAIRE

Yamakawa, Glenn R.; Lengkeek, Connor; Salberg, Sabrina; Spanswick, Simon C.; Mychasiuk, Richelle

2017-01-01

Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI), we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury...

Rates of TBI-related Emergency Department Visits, Hospitalizations, and Deaths - United States, 2001 – 2010

Data.gov (United States)

U.S. Department of Health & Human Services — In general, total combined rates for traumatic brain injury (TBI)-related emergency department (ED) visits, hospitalizations and deaths have increased over the past...

In vitro radiation studies on Ewing's sarcoma cell lines and human bone marrow: application to the clinical use of total body irradiation (TBI)

International Nuclear Information System (INIS)

Kinsella, T.J.; Mitchell, J.B.; McPherson, S.; Miser, J.; Triche, T.; Glatstein, E.

1984-01-01

Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, the authors have studied in the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc. The Ewing's lines showed a larger D 0 and anti-n compared to the bone marrow CFU. No repair of potentially lethal radiation damage (PLDR) was found after 4.5 Gy in plateau phase Ewing's sarcoma cells. A theoretical split dose survival curve for both the Ewing's sarcoma lines and human bone marrow CFUc using this TBI schedule shows a significantly lower surviving fraction (10 -4 -10 -5 ) for the bone marrow CFUc. Based on these in vitro results, two 4.0 Gy fractions separated by 24 hours is proposed as the TBI regimen. Because of the potentially irreversible damage to bone marrow, autologous bone marrow transplantation following the TBI is felt to be necessary. The details of this clinical protocol in high risk Ewing's sarcoma patients are outlined

Active-duty military service members' visual representations of PTSD and TBI in masks.

Science.gov (United States)

Walker, Melissa S; Kaimal, Girija; Gonzaga, Adele M L; Myers-Coffman, Katherine A; DeGraba, Thomas J

2017-12-01

Active-duty military service members have a significant risk of sustaining physical and psychological trauma resulting in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Within an interdisciplinary treatment approach at the National Intrepid Center of Excellence, service members participated in mask making during art therapy sessions. This study presents an analysis of the mask-making experiences of service members (n = 370) with persistent symptoms from combat- and mission-related TBI, PTSD, and other concurrent mood issues. Data sources included mask images and therapist notes collected over a five-year period. The data were coded and analyzed using grounded theory methods. Findings indicated that mask making offered visual representations of the self related to individual personhood, relationships, community, and society. Imagery themes referenced the injury, relational supports/losses, identity transitions/questions, cultural metaphors, existential reflections, and conflicted sense of self. These visual insights provided an increased understanding of the experiences of service members, facilitating their recovery.

Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT)

International Nuclear Information System (INIS)

Gerstein, Johanna; Meyer, Andreas; Fruehauf, Joerg; Karstens, Johann H.; Bremer, Michael; Sykora, Karl-Walter

2009-01-01

Purpose: to retrospectively assess the incidence and time course of renal dysfunction in children (≤ 16 years) following total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Patients and methods: between 1986 and 2003, 92 children (median age, 11 years; range, 3-16 years) underwent TBI before allogeneic SCT. 43 of them had a minimum follow-up of 12 months (median, 51 months; range, 12-186 months) and were included into this analysis. Conditioning regimen included chemotherapy and fractionated TBI with 12 Gy (n = 26) or 11.1 Gy (n = 17). In one patient, renal dose was limited to 10 Gy by customized renal shielding due to known nephropathy prior to SCt. Renal dysfunction was defined as an increase of serum creatinine > 1.25 times the upper limit of age-dependent normal. Results: twelve children (28%) experienced an episode of renal dysfunction after a median of 2 months (range, 1-10 months) following SCT. In all but one patient renal dysfunction was transient and resolved after a median of 8 months (range, 3-16 months). One single patient developed persistent renal dysfunction with onset at 10 months after SCT. None of these patients required dialysis. The actuarial 3-year freedom from persistent renal toxicity for children surviving > 12 months after SCt was 97.3%. Conclusion: the incidence of persistent renal dysfunction after fractionated TBI with total doses ≤ 12 Gy was very low in this analysis. (orig.)

Alterations of total non stimulated salivary flow in patients with squamous cell carcinoma of the mouth and oropharynx submitted to hyperfractionated radiation therapy; Alteracoes do fluxo salivar total nao estimulado em pacientes portadores de carcinoma espinocelular de boca e orofaringe submetidos a radioterapia por hiperfracionamento

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Guebur, Maria Isabela [Faculdades Integradas Espirita, Curitiba, PR (Brazil)]. E-mail: isabelaguebur@aol.com; Rapoport, Abrao [Hospital Heliopolis (HOSPHEL), Sao Paulo, SP (Brazil). Curso de Pos-Graduacao em Ciencias da Saude; Sassi, Laurindo Moacir [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Servico de Cirurgia e Traumatologia Buco-Maxico-Facial; Oliveira, Benedito Valdecir de; Ramos, Gyl Henrique Albrecht [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Servico de Cirurgia de Cabeca e Pescoco; Pereira, Jose Carlos Gasparin [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Servico de Radioterapia

2004-07-01

Prevention and early diagnosis are actually the most effective measures that we dispose to improve the prognostic of the malignant tumors. The mouth and oropharynx tumors are treated with success, when early diagnosed. The radiotherapy is almost always one of the selected treatments for these tumors. When cancer is diagnosed in advanced stages, many a time the treatment needs to be carried out swiftly to be efficient, and consequently the radio therapist use the hyperfractionated therapy, with the patient receiving two lower doses of radiation in two sessions daily, amounting to a higher daily dosage, of about 160 cGy/2x/day. When the major salivary glands are present in the radiated field, the xerostomia appears by the second week of treatment (1500 to 2000 cGy), changing the patient's health, and causing difficulties for him to eat, speak and sleep. The objective of this study was to evaluate the quantitative alterations of the total non stimulated salivate flow of patients who underwent hyperfractionated therapy for the treatment of squamous cell carcinoma of mouth and oropharynx. Samples of twelve male patients saliva from Erasto Gaertner Hospital in Curitiba, PR, Brazil, were examined. Two samples of saliva were collected from each patient, the first one before the beginning of the radiotherapy, and the second at the end of the treatment. As a result, we obtained salivary loss in 91.7% of the patients, with a percentage of total salivary flow loss of 62.9%, registered in the second collection. We concluded that the hyperfractionated therapy causes a marked xerostomia when the major salivary glands are in the radiated field. (author)

School Psychologists' Knowledge and Self-Efficacy in Working with Students with TBI

Science.gov (United States)

Glang, Ann E.; McCart, Melissa; Moore, Christabelle L.; Davies, Susan

2017-01-01

Approximately 145,000 U.S. children experience lasting effects of traumatic brain injury (TBI) that manifest in social, behavioural, physical, and cognitive challenges in the school setting. School psychologists have an essential role in identifying students who need support and in determining eligibility under the Individuals with Disabilities…

Prospective study of cyclophosphamide, thiotepa, carboplatin combined with adoptive DC-CIK followed by metronomic cyclophosphamide therapy as salvage treatment for triple negative metastatic breast cancers patients (aged <45).

Science.gov (United States)

Wang, X; Ren, J; Zhang, J; Yan, Y; Jiang, N; Yu, J; Di, L; Song, G; Che, L; Jia, J; Zhou, X; Yang, H; Lyerly, H K

2016-01-01

The recent immunotherapy treatment on triple-negative breast cancer (TNBC) leads to the breakthrough assignation. In this study, we have tried the new combinations of specific chemo with DC-CIKs immunotherapy to treat those patients. Twenty-three metastatic anthracyclines and taxanes pretreated TNBC younger (mean 41.5 years) patients were initially mobilized with cyclophosphamide (3 g/m(2)) for the preparation of CD34(+) peripheral blood mononuclear cells as the resources for generating DC/CIKs and marrow function supports. All cases were subsequently experienced 2 cycles of chemotherapy with cyclophosphamide 3 g/m(2), thiotepa 150 mg/m(2), and carboplatin AUC = 6, Q4w. The patients then received 3 infusions of DC-CIKs at the chemo intervals and followed by maintenance therapy with oral cyclophosphamide 50 mg daily. The endpoints were progression-free survival and overall survival. The partial response rate was 13.0 %, stable and progressive disease rates were 56.5 and 30.4 %, respectively. The median PFS was 13.5 months (95 % confidence interval (CI) 10.1-16.9 months) and OS was 15.2 months (95 % CI 12.5-18.1 months). The most common serious adverse events were neutropenia (100.0 %) and anemia (69.7 %) but without treatment-related mortality. These data suggested that such combination therapy model be effective and safe for younger metastatic TNBC exposure to previous anthracyclines and taxanes based adjuvant chemotherapy.

A Phase II Study of Preradiotherapy Chemotherapy Followed by Hyperfractionated Radiotherapy for Newly Diagnosed High-Risk Medulloblastoma/Primitive Neuroectodermal Tumor: A Report From the Children's Oncology Group (CCG 9931)

International Nuclear Information System (INIS)

Allen, Jeffrey; Donahue, Bernadine; Mehta, Minesh; Miller, Douglas C.; Rorke, Lucy B.; Jakacki, Regina; Robertson, Patricia; Sposto, Richard; Holmes, Emi; Vezina, Gilbert; Muraszko, Karin; Puccetti, Diane; Prados, Michael; Chan, K.-W.

2009-01-01

Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). Methods and Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm 2 postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. Results: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% ± 5% and 52% ± 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. Conclusions: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.

Phase II study of tolerance and efficacy of hyperfractionated radiotherapy and 5-fluorouracil, cisplatin, and paclitaxel (Taxol) in stage III and IV inoperable and/or unresectable head-and-neck squamous cell carcinoma: A-2 protocol

International Nuclear Information System (INIS)

Abitbol, Andre; Abdel-Wahab, May; Lewin, Alan; Troner, Michael; Rodrigues, Maria-Amelia; Hamilton-Nelson, Kara L.; Markoe, Arnold

2002-01-01

Purpose: To determine the toxicity and efficacy of concurrent 5-fluorouracil (5-FU), cisplatin, and paclitaxel (Taxol) and hyperfractionated radiotherapy in locally advanced squamous cell carcinoma of the head and neck. Methods and Materials: Twenty-seven patients were entered into this Phase II trial. Eligible patients had Stage III or IV head-and-neck squamous cell carcinoma arising from the oral cavity, hypopharynx, oropharynx, nasopharynx, or larynx. The plan of treatment consisted of hyperfractionated radiotherapy (74.4 Gy at twice daily fractions of 1.2 Gy). Chemotherapy was given on Weeks 1, 5, and 8 as follows: 5-FU at 750 mg/m 2 as a constant infusion for 24 h for 3 days; cisplatin at 50 mg/m 2 in 250-500 mL D5 0.5 NS or NS infusion during 2-4 h, and paclitaxel at 70 mg/m 2 infused in 500 mL NS during 3 h. Results: The overall survival rate of the entire group was 81.5%, 66.7%, and 63% at 1, 2, and 3 years, respectively. The median follow-up was 40.2 months (range 30-62). Of the 27 patients, 19 (70%) had a complete response and an overall survival rate of 100% at 1 year and 94% at 2 and 3 years. The disease-free survival rate of the latter group was 95% at 1 year and 84% at 2 and 3 years. Of the 27 patients, 18 (67%) maintained the complete response until the last follow-up visit or death. Percutaneous endoscopic gastrostomy dependency occurred for a median of 7.1 months. Grade 3 and 4 mucositis occurred in 20 and 3 patients, respectively. Six patients were hospitalized for leukopenic fever. Late toxicities included L'Hermitte syndrome (n=3), osteoradionecrosis (n=1), hypothyroidism (n=4), paresthesias (n=1), aspiration pneumonia (n=3), and esophageal strictures (8 patients underwent dilation). Conclusion: Combining hyperfractionated radiotherapy concurrently with 5-FU, cisplatin, and paclitaxel results in acceptable efficacy and toxicity. However, although a locoregional control benefit is suggested by the preliminary results of this trial, it needs to be

ACCELERATED HYPERFRACTIONATED RADIOTHERAPY IN THE TREATMENT FOR INOPERABLE, LOCALLY ADVANCED GASTRIC CANSER

Directory of Open Access Journals (Sweden)

S. S. Litinskiy

2015-01-01

Full Text Available Purpose: to compare survival of patients with locally advanced inoperable gastric cancer (LAIGC, receiving accelerated hyperfractionated (AHF or conventionally fractionated (CF radiation therapy (RT. Methods and Materials. Between November 1993 and March 2010, 137 patients with LAIGC receiving CF (2 Gy daily or AHF (1.3 Gy b.i.d. to total at least 50 Gy RT in combination or without chemotherapy were retrospectively selected from the hospital database of Arkhangelsk clinical oncological dispensary. Overall survival (OS assessed using actuarial analysis, Kaplan – Meier method and Cox regression. results. The CF and AHF groups were 102 and 35 patients, respectively. Median follow-up time for all patients was 12 years. By the time of analysis 123 (90 % patients of all cohort died. Median, 7-year survival were 24 (95 % confidence intervals (CI, 17–31 vs 16 (95 % CI, 11–21 months, hazard ratio (HR=0.71 (95 % CI, 0.46–1.06, р=0.097; and 19 % (95 % CI 8–34 % vs 6% (95 % CI 2–13 % in the AHF and CF groups, respectively. In multivariate OS model the difference decreased to HR=0.87 (95 % CI, 0.49–1.55. The location of the tumor in median third (HR=0.60, 95 % CI, 0.37–0.99 in refer to upper third was the only independent factor influencing survival.  There was no influence of the total dose in chosen level on survival. conclusion. Our retrospective shows trend towards better OS for those LAIGC patients receiving RT in AHF regimen compared to CF. The prospective randomized study with conformal radiation technics is necessary to confirm these findings.

Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI.

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Wiseman-Hakes, Catherine; Murray, Brian; Moineddin, Rahim; Rochon, Elizabeth; Cullen, Nora; Gargaro, Judith; Colantonio, Angela

2013-01-01

To longitudinally examine objective and self-reported outcomes for recovery of cognition, communication, mood and participation in adults with traumatic brain injury (TBI) and co-morbid post-traumatic sleep/wake disorders. Prospective, longitudinal, single blind outcome study. Community-based. Ten adults with moderate-severe TBI and two adults with mild TBI and persistent symptoms aged 18-58 years. Six males and six females, who were 1-22 years post-injury and presented with self-reported sleep/wake disturbances with onset post-injury. Individualized treatments for sleep/wake disorders that included sleep hygiene recommendations, pharmacological interventions and/or treatments for sleep apnea with follow-up. Insomnia Severity Index, Beck Depression and Anxiety Inventories, Latrobe Communication Questionnaire, Speed and Capacity of Language Processing, Test of Everyday Attention, Repeatable Battery for the Assessment of Neuropsychological Status, Daily Cognitive-Communication and Sleep Profile. Group analysis revealed positive trends in change for each measure and across sub-tests of all measures. Statistically significant changes were noted in insomnia severity, p = 0.0003; depression severity, p = 0.03; language, p = 0.01; speed of language processing, p = 0.007. These results add to a small but growing body of evidence that sleep/wake disorders associated with TBI exacerbate trauma-related cognitive, communication and mood impairments. Treatment for sleep/wake disorders may optimize recovery and outcomes.

Neuromodulation and Neurorehabilitation for Treatment of Functional Deficits after TBI Plus PTSD

Science.gov (United States)

2017-10-01

average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...by determining the neurobehavioral and neural effects of repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive technique to... stimulate the brain. The evidence of therapeutic efficacy from the literature in non-TBI related neurologic populations combined with our preliminary

Project Career: Perceived benefits of iPad apps among college students with Traumatic Brain Injury (TBI).

Science.gov (United States)

Jacobs, K; Leopold, A; Hendricks, D J; Sampson, E; Nardone, A; Lopez, K B; Rumrill, P; Stauffer, C; Elias, E; Scherer, M; Dembe, J

2017-09-14

Project Career is an interprofessional five-year development project designed to improve academic and employment success of undergraduate students with a traumatic brain injury (TBI) at two- and four-year colleges and universities. Students receive technology in the form of iPad applications ("apps") to support them in and out of the classroom. To assess participants' perspectives on technology at baseline and perceived benefit of apps after 6 and 12 months of use. This article address a component of a larger study. Participants included 50 college-aged students with traumatic brain injuries. Statistical analysis included data from two Matching Person and Technology (MPT) assessment forms, including the Survey of Technology Use at baseline and the Assistive Technology Use Follow-Up Survey: Apps Currently Using, administered at 6- and 12-months re-evaluation. Analyses included frequencies and descriptives. Average scores at baseline indicated positive perspectives on technology. At 6 months, quality of life (67%) and academics (76%) improved moderately or more from the use of iPad apps. At 12 months, quality of life (65%) and academics (82%) improved moderately or more from the use of iPad apps. Students with a TBI have positive perspectives on technology use. The results on perceived benefit of apps indicated that students with a TBI (including civilians and veterans) report that the apps help them perform in daily life and academic settings.

Traumatic brain injury (TBI) outcomes in an LMIC tertiary care centre and performance of trauma scores.

Science.gov (United States)

Samanamalee, Samitha; Sigera, Ponsuge Chathurani; De Silva, Ambepitiyawaduge Pubudu; Thilakasiri, Kaushila; Rashan, Aasiyah; Wadanambi, Saman; Jayasinghe, Kosala Saroj Amarasiri; Dondorp, Arjen M; Haniffa, Rashan

2018-01-08

This study evaluates post-ICU outcomes of patients admitted with moderate and severe Traumatic Brain Injury (TBI) in a tertiary neurocritical care unit in an low middle income country and the performance of trauma scores: A Severity Characterization of Trauma, Trauma and Injury Severity Score, Injury Severity Score and Revised Trauma Score in this setting. Adult patients directly admitted to the neurosurgical intensive care units of the National Hospital of Sri Lanka between 21st July 2014 and 1st October 2014 with moderate or severe TBI were recruited. A telephone administered questionnaire based on the Glasgow Outcome Scale Extended (GOSE) was used to assess functional outcome of patients at 3 and 6 months after injury. The economic impact of the injury was assessed before injury, and at 3 and 6 months after injury. One hundred and one patients were included in the study. Survival at ICU discharge, 3 and 6 months after injury was 68.3%, 49.5% and 45.5% respectively. Of the survivors at 3 months after injury, 43 (86%) were living at home. Only 19 (38%) patients had a good recovery (as defined by GOSE 7 and 8). Three months and six months after injury, respectively 25 (50%) and 14 (30.4%) patients had become "economically dependent". Selected trauma scores had poor discriminatory ability in predicting mortality. This observational study of patients sustaining moderate or severe TBI in Sri Lanka (a LMIC) reveals only 46% of patients were alive at 6 months after ICU discharge and only 20% overall attained a good (GOSE 7 or 8) recovery. The social and economic consequences of TBI were long lasting in this setting. Injury Severity Score, Revised Trauma Score, A Severity Characterization of Trauma and Trauma and Injury Severity Score, all performed poorly in predicting mortality in this setting and illustrate the need for setting adapted tools.

Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI

Directory of Open Access Journals (Sweden)

Cassavaugh Nicholas D

2011-10-01

Full Text Available Abstract Background Traumatic brain injury (TBI disrupts the central and executive mechanisms of arm(s and postural (trunk and legs coordination. To address these issues, we developed a 3D immersive videogame-- Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component with a system of multiple rewards, making the game challenging, competitive, motivating and fun. Effect of a short-term practice with the Octopus game on arm-postural coordination in patients with TBI was tested. Methods The game was developed using WorldViz Vizard software, integrated with the Qualysis system for motion analysis. Avatars of the participant's hands precisely reproducing the real-time kinematic patterns were synchronized with the simulated environment, presented in the first person 3D view on an 82-inch DLP screen. 13 individuals with mild-to-moderate manifestations of TBI participated in the study. While standing in front of the screen, the participants interacted with a computer-generated environment by popping bubbles blown by the Octopus. The bubbles followed a specific trajectory. Interception of the bubbles with the left or right hand avatar allowed flexible use of the postural segments for balance maintenance and arm transport. All participants practiced ten 90-s gaming trials during a single session, followed by a retention test. Arm-postural coordination was analysed using principal component analysis. Results As a result of the short-term practice, the participants improved in game performance, arm movement time, and precision. Improvements were achieved mostly by adapting efficient arm-postural coordination strategies. Of the 13 participants, 10 showed an immediate increase in arm forward reach and single-leg stance time. Conclusion

Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI.

Science.gov (United States)

Ustinova, Ksenia I; Leonard, Wesley A; Cassavaugh, Nicholas D; Ingersoll, Christopher D

2011-10-31

Traumatic brain injury (TBI) disrupts the central and executive mechanisms of arm(s) and postural (trunk and legs) coordination. To address these issues, we developed a 3D immersive videogame--Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component with a system of multiple rewards, making the game challenging, competitive, motivating and fun. Effect of a short-term practice with the Octopus game on arm-postural coordination in patients with TBI was tested. The game was developed using WorldViz Vizard software, integrated with the Qualysis system for motion analysis. Avatars of the participant's hands precisely reproducing the real-time kinematic patterns were synchronized with the simulated environment, presented in the first person 3D view on an 82-inch DLP screen. 13 individuals with mild-to-moderate manifestations of TBI participated in the study. While standing in front of the screen, the participants interacted with a computer-generated environment by popping bubbles blown by the Octopus. The bubbles followed a specific trajectory. Interception of the bubbles with the left or right hand avatar allowed flexible use of the postural segments for balance maintenance and arm transport. All participants practiced ten 90-s gaming trials during a single session, followed by a retention test. Arm-postural coordination was analysed using principal component analysis. As a result of the short-term practice, the participants improved in game performance, arm movement time, and precision. Improvements were achieved mostly by adapting efficient arm-postural coordination strategies. Of the 13 participants, 10 showed an immediate increase in arm forward reach and single-leg stance time. These results support the feasibility of using the custom-made 3D

The item level psychometrics of the behaviour rating inventory of executive function-adult (BRIEF-A) in a TBI sample.

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Waid-Ebbs, J Kay; Wen, Pey-Shan; Heaton, Shelley C; Donovan, Neila J; Velozo, Craig

2012-01-01

To determine whether the psychometrics of the BRIEF-A are adequate for individuals diagnosed with TBI. A prospective observational study in which the BRIEF-A was collected as part of a larger study. Informant ratings of the 75-item BRIEF-A on 89 individuals diagnosed with TBI were examined to determine items level psychometrics for each of the two BRIEF-A indexes: Behaviour Rating Index (BRI) and Metacognitive Index (MI). Patients were either outpatients or at least 1 year post-injury. Each index measured a latent trait, separating individuals into five-to-six ability levels and demonstrated good reliability (0.94 and 0.96). Four items were identified that did not meet the infit criteria. The results provide support for the use of the BRIEF-A as a supplemental assessment of executive function in TBI populations. However, further validation is needed with other measures of executive function. Recommendations include use of the index scores over the Global Executive Composite score and use of the difficulty hierarchy for setting therapy goals.

Enhanced response rates in pancreatic cancer with concurrent continuous infusion(CI) low dose chemotherapy and hyperfractionated radiotherapy

International Nuclear Information System (INIS)

Bronn, Donald G.; Franklin, Roman; Krishnan, Rajan S.; Richardson, Ralph W.; Conlin, Christopher

1996-01-01

Objective: Many patients with a diagnosis of pancreatic cancer are not offered any therapeutic intervention other than surgical bypass due to very poor prognosis, poor patient tolerance to current therapeutic regimens, and a dismal tumor response to therapy. In view of these circumstances, an acceptable treatment regimen for pancreatic cancer must first demonstrate an ability to obtain a rapid tumor response with a regimen that will be well tolerated enabling the patient to maintain a good quality of life with full ambulatory status. Materials and Methods: Nine unresectable pancreatic cancer patients ((4(9)) had liver metastases) with an average age of 62 (range: 41-79) were treated with a concurrent regimen consisting of 5-Fluorouracil (CI 200-250 mg/m 2 /24 hrs) and Cisplatin (CI 5mg/24 hrs: 2 weeks on, 1 week off) given simultaneously with 3-D planned BID hyperfractionated radiotherapy to the pancreas (5940 cGy/66 fractions/6.5 weeks), and whole liver (1980 cGy/22 fractions/2 weeks), plus additional dose to the partial liver in metastatic disease. Continuous infusion combination chemotherapy was continued alone after radiotherapy for a total of six months. Chemotherapy was delivered by dual light weight portable external pumps. Hyperalimentation was used as needed to maintain nutritional status and warfarin thromboembolic prophylaxis was also utilized. Tumor response was monitored by monthly abdominal CAT scans, serum markers (CEA, CA 19-9), weight gain, and symptomatology. Full radiographic resolution of tumor mass was considered to be a complete response (CR), whereas 50% or greater radiographic decrease in size was considered a partial response (PR). Evaluation was done by independent diagnostic radiologists. Results: CR and PR of the pancreatic mass was achieved in 88% of all patients ((8(9))). CR was achieved in 44% of all patients ((4(9))). Patients with liver metastases exhibited 75% ((3(4))) PR in liver masses and either CR or PR in the primary site. All

Sci-Thur PM - Colourful Interactions: Highlights 08: ARC TBI using Single-Step Optimized VMAT Fields

International Nuclear Information System (INIS)

Hudson, Alana; Gordon, Deborah; Moore, Roseanne; Balogh, Alex; Pierce, Greg

2016-01-01

Purpose: This work outlines a new TBI delivery technique to replace a lateral POP full bolus technique. The new technique is done with VMAT arc delivery, without bolus, treating the patient prone and supine. The benefits of the arc technique include: increased patient experience and safety, better dose conformity, better organ at risk sparing, decreased therapist time and reduction of therapist injuries. Methods: In this work we build on a technique developed by Jahnke et al. We use standard arc fields with gantry speeds corrected for varying distance to the patient followed by a single step VMAT optimization on a patient CT to increase dose inhomogeneity and to reduce dose to the lungs (vs. blocks). To compare the arc TBI technique to our full bolus technique, we produced plans on patient CTs for both techniques and evaluated several dosimetric parameters using an ANOVA test. Results and Conclusions: The arc technique is able reduce both the hot areas to the body (D2% reduced from 122.2% to 111.8% p<0.01) and the lungs (mean lung dose reduced from 107.5% to 99.1%, p<0.01), both statistically significant, while maintaining coverage (D98% = 97.8% vs. 94.6%, p=0.313, not statistically significant). We developed a more patient and therapist-friendly TBI treatment technique that utilizes single-step optimized VMAT plans. It was found that this technique was dosimetrically equivalent to our previous lateral technique in terms of coverage and statistically superior in terms of reduced lung dose.

Sci-Thur PM - Colourful Interactions: Highlights 08: ARC TBI using Single-Step Optimized VMAT Fields

Energy Technology Data Exchange (ETDEWEB)

Hudson, Alana; Gordon, Deborah; Moore, Roseanne; Balogh, Alex; Pierce, Greg [Tom Baker Cancer Centre (Canada)

2016-08-15

Purpose: This work outlines a new TBI delivery technique to replace a lateral POP full bolus technique. The new technique is done with VMAT arc delivery, without bolus, treating the patient prone and supine. The benefits of the arc technique include: increased patient experience and safety, better dose conformity, better organ at risk sparing, decreased therapist time and reduction of therapist injuries. Methods: In this work we build on a technique developed by Jahnke et al. We use standard arc fields with gantry speeds corrected for varying distance to the patient followed by a single step VMAT optimization on a patient CT to increase dose inhomogeneity and to reduce dose to the lungs (vs. blocks). To compare the arc TBI technique to our full bolus technique, we produced plans on patient CTs for both techniques and evaluated several dosimetric parameters using an ANOVA test. Results and Conclusions: The arc technique is able reduce both the hot areas to the body (D2% reduced from 122.2% to 111.8% p<0.01) and the lungs (mean lung dose reduced from 107.5% to 99.1%, p<0.01), both statistically significant, while maintaining coverage (D98% = 97.8% vs. 94.6%, p=0.313, not statistically significant). We developed a more patient and therapist-friendly TBI treatment technique that utilizes single-step optimized VMAT plans. It was found that this technique was dosimetrically equivalent to our previous lateral technique in terms of coverage and statistically superior in terms of reduced lung dose.

Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

Science.gov (United States)

Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

2016-06-01

The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

Parents and teachers reporting on a child's emotional and behavioural problems following severe traumatic brain injury (TBI): the moderating effect of time.

Science.gov (United States)

Silberg, Tamar; Tal-Jacobi, Dana; Levav, Miriam; Brezner, Amichai; Rassovsky, Yuri

2015-01-01

Gathering information from parents and teachers following paediatric traumatic brain injury (TBI) has substantial clinical value for diagnostic decisions. Yet, a multi-informant approach has rarely been addressed when evaluating children at the chronic stage post-injury. In the current study, the goals were to examine (1) differences between parents' and teachers' reports on a child's emotional and behavioural problems and (2) the effect of time elapsed since injury on each rater's report. A sample of 42 parents and 42 teachers of children following severe TBI completed two standard rating scales. Receiver Operating Characteristic (ROC) curves were used to determine whether time elapsed since injury reliably distinguished children falling above and below clinical levels. Emotional-behavioural scores of children following severe TBI fell within normal range, according to both teachers and parents. Significant differences were found between parents' reports relatively close to the time of injury and 2 years post-injury. However, no such differences were observed in teachers' ratings. Parents and teachers of children following severe TBI differ in their reports on a child's emotional and behavioural problems. The present study not only underscores the importance of multiple informants, but also highlights, for the first time, the possibility that informants' perceptions may vary across time.

Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Patel Mayur B

2012-09-01

Full Text Available Abstract Background Severe TBI, defined as a Glasgow Coma Scale ≤ 8, increases intracranial pressure and activates the sympathetic nervous system. Sympathetic hyperactivity after TBI manifests as catecholamine excess, hypertension, abnormal heart rate variability, and agitation, and is associated with poor neuropsychological outcome. Propranolol and clonidine are centrally acting drugs that may decrease sympathetic outflow, brain edema, and agitation. However, there is no prospective randomized evidence available demonstrating the feasibility, outcome benefits, and safety for adrenergic blockade after TBI. Methods/Design The DASH after TBI study is an actively accruing, single-center, randomized, double-blinded, placebo-controlled, two-arm trial, where one group receives centrally acting sympatholytic drugs, propranolol (1 mg intravenously every 6 h for 7 days and clonidine (0.1 mg per tube every 12 h for 7 days, and the other group, double placebo, within 48 h of severe TBI. The study uses a weighted adaptive minimization randomization with categories of age and Marshall head CT classification. Feasibility will be assessed by ability to provide a neuroradiology read for randomization, by treatment contamination, and by treatment compliance. The primary endpoint is reduction in plasma norepinephrine level as measured on day 8. Secondary endpoints include comprehensive plasma and urine catecholamine levels, heart rate variability, arrhythmia occurrence, infections, agitation measures using the Richmond Agitation-Sedation Scale and Agitated Behavior scale, medication use (anti-hypertensive, sedative, analgesic, and antipsychotic, coma-free days, ventilator-free days, length of stay, and mortality. Neuropsychological outcomes will be measured at hospital discharge and at 3 and 12 months. The domains tested will include global executive function, memory, processing speed, visual-spatial, and behavior. Other assessments include

Gemcitabine, cisplatin, and hyperfractionated accelerated radiotherapy for locally advanced non-small cell lung cancer.

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Zwitter, Matjaz; Kovac, Viljem; Smrdel, Uros; Strojan, Primoz

2006-09-01

Due to potent radiosensitization and potential serious or fatal toxicity, concurrent gemcitabine and irradiation should only be applied within clinical trials. We here present experience from a phase I-II clinical trial for patients with locally advanced non-small cell lung cancer (NSCLC) treated with hyperfractionated accelerated radiotherapy and concurrent low-dose gemcitabine. Eligible patients had locally advanced inoperable NSCLC without pleural effusion, Eastern Cooperative Oncology Group performance status 0-1, were chemotherapy naïve and had no previous radiotherapy to the chest, and had adequate hematopoietic, liver, and kidney function. Routine brain computed tomography was not performed, and positron emission tomography/computed tomography was not available. Treatment consisted of three parts: induction chemotherapy with gemcitabine and cisplatin in standard doses, local treatment with concurrent chemotherapy and radiotherapy, and consolidation chemotherapy. Patients were irradiated with opposed AP-PA and oblique fields, using 2.5-D treatment planning. Although corrections for inhomogeneous tissue were made, volume of total lung receiving > or =20 Gy (V20) could not be determined. The trial started as phase I, aimed to determine the dose-limiting toxicity and maximal tolerated dose (MTD) for concurrent hyperfractionated radiotherapy (1.4 Gy twice daily) and gemcitabine 55 mg/m twice weekly as a radiosensitizer. Phase II of the trial then continued at the level of MTD. Twenty-eight patients with NSCLC, nine patients with stage IIIA, 16 patients with IIIB, and three patients with an inoperable recurrence after previous surgery, entered the trial. The first 12 patients entered Phase I of the trial at the initial level of 42 Gy in 30 fractions in 3 weeks. Dose-limiting toxicity was acute esophagitis; 47.6 Gy in 34 fractions in 3.5 weeks was the MTD for this regimen of concurrent chemotherapy and radiotherapy. In phase II of the trial, this dose was applied

Patterns of post-acute health care utilization after a severe traumatic brain injury: Results from the PariS-TBI cohort.

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Jourdan, Claire; Bayen, Eleonore; Darnoux, Emmanuelle; Ghout, Idir; Azerad, Sylvie; Ruet, Alexis; Vallat-Azouvi, Claire; Pradat-Diehl, Pascale; Aegerter, Philippe; Weiss, Jean-Jacques; Azouvi, Philippe

2015-01-01

To assess brain injury services utilization and their determinants using Andersen's model. Prospective follow-up of the PariS-TBI inception cohort. Out of 504 adults with severe traumatic brain injury (TBI), 245 survived and 147 received a 4-year outcome assessment (mean age 33 years, 80% men). Provision rates of medical, rehabilitation, social and re-entry services and their relations to patients' characteristics were assessed. Following acute care discharge, 78% of patients received physiotherapy, 61% speech/cognitive therapy, 50% occupational therapy, 41% psychological assistance, 63% specialized medical follow-up, 21% community re-entry assistance. Health-related need factors, in terms of TBI severity, were the main predictors of services. Provision of each therapy was significantly associated with corresponding speech, motor and psychological impairments. However, care provision did not depend on cognitive impairments and cognitive therapy was related to pre-disposing and geographical factors. Community re-entry assistance was provided to younger and more independent patients. These quantitative findings illustrate strengths and weaknesses of late brain injury care provision in urban France and highlight the need to improve treatment of cognitive impairments.

High Resolution Diffusion Tensor Imaging of Cortical-Subcortical White Matter Tracts in TBI

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2011-12-01

advertisements on Craig’s List and through the University email system to also include placing advertisements on the public transportation systems (both...being 107 months for all TBI subjects. Subjects were recruited from the University of Illinois Medical Center and via advertisements . Eighteen healthy...cognition. Tests included the Tower of London (Shallice, 1982; Culbertson and Zilmer, 2001), Stroop Colour –Word Test (Stroop, 1935; Jensen and Rohwer

Premorbid IQ Predicts Postconcussive Symptoms in OEF/OIF/OND Veterans with mTBI.

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Stewart-Willis, Jada J; Heyanka, Daniel; Proctor-Weber, Zoe; England, Heather; Bruhns, Maya

2018-03-01

Extant literature has demonstrated that symptoms of postconcussive syndrome (PCS) persist well beyond the expected 3-month post-injury recovery period in a minority of individuals with mild traumatic brain injury (mTBI). Suboptimal performance on validity measures and pre- and post-injury psychosocial stressors - rather than actual mTBI or current cognitive functioning - have been identified as predictors of chronic PCS. Whether premorbid IQ has any influence on chronic PCS has been understudied, in the context of established psychogenic etiologies. The sample included 31 veterans, who underwent mTBI neuropsychological evaluations six or more months post-injury in a VA outpatient neuropsychology clinic. A two-step multiple linear regression was conducted to examine the effects on the outcome variable, PCS (Neurobehavioral Symptom Inventory), of the following predictors: cognitive functioning (Repeatable Battery for the Assessment of Neuropsychological Status; Attention, Immediate Memory, and Delayed Memory Indices), performance validity, depression (Beck Depression Inventory-Second Edition), posttraumatic stress disorder (PTSD Checklist, Civilian Version), quality of sleep (Pittsburgh Sleep Quality Index), pain (Brief Pain Inventory), education, and Premorbid IQ (Wechsler Test of Adult Reading). The overall regression model containing all nine predictor variables was statistically significant. Depression (p IQ (p IQ and greater endorsed symptoms of depression were associated with higher PCS scores. In Step 2 of the multiple linear regression, the WTAR explained an additional 6.7% of the variance in PCS after controlling for psychosocial stressors and current cognitive ability. The findings support premorbid IQ as a unique and relevant predictor of chronic PCS, with significance variance accounted for beyond education, cognitive functioning, and psychosocial variables. Given the predictive relationship between premorbid IQ and PCS, adapting postconcussive

Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

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Chen, J.; van de Geijn, J.; Goffman, T. (ROB, DCT, NCI, NIH, Bethesda, Maryland 20892 (US))

1991-05-01

In the conventional linear--quadratic model of single-dose response, the {alpha} and {beta} terms reflect lethal damage created {ital during} the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD.

Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

International Nuclear Information System (INIS)

Chen, J.; van de Geijn, J.; Goffman, T.

1991-01-01

In the conventional linear--quadratic model of single-dose response, the α and β terms reflect lethal damage created during the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with ''unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD

Mixed Reality for PTSD/TBI Assessment.

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Fidopiastis, Cali; Hughes, Charles E; Smith, Eileen

2009-01-01

Mixed Reality (MR) refers to the blending of virtual content into the real world. Using MR, we create contextually meaningful scenarios in which users carry out tasks encountered in the presence of visual and aural distracters. Visual distracters can include subtle ones - people walking; and more abrupt ones - cartons falling. Aural distracters can include gentle ones - fans whirring; and more aggressive ones - automobiles backfiring. The intensity of these distracters can be dynamically controlled by a therapist or software that takes into account the patient's perceived level of stress. Intensity can also be controlled between experiences. For example, one may increase the stress level in a subsequent session, attempting to improve a person's tolerance. Assessment of progress includes psychophysical metrics (stress indicators) and the performance of tasks (accuracy and adherence to time constraints). By accurately capturing a patient's interaction with the environment in the context of simulation events, we can use MR as a tool for assessment and rehabilitation planning for individuals with stress-related injuries. This paper reports on the MR environment we have developed and its efficacy (realized and potential) for the assessment of post-traumatic stress disorder (PTSD) with or without traumatic brain injury (TBI).

Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

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Gerber, Nicolas U., E-mail: nicolas.gerber@kispi.uzh.ch [Department of Pediatric Oncology, University Children' s Hospital, Zurich (Switzerland); Hoff, Katja von; Resch, Anika [Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Ottensmeier, Holger [Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg (Germany); Kwiecien, Robert; Faldum, Andreas [Institute of Biostatistics and Clinical Research, University of Muenster (Germany); Matuschek, Christiane [Department of Radiation Oncology, Medical Faculty, Heinrich Heine University of Duesseldorf, Duesseldorf (Germany); Hornung, Dagmar [Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Bremer, Michael [Institute for Radiation Therapy and Special Oncology, Hannover Medical School, Hannover (Germany); Benesch, Martin [Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz (Austria); Pietsch, Torsten [Department of Neuropathology, University of Bonn, Bonn (Germany); Warmuth-Metz, Monika [Department of Neuroradiology, University of Wuerzburg, Wuerzburg (Germany); Kuehl, Joachim [Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg (Germany); Rutkowski, Stefan [Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kortmann, Rolf D. [Department of Radiation Oncology, University of Leipzig, Leipzig (Germany)

2014-07-15

Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. Methods and Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (±standard error [SE]) were each 58% (±10%) for the entire cohort: CNS-PNET was 53% (±13); pinealoblastoma was 64% (±15%; P=.524 and P=.627, respectively). Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

Underbody Blast Models of TBI Caused by Hyper-Acceleration and Secondary Head Impact

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2017-10-01

brain injury (TBI), with most of these head injuries caused by explosive munitions such as bombs , land mines, improvised explosive devices and missiles...with most of these injuries caused by explosive munitions such as bombs , land mines, improvised explosive devices (IEDs), and missiles.1,2 Little is...Neurosurg. 2008;108: 124–131. 21. Richards EM , Fiskum G, Rosenthal RE, Hopkins I, McKenna MC. Hyperoxic reperfusion after global ischemia decreases

Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury(TBI)

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2016-10-01

after incision and TBI, and the relationship of those changes to CXCR2 expression ST4.1 Establish spinal cord sites and cell types displaying...we plan to use oral preparations of these drugs and establish dose-response relationships as these will be pharmacologically useful and make the...Anesthesiology Annual Awards Dinner . Palo Alto, CA, June, 2016. 4. Epigenetic Regulation of Chronic Pain after Traumatic Brain Injury. De-Yong

Hyperfractionated Radiotherapy Following Induction Chemotherapy for Stage III Non-Small Cell Lung Cancer-Random iced for Adjuvant Chemotherapy vs. Observation

International Nuclear Information System (INIS)

Choi, Eun Kyung; Chang, Hye Sook; Ahn, Seung Do

1993-01-01

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer(NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hypefractionated radiotherapy (120 cGy/fx BID, 0480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 mg/m2, Vinblastin B mg/ m2, Cisplatin 60 Mg/ m2) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient refusal, 39 completed planned therapy. Twenty-three(58%) patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy, 1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hypefractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 35 patients who completed induction chemotherapy and radiotherapy, 25 patients(64%) including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radiotherapy. Nine patients were allocated to adjuvant chemotherapy group and 4/9 shewed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant

Contribution of brain or biological reserve and cognitive or neural reserve to outcome after TBI: A meta-analysis (prior to 2015).

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Mathias, Jane L; Wheaton, Patricia

2015-08-01

Brain/biological (BR) and cognitive/neural reserve (CR) have increasingly been used to explain some of the variability that occurs as a consequence of normal ageing and neurological injuries or disease. However, research evaluating the impact of reserve on outcomes after adult traumatic brain injury (TBI) has yet to be quantitatively reviewed. This meta-analysis consolidated data from 90 studies (published prior to 2015) that either examined the relationship between measures of BR (genetics, age, sex) or CR (education, premorbid IQ) and outcomes after TBI or compared the outcomes of groups with high and low reserve. The evidence for genetic sources of reserve was limited and often contrary to prediction. APOE ∈4 status has been studied most, but did not have a consistent or sizeable impact on outcomes. The majority of studies found that younger age was associated with better outcomes, however most failed to adjust for normal age-related changes in cognitive performance that are independent of a TBI. This finding was reversed (older adults had better outcomes) in the small number of studies that provided age-adjusted scores; although it remains unclear whether differences in the cause and severity of injuries that are sustained by younger and older adults contributed to this finding. Despite being more likely to sustain a TBI, males have comparable outcomes to females. Overall, as is the case in the general population, higher levels of education and pre-morbid IQ are both associated with better outcomes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Tc-99m-hexakis(t-butylisonitrile)-technetium(I) (Tc-99m-TBI)

International Nuclear Information System (INIS)

Angelberger, P.; Dudczak, R.; Jones, A.G.; Lister-James, J.; Wagner-Loffler, M.; Buchheit, O.; Fally, F.

1986-01-01

The potassium analog (Tl-201)/sup +/ is widely used in nuclear cardiology but has inferior scintigraphic (80 keV photons), dosimetric and economic properties as compared to Tc-99m. Therefore considerable efforts have been made to develop a Tc-compound that would accumulate in the myocardium in relation to regional blood flow. This study was aimed at optimizing the preparation of Tc-TBI with n.c.a. Tc-99m, analyze and purify the product with HPLC, verify biodistribution in mice and undertake a clinical evaluation

Primary Blast Injury Criteria for Animal/Human TBI Models using Field Validated Shock Tubes

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2016-09-01

impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determined the mortality rate as a non- linear function of...BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a...8-98) Prescribed by ANSI Std. Z39.18 28 Table of Contents 1. INTRODUCTION

Primary Blast Injury Criteria for Animal/Human TBI Models using Field Validated Shock Tubes

Science.gov (United States)

2017-09-01

acute hemorrhage characterized by partial filling of small groups of alveoli by blood . 240 kPa: Mild multifocal pools of acute hemorrhage which...Neurotrauma, Blast TBI, Primary blast brain injury, Blast overpressure, Blood -brain barrier, Neuroinflammation, Oxidative stress, Neuroproteomics 16...stress, neuroinflammation and BBB damage as a result of blast overpressure in the acute phase (0, 4 and 24 hours post-exposure). Our group

Neurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress

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2014-11-01

previously used such procedures to evaluate the effects of drugs , toxins and ischemic injury (Genovese et al., 1988, 1992, 1993, 2006). Moreover, TBI, from...Lee JLC, Dickinson A, Everitt BJ (2005) Conditioned suppression and freezing as measures of aversive Pavlovian conditioning: effects of discreet...freezing and instrumental suppression in Pavlovian fear conditioning. Behav Brain Res 211:111–117. McDannald MA, Galarce EM (2011) Measuring Pavlovian

The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell–Depleted Hematopoietic Stem Cell Transplantation

International Nuclear Information System (INIS)

Aristei, Cynthia; Carotti, Alessandra; Palazzari, Elisa; Amico, Lucia; Ruggeri, Loredana; Perrucci, Elisabetta; Falcinelli, Lorenzo; Lancellotta, Valentina; Palumbo, Isabella; Falzetti, Franca; Aversa, Franco; Merluzzi, Mara; Velardi, Andrea; Martelli, Massimo Fabrizio

2016-01-01

Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and Materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day −9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.

The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell–Depleted Hematopoietic Stem Cell Transplantation

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Aristei, Cynthia, E-mail: cynthia.aristei@unipg.it [Radiation Oncology Section, Department of Surgery and Biomedical Sciences, University of Perugia and Perugia General Hospital, Perugia (Italy); Carotti, Alessandra [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Palazzari, Elisa [Radiation Oncology Section, University of Perugia, Perugia (Italy); Amico, Lucia; Ruggeri, Loredana [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Perrucci, Elisabetta; Falcinelli, Lorenzo [Radiation Oncology Division, Perugia General Hospital, Perugia (Italy); Lancellotta, Valentina [Radiation Oncology Section, University of Perugia, Perugia (Italy); Palumbo, Isabella [Radiation Oncology Section, Department of Surgery and Biomedical Sciences, University of Perugia and Perugia General Hospital, Perugia (Italy); Falzetti, Franca [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Aversa, Franco [Hematology and Bone Marrow Transplant Unit, Department of Clinical and Experimental Medicine, Parma General Hospital and University, Parma (Italy); Merluzzi, Mara; Velardi, Andrea; Martelli, Massimo Fabrizio [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy)

2016-11-15

Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and Materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day −9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.

Exposure to a predator scent induces chronic behavioral changes in rats previously exposed to low-level blast: Implications for the relationship of blast-related TBI to PTSD

Directory of Open Access Journals (Sweden)

Georgina Perez-Garcia

2016-10-01

Full Text Available Blast-related mild traumatic brain injury (mTBI has been unfortunately common in veterans who served in the recent conflicts in Iraq and Afghanistan. The postconcussion syndrome associated with these mTBIs has frequently appeared in combination with post-traumatic stress disorder (PTSD. The presence of PTSD has complicated diagnosis since clinically PTSD and the postconcussion syndrome of mTBI have many overlapping symptoms. In particular establishing how much of the symptom complex can be attributed to the psychological trauma associated with PTSD in contrast to the physical injury of TBI has proven difficult. Indeed some have suggested that much of what is now being called blast-related postconcussion syndrome is better explained by PTSD. The relationship between the postconcussion syndrome of mTBI and PTSD is complex. Association of the two disorders might be viewed as additive effects of independent psychological and physical traumas suffered in a war zone. However we previously found that rats exposed to repetitive low-level blast exposure in the absence of a psychological stressor developed a variety of anxiety and PTSD-related behavioral traits that were present months following the last blast exposure. Here we show that a single predator scent challenge delivered 8 months after the last blast exposure induces chronic anxiety related changes in blast-exposed rats that are still present 45 days later. These observations suggest that in addition to independently inducing PTSD-related traits, blast exposure sensitizes the brain to react abnormally to a subsequent psychological stressor. These studies have implications for conceptualizing the relationship between blast-related mTBI and PTSD and suggest that blast-related mTBI in humans may predispose to the later development of PTSD in reaction to subsequent psychological stressors.

'I kind of figured it out': the views and experiences of people with traumatic brain injury (TBI) in using social media-self-determination for participation and inclusion online.

Science.gov (United States)

Brunner, Melissa; Palmer, Stuart; Togher, Leanne; Hemsley, Bronwyn

2018-06-05

Social media can support people with communication disability to access information, social participation and support. However, little is known about the experiences of people with traumatic brain injury (TBI) who use social media to determine their needs in relation to social media use. To determine the views and experiences of adults with TBI and cognitive-communication disability on using social media, specifically: (1) the nature of their social media experience; (2) barriers and facilitators to successful use; and (3) strategies that enabled their use of social media. Thirteen adults (seven men, six women) with TBI and cognitive-communication disability were interviewed about their social media experiences, and a content thematic analysis was conducted. Participants used several social media platforms including Facebook, Twitter, Instagram and virtual gaming worlds. All but one participant used social media several times each day and all used social media for social connection. Five major themes emerged from the data: (1) getting started in social media for participation and inclusion; (2) drivers to continued use of social media; (3) manner of using social media; (4) navigating social media; and (5) an evolving sense of social media mastery. In using platforms in a variety of ways, some participants developed an evolving sense of social media mastery. Participants applied caution in using social media, tended to learn through a process of trial and error, and lacked structured supports from family, friends or health professionals. They also reported several challenges that influenced their ability to use social media, but found support from peers in using the social media platforms. This information could be used to inform interventions supporting the use of social media for people with TBI and directions for future research. Social media offers adults with TBI several opportunities to communicate and for some to develop and strengthen social relationships

ANAM4 TBI Reaction Time-Based Tests have Prognostic Utility for Acute Concussion

Science.gov (United States)

2013-07-01

7:767. 2013 ANAM4 TBI Reaction Time-Based Tests Have Prognostic Utility for Acute Concussion LT Jacob N. Norris, MSC USN*; LCDR Waiter Carr, MSC USN...CDR Thomas Herzig, MSC USNf; CDR D. Waiter Labrie, MSC USNf; CDR Richard Sams, MC USN§ ABSTRACT The Concussion Restoration Care Center has used the...Work Unit No. N24LB. REFERENCES 1. Department of Defense: DoD Poiicy Guidance for Management of Mild Traumatic Brain Injury/Concussion in the Deployed

Assessment and Rehabilitation of Central Sensory Impairments for Balance in mTBI

Science.gov (United States)

2016-10-01

date will help establish normative values as we begin to recruit more mTBI subjects in the upcoming year. Our current enrollment includes 8 men , 11... women with a mean age of 26.4 years. Fifteen people reported ethnicity as non-hispanic/Latino and 4 as hispanic/Latino. Seventeen people reported as...SD Average ± SD Video Head Impulse Test (vHIT) Right Horizontal Gain 0.96 ± 0.07 1.00 ± 0.02 Left Horizontal Gain 0.87 ± 0.15 0.92 ± 0.04

Role of APOE Isforms in the Pathogenesis of TBI Induced Alzheimer’s Disease

Science.gov (United States)

2014-10-01

the inheritance of APOe4 is the only proven genetic risk factor for sporadic Alzheimer disease (AD). Importantly, TBI is a risk factor for the...mediated through ABCA1. 2 Keywords Traumatic brain injury, APOE isoforms, ABCA1, Alzheimer disease, APPmice, amyloid beta, axonal injury, inflamma...and Anticipated problems 3 OVERALL PROJECT SUMMARY Trough activation of LXR/RXR transcription factors this ligand causes up regulation of Abca1 and

A prospective randomized trial of hyperfractionated versus conventional once daily radiation for advanced squamous cell carcinomas of the larynx and pharynx

International Nuclear Information System (INIS)

Cummings, B.J.; Keane, T.J.; Pintilie, M.; O'Sullivan, B.; Payne, D.; Warde, P.; McLean, M.; Waldron, J.; Liu, F.-F.; Gullane, P.

1996-01-01

Purpose: To examine the effects of an increased dose of radiation therapy (RT) delivered by a hyperfractionated schedule compared to conventional once daily RT on toxicity, locoregional control and survival in the treatment of squamous cell carcinomas (SCC) of the larynx and pharynx. Materials/Methods: Between 1988 and 1995 336 patients were randomized to receive RT with curative intent. Eligible patients had biopsy proven SCC of the larynx or pharynx, with TN stages (AJC-UICC 1987) T3 or T4 N0, or any T with any N+. All patients were M0. Patients were stratified by site (larynx/oropharynx/hypopharynx), node status (clinically positive/negative), and performance status. Patients were treated with either 51 Gy TAD/20 fractions/4 wk (2.55 Gy 1x/d, conventional RT=CRT) or 58 Gy TAD/40 fractions/4 wk (1.45 Gy 2x/d, hyperfractionated RT=HFRT). Patients underwent EUA and selective biopsies 10 wk after RT; surgical salvage was performed for residual or recurrent cancer whenever possible. Results: The primary cancer arose in the oropharynx (138), larynx (133) or hypopharynx (65). T stages were distributed T1 22, T2 72, T3 133 and T4 109. N stage distribution was N0 127, N1 74, N2 117 and N3 18. The proportion of patients with acute mucosal toxicity (RTOG Grade 3 or 4) was increased by HFRT (60% versus 40%), but other acute and late toxicity was not significantly different. There was no difference in the incidence of morbidity in the two treatment groups in those who underwent surgery following RT. The locoregional control rates at 3 yrs for all cases were 45% (HFRT) vs 40% (CRT) log rank p=0.16; for primary tumors <4 cm 54% (HFRT) vs 42% (CRT) p=0.04; for primary tumors ≥ 4 cm 38% (HFRT) vs 41% (CRT) p=0.73. Local control was improved to some extent in SCC which arose in all sites, but most noticeably in hypopharyngeal cancers. The disease free survival rates at 3 yr for all cases were 37% (HFRT) vs 30% (CRT) p=0.15; for primary tumors < 4 cm 47% (HFRT) vs 34% (CRT) p=0

Prospective memory rehabilitation using smartphones in patients with TBI: What do participants report?

Science.gov (United States)

Evald, Lars

2015-01-01

Use of assistive devices has been shown to be beneficial as a compensatory memory strategy among brain injury survivors, but little is known about possible advantages and disadvantages of the technology. As part of an intervention study participants were interviewed about their experiences with the use of low-cost, off-the-shelf, unmodified smartphones combined with Internet calendars as a compensatory memory strategy. Thirteen community-dwelling patients with traumatic brain injury (TBI) received a 6-week group-based instruction in the systematic use of a smartphone as a memory compensatory aid followed by a brief structured open-ended interview regarding satisfaction with and advantages and disadvantages of the compensatory strategy. Ten of 13 participants continued to use a smartphone as their primary compensatory strategy. Audible and visual reminders were the most frequently mentioned advantages of the smartphone, and, second, the capability as an all-in-one memory device. In contrast, battery life was the most often mentioned disadvantage, followed by concerns about loss or failure of the device. Use of a smartphone seems to be a satisfactory compensatory memory strategy to many patients with TBI and smartphones come with features that are advantageous to other compensatory strategies. However, some benefits come hand-in-hand with drawbacks, such as the feeling of dependency. These aspects should be taken into account when choosing assistive technology as a memory compensatory strategy.

Prospective memory rehabilitation using smartphones in patients with TBI

DEFF Research Database (Denmark)

Evald, Lars

2015-01-01

with the use of low-cost, off-the-shelf, unmodified smartphones combined with Internet calendars as a compensatory memory strategy. Thirteen community-dwelling patients with traumatic brain injury (TBI) received a 6-week group-based instruction in the systematic use of a smartphone as a memory compensatory aid...... followed by a brief structured open-ended interview regarding satisfaction with and advantages and disadvantages of the compensatory strategy. Ten of 13 participants continued to use a smartphone as their primary compensatory strategy. Audible and visual reminders were the most frequently mentioned...... advantages of the smartphone, and, second, the capability as an all-in-one memory device. In contrast, battery life was the most often mentioned disadvantage, followed by concerns about loss or failure of the device. Use of a smartphone seems to be a satisfactory compensatory memory strategy to many patients...

VA/DoD Clinical Practice Guideline for Management of Concussion/Mild Traumatic Brain Injury (mTBI)

Science.gov (United States)

2009-04-01

responsibilities, and teaching compensatory strategies and environmental modifications. Most patients with symptoms following a single concussion...better outcomes in individuals with mTBI-related symptoms? 5. Are there compensatory strategies /techniques that have been shown to result in better...with increased environmental stimulation • Squinting/closing one eye during activities • Difficulty standing in midline or noted head tilt

Independent validation of the MMPI-2-RF Somatic/Cognitive and Validity scales in TBI Litigants tested for effort.

Science.gov (United States)

Youngjohn, James R; Wershba, Rebecca; Stevenson, Matthew; Sturgeon, John; Thomas, Michael L

2011-04-01

The MMPI-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) is replacing the MMPI-2 as the most widely used personality test in neuropsychological assessment, but additional validation studies are needed. Our study examines MMPI-2-RF Validity scales and the newly created Somatic/Cognitive scales in a recently reported sample of 82 traumatic brain injury (TBI) litigants who either passed or failed effort tests (Thomas & Youngjohn, 2009). The restructured Validity scales FBS-r (restructured symptom validity), F-r (restructured infrequent responses), and the newly created Fs (infrequent somatic responses) were not significant predictors of TBI severity. FBS-r was significantly related to passing or failing effort tests, and Fs and F-r showed non-significant trends in the same direction. Elevations on the Somatic/Cognitive scales profile (MLS-malaise, GIC-gastrointestinal complaints, HPC-head pain complaints, NUC-neurological complaints, and COG-cognitive complaints) were significant predictors of effort test failure. Additionally, HPC had the anticipated paradoxical inverse relationship with head injury severity. The Somatic/Cognitive scales as a group were better predictors of effort test failure than the RF Validity scales, which was an unexpected finding. MLS arose as the single best predictor of effort test failure of all RF Validity and Somatic/Cognitive scales. Item overlap analysis revealed that all MLS items are included in the original MMPI-2 Hy scale, making MLS essentially a subscale of Hy. This study validates the MMPI-2-RF as an effective tool for use in neuropsychological assessment of TBI litigants.

Hyperfractionated radiation therapy for incompletely resected supratentorial low-grade glioma. A phase II study

International Nuclear Information System (INIS)

Jeremic, B.; Milicic, B.; Stojanovic, M.; Nikolic, N.; Dagovic, A.; Shibamoto, Y.; Grujicic, D.

1998-01-01

Background and purpose: In order to investigate the feasibility, toxicity and antitumor efficacy of hyperfractionated radiation therapy, 37 adult patients with incompletely resected supratentorial low-grade glioma were entered into a phase II study. Materials and methods: The radiation therapy dose was 55 Gy in 50 fractions in 25 treatment days over 5 weeks to the tumor plus a 2-cm margin, with an additional 17.6 Gy given in 16 fractions in 8 treatment days over 1.5 weeks to the tumor plus a 1-cm margin, using 1.1 Gy b.i.d. fractionation with a 6 h interfraction interval. The total tumor dose was 72.6 Gy in 66 fractions in 33 treatment days over 6.5 weeks. Results: The median survival time (MST) for all 37 patients has not yet been attained, while 5- and 7-year survival rates were 75% and 69%, respectively. The median time to tumor progression (MTP) has also not yet been attained, while 5- and 7-year progression-free survival (PFS) rates were both 70%. There was no difference in survival or PFS regarding histology, although patients with oligodendroglioma and mixed glioma had similar survival, both being higher than that of ordinary astrocytoma. On univariate analysis of potential prognostic factors, age, Karnofsky performance status (KPS), neurologic status and extent of surgery were found to influence survival. The toxicity of HFX RT was generally assessed as mild to moderate. Conclusion: HFX RT is feasible with mild to moderate toxicity. Further studies are warranted with more patients and longer follow-up before testing it against standard fractionation RT in this patient population. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Quantitative Tractography and Volumetric MRI in Blast and Blunt Force TBI: Predictors of Neurocognitive and Behavioral Outcome

Science.gov (United States)

2013-10-01

Examining the psycho - metric properties of the MFIS in TBI is important for researchers and clinicians who may wish to use this scale to evaluate...limited in regions with more complex architecture (eg, where crossing fibers exist within a single voxel), and thus the measured FA may be attenuated in

Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and -IV carcinomas of the head and neck. Long-term results including functional outcome

International Nuclear Information System (INIS)

Huguenin, P.; Glanzmann, C.; Taussky, D.; Luetolf, U.M.; Schmid, S.; Moe, K.

1998-01-01

Purpose: To assess the survival rate, the probability of local control, the patterns of relapse and late sequelae including self-reported quality of life in patients treated with hyperfractionated radiotherapy (RT) and simultaneous CDDP chemotherapy for stage-III to stage-IV carcinomas of the head and neck. Methods: From 1988 to 1994, 64 patients (median age 55.5 years) with carcinomas of different subsites, excluding the nasopharynx, were treated in a pilot study with 1.2 Gy bid (6 h interval; total dose 74.4 Gy) and simultaneous CDDP (20 mg/m 2 daily, 5 days in week 1 and 5) and followed at regular intervals. Overall survival and local control, as well as the rates of late toxicity, were estimated using the actuarial method. Median follow-up was 3.3 years for all and 5.2 years for surviving patients. To assess the quality of life, the EORTC QLQ-C 30 questionnaire and the H and N35 module questionnaire were sent to the patients surviving with no evidence of disease or second primary tumors; they were answered by 15/23 (67%). Results: Overall survival was 37% at 5 years, whereas disease-specific survival was 59%. Twenty-three patients died from uncontrolled head and neck cancer. Second primary tumors were observed in 13 patients, most frequently in the lung. Local control without salvage surgery was 74% at 5 years for all subsites and stages, and loco-regional disease-free survival was 72%. Eleven patients developed distant metastases, which was the only site of failure in 6 cases. Salvage surgery was successful in 2 cases. The actuarial estimates of ≥grade-3 late toxicity was 4% for the mandibular bone and 23% for dysphagia, and 50% of the patients experienced a permanent xerostomy. Self-reported global quality of life in surviving patients was good (mean 68 points on a scale 0 to 100); consequences of impaired salivary function had most impact on nutritional and social aspects. Conclusions: Hyperfractionated RT with concomitant CDDP is well tolerated and highly

SU-E-T-515: Field-In-Field Compensation Technique Using Multi-Leaf Collimator to Deliver Total Body Irradiation (TBI) Dose

Energy Technology Data Exchange (ETDEWEB)

Lakeman, T [The State University of New York at Buffalo (United States); Wang, IZ [The State University of New York at Buffalo (United States); Roswell Park Cancer Institute, Buffalo, NY (United States)

2014-06-01

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been used conventionally to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern field-in-field (FIF) technique with the multi-leaf collimator (MLC) to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the FIF technique to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Treatment fields include one pair of opposed open large fields (collimator=45°) with a specific weighting and a succession of smaller fields (collimator=90°) each with their own weighting. The smaller fields are shaped by moving MLC to block the sections of the patient which have already received close to 100% of the prescribed dose. The weighting factors for each of these fields were calculated using the attenuation coefficient of the initial lead compensators and the separation of the patient in different positions in the axial plane. Results: Dose-volume histograms (DVH) were calculated for evaluating the FIF compensation technique. The maximum body doses calculated from the DVH were reduced from the non-compensated 179.3% to 148.2% in the FIF plans, indicating a more uniform dose with the FIF compensation. All calculated monitor units were well within clinically acceptable limits and exceeded those of the original lead compensation plan by less than 50 MU (only ~1.1% increase). Conclusion: MLC FIF technique for TBI will not significantly increase the beam on time while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.

Finding What Works in a Complicated Transition: Considerations for Soldiers with PTSD and mTBI

Science.gov (United States)

2014-06-13

transition into civilian life, while simultaneously dealing with TBI and or PTSD. Background “Regardless of gender or combat occupation specialty, today’s...to the Nation when they volunteer to serve, we incur an equally binding pledge to return them to society as better citizens. We must safeguard...Assistant Secretary of Defense for Health Affairs should standardize the policies of PTSD psychotherapies in order to promote parity across all

A multidisciplinary TBI inpatient rehabilitation programme for active duty service members as part of a randomized clinical trial.

Science.gov (United States)

Braverman, S E; Spector, J; Warden, D L; Wilson, B C; Ellis, T E; Bamdad, M J; Salazar, A M

1999-06-01

To design and describe an effective rehabilitation programme for use in an ongoing trial on the efficacy of multidisciplinary brain injury rehabilitation for moderately head injury military service members. Treatment arm of a randomized control trial. US military tertiary care hospital inpatient rehabilitation programme. Sixty seven active duty military with moderate to severe TBI who were randomized to the treatment arm of the protocol. Eight week rehabilitation programme combining group and individual therapies with an inpatient milieu-oriented neuropsychological focus. Group therapies included fitness, planning and organization, cognitive skills, work skills, medication, and milieu groups, and community re-entry outings. Individual therapy included neuropsychology, work therapy, occupational therapy, and speech and language pathology. Successful return to work and return to duty. At 1 year follow-up, 64 patients returned to work (96%) and 66% (44/67) returned to duty. The described rehabilitation programme demonstrates one successful effort to rehabilitate active duty military service members with TBI who have the potential to return to duty.

SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

Energy Technology Data Exchange (ETDEWEB)

Lee, M; Suh, T [Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Han, B; Xing, L [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA (United States); Jenkins, C [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA (United States); Department of Mechanical Engineering, Stanford University, Palo Alto, CA (United States)

2015-06-15

Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery.

SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

International Nuclear Information System (INIS)

Lee, M; Suh, T; Han, B; Xing, L; Jenkins, C

2015-01-01

Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery

Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors

International Nuclear Information System (INIS)

Allen, Jeffrey C.; Donahue, Bernadine; DaRosso, Robert; Nirenberg, Anita

1996-01-01

Purpose: This single-institution Phase I/II study conducted from 1989 to 1995 evaluates the feasibility of a multi-modality protocol combining hyperfractionated craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the central nervous system. Methods and Materials: All 23 patients had a histologically confirmed PNET and were over 3 years of age at diagnosis. The eligibility criteria for PNET patients with cerebellar primaries (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1-3). All patients with noncerebellar primaries were eligible regardless of T or M stage. The median age of the 23 patients was 9 years (mean 3-25); 11 were female. The primary tumor arose in the cerebellum in 19. Of these medulloblastoma patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these patients had gross total resections. Four other medulloblastoma patients had both high T and high M stages, constituting Group 2. Group 3 consisted of four other patients with exocerebellar primaries (two brain, one brain stem, and one cauda equina), three of whom were M3. Hyperfractionated radiotherapy was administered within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated by 4-6 h. The total dose to the primary intracranial tumor and other areas of measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis dose was 36 Gy, and boosts of 44-56 Gy were administered to metastatic spinal deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were administered sequentially (cyclophosphamide-vincristine followed by cisplatin-etoposide followed by carboplatin-vincristine) for a total of 9 months. Results: All patients completed radiotherapy as planned. Only three patients lost >10% of their body weight. One patient

Influence of refractive error on pupillary dynamics in the normal and mild traumatic brain injury (mTBI populations

Directory of Open Access Journals (Sweden)

James Q. Truong

2018-04-01

Full Text Available Purpose: There have been several studies investigating static, baseline pupil diameter in visually-normal individuals across refractive error. However, none have assessed the dynamic pupillary light reflex (PLR. In the present study, both static and dynamic pupillary parameters of the PLR were assessed in both the visually-normal (VN and the mild traumatic brain injury (mTBI populations and compared as a function of refractive error. Methods: The VN population comprised 40 adults (22–56 years of age, while the mTBI population comprised 32 adults (21–60 years of age over a range of refractive errors (−9.00 D to +1.25 D. Seven pupillary parameters (baseline static diameter, latency, amplitude, and peak and average constriction and dilation velocities were assessed and compared under four white-light stimulus conditions (dim pulse, dim step, bright pulse, and bright step. The Neuroptics, infrared, DP-2000 binocular pupillometer (30 Hz sampling rate; 0.05 mm resolution was used in the monocular (right eye stimulation mode. Results: For the majority of pupillary parameters and stimulus conditions, a Gaussian distribution best fit the data, with the apex centered in the low myopic range (−2.3 to −4.9D. Responsivity was reduced to either side of the apex. Conclusions: Over a range of dynamic and static pupillary parameters, the PLR was influenced by refractive error in both populations. In cases of high refractive error, the PLR parameters may need to be compensated for this factor for proper categorization and diagnosis. Resumen: Objetivo: Existen diversos estudios que han investigado el diámetro pupilar estático y basal en individuos con visión normal en todo el espectro de errores refractivos. Sin embargo, ninguno de ellos ha evaluado el reflejo dinámico pupilar a la luz (RPL. En el presente estudio, se evaluaron tanto los parámetros pupilares estáticos como los dinámicos en poblaciones con visión normal (VN y en las afectadas

Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI

OpenAIRE

Ustinova, Ksenia I; Leonard, Wesley A; Cassavaugh, Nicholas D; Ingersoll, Christopher D

2011-01-01

Abstract Background Traumatic brain injury (TBI) disrupts the central and executive mechanisms of arm(s) and postural (trunk and legs) coordination. To address these issues, we developed a 3D immersive videogame-- Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component...

Role of APOE Isoforms in the Pathogenesis of TBI induced Alzheimer’s Disease

Science.gov (United States)

2016-10-01

gene networks correlated to the traits (age / injury / genotype) in response to TBI. The results clearly demonstrate segregation by injury status...7 7. Participants & Other Collaborating Organizations….……………...…8 8. Figures ……………………………………………………………………10 1 1...entire maze is raised 40 cm off the ground . The elevated plus maze tests anxiety-related behavior by utilizing rodent’s fear of open and elevated

Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

Directory of Open Access Journals (Sweden)

Paul E. Rapp

2013-07-01

Full Text Available Psychophysiological investigations of traumatic brain injury (TBI are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP component properties (e.g. timing, amplitude, scalp distribution, and a participant’s clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that traumatic brain injury is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing traumatic brain injury, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records.

Comparison of neurite density measured by MRI and histology after TBI.

Directory of Open Access Journals (Sweden)

Shiyang Wang

Full Text Available Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI with and without MSC treatment.Fifteen male Wistar rats, were treated with saline (n = 6 or MSCs (n = 9 and were sacrificed at 6 weeks after controlled cortical impact (CCI. Healthy non-CCI rats (n = 5, were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients.Neurite densities exhibited a significant correlation (R(2>0.80, p<1E-20 between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC as 0.86. The conventional fractional anisotropy (FA correlated moderately with histological neurite density (R(2 = 0.59, P<1E-5 with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region.The present studies

A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

Budach, W; Hehr, T; Budach, V; Belka, C; Dietz, K

2006-01-01

Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as

CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine.

Science.gov (United States)

Zhou, Xinna; Qiao, Guoliang; Wang, Xiaoli; Song, Qingkun; Morse, Michael A; Hobeika, Amy; Gwin, William R; Ren, Jun; Lyerly, H Kim

2018-02-01

A prospective study was performed to compare the outcome for metastatic breast cancer (MBC) patients treated with docetaxel plus thiotepa (DT) or docetaxel plus capecitabine (DC), and to explore the value of CYP1A1*2C polymorphisms in predicting clinical efficacy of these chemotherapies. MBC patients (n = 130) were randomized to treatment with DT (n = 65) or DC (n = 65). Response rate, disease control rate, progression-free and overall survival were monitored. Genotyping of CYP1A1*2C was performed in all patients. DT and DC produced similar overall disease control rates (76.9 vs 69.2%), median PFS (6.7 vs. 7.5 months) and OS (20.1 vs. 21.0 months) (P > 0.05 for all comparisons); however, DT exhibited a higher rate of control of localized liver metastases (78.6 vs 41.2%, P = 0.023). Among patients homozygous for wild-type CYP1A1*1 genotype (AA), DT treatment was associated with a significantly longer PFS (8.4 vs. 6.4 months, P = 0.019) and OS (33.4 vs. 15.8 months, P = 0.018). Conversely, among patients carrying the variant CYP1A1*2C genotype (AG/GG), DC treatment was associated with a significantly longer PFS (8.4 vs. 5.5 month, P = 0.005), and OS (28.5 vs. 19.6 months, P = 0.010). After adjusting for competing risk factors, CYP1A1*2C genotype was confirmed to be an independent predictor of PFS and OS for each chemotherapy combination. Overall, DT and DC result in similar clinical efficacy for MBC patients; however, efficacy for each therapy differs depending on CYP1A1*2C genotype.

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.

Science.gov (United States)

Staar, S; Rudat, V; Stuetzer, H; Dietz, A; Volling, P; Schroeder, M; Flentje, M; Eckel, H E; Mueller, R P

2001-08-01

To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC). Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors). This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations

Potentiating effects of caffeine on teratogenicity of alkylating agents in mice

International Nuclear Information System (INIS)

Fujii, T.; Nakatsuka, T.

1983-01-01

Teratogenic to subteratogenic doses of x-ray, mitomycin C, MNNG, thio-TEPA, cyclophosphamide, and chlorambucil were administered to pregnant ICR mice together with caffeine at doses of 12.5, 25, or 50 mg/kg on day 11 of gestation. Fetuses were examined for gross malformations on day 18 of gestation. The teratogenicity of mitomycin C was significantly potentiated by caffeine at a dose as low as 12.5 mg/kg. The teratogenicity of chlorambucil was also significantly potentiated by caffeine at 50 mg/kg, but similar potentiation was not observed for x-ray, MNNG, thio-TEPA, and cyclophosphamide

Wake-promoting actions of median nerve stimulation in TBI-induced coma: An investigation of orexin-A and orexin receptor 1 in the hypothalamic region.

Science.gov (United States)

Zhong, Ying-Jun; Feng, Zhen; Wang, Liang; Wei, Tian-Qi

2015-09-01

A coma is a serious complication, which can occur following traumatic brain injury (TBI), for which no effective treatment has been established. Previous studies have suggested that neural electrical stimulation, including median nerve stimulation (MNS), may be an effective method for treating patients in a coma, and orexin‑A, an excitatory hypothalamic neuropeptide, may be involved in wakefulness. However, the exact mechanisms underlying this involvement remain to be elucidated. The present study aimed to examine the arousal‑promoting role of MNS in rats in a TBI‑induced coma and to investigate the potential mechanisms involved. A total of 90 rats were divided into three groups, comprising a control group, sham‑stimulated (TBI) group and a stimulated (TBI + MNS) group. MNS was performed on the animals, which were in a TBI‑induced comatose state. Changes in the behavior of the rats were observed following MNS. Subsequently, hypothalamic tissues were extracted from the rats 6, 12 and 24 h following TBI or MNS, respectively. The expression levels of orexin‑A and orexin receptor‑1 (OX1R) in the hypothalamus were examined using immunohistochemistry, western blotting and an enzyme‑linked immunosorbent assay. The results demonstrated that 21 rats subjected to TBI‑induced coma exhibited a restored righting reflex and response to pain stimuli following MNS. In addition, ignificant differences in the expression levels of orexin‑A and OXIR were observed among the three groups and among the time‑points. Orexin‑A and OX1R were upregulated following MNS. The rats in the stimulated group reacted to the MNS and exhibited a re‑awakening response. The results of the present study indicated that MNS may be a therapeutic option for TBI‑induced coma. The mechanism may be associated with increasing expression levels of the excitatory hypothalamic neuropeptide, orexin-A, and its receptor, OX1R, in the hypothalamic region.

Normalized power transmission between ABP and ICP in TBI.

Science.gov (United States)

Shahsavari, S; Hallen, T; McKelvey, T; Ritzen, C; Rydenhag, B

2009-01-01

A new approach to study the pulse transmission between the cerebrovascular bed and the intracranial space is presented. In the proposed approach, the normalized power transmission between ABP and ICP has got the main attention rather than the actual power transmission. Evaluating the gain of the proposed transfer function at any single frequency can reveal how the percentage of contribution of that specific frequency component has been changed through the cerebrospinal system. The gain of the new transfer function at the fundamental cardiac frequency was utilized to evaluate the state of the brain in three TBI patients. Results were assessed using the reference evaluations achieved by a novel CT scan-based scoring scheme. In all three study cases, the gain of the transfer function showed a good capability to follow the trend of the CT scores and describe the brain state. Comparing the new transfer function with the traditional one and also the index of compensatory reserve, the proposed transfer function was found more informative about the state of the brain in the patients under study.

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: A stepwise developed treatment schedule for advanced head-and-neck cancer

International Nuclear Information System (INIS)

Martinez, Jose Carlos; Villar, Alfonso; Cabezon, Maria Auxiliadora; Serdio, Jose Luis de; Fuentes, Claudio; Espineira, Manuel; Perez, Maria Dolores; Gil, Jose; Artazkoz, Juan Jose; Borque, Carlos; Suner, Marcos; Saavedra, Juan Antonio

2001-01-01

Purpose: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. Methods and Materials: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m 2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m 2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. Results: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. Conclusions: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions

To Fear is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls

NARCIS (Netherlands)

Visser-Keizer, Annemarie C.; Westerhof-Evers, Herma J.; Gerritsen, Marleen J.J.; van der Naalt, Joukje; Spikman, Jacoba M.

2016-01-01

Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has

To Fear Is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls

NARCIS (Netherlands)

Visser-Keizer, A.C.; Westerhof-Evers, H.J.; Gerritsen, M.J.P.; Naalt, J. van der; Spikman, J.M.

2016-01-01

Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has

Hyperfractionated radiation in the treatment of squamous cell carcinomas of the head and neck: a comparison of two fractionation schedules

Energy Technology Data Exchange (ETDEWEB)

Garden, Adam S; Morrison, William H; Ang, K Kian; Peters, Lester J

1995-02-01

Purpose: In 1984 we began treating patients with squamous cell carcinomas of the larynx and hypopharynx with hyperfractionated radiotherapy. Patients received 76.8 Gy in 1.2 Gy fractions twice daily, with a 4 h interfraction interval. In 1988, this schedule was modified in patients treated with shrinking field techniques. The dose per fraction was slightly reduced (while not changing the total dose), and the interfraction interval was increased to 6 h. The goal was to decrease toxicity while maintaining satisfactory local-regional control. This retrospective study analyzes the results of this schedule modification. Methods and Materials: Two hundred thirty-six patients were included in the analysis. Distribution of patients by primary site and T stage was as follows: supraglottic larynx, 120 patients; hypopharynx, 70; true vocal cord, 24; and oropharynx, 22; T1, 5 patients; T2, 118; T3, 93; T4, 19; and Tx, 1. Ninety-nine patients presented with cervical nodal disease. Seventy-eight patients (group A), including 16 treated with induction chemotherapy, were treated throughout with 1.2 Gy fractions twice daily and a 4-h interfraction interval. Subsequently, 158 patients (group B), 57 of whom received chemotherapy, received 1.1 Gy fractions to 55 Gy, and then 1.2 Gy fractions to their boost volumes to 76.6 Gy. The interfraction interval was 6 h. Median follow-up was 91 and 35 months for group A and B, respectively. Results: Two-year actuarial survival, local control, and ultimate local rates were 70%, 75%, and 85%, respectively. Differences between survival rates for group A and group B were not statistically significant, with 2-year rates of 66% and 72%, respectively. Overall local control rates at 2 years were 77% and 74%, respectively, for groups A and B (p = 0.22). However, there was a trend toward inferior results in group B patients with T3 disease (67% at 2 years compared to 76% in group A, p = 0.13). Confluent mucositis and persistent mucositis developed in 52

The Relatives' Big Five Personality Influences the Trajectories of Recovery of Patients After Severe TBI: A Multilevel Analysis.

Science.gov (United States)

Haller, Chiara S

2017-08-01

This study examines the influence of the personality of relatives on the trajectories of recovery of patients with severe traumatic brain injury (TBI). The present subsample (N = 376) of a larger population-based, prospective, 12-month multicenter cohort study in Switzerland (2007-2011) consists of patients with severe TBI (age ≥ 16) and their relatives. The predictors are the NEO Five-Factor Inventory and time (trajectory of functioning of the patient over time). The outcomes are the patients' (a) neurological functioning; (b) reported emotional, interpersonal, cognitive, and total functioning post-injury; and (c) health-related quality of life (HRQoL). The covariates included Abbreviated Injury Scale score of the head region and age. Results for patients > 50 are (a) relatives' Extraversion influenced patients' total, interpersonal, and cognitive functioning; (b) relatives' Agreeableness influenced patients' interpersonal functioning; and (c) relatives' Conscientiousness influenced patients' physical HRQoL (ps personality traits of the relative covary with the functioning of the patient, and psychological adaptation to the loss of function may progress at a later stage after physical health improvements have been achieved. Thus, a biopsychosocial perspective on the rehabilitation process is needed. © 2016 Wiley Periodicals, Inc.

The contribution of retrospective memory, attention and executive functions to the prospective and retrospective components of prospective memory following TBI.

LENUS (Irish Health Repository)

Clune-Ryberg, Melanie

2011-01-01

Despite the prevalence of prospective memory (PM) problems, relatively little is known about the processes underlying impairment following TBI. This study sought to examine PM performance, using a multiple-task, multiple-response video-based paradigm in which initial encoding of the cue-action associations was ensured (Video-Assessment of Prospective Memory; VAPM).

Clinical study of four patients with hematological malignancy treated with allogeneic bone marrow transplantation after conditioning including hyperfractionated total body irradiation

International Nuclear Information System (INIS)

Kubo, Kazuaki; Naito, Kazuyuki; Akao, Yukihiro; Hiraiwa, Akikazu; Naoe, Tomoki; Yamada, Kazumasa; Matsunaga, Kayoko; Kobayashi, Hidetoshi; Matsuzaki, Michio.

1987-01-01

Based on the cytoreductive regimen reported by O'Reilly et al, we transplanted to four patients with hematological malignancy the bone marrow cells harvested from their HLA identical siblings. In our method, they were pretreated with hyperfractionated total body irradiation (120R x 11 times) and high dose of cyclophosphamide prior to transplantation. Case 1: 19 year-old, female, ALL. She had a temporal GVHD (Grade I) on day 23, and suffered from interstitial pneumonia (IP) on day 72 that responded well to the steroid therapy. She is now healthy (day 717). Case 2: 15 year-old, female, ALL. She had a mild GVHD on day 20 and IP on day 175 that recovered shortly after treated with steroid. She had an acute nephritis temporarily on day 410, as well. She is now healthy (day 668). Case 3: 39 year-old, female, AML. She suffered from a GVHD (Grade IV) with severe skin eruption, diarrhea and jaundice, which started on day 15. She died of hepatic failure on day 74, for which GVHD was responsible. Case 4: 25 year-old, male, Burkitt Lymphoma. He had a mild GVHD on day 33, which recovered soon with the steroid therapy. On day 150, he suffered from IP to which the steroid therapy was effective. However, IP was recurrent as well as his pneumothorax that happened subsequently. He is now healthy (day 458). (author)

Facial Emotion Recognition Deficits following Moderate-Severe Traumatic Brain Injury (TBI): Re-examining the Valence Effect and the Role of Emotion Intensity

NARCIS (Netherlands)

Rosenberg, H.; McDonald, S.; Dethier, M.; Kessels, R.P.C.; Westbrook, R.F.

2014-01-01

Many individuals who sustain moderate-severe traumatic brain injuries (TBI) are poor at recognizing emotional expressions, with a greater impairment in recognizing negative (e.g., fear, disgust, sadness, and anger) than positive emotions (e.g., happiness and surprise). It has been questioned whether

Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for Stage IIIA and Stage IIIB non-small cell lung cancer: results of a Phase I-II study by the GOTHA group

Energy Technology Data Exchange (ETDEWEB)

Alberto, P.; Mermillod, B. [Hopital Cantonal Geneve, Geneva (Switzerland); Mirimanoff, R.O.; Leyvraz, S.; Nagy-Mignotte, H.; Bolla, M.; Wellmann, D.; Moro, D.; Brambilla, E. [Hopital Cantonal Universitaire, Lausanne (Switzerland)

1995-08-01

The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy. (author).

"Help seniors live better, longer: prevent brain injury": an overview of CDC's education initiative to prevent fall-related TBI among older adults.

Science.gov (United States)

Sarmiento, Kelly; Langlois, Jean A; Mitchko, Jane

2008-01-01

Falls are the leading cause of traumatic brain injury (TBI) among older adults aged 75 and older. Despite this burden, many older adults, their caregivers, and professionals are not aware of the importance of TBI as an outcome of falls among older adults. To address this important public health problem, the Centers for Disease Control and Prevention (CDC) developed the "Help Seniors Live Better, Longer: Prevent Brain Injury" initiative to help raise awareness about methods to prevent, recognize and respond to fall-related TBIs among older adults aged 75 and older. The initiative was launched in March 2008, in collaboration with 26 participating organizations, and included a multipronged outreach strategy to help blanket the country with the messages of the initiative at the national, state, and local levels. Adherence to a logical, comprehensive health-education approach has proven to be highly effective in furthering the initial goals of the project.

Statistical Issues in TBI Clinical Studies

Directory of Open Access Journals (Sweden)

Paul eRapp

2013-11-01

Full Text Available The identification and longitudinal assessment of traumatic brain injury presents several challenges. Because these injuries can have subtle effects, efforts to find quantitative physiological measures that can be used to characterize traumatic brain injury are receiving increased attention. The results of this research must be considered with care. Six reasons for cautious assessment are outlined in this paper. None of the issues raised here are new. They are standard elements in the technical literature that describes the mathematical analysis of clinical data. The purpose of this paper is to draw attention to these issues because they need to be considered when clinicians evaluate the usefulness of this research. In some instances these points are demonstrated by simulation studies of diagnostic processes. We take as an additional objective the explicit presentation of the mathematical methods used to reach these conclusions. This material is in the appendices. The following points are made:1. A statistically significant separation of a clinical population from a control population does not ensure a successful diagnostic procedure.2. Adding more variables to a diagnostic discrimination can, in some instances, actually reduce classification accuracy.3. A high sensitivity and specificity in a TBI versus control population classification does not ensure diagnostic successes when the method is applied in a more general neuropsychiatric population. 4. Evaluation of treatment effectiveness must recognize that high variability is a pronounced characteristic of an injured central nervous system and that results can be confounded by either disease progression or spontaneous recovery. A large pre-treatment versus post-treatment effect size does not, of itself, establish a successful treatment.5. A procedure for discriminating between treatment responders and nonresponders requires, minimally, a two phase investigation. This procedure must include a

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer

International Nuclear Information System (INIS)

Staar, Susanne; Rudat, Volker; Stuetzer, Hartmut; Dietz, Andreas; Volling, Peter; Schroeder, Michael; Flentje, Michael; Eckel, Hans Edmund; Mueller, Rolf-Peter

2001-01-01

Purpose: To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC). Methods and Materials: Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m 2 /day)/carboplatinum (70 mg/m 2 ) on days 1-5 and 29-33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 μg, days 15-19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1-3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors). Results: This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p=0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p=0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p=0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p=0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p=0.84). For both

Quantitative Tractography and Volumetric MRI in Blast and Blunt Force TBI: Predictors of Neurocognitive and Behavioral Outcome

Science.gov (United States)

2014-10-01

domains based on the Caplan and colleagues26 factor analytic study with soldiers who sus- tained a mild to severe TBI. A full listing of symptoms assessed...in the NSI, categorized according to the Caplan et al26 suggested symptom groupings, can be found in Table 2. Statistical analyses Differences in... Caplan LJ, Ivins B, Poole JH, Vanderploeg R, Jaffee MS, Schwab K. The structure of postconcussive symptoms in 3 US military samples. J Head Trauma

Proceedings of the 2011 AFMS Medical Research Symposium. Volume 6. Traumatic Brain Injury (TBI) & Psychological Health Track

Science.gov (United States)

2011-08-02

million effort to study imagrtg d TBI in th e military Started af Walter Reed end USU 2 yea-s ago Advanced Imaging Study in ifiated St:andzud MRI ...Imaging-some MRI techniques are useful: OTI, SWI 4. Physiological-focus of this IPT (Non--Invasive Neurodiagnostic IPT) Three step approach to...the e ye a re d etected with i1frared sensors • In addition to the helmet a l.llptop complier (or tablet ) is attached • Developers are marketing as

Group therapy use and its impact on the outcomes of inpatient rehabilitation following traumatic brain injury: Data from TBI-PBE project

Science.gov (United States)

Hammond, Flora M.; Barrett, Ryan; Dijkers, Marcel P.; Zanca, Jeanne M.; Horn, Susan D.; Smout, Randall J.; Guerrier, Tami; Hauser, Elizabeth; Dunning, Megan R.

2015-01-01

Objective To describe the amount and content of group therapies provided during inpatient rehabilitation for traumatic brain injury (TBI), and assess the relationships of group therapy with patient, injury, and treatment factors as well as outcomes. Design Prospective observational cohort. Setting Inpatient rehabilitation. Participants 2,130 consecutive admissions for initial TBI rehabilitation at 10 inpatient rehabilitation facilities (9 in US and 1 Canada) from October 2008 to September 2011. Interventions n/a Main Outcome Measure(s) proportion of sessions that were group therapy (two or more patients were treated simultaneously by one or more clinicians); proportion of patients receiving group therapy; type of activity performed and amount of time spent in group therapy, by discipline; rehabilitation length of stay (RLOS); discharge location; FIM Cognitive and Motor scores at discharge. Results 79% of patients received at least 1 session of group therapy, with group therapy accounting for 13.7% of all therapy sessions and 15.8% of therapy hours. On average, patients spent 2.9 hours per week in group therapy. The greatest proportion of treatment time in group format was in Therapeutic Recreation (25.6%), followed by Speech Therapy (16.2%), Occupational Therapy (10.4%), Psychology (8.1%), and Physical Therapy (7.9%). Group therapy time and type of treatment activities varied among admission FIM cognitive subgroups and treatment sites. Several factors appear to be predictive of receiving group therapy, with treatment site being a major influence. However, group therapy as a whole offered little explanation of differences in the outcomes studied. Conclusion(s) Group therapy is commonly used in TBI rehabilitation, to varying degrees among disciplines, sites, and cognitive impairment subgroups. Various therapeutic activities take place in group therapy, indicating its perceived value in addressing many domains of functioning. Variation in outcomes is not explained

A pilot study of hyperfractionated radiotherapy for infants with retinoblastoma

International Nuclear Information System (INIS)

Harris, Eleanor E.R.; Meadows, Anna T.; Shields, Jerry; D'Angio, Giulio J.; Goldwein, Joel W.

1996-01-01

was preserved in 70% of patients. Radiation complications include none in 3 of 10 patients, mild orbital hypoplasia in the radiation field in 5 patients, cataracts in 3 patients and ocular loss in 1 patient (2 eyes) with bilateral local recurrences who was salvaged with bilateral plaque therapy but later required bilateral enucleations for pain and glaucoma. All cataracts were successfully treated. One patient developed an in-field second malignancy (nasopharyngeal sarcoma) at 4 years. Cataracts and bony hypoplasia were seen in patients treated with both en face electrons and opposed lateral photon fields. Conclusions: Twice daily external beam radiation therapy to 43-45 Gy in combination with other local therapies achieved survival of 80%, a local control rate of 84%, and an ocular preservation rate of 74% in a group of 10 infants with advanced intraocular retinoblastoma. These results compare favorably to other series reporting on patients with advanced intraocular disease. Our results suggest that hyperfractionated irradiation as primary therapy has an acceptable complication rate including mild orbital hypoplasia and treatable cataracts with no vision loss attributable to external beam irradiation alone. In addition, based on our review of the literature, the tumor control and ocular preservation may be better than with conventional fractionation

'The biggest thing is trying to live for two people': Spousal experiences of supporting decision-making participation for partners with TBI.

Science.gov (United States)

Knox, Lucy; Douglas, Jacinta M; Bigby, Christine

2015-01-01

To understand how the spouses of individuals with severe TBI experience the process of supporting their partners with decision-making. This study adopted a constructivist grounded theory approach, with data consisting of in-depth interviews conducted with spouses over a 12-month period. Data were analysed through an iterative process of open and focused coding, identification of emergent categories and exploration of relationships between categories. Participants were four spouses of individuals with severe TBI (with moderate-severe disability). Spouses had shared committed relationships (marriage or domestic partnerships) for at least 4 years at initial interview. Three spouses were in relationships that had commenced following injury. Two main themes emerged from the data. The first identified the saliency of the relational space in which decision-making took place. The second revealed the complex nature of decision-making within the spousal relationship. Spouses experience decision-making as a complex multi-stage process underpinned by a number of relational factors. Increased understanding of this process can guide health professionals in their provision of support for couples in exploring decision-making participation after injury.

Deficits in Visual System Functional Connectivity after Blast-Related Mild TBI are Associated with Injury Severity and Executive Dysfunction

Science.gov (United States)

2016-08-24

W. Jung. 2003. Long-term potentiation in visual cortical projections to the medial prefrontal cortex of the rat . Neuroscience 120:283–289. Kim, J., J...functional connec- tivity (FC) of four key nodes within the visual system: lateral geniculate nucleus (LGN), primary visual cortex (V1), lateral...related TBI may be accompanied by involvement of the visual system through optic nerve injury, diffuse or focal cerebral injury, or ocular motor

Assessment of the role of intracranial hypertension and stress on hippocampal cell apoptosis and hypothalamic-pituitary dysfunction after TBI.

Science.gov (United States)

Tan, Huajun; Yang, Weijian; Wu, Chenggang; Liu, Baolong; Lu, Hao; Wang, Hong; Yan, Hua

2017-06-19

In recent years, hypopituitarism caused by traumatic brain injury (TBI) has been explored in many clinical studies; however, few studies have focused on intracranial hypertension and stress caused by TBI. In this study, an intracranial hypertension model, with epidural hematoma as the cause, was used to explore the physiopathological and neuroendocrine changes in the hypothalamic-pituitary axis and hippocampus. The results demonstrated that intracranial hypertension increased the apoptosis rate, caspase-3 levels and proliferating cell nuclear antigen (PCNA) in the hippocampus, hypothalamus, pituitary gland and showed a consistent rate of apoptosis within each group. The apoptosis rates of hippocampus, hypothalamus and pituitary gland were further increased when intracranial pressure (ICP) at 24 hour (h) were still increased. The change rates of apoptosis in hypothalamus and pituitary gland were significantly higher than hippocampus. Moreover, the stress caused by surgery may be a crucial factor in apoptosis. To confirm stress leads to apoptosis in the hypothalamus and pituitary gland, we used rabbits to establish a standard stress model. The results confirmed that stress leads to apoptosis of neuroendocrine cells in the hypothalamus and pituitary gland, moreover, the higher the stress intensity, the higher the apoptosis rate in the hypothalamus and pituitary gland.

Phase II, two-arm RTOG trial (94-11) of bischloroethyl-nitrosourea plus accelerated hyperfractionated radiotherapy (64.0 or 70.4 Gy) based on tumor volume (> 20 or ≤ 20 cm2, respectively) in the treatment of newly-diagnosed radiosurgery-ineligible glioblastoma multiforme patients

International Nuclear Information System (INIS)

Coughlin, C.; Scott, C.; Langer, C.; Coia, L.; Curran, W.; Rubin, P.

2000-01-01

Purpose: To compare survivorship, and acute and delayed toxicities following radiation therapy (RT) of radiosurgery-ineligible glioblastoma multiforme (GBM) patients treated with tumor volume-influenced, high-dose accelerated, hyperfractionated RT plus bischloroethyl-nitrosourea (BCNU), using prior RTOG malignant glioblastoma patients as historical controls. Methods and Materials: One hundred four of 108 patients accrued from June 1994 through May 1995 from 26 institutions were analyzable. Patients were histologically confirmed with GBM, and previously untreated. Treatment assignment (52 patients/arm) was based on tumor mass (TM), defined as the product of the maximum diameter and greatest perpendicular dimension of the titanium-gadolinium-enhanced postoperative MRI: Arm A, 64 Gy, TM > 20 cm 2 ; or Arm B, 70.4 Gy, TM ≤ 20 cm 2 . Both Arms A and B received BCNU (80 mg/m 2 , under hyperhydration) days 1-3, 56-58, then 4 cycles, each 8 weeks, for a total of 6 treatment series. Results: During the 24 months immediately post-treatment, the overall median survival was 9.1 months in Arm A (64 Gy) and 11.0 months in Arm B (70.4 Gy). Median survival in recursive partitioning analysis (RPA) Class III/IV was 10.4 months in Arm A and 12.2 months in Arm B, while RPA Class V/VI was 7.6 months in Arm A and 6.1 months in Arm B. There were no grade 4 neurological toxicities in Arm A; 2 grade 4 neurological toxicities were observed in Arm B (1 motor deficit, 1 necrosis at 157 days post-treatment). Conclusion: This strategy of high-dose, accelerated hyperfractionated radiotherapy shortens overall RT treatment times while allowing dose escalation, and it provides the potential for combination with currently available, as well as newer, chemotherapy agents. Survival is comparable with previously published RTOG data, and toxicities are within acceptable limits.

Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

International Nuclear Information System (INIS)

Henríquez Hernández, Luis Alberto; Lara, Pedro Carlos; Pinar, Beatriz; Bordón, Elisa; Gallego, Carlos Rodríguez; Bilbao, Cristina; Pérez, Leandro Fernández; Morales, Amílcar Flores

2009-01-01

Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database http://www.ncbi.nlm.nih.gov/geo/ (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results

Effects of continuous hyperfractionated accelerated and conventionally fractionated radiotherapy on the parotid and submandibular salivary glands of rhesus monkeys

International Nuclear Information System (INIS)

Price, R.E.; Ang, K.K.; Stephens, L.C.; Peters, L.J.

1995-01-01

Radiotherapy is a major treatment modality for head and neck cancer. It is often not possible to exclude the salivary glands from the treatment fields. The unique susceptibility of the serous cells of the salivary glands to irradiation often results in xerostomia with ensuing secondary complications and discomfort to the patients. Recent reports have suggested that continuous hyperfractionated accelerated radiotherapy (CHART) can lead to considerably less reduction in salivary flow of the parotid salivary gland than conventional radiotherapy. This study was undertaken to assess histologic changes of salivary glands induced by CHART and conventional radiation fractionation schedules. The parotid and submandibular salivary glands of adult rhesus monkeys were irradiated with cobalt-60 γ radiation at 50 Gy/20 fractions/4 weeks, 55 Gy/25 fractions/5 weeks, or 54 Gy/36 fractions/12 days (CHART). Salivary tissues were harvested at 16 weeks following irradiation and evaluated histopathologically. Microscopically, the glands receiving 50 Gy, 55 Gy, or CHART were virtually indistinguishable. There was severe atrophy and fibrosis of all glands. Quantitative analysis revealed that 50 Gy, 55 Gy, and CHART induced a reduction of serous acini in parotid glands by 86.4%, 84.8%, and 88.8%, respectively. In submandibular glands, serous acini were reduced by 99.4%, 99.0%, and 100%, respectively. The corresponding reduction in mucous acini were 98.4%, 98.4%, and 99.2%, respectively. These histopathologic and quantitative morphologic studies show that the magnitude of serous gland atrophy in the parotid and submandibular salivary glands of rhesus monkeys was similar at 16 weeks after receiving 50 Gy in 20 fractions, 55 Gy in 25 fractions, or CHART

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

International Nuclear Information System (INIS)

Chitapanarux, Imjai; Kamnerdsupaphon, Pimkhuan; Pukanhapan, Nantaka; Tharavichitkul, Ekkasit; Vongtama, Roy

2013-01-01

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III-IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3-102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3 - 4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer. (author)

Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: A survey in 66 neurotrauma centers participating in the CENTER-TBI study

NARCIS (Netherlands)

M.C. Cnossen (Maryse); Huijben, J.A. (Jilske A.); van der Jagt, M. (Mathieu); Volovici, V. (Victor); van Essen, T. (Thomas); S. Polinder (Suzanne); D. Nelson (David); Ercole, A. (Ari); Stocchetti, N. (Nino); Citerio, G. (Giuseppe); W.C. Peul (Wilco); A.I.R. Maas (Andrew I.R.); D.K. Menon (David ); E.W. Steyerberg (Ewout W.); Lingsma, H.F. (Hester F.); Adams, H. (Hadie); Alessandro, M. (Masala); J.E. Allanson (Judith); Amrein, K. (Krisztina); Andaluz, N. (Norberto); N. Andelic (Nada); Andrea, N. (Nanni); L. Andreassen (Lasse); Anke, A. (Audny); Antoni, A. (Anna); Ardon, H. (Hilko); Audibert, G. (Gérard); Auslands, K. (Kaspars); Azouvi, P. (Philippe); Baciu, C. (Camelia); Bacon, A. (Andrew); Badenes, R. (Rafael); Baglin, T. (Trevor); R.H.M.A. Bartels (Ronald); P. Barzo (P.); Bauerfeind, U. (Ursula); R. Beer (Ronny); Belda, F.J. (Francisco Javier); B.-M. Bellander (Bo-Michael); A. Belli (Antonio); Bellier, R. (Rémy); H. Benali (Habib); Benard, T. (Thierry); M. Berardino (Maurizio); L. Beretta (Luigi); Beynon, C. (Christopher); Bilotta, F. (Federico); H. Binder (Harald); Biqiri, E. (Erta); Blaabjerg, M. (Morten); Lund, S.B. (Stine Borgen); Bouzat, P. (Pierre); Bragge, P. (Peter); Brazinova, A. (Alexandra); F. Brehar (Felix); Brorsson, C. (Camilla); Buki, A. (Andras); M. Bullinger (Monika); Bucková, V. (Veronika); Calappi, E. (Emiliana); P. Cameron (Peter); Carbayo, L.G. (Lozano Guillermo); Carise, E. (Elsa); K.L.H. Carpenter (Keri L.H.); Castaño-León, A.M. (Ana M.); Causin, F. (Francesco); Chevallard, G. (Giorgio); A. Chieregato (Arturo); G. Citerio (Giuseppe); Cnossen, M. (Maryse); M. Coburn (Mark); J.P. Coles (Jonathan P.); Cooper, J.D. (Jamie D.); Correia, M. (Marta); A. Covic (Amra); N. Curry (Nicola); E. Czeiter (Endre); M. Czosnyka (Marek); Dahyot-Fizelier, C. (Claire); F. Damas (François); P. Damas (Pierre); H. Dawes (Helen); De Keyser, V. (Véronique); F.D. Corte (Francesco); B. Depreitere (Bart); Ding, S. (Shenghao); D.W.J. Dippel (Diederik); K. Dizdarevic (Kemal); Dulière, G.-L. (Guy-Loup); Dzeko, A. (Adelaida); G. Eapen (George); Engemann, H. (Heiko); A. Ercole (Ari); P. Esser (Patrick); Ezer, E. (Erzsébet); M. Fabricius (Martin); V.L. Feigin (V.); Feng, J. (Junfeng); Foks, K. (Kelly); F. Fossi (Francesca); Francony, G. (Gilles); J. Frantzén (Janek); Freo, U. (Ulderico); S.K. Frisvold (Shirin Kordasti); Furmanov, A. (Alex); Gagliardo, P. (Pablo); D. Galanaud (Damien); G. Gao (Guoyi); K. Geleijns (Karin); A. Ghuysen (Alexandre); Giraud, B. (Benoit); Glocker, B. (Ben); Gomez, P.A. (Pedro A.); Grossi, F. (Francesca); R.L. Gruen (Russell); Gupta, D. (Deepak); J.A. Haagsma (Juanita); E. Hadzic (Ermin); I. Haitsma (Iain); J.A. Hartings (Jed); R. Helbok (Raimund); E. Helseth (Eirik); Hertle, D. (Daniel); S. Hill (Sean); Hoedemaekers, A. (Astrid); S. Hoefer (Stefan); P.J. Hutchinson (Peter J.); Håberg, K.A. (Kristine Asta); B.C. Jacobs (Bart); Janciak, I. (Ivan); K. Janssens (Koen); Jiang, J.-Y. (Ji-Yao); Jones, K. (Kelly); Kalala, J.-P. (Jean-Pierre); Kamnitsas, K. (Konstantinos); Karan, M. (Mladen); Karau, J. (Jana); A. Katila (Ari); M. Kaukonen (Maija); Keeling, D. (David); Kerforne, T. (Thomas); N. Ketharanathan (Naomi); Kettunen, J. (Johannes); Kivisaari, R. (Riku); A.G. Kolias (Angelos G.); Kolumbán, B. (Bálint); E.J.O. Kompanje (Erwin); D. Kondziella (Daniel); L.-O. Koskinen (Lars-Owe); Kovács, N. (Noémi); F. Kalovits (Ferenc); A. Lagares (Alfonso); L. Lanyon (Linda); S. Laureys (Steven); Lauritzen, M. (Martin); F.E. Lecky (Fiona); C. Ledig (Christian); R. Lefering; V. Legrand (Valerie); Lei, J. (Jin); L. Levi (Leon); R. Lightfoot (Roger); H.F. Lingsma (Hester); D. Loeckx (Dirk); Lozano, A. (Angels); Luddington, R. (Roger); Luijten-Arts, C. (Chantal); Maas, A.I.R. (Andrew I.R.); MacDonald, S. (Stephen); MacFayden, C. (Charles); M. Maegele (Marc); M. Majdan (Marek); Major, S. (Sebastian); A. Manara (Alex); Manhes, P. (Pauline); G. Manley (Geoffrey); Martin, D. (Didier); C. Martino (Costanza); Maruenda, A. (Armando); H. Maréchal (Hugues); Mastelova, D. (Dagmara); Mattern, J. (Julia); McMahon, C. (Catherine); Melegh, B. (Béla); Menon, D. (David); T. Menovsky (Tomas); Morganti-Kossmann, C. (Cristina); Mulazzi, D. (Davide); Mutschler, M. (Manuel); H. Mühlan (Holger); Negru, A. (Ancuta); Nelson, D. (David); E. Neugebauer (Eddy); V.F. Newcombe (Virginia F.); Noirhomme, Q. (Quentin); Nyirádi, J. (József); M. Oddo (Mauro); A.W. Oldenbeuving; M. Oresic (Matej); Ortolano, F. (Fabrizio); A. Palotie (Aarno); P.M. Parizel; Patruno, A. (Adriana); J.-F. Payen (Jean-François); Perera, N. (Natascha); V. Perlbarg (Vincent); Persona, P. (Paolo); Peul, W. (Wilco); N. Pichon (Nicolas); Piilgaard, H. (Henning); A. Piippo (Anna); S.P. Floury (Sébastien Pili); M. Pirinen (Matti); H. Ples (Horia); Polinder, S. (Suzanne); Pomposo, I. (Inigo); M. Psota (Marek); P. Pullens (Pim); L. Puybasset (Louis); A. Ragauskas (Arminas); R. Raj (Rahul); Rambadagalla, M. (Malinka); Rehorcíková, V. (Veronika); J.K.J. Rhodes (Jonathan K.J.); S. Richardson (Sylvia); S. Ripatti (Samuli); S. Rocka (Saulius); Rodier, N. (Nicolas); Roe, C. (Cecilie); Roise, O. (Olav); C.M.A.A. Roks (Gerwin); Romegoux, P. (Pauline); J. Rosand (Jonathan); Rosenfeld, J. (Jeffrey); C. Rosenlund (Christina); G. Rosenthal (Guy); R. Rossaint (Rolf); S. Rossi (Sandra); Rostalski, T. (Tim); D. Rueckert (Daniel); de Ruiz, A.F. (Arcaute Felix); M. Rusnák (Martin); Sacchi, M. (Marco); Sahakian, B. (Barbara); J. Sahuquillo (Juan); O. Sakowitz (Oliver); Sala, F. (Francesca); Sanchez-Pena, P. (Paola); Sanchez-Porras, R. (Renan); Sandor, J. (Janos); Santos, E. (Edgar); N. Sasse (Nadine); Sasu, L. (Luminita); Savo, D. (Davide); I.B. Schipper (Inger); Schlößer, B. (Barbara); S. Schmidt (Silke); Schneider, A. (Annette); H. Schoechl (Herbert); G.G. Schoonman; Rico, F.S. (Frederik Schou); E. Schwendenwein (Elisabeth); Schöll, M. (Michael); Sir, O. (özcan); T. Skandsen (Toril); Smakman, L. (Lidwien); D. Smeets (Dominique); Smielewski, P. (Peter); Sorinola, A. (Abayomi); E. Stamatakis (Emmanuel); S. Stanworth (Simon); Stegemann, K. (Katrin); Steinbüchel, N. (Nicole); R. Stevens (Robert); W. Stewart (William); E.W. Steyerberg (Ewout); N. Stocchetti (Nino); Sundström, N. (Nina); Synnot, A. (Anneliese); J. Szabó (József); J. Söderberg (Jeannette); F.S. Taccone (Fabio); Tamás, V. (Viktória); Tanskanen, P. (Päivi); A. Tascu (Alexandru); Taylor, M.S. (Mark Steven); Te, A.B. (Ao Braden); O. Tenovuo (Olli); Teodorani, G. (Guido); A. Theadom (Alice); Thomas, M. (Matt); D. Tibboel (Dick); C.M. Tolias (Christos M.); Tshibanda, J.-F.L. (Jean-Flory Luaba); Tudora, C.M. (Cristina Maria); P. Vajkoczy (Peter); Valeinis, E. (Egils); Hecke, W.V. (Wim Van); Praag, D.V. (Dominique Van); Dirk, V.R. (Van Roost); Vlierberghe, E.V. (Eline Van); Vyvere, T.V. (Thijs vande); Vanhaudenhuyse, A. (Audrey); A. Vargiolu (Alessia); E. Vega (Emmanuel); J. Verheyden (Jan); Vespa, P.M. (Paul M.); A. Vik (Anne); R. Vilcinis (Rimantas); Vizzino, G. (Giacinta); C.L.A.M. Vleggeert-Lankamp (Carmen); V. Volovici (Victor); P. Vulekovic (Peter); Vámos, Z. (Zoltán); Wade, D. (Derick); Wang, K.K.W. (Kevin K.W.); Wang, L. (Lei); E.D. Wildschut (Enno); G. Williams (Guy); Willumsen, L. (Lisette); Wilson, A. (Adam); Wilson, L. (Lindsay); Winkler, M.K.L. (Maren K.L.); P. Ylén (Peter); Younsi, A. (Alexander); M. Zaaroor (Menashe); Zhang, Z. (Zhiqun); Zheng, Z. (Zelong); Zumbo, F. (Fabrizio); de Lange, S. (Stefanie); G.C.W. De Ruiter (Godard C.W.); den Boogert, H. (Hugo); van Dijck, J. (Jeroen); T.A. van Essen (T.); C.M. van Heugten (Caroline M.); M. van der Jagt (Mathieu); J. van der Naalt (Joukje)

2017-01-01

textabstractBackground: No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP)

Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

Directory of Open Access Journals (Sweden)

Caroline I. E. Renner

2015-09-01

Full Text Available Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed.

Time-dose modifications

International Nuclear Information System (INIS)

Kian Ang, K.

1987-01-01

Changes in fractionation schedule can be made by various approaches. However, from the first principle, it is anticipated that strategies of hyperfractionation and/or accelerated fractionation offer the most promised in improving the therapeutic ratio. Hyperfractionation is defined as a treatment schedule in which a large number of significantly reduced dose fractions (--1.2 Gy/fraction) is used to give a greater total dose in a conventional overall time period. The results of the pilot studies testing the efficacy of hyperfractionation have been encouraging. The most valid clinical trial of pure hyperfractionation, however, is that conducted by the EORTC. This study compared 70 Gy in 35 fractions or 80.5 Gy in 70 fractions over 7 weeks in the treatment of patients with oropharyngeal carcinomas. The local tumor control was significantly improved in the hyperfractionated arm without increasing the morbidity. Accelerated fractionation is defined as a schedule in which the overall time of treatment is reduced without significant changes in the total dose and fraction size. The strategy has been used to treat patients with malignant gliomas, melanomas and Head and Neck cancers. The data in Head and Neck Cancers seem to be promising

SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

International Nuclear Information System (INIS)

Lamichhane, N; Studenski, M

2016-01-01

Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobend block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.

SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

Energy Technology Data Exchange (ETDEWEB)

Lamichhane, N; Studenski, M [University of Miami, Miami, FL (United States)

2016-06-15

Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobend block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.

Using information from the electronic health record to improve measurement of unemployment in service members and veterans with mTBI and post-deployment stress.

Directory of Open Access Journals (Sweden)

Christina Dillahunt-Aspillaga

Full Text Available The purpose of this pilot study is 1 to develop an annotation schema and a training set of annotated notes to support the future development of a natural language processing (NLP system to automatically extract employment information, and 2 to determine if information about employment status, goals and work-related challenges reported by service members and Veterans with mild traumatic brain injury (mTBI and post-deployment stress can be identified in the Electronic Health Record (EHR.Retrospective cohort study using data from selected progress notes stored in the EHR.Post-deployment Rehabilitation and Evaluation Program (PREP, an in-patient rehabilitation program for Veterans with TBI at the James A. Haley Veterans' Hospital in Tampa, Florida.Service members and Veterans with TBI who participated in the PREP program (N = 60.Documentation of employment status, goals, and work-related challenges reported by service members and recorded in the EHR.Two hundred notes were examined and unique vocational information was found indicating a variety of self-reported employment challenges. Current employment status and future vocational goals along with information about cognitive, physical, and behavioral symptoms that may affect return-to-work were extracted from the EHR. The annotation schema developed for this study provides an excellent tool upon which NLP studies can be developed.Information related to employment status and vocational history is stored in text notes in the EHR system. Information stored in text does not lend itself to easy extraction or summarization for research and rehabilitation planning purposes. Development of NLP systems to automatically extract text-based employment information provides data that may improve the understanding and measurement of employment in this important cohort.

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation

DEFF Research Database (Denmark)

Cahu, X; Labopin, M; Giebel, S

2016-01-01

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown...... patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.Bone Marrow Transplantation advance online publication, 30 November 2015; doi:10.1038/bmt.2015.278....

Effect of interfraction interval in hyperfractionated radiotherapy with or without concurrent chemotherapy for stage III nonsmall cell lung cancer

International Nuclear Information System (INIS)

Jeremic, Branislav; Shibamoto, Yuta

1996-01-01

Purpose: To explore the influence of interfraction interval in hyperfractionated radiotherapy (HFX RT) with or without concurrent chemotherapy for Stage III nonsmall cell lung cancer. Methods and Materials: One hundred sixty-nine patients treated in a randomized study were retrospectively analyzed. Group I patients were treated by HFX RT with 1.2 Gy twice daily with a total dose of 64.8 Gy in 27 treatment days, while Groups II and III patients were treated by the same HFX RT and concurrent chemotherapy with carboplatin and etoposide (every week in Group II and every other week in Group III). Interfraction intervals of either 4.5-5 h or 5.5-6 h were used for each patient. Results: Patients treated with shorter interfraction intervals (4.5-5 h) had a better prognosis than those treated with longer intervals (5.5-6 h) (median survival: 22 vs. 7 months; 5-year survival rate: 27% vs. 0%, p = 0.00000). This phenomenon was observed in all treatment groups. Patients ≥ 60 years of age, with Stage IIIA disease, or with previous weight loss ≤ 5% were treated more often with the shorter intervals than those 5%, respectively, but in all of these subgroups of patients, the shorter intervals were associated with a better prognosis. Multivariate analysis showed that the interfraction interval was an independent prognostic factor, together with sex, age, performance status, and stage. The shorter intervals were associated with an increased incidence of acute high grade toxicity, but not with an increase in late toxicity. Conclusion: Patients treated with shorter interfraction intervals (4.5-5 h) appeared to have a better survival than those treated with longer intervals (5.5-6 h). Prospective randomized studies are warranted to further investigate the influence of interfraction interval in HFX RT

Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

International Nuclear Information System (INIS)

Gupta, Tejpal; Jalali, Rakesh; Goswami, Savita; Nair, Vimoj; Moiyadi, Aliasgar; Epari, Sridhar; Sarin, Rajiv

2012-01-01

Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children ≥5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5–14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56–70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16–58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Gupta, Tejpal, E-mail: tejpalgupta@rediffmail.com [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Jalali, Rakesh [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Goswami, Savita [Department of Clinical Psychology and Psychiatry Unit, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Nair, Vimoj [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Moiyadi, Aliasgar [Division of Neuro-Surgery, Department of Surgical Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Epari, Sridhar [Department of Pathology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Sarin, Rajiv [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India)

2012-08-01

Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children {>=}5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5-14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56-70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16-58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

Feasibility of TBI Assessment Measures in a Field Environment: A Pilot Study for the Environmental Sensors in Training (ESiT) Project

Science.gov (United States)

2016-12-22

MRI ]) afterwards. More severe TBI symptoms may last from a few days to multiple years following the injurious event, and repeated TBIs may result...touch-screen tablet computer that provides administrative capabilities to the tester, a virtual reality goggle visor with motion detection (see Figure 6...Evidence from functional MRI and neurogenetics. Journal of Neurotrauma, 23(10), 1450-1467. Mirksy, A. F. & van Buren, J. M. (1965). On the nature of

Technical problems of TBI in case of the moving couch method

Energy Technology Data Exchange (ETDEWEB)

Tsuda, Masayuki (Tokai Univ., Isehara, Kanagawa (Japan). Hospital)

1991-12-01

In Tokai University Hospital ever since 1982, TBI for bone marrow transplantation has been performed by the moving couch method. In this method, the patient is irradiated from the opposite direction of A-P and P-A in a comfortable supine position as is. This technique has been well studied and greatly improved. For example, the moving speed of the couch is automatically varied depending on the dose rate deviation of the electron linear accelerator, function having variable speed with the dose rate (VSDR). Another function in variable speed with division (VSDV). In addition it has a self-recording function for the actual condition for the dose and couch movement. In such small areas as the eyes and gonad, the shielding effect cannot be effectively used. For the lungs, but it is able to shield and compensate to a sufficient extent. It applied to actual treatment resulting from data obtained from the measurements using a phantom. During the irradiation we must check the reproducibility of the systems which are dose rate, couch position, and so on. This is one reasonable concept of the dose monitor. (author).

Increased prognostic accuracy of TBI when a brain electrical activity biomarker is added to loss of consciousness (LOC).

Science.gov (United States)

Hack, Dallas; Huff, J Stephen; Curley, Kenneth; Naunheim, Roseanne; Ghosh Dastidar, Samanwoy; Prichep, Leslie S

2017-07-01

Extremely high accuracy for predicting CT+ traumatic brain injury (TBI) using a quantitative EEG (QEEG) based multivariate classification algorithm was demonstrated in an independent validation trial, in Emergency Department (ED) patients, using an easy to use handheld device. This study compares the predictive power using that algorithm (which includes LOC and amnesia), to the predictive power of LOC alone or LOC plus traumatic amnesia. ED patients 18-85years presenting within 72h of closed head injury, with GSC 12-15, were study candidates. 680 patients with known absence or presence of LOC were enrolled (145 CT+ and 535 CT- patients). 5-10min of eyes closed EEG was acquired using the Ahead 300 handheld device, from frontal and frontotemporal regions. The same classification algorithm methodology was used for both the EEG based and the LOC based algorithms. Predictive power was evaluated using area under the ROC curve (AUC) and odds ratios. The QEEG based classification algorithm demonstrated significant improvement in predictive power compared with LOC alone, both in improved AUC (83% improvement) and odds ratio (increase from 4.65 to 16.22). Adding RGA and/or PTA to LOC was not improved over LOC alone. Rapid triage of TBI relies on strong initial predictors. Addition of an electrophysiological based marker was shown to outperform report of LOC alone or LOC plus amnesia, in determining risk of an intracranial bleed. In addition, ease of use at point-of-care, non-invasive, and rapid result using such technology suggests significant value added to standard clinical prediction. Copyright © 2017 Elsevier Inc. All rights reserved.

Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

Science.gov (United States)

Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

2013-10-01

We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

TBI Patient, Injury, Therapy, and Ancillary Treatments Associated with Outcomes at Discharge and 9 Months Post-discharge

Science.gov (United States)

Horn, Susan D.; Corrigan, John D.; Beaulieu, Cynthia L.; Bogner, Jennifer; Barrett, Ryan S.; Giuffrida, Clare G.; Ryser, David K.; Cooper, Kelli; Carroll, Deborah M.; Deutscher, Daniel

2015-01-01

Objective To examine associations of patient and injury characteristics, inpatient rehabilitation therapy activities, and neurotropic medications with outcomes at discharge and 9 months post-discharge for patients with traumatic brain injury (TBI) Design Prospective, longitudinal observational study Setting 10 inpatient rehabilitation centers (9 US, 1 Canada) Participants Consecutive patients (n=2130) enrolled between 2008 and 2011, admitted for inpatient rehabilitation after an index TBI injury Interventions Not applicable Main Outcome Measures Rehabilitation length of stay, discharge to home, and Functional Independence Measure (FIM) at discharge and 9 months post-discharge Results The admission FIM Cognitive score was used to create 5 relatively homogeneous subgroups for subsequent analysis of treatment outcomes. Within each subgroup, significant associations were found between outcomes and patient and injury characteristics, time spent in therapy activities, and medications used. Patient and injury characteristics explained on average 35.7% of the variation in discharge outcomes and 22.3% in 9-month outcomes. Adding time spent and level of effort in therapy activities, as well as percent of stay using specific medications, explained approximately 20.0% more variation for discharge outcomes and 12.9% for 9-month outcomes. After patient, injury, and treatment characteristics were used to predict outcomes, center differences added only approximately 1.9% additional variance explained. Conclusions At discharge, greater effort during therapy sessions, time spent in more complex therapy activities, and use of specific medications were associated with better outcomes for patients in all admission FIM Cognitive subgroups. At 9 months post-discharge, similar but less pervasive associations were observed for therapy activities, but not classes of medications. Further research is warranted to examine more specific combinations of therapy activities and medications that

Impact of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and Positron Emission Tomography/Computed Tomography (PET/CT) in the Diagnosis of Traumatic Brain Injury (TBI): Case Report.

Science.gov (United States)

Molina-Vicenty, Irma L; Santiago-Sánchez, Michelaldemar; Vélez-Miró, Iván; Motta-Valencia, Keryl

2016-09-01

Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external force. TBI, a global leading cause of death and disability, is associated with serious social, economic, and health problems. In cases of mild-to-moderate brain damage, conventional anatomical imaging modalities may or may not detect the cascade of metabolic changes that have occurred or are occurring at the intracellular level. Functional nuclear medicine imaging and neurophysiological parameters can be used to characterize brain damage, as the former provides direct visualization of brain function, even in the absence of overt behavioral manifestations or anatomical findings. We report the case of a 30-year-old Hispanic male veteran who, after 2 traumatic brain injury events, developed cognitive and neuropsychological problems with no clear etiology in the presence of negative computed tomography (CT) findings.

Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients

NARCIS (Netherlands)

Schagen, S. B.; Muller, M. J.; Boogerd, W.; Rosenbrand, R. M.; van Rhijn, D.; Rodenhuis, S.; van Dam, F. S. A. M.

2002-01-01

BACKGROUND: Neuropsychological examinations have shown an elevated risk for cognitive impairment 2 years after therapy in breast cancer patients randomized to receive adjuvant high-dose cyclophosphamide, thiotepa, carboplatin (CTC) chemotherapy compared with a non-treated control group of stage I

Radiation therapy for hypopharyngeal carcinoma. Impact of fractionation on treatment outcome

International Nuclear Information System (INIS)

Niibe, Yuzuru; Karasawa, Katsuyuki; Igaki, Hiroshi; Miyashita, Hisao; Tanaka, Yoshiaki

2003-01-01

The purpose of the current study was to evaluate the impact of fractionation on the treatment outcome of radiation therapy for hypopharyngeal carcinoma. Thirty-six inoperable or operation-refused hypopharyngeal patients were treated with curative-intended radiation therapy between 1976 and May 2001. Seventeen patients were treated with conventional radiation therapy, 1.8-2.0 Gy per fraction, totaling 64.0 Gy (conventional fractionation (CF) group), and 19 were treated with hyperfractionated radiation therapy, 1.2 Gy per fraction, totaling 74.4 Gy (hyperfractionation (HF) group). The radiation response of the two groups at the end of radiation therapy was almost the same. However, the 2-year local control rates of the HF and CF groups were 59.0% and 26.1% (p=0.012), respectively, a statistically significant differences. Moreover, multivariate analysis showed that HF was an independent prognostic factor for local control. Hyperfractionated radiation therapy was superior to conventional radiation therapy for local control. Local control of hypopharyngeal carcinoma correlated with laryngeal preservation, suggesting that hyperfractionated radiation therapy for hypopharyngeal carcinoma could be beneficial for patient quality of life (QOL). (author)

PENINGKATAN KETERAMPILAN BERBICARA BAHASA INGGRIS DENGAN METODE SUGGESTOPEDIA PADA MAHASISWA SEMESTER II-E TBI STAIN PAMEKASAN

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Sumihatul Ummah

2015-11-01

Full Text Available There are two problems in the result of research that will be discussed in this article. They are (1 how are the steps of the implementation of suggestopedia method in learning speaking English at the second semester students of E class TBI STAIN Pamekasan and (2 How are the increasing of speaking English skill for the second semester students of E class TBI STAIN Pamekasan in learning speaking English by using the suggestopedia method. The research method is classroom action research by using research strategy of Kemmis and Mc Taggert Model which consist of four (4 steps, namely planning, acting, observing, and reflecting. The result of research provided that classically for the 1st, 2nd, and 3rd cycle indicated the increasing of students learning completeness scores, each of them are 38.23%, 67.54%, and 82.35%. While the students performance for each aspects are increasing from the 1st cycle up to 3rd cycle. The students performance of speaking English activities in the classroom from each aspects that more appear was grammar with score 85.2%. for the 2nd cycle was comprehensibility with score 88.2% and vocabulary with score 88.2%, and for the 3rd  cycle that more appear was fluency with score 91.2%.  Besides, for the frequency percentage of students performance from each cycles are more increasing, by the 1st  cycle 55% (enough, the 2nd cycle 70% (good, and the 3rd cycle 85% (very good. Finally, the suggestopedia method in learning speaking English can increase the result of students learning. In fact, the students look like be enthusiastic in learning speaking English. The students were active to joint with this subject from each cycle. By the good atmosphere, conducive situation of the classroom, and soft music made the students to be relax in learning the subject. It also was increase imagination, concentration, and liveliness for the students.

Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies.

Science.gov (United States)

Bhatnagar, Bhavana; Rapoport, Aaron P; Fang, Hong-Bin; Ilyas, Can; Marangoz, Deniz; Akbulut, Vinil; Ruehle, Kathleen; Badros, Ashraf; Yanovich, Saul; Akpek, Görgün

2014-04-01

We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6-28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.

Sensitive Bioanalytical Methods for Mustard Gas Exposure Diagnosis

Science.gov (United States)

2006-11-01

bis (2-chloreoethyl0-1- nitrosourea ), thio-TEPA (N, N’N’-triethylenethiophosphoramide), busulfan (1, 4-butanediol dimethanesulfonate), MNNG (1...N- nitrosourea ), mounting solution, sucrose, and colloidal gold solution were purchased from Sigma (St. Louis, MO). 2.2 Cell culture Frozen

Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer

International Nuclear Information System (INIS)

Shaw, Edward G.; Deming, Richard L.; Creagan, Edward T.; Nair, Suresh; Su, John Q.; Levitt, Ralph; Steen, Preston D.; Wiesenfeld, Martin; Mailliard, James A.

1995-01-01

Purpose: Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population. Methods and Materials: Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease. Results: Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively. Conclusion: Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting

Costs of conventional radical radiotherapy versus continuous hyperfractionated accelerated radiotherapy (CHART) in the treatment of patients with head and neck cancer or carcinoma of the bronchus. Medical Research Council CHART Steering Committee.

Science.gov (United States)

Coyle, D; Drummond, M F

1997-01-01

The objective of this study was to compare the costs of treatment with continuous hyperfractionated accelerated radiotherapy (CHART) and those of conventional radiotherapy for patients with (1) head and neck cancer and (2) carcinoma of the bronchus. The study was conducted concurrently with two multicentre randomized controlled trials. Data were collected on the use of hospital and community service resources and patients' travel for treatment. Data on resource use up to 3 months after entry to the study were available for 526 head and neck patients (314 receiving CHART and 212 conventional therapy) and 284 bronchus patients (175 CHART and 109 conventional therapy). For patients with head and neck cancer, CHART cost Pounds 1092 (P hostel facilities. The results of this cost analysis will help to facilitate a decision about whether the benefits of CHART, as determined by the clinical trials, are worth the additional costs of hospital-based resource use. The collection of detailed patient-specific resource-use data from a number of centres allows the determination of ways for reducing the cost differential between therapies and making CHART a more cost effective treatment alternative.

Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in esophageal cancer followed by transhiatal esophagectomy

International Nuclear Information System (INIS)

Chang, H.S.; Choi, E.K.; Kim, J.H.; Kim, S.B.; Kim, S.H.; Lee, K.H.; Lee, J.S.; Min, Y.I.; Lee, Y.S.; Sohn, K.H.; Lee, J.W.; Park, S.I.; Lee, I.; Song, H.Y.

1995-01-01

Purpose/Objectives: A prospective study for localized esophageal cancer using hyperfractionated radiotherapy(1.2Gy/fx, BID, 48Gy/4wks) with concurrent chemotherapy FP(CDDP 60mg/M 2 /d, d1 and d29, 5-FU 1gm/M 2 /d, continuous infusion d2-6 and d30-34) followed by esophagectomy has been conducted to evaluate the efficacy and toxicity of chemoradiation followed by surgery and curative potential of transhiatal esophagecomy. We analyze the clinical/pathological response and toxicity of preoperative regimen and report the patterns of failure and the survival of patients in esophagectomy group compared with patients who treated with definitive radiotherapy. Materials and Methods: Since May 1993, 48 patients with localized esophageal cancer entered on this trial and 42 patients were evaluated for response and toxicity in 4 weeks after completion of preoperative regimen. 15 patients underwent surgery and 5 are waiting for surgery. Among 22 patients who refused the surgery, 11 patients received the definitive radiotherapy (≥60Gy) and 11 of them refused further therapy. In 41 men and 1 women with median age of 61 years old (range 41-75 years), 8 patients were staged as SI, 22 SII, and 12 SIII with endoscopic, histologic and radiologic evaluation. Results: Clinical tumor response was observed in 79%((33(42))) and 66%((23(35))) of patients who had histologic evaluation showed complete pathologic response. (13(15)) who underwent surgery achieved complete resection and surgical specimen of 7(47%) patients showed no histologic evidence of disease. 20% ((3(15))) surgical mortality was observed. Among 15 patients who underwent surgery, 53% ((8(15))) are alive NED in 3-19 months (median 7 months), 1 patient is alive with disease in 3 months, 2 patients died of progression, 3 postoperative mortality and 1 patient died of lung cancer in 5 months. Among 11 patients who received curative radiotherapy, 6 are alive with good performance, NED in 9-15 months (median 10 months), 3 are alive

Late neurotoxicity after nasopharyngeal carcinoma treatment

International Nuclear Information System (INIS)

Siala, W.; Mnejja, W.; Daoud, J.; Khabir, A.; Boudawara, T.; Ben Mahfoudh, K.; Ghorbel, A.; Frikha, M.

2009-01-01

Purpose A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy. Patients and methods Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity. Results After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p = 0.02). On multivariate analysis, hyperfractionation and age were insignificant. Conclusion Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study

Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

International Nuclear Information System (INIS)

Canyilmaz, Emine; Yavuz, Melek Nur; Serdar, Lasif; Uslu, Gonca Hanedan; Zengin, Ahmet Yasar; Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan

2014-01-01

Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy

Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Canyilmaz, Emine, E-mail: dremocan@yahoo.com [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey); Yavuz, Melek Nur [Department of Radiation Oncology, Akdeniz University, Antalya (Turkey); Serdar, Lasif [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey); Uslu, Gonca Hanedan; Zengin, Ahmet Yasar [Department of Radiation Oncology, Kanuni Research and Education Hospital, Trabzon (Turkey); Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey)

2014-11-01

Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

International Nuclear Information System (INIS)

Hall, Matthew D.; Schultheiss, Timothy E.; Smith, David D.; Nguyen, Khanh H.; Wong, Jeffrey Y.C.

2015-01-01

Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

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Hall, Matthew D. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E., E-mail: schultheiss@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Smith, David D. [Division of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Nguyen, Khanh H. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Department of Radiation Oncology, Bayhealth Cancer Center, Dover, Delaware (United States); Wong, Jeffrey Y.C. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

2015-01-01

Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

Molecular programs induced by heat acclimation confer neuroprotection against TBI and hypoxic insults via cross-tolerance mechanisms

Directory of Open Access Journals (Sweden)

Michal eHorowitz

2015-07-01

Full Text Available Neuroprotection following prolonged exposure to high ambient temperatures (heat acclimation HA develops via altered molecular programs such as cross-tolerance (Heat Acclimation -Neuroprotection Cross-Tolerance -HANCT. The mechanisms underlying cross-tolerance depend on enhanced on-demand protective pathways evolving during acclimation. The protection achieved is long lasting and limits the need for de novo recruitment of cytoprotective pathways upon exposure to novel stressors. Using mouse and rat acclimated phenotypes, we will focus on the impact of heat acclimation on Angiotensin II-AT2 receptors in neurogenesis and on HIF-1 as key mediators in spontaneous recovery and HANCT after traumatic brain injury (TBI. The neuroprotective consequences of heat acclimation on NMDA and AMPA receptors will be discussed using the global hypoxia model. A behavioral-molecular link will be crystallized. The differences between HANCT and consensus preconditioning will be reviewed.

Comparison of two dimensional and three dimensional radiotherapy treatment planning in locally advanced non-small cell lung cancer treated with continuous hyperfractionated accelerated radiotherapy weekend less

International Nuclear Information System (INIS)

Wilson, Elena M.; Joy Williams, Frances; Ethan Lyn, Basil; Aird, Edwin G.A.

2005-01-01

Background and purpose: Patients with inoperable non-small cell lung cancer being treated with continuous hyperfractionated accelerated radiotherapy weekend less (CHARTWEL) were planned and treated with a three dimensional (3D) conformal protocol and comparison made with two dimensional (2D) planning, as used previously, to compare past practice and methods. Patients and methods: Twenty-four patients were planned initially using 3D and then replanned using a 2D system. The 2D plans were transferred onto the 3D system and recalculated. Dose volume histograms could then be constructed of planning target volumes for phases 1 and 2 (PTV 1 and 2, respectively), lung and spinal cord for the 2D plans and compared with the 3D plans. Results: There was a significantly lower absolute dose to the isocentre with 2D compared to 3D planning with dose reductions of 3.9% for phase 1, 4.4% for phase 2 and 4.7% for those treated with a single phase. Maximum dose to spinal cord was greater in 17 of the 24 2D plans with a median dose reduction of 0.82 Gy for 3D (P=0.04). The percentage volume of whole lung receiving ≥20 Gy (V 20 ) was greater in 16 of the 24 2D plans with a median reduction in V 20 of 2.4% for 3D (P=0.03). Conclusions: A lower dose to tumour was obtained using 2D planning due to the method of dose calculation and spinal cord and lung doses were significantly higher

Concurrent chemotherapy, accelerated hyperfractionated split course radiation therapy and surgery for esophageal cancer

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Becker, M.; Adelstein, D.J.; Rice, T.W.; Kirk, M.A. van; Kirby, T.J.; Koka, A.; Tefft, M.; Zuccaro, G.

1996-01-01

Purpose/Objectives: A prospective single arm trial was undertaken to determine the toxicity, the clinical and pathologic response rates and survival for patients with esophageal cancer treated with concurrent chemotherapy(CC) and accelerated hyperfractionated split course radiotherapy(AHFSCRT) followed by surgical resection. Materials and Methods: A prospective single arm trial was conducted between 1991 and 1995 for patients with T1-4, N0-1, M1(celiac or supraclavicular) adenocarcinoma or squamous cell carcinoma of the esophagus. A total of 74 patients entered onto the protocol, and 72 are eligible and evaluable. Neoadjuvant chemotherapy consisting of two cycles of Cisplatin(20mg/m2/day) and 5-fluorouracil (1000mg/m2/day) given concurrently with AHSCRT 1.5Gy BID (at least 6 hour between fractions) to 2400cGy and 2100cGy, with cycles 1 and 2 of chemotherapy respectively. Patients were staged/restaged with barium esophagram(BS), computerized tomograph of the chest(CAT), upper endoscopy(EGD) with ultrasound (EUS) and evaluated for surgical resection. A single adjuvant course of concurrent chemotherapy and AHSCRT was delivered for those patients who were pathologic partial responders(pPR). Results: Initial clinical staging revealed one patient stage I, 24 patients' stage IIA, 2 patients' with stage IIB, 34 patients' with stage III and 6 patients' with stage IV disease. Five patients could not be staged adequately. The toxicity to neoadjuvant therapy included nausea in 85% (grade 3 in 1%), esophagitis 90% (grade 3 in 18%), neutropenia grade 3 of 43% (with fever 17%), thrombocytopenia grade 4 in 10% and nephrotoxicity in 8%. There was one death due to neoadjuvant therapy. Of the 72 evaluable patients, 67 underwent surgery, and 65(90%) had a complete resection. Twenty-seven percent were pathologic complete responders, including 22% with adenocarcinoma and 36% with squamous cell carcinoma. Complete pathologic response after neoadjuvant therapy was accurately predicted by

ACPSEM ROSG TBI working group recommendations for quality assurance in total body irradiation

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Nelligan, Raelene; Bailey, Michael; Tran, Thu; Baldwin, Zoe

2015-01-01

The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) radiation oncology specialty group (ROSG) formed a series of working groups in 2011 to develop recommendations for guidance of radiation oncology medical physics practice within the Australasian setting. These recommendations are intended to provide guidance for safe work practices and a suitable level of quality control without detailed work instructions. It is the responsibility of the medical physicist to ensure that locally available equipment and procedures are sufficiently sensitive to establish compliance to these recommendations. The recommendations are endorsed by the ROSG, and have been subject to independent expert reviews. For the Australian audience, these recommendations should be read in conjunction with the tripartite radiation oncology practice standards [1, 2]. This publication presents the recommendations of the ACPSEM total body irradiation working group (TBIWG) and has been developed in alignment with other international associations. However, these recommendations should be read in conjunction with relevant national, state or territory legislation and local requirements, which take precedence over the ACPSEM recommendations. It is hoped that the users of this and other ACPSEM recommendations will contribute to the development of future versions through the ROSG of the ACPSEM. This document serves as a guideline for calibration and quality assurance of equipment used for TBI in Australasia.

Altered fractionated radiotherapy has a survival benefit for head and neck cancers. Is it true?

International Nuclear Information System (INIS)

Hatano, Kazuo; Sakai, Mitsuhiro; Araki, Hitoshi; Doi, Katsuyuki; Asano, Takanori; Fujikawa, Akira

2007-01-01

There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years. The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years). The effect was greater for the primary tumor than for nodal disease. The effect was also more pronounced in younger patients and in those with good performance status. Hyperfractionation seemed to yield a more consistent advantage for survival than accelerated fractionated radiotherapy. However, accelerated radiotherapy might be associated with higher non-cancer related death. We have to evaluate whether the benefit of hyperfractionated radiotherapy versus standard radiotherapy persists when combined with concomitant chemotherapy and the benefit of intensity-modulated radiation therapy (IMRT) compared with altered fractionation. (author)

Efficacy of memory rehabilitation therapy: a meta-analysis of TBI and stroke cognitive rehabilitation literature.

Science.gov (United States)

Elliott, Madison; Parente, Frederick

2014-01-01

To examine the efficacy of cognitive rehabilitation strategies specifically designed to improve memory after traumatic brain injury (TBI) and stroke vs. memory improvement with the passage of time. A meta-analysis was performed on 26 studies of memory retraining and recovery that were published between the years of 1985 and 2013. Effect sizes (ESs) from each study were calculated and converted to Pearson's r and then analysed to assess the overall effect size and the relationship among the ESs, patient demographics and treatment interventions. RESULTS indicated a significant average ES (r = 0.51) in the treatment intervention conditions, as well as a significant average ES (r = 0.31) in the control conditions, in which participants did not receive any treatment. The largest ESs occurred in studies of stroke patients and studies concerning working memory rehabilitation. RESULTS showed that memory rehabilitation was an effective therapeutic intervention, especially for stroke patients and for working memory as a treatment domain. However, the results also indicated that significant memory improvement occurred spontaneously over time.

Monte Carlo techniques for the study of cancer patients fractionation in head and neck treated with radiotherapy; Tecnicas de Monte Carlo para el estudio del fraccionamiento en pacientes de cancer de cabeza y cuello tratados con radioterapia

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Carrasco Herrera, M. A.; Jimenez Dominguez, M.; Perucha Ortega, M.; Herrador Cordoba, M.

2011-07-01

The dose fractionation than the standard head and neck cancer in some situations involve a significant increase of local control and overall survival. There is clinical evidence of these results in case of hyperfractionated treatments, although the choice of optimal fractionation generally is not obtained from the results of any model, in this study has provided the tumor control probability (TCP) for various subdivisions modified (hypo fractionated and hyperfractionated) using Monte Carlo simulation techniques.

Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

International Nuclear Information System (INIS)

Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

2011-01-01

Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

International Nuclear Information System (INIS)

Graf, Reinhold; Hildebrandt, Bert; Tilly, Wolfgang; Riess, Hanno; Felix, Roland; Budach, Volker; Wust, Peter

2006-01-01

The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987–1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups. Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

Directory of Open Access Journals (Sweden)

Felix Roland

2006-02-01

Full Text Available Abstract Background The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. Methods Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck cancer by two different protocols. The sequential protocol (SEQ; 1987–1992 started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i. of folinic acid [FA] and 5-fluorouracil [5-FU], followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993 combined two courses of FA/5-FU c.i. plus mitomycin (MMC concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. Results Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.. Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00, response rates (67 vs. 90 % for primary, p = 0.02, and local control (LC; 17.6% vs. 41%, p = 0.03, were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08 and overall (14.7% vs. 23.7%, p = 0.11 survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%. Late toxicity was similar in both groups. Conclusion Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival.

Concurrent hyperfractionated accelerated radiotherapy with 5-FU and once weekly cisplatin in locally advanced head and neck cancer. The 10-year results of a prospective phase II trial

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Budach, V.; Boehmer, D.; Badakhshi, H.; Jahn, U.; Stromberger, C. [Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Department for Radiooncology, Clinic for Radiooncology, Berlin (Germany); Becker, E.T. [Charite Universitaetsmedizin, Department of Otorhinolaryngology, Berlin (Germany); Wernecke, K.D. [Sostana Statistics GmbH, Charite Universitaetsmedizin Berlin, Berlin (Germany)

2014-03-15

In this study, the acute toxicity and long-term outcome of a hyperfractionated accelerated chemoradiation regimen with cisplatin/5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinomas of head and neck were evaluated. From 2000-2002, 38 patients with stage III (5.3 %) and stage IV (94.7 %) head and neck cancer were enrolled in a phase II study. Patients received hyperfractionated-accelerated radiotherapy with 72 Gy in 15 fractions of 2 Gy followed by 1.4 Gy twice daily with concurrent, continuous infusion 5-FU of 600 mg/m{sup 2} on days 1-5 and 6 cycles of weekly cisplatin (30 mg/m{sup 2}). Acute toxicities (CTCAEv2.0), locoregional control (LRC), metastases-free (MFS), and overall survival (OS) were analyzed and exploratively compared with the ARO 95-06 trial. Median follow-up was 11.4 years (95 % CI 8.6-14.2) and mean dose 71.6 Gy. Of the patients, 82 % had 6 (n = 15) or 5 (n = 16) cycles of cisplatin, 5 and 2 patients received 4 and 3 cycles, respectively. Grade 3 anemia, leukopenia, and thrombocytopenia were observed in 15.8, 15.8, and 2.6 %, respectively. Grade 3 mucositis in 50 %, grade 3 and 4 dysphagia in 55 and 13 %. The 2-, 5-, and 10-year LRC was 65, 53.6, and 48.2 %, the MFS was 77.5, 66.7, and 57.2 % and the OS 59.6, 29.2, and 15 %, respectively. Chemoradiation with 5-FU and cisplatin seems feasible and superior in terms of LRC and OS to the ARO 95-06C-HART arm at 2 years. However, this did not persist at the 5- and 10-year follow-ups. (orig.) [German] Untersuchung der Akuttoxizitaet und des Langzeitueberlebens einer hyperfraktioniert-akzelerierten simultanen Radiochemotherapie mit Cisplatin/5-Fluorouracil (5-FU) bei Patienten mit lokal fortgeschrittenen Kopf-Hals-Tumoren. Von 2000 bis 2002 wurden 38 Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region im Stadium III (5,3 %) und IV (94,7 %) eingeschlossen. Es erfolgte eine simultane hyperfraktionierte akzelerierte Radiochemotherapie mit 72 Gy in 15 Fraktionen a 2 Gy

Traumatic Brain Injury: A Guide for Caregivers of Service Members and Veterans: Becoming a Family Caregiver for a Service Member/Veteran with TBI. Module 3

Science.gov (United States)

2010-04-01

in fiber from whole grains, fruits, and vegetables, and includes lean cuts of meat , poultry , eggs and other protein sources. A healthy diet also...5 - Helping Your Children Cope with TBI32 “When Tim was starting to read and do word finding, those games were fun activities for the kids to do with...like playing board games , taking a walk or run, or baking cookies. Find activities where everyone in the family can play a role. • In addition to

Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.

Science.gov (United States)

Wagner, Amy K; Brayer, Samuel W; Hurwitz, Max; Niyonkuru, Christian; Zou, Huichao; Failla, Michelle; Arenth, Patricia; Manole, Mioara D; Skidmore, Elizabeth; Thiels, Edda

2013-11-01

Explicit and implicit learning and memory networks exist where each network can facilitate or inhibit cognition. Clinical evidence suggests that implicit networks are relatively preserved after traumatic brain injury (TBI). Non-spatial pre-training (NSPT) in the Morris Water Maze (MWM) provides the necessary behavioral components to complete the task, while limiting the formation of spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit learning and memory system deficits in the controlled cortical impact (CCI) model of TBI. 76 adult male Sprague-Dawley rats were divided: CCI vs. sham surgery, NSPT vs. No-NSPT, and cued vs. non-cued groups. NSPT occurred for 4d prior to surgery (dynamic hidden platform location, extra-maze cues covered, static pool entry point). Acquisition (d14-18), Probe/Visible Platform (d19), and Reversal (d20-21) trials were conducted with or without extra-maze cues. Novel time allocation and search strategy selection metrics were utilized. Results indicated implicit and explicit learning/memory networks are distinguishable in the MWM. In the cued condition, NSPT reduced thigmotaxis, improved place learning, and largely eliminated the apparent injury-induced deficits typically observed between untrained CCI and sham rats. However, among NSPT groups, incorporation of cues into search strategy selection for CCI rats was relatively impaired compared to shams. Non-cued condition performance showed sham/NSPT and CCI/NSPT rats perform similarly, suggesting implicit memory networks are largely intact 2weeks after CCI. Place learning differences between CCI/NSPT and sham/NSPT rats more accurately reflect spatial deficits in our CCI model compared to untrained controls. These data suggest NSPT as a clinically relevant construct for evaluating potential neurorestorative and neuroprotective therapies. These findings also support development of non-spatial cognitive training paradigms for evaluating rehabilitation relevant

A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

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Tada, Takuhito, E-mail: tada@msic.med.osaka-cu.ac.jp [Department of Radiology, Osaka City University Graduate School of Medicine, Osaka (Japan); Department of Radiology, Izumi Municipal Hospital, Izumi (Japan); Chiba, Yasutaka [Department of Environmental Medicine and Behavioural Science, Kinki University Faculty of Medicine, Osaka-sayama (Japan); Tsujino, Kayoko [Department of Radiation Oncology, Hyogo Cancer Center, Akashi (Japan); Fukuda, Haruyuki [Department of Radiology, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino (Japan); Nishimura, Yasumasa [Department of Radiation Oncology, Kinki University Faculty of Medicine, Osaka-sayama (Japan); Kokubo, Masaki [Division of Radiation Oncology, Institute of Biomedical Research and Innovation, Kobe (Japan); Negoro, Shunichi [Department of Medical Oncology, Hyogo Cancer Center, Akashi (Japan); Kudoh, Shinzoh [Department of Respiratory Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Fukuoka, Masahiro [Department of Medical Oncology, Izumi Municipal Hospital, Izumi (Japan); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-sayama (Japan); Nakanishi, Yoichi [Research Institute for Disease of the Chest, Graduate School of Medical Science, Kyusyu University, Fukuoka (Japan)

2012-05-01

Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.

A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

International Nuclear Information System (INIS)

Tada, Takuhito; Chiba, Yasutaka; Tsujino, Kayoko; Fukuda, Haruyuki; Nishimura, Yasumasa; Kokubo, Masaki; Negoro, Shunichi; Kudoh, Shinzoh; Fukuoka, Masahiro; Nakagawa, Kazuhiko; Nakanishi, Yoichi

2012-01-01

Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non–small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non–small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m 2 ) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m 2 ). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade ≥4 esophagitis and neutropenic fever and Grade ≥3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.

Effect of Black Grape Juice against Heart Damage from Acute Gamma TBI in Rats

Directory of Open Access Journals (Sweden)

Edson Ramos de Andrade

2013-09-01

Full Text Available The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ on lipid peroxidation considering Total Body Irradiation (TBI in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH levels were evaluated as a marker for heart damage from acute radiation syndrome (ARS. Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH on serum and lipid peroxidation on heart tissue were evaluated. High concentration of metabolites from lipid peroxidation in heart, and high LDH level on serum were found only in gamma-irradiated group given placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD analysis, which showed resveratrol as the major constituent. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier.

Music therapy for early cognitive rehabilitation post-childhood TBI: an intrinsic mixed methods case study.

Science.gov (United States)

Bower, Janeen; Catroppa, Cathy; Grocke, Denise; Shoemark, Helen

2014-10-01

The primary aim of this case study was to explore the behavioural changes of a paediatric patient in post-traumatic amnesia (PTA) during a music therapy session. A secondary objective was to measure the effect of the music therapy intervention on agitation. Video data from pre, during and post-music therapy sessions were collected and analysed using video micro-analysis and the Agitated Behaviour Scale. The participant displayed four discrete categories of behaviours: Neutral, Acceptance, Recruitment and Rejection. Further analysis revealed brief but consistent and repeated periods of awareness and responsiveness to the live singing of familiar songs, which were classified as Islands of Awareness. Song offered an Environment of Potential to maximise these periods of emerging consciousness. The quantitative data analysis yielded inconclusive results in determining if music therapy was effective in reducing agitation during and immediately post the music therapy sessions. The process of micro-analysis illuminated four discrete participant behaviours not apparent in the immediate clinical setting. The results of this case suggest that the use of familiar song as a music therapy intervention may harness early patient responsiveness to foster cognitive rehabilitation in the early acute phase post-TBI.

Application of ERPs neuromarkers for assessment and treatment of a patient with chronic crossed aphasia after severe TBI and long-term coma - Case Report.

Science.gov (United States)

Chantsoulis, Marzena; Półrola, Paweł; Góral-Półrola, Jolanta; Hajdukiewicz, Anna; Supiński, Jan; Kropotov, Juri D; Pachalska, Maria

2017-03-31

 Objective. The study aimed to evaluate the application of ERPs neuromarkers for the assessment and treatment of a patient with chronic crossed aphasia after severe TBI and a long-term coma. An ambidextrous female patient, aged 29, suffered from posttraumatic chronic crossed aphasia, severe TBI and a prolonged coma after a car accident. The patient took part in two differentiated rehabilitation programmes of neurotherapy included 20 sessions of relative beta training and 20 sessions of rTMS; both programmes were combined with behavioural training. The patient was tested 3 times: before the experiment, after completion of programme A, and after completion of programme B. In the 1st recording, the neuromarker of aphasia was found - an excess of the P2 wave over the left temporal area. There was a cognitive control deficit - an excess of omission errors and an increase of RT variability - all indexes of sporadic ADHD. In the 2nd recording, slight improvements in cognitive control, and language functions were found. In the 3rd recording, after the rTMS sessions most of her cognitive dysfunctions had been resolved, including language functions. It should be stressed that the activation (especially the increase in the ERP potential of the right side over the frontal lobe) was found. The neuromarker of aphasia did not change, only the location had slightly moved frontally. The application of ERP neuromarkers assists in the diagnosis, treatment, and academic success of an ambidextrous patient with chronic posttraumatic aphasia and sporadic ADHD. ERPs can be used to assess the functional brain changes induced by neurotherapeutical programmes.

Care management of the agitation or aggressiveness crisis in patients with TBI. Systematic review of the literature and practice recommendations.

Science.gov (United States)

Luauté, Jacques; Plantier, David; Wiart, Laurent; Tell, Laurence

2016-02-01

The agitation crisis in the awakening phase after traumatic brain injury (TBI) is one of the most difficult behavioral disorders to alleviate. Current treatment options are heterogeneous and may involve excessive sedation. Practice guidelines are required by professionals in charge of TBI patients. Few reviews were published but those are old and based on expert opinions. The purpose of this work is to propose evidence-based guidelines to treat the agitation crisis. The elaboration of these guidelines followed the procedure validated by the French health authority for good practice recommendations, close to the Prisma statement. Guidelines were elaborated on the basis of a systematic and critical review of the literature. Twenty-eight articles concerning 376 patients were analyzed. Recommendations are: when faced with an agitation crisis, the management strategy implies to search for an underlying factor that should be treated such as pain, acute sepsis, and drug adverse effect (expert opinion). Physical restraints should be discarded when possible (expert opinion). Neuroleptic agent with a marketing authorization can be used in order to obtain a quick sedation so as to protect the patient from himself, closed ones or the healthcare team but the duration should be as short as possible (expert opinion). The efficacy of beta-blockers and antiepileptics with mood regulation effects like carbamazepine and valproate yield the most compelling evidence and should be preferably used when a background regimen is envisioned (grade B for beta-blocker and C for antiepileptics). Neuroleptics, antidepressants, benzodiazepines, buspirone may be prescribed but are considered second-line treatments (expert opinion). This study provides a strategy for treating the agitation crisis based on scientific data and expert opinion. The level of evidence remains low and published data are often old. New studies are essential to validate results from previous studies and test new drugs and

A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brain stem glioma

International Nuclear Information System (INIS)

Dutton, S.C.; Pomeroy, S.L.; Billett, A.L.; Barnes, P.; Kuhlman, C.; Riese, N.E.; Goumnerova, L.; Scott, R.M.; Coleman, C.N.; Tarbell, N.J.

1997-01-01

Objective: Prospective phase I study to evaluate the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brain stem glioma. Materials and Methods: Eighteen patients with brain stem glioma were treated with etanidazole and HRT from 1990-1996. Eligibility required MRI confirmation of diffuse glioma of medulla, pons or mesencephalon, and signs/symptoms of cranial nerve deficit, ataxia or long tract signs of ≤ 6 months duration. Cervico-medullary tumors were excluded. Patients (median age 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2 cm margin with parallel opposed 6-15 MV photons. The total dose was 66 Gy for the first 3 patients, followed by 63 Gy over 4.2 weeks (1.5 Gy BID with 6 hours between fractions) for the subsequent 15 patients. Etanidazole was administered as a rapid IV infusion 30 minutes prior to the morning fraction of HRT at doses of 1.8 gm/m2 x 17 doses (30.6 gm/m2) at step 1 to a maximum of 2.4 gm/m2 x 21 doses (50.4 gm/m2) at step 8. Dose escalation was planned with 3 patients at each of the 8 levels. Results: Three patients were treated at each dose level except level 2, on which only one patient was treated. The highest dose level achieved was step 7 which delivered a total etanidazole dose of 46.2 gm/m2. Two patients were treated at this level, and both patients experienced grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 gm/m2 without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 24 cases of grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 skin erythema, 1 weight loss, 3 other), eleven cases of grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, 1 arthalgia, 1 urinary retention, 1 hematologic), and four grade b 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral

Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and -IV carcinomas of the head and neck. Long-term results including functional outcome

Energy Technology Data Exchange (ETDEWEB)

Huguenin, P.; Glanzmann, C.; Taussky, D.; Luetolf, U.M. [Univ. Hospital Zurich (Switzerland). Radiation Oncology Dept.; Schmid, S.; Moe, K. [Univ. Hospital Zurich (Switzerland). Dept. of Head and Neck Surgery

1998-08-01

Purpose: To assess the survival rate, the probability of local control, the patterns of relapse and late sequelae including self-reported quality of life in patients treated with hyperfractionated radiotherapy (RT) and simultaneous CDDP chemotherapy for stage-III to stage-IV carcinomas of the head and neck. Methods: From 1988 to 1994, 64 patients (median age 55.5 years) with carcinomas of different subsites, excluding the nasopharynx, were treated in a pilot study with 1.2 Gy bid (6 h interval; total dose 74.4 Gy) and simultaneous CDDP (20 mg/m{sup 2} daily, 5 days in week 1 and 5) and followed at regular intervals. Overall survival and local control, as well as the rates of late toxicity, were estimated using the actuarial method. Median follow-up was 3.3 years for all and 5.2 years for surviving patients. To assess the quality of life, the EORTC QLQ-C 30 questionnaire and the H and N35 module questionnaire were sent to the patients surviving with no evidence of disease or second primary tumors; they were answered by 15/23 (67%). Results: Overall survival was 37% at 5 years, whereas disease-specific survival was 59%. Twenty-three patients died from uncontrolled head and neck cancer. Second primary tumors were observed in 13 patients, most frequently in the lung. Local control without salvage surgery was 74% at 5 years for all subsites and stages, and loco-regional disease-free survival was 72%. Eleven patients developed distant metastases, which was the only site of failure in 6 cases. Salvage surgery was successful in 2 cases. The actuarial estimates of {>=}grade-3 late toxicity was 4% for the mandibular bone and 23% for dysphagia, and 50% of the patients experienced a permanent xerostomy. Self-reported global quality of life in surviving patients was good (mean 68 points on a scale 0 to 100); consequences of impaired salivary function had most impact on nutritional and social aspects. Conclusions: Hyperfractionated RT with concomitant CDDP is well tolerated and

Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation study

Energy Technology Data Exchange (ETDEWEB)

Cvek, J.; Skacelikova, E.; Otahal, B.; Halamka, M.; Feltl, D. [University Hospital Ostrava (Czech Republic). Dept. of Oncology; Kubes, J. [University Hospital Bulovka, Prague (Czech Republic). Dept. of Radiation Oncology; Kominek, P. [University Hospital Ostrava (Czech Republic). Dept. of Otolaryngology

2012-08-15

Background and purpose: The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. Methods and materials: A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV{sub tumor}) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV{sub uninvolved}) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. Results: Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was {<=} 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. Conclusion: HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94)

International Nuclear Information System (INIS)

Ghadjar, Pirus; Simcock, Mathew; Zimmermann, Frank; Betz, Michael; Bodis, Stephan; Bernier, Jacques; Studer, Gabriela; Aebersold, Daniel M.

2012-01-01

Background and purpose: This secondary analysis was performed to identify predictive factors for severe late radiotherapy (RT)-related toxicity after treatment with hyperfractionated RT +/− concomitant cisplatin in locally advanced head and neck cancer. Materials and methods: Patients were retrospectively analyzed from the previously reported randomized phase III trial: SAKK 10/94. Severe late RT-related toxicity was defined as late RTOG ⩾ grade 3 toxicity starting 3 months after end of RT and/or potential treatment-related death within 3 years of randomization. Results: Two hundred and thirteen randomized patients were analyzed; 84 (39%) experienced severe late RT-related toxicity. With median follow-up of 9.7 years (range, 0.4–15.4 years), median time to severe late RT-related toxicity was 9.6 years. In the univariate Cox proportional hazards model the following variables were associated with severe late RT-related toxicity: advanced N-classification (p < 0.001); technically unresectable disease (p = 0.04); weight loss ratio (p = 0.003); supportive measures (p = 0.009) and severe acute dysphagia (p = 0.001). In the subsequent multivariate analysis all variables except use of supportive measures remained statistically significant. Conclusions: Chemotherapy did not appear to affect severe late RT-related toxicity, but advanced N-classification, technically unresectable disease, weight loss ratio, and severe acute dysphagia were independent predictive factors for severe late RT-related toxicity.

TH-EF-BRB-06: Implementation of a Modulated-Arc Total Body Irradiation (TBI) Technique Using the RayStation Treatment Planning System

Energy Technology Data Exchange (ETDEWEB)

Phillips, J; Cheung, J; Held, M; Han, D; Morin, O [UCSF, San Francisco, CA (United States)

2016-06-15

Purpose: To develop a clinical workflow for delivering a modulated-arc total body irradiation (TBI) with RayStation scripting. This technique uses arc fields with the patient lying at floor level on a padded table and is validated through measurements taken on a custom-made TBI phantom. Methods: Treatment planning was performed for a retrospective cohort of eight patients with a diverse range of heights and body types. Each was replanned using an open-field dual arc method, with the patient in supine and prone positions on the floor of the vault. All plans were optimized using Raystation Planning 4.7.2.5 (RaySearch Laboratories, Stockholm, Sweden), with 200 cGy prescribed to the 95% of the body contour − 5mm. This results in an open-field beam that sweeps craniocaudally across the length of the patient. The technique is validated with measurements at 10 cm intervals in a custom-milled, 5 cm thick acrylic phantom. A centrally located CC13 ion chamber and a Mobile MOSFET (Best Medical Canada, Ottawa, ON) detector array were used to measure dose. Supine and prone arcs for each patient were consecutively delivered, and the aggregate dose at each point was compared to the planned dose calculated in the phantom. Results: The ion chamber measurements differed from the planned dose by an average of .5%, with a standard deviation of 2.1%. All measured data for the MOSFETS were within 10% of the corresponding planned dose except for two outlying points. The standard deviation of dose differences across the entire cohort was 4.0%. Most significant discrepancies occurred either in inhomogeneous regions with large gradients, or at inferior points where beam angle was steepest. Conclusion: We have confirmed that the planned dose is well matched to our measurements within 10% for this method of planning and delivery. We are currently incorporating this technique into our clinical workflow. This work is supported by RaySearch.

Clinical utility of the mBIAS and NSI validity-10 to detect symptom over-reporting following mild TBI: A multicenter investigation with military service members.

Science.gov (United States)

Armistead-Jehle, Patrick; Cooper, Douglas B; Grills, Chad E; Cole, Wesley R; Lippa, Sara M; Stegman, Robert L; Lange, Rael T

2018-04-01

Self-report measures are commonly relied upon in military healthcare environments to assess service members following a mild traumatic brain injury (mTBI). However, such instruments are susceptible to over-reporting and rarely include validity scales. This study evaluated the utility of the mild Brain Injury Atypical Symptoms scale (mBIAS) and the Neurobehavioral Symptom Inventory Validity-10 scale to detect symptom over-reporting. A total of 359 service members with a reported history of mTBI were separated into two symptom reporting groups based on MMPI-2-RF validity scales (i.e., non-over-reporting versus symptom over-reporting). The clinical utility of the mBIAS and Validity-10 as diagnostic indicators and screens of symptom over-reporting were evaluated by calculating sensitivity, specificity, positive test rate, positive predictive power (PPP), and negative predictive power (NPP) values. An mBIAS cut score of ≥10 was optimal as a diagnostic indicator, which resulted in high specificity and PPP; however, sensitivity was low. The utility of the mBIAS as a screening instrument was limited. A Validity-10 cut score of ≥33 was optimal as a diagnostic indicator. This resulted in very high specificity and PPP, but low sensitivity. A Validity-10 cut score of ≥7 was considered optimal as a screener, which resulted in moderate sensitivity, specificity, NPP, but relatively low PPP. Owing to low sensitivity, the current data suggests that both the mBIAS and Validity-10 are insufficient as stand-alone measures of symptom over-reporting. However, Validity-10 scores above the identified cut-off of ≥7should be taken as an indication that further evaluation to rule out symptom over-reporting is necessary.

Identifizierung Apoptose-induzierender Alkaloide der Pflanze Chelidonium Majus und des Präparates Ukrain in einem Lymphom-Modell

OpenAIRE

Habermehl, Daniel Frédéric

2009-01-01

Für das Krebsmedikament Ukrain, von Herstellerseite als semisynthetisches Derivat aus dem Schöllkraut-Alkaloid Chelidonin und dem Alkylanz Thiotepa beschrieben, wurde eine selektive zytotoxische Wirkung auf humane Tumor-Zelllinien in vitro beschrieben. Auch einige klinische Studien berichten über eine positive Wirkung des Präparates in der onkologischen Therapie. Allerdings werden Wirksamkeit und Zusammensetzung des Präparates kontrovers diskutiert. Ziel der vorliegenden Arbeit war die An...

Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04

International Nuclear Information System (INIS)

Regine, W.F.; Scott, C.; Murray, K.; Curran, W.

2001-01-01

Purpose: To evaluate neurocognitive outcome as measured by the Mini-Mental Status Examination (MMSE) among patients with unresectable brain metastases randomly assigned to accelerated fractionation (AF) vs. accelerated hyperfractionated (AH) whole-brain radiation therapy (WBRT). Methods and Materials: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients with unresectable brain metastases to a Phase III comparison of AH (1.6 Gy b.i.d. to 54.4 Gy) vs. AF (3 Gy q.d. to 30 Gy). All had a KPS of ≥ 70 and a neurologic function status of 0-2. Three hundred fifty-nine patients had MMSEs performed and were eligible for this analysis. Changes in the MMSE were analyzed according to criteria previously defined in the literature. Results: The median survival was 4.5 months for both arms. The average change in MMSE at 2 and 3 months was a drop of 1.4 and 1.1, respectively, in the AF arm as compared to a drop of 0.7 and 1.3, respectively, in the AH arm (p=NS). Overall, 91 patients at 2 months and 23 patients at 3 months had both follow-up MMSE and computed tomography/magnetic resonance imaging documentation of the status of their brain metastases. When an analysis was performed taking into account control of brain metastases, a significant effect on MMSE was observed with time and associated proportional increase in uncontrolled brain metastases. At 2 months, the average change in MMSE score was a drop of 0.6 for those whose brain metastases were radiologically controlled as compared to a drop of 1.9 for those with uncontrolled brain metastases (p=0.47). At 3 months, the average change in MMSE score was a drop of 0.5 for those whose brain metastases were radiologically controlled as compared to a drop of 6.3 for those with uncontrolled brain metastases (p=0.02). Conclusion: Use of AH as compared to AF-WBRT was not associated with a significant difference in neurocognitive function as measured by MMSE in this patient population with unresectable brain metastases and

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko; Yoshida, Ken; Yoshioka, Yasuo; Shimamoto, Shigetoshi; Tanaka, Eiichi; Yamazaki, Hideya; Shimizutani, Kimishige; Teshima, Teruki; Furukawa, Souhei

2001-01-01

Purpose: Early mobile tongue cancer can be controlled with interstitial radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment results of low-dose-rate (Ld) ISRT and high-dose-rate (HDR) ISRT for early mobile tongue cancer. Methods and Materials: From April 1992 through October 1996, 59 patients with cancer of the early mobile tongue were registered in this Phase III study. Eight patients were excluded from the evaluation because of violations of the requirements for this study. Of 51 eligible patients, 26 patients were treated with LDR-ISRT (70 Gy/4-9 days) and 25 patients with HDR-ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time interval between 2 fractions was more than 6 h. Results: Five-year local control rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis occurred in 6 patients in each group. Five-year nodal control rates of the LDR and HDR groups were 77% and 76%, respectively. Conclusion: Hyperfractionated HDR-ISRT for early mobile tongue cancer has the same local control compared with continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for continuous LDR-ISRT

Radio-chemotherapy in advanced tumors of the oral cavity, oro- and hypopharynx

International Nuclear Information System (INIS)

Schmitt, G.; Schnabel, T.

1992-01-01

Among combined radio-chemotherapy regimens of advanced head and neck tumors four modalities can be discriminated: 1. Induction chemotherapy, 2. simultaneous radio-chemotherapy, 3. adjuvant chemotherapy, 4. accelerated-hyperfractionated radiotherapy and chemotherapy. The results of the presently available randomized trials are as follows: 1. Induction chemotherapy has no influence on long-term recurrence-free survival. 2. With respect to simultaneous radio-chemotherapy, recurrence-free survival has been unproved with 5-FU and Mitomycin C. 3. There is evidence that adjuvant cis-platin therapy improves recurrence-free survival. 4. No results are available to date using hyperfractionated accelerated radiotherapy regimens in combination with chemotherapy. (orig.) [de

Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

Energy Technology Data Exchange (ETDEWEB)

Liu, Yu-Ming; Shiau, Cheng-Ying; Wong, Tai-Tong; Wang, Ling-Wei; Wu, Le-Jung; Chi, Kwan-Hwa; Chen, Kuang Y.; Yen, Sang-Hue [Veterans General Hospital-Taipei, Taipei, Taiwan (China)

1998-08-01

A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n=7), radiotherapy alone (n=10) and radiotherapy with adjuvant chemotherapy (n=5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P=0.017 and 0.036). A trend of better outcome with radiation dose >6600 cGy and the hyperfractionation scheme was also noted in our study (P=0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P=0.0355). Survival was not significantly affected by age, gender or method of diagnosis. Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival. (author)

Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

International Nuclear Information System (INIS)

Liu, Yu-Ming; Shiau, Cheng-Ying; Wong, Tai-Tong; Wang, Ling-Wei; Wu, Le-Jung; Chi, Kwan-Hwa; Chen, Kuang Y.; Yen, Sang-Hue

1998-01-01

A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n=7), radiotherapy alone (n=10) and radiotherapy with adjuvant chemotherapy (n=5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P=0.017 and 0.036). A trend of better outcome with radiation dose >6600 cGy and the hyperfractionation scheme was also noted in our study (P=0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P=0.0355). Survival was not significantly affected by age, gender or method of diagnosis. Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival. (author)

Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications

International Nuclear Information System (INIS)

Teo, Peter Man Lung; Leung, Sing Fai; Chan, Anthony Tak Cheung; Leung, Thomas Wai Tong; Choi, Peter Ho Keung; Kwan, Wing Hong; Lee, Wai Yee; Chau, Ricky Ming Chun; Yu, Peter Kau Wing; Johnson, Philip James

2000-01-01

Purpose: The aim of the present study was to compare the survival, local control and complications of conventional/accelerated-hyperfractionated radiotherapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcinoma (NPC). Methods and Materials: From February 1993 to October 1995, 159 patients with newly diagnosed nonmetastatic (M0) NPC with N0 or 4 cm or less N1 disease (Ho's N-stage classification, 1978) were randomized to receive either conventional radiotherapy (Arm I, n = 82) or conventional/accelerated-hyperfractionated radiotherapy (Arm II, n = 77). Stratification was according to the T stage. The biologic effective dose (10 Grays) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. Results: With comparable distribution among the T stages between the two arms, the free from local failure rate at 5 years after radiotherapy was not significantly different between the two arms (85.3%; 95% confidence interval, 77.2-93.4% for Arm I; and 88.9%; 95% confidence interval, 81.7-96.2% for Arm II). The two arms were also comparable in overall survival, relapse-free survival, and rates of distant metastasis and regional relapse. Conventional/accelerated-hyperfractionated radiotherapy was associated with significantly increased radiation-induced damage to the central nervous system (including temporal lobe, cranial nerves, optic nerve/chiasma, and brainstem/spinal cord) in Arm II. Although insignificant, radiation-induced cranial nerve(s) palsy (typically involving VIII-XII), trismus, neck soft tissue fibrosis, and hypopituiturism and hypothyroidism occurred more often in Arm II. In addition, the complications occurred at significantly shorter intervals after radiotherapy in Arm II. Conclusion: Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Ho's technique, resulted in increased radiation damage to the central

Role of radiotherapy fractionation in head and neck cancers (MARCH)

DEFF Research Database (Denmark)

Lacas, Benjamin; Bourhis, Jean; Overgaard, Jens

2017-01-01

BACKGROUND: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing...... the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. METHODS......: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation...

A multi-institutional phase II study of hyperfractionated accelerated radiation therapy for unresectable non-small cell lung cancer: initial report of ECOG 4593

International Nuclear Information System (INIS)

Tannehill, Scott P.; Froseth, Carrie; Wagner, Henry; Petereit, Dan P.; Mehta, Minesh P.

1996-01-01

Purpose: To assess the feasibility, acute toxicity, response and survival in a trial of hyperfractionated accelerated radiation therapy for unresectable locally advanced non-small cell lung cancer (NSCLC) using a t.i.d. regimen 5 days a week in an 8 hour schedule. Materials and Methods: Thirty patients (pts) from 6 institutions were enrolled in this pilot trial. Pt characteristics: 24 male, 6 female; median age 67 yrs (range 47-84); ECOG PS 0 in 22 pts, 1 in 8 pts; weight loss >5% in 7 pts. Stage was II (inoperable) in 1 pt, IIIA in 12 pts, and IIIB in 17 pts. Radiation therapy (total 57.6 Gy/36 fx) encompassing gross disease and draining lymphatics to 36 Gy (1.5 Gy b.i.d., 8 hours apart) with daily off-cord concomitant boost to 21.6 Gy (1.8 Gy 4 hours after first fraction) was given over 12 treatment days (15 elapsed days). Results: (28(30)) (93%) pts completed radiation therapy on schedule without toxicity-related treatment interruptions. Two pts did not complete radiation therapy; 1 due to in-field progression and 1 due to fatal acute gastric bleed unrelated to therapy. Two additional pts died in the first 6 weeks: 1 due to a presumed acute cardiovascular event and another due to complications of pre-existing cardiovascular disease. The major treatment-related toxicities were esophagitis in 6 pts (18%: 5 Grade 3 and 1 Grade 4) scored using a study specific esophagitis grading tool and 2 grade 3 dermatitis, in a total of 6 pts. Only 1 pt (3%) required hospitalization for IV hydration (Grade 4 esophagitis). Median weight loss at 6 weeks was 3 kg. Response data are pending in 2 pts and unavailable in 2 due to early death. Of the remaining 26 pts, local response analysis showed CR in 4, PR in 14, stable in 7 and progressive disease in 1 for an overall response rate of (18(26)) (69%). With a median potential follow-up of 13 months, the median survival has not yet been reached. The 1-yr actuarial survival is 63%. Exclusion of the 3 pts experiencing early death (in

Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with a corresponding signature in xenografts

DEFF Research Database (Denmark)

Monks, A.; Hose, C.D.; Pezzoli, P.

2009-01-01

gene modulation were significantly correlated. A belinostat-gene profile was specific for HDACi in three cell lines when compared with equipotent concentrations of four mechanistically different chemotherapeutic agents: 5-fluorouracil, cisplatin, paclitaxel, and thiotepa. Belinostat- and trichostatin...... in a drug-sensitive tumor than a more resistant model. We have demonstrated a gene signature that is selectively regulated by HDACi when compared with other clinical agents allowing us to distinguish HDACi responses from those related to other mechanisms Udgivelsesdato: 2009/9...

Orbital rhabdomyosarcoma of the child: the role of PDR brachytherapy in eye preservation

International Nuclear Information System (INIS)

Kovacs, G.; Rochels, R.; Mehdorn, H.M.; Werner, J.; Wilhelm, R.; Kohr, P.; Kimmig, B. N.

1996-01-01

Material and Methods: There were four children (8-7-5 years and(15(12)) months old) with recurrent/primary embryonal rhabdomyosarcoma treated with curative intention by peroperative PDR boost brachytherapy in combination with radio-chemotherapy and/or surgery. PDR brachytherapy according to the Kiel protocol: daily five pulses, two hours each, with 1 Gy on the reference isodose which is usually 2-3 mm close to the applicator surface. CT simulation based conformal treatment planning was carried out in each case. The implant was done intraoperatively using the free-hand plastic tube method, after a macroscopically complete excision of the tumor. Due to treatment planning individual target volume, eye with N, opticus and bone structures, as well as the applicators and other regions of interest were visualized. Manual volume optimisation was practiced and natural volumen-dose histograms were analysed in 'classic' graphic mode as well as in a special colour coded three-dimensional visualization in cine mode on the screen. One child received, three months before the recurrence was operated, 50 Gy hyperfractionated external beam radiation (2 Gy fractions) and was irradiated with 20 Gy brachytherapy in four days. The second patient received ten days after 20 Gy brachytherapy 32 Gy hyperfractionated external beam radiation. The third child (external beam treatment outside of our clinic), received conventional fractionated irradiation with 1.6 Gy fraction dose instead of a prescribed hyperfractionated external beam therapy and her brachytherapy dose was 25 Gy. At the (15(12)) months old child with primary embryonal rhabdomyosarcoma we applied 20 Gy brachytherapy and 24 Gy hyperfractionated external beam irradiation. All patients received multidrug chemotherapy according to the German Study Protocol (CWS-91). Results: Follow-up is 34, 28, 22, and 6 months for recurrent embryonal rhabdomyosarcoma patients (stand February 96). We observed at 9 months one rhabdomyosarcoma

Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy - a multicenter randomized trial

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Olmi, Patrizia; Crispino, Sergio; Fallai, Carlo; Torri, Valter; Rossi, Francesca; Bolner, Andrea; Amichetti, Maurizio; Signor, Marco; Taino, Raffaella; Squadrelli, Massimo; Colombo, Alessandro; Ardizzoia, Alessandro; Ponticelli, Pietro; Franchin, Giovanni; Minatel, Emilio; Gobitti, Carlo; Atzeni, Guido; Gava, Alessandro; Flann, Monica; Marsoni, Silvia

2003-01-01

Purpose: To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx. Methods and Materials: Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m 2 , Days 1-4; 5-FU 1,000 mg/m 2 i.v. over 96 h, Days 1-4, recycling every 28 days (at 1st, 5th, and 9th week). Results: No statistically significant difference was detected in overall survival (p=0.129): 40% Arm A vs. 37% Arm B vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p=0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (p = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and 20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from 1 case of fatal nephrotoxicity, only hematologic G3+ (Grade 3

Predictive value of the flow cytometric PCNA - assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy

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Wenz, F; Lohr, F; Rudat, V; Dietz, A; Flentje, M; Wannenmacher, M

1995-07-01

Purpose/Objective: Proliferation of surviving tumor cells during fractionated radiotherapy may limit tumor control, especially in rapidly proliferating tumors. It has been widely accepted, that this may play a major role in head and neck tumors. Several methods for the assessment of tumor proliferation have been developed, however, most of them are either laborious, invasive or potentially toxic. Today, the gold standard is the flow cytometric BrdUrd assay. We present a flow cytometric method for detection of PCNA, which is an intranuclear proliferation associated protein, in solid human head and neck tumors and how these data correlate with outcome. Materials and Methods: Pretherapeutic biopsies of 20 inoperable patients with squamous cell carcinoma of the head and neck (T3-4N2M0) were examined. The tissue was disaggregated with pepsin/HCl, antibody staining was performed using the clone PC10. Biparametric flow cytometry was performed after a FITC conjugated secondary antibody and propidiumjodine staining was applied. The PCNA-index (i.e. percentage PCNA-positive cells), the DNA-index and the S-phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of combined accelerated-hyperfractionated radiochemotherapy (66 Gy in 5 wks, concomittant boost of 1.6 Gy/d in wks 4+5, Carboplatin in wks 1+5). The median follow-up time was 14 mths (5 - 28), the clinical partners (V.R., A.D.) were 'blinded' towards the PCNA-values. Results: 13 patients suffered from disease progession and 11 died. The actuarial median survival and disease free survival (DFS) were 14.4 and 10.7 mths, respectively. The PCNA-values ranged from 3.2 to 70% (median 9%), there were 7 aneuploid and 13 euploid tumors. SFP in the euploid tumors ranged from 4 to 14.5% (median 10.5%). Neither SFP nor ploidy had a significant influence on the outcome. The patients were divided according to their PCNA-value in higher (n=10) and lower (n=10) than the median. The survival and DFS were 13

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

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Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Melotek, James M. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Blair, Elizabeth A. [Department of Otolaryngology, University of Chicago, Chicago, Illinois (United States); Stenson, Kerstin M. [Department of Otolaryngology, Rush University, Chicago, Illinois (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Witt, Mary Ellyn [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Kocherginsky, Masha [Department of Public Health Sciences, University of Chicago, Chicago, Illinois (United States); Villaflor, Victoria M. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Cohen, Ezra E.W. [Moores Cancer Center, University of California, San Diego, San Diego, California (United States); Haraf, Daniel J. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Vokes, Everett E. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States)

2016-09-01

Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

International Nuclear Information System (INIS)

Seiwert, Tanguy Y.; Melotek, James M.; Blair, Elizabeth A.; Stenson, Kerstin M.; Salama, Joseph K.; Witt, Mary Ellyn; Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison; Lingen, Mark W.; Kocherginsky, Masha; Villaflor, Victoria M.; Cohen, Ezra E.W.; Haraf, Daniel J.; Vokes, Everett E.

2016-01-01

Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma--a report from the IRSG

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Donaldson, Sarah S.; Meza, Jane; Breneman, John C.; Crist, William M.; Laurie, Fran; Qualman, Stephen J.; Wharam, Moody

2001-01-01

Purpose: To evaluate the outcome and toxicity of hyperfractionated radiotherapy (HFRT) vs. conventionally fractionated radiotherapy (CFRT) in children with Group III rhabdomyosarcoma (RMS). Methods and Materials: Five hundred fifty-nine children were enrolled into the Intergroup Rhabdomyosarcoma Study IV with Group III RMS. Sixty-nine were ineligible for the analysis because of incorrect group or pathologic findings. Of the 490 remaining, 239 were randomized to HFRT (59.4 Gy in 54 1.1-Gy twice daily fractions) and 251 to CFRT (50.4 Gy in 28 1.8-Gy daily fractions). The age range was <1-21 years. All patients received chemotherapy. RT began at Week 9 after induction chemotherapy for all but those with high-risk parameningeal tumors who received RT during induction chemotherapy. The patient groups were equally balanced. The median follow-up was 3.9 years. Results: Analysis by randomized treatment assignment (intent to treat) revealed an estimated 5-year failure-free survival (FFS) rate of 70% and overall survival (OS) of 75%. In the univariate analysis, the factors associated with the best outcome were age 1-9 years at diagnosis; noninvasive tumors; tumor size <5 cm; uninvolved lymph nodes; Stage 1 or 2 disease; primary site in the orbit or head and neck; and embryonal histologic features (p=0.001 for all factors). No differences in the FFS or OS between the two RT treatment methods and no differences in the FFS or OS between HFRT and CFRT were found when analyzed by age, gender, tumor size, tumor invasiveness, nodal status, histologic features, stage, or primary site. Treatment compliance differed by age. Of the children <5 years, 57% assigned to HFRT received HFRT and 77% assigned to CFRT received CFRT. Of the children ≥5 years, 88% assigned to both HFRT and CFRT received their assigned treatment. The reasons for not receiving the appropriate randomized treatment were progressive disease, early death, parent or physician refusal, young age, or surgery. The

Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

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Câmara-Costa, Hugo; Resch, Anika; Kieffer, Virginie; Lalande, Clémence; Poggi, Geraldina; Kennedy, Colin; Bull, Kim; Calaminus, Gabriele; Grill, Jacques; Doz, François; Rutkowski, Stefan; Massimino, Maura; Kortmann, Rolf-Dieter; Lannering, Birgitta; Dellatolas, Georges; Chevignard, Mathilde

2015-01-01

Purpose: In the European HIT-SIOP PNET4 randomized controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy (HFRT arm, including a partially focused boost) or standard radiation therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children <8 years of age at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms. Methods and Materials: Neuropsychological data were collected prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven's Progressive Matrices, we estimated full-scale intelligence quotient (FSIQ) and, when available, verbal IQ (VIQ), performance IQ (PIQ), working memory index (WMI), and processing speed index (PSI). Results: Among the 137 participants (HFRT arm n=71, STRT arm n=66, 63.5% males), mean (±SD) ages at diagnosis and assessment respectively were 9.3 (±3.2) years of age (40.8% < 8 years of age at diagnosis) and 14.6 (±4.3) years of age. Mean (±SD) FSIQ was 88 (±19), and mean intergroup difference was 3.88 (95% confidence interval: −2.66 to 10.42, P=.24). No significant differences were found in children >8 years of age at diagnosis. In children <8 years of age at diagnosis, a marginally significant trend toward higher VIQ was found in those treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI, or FSIQ (mean intergroup differences were: 12.02 for VIQ [95% CI: 2.37-21.67; P=.02]; 3.77 for PIQ [95% CI: −5.19 to 12.74; P>.10]; 5.20 for WMI [95% CI: −2.07 to 12.47; P>.10]; 10.90 for PSI [95% CI: −1.54 to 23.36; P=.08]; and 5.28 for FSIQ [95% CI: −4.23 to 14.79; P>.10]). Conclusions: HFRT was associated with

Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

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Câmara-Costa, Hugo, E-mail: hugocamaracosta@gmail.com [National Institute of Health and Medical Research, INSERM U1178, Paris (France); Resch, Anika [University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kieffer, Virginie [Saint Maurice Hospitals, Saint Maurice (France); Lalande, Clémence [Institut Gustave Roussy, Villejuif (France); Poggi, Geraldina [Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco (Italy); Kennedy, Colin; Bull, Kim [University of Southampton, Faculty of Medicine, Southampton (United Kingdom); Calaminus, Gabriele [Paediatric Oncology, University of Muenster, Muenster (Germany); Grill, Jacques [Institut Gustave Roussy, Villejuif (France); Doz, François [Institut Curie and University Paris Descartes, Sorbonne Paris Cité, Paris (France); Rutkowski, Stefan [University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Massimino, Maura [Fondazione IRCCS, Istituto Nazionale Tumori, Milan (Italy); Kortmann, Rolf-Dieter [Department of Radiation Therapy, University of Leipzig, Leipzig (Germany); Lannering, Birgitta [Paediatric Oncology, University of Gothenburg, Gothenburg (Sweden); Dellatolas, Georges [National Institute of Health and Medical Research, INSERM U1178, Paris (France); Chevignard, Mathilde [Rehabilitation Department for Children With Acquired Neurological Injury, Saint Maurice Hospitals, Saint Maurice, and Sorbonne Universités, UPMC Universités Paris, INSERM CNRS, Paris (France)

2015-08-01

Purpose: In the European HIT-SIOP PNET4 randomized controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy (HFRT arm, including a partially focused boost) or standard radiation therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children <8 years of age at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms. Methods and Materials: Neuropsychological data were collected prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven's Progressive Matrices, we estimated full-scale intelligence quotient (FSIQ) and, when available, verbal IQ (VIQ), performance IQ (PIQ), working memory index (WMI), and processing speed index (PSI). Results: Among the 137 participants (HFRT arm n=71, STRT arm n=66, 63.5% males), mean (±SD) ages at diagnosis and assessment respectively were 9.3 (±3.2) years of age (40.8% < 8 years of age at diagnosis) and 14.6 (±4.3) years of age. Mean (±SD) FSIQ was 88 (±19), and mean intergroup difference was 3.88 (95% confidence interval: −2.66 to 10.42, P=.24). No significant differences were found in children >8 years of age at diagnosis. In children <8 years of age at diagnosis, a marginally significant trend toward higher VIQ was found in those treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI, or FSIQ (mean intergroup differences were: 12.02 for VIQ [95% CI: 2.37-21.67; P=.02]; 3.77 for PIQ [95% CI: −5.19 to 12.74; P>.10]; 5.20 for WMI [95% CI: −2.07 to 12.47; P>.10]; 10.90 for PSI [95% CI: −1.54 to 23.36; P=.08]; and 5.28 for FSIQ [95% CI: −4.23 to 14.79; P>.10]). Conclusions: HFRT was associated with

Is the alpha-beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy

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Valdagni, Riccardo; Italia, Corrado; Montanaro, Paolo; Lanceni, Angelo; Lattuada, Paola; Magnani, Tiziana; Fiorino, Claudio; Nahum, Alan

2005-01-01

Background and purpose: The objectives of the current study were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities as well as biochemical control (bRFS) in prostate cancer, utilizing conventional (2.0 Gy daily) (STD) or hyperfractionated (HFX) conformal irradiation (CRT). HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control. Patients and methods: Three-hundred-and-seventy consecutive patients (pts) entered this prospective, non-randomized trial in the period January 1993-January 2003; 209 were treated with STD and 161 with HFX CRT. All were evaluable for acute toxicity analysis, 179 (STD) and 151 pts (HFX) being evaluable for late sequelae and bRFS analyses. Pt characteristics were not statistically different in the two groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 and 79.2 Gy for STD and HFX patients respectively, the latter dose being isoeffective for tumour control assuming α/β=10 (EQD 2 =73.9 Gy). Median follow-up was 29.4 months (25.2 mos for STD; 37.7 mos for HFX; P<0.01). The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses. Results: Acute grade≥2 GU toxicity was higher in the STD group (48.6% versus 37.3% in HFX, P=0.03), while no significant difference was found for acute GI toxicity. Late grade≥2 GU and GI toxicities were lower in the HFX group (5-year actuarial rate: GU: 10.1% versus 20.3%, P=0.05; GI: 6.0% versus 10.6%, P=0.18). Five-year bRFS were 70% (±13.8%, 95% CI) and 82.6% (±7.2%) for STD and HFX, respectively (P=0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9%±12.4% versus 63.9%±23.8%, P=0.15). Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation

Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

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Sprague Lisa D

2006-12-01

Full Text Available Abstract Background The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. Methods From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %, one third with tongue and floor of mouth tumors (29 % and one fifth (19 % suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m2/d DDP + 750–1000 mg/m2/d 5FU (cont. infusion. This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy. All patients assigned to this scheme were included in the survival evaluation. Results Forty patients (63 % received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d and the median follow up was 1.9 years (678 d, respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 % had acute grade 2–3 mucositis, and 33 patients (58 % suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient 10.5 g/dl and for patients who completed the protocol. Conclusion The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients

Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

International Nuclear Information System (INIS)

Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

2006-01-01

The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol 'SCHARC' and the overall survival of our patients. From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m 2 /d DDP + 750–1000 mg/m 2 /d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2–3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led

Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis.

Science.gov (United States)

Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

2006-12-07

The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1-5: 20 mg/m2/d DDP + 750-1000 mg/m2/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69-70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2-3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in

Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

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Villar, Alfonso; Martinez, Jose Carlos; Serdio, Jose Luis de

2008-01-01

Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m 2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m 2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal

Prevalence of traumatic brain injury in the general adult population: a meta-analysis.

Science.gov (United States)

Frost, R Brock; Farrer, Thomas J; Primosch, Mark; Hedges, Dawson W

2013-01-01

Traumatic brain injury (TBI) is a significant public-health concern. To understand the extent of TBI, it is important to assess the prevalence of TBI in the general population. However, the prevalence of TBI in the general population can be difficult to measure because of differing definitions of TBI, differing TBI severity levels, and underreporting of sport-related TBI. Additionally, prevalence reports vary from study to study. In this present study, we used meta-analytic methods to estimate the prevalence of TBI in the adult general population. Across 15 studies, all originating from developed countries, which included 25,134 adults, 12% had a history of TBI. Men had more than twice the odds of having had a TBI than did women, suggesting that male gender is a risk factor for TBI. The adverse behavioral, cognitive and psychiatric effects associated with TBI coupled with the high prevalence of TBI identified in this study indicate that TBI is a considerable public and personal-health problem. Copyright © 2012 S. Karger AG, Basel.

NEOADJUVANT RADIOTHERAPY FOR BLADDER CARCINOMA IN ...

African Journals Online (AJOL)

Objective To evaluate the impact of preoperative accelerated hyperfractionated radiotherapy in the management of bladder carcinoma in Egyptian patients. Patients and Methods Between December 1996 and February 2000, 104 Egyptian patients with pathologically proven infiltrative bladder carcinoma were enrolled in ...

Altered metabolites of the rat hippocampus after mild and moderate traumatic brain injury - a combined in vivo and in vitro 1 H-MRS study.

Science.gov (United States)

Singh, Kavita; Trivedi, Richa; Verma, Ajay; D'souza, Maria M; Koundal, Sunil; Rana, Poonam; Baishya, Bikash; Khushu, Subash

2017-10-01

Traumatic brain injury (TBI) has been shown to affect hippocampus-associated learning, memory and higher cognitive functions, which may be a consequence of metabolic alterations. Hippocampus-associated disorders may vary depending on the severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since injury. The underlying hippocampal metabolic irregularities may provide an insight into the pathological process following TBI. In this study, in vivo and in vitro proton magnetic resonance spectroscopy ( 1 H-MRS) data were acquired from the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre-injury), 4 h, Day 1 and Day 5 post-injury (PI). In vitro MRS results indicated trauma-induced changes in both miTBI and moTBI; however, in vivo MRS showed metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of osmolytes indicating injury-induced edema. Altered levels of citric acid cycle intermediates, glutamine/glutamate and amino acid metabolism indicated injury-induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall similar pattern of pathological process was observed in both miTBI and moTBI, with the distinction of depleted N-acetylaspartate levels (indicating neuronal loss) at 4 h and Day 1 and enhanced lactate production (indicating heightened energy depletion leading to the commencement of the anaerobic pathway) at Day 5 in moTBI. To the best of our knowledge, this is the first study to investigate the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo and in vitro MRS. Copyright © 2017 John Wiley & Sons, Ltd.

Busulfan, Fludarabine, and Thiotepa Conditioning Regimen for Non Malignant Disease

Science.gov (United States)

2018-04-19

Bone Marrow Failure Syndrome; Thalassemia; Sickle Cell Disease; Diamond Blackfan Anemia; Acquired Neutropenia in Newborn; Acquired Anemia Hemolytic; Acquired Thrombocytopenia; Hemophagocytic Lymphohistiocytoses; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Common Variable Immunodeficiency; X-linked Lymphoproliferative Disease; Severe Combined Immunodeficiency; Hurler Syndrome; Mannosidosis; Adrenoleukodystrophy

Implicit and explicit memory outcome in children who have sustained severe traumatic brain injury: impact of age at injury (preliminary findings).

Science.gov (United States)

Lah, Suncica; Epps, Adrienne; Levick, Wayne; Parry, Louise

2011-01-01

To examine implicit and explicit memory outcome in children who had sustained severe traumatic brain injury (TBI) through childhood. Opposite patterns of impairments were expected: (i) impaired implicit memory in children with early TBI (TBI-EC, explicit memory in children with late TBI (TBI-LC, ≥ 6 years). Children who had sustained severe TBI more then 1 year ago were assessed. Fourteen children who had sustained severe TBI (TBI-EC, n = 10 and TBI-LC, n = 4) between 8 months and 13 years 7 months of age and 13 non-injured control subjects (NC) participated. Implicit (repetition priming and skill learning) and explicit verbal memory were examined. The TBI group performed worse on implicit (repetition priming) and explicit memory tasks compared to the NC group. Moreover, impairments were found in implicit and explicit memory in the TBI-EC, but not in the TBI-LC group. This study has shown, for the first time, that severe childhood TBI may compromise not only explicit, but also implicit memory. Nevertheless, instead of a selective implicit memory impairment, it was found that children who sustained injuries in early childhood present with impairments in both memory systems.

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

Science.gov (United States)

Washington, Patricia M; Villapol, Sonia; Burns, Mark P

2016-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Recovery of episodic memory subprocesses in mild and complicated mild traumatic brain injury at 1 and 12 months post injury.

Science.gov (United States)

Tayim, Fadi M; Flashman, Laura A; Wright, Matthew J; Roth, Robert M; McAllister, Thomas W

2016-11-01

Episodic memory complaints are commonly reported after traumatic brain injury (TBI). The contributions of specific memory subprocesses (encoding, consolidation, and retrieval), however, are not well understood in mild TBI (mTBI). In the present study, we evaluated subprocesses of episodic memory in patients with mTBI using the item-specific deficit approach (ISDA), which analyzes responses on list learning tasks at an item level. We also conducted exploratory analyses to evaluate the effects of complicated mTBI (comp-mTBI) on memory. We compared episodic verbal memory performance in mTBI (n = 92) at approximately 1 and 12 months post TBI, as well as in a healthy comparison (HC) group (n = 40) at equivalent time points. Episodic memory was assessed using the California Verbal Learning Test-2nd Edition (CVLT-II), and both standard CVLT-II scores and ISDA indices were evaluated. Compared to the HC group, the mTBI group showed significantly poorer encoding and learning across time, as measured by ISDA and CVLT-II. Further analyses of these mTBI subgroups [(noncomplicated mTBI (NC-mTBI, n = 77) and comp-mTBI (n = 15)], indicated that it was the comp-mTBI group who continued to demonstrate poorer encoding ability than the HC group. When the patient groups were directly compared, the NC-mTBI group improved slightly on the ISDA Encoding Deficit Index. While the comp-mTBI group worsened slightly over time, their poorer encoding ability was not likely clinically meaningful. These findings indicate that, while the NC-mTBI and HC groups' performances were comparable by 12 months, a primary, long-term deficit in encoding of auditory verbal information remained problematic in the comp-mTBI group.

Differences in cerebral perfusion deficits in mild traumatic brain injury and depression using single photon emission computed tomography

OpenAIRE

Kristoffer eRomero; Sandra E Black; Sandra E Black; Anthony eFeinstein

2014-01-01

Background: Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI). However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI.Methods: Mild TBI patients without depressive symptoms (mTBI-noD, n = 39), TBI patients with depressive symptoms (mTBI-D, n = 13), and 15 patients with major depr...

Differences in Cerebral Perfusion Deficits in Mild Traumatic Brain Injury and Depression Using Single-Photon Emission Computed Tomography

OpenAIRE

Romero, Kristoffer; Black, Sandra E.; Feinstein, Anthony

2014-01-01

Background: Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI). However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI. Methods: Mild TBI patients without depressive symptoms (mTBI-noD, n = 39), TBI patients with depressive symptoms (mTBI-D, n = 13), and 15 patients with major ...

Prevalence of Self-Reported Lifetime History of Traumatic Brain Injury and Associated Disability: A Statewide Population-Based Survey.

Science.gov (United States)

Whiteneck, Gale G; Cuthbert, Jeffrey P; Corrigan, John D; Bogner, Jennifer A

2016-01-01

To investigate the prevalence of all severities of traumatic brain injury (TBI), regardless of treatment setting, and their associated negative outcomes. A total of 2701 adult Coloradoans. A statewide, population-based, random digit-dialed telephone survey. The lifetime history of TBI was assessed by a modification of the Ohio State University TBI Identification Method; activity limitation and life satisfaction were also assessed. The distribution of self-reported lifetime injury was as follows: 19.8%, no injury; 37.7%, injury but no TBI; 36.4%, mild TBI; and 6.0%, moderate-severe TBI. Of those reporting a TBI, 23.1% were hospitalized, 38.5% were treated in an emergency department, 9.8% were treated in a physician's office, and 27.5% did not seek medical care. A clear gradient of activity limitations and low life satisfaction was seen, with the highest proportions of these negative outcomes occurring in people reporting more severe TBI and the lowest proportions in those not reporting a TBI. Approximately twice as many people reported activity limitations and low life satisfaction after nonhospitalized TBI compared with hospitalized TBI. This investigation highlights the seriousness of TBI as a public health problem and the importance of including all severities of TBI, no matter where, or if treated, in estimating the prevalence of disability co-occurring with TBI.

Traumatic brain injury precipitates cognitive impairment and extracellular Aβ aggregation in Alzheimer's disease transgenic mice.

Directory of Open Access Journals (Sweden)

Naoki Tajiri

Full Text Available Traumatic brain injury (TBI has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Aβ-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Aβ deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Aβ deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Aβ deposition in the brain.

The Wechsler Test of Adult Reading as a Measure of Premorbid Intelligence Following Traumatic Brain Injury.

Science.gov (United States)

Steward, Kayla A; Novack, Thomas A; Kennedy, Richard; Crowe, Michael; Marson, Daniel C; Triebel, Kristen L

2017-02-01

The current study sought to determine whether the Wechsler Test of Adult Reading (WTAR) provides a stable estimate of premorbid intellectual ability in acutely injured patients recovering from traumatic brain injury (TBI). A total of 135 participants (43 mild TBI [mTBI], 40 moderate/severe TBI [msevTBI], 52 healthy controls) were administered the WTAR at 1 and 12 months post-injury. Despite similar demographic profiles, participants with msevTBI performed significantly worse than controls on the WTAR at both time points. Moreover, the msevTBI group had a significant improvement in WTAR performance over the 1-year period. In contrast, those participants with mTBI did not significantly differ from healthy controls and both the mTBI and control groups demonstrated stability on the WTAR over time. Results indicate that word-reading tests may underestimate premorbid intelligence during the immediate recovery period for patients with msevTBI. Clinicians should consider alternative estimation measures in this TBI subpopulation. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Differences in cerebral perfusion deficits in mild traumatic brain injury and depression using single-photon emission computed tomography.

Science.gov (United States)

Romero, Kristoffer; Black, Sandra E; Feinstein, Anthony

2014-01-01

Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI). However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI. Mild TBI patients without depressive symptoms (mTBI-noD, n = 39), TBI patients with depressive symptoms (mTBI-D, n = 13), and 15 patients with major depressive disorder (MDD), but no TBI were given 99m T-ECD single-photon emission computed tomography (SPECT) scans within 2 weeks of injury. All subjects completed tests of information processing speed, complex attention, and executive functioning, and a self-report questionnaire measuring symptoms of psychological distress. Between-group comparisons of quantified SPECT perfusion were undertaken using univariate and multivariate (partial least squares) analyses. mTBI-D and mTBI-noD groups did not differ in terms of cerebral perfusion. However, patients with MDD showed hypoperfusion compared to both TBI groups in several frontal (orbitofrontal, middle frontal, and superior frontal cortex), superior temporal, and posterior cingulate regions. The mTBI-D group showed poorer performance on a measure of complex attention and working memory compared to both the mTBI-noD and MDD groups. These results suggest that depressive symptoms do not affect SPECT perfusion in the sub-acute phase following a mild TBI. Conversely, MDD is associated with hypoperfusion primarily in frontal regions.

Modelling altered fractionation schedules

International Nuclear Information System (INIS)

Fowler, J.F.

1993-01-01

The author discusses the conflicting requirements of hyperfractionation and accelerated fractionation used in radiotherapy, and the development of computer modelling to predict how to obtain an optimum of tumour cell kill without exceeding normal-tissue tolerance. The present trend is to shorten hyperfractionated schedules from 6 or 7 weeks to give overall times of 4 or 5 weeks as in new schedules by Herskovic et al (1992) and Harari (1992). Very high doses are given, much higher than can be given when ultrashort schedules such as CHART (12 days) are used. Computer modelling has suggested that optimum overall times, to yield maximum cell kill in tumours ((α/β = 10 Gy) for a constant level of late complications (α/β = 3 Gy) would be X or X-1 weeks, where X is the doubling time of the tumour cells in days (Fowler 1990). For median doubling times of about 5 days, overall times of 4 or 5 weeks should be ideal. (U.K.)

Anodal Transcranial Direct Current Stimulation Provokes Neuroplasticity in Repetitive Mild Traumatic Brain Injury in Rats

Directory of Open Access Journals (Sweden)

Ho Jeong Kim

2017-01-01

Full Text Available Repetitive mild traumatic brain injury (rmTBI provokes behavioral and cognitive changes. But the study about electrophysiologic findings and managements of rmTBI is limited. In this study, we investigate the effects of anodal transcranial direct current stimulation (tDCS on rmTBI. Thirty-one Sprague Dawley rats were divided into the following groups: sham, rmTBI, and rmTBI treated by tDCS. Animals received closed head mTBI three consecutive times a day. Anodal tDCS was applied to the left motor cortex. We evaluated the motor-evoked potential (MEP and the somatosensory-evoked potential (SEP. T2-weighted magnetic resonance imaging was performed 12 days after rmTBI. After rmTBI, the latency of MEP was prolonged and the amplitude in the right hind limb was reduced in the rmTBI group. The latency of SEP was delayed and the amplitude was decreased after rmTBI in the rmTBI group. In the tDCS group, the amplitude in both hind limbs was increased after tDCS in comparison with the values before rmTBI. Anodal tDCS after rmTBI seems to be a useful tool for promoting transient motor recovery through increasing the synchronicity of cortical firing, and it induces early recovery of consciousness. It can contribute to management of concussion in humans if further study is performed.

Enlarged thalamic volumes and increased fractional anisotropy in the thalamic radiations in Veterans with suicide behaviors

Directory of Open Access Journals (Sweden)

Melissa eLopez-Larson

2013-08-01

Full Text Available Post-mortem studies have suggested a link between the thalamus, psychiatric disorders, and suicide. We evaluated the thalamus and anterior thalamic radiations (ATR in a group of Veterans with and without a history of suicidal behavior (SB to determine if thalamic abnormalities were associated with an increased risk of SB. Forty Veterans with mild traumatic brain injury (TBI and no SB (TBI-SB, 19 Veterans with mild TBI and a history of SB (TB+SB and 15 healthy controls (HC underwent MRI scanning including a structural and diffusion tensor imaging scan. Suicidal behaviors were evaluated utilizing the Columbia Suicide Rating Scale and impulsivity was measured using the Barratt Impulsiveness Scale (BIS. Differences in thalamic volumes and ATR fractional anisotropy (FA were examined between 1 TBI+SB versus HC and 2 TBI+SB versus combined HC and TBI-SB and 2 between TBI+SB and TBI-SB. Left and right thalamic volumes were significantly increased in those with TBI+SB compared to the HC, TBI-SB and the combined group. Veterans with TBI+SB had increased FA bilaterally compared to the HC, HC and TBI-SB group, and the TBI-SB only group. Significant positive associations were found for bilateral ATR and BIS in the TBI+SB group. Our findings of thalamic enlargement and increased FA in individuals with TBI+SB suggest that this region may be a biomarker for suicide risk. Our findings are consistent with previous evidence indicating that suicide may be associated with behavioral disinhibition and frontal-thalamic-limbic dysfunction and suggest a neurobiologic mechanism that may increase vulnerability to suicide.

Neurobiological mechanisms associated with facial affect recognition deficits after traumatic brain injury.

Science.gov (United States)

Neumann, Dawn; McDonald, Brenna C; West, John; Keiski, Michelle A; Wang, Yang

2016-06-01

The neurobiological mechanisms that underlie facial affect recognition deficits after traumatic brain injury (TBI) have not yet been identified. Using functional magnetic resonance imaging (fMRI), study aims were to 1) determine if there are differences in brain activation during facial affect processing in people with TBI who have facial affect recognition impairments (TBI-I) relative to people with TBI and healthy controls who do not have facial affect recognition impairments (TBI-N and HC, respectively); and 2) identify relationships between neural activity and facial affect recognition performance. A facial affect recognition screening task performed outside the scanner was used to determine group classification; TBI patients who performed greater than one standard deviation below normal performance scores were classified as TBI-I, while TBI patients with normal scores were classified as TBI-N. An fMRI facial recognition paradigm was then performed within the 3T environment. Results from 35 participants are reported (TBI-I = 11, TBI-N = 12, and HC = 12). For the fMRI task, TBI-I and TBI-N groups scored significantly lower than the HC group. Blood oxygenation level-dependent (BOLD) signals for facial affect recognition compared to a baseline condition of viewing a scrambled face, revealed lower neural activation in the right fusiform gyrus (FG) in the TBI-I group than the HC group. Right fusiform gyrus activity correlated with accuracy on the facial affect recognition tasks (both within and outside the scanner). Decreased FG activity suggests facial affect recognition deficits after TBI may be the result of impaired holistic face processing. Future directions and clinical implications are discussed.

Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities.

Science.gov (United States)

Di Pietro, Valentina; Lazzarino, Giacomo; Amorini, Angela Maria; Signoretti, Stefano; Hill, Lisa J; Porto, Edoardo; Tavazzi, Barbara; Lazzarino, Giuseppe; Belli, Antonio

2017-08-23

Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.

Risk and mortality of traumatic brain injury in stroke patients: two nationwide cohort studies.

Science.gov (United States)

Chou, Yi-Chun; Yeh, Chun-Chieh; Hu, Chaur-Jong; Meng, Nai-Hsin; Chiu, Wen-Ta; Chou, Wan-Hsin; Chen, Ta-Liang; Liao, Chien-Chang

2014-01-01

Patients with stroke had higher incidence of falls and hip fractures. However, the risk of traumatic brain injury (TBI) and post-TBI mortality in patients with stroke was not well defined. Our study is to investigate the risk of TBI and post-TBI mortality in patients with stroke. Using reimbursement claims from Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study of 7622 patients with stroke and 30 488 participants without stroke aged 20 years and older as reference group. Data were collected on newly developed TBI after stroke with 5 to 8 years' follow-up during 2000 to 2008. Another nested cohort study including 7034 hospitalized patients with TBI was also conducted to analyze the contribution of stroke to post-TBI in-hospital mortality. Compared with the nonstroke cohort, the adjusted hazard ratio of TBI risk among patients with stroke was 2.80 (95% confidence interval = 2.58-3.04) during the follow-up period. Patients with stroke had higher mortality after TBI than those without stroke (10.2% vs 3.2%, P stroke (RR = 1.60), hemorrhagic stroke (RR = 1.68), high medical expenditure for stroke (RR = 1.80), epilepsy (RR = 1.79), neurosurgery (RR = 1.94), and hip fracture (RR = 2.11) were all associated with significantly higher post-TBI mortality among patients with stroke. Patients with stroke have an increased risk of TBI and in-hospital mortality after TBI. Various characteristics of stroke severity were all associated with higher post-TBI mortality. Special attention is needed to prevent TBI among these populations.

Prevalence of traumatic brain injury in intimate partner violence offenders compared to the general population: a meta-analysis.

Science.gov (United States)

Farrer, Thomas J; Frost, R Brock; Hedges, Dawson W

2012-04-01

Intimate partner violence (IPV) is widespread. Several risk factors are associated with IPV perpetuation, including alcohol use and educational level. The aggression and violence associated with traumatic brain injury (TBI) suggest that brain trauma may also be a risk factor for IPV. To examine the association between TBI and IPV, the authors conducted a meta-analysis of peer-reviewed published studies reporting the prevalence of TBI in IPV perpetrators. The authors compared the frequency of TBI among IPV perpetuators to estimates of TBI in the general population using a single-sample test of proportions. Six studies containing a total of 222 subjects met inclusion criteria. Fifty-three percent (119) of the IPV perpetuators had a history of TBI, a prevalence significantly higher (p < .0001) than estimates of TBI in the general population. The prevalence of TBI among perpetuators of IPV appears significantly higher than the prevalence of TBI in the general population. To the extent that this association is causal, TBI may be a risk factor for interpersonal violence, although comparatively few source studies, lack of standardized information about TBI severity, and the inability to investigate potential confounding variables necessarily limit this conclusion.

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group.

Science.gov (United States)

Wickwire, Emerson M; Williams, Scott G; Roth, Thomas; Capaldi, Vincent F; Jaffe, Michael; Moline, Margaret; Motamedi, Gholam K; Morgan, Gregory W; Mysliwiec, Vincent; Germain, Anne; Pazdan, Renee M; Ferziger, Reuven; Balkin, Thomas J; MacDonald, Margaret E; Macek, Thomas A; Yochelson, Michael R; Scharf, Steven M; Lettieri, Christopher J

2016-04-01

Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders.

Differences in cerebral perfusion deficits in mild traumatic brain injury and depression using single photon emission computed tomography

Directory of Open Access Journals (Sweden)

Kristoffer eRomero

2014-08-01

Full Text Available Background: Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI. However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI.Methods: Mild TBI patients without depressive symptoms (mTBI-noD, n = 39, TBI patients with depressive symptoms (mTBI-D, n = 13, and 15 patients with major depressive disorder, but no TBI (MDD were given 99-m T-ECD SPECT scans within 2 weeks of injury. All subjects completed tests of information processing speed, complex attention, and executive functioning, and a self-report questionnaire measuring symptoms of psychological distress. Between group comparisons of quantified SPECT perfusion were undertaken, using univariate and multivariate (partial least squares analyses.Results: mTBI-D and mTBI-noD groups did not differ in terms of cerebral perfusion. However, patients with MDD showed hypoperfusion in several frontal (orbitofrontal, middle frontal, and superior frontal cortex, superior temporal, and posterior cingulate regions. The mTBI-D group showed poorer performance on a measure of complex attention and working memory, compared to both the mTBI-noD and MDD groups.Conclusions: These results suggest that depressive symptoms do not affect SPECT perfusion in the sub-acute phase following a mild TBI. Conversely, MDD is associated with hypoperfusion primarily in frontal regions.

Personality Assessment Inventory profiles of veterans: Differential effects of mild traumatic brain injury and psychopathology.

Science.gov (United States)

Miskey, Holly M; Shura, Robert D; Yoash-Gantz, Ruth E; Rowland, Jared A

2015-09-01

Neuropsychiatric complaints often accompany mild traumatic brain injury (mTBI), a common condition in post-deployed Veterans. Self-report, multi-scale personality inventories may elucidate the pattern of psychiatric distress in this cohort. This study investigated valid Personality Assessment Inventory (PAI) profiles in post-deployed Veterans. Measures of psychopathology and mTBI were examined in a sample of 144 post-deployed Veterans divided into groups: healthy controls (n = 40), mTBI only (n = 31), any mental health diagnosis only (MH; n = 25), comorbid mTBI and Posttraumatic Stress Disorder (mTBI/PTSD; n = 23), and comorbid mTBI, PTSD, and other psychological diagnoses (mTBI/PTSD/MDD+; n = 25). There were no significant differences between the mTBI and the control group on mean PAI subscale elevation, or number of subscale elevations above 60T or 70T. The other three groups had significantly higher overall mean scores, and more elevations above 60 and 70T compared to both controls and mTBI only. The mTBI/PTSD/MDD+ group showed the highest and most elevations. After entering demographics, PTSD, and number of other psychological diagnoses into hierarchical regressions using the entire sample, mTBI history did not predict mean PAI subscale score or number of elevations above 60T or 70T. PTSD was the only significant predictor. There were no interaction effects between mTBI and presence of PTSD, or between mTBI and total number of diagnoses. This study suggests that mTBI alone is not uniquely related to psychiatric distress in Veterans, but that PTSD accounts for self-reported symptom distress.

Surviving severe traumatic brain injury in Denmark

DEFF Research Database (Denmark)

Odgaard, Lene; Poulsen, Ingrid; Kammersgaard, Lars Peter

2015-01-01

PURPOSE: To identify all hospitalized patients surviving severe traumatic brain injury (TBI) in Denmark and to compare these patients to TBI patients admitted to highly specialized rehabilitation (HS-rehabilitation). PATIENTS AND METHODS: Patients surviving severe TBI were identified from...... severe TBI were admitted to HS-rehabilitation. Female sex, older age, and non-working status pre-injury were independent predictors of no HS-rehabilitation among patients surviving severe TBI. CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI was stable in Denmark...

Energy Drinks, Alcohol, Sports and Traumatic Brain Injuries among Adolescents.

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Ilie, Gabriela; Boak, Angela; Mann, Robert E; Adlaf, Edward M; Hamilton, Hayley; Asbridge, Mark; Rehm, Jürgen; Cusimano, Michael D

2015-01-01

The high prevalence of traumatic brain injuries (TBI) among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI. We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption. Data were derived from the Centre for Addiction and Mental Health's 2013 Ontario Student Drug Use and Health Survey (OSDUHS). This population-based cross-sectional school survey included 10,272 7th to 12th graders (ages 11-20) who completed anonymous self-administered questionnaires in classrooms. Mild to severe TBI were defined as those resulting in a loss of consciousness for at least five minutes, or being hospitalized for at least one night. Mechanism of TBI, prevalence estimates of TBI, and odds of energy drink consumption, alcohol use, and consumption of energy drinks mixed with alcohol are assessed. Among all students, 22.4% (95% CI: 20.7, 24.1) reported a history of TBI. Sports injuries remain the main mechanism of a recent (past year) TBI (45.5%, 95% CI: 41.0, 50.1). Multinomial logistic regression showed that relative to adolescents who never sustained a TBI, the odds of sustaining a recent TBI were greater for those consuming alcohol, energy drinks, and energy drinks mixed in with alcohol than abstainers. Odds ratios were higher for these behaviors among students who sustained a recent TBI than those who sustained a former TBI (lifetime but not past 12 months). Relative to recent TBI due to other causes of injury, adolescents who sustained a recent TBI while playing sports had higher odds of recent energy drinks consumption than abstainers. TBI remains a disabling and common condition among adolescents and the consumption of alcohol, energy drinks, and alcohol mixed with

Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

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Sandra A Acosta

Full Text Available Long-term consequences of traumatic brain injury (TBI are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD, yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long

Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

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Acosta, Sandra A; Diamond, David M; Wolfe, Steven; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G; Sanberg, Paul R; Kaneko, Yuji; Borlongan, Cesar V

2013-01-01

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

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Diamond, David M.; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G.; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesar V.

2013-01-01

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

Association of Mild Traumatic Brain Injury With and Without Loss of Consciousness With Dementia in US Military Veterans.

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Barnes, Deborah E; Byers, Amy L; Gardner, Raquel C; Seal, Karen H; Boscardin, W John; Yaffe, Kristine

2018-05-07

Traumatic brain injury (TBI) is common in both veteran and civilian populations. Prior studies have linked moderate and severe TBI with increased dementia risk, but the association between dementia and mild TBI, particularly mild TBI without loss of consciousness (LOC), remains unclear. To examine the association between TBI severity, LOC, and dementia diagnosis in veterans. This cohort study of all patients diagnosed with a TBI in the Veterans Health Administration health care system from October 1, 2001, to September 30, 2014, and a propensity-matched comparison group. Patients with dementia at baseline were excluded. Researchers identified TBIs through the Comprehensive TBI Evaluation database, which is restricted to Iraq and Afghanistan veterans, and the National Patient Care Database, which includes veterans of all eras. The severity of each TBI was based on the most severe injury recorded and classified as mild without LOC, mild with LOC, mild with LOC status unknown, or moderate or severe using Department of Defense or Defense and Veterans Brain Injury Center criteria. International Classification of Diseases, Ninth Revision codes were used to identify dementia diagnoses during follow-up and medical and psychiatric comorbidities in the 2 years prior to the index date. Dementia diagnosis in veterans who had experienced TBI with or without LOC and control participants without TBI exposure. The study included 178 779 patients diagnosed with a TBI in the Veterans Health Administration health care system and 178 779 patients in a propensity-matched comparison group. Veterans had a mean (SD) age of nearly 49.5 (18.2) years at baseline; 33 250 (9.3%) were women, and 259 136 (72.5%) were non-Hispanic white individuals. Differences between veterans with and without TBI were small. A total of 4698 veterans (2.6%) without TBI developed dementia compared with 10 835 (6.1%) of those with TBI. After adjustment for demographics and medical and psychiatric

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

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Cesar Reis

2015-05-01

Full Text Available Traumatic brain injury (TBI, defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI, diffusion tensor imaging (DTI, positron emission tomography (PET, and high definition fiber tracking (HDFT show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI.

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

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Reis, Cesar; Wang, Yuechun; Akyol, Onat; Ho, Wing Mann; Applegate II, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

2015-01-01

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI. PMID:26016501

Education attenuates the negative impact of traumatic brain injury on cognitive status.

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Sumowski, James F; Chiaravalloti, Nancy; Krch, Denise; Paxton, Jessica; Deluca, John

2013-12-01

To investigate whether the cognitive reserve hypothesis helps to explain differential cognitive impairment among survivors of traumatic brain injury (TBI), whereby survivors with greater intellectual enrichment (estimated with education) are less vulnerable to cognitive impairment. Cross-sectional study. Medical rehabilitation research center. Survivors of moderate or severe TBI (n=44) and healthy controls (n=36). Not applicable. Intellectual enrichment was estimated with educational attainment. Group was defined as TBI or healthy control. Current cognitive status (processing speed, working memory, episodic memory) was evaluated with neuropsychological tasks. TBI survivors exhibited worse cognitive status than healthy persons (Peducation was positively correlated with cognitive status in TBI survivors (r=.54, Peducation (R(2) change=.036, P=.004), whereas higher education attenuated the negative impact of TBI on cognitive status. TBI survivors with lower education performed much worse than matched healthy persons, but this TBI-related performance discrepancy was attenuated at higher levels of education. Higher intellectual enrichment (estimated with education) reduces the negative effect of TBI on cognitive outcomes, thereby supporting the cognitive reserve hypothesis in persons with TBI. Future work is necessary to investigate whether intellectual enrichment can build cognitive reserve as a rehabilitative intervention in survivors of TBI. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Is temperature an important variable in recovery after mild traumatic brain injury? [version 1; referees: 2 approved

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Coleen M. Atkins

2017-11-01

Full Text Available With nearly 42 million mild traumatic brain injuries (mTBIs occurring worldwide every year, understanding the factors that may adversely influence recovery after mTBI is important for developing guidelines in mTBI management. Extensive clinical evidence exists documenting the detrimental effects of elevated temperature levels on recovery after moderate to severe TBI. However, whether elevated temperature alters recovery after mTBI or concussion is an active area of investigation. Individuals engaged in exercise and competitive sports regularly experience body and brain temperature increases to hyperthermic levels and these temperature increases are prolonged in hot and humid ambient environments. Thus, there is a strong potential for hyperthermia to alter recovery after mTBI in a subset of individuals at risk for mTBI. Preclinical mTBI studies have found that elevating brain temperature to 39°C before mTBI significantly increases neuronal death within the cortex and hippocampus and also worsens cognitive deficits. This review summarizes the pathology and behavioral problems of mTBI that are exacerbated by hyperthermia and discusses whether hyperthermia is a variable that should be considered after concussion and mTBI. Finally, underlying pathophysiological mechanisms responsible for hyperthermia-induced altered responses to mTBI and potential gender considerations are discussed.

Social information processing skills in adolescents with traumatic brain injury: Relationship with social competence and behavior problems.

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Walz, Nicolay Chertkoff; Yeates, Keith Owen; Wade, Shari L; Mark, Erin

2009-01-01

To examine social information processing (SIP) skills, behavior problems, and social competence following adolescent TBI and to determine whether SIP skills were predictive of behavior problems and social competence. Cross-sectional analyses of adolescents with TBI recruited and enrolled in a behavioral treatment study currently in progress. Two tertiary care children's hospitals with Level 1 trauma centers. Adolescents aged 11 to 18 years with severe TBI (n=19) and moderate TBI (n=24) who were injured up to 24 months prior to recruitment. TBI severity, race, maternal education, and age at testing. a measure of SIP skills, Child Behavior Checklist (CBCL), Youth Self Report (YSR), and Home and Community Social Behavior Scale (HCSBS). The severe TBI group did not obtain significantly lower scores on the SIP measures than the moderate TBI group. In comparison to adolescents with moderate TBI, those with severe TBI had significantly more parent-reported externalizing behaviors and self-reported weaknesses in social competence. SIP skills were strong predictors of problems and social competence in adolescents with TBI. More specifically, an aggressive SIP style predicted externalizing problems and a passive SIP style predicted internalizing problems. Both passive and aggressive SIP skills were related to social competence and social problems. Adolescents with TBI are at risk for deficits in social and behavioral outcomes. SIP skills are strongly related to behavior problems and social competence in adolescents with TBI. SIP skills, social competence, and behavior problems are important targets for intervention that may be amenable to change and lead to improved functional outcomes following TBI.

Fear learning alterations after traumatic brain injury and their role in development of posttraumatic stress symptoms.

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Glenn, Daniel E; Acheson, Dean T; Geyer, Mark A; Nievergelt, Caroline M; Baker, Dewleen G; Risbrough, Victoria B

2017-08-01

It is unknown how traumatic brain injury (TBI) increases risk for posttraumatic stress disorder (PTSD). One potential mechanism is via alteration of fear-learning processes that could affect responses to trauma memories and cues. We utilized a prospective, longitudinal design to determine if TBI is associated with altered fear learning and extinction, and if fear processing mediates effects of TBI on PTSD symptom change. Eight hundred fifty two active-duty Marines and Navy Corpsmen were assessed before and after deployment. Assessments included TBI history, PTSD symptoms, combat trauma and deployment stress, and a fear-potentiated startle task of fear acquisition and extinction. Startle response and self-reported expectancy and anxiety served as measures of fear conditioning, and PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Individuals endorsing "multiple hit" exposure (both deployment TBI and a prior TBI) showed the strongest fear acquisition and highest fear expression compared to groups without multiple hits. Extinction did not differ across groups. Endorsing a deployment TBI was associated with higher anxiety to the fear cue compared to those without deployment TBI. The association of deployment TBI with increased postdeployment PTSD symptoms was mediated by postdeployment fear expression when recent prior-TBI exposure was included as a moderator. TBI associations with increased response to threat cues and PTSD symptoms remained when controlling for deployment trauma and postdeployment PTSD diagnosis. Deployment TBI, and multiple-hit TBI in particular, are associated with increases in conditioned fear learning and expression that may contribute to risk for developing PTSD symptoms. © 2017 Wiley Periodicals, Inc.

Volumetrics relate to the development of depression after traumatic brain injury.

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Maller, Jerome J; Thomson, Richard H S; Pannek, Kerstin; Bailey, Neil; Lewis, Philip M; Fitzgerald, Paul B

2014-09-01

Previous research suggests that many people who sustain a traumatic brain injury (TBI), even of the mild form, will develop major depression (MD). We previously reported white matter integrity differences between those who did and did not develop MD after mild TBI. In this current paper, we aimed to investigate whether there were also volumetric differences between these groups, as suggested by previous volumetric studies in mild TBI populations. A sample of TBI-with-MD subjects (N=14), TBI-without-MD subjects (N=12), MD-without-TBI (N=26) and control subjects (no TBI or MD, N=23), received structural MRI brain scans. T1-weighted data were analysed using the Freesurfer software package which produces automated volumetric results. The findings of this study indicate that (1) TBI patients who develop MD have reduced volume in temporal, parietal and lingual regions compared to TBI patients who do not develop MD, and (2) MD patients with a history of TBI have decreased volume in the temporal region compared to those who had MD but without a history of TBI. We also found that more severe MD in those with TBI-with-MD significantly correlated with reduced volume in anterior cingulate, temporal lobe and insula. These findings suggest that volumetric reduction to specific regions, including parietal, temporal and occipital lobes, after a mild TBI may underlie the susceptibility of these patients developing major depression, in addition to altered white matter integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

Health-related quality of life after mild, moderate and severe traumatic brain injury: patterns and predictors of suboptimal functioning during the first year after injury.

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Scholten, A C; Haagsma, J A; Andriessen, T M J C; Vos, P E; Steyerberg, E W; van Beeck, E F; Polinder, S

2015-04-01

The Glasgow Outcome Scale Extended (GOSE) is the established functional outcome scale to assess disability following traumatic brain injury (TBI), however does not capture the patient's subjective perspective. Health-related quality of life (HRQL) does capture the individual's perception of disability after TBI, and has therefore been recognized as an important outcome in TBI. In contrast to GOSE, HRQL enables comparison of health outcome across various disease states and with healthy individuals. We aimed to assess functional outcome, HRQL, recovery, and predictors of 6 and 12-month outcome in a comprehensive sample of patients with mild, moderate or severe TBI, and to examine the relationship between functional impairment (GOSE) and HRQL. A prospective cohort study was conducted among a sample of 2066 adult TBI patients who attended the emergency department (ED). GOSE was determined through questionnaires or structured interviews. Questionnaires 6 and 12 months after ED treatment included socio-demographic information and HRQL measured with Short-Form Health Survey (SF-36; reflecting physical, mental and social functioning) and Perceived Quality of Life Scale (PQoL; measuring degree of satisfaction with functioning). 996 TBI survivors with mild, moderate or severe TBI completed the 6-month questionnaire. Functional outcome and HRQL after moderate or severe TBI was significantly lower than after mild TBI. Patients with moderate TBI showed greatest improvement. After one year, the mild TBI group reached outcomes comparable to population norms. TBI of all severities highly affected SF-36 domains physical and social functioning, and physical and emotional role functioning. GOSE scores were highly related to all SF-36 domains and PQoL scores. Female gender, older age, co-morbidity and high ISS were strongest independent predictors of decreased HRQL at 6 and 12 months after TBI. HRQL and recovery patterns differ for mild, moderate and severe TBI. This study indicates

Two children with chronic progressive radiation myelopathy

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Ohta, Hideaki; Takai, Kenji; Hosoi, Gaku; Okamura, Takayuki; Osugi, Yuko; Ishihara, Shigehiko; Hara, Junichi; Tawa, Akio; Okada, Shintaro

1995-01-01

We report two patients who developed chronic progressive radiation myelopathy (CPRM). Patient 1 was a 16-year-old boy with group IV rhabdomyosarcoma of cervical soft tissue. He underwent partial excision of the tumor and received systemic and intrathecal chemotherapy and 44 Gy of local radiotherapy (C4 through Th3). These therapies were followed by high-dose chemotherapy including thio-TEPA and busulfan with autologous bone marrow rescue. One year after the completion of the therapies, he developed CPRM. Patient 2 was a 15-year-old girl with acute lymphoblastic leukemia on the 3rd complete remission. She received 18 Gy of irradiation to whole brain during the 1st remission and another 18 Gy to whole brain and 9 Gy to spinal cord after her 1st CNS relapse. After successful reinduction therapy for the 2nd relapse in CNS and bone marrow, she underwent an allogeneic bone marrow transplantation (BMT). The preconditioning regimen consisted of 12 Gy total body irradiation, thio-TEPA and cyclophosphamide. Seven months after BMT, she developed CPRM at C0-C1 level, which was included in the area of whole-brain irradiation. In both patients, MR images showed a swelling of the cervical cord and ring-like images by gadolinium enhancement. Their neurological disability transiently responded to the administration of corticosteroid, but they developed progressive quadriplegia. Although it is reported that a dose of 45-50 Gy may be safe, these cases suggest that administration of high-dose chemotherapy combined with intrathecal chemotherapy and radiotherapy to the cord might increase the rink of developing CPRM. (author)

Two children with chronic progressive radiation myelopathy

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Ohta, Hideaki; Takai, Kenji; Hosoi, Gaku; Okamura, Takayuki; Osugi, Yuko; Ishihara, Shigehiko; Hara, Junichi; Tawa, Akio; Okada, Shintaro [Osaka Univ. (Japan). Faculty of Medicine

1995-06-01

We report two patients who developed chronic progressive radiation myelopathy (CPRM). Patient 1 was a 16-year-old boy with group IV rhabdomyosarcoma of cervical soft tissue. He underwent partial excision of the tumor and received systemic and intrathecal chemotherapy and 44 Gy of local radiotherapy (C4 through Th3). These therapies were followed by high-dose chemotherapy including thio-TEPA and busulfan with autologous bone marrow rescue. One year after the completion of the therapies, he developed CPRM. Patient 2 was a 15-year-old girl with acute lymphoblastic leukemia on the 3rd complete remission. She received 18 Gy of irradiation to whole brain during the 1st remission and another 18 Gy to whole brain and 9 Gy to spinal cord after her 1st CNS relapse. After successful reinduction therapy for the 2nd relapse in CNS and bone marrow, she underwent an allogeneic bone marrow transplantation (BMT). The preconditioning regimen consisted of 12 Gy total body irradiation, thio-TEPA and cyclophosphamide. Seven months after BMT, she developed CPRM at C0-C1 level, which was included in the area of whole-brain irradiation. In both patients, MR images showed a swelling of the cervical cord and ring-like images by gadolinium enhancement. Their neurological disability transiently responded to the administration of corticosteroid, but they developed progressive quadriplegia. Although it is reported that a dose of 45-50 Gy may be safe, these cases suggest that administration of high-dose chemotherapy combined with intrathecal chemotherapy and radiotherapy to the cord might increase the rink of developing CPRM. (author).

Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

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Janna eMantua

2015-06-01

Full Text Available Individuals with a history of traumatic brain injury (TBI often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations. Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-hrs later, following an interval awake or with overnight sleep. Young adult participants (18-22 yrs were assigned to one of four experimental groups: TBI Sleep (n=14, TBI Wake (n=12, non-TBI Sleep (n=15, non-TBI Wake (n=15. Each TBI participant was >1 yr post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-hr intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation.

Is performance on the Wechsler test of adult reading affected by traumatic brain injury?

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Mathias, J L; Bowden, S C; Bigler, E D; Rosenfeld, J V

2007-11-01

The validity of the National Adult Reading Test (NART) as a predictor of premorbid IQ when used with patients who have sustained a traumatic brain injury (TBI) has been questioned in recent years. This study examined whether performance on the Wechsler Test of Adult Reading (WTAR) is similarly affected by TBI in the first year after an injury. The WTAR scores of participants who had sustained a mild TBI (N=82), moderate TBI (N=73), severe TBI (N=61) or an orthopaedic injury (N=95) were compared (cross-sectional study). A subset of 21 mild TBI, 31 moderate TBI, 26 severe TBI and 21 control group participants were additionally reassessed 6 months later to assess the impact of recovery on WTAR scores (longitudinal study). The severe TBI group had significantly lower scores on the WTAR than the mild TBI, moderate TBI and control groups in the cross-sectional study, despite being matched demographically. The findings from the longitudinal study revealed a significant group difference and a small improvement in performance over time but the interaction between group and time was not significant, suggesting that the improvements in WTAR performance over time were not restricted to more severely injured individuals whose performance was temporarily suppressed. These findings suggest that reading performance may be affected by severe TBI and that the WTAR may underestimate premorbid IQ when used in this context, which may cause clinicians to underestimate the cognitive deficits experienced by these patients.

Decreased apparent diffusion coefficient in the pituitary and correlation with hypopituitarism in patients with traumatic brain injury.

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Zheng, Ping; He, Bin; Guo, Yijun; Zeng, Jingsong; Tong, Wusong

2015-07-01

The relationship between microstructural abnormality in patients with traumatic brain injury (TBI) and hormone-secreting status remains unknown. In this study, the authors aimed to identify the role of the apparent diffusion coefficient (ADC) using a diffusion-weighted imaging (DWI) technique and to evaluate the association of such changes with hypopituitarism in patients with TBI. Diffusion-weighted images were obtained in 164 consecutive patients with TBI within 2 weeks after injury to generate the pituitary ADC as a measure of microstructural change. Patients with TBI were further grouped into those with and those without hypopituitarism based on the secretion status of pituitary hormones at 6 months postinjury. Thirty healthy individuals were enrolled in the study and underwent MRI examinations for comparison. Mean ADC values were compared between this control group, the patients with TBI and hypopituitarism, and the patients with TBI without hypopituitarism; correlational studies were also performed. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS) for all TBI patients 6 months postinjury. In the TBI group, 84 patients had hypopituitarism and 80 had normal pituitary function. The pituitary ADC in TBI patients was significantly less than that in controls (1.83 ± 0.16 vs 4.13 ± 0.33, p correlated with neurological outcome at 6 months following TBI (r = 0.602, p correlated with hormone-secreting status in TBI patients. The authors suggest that pituitary ADC may be a useful biomarker to predict pituitary function in patients with TBI.

Radiobiological speculations on therapeutic total body irradiation

International Nuclear Information System (INIS)

Vriesendorp, H.M.

1990-01-01

Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references

Hyperfractionated radiaton therapy and bis-chlorethyl nitrosourea in the treatment of malignant glioma - possible advantage observed at 72.0 Gy in 1.2 Gy B.I.D. fractions: Report of the radiation therapy oncology group protocol 8302

International Nuclear Information System (INIS)

Nelson, D.F.; Curran, W.J.; Powlis, W.D.; Scott, C.; Nelson, J.S.; Weinstein, A.S.; Ahmad, K.; Constine, L.S.; Murray, K.; Mohiuddin, M.; Fischbach, J.

1993-01-01

Between January 1983 and November 1987, the Radiation Therapy Oncology Group conducted a prospective, randomized, multi-institutional, dose searching Phase I/II trial to evaluate hyperfractionated radiation therapy in the treatment of supratentorial malignant glioma. Patients with anaplastic astrocytoma, or glioblastoma multiforme, age 18-70 years with a Karnofsky performance status of 40-100 were stratified according to age, Karnofsky performance status, and histology, and were randomized. Initially randomization was to one of three arms: 64.8 Gy, 72.0 Gy, and 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week, with intervals of 4 to 8 hr. All patients received bis-chlorethyl nitrosourea (BCNU) 80 mg/m2 on days 3, 4, 5 of radiation therapy and then every 8 weeks for 1 year. After acceptable rates of acute and late effects were found, the randomization was changed to 81.6 Gy and 72.0 Gy with a weighting of 2:1. Out of 466 patients randomized, 435 were analyzed. The distribution of prognostic factors was comparable among the 76.8 Gy arm, 81.6 Gy arm, and the final randomization of the 72 Gy arm. The 64.8 Gy arm and the initial randomization of the 72 Gy arm had somewhat worse prognostic variables. Late radiation toxicity occurred in 1.3-6.8% of the patients, with a modest increase with increasing radiation dose. The best survival occurred in those patients treated with 72 Gy. The Cox proportional hazards model confirmed the prognostic variables of age, histology and Karnofsky performance status. In addition, the longer interval of 4.5-8 hr was associated with a worse prognosis than the 4-4.4 hr interval. The difference in survival between the 81.6 Gy arm and the lower three arms approached significance with inferior survival observed in the 81.6 Gy arm. 72 Gy delivered by 1.2 Gy twice daily is no more toxic than 60 Gy delivered conventionally. 26 refs., 6 figs., 7 tabs

Sleep-wake disturbances after traumatic brain injury.

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Ouellet, Marie-Christine; Beaulieu-Bonneau, Simon; Morin, Charles M

2015-07-01

Sleep-wake disturbances are extremely common after a traumatic brain injury (TBI). The most common disturbances are insomnia (difficulties falling or staying asleep), increased sleep need, and excessive daytime sleepiness that can be due to the TBI or other sleep disorders associated with TBI, such as sleep-related breathing disorder or post-traumatic hypersomnia. Sleep-wake disturbances can have a major effect on functional outcomes and on the recovery process after TBI. These negative effects can exacerbate other common sequelae of TBI-such as fatigue, pain, cognitive impairments, and psychological disorders (eg, depression and anxiety). Sleep-wake disturbances associated with TBI warrant treatment. Although evidence specific to patients with TBI is still scarce, cognitive-behavioural therapy and medication could prove helpful to alleviate sleep-wake disturbances in patients with a TBI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Subjective and objective cognitive function among older adults with a history of traumatic brain injury: A population-based cohort study.

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Gardner, Raquel C; Langa, Kenneth M; Yaffe, Kristine

2017-03-01

Traumatic brain injury (TBI) is extremely common across the lifespan and is an established risk factor for dementia. The cognitive profile of the large and growing population of older adults with prior TBI who do not have a diagnosis of dementia, however, has not been well described. Our aim was to describe the cognitive profile associated with prior TBI exposure among community-dwelling older adults without dementia-an understudied but potentially vulnerable population. In this population-based cohort study, we studied 984 community-dwelling older adults (age 51 y and older and their spouses) without dementia who had been randomly selected from respondents to the 2014 wave of the Health and Retirement Study to participate in a comprehensive TBI survey and who either reported no prior TBI (n = 737) or prior symptomatic TBI resulting in treatment in a hospital (n = 247). Mean time since first TBI was 38 ± 19 y. Outcomes assessed included measures of global cognitive function, verbal episodic memory, semantic fluency, and calculation as well as a measure of subjective memory ("How would you rate your memory at the present time?"). We compared outcomes between the two TBI groups using regression models adjusting for demographics, medical comorbidities, and depression. Sensitivity analyses were performed stratified by TBI severity (no TBI, TBI without loss of consciousness [LOC], and TBI with LOC). Respondents with TBI were younger (mean age 64 ± 10 y versus 68 ± 11 y), were less likely to be female, and had higher prevalence of medical comorbidities and depression than respondents without TBI. Respondents with TBI did not perform significantly differently from respondents without TBI on any measure of objective cognitive function in either raw or adjusted models (fully adjusted: global cognitive function score 15.4 versus 15.2, p = 0.68; verbal episodic memory score 4.4 versus 4.3, p = 0.79; semantic fluency score 15.7 versus 14.0, p = 0.21; calculation impairment

Subjective and objective cognitive function among older adults with a history of traumatic brain injury: A population-based cohort study.

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Raquel C Gardner

2017-03-01

Full Text Available Traumatic brain injury (TBI is extremely common across the lifespan and is an established risk factor for dementia. The cognitive profile of the large and growing population of older adults with prior TBI who do not have a diagnosis of dementia, however, has not been well described. Our aim was to describe the cognitive profile associated with prior TBI exposure among community-dwelling older adults without dementia-an understudied but potentially vulnerable population.In this population-based cohort study, we studied 984 community-dwelling older adults (age 51 y and older and their spouses without dementia who had been randomly selected from respondents to the 2014 wave of the Health and Retirement Study to participate in a comprehensive TBI survey and who either reported no prior TBI (n = 737 or prior symptomatic TBI resulting in treatment in a hospital (n = 247. Mean time since first TBI was 38 ± 19 y. Outcomes assessed included measures of global cognitive function, verbal episodic memory, semantic fluency, and calculation as well as a measure of subjective memory ("How would you rate your memory at the present time?". We compared outcomes between the two TBI groups using regression models adjusting for demographics, medical comorbidities, and depression. Sensitivity analyses were performed stratified by TBI severity (no TBI, TBI without loss of consciousness [LOC], and TBI with LOC. Respondents with TBI were younger (mean age 64 ± 10 y versus 68 ± 11 y, were less likely to be female, and had higher prevalence of medical comorbidities and depression than respondents without TBI. Respondents with TBI did not perform significantly differently from respondents without TBI on any measure of objective cognitive function in either raw or adjusted models (fully adjusted: global cognitive function score 15.4 versus 15.2, p = 0.68; verbal episodic memory score 4.4 versus 4.3, p = 0.79; semantic fluency score 15.7 versus 14.0, p = 0.21; calculation

Social Environmental Moderators of Long-term Functional Outcomes of Early Childhood Brain Injury

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Wade, Shari L.; Zhang, Nanhua; Yeates, Keith Owen; Stancin, Terry; Taylor, H. Gerry

2017-01-01

IMPORTANCE Pediatric traumatic brain injury (TBI) contributes to impairments in behavior and academic performance. However, the long-term effects of early childhood TBI on functioning across settings remain poorly understood. OBJECTIVE To examine the long-term functional outcomes of early childhood TBI relative to early childhood orthopedic injuries (OIs). We also examine the moderating role of the social environment as defined by parent report and observational measures of family functioning, parenting practices, and home environment. DESIGN, SETTING, AND PARTICIPANTS A prospective, longitudinal, observational cohort study conducted at each child’s home, school, and hospital, including 3 children’s hospitals and 1 general hospital in the Midwest. Patients were enrolled in the initial study between January 2003 and October 2006. Follow-ups were completed between January 2010 and April 2015. Fifty-eight children who sustained a TBI (67%of original enrolled cohort) and 72 children who sustained an OI (61% of the original enrolled cohort) were prospectively followed up from shortly after injury (between the ages of 3 and 7 years at enrollment) to an average of 6.7 years after injury, with assessments occurring at multiple points. MAIN OUTCOMES AND MEASURES Long-term functional outcomes in everyday settings, as assessed through the Child and Adolescent Functional Assessment Scale (CAFAS). RESULTS Of the 130 children included, the median age for those with OIs was 11.72 years and 11.97, 12.21, and 11.72 years for those with complicated mild, moderate, and severe TBIs, respectively. Children with moderate and severe TBI were rated as having more functional impairments in multiple domains than those with OIs (P authoritarian (mean CAFAS of 56.45, 41.80, 54.90, and 17.12 for severe TBI, moderate TBI, complicated mild TBI, and OI, respectively, with significant difference between severe TBI and OI [difference = 39.33; P < .001], moderate TBI and OI [difference = 24

Comparison of total body irradiation-based or non-total body irradiation-based conditioning regimens for allogeneic stem cell transplantation in pediatric leukemia patients

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Sang Jeong Kim

2010-04-01

Full Text Available Purpose : This study aims to compare the outcome of total body irradiation (TBI- or non-TBI-containing conditioning regimens for leukemia in children. Methods : We retrospectively evaluated 77 children conditioned with TBI (n=40 or non-TBI (n=37 regimens, transplanted at Chonnam National University Hospital between January 1996 and December 2007. The type of transplantation, disease status at the time of transplant, conditioning regimen, engraftment kinetics, development of graft-versus-host disease (GVHD, complications, cause of deaths, overall survival (OS, and event-free survival (EFS were compared between the 2 groups. Results : Among 34 patients with acute lymphoblastic leukemia (ALL, 28 (82.4% were in the TBI group, while 72.7% (24/33 of patients with myeloid leukemia were in the non-TBI group. Although the 5-year EFS of the 2 groups was similar for all patients (62% vs 63%, the TBI group showed a better 5-year EFS than the non-TBI group when only ALL patients were analyzed (65% vs 17%; P =0.005. In acute myelogenous leukemia patients, the non-TBI group had better survival tendency (73% vs 38%; P=0.089. The incidence of GVHD, engraftment, survival, cause of death, and late complications was not different between the 2 groups. Conclusion : The TBI and non-TBI groups showed comparable results, but the TBI group showed a significantly higher 5-year EFS than the non-TBI group in ALL patients. Further prospective, randomized controlled studies involving larger number of patients are needed to assess the late-onset complications and to compare the socioeconomic quality of life.

Total-body irradiation - role and indications. Results from the German Registry for Stem Cell Transplantation (DRST)

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Heinzelmann, F.; Bamberg, M.; Belka, C.; Ottinger, H.; Mueller, C.H.; Allgaier, S.; Faul, C.

2006-01-01

Background and purpose: total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. Material and methods: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. Results: for autologous HSCT ∝10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, ∝80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, ∝35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. Conclusion: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished. (orig.)

Total-body irradiation - role and indications. Results from the German Registry for Stem Cell Transplantation (DRST)

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Heinzelmann, F.; Bamberg, M.; Belka, C. [Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Ottinger, H. [German Registry for Stem Cell Transplantation (DRST) Secretary, Univ. of Essen (Germany); Mueller, C.H.; Allgaier, S. [DRST Datacenter, DRK Bloodbank Center Ulm (Germany); Faul, C. [Dept. of Internal Medicine II, Univ. of Tuebingen (Germany)

2006-04-15

Background and purpose: total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. Material and methods: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. Results: for autologous HSCT {proportional_to}10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, {proportional_to}80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, {proportional_to}35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. Conclusion: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished. (orig.)

Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

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Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Becker, A. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Dept. of Radiotherapy, Municipial Hospital, Dessau (Germany); Bloching, M.; Passmann, M. [Dept. of Head and Neck Surgery, Martin Luther Univ., Halle (Germany); Lotterer, E. [Dept. of Internal Medicine I, Martin Luther Univ., Halle (Germany)

2003-10-01

We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m{sup 2} on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m{sup 2} twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 {+-} 61 cm{sup 3}. The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m{sup 2} paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m{sup 2} twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30

Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

International Nuclear Information System (INIS)

Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J.; Becker, A.; Bloching, M.; Passmann, M.; Lotterer, E.

2003-01-01

We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m 2 on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m 2 twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 ± 61 cm 3 . The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m 2 paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m 2 twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30 of neutropenic infection

Administration of Protocatechuic Acid Reduces Traumatic Brain Injury-Induced Neuronal Death

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Sang Hwon Lee

2017-11-01

Full Text Available Protocatechuic acid (PCA was first purified from green tea and has shown numerous biological activities, including anti-apoptotic, anti-inflammatory, and anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI-induced neuronal death has not previously been evaluated. TBI is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. TBI causes neuronal death in the hippocampus and cerebral cortex. The present study aimed to evaluate the therapeutic potential of PCA on TBI-induced neuronal death. Here, TBI was induced by a controlled cortical impact model using rats. PCA (30 mg/kg was injected into the intraperitoneal (ip space immediately after TBI. Neuronal death was evaluated with Fluoro Jade-B (FJB staining at 24 h after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE, glutathione (GSH concentration was analyzed by glutathione adduct with N-ethylmaleimide (GS-NEM staining at 24 h after TBI, and microglial activation in the hippocampus was detected by CD11b immunohistochemistry at one week after TBI. We found that the proportion of degenerating neurons, oxidative injury, GSH depletion, and microglia activation in the hippocampus and cortex were all reduced by PCA treatment following TBI. Therefore, our study suggests that PCA may have therapeutic potential in preventing TBI-induced neuronal death.

Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

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Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

2016-09-01

Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.

Energy Drinks, Alcohol, Sports and Traumatic Brain Injuries among Adolescents.

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Gabriela Ilie

Full Text Available The high prevalence of traumatic brain injuries (TBI among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI.We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption.Data were derived from the Centre for Addiction and Mental Health's 2013 Ontario Student Drug Use and Health Survey (OSDUHS. This population-based cross-sectional school survey included 10,272 7th to 12th graders (ages 11-20 who completed anonymous self-administered questionnaires in classrooms.Mild to severe TBI were defined as those resulting in a loss of consciousness for at least five minutes, or being hospitalized for at least one night. Mechanism of TBI, prevalence estimates of TBI, and odds of energy drink consumption, alcohol use, and consumption of energy drinks mixed with alcohol are assessed.Among all students, 22.4% (95% CI: 20.7, 24.1 reported a history of TBI. Sports injuries remain the main mechanism of a recent (past year TBI (45.5%, 95% CI: 41.0, 50.1. Multinomial logistic regression showed that relative to adolescents who never sustained a TBI, the odds of sustaining a recent TBI were greater for those consuming alcohol, energy drinks, and energy drinks mixed in with alcohol than abstainers. Odds ratios were higher for these behaviors among students who sustained a recent TBI than those who sustained a former TBI (lifetime but not past 12 months. Relative to recent TBI due to other causes of injury, adolescents who sustained a recent TBI while playing sports had higher odds of recent energy drinks consumption than abstainers.TBI remains a disabling and common condition among adolescents and the consumption of alcohol, energy drinks, and alcohol

Repeated mild traumatic brain injury in female rats increases lipid peroxidation in neurons.

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Yates, Nathanael J; Lydiard, Stephen; Fehily, Brooke; Weir, Gillian; Chin, Aaron; Bartlett, Carole A; Alderson, Jacqueline; Fitzgerald, Melinda

2017-07-01

Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function. We use a closed head, weight drop model of mTBI that allows head movement following impact, in adult female rats to determine the role of the number and location of mTBI on brain pathology and behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact sites were used, anterior (bregma) and posterior (lambda). Location of the impact had no significant effect on impact forces (450 N), and the weight impact locations were on average 5.4 mm from the desired impact site. No between location vertical linear head kinematic differences were observed immediately following impact, however, in the 300 ms post-impact, significantly higher mean vertical head displacement and velocity were observed in the mTBI lambda trials. Breaches of the blood brain barrier were observed with three mTBI over bregma, associated with immunohistochemical indicators of damage. However, an increased incidence of hairline fractures of the skull and macroscopic haemorrhaging made bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over lambda did not cause skull fractures and were examined more comprehensively, with outcomes following one, two or three mTBI or sham, delivered at 1 day intervals, assessed on days 1-4. We observe a mild behavioural phenotype, with subtle deficits in cognitive function, associated with no identifiable neuroanatomical or inflammatory changes. However, an increase in lipid peroxidation in a subset of cortical neurons following two mTBI indicates increasing oxidative damage with repeated injury in female rats, supported by increased amyloid precursor protein immunoreactivity with three mTBI

Differences according to Sex in Sociosexuality and Infidelity after Traumatic Brain Injury

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Jhon Alexander Moreno

2015-01-01

Full Text Available Objective. To explore differences according to sex in sociosexuality and infidelity in individuals with TBI and in healthy controls. Participants. Forty-two individuals with mild, moderate, and severe TBI having completed a postacute TBI rehabilitation program, at least six months after injury, and 47 healthy controls. Main Measures. Sociosexual Orientation Inventory-Revised (SOI-R and Attitudes toward Infidelity Scale. Results. Overall, men score significantly higher than women in sociosexuality. However, there was a nonsignificant trend towards a reduction of sociosexuality levels in men with TBI. Infidelity levels were comparable in healthy controls and individuals with TBI. In individuals with TBI, less acceptance of infidelity was significantly associated with an unrestricted sociosexual orientation, but not in healthy controls. Conclusions. As documented in previous cross-cultural studies, men have higher levels of sociosexuality than women. However, men with TBI showed a tendency towards the reduction of sociosexuality. The possibility of a latent explanatory variable is suggested (e.g., post-TBI neuroendocrinological changes. TBI does not seem to have an impact on infidelity, but individuals with TBI who express less acceptance of infidelity also report a more promiscuous mating strategy regarding their behavior, attitudes, and desire. Theoretical implications are discussed in terms of evolutionary theories of human sexuality and neuropsychology.

Differences according to Sex in Sociosexuality and Infidelity after Traumatic Brain Injury.

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Moreno, Jhon Alexander; McKerral, Michelle

2015-01-01

To explore differences according to sex in sociosexuality and infidelity in individuals with TBI and in healthy controls. Forty-two individuals with mild, moderate, and severe TBI having completed a postacute TBI rehabilitation program, at least six months after injury, and 47 healthy controls. Sociosexual Orientation Inventory-Revised (SOI-R) and Attitudes toward Infidelity Scale. Overall, men score significantly higher than women in sociosexuality. However, there was a nonsignificant trend towards a reduction of sociosexuality levels in men with TBI. Infidelity levels were comparable in healthy controls and individuals with TBI. In individuals with TBI, less acceptance of infidelity was significantly associated with an unrestricted sociosexual orientation, but not in healthy controls. As documented in previous cross-cultural studies, men have higher levels of sociosexuality than women. However, men with TBI showed a tendency towards the reduction of sociosexuality. The possibility of a latent explanatory variable is suggested (e.g., post-TBI neuroendocrinological changes). TBI does not seem to have an impact on infidelity, but individuals with TBI who express less acceptance of infidelity also report a more promiscuous mating strategy regarding their behavior, attitudes, and desire. Theoretical implications are discussed in terms of evolutionary theories of human sexuality and neuropsychology.

Anaemia worsens early functional outcome after traumatic brain injury: a preliminary study.

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Litofsky, N Scott; Miller, Douglas C; Chen, Zhenzhou; Simonyi, Agnes; Klakotskaia, Diana; Giritharan, Andrew; Feng, Qi; McConnell, Diane; Cui, Jiankun; Gu, Zezong

2018-01-01

To determine early effects on outcome from traumatic brain injury (TBI) induced by controlled cortical impact (CCI) associated with anaemia in mice. Outcome from TBI with concomitant anaemia would be worse than TBI without anaemia. CCI was induced with electromagnetic impaction in four groups of C57BL/6J mice: sham, sham+anaemia; TBI; and TBI+anaemia. Anaemia was created by withdrawal of 30% of calculated intravascular blood volume and saline replacement of equal volume. Functional outcome was assessed by beam-walking test and open field test (after pre-injury training) on post-injury days 3 and 7. After functional assessment, brains removed from sacrificed animals were pathological reviewed with haematoxylin and eosin, cresyl violet, Luxol Fast Blue, and IBA-1 immunostains. Beam-walking was similar between animals with TBI and TBI+anaemia (p = 0.9). In open field test, animals with TBI+anaemia walked less distance than TBI alone or sham animals on days 3 (p < 0.001) and 7 (p < 0.05), indicating less exploratory and locomotion behaviours. No specific pathologic differences could be identified. Anaemia associated with TBI from CCI is associated with worse outcome as measured by less distance travelled in the open field test at three days than if anaemia is not present.

Association of traumatic brain injury and Alzheimer disease onset: A systematic review.

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Julien, J; Joubert, S; Ferland, M-C; Frenette, L C; Boudreau-Duhaime, M M; Malo-Véronneau, L; de Guise, E

2017-09-01

Inconsistencies regarding the risk of developing Alzheimer disease after traumatic brain injury (TBI) remain in the literature. Indeed, why AD develops in certain TBI patients while others are unaffected is still unclear. The aim of this study was to performed a systematic review to investigate whether certain variables related to TBI, such as TBI severity, loss of consciousness (LOC) and post-traumatic amnesia (PTA), are predictors of risk of AD in adults. From 841 citations retrieved from MEDLINE via PubMed, EMBASE, PSYINFO and Cochrane Library databases, 18 studies were eligible for the review. The review revealed that about 55.5% of TBI patients may show deteriorated condition, from acute post-TBI cognitive deficits to then meeting diagnostic criteria for AD, but whether TBI is a risk factor for AD remains elusive. Failure to establish such a link may be related to methodological problems in the studies. To shed light on this dilemma, future studies should use a prospective design, define the types and severities of TBI and use standardized AD and TBI diagnostic criteria. Ultimately, an AD prediction model, based on several variables, would be useful for clinicians detecting TBI patients at risk of AD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Pathological Laughter and Crying and Psychiatric Comorbidity After Traumatic Brain Injury.

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Roy, Durga; McCann, Una; Han, Dingfen; Rao, Vani

2015-01-01

There are limited data regarding the incidence of pathological laughter and crying (PLC) after traumatic brain injury (TBI). This study aimed to identify the occurrence of PLC in the first year after TBI and to determine whether there is a relationship between PLC and other clinical features or demographics. Subjects who sustained a first-time TBI were recruited from acute trauma units and were assessed at 3, 6, and 12 months after TBI. Rates of PLC at 3, 6, and 12 months after TBI were 21.4%, 17.5%, and 15.5%, respectively. Patients with PLC had higher percentages of psychiatric diagnoses, including personality changes, depressive disorders, and mood disorders secondary to a general medical condition, as well as higher rates of posttraumatic stress disorder. Univariate logistic and linear regression analyses indicated a significant association between PLC and scores on the Clinical Anxiety Scale 3 months after TBI and on the Hamilton Depression Rating Scale 12 months after TBI. Individuals who have PLC during the first year after TBI are more likely to have any psychiatric diagnosis as well as higher rates of mood and anxiety symptoms. In addition, PLC in the early TBI period may serve as a predictor of depression and anxiety symptoms at 12 months after TBI.

Cerebral Vascular Injury in Traumatic Brain Injury.

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Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

2016-01-01

Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. Published by Elsevier Inc.

Environmental Enrichment Mitigates Deficits after Repetitive Mild Traumatic Brain Injury.

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Liu, Xixia; Qiu, Jianhua; Alcon, Sasha; Hashim, Jumana; Meehan, William P; Mannix, Rebekah

2017-08-15

Although environmental enrichment has been shown to improve functional and histologic outcomes in pre-clinical moderate-to-severe traumatic brain injury (TBI), there are a paucity of pre-clinical data regarding enrichment strategies in the setting of repetitive mild traumatic brain injury (rmTBI). Given the vast numbers of athletes and those in the military who sustain rmTBI, the mounting evidence of the long-term and progressive sequelae of rmTBI, and the lack of targeted therapies to mitigate these sequelae, successful enrichment interventions in rmTBI could have large public health significance. Here, we evaluated enrichment strategies in an established pre-clinical rmTBI model. Seventy-one male C57BL/6 mice were randomized to two different housing conditions, environmental enrichment (EE) or normal condition (NC), then subjected to rmTBI injury (seven injuries in 9 days) or sham injury (anesthesia only). Functional outcomes in all four groups (NC-TBI, EE-TBI, NC-sham, and EE-sham) were assessed by motor, exploratory/anxiety, and mnemonic behavioral tests. At the synaptic level, N-methyl d-aspartate receptor (NMDAR) subunit expression of phosphorylated glutamate receptor 1 (GluR1), phosphorylated Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), and calpain were evaluated by western blot. Compared to injured NC-TBI mice, EE-TBI mice had improved memory and decreased anxiety and exploratory activity post-injury. Treatment with enrichment also corresponded to normal NMDAR subunit expression, decreased GluR1 phosphorylation, decreased phosphorylated CaMKII, and normal calpain expression post-rmTBI. These data suggest that enrichment strategies may improve functional outcomes and mitigate synaptic changes post-rmTBI. Given that enrichment strategies are feasible in the clinical setting, particularly for athletes and soldiers for whom the risk of repetitive injury is greatest, these data suggest that clinical trials may be warranted.

Traumatic Brain Injury: Caregivers’ Problems and Needs

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syed tajjudin syed hassan; WF Khaw; AR Rosna; J Husna

2011-01-01

Traumatic brain injury (TBI) is an increasingly major world health problem. This short review using the most pertinent articles on TBI caregiving problems and needs highlights the pressing issues. Articles focusing on both TBI-caregivers’ problems and needs are rarely found, especially for developing countries. Most TBI-caregiving is done by family members, whose altered lives portend burden and stresses which add to the overwhelming demand of caring for the TBI-survivor. Lack of information,...

Alterations in autobiographical memory for a blast event in Operation Enduring Freedom and Operation Iraqi Freedom veterans with mild traumatic brain injury.

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Palombo, Daniela J; Kapson, Heather S; Lafleche, Ginette; Vasterling, Jennifer J; Marx, Brian P; Franz, Molly; Verfaellie, Mieke

2015-07-01

Although loss of consciousness associated with moderate or severe traumatic brain injury (TBI) is thought to interfere with encoding of the TBI event, little is known about the effects of mild TBI (mTBI), which typically involves only transient disruption in consciousness. Blast-exposed Afghanistan and Iraq War veterans were asked to recall the blast event. Participants were stratified based on whether the blast was associated with probable mTBI (n = 50) or not (n = 25). Narratives were scored for organizational structure (i.e., coherence) using the Narrative Coherence Coding Scheme (Reese et al., 2011) and episodic recollection using the Autobiographical Interview Coding Procedures (Levine et al., 2002). The mTBI group produced narratives that were less coherent but contained more episodic details than those of the no-TBI group. These results suggest that mTBI interferes with the organizational quality of memory in a manner that is independent of episodic detail generation. (c) 2015 APA, all rights reserved).

Intelligence after traumatic brain injury: meta-analysis of outcomes and prognosis.

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Königs, M; Engenhorst, P J; Oosterlaan, J

2016-01-01

Worldwide, 54-60 million individuals sustain traumatic brain injury (TBI) each year. This meta-analysis aimed to quantify intelligence impairments after TBI and to determine the value of age and injury severity in the prognosis of TBI. An electronic database search identified 81 relevant peer-reviewed articles encompassing 3890 patients. Full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ) impairments were quantified (Cohen's d) for patients with mild, moderate and severe TBI in the subacute phase of recovery and the chronic phase. Meta-regressions explored prognostic values of age and injury severity measures for intelligence impairments. The results showed that, in the subacute phase, FSIQ impairments were absent for patients with mild TBI, medium-sized for patients with moderate TBI (d = -0.61, P intelligence impairments, where children may have better recovery from mild TBI and poorer recovery from severe TBI than adults. Injury severity measures predict intelligence impairments and do not outperform one another. © 2015 EAN.

Morphological correlates of fractionated radiation of the mouse lung: Early and late effects

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Penney, D.P.; Siemann, D.W.; Rubin, P.; Maltby, K.

1994-01-01

The definition and quantitation of radiation-induced morphologic alterations in murine lungs is presented. The extent of injury to the lung, which is the dose-limiting organ in the thorax, may be reduced by fractionating the total radiation exposure to permit partial repair of radiation-induced damage between fraction administration and also to permit a larger total exposure to be administered. The authors previously reported that, following fractionated radiation exposures, as the dose/fraction decreases, the total dose to reach an isoeffect increases, with an α/β ratio of 3.2 and 3.0 for breathing rates and lethality, respectively. In the present report, they provide comparative morphologic evaluation of the effects of weekly fractionated, daily fractionated, and hyperfractionated radiation exposures. The doses administered within each group were uniform. To determine morphologic alterations, LAF1 mice were irradiated with 3, 15, and 30 fractions delivered in 19 days overall treatment time. In the hyperfractionation schedule, the two fractions per day were separated by a 6-h time interval. Total doses were as follows: 15-21 Gy for weekly fractionation, 30-41.5 Gy for daily fractionation, and 30-49.5 Gy for hyperfractionated schedules. Lung tissue, recovered either 24 or 72 weeks following the final exposure, was evaluated by transmission and scanning electron microscopy and light microscopy. Morphological damage was not uniform throughout the exposed lung and tended to be concentrated in lobes or portions of lobes. In the three fractionation regimens studied, there is progressive sparing of the lung with increased fractionation during the pnuemonitic state (24 weeks postirradiation). Both daily and twice daily fractionations provide increased sparing over weekly fractionation during the fibrotic stages (72 weeks postirradiation), but were not markedly different from each other (i.e. weekly < daily = twice daily). 41 refs., 15 figs., 2 tabs

Altered fractionation of hemithorax irradiation for pleural mesothelioma and failure patterns after treatment

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Holsti, L.R. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Pyrhoenen, S. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Kajanti, M. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Maentylae, M. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Mattson, K. [Dept. of Internal Medicine, Div. of Pulmonary Medicine, Helsinki University Central Hospital (Finland); Maasilta, P. [Dept. of Internal Medicine, Div. of Pulmonary Medicine, Helsinki University Central Hospital (Finland); Kivisaari, L. [Dept. of Diagnostic Radiology, Helsinki University Central Hospital (Finland)

1997-09-01

Malignant pleural mesothelioma is a rare malignancy with a bleak prognosis. The role of radiotherapy has not yet been clarified. Our aim was to study the effect of altered fractionation on mesothelioma. We have treated 57 patients, 41 males and 16 females, with hemithorax irradiation with six different fractionation schedules. All the patients have been included in a combined modality program consisting of surgery followed by chemotherapy and finally by hemithorax irradiation. The radiotherapy schedules used were: I. Conventional fractionation of 20 Gy in 10 fractions over 12 days. II, Split-course radiotherapy 55 Gy in 25 fractions of 2.2 Gy over 7 weeks (a two weeks rest halfways) followed by a boost dose of 15 Gy over 8 days to the major tumour area. III. Hyperfractionation of 70 Gy over 7 weeks, 1.25 Gy BID with a 6-h interval and a 10-day rest halfways. IV. Combined hyperfractionation and hypofractionation, 35 Gy hyperfractionation in 28 fractions (1.25 Gy BID with a 6-h interval) over three weeks followed by 36 Gy hypofractionation 9 fractions of 4 Gy given every other day over 3 weeks to the major tumour areas only. V. Hypofractionation of 38.5 Gy over 15 days (9x3.5 Gy). VI. Combined conventional radiotherapy and hypofractionation with 20 Gy given conventionally in 10 fractions followed by 10 fractions of 3 Gy over two weeks, overall time 4 weeks. The 2-year survival rate of all patients was 21% and the 5-year survival rate 9%. Two patients are still alive more than 6 and 9 years after radiotherapy. Progression occurred after surgery in four patients, during and after chemotherapy in 22 patients and after completed radiotherapy in 29 patients. The pattern of progression was similar in each treatment group. (orig.).

Effect of Intermediate-Frequency Repetitive Transcranial Magnetic Stimulation on Recovery following Traumatic Brain Injury in Rats

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Leticia Verdugo-Diaz

2017-01-01

Full Text Available Traumatic brain injury (TBI represents a significant public health concern and has been associated with high rates of morbidity and mortality. Although several research groups have proposed the use of repetitive transcranial magnetic stimulation (rTMS to enhance neuroprotection and recovery in patients with TBI, few studies have obtained sufficient evidence regarding its effects in this population. Therefore, we aimed to analyze the effect of intermediate-frequency rTMS (2 Hz on behavioral and histological recovery following TBI in rats. Male Wistar rats were divided into six groups: three groups without TBI (no manipulation, movement restriction plus sham rTMS, and movement restriction plus rTMS and three groups subjected to TBI (TBI only, TBI plus movement restriction and sham rTMS, and TBI plus movement restriction and rTMS. The movement restriction groups were included so that rTMS could be applied without anesthesia. Our results indicate that the restriction of movement and sham rTMS per se promotes recovery, as measured using a neurobehavioral scale, although rTMS was associated with faster and superior recovery. We also observed that TBI caused alterations in the CA1 and CA3 subregions of the hippocampus, which are partly restored by movement restriction and rTMS. Our findings indicated that movement restriction prevents damage caused by TBI and that intermediate-frequency rTMS promotes behavioral and histologic recovery after TBI.

Adult functioning of mothers with traumatic brain injury at high risk of child abuse: a pilot study.

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van Vliet-Ruissen, Cora; McKinlay, Audrey; Taylor, Annabel

2014-01-01

There is little information regarding the impact that traumatic brain injury (TBI) has on the functioning of mothers at risk of child abuse. This study evaluated adult functioning (e.g. child abuse, substance use, criminal convictions, and mental health problems) of mothers, at high risk for child abuse, who also had a history of TBI compared with those without TBI. It was hypothesised that mothers with a history of TBI would engage in higher rates of dysfunctional behaviour compared to those with no history of TBI. Participants were 206 women engaged in a child abuse prevention programme for mothers who are highly socially disadvantaged, and at high risk for child abuse. Using historical data collected as part of the referral, and self report intake process, this study compared child abuse, mental health problems (depression, anxiety, substance use) and rates of criminal offending for mothers with a history of TBI versus those with no history of TBI. Mothers with TBI were no more likely than those without TBI to have engaged in child abuse. However, mothers with a history of TBI were significantly more likely to have one or more mental health problems, engage in substance use and have a history of criminal offending. Parents with TBI who have been identified as high risk for engaging in child abuse have increased risk for mental health problems and criminal offending. These issues need to be considered when designing parenting programmes in order for intervention strategies to be effective.

Mild traumatic brain injury diagnosis frequently remains unrecorded in subjects with craniofacial fractures.

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Puljula, Jussi; Cygnel, Hanna; Mäkinen, Elina; Tuomivaara, Veli; Karttunen, Vesa; Karttunen, Ari; Hillbom, Matti

2012-12-01

Traumatic brain injuries (TBI) in subjects with craniofacial fractures are usually diagnosed by emergency room physicians. We investigated how often TBI remains unrecorded in these subjects, and whether diagnostic accuracy has improved after the implementation of new TBI guidelines. All subjects with craniofacial fractures admitted to Oulu University Hospital in 1999 and in 2007 were retrospectively identified. New guidelines for improving the diagnostic accuracy of TBI were implemented between 2000 and 2006. Clinical symptoms of TBI were gathered from notes on hospital charts and compared to the recorded diagnoses at discharge. Logistic regression was used to identify independent predictors for TBI to remain unrecorded. Of 194 subjects with craniofacial fracture, 111(57%) had TBI, 40 in 1999 and 71 in 2007. Fifty-one TBIs (46%) remained unrecorded at discharge, 48 being mild and 3 moderate-to-severe. Subjects with unrecorded TBI were significantly less frequently referred to follow-up visits. Failures to record the TBI diagnosis were less frequent (29/71, 41%) in 2007 than in 1999 (22/40, 55%), but the difference was not statistically significant. The most significant independent predictor for this failure was the clinical specialty (other than neurology/neurosurgery) of the examining physician (palcohol intoxication did not hamper the diagnosis of TBI. TBIs remain frequently unrecorded in subjects with craniofacial fractures. Recording of mild TBI slightly but insignificantly improved after the implementation of new guidelines. Copyright © 2012 Elsevier Ltd. All rights reserved.

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

International Nuclear Information System (INIS)

Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

1981-01-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice.

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Sabir, Meriem; Gaudreault, Pierre-Olivier; Freyburger, Marlène; Massart, Renaud; Blanchet-Cohen, Alexis; Jaber, Manar; Gosselin, Nadia; Mongrain, Valérie

2015-07-01

Traumatic brain injury (TBI), including mild TBI (mTBI), is importantly associated with vigilance and sleep complaints. Because sleep is required for learning, plasticity and recovery, we here evaluated the bidirectional relationship between mTBI and sleep with two specific objectives: (1) Test that mTBI rapidly impairs sleep-wake architecture and the dynamics of the electrophysiological marker of sleep homeostasis (i.e., non-rapid eye movement sleep delta (1-4Hz) activity); (2) evaluate the impact of sleep loss following mTBI on the expression of plasticity markers that have been linked to sleep homeostasis and on genome-wide gene expression. A closed-head injury model was used to perform a 48h electrocorticographic (ECoG) recording in mice submitted to mTBI or Sham surgery. mTBI was found to immediately decrease the capacity to sustain long bouts of wakefulness as well as the amplitude of the time course of ECoG delta activity during wakefulness. Significant changes in ECoG spectral activity during wakefulness, non-rapid eye movement and rapid eye movement sleep were observed mainly on the second recorded day. A second experiment was performed to measure gene expression in the cerebral cortex and hippocampus after a mTBI followed either by two consecutive days of 6h sleep deprivation (SD) or of undisturbed behavior (quantitative PCR and next-generation sequencing). mTBI modified the expression of genes involved in immunity, inflammation and glial function (e.g., chemokines, glial markers) and SD changed that of genes linked to circadian rhythms, synaptic activity/neuronal plasticity, neuroprotection and cell death and survival. SD appeared to affect gene expression in the cerebral cortex more importantly after mTBI than Sham surgery including that of the astrocytic marker Gfap, which was proposed as a marker of clinical outcome after TBI. Interestingly, SD impacted the hippocampal expression of the plasticity elements Arc and EfnA3 only after mTBI. Overall, our

Behavioral inhibition and activation systems in traumatic brain injury.

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Wong, Christina G; Rapport, Lisa J; Meachen, Sarah-Jane; Hanks, Robin A; Lumley, Mark A

2016-11-01

Personality has been linked to cognitive appraisal and health outcomes; however, research specific to traumatic brain injury (TBI) has been sparse. Gray's theory of behavioral inhibition system and behavioral activation system (BIS/BAS) offers a neurobiologic view of personality that may be especially relevant to neurobehavioral change associated with TBI. The present study examined theoretical and psychometric issues of using the BIS/BAS scale among adults with TBI as well as BIS/BAS personality correlates of TBI. Research Method/Design: Eighty-one adults with complicated-mild to severe TBI and 76 of their significant others (SOs) participated. Measures included the BIS/BAS scale, Positive and Negative Affect Schedule, and Awareness Questionnaire. Among adults with TBI, BIS/BAS internal consistency reliabilities were similar to those found in normative samples of adults without TBI. The TBI group endorsed significantly higher BAS than did the SO group, and injury severity was positively correlated to BAS. The SO group showed expected patterns of correlation between personality and affect; positive affect was associated with BAS, and negative affect with BIS. In contrast, in the TBI group, BAS was positively correlated to both positive and negative affect. Impaired awareness of abilities moderated the intensity of relationships between BIS/BAS and affect. TBI was associated with relatively intensified BAS (approach behavior) but not BIS (avoidance behavior). The observed pattern is consistent with the neurobiology of TBI-related personality change and with theory regarding the independence of the BIS and BAS systems. The BIS/BAS scale shows promise as a personality measure in TBI. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Time-dependent differences in cortical measures and their associations with behavioral measures following mild traumatic brain injury.

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Bajaj, Sahil; Dailey, Natalie S; Rosso, Isabelle M; Rauch, Scott L; Killgore, William D S

2018-05-01

There is currently a critical need to establish an improved understanding of time-dependent differences in brain structure following mild traumatic brain injury (mTBI). We compared differences in brain structure, specifically cortical thickness (CT), cortical volume (CV), and cortical surface area (CSA) in 54 individuals who sustained a recent mTBI and 33 healthy controls (HCs). Individuals with mTBI were split into three groups, depending on their time since injury. By comparing structural measures between mTBI and HC groups, differences in CT reflected cortical thickening within several areas following 0-3 (time-point, TP1) and 3-6 months (TP2) post-mTBI. Compared with the HC group, the mTBI group at TP2 showed lower CSA within several areas. Compared with the mTBI group at TP2, the mTBI group during the most chronic stage (TP3: 6-18 months post-mTBI) showed significantly higher CSA in several areas. All the above reported differences in CT and CSA were significant at a cluster-forming p < .01 (corrected for multiple comparisons). We also found that in the mTBI group at TP2, CT within two clusters (i.e., the left rostral middle frontal gyrus (L. RMFG) and the right postcentral gyrus (R. PostCG)) was negatively correlated with basic attention abilities (L. RMFG: r = -.41, p = .05 and R. PostCG: r = -.44, p = .03). Our findings suggest that alterations in CT and associated neuropsychological assessments may be more prominent during the early stages of mTBI. However, alterations in CSA may reflect compensatory structural recovery during the chronic stages of mTBI. © 2018 Wiley Periodicals, Inc.

Isoflurane exerts neuroprotective actions at or near the time of severe traumatic brain injury.

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Statler, Kimberly D; Alexander, Henry; Vagni, Vincent; Holubkov, Richard; Dixon, C Edward; Clark, Robert S B; Jenkins, Larry; Kochanek, Patrick M

2006-03-03

Isoflurane improves outcome vs. fentanyl anesthesia, in experimental traumatic brain injury (TBI). We assessed the temporal profile of isoflurane neuroprotection and tested whether isoflurane confers benefit at the time of TBI. Adult, male rats were randomized to isoflurane (1%) or fentanyl (10 mcg/kg iv bolus then 50 mcg/kg/h) for 30 min pre-TBI. Anesthesia was discontinued, rats recovered to tail pinch, and TBI was delivered by controlled cortical impact. Immediately post-TBI, rats were randomized to 1 h of isoflurane, fentanyl, or no additional anesthesia, creating 6 anesthetic groups (isoflurane:isoflurane, isoflurane:fentanyl, isoflurane:none, fentanyl:isoflurane, fentanyl:fentanyl, fentanyl:none). Beam balance, beam walking, and Morris water maze (MWM) performances were assessed over post-trauma d1-20. Contusion volume and hippocampal survival were assessed on d21. Rats receiving isoflurane pre- and post-TBI exhibited better beam walking and MWM performances than rats treated with fentanyl pre- and any treatment post-TBI. All rats pretreated with isoflurane had better CA3 neuronal survival than rats receiving fentanyl pre- and post-TBI. In rats pretreated with fentanyl, post-traumatic isoflurane failed to affect function but improved CA3 neuronal survival vs. rats given fentanyl pre- and post-TBI. Post-traumatic isoflurane did not alter histopathological outcomes in rats pretreated with isoflurane. Rats receiving fentanyl pre- and post-TBI had the worst CA1 neuronal survival of all groups. Our data support isoflurane neuroprotection, even when used at the lowest feasible level before TBI (i.e., when discontinued with recovery to tail pinch immediately before injury). Investigators using isoflurane must consider its beneficial effects in the design and interpretation of experimental TBI research.

A preliminary model for posttraumatic brain injury depression.

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Malec, James F; Brown, Allen W; Moessner, Anne M; Stump, Timothy E; Monahan, Patrick

2010-07-01

To develop, based on previous research, and evaluate a model for depression after traumatic brain injury (TBI). Cross-sectional structural equation modeling (SEM) of data from consecutively recruited patients. Acute hospital and inpatient rehabilitation units. Adult patients (N=158) after hospital admission for moderate to severe TBI. Not applicable. External appraisal of ability in participants was measured by the Mayo-Portland Adaptability Inventory (MPAI-4) Ability Index completed by a TBI clinical nurse specialist. Patient self-appraisal of post-TBI ability and depression were measured by the Awareness Questionnaire and Beck Depression Inventory-II. Functional outcome 1 year after injury was assessed with the MPAI-4 Participation Index. Successive SEM resulted in a parsimonious model with excellent fit. Consistent with prior research, a moderately strong association between self-appraisal of post-TBI ability and depression was found. Injury severity, as measured by the duration of posttraumatic amnesia (PTA), was not significantly associated with post-TBI depression. The 1-year functional outcome was associated with depression and TBI severity. The strong association between self-appraisal of post-TBI ability and depression is consistent with the cognitive-behavioral model of depression and recommends consideration and further study of cognitive-behavioral therapy for post-TBI depression. The lack of association between TBI severity and depression may represent the indirect and proxy nature of current measures of TBI severity such as PTA. Emerging neuroimaging techniques (eg, diffusion tensor imaging, magnetic resonance imaging spectroscopy) may provide the more direct measures of disruption of brain function after TBI that are needed to advance this line of research. Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The Effects of Female Sex Steroids on Gastric Secretory Responses of Rat Following Traumatic Brain Injury

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Zakieh Keshavarzi

2011-05-01

Full Text Available AbstractObjective(sGastric ulceration is induced by various forms of stress like surgery, ischemia and trauma. The female sex has more resistance to stress and the gastrointestinal lesions happen fewer than male sex. The purpose of this study was to evaluate the role of estradiol and progesterone on the gastric acid and pepsin levels following traumatic brain injury (TBI induction.Materials and MethodsDiffuse TBI was induced by Marmarou method in female rats. Rats randomly assigned into 9 groups: intact, OVX (ovarectomized rat, Sham+OVX, TBI (intact rats under TBI, TBI+OVX (ovarectomized rats under TBI and treated OVX rats with vehicle (sesame oil, E2 (estradiol, P4 (progesterone or E2+P4 combination. The acid content and pepsin levels of each gastric washout sample were measured 5 days after the TBI induction.ResultsThere was no significant difference in gastric acid output between groups either after TBI induction or after treatment with E2 or P4 or E2+P4. Gastric pepsin levels were increased in Sham+OVX, TBI (P< 0.001 and TBI+OVX (P< 0.05 compared to intact group. Gastric pepsin levels were significantly lower in E2 and E2+ P4 treated rats than vehicle treated group (P< 0.01. P4 treatment increased gastric pepsin level compared to TBI+OVX group (P< 0.05 and this increment was higher than rats that were treated with the E2 and E2+P4 (P< 0.01.ConclusionThese results suggest that protective effect of estradiol and E2+P4 combination against mucosal damage after TBI, might be mediated by inhibition of pepsin secretion.