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Sample records for therapy improves survival

  1. Adjuvant Medications That Improve Survival after Locoregional Therapy.

    Science.gov (United States)

    Boas, F Edward; Ziv, Etay; Yarmohammadi, Hooman; Brown, Karen T; Erinjeri, Joseph P; Sofocleous, Constantinos T; Harding, James J; Solomon, Stephen B

    2017-07-01

    To determine if outpatient medications taken at the time of liver tumor embolization or ablation affect survival. A retrospective review was done of 2,032 liver tumor embolization, radioembolization, and ablation procedures performed in 1,092 patients from June 2009 to April 2016. Pathology, hepatocellular carcinoma (HCC) stage (American Joint Committee on Cancer), neuroendocrine tumor (NET) grade, initial locoregional therapy, overall survival after initial locoregional therapy, Child-Pugh score, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index, and outpatient medications taken at the time of locoregional therapy were analyzed for each patient. Kaplan-Meier survival curves were calculated for patients taking 29 medications or medication classes (including prescription and nonprescription medications) for reasons unrelated to their primary cancer diagnosis. Kaplan-Meier curves were compared using the log-rank test. For patients with HCC initially treated with embolization (n = 304 patients), the following medications were associated with improved survival when taken at the time of embolization: beta-blockers (P = .0007), aspirin (P = .0008) and other nonsteroidal antiinflammatory drugs (P = .009), proton pump inhibitors (P = .004), and antivirals for hepatitis B or C (P = .01). For colorectal liver metastases initially treated with ablation (n = 172 patients), beta-blockers were associated with improved survival when taken at the time of ablation (P = .02). Aspirin and beta-blockers are associated with significantly improved survival when taken at the time of embolization for HCC. Aspirin was not associated with survival differences after locoregional therapy for NET or colorectal liver metastases, suggesting an HCC-specific effect. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  2. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

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    Coventry BJ

    2015-04-01

    had died. Published studies of melanoma therapies were tabled for comparison. Conclusion: The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself. Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches. Keywords: advanced melanoma, clinical responses, immunotherapy, prolonged survival

  3. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

    2015-01-01

    . Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches

  4. Survival improvement in patients with disseminated medullary thyroid carcinoma treated with 131I-MIBG therapy

    International Nuclear Information System (INIS)

    Mihaljevic, I.; Topuzovi, N.; Snajder, D.

    2015-01-01

    Full text of publication follows. Introduction and aim: The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of medullary thyroid carcinoma (MTC) with local and distant metastases. MTC is an uncommon thyroid tumor, accounting from 3-5% of all thyroid malignancies, and arises from para-follicular C cells which produce calcitonin (CT). Prognosis of MTC is related to tumor extension at disease detection, but long-term survival in patients with disseminated MTC is still unsatisfactory. Methods: 4 female patients with metastatic MTC (63, 69 and 2 patients aged 73 years), which already underwent total thyroidectomy and selective neck dissection, received therapy with 100 mCi 131 I-MIBG in our Institute. Patients had widespread disease with neck recurrences (all 4 cases), liver and bone metastases (2 cases) and lung metastases (1 case). All those patients received the therapy twice, second one 3 months up to 1 year after the first cycle. After therapy, whole body scintigraphy was performed; tumor marker levels (CT, carcinoembryonic antigen - CEA, neuron specific enolase - NSE, chromogranin A - CgA and pro-gastrin releasing peptide - pro-GRP) were measured before and after therapy. Results: in one patient we observed a slight decrease in CT level after first MIBG therapy, in another one a slight decrease in CEA serum level, and no lung metastases were visible on whole body scan after second 131 I-MIBG therapy. In one of the two remaining cases there was a significant decrease in CT serum level only after neck dissection. In all cases the patients reported an improvement in subjective symptom reduction. Conclusion: 131 I-MIBG therapy could provide additional benefit to patients with MTC and could improve overall survival, but more patient should be treated in order to define the true potential of the therapy. The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of

  5. Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

    Science.gov (United States)

    Eeles, Rosalind A; Morden, James P; Gore, Martin; Mansi, Janine; Glees, John; Wenczl, Miklos; Williams, Christopher; Kitchener, Henry; Osborne, Richard; Guthrie, David; Harper, Peter; Bliss, Judith M

    2015-12-10

    To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life. © 2015 by American Society of Clinical Oncology.

  6. High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease.

    Science.gov (United States)

    Foley, T Raymond; Singh, Gagan D; Kokkinidis, Damianos G; Choy, Ho-Hin K; Pham, Thai; Amsterdam, Ezra A; Rutledge, John C; Waldo, Stephen W; Armstrong, Ehrin J; Laird, John R

    2017-07-15

    The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P =0.14). Demographics including age (68±12 versus 67±10 years, P =0.25), smoking history (76% versus 80%, P =0.42), diabetes mellitus (54% versus 48%, P =0.17), and hypertension (88% versus 89%, P =0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P =0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P =0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P =0.02). In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

    Science.gov (United States)

    Liao, Yueh-Hsiang; Li, Chia-Ing; Lin, Cheng-Chieh; Lin, Jaung-Geng; Chiang, Jen-Huai; Li, Tsai-Chung

    2017-12-01

    Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

  8. Improved Survival With Radiation Therapy in High-Grade Soft Tissue Sarcomas of the Extremities: A SEER Analysis

    International Nuclear Information System (INIS)

    Koshy, Matthew; Rich, Shayna E.; Mohiuddin, Majid M.

    2010-01-01

    Purpose: The benefit of radiation therapy in extremity soft tissue sarcomas remains controversial. The purpose of this study was to determine the effect of radiation therapy on overall survival among patients with primary soft tissue sarcomas of the extremity who underwent limb-sparing surgery. Methods and Materials: A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from January 1, 1988, to December 31, 2005. A total of 6,960 patients constituted the study population. Overall survival curves were constructed using the Kaplan-Meir method and for patients with low- and high-grade tumors. Hazard ratios were calculated based on multivariable Cox proportional hazards models. Results: Of the cohort, 47% received radiation therapy. There was no significant difference in overall survival among patients with low-grade tumors by radiation therapy. In high-grade tumors, the 3-year overall survival was 73% in patients who received radiation therapy vs. 63% for those who did not receive radiation therapy (p < 0.001). On multivariate analysis, patients with high-grade tumors who received radiation therapy had an improved overall survival (hazard ratio 0.67, 95% confidence interval 0.57-0.79). In patients receiving radiation therapy, 13.5% received it in a neoadjuvant setting. The incidence of patients receiving neoadjuvant radiation did not change significantly between 1988 and 2005. Conclusions: To our knowledge, this is the largest population-based study reported in patients undergoing limb-sparing surgery for soft tissue sarcomas of the extremities. It reports that radiation was associated with improved survival in patients with high-grade tumors.

  9. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

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    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  10. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    International Nuclear Information System (INIS)

    Barker, Christopher A.; Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A.

    2013-01-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted

  11. Augmented therapy of extensive Hodgkin's disease: radiation to bulk disease or prolongation of induction chemotherapy did not improve survival

    International Nuclear Information System (INIS)

    Rafla, S.; Coleman, M.; Propert, K.; Glicksman, A.; Peterson, B.; Nissen, N.; Brunner, K.; Kaufmann, T.; Holland, J.; Anderson, J.; Gottlieb, A.

    1996-01-01

    Purpose: This prospective, randomized trial in extensive, untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to 'bulk' disease) compared to standard, six months chemotherapy. Materials and Methods: Two-hundred fifty-eight patients, mostly stage IV, were randomized to four treatment regimens consisting of 6 cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; 6 cycles of CVPP followed by 25 Gray (Gy) radiotherapy; or 3 cycles CVPP, 25 Gy radiotherapy, and 3 cycles CVPP. Results: Complete remissions were achieved in 65% of all patients. A 58% overall 5 year survival was obtained. Relapses in irradiated areas of bulk disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease free survival or overall survival amongst the four regimens. Elderly patients responded less frequently. Conclusion: While radiotherapy provided control of local (bulk) disease, no impact on overall survival was apparent. Likewise doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit when compared to the standard six months of treatment

  12. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

    International Nuclear Information System (INIS)

    Kinuya, Seigo; Yokoyama, Kunihiko; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki

    2004-01-01

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131 I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P 131 I-A7 RIT displayed a marked therapeutic effect (n=8) (P 131 I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P 131 I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  13. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

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    Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

    2016-03-15

    Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

  14. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2016-06-01

    Euthanasia 24 hours Euthanasia 72 hours Normal Saline 2 2 20% DMSO 2 2 BHB/M 1:10 2 2 BHB/M 1:5 2 2 BHB/M 1:2 2 2 BHB/M 1:1...and processed using H&E staining. 4 Table 2. Completed Randomization Groups Randomization Euthanasia 24 hours Euthanasia 72 hours Normal Saline 2...contribution o the individual components of BHB/M to the toxicity profile of the product at MTD. Observation of the preservation of survival benefit

  15. Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis

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    Abrams, Matthew J., E-mail: mabrams@tuftsmedicalcenter.org [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Koffer, Paul P. [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Wazer, David E. [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (United States); Hepel, Jaroslaw T. [Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (United States)

    2017-06-01

    Purpose: Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Methods and Materials: The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. Results: A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor–positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). Conclusions: There may be a survival benefit with the

  16. Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

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    Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

    2017-07-01

    Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  17. Radiation therapy improves survival in rectal small cell cancer - Analysis of Surveillance Epidemiology and End Results (SEER) data.

    Science.gov (United States)

    Modrek, Aram S; Hsu, Howard C; Leichman, Cynthia G; Du, Kevin L

    2015-04-24

    Small cell carcinoma of the rectum is a rare neoplasm with scant literature to guide treatment. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of radiation therapy in the treatment of this cancer. The SEER database (National Cancer Institute) was queried for locoregional cases of small cell rectal cancer. Years of diagnosis were limited to 1988-2010 (most recent available) to reduce variability in staging criteria or longitudinal changes in surgery and radiation techniques. Two month conditional survival was applied to minimize bias by excluding patients who did not survive long enough to receive cancer-directed therapy. Patient demographics between the RT and No_RT groups were compared using Pearson Chi-Square tests. Overall survival was compared between patients who received radiotherapy (RT, n = 43) and those who did not (No_RT, n = 28) using the Kaplan-Meier method. Multivariate Cox proportional hazards model was used to evaluate important covariates. Median survival was significantly longer for patients who received radiation compared to those who were not treated with radiation; 26 mo vs. 8 mo, respectively (log-rank P = 0.009). We also noted a higher 1-year overall survival rate for those who received radiation (71.1% vs. 37.8%). Unadjusted hazard ratio for death (HR) was 0.495 with the use of radiation (95% CI 0.286-0.858). Among surgery, radiotherapy, sex and age at diagnosis, radiation therapy was the only significant factor for overall survival with a multivariate HR for death of 0.393 (95% CI 0.206-0.750, P = 0.005). Using SEER data, we have identified a significant survival advantage with the use of radiation therapy in the setting of rectal small cell carcinoma. Limitations of the SEER data apply to this study, particularly the lack of information on chemotherapy usage. Our findings strongly support the use of radiation therapy for patients with locoregional small cell rectal cancer.

  18. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels.

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    Vyas, Dinesh; Javadi, Pardis; Dipasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-10-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P 14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P 14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.

  19. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

    Science.gov (United States)

    Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-01-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

  20. Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

    LENUS (Irish Health Repository)

    2011-04-01

    Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study.

  1. Intracranial AAV-IFN-β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model.

    Science.gov (United States)

    GuhaSarkar, Dwijit; Neiswender, James; Su, Qin; Gao, Guangping; Sena-Esteves, Miguel

    2017-02-01

    The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard-of-care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon-beta (IFN-β) gene therapy by locally administered adeno-associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models. First, we show that a single intracranial injection of AAV encoding human IFN-β eliminates invasive human GBM8 tumors and promotes long-term survival. Next, we screened five AAV-IFN-β vectors with different promoters to drive safe expression of mouse IFN-β in the brain in the context of syngeneic GL261 tumors. Two AAV-IFN-β vectors were excluded due to safety concerns, but therapeutic studies with the other three vectors showed extensive tumor cell death, activation of microglia surrounding the tumors, and a 56% increase in median survival of the animals treated with AAV/P2-Int-mIFN-β vector. We also assessed the therapeutic effect of combining AAV-IFN-β therapy with temozolomide (TMZ). As TMZ affects DNA replication, an event that is crucial for second-strand DNA synthesis of single-stranded AAV vectors before active transcription, we tested two TMZ treatment regimens. Treatment with TMZ prior to AAV-IFN-β abrogated any benefit from the latter, while the reverse order of treatment doubled the median survival compared to controls. These studies demonstrate the therapeutic potential of intracranial AAV-IFN-β therapy in a highly migratory GBM model as well as in a syngeneic mouse model and that combination with TMZ is likely to enhance its antitumor potency. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  2. Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2014-01-01

    Full Text Available Exposure to ionizing radiation alone (RI or combined with traumatic tissue injury (CI is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral followed by 15% total-body-surface-area skin wounds (R-W CI or burns (R-B CI experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit.

  3. Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma.

    Science.gov (United States)

    Watanabe, Shinichi; Kuwabara, Yui; Suehiro, Satoshi; Yamashita, Daisuke; Tanaka, Mamoru; Tanaka, Akihiro; Ohue, Shiro; Araki, Hiroaki

    2017-03-01

    Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS). Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

  4. Memory and survival after microbeam radiation therapy

    International Nuclear Information System (INIS)

    Schueltke, Elisabeth; Juurlink, Bernhard H.J.; Ataelmannan, Khalid; Laissue, Jean; Blattmann, Hans; Braeuer-Krisch, Elke; Bravin, Alberto; Minczewska, Joanna; Crosbie, Jeffrey; Taherian, Hadi; Frangou, Evan; Wysokinsky, Tomasz; Chapman, L. Dean; Griebel, Robert; Fourney, Daryl

    2008-01-01

    Background: Disturbances of memory function are frequently observed in patients with malignant brain tumours and as adverse effects after radiotherapy to the brain. Experiments in small animal models of malignant brain tumour using synchrotron-based microbeam radiation therapy (MRT) have shown a promising prolongation of survival times. Materials and methods: Two animal models of malignant brain tumour were used to study survival and memory development after MRT. Thirteen days after implantation of tumour cells, animals were submitted to MRT either with or without adjuvant therapy (buthionine-SR-sulfoximine = BSO or glutamine). We used two orthogonal 1-cm wide arrays of 50 microplanar quasiparallel microbeams of 25 μm width and a center-to-center distance of about 200 μm, created by a multislit collimator, with a skin entrance dose of 350 Gy for each direction. Object recognition tests were performed at day 13 after tumour cell implantation and in monthly intervals up to 1 year after tumour cell implantation. Results: In both animal models, MRT with and without adjuvant therapy significantly increased survival times. BSO had detrimental effects on memory function early after therapy, while administration of glutamine resulted in improved memory

  5. Improving Survival in Decompensated Cirrhosis

    Directory of Open Access Journals (Sweden)

    Amar Nath Mukerji

    2012-01-01

    Full Text Available Mortality in cirrhosis is consequent of decompensation, only treatment being timely liver transplantation. Organ allocation is prioritized for the sickest patients based on Model for End Stage Liver Disease (MELD score. In order to improve survival in patients with high MELD score it is imperative to preserve them in suitable condition till transplantation. Here we examine means to prolong life in high MELD score patients till a suitable liver is available. We specially emphasize protection of airways by avoidance of sedatives, avoidance of Bilevel Positive Airway Pressure, elective intubation in grade III or higher encephalopathy, maintaining a low threshold for intubation with lesser grades of encephalopathy when undergoing upper endoscopy or colonoscopy as pre transplant evaluation or transferring patient to a transplant center. Consider post-pyloric tube feeding in encephalopathy to maintain muscle mass and minimize risk of aspiration. In non intubated and well controlled encephalopathy, frequent physical mobility by active and passive exercises are recommended. When renal replacement therapy is needed, night-time Continuous Veno-Venous Hemodialysis may be useful in keeping the daytime free for mobility. Sparing and judicious use of steroids needs to be borne in mind in treatment of ARDS and acute hepatitis from alcohol or autoimmune process.

  6. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    International Nuclear Information System (INIS)

    Breslow, Norman E.; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-01-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes

  7. Brachytherapy Improves Biochemical Failure–Free Survival in Low- and Intermediate-Risk Prostate Cancer Compared With Conventionally Fractionated External Beam Radiation Therapy: A Propensity Score Matched Analysis

    International Nuclear Information System (INIS)

    Smith, Graham D.; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Vigneault, Eric; Cury, Fabio L.; Morris, Jim; Catton, Charles; Lukka, Himu; Warner, Andrew; Yang, Ying; Rodrigues, George

    2015-01-01

    Purpose: To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone. Methods and Materials: Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups. Results: Propensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500). Conclusions: Propensity score matched analysis showed that BT options led

  8. Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery

    Directory of Open Access Journals (Sweden)

    Sarah E. Sinnett

    2017-06-01

    Full Text Available Intravenous administration of adeno-associated virus serotype 9 (AAV9/hMECP2 has been shown to extend the lifespan of Mecp2−/y mice, but this delivery route induces liver toxicity in wild-type (WT mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the cisterna magna (ICM. AAV9/hMECP2 (1 × 1012 viral genomes [vg]; ICM extended Mecp2−/y survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 1012 vg of AAV9/hMECP2 induced clasping and abnormal gait. A lower dose mitigated these adverse phenotypes but failed to extend survival of Mecp2−/y mice. Thus, ICM delivery of this vector is impractical as a treatment for Rett syndrome (RTT. To improve the safety of MeCP2 gene therapy, the gene expression cassette was modified to include more endogenous regulatory elements believed to modulate MeCP2 expression in vivo. In Mecp2−/y mice, ICM injection of the modified vector extended lifespan and was well tolerated by the liver but did not rescue RTT behavioral phenotypes. In WT mice, these same doses of the modified vector had no adverse effects on survival or neurological phenotypes. In summary, we identified limitations of the original vector and demonstrated that an improved vector design extends Mecp2−/y survival, without apparent toxicity.

  9. Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: a study based on nationwide Korean Breast Cancer Registry database.

    Science.gov (United States)

    Hwang, Ki-Tae; Kim, Eun-Kyu; Jung, Sung Hoo; Lee, Eun Sook; Kim, Seung Il; Lee, Seokwon; Park, Heung Kyu; Kim, Jongjin; Oh, Sohee; Kim, Young A

    2018-06-01

    To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.

  10. Hyperbaric oxygen therapy and surgical delay improve flap survival of reverse pedicle flaps for lower third leg and foot reconstruction

    Directory of Open Access Journals (Sweden)

    Pradeoth Mukundan Korambayil

    2015-06-01

    Full Text Available Aim: The purpose of the study is to present a management protocol for various types of soft tissue defects of the distal third region of leg and foot treated with pedicle flaps, by including hyperbaric oxygen (HBO therapy in the treatment regimen with flap delay. Methods: We present a prospective study of 23 patients with various types of soft tissue defects of the foot, and lower third of leg managed in our institution from December 2012 to December 2013. All soft tissue defects were treated by a reverse pedicle flap. Twelve patients were managed with flap delay with HBO therapy and 11 patients with immediate flaps without HBO therapy. The postoperative period, hospital course, and follow-up were documented. Results: Of 12 patients with flap delay and HBO, 10 patients did not suffer any complications secondary to flap transfer. One patient had discoloration of the tip of the flap, which settled without the intervention, and 1 patient had recurrent abscess formation, which required debridement and closure. Of 11 patients with direct transfer, 6 patients presented with complications including flap congestion, partial flap loss, and tip necrosis, which required secondary intervention. Conclusion: HBO therapy is a useful adjunct in flap delay of the reverse pedicle flap for soft tissue reconstruction of the lower third of the leg and foot regions.

  11. Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Matthew W., E-mail: matthew.jackson@ucdenver.edu [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Rusthoven, Chad G.; Jones, Bernard L. [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Kamdar, Manali [Department of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States); Rabinovitch, Rachel [Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, Colorado (United States)

    2016-01-01

    Background: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. Methods and Materials: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. Results: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. Conclusion: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early

  12. Improving fish survival through turbines

    International Nuclear Information System (INIS)

    Ferguson, J.W.

    1993-01-01

    Much of what is known about fish passage through hydroturbines has been developed by studying migratory species of fish passing through large Kaplan turbine units. A review of the literature on previous fish passage research presented in the accompanying story illustrates that studies have focused on determining mortality levels, rather than identifying the causal mechanism involved. There is a need for understanding how turbine designs could be altered to improve fish passage conditions, how to retrofit existing units, and how proposed hydro plant operational changes may affect fish survival. The US Army Corps of Engineers has developed a research program to define biologically based engineering criteria for improving fish passage conditions. Turbine designs incorporating these criteria can be evaluated for their effects on fish survival, engineering issues, costs, and power production. The research program has the following objectives: To gain a thorough knowledge of the mechanisms of fish mortality; To define the biological sensitivities of key fish species to these mechanisms of mortality; To develop new turbine design criteria to reduce fish mortality; To construct prototype turbine designs, and to test these designs for fish passage, hydro-mechanical operation, and power production; and To identify construction and power costs associated with new turbine designs

  13. Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

    DEFF Research Database (Denmark)

    Sørensen, Anne V.; Donskov, Frede; Hermann, Gregers G.

    2014-01-01

    AbstractAim To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). Methods All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between...

  14. Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

    Science.gov (United States)

    Chen, V L; Yeh, M-L; Le, A K; Jun, M; Saeed, W K; Yang, J D; Huang, C-F; Lee, H Y; Tsai, P-C; Lee, M-H; Giama, N; Kim, N G; Nguyen, P P; Dang, H; Ali, H A; Zhang, N; Huang, J-F; Dai, C-Y; Chuang, W-L; Roberts, L R; Jun, D W; Lim, Y-S; Yu, M-L; Nguyen, M H

    2018-07-01

    Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed. © 2018 John Wiley & Sons Ltd.

  15. Augmented therapy of extensive Hodgkin's disease: radiation to known disease or prolongation of induction chemotherapy did not improve survival--results of a cancer and leukemia group B study

    International Nuclear Information System (INIS)

    Coleman, Morton; Rafla, Sameer; Propert, Kathleen J.; Glicksman, Arvin; Peterson, Bruce; Nissen, Nis; Brunner, Kurt; Holland, James F.; Anderson, James R.; Gottlieb, Arlan; Kaufman, Thomas

    1998-01-01

    Purpose: This prospective randomized trial in extensive untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to known disease) compared to standard 6 months chemotherapy. Patient and Methods: A total of 258 patients, mostly Stage IV, were randomized to four treatment regimens consisting of six cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy, and three cycles CVPP. Results: Complete remissions were achieved in 65% of all patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated areas of known disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease-free survival, or overall survival among the four regimens. Elderly patients responded less frequently. Conclusion: While radiotherapy provided control of local (known) disease, no impact on overall survival was apparent. Likewise, doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit compared to the standard 6 months of treatment

  16. Complementary Chinese herbal medicine therapy improves survival of patients with gastric cancer in Taiwan: A nationwide retrospective matched-cohort study.

    Science.gov (United States)

    Hung, Kuo-Feng; Hsu, Ching-Ping; Chiang, Jen-Huai; Lin, Hung-Jen; Kuo, Yi-Ting; Sun, Mao-Feng; Yen, Hung-Rong

    2017-03-06

    Many patients with gastric cancer seek traditional medicine consultations in Asian countries. This study aimed to investigate the prescription of Chinese herbal medicine (CHM) and its benefits for the patients with gastric cancer in Taiwan. From the Registry for Catastrophic Illness Patients Database, we included all patients with gastric cancer whose age at diagnosis was ≥18 from 1997 to 2010 in Taiwan. We used 1:1 frequency matching by age, sex, Charlson comorbidity score, treatment and index year to compare the CHM users and non-CHM users. We used the Cox regression model to compare the hazard ratios (HR) for the risk of mortality and the Kaplan-Meier curve for the survival time. There was a total of 1333 patients in the CHM-cohort and 44786 patients in the non-CHM cohort. After matching, we compared 962 newly diagnosed CHM users and 962 non-CHM users. Adjusted HRs (aHR) were higher among patients of above 60-year-old group, with a Charlson Comorbidity Index score ≥2 before the index date, and those who need surgery combined with chemotherapy or radiotherapy. CHM users had a lower HR of mortality risk (adjusted HR: 0.55, 95% CI: 0.48-0.62). Compared to the non-CHM users, the aHR among CHM-users is 0.37 (95% CI:0.2-0.67) for those who used CHM more than 180 days annually. The Kaplan-Meier curve revealed that the survival probability was higher for complementary CHM-users. Bai-Hua-She-She-Cao (Herba Hedyotidis Diffusae) was the most commonly used single herb and Xiang-Sha-Liu-Jun-Zi-Tang was the most commonly used herbal formula among CHM prescriptions. Complementary CHM improves the overall survival among patients with gastric cancer in Taiwan. Further ethnopharmacological investigations and clinical trials are required to validate the efficacy and safety. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Prasongsook, Naiyarat; Kumar, Aditi; Chintakuntlawar, Ashish V; Foote, Robert L; Kasperbauer, Jan; Molina, Julian; Garces, Yolanda; Ma, Daniel; Wittich, Michelle A Neben; Rubin, Joseph; Richardson, Ronald; Morris, John; Hay, Ian; Fatourechi, Vahab; McIver, Bryan; Ryder, Mabel; Thompson, Geoffrey; Grant, Clive; Richards, Melanie; Sebo, Thomas J; Rivera, Michael; Suman, Vera; Jenkins, Sarah M; Smallridge, Robert C; Bible, Keith C

    2017-12-01

    Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease. Copyright © 2017 Endocrine Society

  18. Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

    Science.gov (United States)

    Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

    2017-10-01

    To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a

  19. Improved survival after rectal cancer in Denmark

    DEFF Research Database (Denmark)

    Bülow, S; Harling, H; Iversen, L H

    2010-01-01

    Objective In 1995, an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group (DCCG) was established with the aim of improving the prognosis, and in this study we present a survival analysis of patients...... treated from 1994 to 2006. Method The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival. Results A total of 10 632 patients were...

  20. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Paximadis, Peter, E-mail: ppaximad@med.wayne.edu [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States); Yoo, George; Lin, Ho-Sheng; Jacobs, John [Department of Otolaryngology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Sukari, Ammar [Department of Medical Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Dyson, Greg [Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Christensen, Michael; Kim, Harold [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States)

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  1. Combinatorial gene therapy renders increased survival in cirrhotic rats

    Directory of Open Access Journals (Sweden)

    Armendáriz-Borunda Juan S

    2010-05-01

    Full Text Available Abstract Background Liver fibrosis ranks as the second cause of death in México's productive-age population. This pathology is characterized by acummulation of fibrillar proteins in hepatic parenchyma causing synthetic and metabolic disfunction. Remotion of excessive fibrous proteins might result in benefit for subjects increasing survival index. The goal of this work was to find whether the already known therapeutical effect of human urokinase Plasminogen Activator and human Matrix Metalloprotease 8 extends survival index in cirrhotic animals. Methods Wistar rats (80 g underwent chronic intoxication with CCl4: mineral oil for 8 weeks. Cirrhotic animals were injected with a combined dose of Ad-delta-huPA plus Ad-MMP8 (3 × 1011 and 1.5 × 1011 vp/Kg, respectively or with Ad-beta-Gal (4.5 × 1011 and were killed after 2, 4, 6, 8 and 10 days. Then, liver and serum were collected. An additional set of cirrhotic animals injected with combined gene therapy was also monitored for their probability of survival. Results Only the cirrhotic animals treated with therapeutical genes (Ad-delta-huPA+Ad-MMP-8 showed improvement in liver fibrosis. These results correlated with hydroxyproline determinations. A significant decrement in alpha-SMA and TGF-beta1 gene expression was also observed. Cirrhotic rats treated with Ad-delta-huPA plus Ad-MMP8 had a higher probability of survival at 60 days with respect to Ad-beta-Gal-injected animals. Conclusion A single administration of Ad-delta-huPA plus Ad-MMP-8 is efficient to induce fibrosis regression and increase survival in experimental liver fibrosis.

  2. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia.

    Science.gov (United States)

    Tamma, Pranita D; Han, Jennifer H; Rock, Clare; Harris, Anthony D; Lautenbach, Ebbing; Hsu, Alice J; Avdic, Edina; Cosgrove, Sara E

    2015-05-01

    The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of

  3. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-01-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10

  4. Improved survival for women with stage I breast cancer in south-east Sweden: A comparison between two time periods before and after increased use of adjuvant systemic therapy

    International Nuclear Information System (INIS)

    Johansson, Patrik; Fohlin, Helena; Arnesson, Lars-Gunnar

    2009-01-01

    Purpose. Continuous minor steps of improvement in the management of breast cancer have resulted in decreased mortality rates during the last decades. The aim of this study was to compare the clinical outcome of patients with stage I breast cancer diagnosed during two time periods that differed with respect to adjuvant systemic therapy. Material and methods. The studied population consisted of all women < 60 years of age, who were diagnosed breast cancer stage I between 1986 and 1999 in south-east Sweden, a total of 1 407 cases. The cohort was divided into two groups based on the management programmes of 1986 and 1992, hereafter referred to as Period 1 and Period 2. Before 1992 the only adjuvant systemic therapy recommended was tamoxifen for hormone receptor positive patients aged 50 years or older. During Period 2 the use of adjuvant treatment was extended to younger patients at high risk, identified by a high tumour S-phase fraction, with either hormonal or cytotoxic treatment. Results. The estimated distant recurrence-free survival rate was significantly higher during Period 2 than during Period 1 (p = 0.008). Subgroup analysis showed that the most evident reduction of distant recurrence risk was among hormone receptor-negative patients (HR = 0.58, 95% CI 0.31-1.09, p = 0.09) and among patients with a high tumour S-phase fraction (HR = 0.53, 0.30-0.93, p = 0.028). The risk reduction between the periods was still statistically significant in multivariate analysis when adjusting for different tumour characteristics and treatment modalities, indicating an influence of other factors not controlled for. One such factor may be the duration of tamoxifen treatment, which likely was more frequently five years during Period 2 than during Period 1. Conclusions. We conclude that the causes of the increase in distant recurrence free survival for women with breast cancer stage I are complex. The results support though that high-risk subgroups of stage I breast cancer patients

  5. Survival of lung cancer patients after combined therapy with hyperglycemia

    International Nuclear Information System (INIS)

    Zharkov, V.V.; Demidchik, Yu.E.; Khodina, T.V.

    1991-01-01

    The results of a randomized study of combined therapy of lung cancer patients including large field radiotherapy (total irradiation of 20 Gy, daily fractionation of 4 Gy) and induced hyperglycemia (22-23 mmol/1) are presented. The use of new variants of combined therapy was shown to increase significantly the survival of patients, however therapeutic efficacy was different depending on the time of hyperglycemia: wheter it was used before radiotherapy sessions of after their discontinuation

  6. How can survival processing improve memory encoding?

    Science.gov (United States)

    Luo, Meng; Geng, Haiyan

    2013-11-01

    We investigated the psychological mechanism of survival processing advantage from the perspective of false memory in two experiments. Using a DRM paradigm in combination with analysis based on signal detection theory, we were able to separately examine participants' utilization of verbatim representation and gist representation. Specifically, in Experiment 1, participants rated semantically related words in a survival scenario for a survival condition but rated pleasantness of words in the same DRM lists for a non-survival control condition. The results showed that participants demonstrated more gist processing in the survival condition than in the pleasantness condition; however, the degree of item-specific processing in the two encoding conditions did not significantly differ. In Experiment 2, the control task was changed to a category rating task, in which participants were asked to make category ratings of words in the category lists. We found that the survival condition involved more item-specific processing than did the category condition, but we found no significant difference between the two encoding conditions at the level of gist processing. Overall, our study demonstrates that survival processing can simultaneously promote gist and item-specific representations. When the control tasks only promoted either item-specific representation or gist representation, memory advantages of survival processing occurred.

  7. Effects of highly active antiretroviral therapy on the survival of HIV ...

    African Journals Online (AJOL)

    Recent improvements in access to Anti-Retroviral Therapy (ART) have radically reduced hospitalizations and deaths associated with HIV infection in both developed countries and sub-Saharan Africa. Not much is known about survival of patients on ART in slums. The objective of this study was to identify factors associated ...

  8. Home visit program improves technique survival in peritoneal dialysis.

    Science.gov (United States)

    Martino, Francesca; Adıbelli, Z; Mason, G; Nayak, A; Ariyanon, W; Rettore, E; Crepaldi, Carlo; Rodighiero, Mariapia; Ronco, Claudio

    2014-01-01

    Peritoneal dialysis (PD) is a home therapy, and technique survival is related to the adherence to PD prescription at home. The presence of a home visit program could improve PD outcomes. We evaluated its effects on clinical outcome during 1 year of follow-up. This was a case-control study. The case group included all 96 patients who performed PD in our center on January 1, 2013, and who attended a home visit program; the control group included all 92 patients who performed PD on January 1, 2008. The home visit program consisted of several additional visits to reinforce patients' confidence in PD management in their own environment. Outcomes were defined as technique failure, peritonitis episode, and hospitalization. Clinical and dialysis features were evaluated for each patient. The case group was significantly older (p = 0.048), with a lower grade of autonomy (p = 0.033), but a better hemoglobin level (p = 0.02) than the control group. During the observational period, we had 11 episodes of technique failure. We found a significant reduction in the rate of technique failure in the case group (p = 0.004). Furthermore, survival analysis showed a significant extension of PD treatment in the patients supported by the home visit program (52 vs. 48.8 weeks, p = 0.018). We did not find any difference between the two groups in terms of peritonitis and hospitalization rate; however, trends toward a reduction of Gram-positive peritonitis rates as well as prevalence and duration of hospitalization related to PD problems were identified in the case group. The retrospective nature of the analysis was a limitation of this study. The home visit program improves the survival of PD patients and could reduce the rate of Gram-positive peritonitis and hospitalization. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=365168.

  9. Locoregional control and survival after breast conserving therapy

    International Nuclear Information System (INIS)

    Rajer, M.; Majdic, E.

    2006-01-01

    Background. The purpose of our study was to present a 5-year survival and locoregional control rates in breast cancer patients and to establish eventual impact of the treatment and patient characteristics on locoregional control and survival. Methods. From January 1998 to December 1999 564 stage 1 and 2 breast cancer patients were treated with breast conserving therapy. We evaluated the following characteristics: age, histological diagnosis, grade, size, number of metastatic lymph nodes, hormonal receptor status, extensive intraductal component (EIDC), vascular invasion, pathologic tumour margins, type of surgery and use of adjuvant therapy. Results. The mean age of our patients was 54.2 years. Invasive ductal carcinoma was the most common diagnosis (82.4%), followed by invasive lobular carcinoma (10.6%). Most of the tumours were grade 2. Seventy-two % of patients had T1 tumours, 24% T2 and 3% T is tumours. Metastatic lymph nodes were present in 44% of patients. All patients were treated with breast conserving surgery followed by radiotherapy (RT). Fifty % of patients received adjuvant chemotherapy and/ or hormonal therapy. The 5-year survival rate was 88.5%. Tumour size, number of metastatic lymph nodes, grade, hormonal receptors and vascular invasion proved to be statistically significant prognostic factors for the survival, while age and histological diagnosis were not. Local recurrence developed in 4.3% of our patients, while in 3.4% regional recurrence developed. Conclusions. Breast conserving surgery followed by RT was associated with good rates of locoregional control and survival, comparable to those reported in the literature. (author)

  10. The effect of carbon dioxide therapy on composite graft survival.

    Science.gov (United States)

    Durães, Eliana Ferreira Ribeiro; Durães, Leonardo de Castro; Carneiro, Fabiana Pirani; Lino, Ruy de Souza; Sousa, João Batista de

    2013-08-01

    To investigate the effect of carboxytherapy in auricular composite grafts in rabbits. An experimental study was conducted using 20 rabbits randomly assigned to a treatment group of carboxytherapy or a control group of saline solution. In each ear, a circular graft with 1.5 cm or 2 cm of diameter was amputated and reattached. Animals underwent carbon dioxide or saline injection four times during the experiment. We analyzed clinical evolution of the animals, grafts survival, histopathology features and histomorphometry of collagen. The treated group had a significantly lower weight gain (p=0.038). Histopathology was not significantly different between groups. There was an increase in amount of collagen in 2 cm grafts submitted to carbon dioxide therapy (p=0.003). Carboxytherapy didn't influence graft survival rate for 1.5 cm grafts or 2 cm grafts (p=0.567 and p=0.777, respectively). Carbon dioxide therapy increased the amount of collagen in 2 cm grafts. CO2 was not significantly different from saline infusion on composite grafts survival, but this study suggests that there is a mechanical effect caused by distension which favored graft survival.

  11. Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates

    International Nuclear Information System (INIS)

    Malzoni, Carlos Eduardo

    1996-01-01

    The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author)

  12. Improved survival for multiple myeloma in denmark based on autologous stem cell transplantation and novel drug therapy in collaborative trials: analysis of accrual, prognostic variables, selection bias, and clinical behavior on survival in more than 1200 patients in trials of the nordic myeloma study group

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Klausen, Tobias W; Boegsted, Martin

    2010-01-01

    An unexplained survival difference was observed in the Nordic Myeloma Study Group (NMSG) high-dose therapy trial 5/94 in Denmark compared with Sweden and Norway; however, this difference was eliminated in the subsequent NMSG trial 7/98. It was hypothesized that a detailed analysis of potential ex...

  13. Strategies to improve macroencapsulated islet graft survival

    OpenAIRE

    Sörenby, Anne

    2007-01-01

    Chronic immunosuppressive therapy may have severe side-effects. In cell transplantation, the graft can be encapsulated within a membrane chamber, providing a physical barrier against the immune system. The cell graft then becomes dependent on the diffusion of nutrients and oxygen from the surrounding microcirculation. A major drawback has been the formation of avascular fibrotic tissue around the chamber. The immunoprotective device studied (TheraCyte ) has an outer membrane...

  14. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  15. The impact of adjuvant radiation therapy on survival in women with uterine carcinosarcoma

    International Nuclear Information System (INIS)

    Clayton Smith, D.; Kenneth Macdonald, O.; Gaffney, David K.

    2008-01-01

    Background and purpose: Uterine carcinosarcoma is an aggressive neoplasm and the benefit of adjuvant radiation therapy (RT) is unclear. This retrospective study analyzes the influence of RT on survival using a large population database. Materials and methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute. Women with uterine carcinosarcoma who underwent primary surgery were eligible. Survival rates and multivariate analyses were performed by standard methods. Results: Of the 2461 women in the analysis, 890 received adjuvant RT. Five-year rates of overall survival were 41.5% and 33.2% (P < 0.001) and uterine-specific survival were 56.0% and 50.8% (P = 0.005), for women receiving RT compared to those who did not. Women with stages I-III disease experienced a benefit in overall survival (HR 0.87, P = 0.03) while women with stage IV disease experienced benefits in overall (HR 0.63, P < 0.001) and uterine-specific survival (HR 0.63, P = 0.004) with RT. Conclusions: RT predicted for improved overall and disease specific survival in women with uterine carcinosarcoma within the SEER database. The benefit in disease specific survival was restricted to stage IV disease. These benefits may indicate a role for adjuvant RT in future prospective trials in the treatment of uterine carcinosarcoma

  16. Play Therapy: Role in Reading Improvement.

    Science.gov (United States)

    Carmichael, Karla

    1991-01-01

    Reviews the literature concerning the role of play therapy (particularly sandplay and nondirected play therapy) in the improvement of reading. Suggests that the role of play therapy is to support the child, encourage the child, and build self-esteem thus creating the optimal learning environment for reading improvement. (RS)

  17. Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Ottosen, Tobias Pilgaard; Grijota, Miriam; Hansen, Morten Lock

    2016-01-01

    inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality......BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage...... and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were...

  18. Improved outcome in solitary bone plasmacytomata with combined therapy.

    Science.gov (United States)

    Avilés, A; Huerta-Guzmán, J; Delgado, S; Fernández, A; Díaz-Maqueo, J C

    1996-09-01

    Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease-free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow-up of 8.9 years, disease-free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p radiotherapy in patients with SBP improved duration of remission and survival without severe side-effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

  19. Dying scenarios improve recall as much as survival scenarios.

    Science.gov (United States)

    Burns, Daniel J; Hart, Joshua; Kramer, Melanie E

    2014-01-01

    Merely contemplating one's death improves retention for entirely unrelated material learned subsequently. This "dying to remember" effect seems conceptually related to the survival processing effect, whereby processing items for their relevance to being stranded in the grasslands leads to recall superior to that of other deep processing control conditions. The present experiments directly compared survival processing scenarios with "death processing" scenarios. Results showed that when the survival and dying scenarios are closely matched on key dimensions, and possible congruency effects are controlled, the dying and survival scenarios produced equivalently high recall levels. We conclude that the available evidence (cf. Bell, Roer, & Buchner, 2013; Klein, 2012), while not definitive, is consistent with the possibility of overlapping mechanisms.

  20. Parental care improves offspring survival and growth in burying beetles

    Science.gov (United States)

    Eggert; Reinking; MULLER

    1998-01-01

    Burying beetles (genus Nicrophorus) provide elaborate parental care to their offspring. Parental beetles defend a small vertebrate carcass, which constitutes the sole food source for the larvae. They also manipulate the carcass in various ways and directly regurgitate pre-digested carrion to the young. The benefits of carcass manipulation and regurgitation have been the subject of a few small-scale studies that have yielded conflicting results. In this study, we investigated the benefits of these behaviours and tested for possible beneficial effects on larval survival rates and final body mass in N. vespilloides. In this species: (1) larval survival and mass were significantly higher in broods receiving parental care throughout larval development on the carcass than in broods developing in the absence of adults; (2) parental presence immediately subsequent to larval hatching greatly improved larval survival rates; (3) continued parental presence for several days further improved larval growth, leading to a greater final mass of individual larvae; (4) larval survival and growth were improved by parental preparation of carcasses and by an excision made in the integument of the carcass surface by the parents that allows the larvae ready access to their food; (5) positive effects of parental feeding on larval survival and growth were not mediated by the transfer of symbionts. Copyright 1998 The Association for the Study of Animal Behaviour.

  1. Improved survival in HIV treatment programs in Asia

    Science.gov (United States)

    De La Mata, Nicole L; Kumarasamy, Nagalingeswaran; Khol, Vohith; Ng, Oon Tek; Van Nguyen, Kinh; Merati, Tuti Parwati; Pham, Thuy Thanh; Lee, Man Po; Durier, Nicolas; Law, Matthew

    2016-01-01

    Background Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last ten years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia. Methods We included HIV-positive adult patients who initiated ART between 2003–2013 (n=16 546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 count at ART initiation, and CD4 and HIV viral load testing frequencies. Results There were 880 deaths observed over 54 532 person-years of follow-up, a crude rate of 1.61 (1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probabilities at 4 years follow-up for those initiating ART in 2003–05 was 92.1%, 2006–09 was 94.3% and 2010–2013 was 94.5% (pAsia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment and, patient management and monitoring over time. PMID:26961354

  2. Survival Benefit of Adjuvant Radiation Therapy for Gastric Cancer following Gastrectomy and Extended Lymphadenectomy

    Directory of Open Access Journals (Sweden)

    R. A. Snyder

    2012-01-01

    Full Text Available Purpose. Although randomized trials suggest a survival benefit of adjuvant chemotherapy and radiation therapy (XRT for gastric adenocarcinoma, its use in patients who undergo an extended lymphadenectomy is less clear. The purpose of this study was to determine if a survival benefit exists in gastric cancer patients who receive adjuvant XRT following resection with extended lymphadenectomy. Methods. The SEER registry was queried for records of patients with resected gastric adenocarcinoma from 1988 to 2007. Multivariable Cox regression models were used to assess independent prognostic factors affecting overall survival (OS and disease-specific survival (DSS. Results. Of 15,060 patients identified, 3,208 (21% received adjuvant XRT. Adjuvant XRT was independently associated with improved OS (HR 0.67, CI 0.64–0.71 and DSS (HR 0.69, CI 0.65–0.73 in stages IB through IV (M0. This OS and DSS benefit persisted regardless of the extent of lymphadenectomy. Furthermore, lymphadenectomy with >25 LN resected was associated with improved OS and DSS compared with 25 LNs results in improved OS and DSS compared with patients who have fewer LNs resected.

  3. ABO blood type correlates with survival on prostate cancer vaccine therapy.

    Science.gov (United States)

    Muthana, Saddam M; Gulley, James L; Hodge, James W; Schlom, Jeffrey; Gildersleeve, Jeffrey C

    2015-10-13

    Immunotherapies for cancer are transforming patient care, but clinical responses vary considerably from patient to patient. Simple, inexpensive strategies to target treatment to likely responders could substantially improve efficacy while simultaneously reducing health care costs, but identification of reliable biomarkers has proven challenging. Previously, we found that pre-treatment serum IgM to blood group A (BG-A) correlated with survival for patients treated with PROSTVAC-VF, a therapeutic cancer vaccine in phase III clinical trials for the treatment of prostate cancer. These results suggested that ABO blood type might influence efficacy. Unfortunately, blood types were not available in the clinical records for all but 8 patients and insufficient amounts of sera were left for standard blood typing methods. To test the hypothesis, therefore, we developed a new glycan microarray-based method for determining ABO blood type. The method requires only 4 μL of serum, provides 97% accuracy, and allows simultaneous profiling of many other serum anti-glycan antibodies. After validation with 220 healthy subjects of known blood type, the method was then applied to 74 PROSTVAC-VF patients and 37 control patients from a phase II trial. In this retrospective study, we found that type B and O PROSTVAC-VF patients demonstrated markedly improved clinical outcomes relative to A and AB patients, including longer median survival, longer median survival relative to Halabi predicted survival, and improved overall survival via Kaplan-Meier survival analysis (p = 0.006). Consequently, blood type may provide an inexpensive screen to pre-select patients likely to benefit from PROSTVAC-VF therapy.

  4. Improving adherence to antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Nischal K

    2005-01-01

    Full Text Available Antiretroviral therapy (ART has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen′s pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression, lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.

  5. Cyber Foraging for Improving Survivability of Mobile Systems

    Science.gov (United States)

    2016-02-10

    Cyber-Foraging for Improving Survivability of Mobile Systems Sebastián Echeverría ( Universidad de los Andes) Grace A. Lewis James Root Ben...NUMBERS FA8721-05-C-0003 6. AUTHOR(S) Sebastián Echeverría ( Universidad de los Andes), Grace A. Lewis, James Root, & Ben Bradshaw 7. PERFORMING

  6. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    International Nuclear Information System (INIS)

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-01-01

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16 INK , p21 and p19 ARF . VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI

  7. Will Incremental Hemodialysis Preserve Residual Function and Improve Patient Survival?

    Science.gov (United States)

    Davenport, Andrew

    2015-01-01

    The progressive loss of residual renal function in peritoneal dialysis patients is associated with increased mortality. It has been suggested that incremental dialysis may help preserve residual renal function and improve patient survival. Residual renal function depends upon both patient related and dialysis associated factors. Maintaining patients in an over-hydrated state may be associated with better preservation of residual renal function but any benefit comes with a significant risk of cardiovascular consequences. Notably, it is only observational studies that have reported an association between dialysis patient survival and residual renal function; causality has not been established for dialysis patient survival. The tenuous connections between residual renal function and outcomes and between incremental hemodialysis and residual renal function should temper our enthusiasm for interventions in this area. PMID:25385441

  8. Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

    International Nuclear Information System (INIS)

    Bingham, Brian; Orton, Andrew; Boothe, Dustin; Stoddard, Greg; Huang, Y. Jessica; Gaffney, David K.; Poppe, Matthew M.

    2017-01-01

    Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

  9. Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, Brian [Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee (United States); Orton, Andrew; Boothe, Dustin [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Stoddard, Greg [Division of Epidemiology, University of Utah, Salt Lake City, Utah (United States); Huang, Y. Jessica; Gaffney, David K. [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Poppe, Matthew M., E-mail: Matthew.poppe@hci.utah.edu [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States)

    2017-04-01

    Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

  10. [Survival in acute renal failure with conventional therapy or continuous replacement therapy].

    Science.gov (United States)

    Santibáñez-Velázquez, Martín; Sánchez-Montoya, Felipe; Alvirde-Gutiérrez, Luis

    2014-01-01

    To know the survival rate in patients with RIFLE I and II stages on acute renal failure, treated with supportive care or continuous renal replacement therapy with PRISMA machine, at an intensive care unit. There were included patients of both sexes, aged 16 to 69 years, with acute renal failure in RIFLE I and II stages and score of scale APACHE II lower than 36 points. The sample studied was divided in two groups: a group was treated with supportive care, and the other group received continuous renal replacement therapy via PRISMA machine. We compared mortality between both groups and the association with the RIFLE stages with Pearson's chi-squared test. The average score of the scale APACHE I was 14 points, and the probability of death was 15 %. The patients with acute renal failure RIFLE I were 54.5 % and RIFLE II 45.5 %, with mortality of 30.4 % and 38.8 %, respectively. Patients in RIFLE I stage who received supportive care and continuous replacement therapy had non-statistical differences in mortality (p = 0.356). The mortality in patients with acute renal failure in RIFLE II stage treated with continuous replacement therapy was higher (p = 0.000). Because of its accessibility and lower mortality, supportive care should be the initial procedure in patients with acute renal failure in RIFLE I and II stages.

  11. Hepatorenal Syndrome: Outcome of Response to Therapy and Predictors of Survival

    Directory of Open Access Journals (Sweden)

    Jan Heidemann

    2015-01-01

    Full Text Available Aim. Treatment of hepatorenal syndrome (HRS in patients with liver cirrhosis is still challenging and characterized by a very high mortality. This study aimed to delineate treatment patterns and clinical outcomes of patients with HRS intravenously treated with terlipressin. Methods. In this retrospective single-center cohort study, 119 patients (median [IQR]; 56.50 [50.75–63.00] years of age with HRS were included. All patients were treated with terlipressin and human albumin intravenously. Those with response to treatment (n=65 were compared to the patient cohort without improvement (n=54. Patient characteristics and clinical parameters (Child stage, ascites, hepatic encephalopathy, HRS type I/II, and initial MELD score were retrieved. Univariate analysis of factors influencing the success of terlipressin therapy and Cox regression analysis of factors influencing survival was carried out. Results. One-month survival was significantly longer in the group of responders (p=0.048. Cox regression analysis identified age [Hazard ratio, 95% confidence interval (CI; 1.05, 1.01–1.09, resp.], alcohol abuse [HR 3.05, 95% CI 1.11–8.38], duration of treatment [HR 0.92, 95% CI 0.88–0.96], and MELD score [HR 1.08, 95% CI 1.02–1.14] to be independent predictors of survival. Conclusions. Survival of HRS patients after treatment depends on age, etiology of liver disease, and the duration of treatment.

  12. Pravastatin But Not Simvastatin Improves Survival and Neurofunctional Outcome After Cardiac Arrest and Cardiopulmonary Resuscitation

    Directory of Open Access Journals (Sweden)

    Stefan Bergt, MD

    2017-04-01

    Full Text Available Summary: Cardiac arrest (CA followed by cardiopulmonary resuscitation (CPR is associated with high mortality and poor neurological outcome. We compared the effects of pravastatin and simvastatin on survival and neurofunction in a murine model of CA/CPR. Pravastatin, a hydrophilic statin, increased survival and neurofunction during a 28-day follow-up period. This therapy was associated with improved pulmonary function, reduced pulmonary edema, and increased endothelial cell function in vitro. In contrast, lipophilic simvastatin did not modulate survival but increased pulmonary edema and impaired endothelial cell function. Although pravastatin may display a therapeutic option for post-CA syndrome, the application of simvastatin may require re-evaluation. Key Words: cardiac arrest, endothelial cell function, ischemia and reperfusion injury, pravastatin, resuscitation, simvastatin

  13. Androgen deprivation does predict bNED survival in unfavorable prostate cancer PTS treated with external beam radiation therapy

    International Nuclear Information System (INIS)

    Anderson, Penny R.; Hanlon, Alexandra L.; Hanks, Gerald E.

    1996-01-01

    therapy. Figure 1 presents a comparison of bNED survival according to treatment using the 214 matched case/controls and Kaplan-Meier methodology. It supports the finding that hormonal therapy translates to improved bNED survival (at 5 yrs, 55% vs 37%, p=.0001) although there is not survival advantage. Multivariate analysis demonstrates that hormonal treatment is the most significant independent predictor of bNED survival (p 15) benefit from adjuvant hormonal therapy. 2) Upon multivariate analysis, hormonal therapy is determined to be the most significant predictor of bNED survival, followed by prerx PSA and palpation stage. 3) The 5-yr bNED survival rates of 55% for RT+H vs 37% for RT alone clearly demonstrate that those pts do benefit from adjuvant hormone therapy. 4) The bNED survival curves are separated by about 20 mos, representing a delay in disease progression with adjuvant hormonal therapy

  14. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

    Science.gov (United States)

    Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

    2016-04-07

    Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

  15. Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

    Science.gov (United States)

    Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

    2017-01-06

    Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor -alpha (TNF-α), prostaglandin E₂ (PGE₂) , and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice ( n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

  16. Combining Gene Signatures Improves Prediction of Breast Cancer Survival

    Science.gov (United States)

    Zhao, Xi; Naume, Bjørn; Langerød, Anita; Frigessi, Arnoldo; Kristensen, Vessela N.; Børresen-Dale, Anne-Lise; Lingjærde, Ole Christian

    2011-01-01

    Background Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123) and test set (n = 81), respectively. Gene sets from eleven previously published gene signatures are included in the study. Principal Findings To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014). Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001). The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. Conclusion Combining the predictive strength of multiple gene signatures improves prediction of breast

  17. Combining gene signatures improves prediction of breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  18. End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

    Science.gov (United States)

    Gill, Sharlene; Sargent, Daniel

    2006-06-01

    The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

  19. Concurrent chemoradiotherapy improves survival outcome in muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon

    2015-01-01

    To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer

  20. Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

    Science.gov (United States)

    Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

    2010-01-01

    Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

  1. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013

    DEFF Research Database (Denmark)

    Trickey, Adam; May, Margaret T.; Vehreschild, Jorg Janne

    2017-01-01

    Background Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year...... survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013. Methods We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between...... ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART. Findings 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second...

  2. Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study.

    Science.gov (United States)

    Amit, Moran; Yen, Tzu-Chen; Liao, Chun-Ta; Chaturvedi, Pankaj; Agarwal, Jai Prakash; Kowalski, Luiz P; Ebrahimi, Ardalan; Clark, Jonathan R; Kreppel, Matthias; Zöller, Joachim; Fridman, Eran; Bolzoni, Villaret A; Shah, Jatin P; Binenbaum, Yoav; Patel, Snehal G; Gil, Ziv

    2013-12-15

    An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established. This was a retrospective, longitudinal, international, population-based study of 2738 patients who underwent resection of OCSCC during 2 different decades. Characteristics of patients from 7 international cancer centers who received treatment between 1990 and 2000 (group A; n = 735) were compared with patients who received treatment between 2001 and 2011 (group B; n = 2003). Patients in group B had more advanced tumors and tended to develop distant metastases more frequently than patients in group A (P = .005). More group B patients underwent selective neck dissection and received adjuvant radiotherapy (P < .001). Outcome analysis revealed a significant improvement in 5-year overall survival, from 59% for group A to 70% for group B (P < .001). There was also a significant improvement in disease-specific survival associated with operations performed before and after 2000 (from 69% to 81%, respectively; P < .001). Surgery after 2000, negative margins, adjuvant treatment, and early stage disease were independent predictors of a better outcome in multivariate analysis. The decade of treatment was an independent prognostic factor for cancer-specific mortality (hazard ratio, 0.42; 95% confidence interval, 0.3-0.6). The survival rate of patients with OCSCC improved significantly during the past 2 decades despite older age, more advanced disease stage, and a higher rate of distant metastases. The current results suggest that the prognosis for patients with OCSCC has improved over time, presumably because of advances in imaging and therapy. © 2013 American Cancer Society.

  3. [Medulloblastoma: improved survival in recent decades. Unicentric experience].

    Science.gov (United States)

    Igual Estellés, Lucía; Berlanga Charriel, Pablo; Cañete Nieto, Adela

    2017-01-01

    The aim of the study is to analyse variations in the treatment of medulloblastoma, the most common childhood brain tumour, and its impact on survival over the past two decades, as well as its clinical and pathological features. Survival analysis of all patients under 14 years old diagnosed with medulloblastoma between January 1990 and December 2013 in a Paediatric Oncology Unit. Sixty-three patients were diagnosed and treated for medulloblastoma, with a median follow-up of 5.1 years (range 0.65-21.7 years). The overall survival (OS) at 3 and 5 years was 66±13% and 55±14%, respectively. The OS at 5 years was 44%±25% in patients diagnosed in the 1990's, showing an increase to 70%±23% (p=0.032) since 2000. Clinical prognosis factors were included in the logistic regression model: age (p=0.008), presence of metastases and/or residual tumour (p=0.007), and receiving chemotherapy with radiotherapy after surgery (p=0.008). Statistically significant differences were observed for all of them. In our institution there has been a significant increase in medulloblastoma survival in the last decades. Multivariate analysis showed that this improvement was not related to the date of diagnosis, but with the introduction of chemotherapy in adjuvant treatment. This study confirmed that clinical factors significantly associated with worse outcome were age and presence of metastases at diagnosis. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Post-mastectomy radiation therapy and overall survival after neoadjuvant chemotherapy.

    Science.gov (United States)

    Kantor, Olga; Pesce, Catherine; Singh, Puneet; Miller, Megan; Tseng, Jennifer; Wang, Chi-Hsiung; Winchester, David J; Yao, Katharine

    2017-05-01

    The role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) and mastectomy is unclear, especially in patients that have post-treatment tumor negative axillary nodes (ypN0). The National Cancer Data Base was used to identify women that had PMRT after NAC and mastectomy for clinically node positive (cN1-2) disease from 2004 to 2008. Median follow-up time was 69 months. 8,321 patients were included for analysis, and 6140 (65.6%) had cN1 disease and 2181 (23.3%) had cN2 disease. On adjusted survival analysis, PMRT was associated with an overall survival (OS) benefit in both patients with cN1 (5-yr OS 75.8% vs. 71.9%, P  0.11) for PMRT compared to those patients who were not ypN0, except for patients with hormone-receptor negative tumors, who had improved OS with PMRT (HR 0.65, P < 0.01). PMRT is associated with improved OS in patients with cN1 and cN2 disease after NAC and mastectomy. However, in the subgroup of patients that were ypN0 after NAC, PMRT improved OS for hormone-receptor negative patients but not hormone-receptor positive patients. © 2017 Wiley Periodicals, Inc.

  5. The survival analysis on localized prostate cancer treated with neoadjuvant endocrine therapy followed by intensity modulated radiation therapy

    International Nuclear Information System (INIS)

    Gao Hong; Li Gaofeng; Wu Qinhong; Li Xuenan; Zhong Qiuzi; Xu Yonggang

    2010-01-01

    Objective: To retrospectively investigate clinical outcomes and prognostic factors in localized prostate cancer treated with neoadjuvant endocrine therapy followed by intensity modulated radiotherapy (IMRT). Methods: Between March 2003 and October 2008, 54 localized prostate cancer treated by IMRT were recruited. All patients had received endocrine therapy before IMRT. The endocrine therapy included surgical castration or medical castration in combination with antiandrogens. The target of IMRT was the prostate and seminal vesicles with or without pelvis. The biochemical failure was defined according to the phoenix definition. By using the risk grouping standard proposed by D'Amico, patients were divided into three groups: low-risk group (n = 5), intermediate-risk group (n = 12), and high-risk group (n = 37). Kaplan-Meier method was used to calculate the overall survival rate. Prognostic factors were analyzed by univariate and multiple Cox regression analysis. Results: The follow-up rate was 98%. The number of patients under follow-up was 39 at 3 years and 25 at 5 years. Potential prognostic factors, including risk groups, mode of endocrine therapy, time of endocrine therapy, phoenix grouping before IMRT, the prostate specific antigen doubling time (PSADT) before radiotherapy, PSA value before IMRT, interval of endocrine therapy and IMRT, irradiation region, and irradiation dose were analyzed by survival analysis. In univariate analysis, time of endocrine therapy (75 % vs 95 %, χ 2 = 6. 45, P = 0. 011), phoenix grouping before IMRT (87% vs 96%, χ 2 = 4. 36, P = 0. 037), interval of endocrine therapy and IMRT (80% vs 95%, χ 2 = 11.60, P= 0. 001), irradiation dose (75% vs 91%, χ 2 =5.92, P= 0. 015) were statistically significant prognostic factors for 3 - year overall survival , and risk groups (85 vs 53 vs 29, χ 2 = 6. 40, P =0. 041) and PSADT before IMRT (62 vs 120, U =24. 50, P =0. 003) were significant factors for the median survival time. In the multiple Cox

  6. Improved exercise myocardial perfusion during lidoflazine therapy

    International Nuclear Information System (INIS)

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-01-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise

  7. Survival and Complication Rate of Radiation Therapy in Stage I and II Carcinoma of uterine Cervix

    International Nuclear Information System (INIS)

    Ma, Sun Young; Cho, Heung Lea; Sohn, Seung Chang

    1995-01-01

    difference for survival rate or bladder complication incidence as a function of dose to whole pelvis, Grade 2 rectal complication incidence was significantly lower for the patients receiving less than 4500cGy(6.3% v 25.5%, p<0.05). There was no significant difference between HDR ICRT group and LDR ICRT group for survival rate according to stage, on the other hand complication incidence was higher in the HDR group than LDR group. This was maybe due to different prescription doses between HDR group and LDR group. Midline shield neither improved survival rate nor deceased complication rate. The number of insertion in LDR ICRT group did not affect on survival and complication rate. Conclusion : In stage I and II carcinoma of uterine cervix, there was no significant difference for 5 year survival rate by radiation therapy technique. Rectal complication incidence was as a function of dose to whole pelvis and there were positive correlations of maximum dose of rectum and bladder and each complication incidence. So we recommand whole pelvis dose less than 4500cGy and maximum dose of rectum and bladder as low as possible

  8. Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction

    Science.gov (United States)

    Illa, Miriam; Pla, Laura; Zamora, Monica; Crispi, Fatima; Gratacos, Eduard

    2018-01-01

    Objective To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). Methods IUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40–50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight. Results Survival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups. Conclusion Intra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficiency. PMID:29466434

  9. Survival and failure types after radiation therapy of vulvar cancer

    DEFF Research Database (Denmark)

    Vorbeck, Christina Steen; Vogelius, Ivan Richter; Banner-Voigt, Marie Louise Vorndran Cøln

    2017-01-01

    Background and purpose: Describe the survival rates and distribution of events on competing failure types in vulvar carcinoma after treatment with chemoradiation (CRT) or radiation (RT) alone. Material and methods: We included patients with vulvar carcinoma treated with CRT or RT between 2009...

  10. Toyota production system quality improvement initiative improves perioperative antibiotic therapy.

    Science.gov (United States)

    Burkitt, Kelly H; Mor, Maria K; Jain, Rajiv; Kruszewski, Matthew S; McCray, Ellesha E; Moreland, Michael E; Muder, Robert R; Obrosky, David Scott; Sevick, Mary Ann; Wilson, Mark A; Fine, Michael J

    2009-09-01

    To assess the role of a Toyota production system (TPS) quality improvement (QI) intervention on appropriateness of perioperative antibiotic therapy and in length of hospital stay (LOS) among surgical patients. Pre-post quasi-experimental study using local and national retrospective cohorts. We used TPS methods to implement a multifaceted intervention to reduce nosocomial methicillin-resistant Staphylococcus aureus infections on a Veterans Affairs surgical unit, which led to a QI intervention targeting appropriate perioperative antibiotic prophylaxis. Appropriate perioperative antibiotic therapy was defined as selection of the recommended antibiotic agents for a duration not exceeding 24 hours from the time of the operation. The local computerized medical record system was used to identify patients undergoing the 25 most common surgical procedures and to examine changes in appropriate antibiotic therapy and LOS over time. Overall, 2550 surgical admissions were identified from the local computerized medical records. The proportion of surgical admissions receiving appropriate perioperative antibiotics was significantly higher (P <.01) in 2004 after initiation of the TPS intervention (44.0%) compared with the previous 4 years (range, 23.4%-29.8%) primarily because of improvements in compliance with antibiotic therapy duration rather than appropriate antibiotic selection. There was no statistically significant decrease in LOS over time. The use of TPS methods resulted in a QI intervention that was associated with an increase in appropriate perioperative antibiotic therapy among surgical patients, without affecting LOS.

  11. Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis.

    Science.gov (United States)

    Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

    2008-04-01

    Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage.

  12. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    International Nuclear Information System (INIS)

    Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

    2013-01-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults

  13. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Naamit Kurshan [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wexler, Leonard H. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Singer, Samuel [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Keohan, Mary Louise [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne, E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-05-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

  14. The effect of carbon dioxide therapy on composite graft survival

    OpenAIRE

    Durães, Eliana Ferreira Ribeiro; Durães, Leonardo de Castro; Carneiro, Fabiana Pirani; Lino Júnior, Ruy de Souza; Sousa, João Batista de

    2013-01-01

    PURPOSE: To investigate the effect of carboxytherapy in auricular composite grafts in rabbits. METHODS: An experimental study was conducted using 20 rabbits randomly assigned to a treatment group of carboxytherapy or a control group of saline solution. In each ear, a circular graft with 1.5 cm or 2 cm of diameter was amputated and reattached. Animals underwent carbon dioxide or saline injection four times during the experiment. We analyzed clinical evolution of the animals, grafts survival, h...

  15. Chemoradiation therapy of esophageal cancer. Relationship between improvement of dysphagia and treatment outcome

    International Nuclear Information System (INIS)

    Mizutani, Yoshihide; Kitahara Tadashi

    2004-01-01

    The purpose of the study was to determine retrospectively whether the extent of dysphagia influenced the survival rate after chemoradiation therapy in patients with advanced esophageal cancer. 46 patients had dysphagia before treatment, in which 39 patients were treated with a combination of chemotherapy and irradiation. The remaining 7 patients were treated with irradiation alone. Forty six patients were divided into 5 groups according to the dysphagia score standard to obtain a relationship between the extent of dysphagia and the survival rate of the patients after treatment. Thirty out of 46 patients (65.2%) became able to swallow solid food after treatment. In these patients, the median survival period was 12 months and the one-year survival rate was 53.2%. However, dysphagia was not improved in 16 patients and their median survival period was 4 months, the one-year survival rate was 17.9%. The survival rate after treatment was definitely higher in the patients with improvement of dysphagia. Regarding esophageal cancer, the patients with cancer in the upper esophagus had the worse survival rate. Improvement of dysphagia was an important factor to control the survival rate after chemoradiation therapy in patients with advanced esophageal cancer. (author)

  16. PPARγ agonists improve survival and neurocognitive outcomes in experimental cerebral malaria and induce neuroprotective pathways in human malaria.

    Directory of Open Access Journals (Sweden)

    Lena Serghides

    2014-03-01

    Full Text Available Cerebral malaria (CM is associated with a high mortality rate, and long-term neurocognitive impairment in approximately one third of survivors. Adjunctive therapies that modify the pathophysiological processes involved in CM may improve outcome over anti-malarial therapy alone. PPARγ agonists have been reported to have immunomodulatory effects in a variety of disease models. Here we report that adjunctive therapy with PPARγ agonists improved survival and long-term neurocognitive outcomes in the Plasmodium berghei ANKA experimental model of CM. Compared to anti-malarial therapy alone, PPARγ adjunctive therapy administered to mice at the onset of CM signs, was associated with reduced endothelial activation, and enhanced expression of the anti-oxidant enzymes SOD-1 and catalase and the neurotrophic factors brain derived neurotrophic factor (BDNF and nerve growth factor (NGF in the brains of infected mice. Two months following infection, mice that were treated with anti-malarials alone demonstrated cognitive dysfunction, while mice that received PPARγ adjunctive therapy were completely protected from neurocognitive impairment and from PbA-infection induced brain atrophy. In humans with P. falciparum malaria, PPARγ therapy was associated with reduced endothelial activation and with induction of neuroprotective pathways, such as BDNF. These findings provide insight into mechanisms conferring improved survival and preventing neurocognitive injury in CM, and support the evaluation of PPARγ agonists in human CM.

  17. Ovarian carcinoma: improved survival following abdominopelvic irradiation in patients with a completed pelvic operation

    International Nuclear Information System (INIS)

    Dembo, A.J.; Bush, R.S.; Beale, F.A.; Bean, H.A.; Pringle, J.F.; Sturgeon, J.; Reid, J.G.

    1979-01-01

    A prospective, stratified, randomized study of 190 postoperative ovarian carcinoma patients with Stages IB, II, and III (asymptomatic) presentations is reported. The median time of follow-up was 52 months. Patients in whom bilateral salpingo-oophorectomy and hysterectomy (BSOH) could not be completed because of extensive pelvic tumor had a poor prognosis which did not differ for any of the therapies tested. When BSOH was completed, pelvic plus abdominopelvic irradiation (P + AB) with no diaphragmatic shielding significantly improved patient survival rate and long-term control of occult upper abdominal disease in approximately 25% more patients than pelvic irradiation alone or followed by adjuvant daily chlorambucil therapy. The effectiveness of P + AB in BSOH-completed patients was independent of stage or tumor grade and was most clearly appreciated in patients with all gross tumor removed. Chlorambucil added to pelvic irradiation delayed the time to treatment failure without reducing the number of treatment failures

  18. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    International Nuclear Information System (INIS)

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-01-01

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip® HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  19. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    International Nuclear Information System (INIS)

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A.; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    2015-01-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered

  20. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  1. STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma

    International Nuclear Information System (INIS)

    Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E.

    2006-01-01

    Purpose: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is essentially incurable. Although radiation therapy prolongs survival, GBMs progress within areas of irradiation. Recent studies in invertebrates have shown that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of ionizing radiation. In the present study, the effectiveness of STI571 in combination with radiation was studied in mouse models of GBM. Methods and Materials: Murine GL261 and human D54 GBM cell lines formed tumors in brains and hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were treated with 5 μmol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR) α and β. Tumor volumes were assessed in mice bearing GL261 or D54 tumors treated with 21 Gy administered in seven fractionated doses. Histologic sections from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR β antibodies. Kaplan-Meier survival curves were used to study the response of mice bearing intracranial implants of GL261. Results: STI571 penetrated the blood-brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571-induced apoptosis in GBM was significantly enhanced by irradiation. STI571 combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma multiforme response to therapy correlated with an increase in tumor growth delay and survival when STI571 was administered in conjunction with daily irradiation. Conclusion: These findings suggest that STI571 has the potential to augment radiotherapy and thereby improve median survival

  2. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    Energy Technology Data Exchange (ETDEWEB)

    Li Baoqing, E-mail: bal9018@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Margaret [Department of Surgery, Weill Cornell Medical College, New York, New York (United States); Nori, Dattatreyudu; Chao, K.S. Clifford [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Allen M. [Department of Radiation Oncology, University of California Davis Cancer Center, Sacramento, California (United States); Chen, Steven L. [Department of Surgery, University of California Davis Cancer Center, Sacramento, California (United States)

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  3. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

    Science.gov (United States)

    Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

    2007-01-01

    Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

  4. Utilization pattern and survival outcomes of adjuvant therapies in high-grade nonretroperitoneal abdominal soft tissue sarcoma: A population-based study.

    Science.gov (United States)

    Green, William Ross; Chokshi, Ravi; Jabbour, Salma K; DeLaney, Thomas F; Mahmoud, Omar

    2018-02-01

    Nonretroperitoneal abdominal soft tissue sarcoma (NRA-STS) is a rare disease with limited data supporting its management. Our study aimed to reveal the utilization patterns of adjuvant therapy and its potential survival benefits using the National Cancer Data Base. The analysis included patients with resected high-grade NRA-STS. Chi-square analysis was used to evaluate distribution of patient and tumor-related factors within treatment groups. The Kaplan-Meier and Cox proportional hazards model were utilized to evaluate overall survival according to treatment approach. Multivariate analysis was used to determine the impact of these factors on patients' outcome. Matched propensity score analysis was implemented to control for imbalance of confounding variables. At median follow-up of 49 months, 5-year overall survival improved from 46% without adjuvant radiation therapy to 52% (P = 0.009) with radiotherapy delivery with a 30% reduction in hazard of death (95% confidence interval = 0.58-0.84). On multivariate analysis, age <50, tumor <8 cm, negative margins and radiotherapy delivery were significant predictors of improved survival. Chemotherapy was not associated with significant survival improvement (Hazard Ratios [HR]: 0.89, P = 0.28). Adjuvant radiotherapy was associated with improved survival in high-grade NRA-STS. Chemotherapy was not associated with a survival improvement; however, further studies are needed to refine treatment strategies. © 2017 John Wiley & Sons Australia, Ltd.

  5. Precision oncology in advanced cancer patients improves overall survival with lower weekly healthcare costs

    Science.gov (United States)

    Haslem, Derrick S.; Chakravarty, Ingo; Fulde, Gail; Gilbert, Heather; Tudor, Brian P.; Lin, Karen; Ford, James M.; Nadauld, Lincoln D.

    2018-01-01

    The impact of precision oncology on guiding treatment decisions of late-stage cancer patients was previously studied in a retrospective analysis. However, the overall survival and costs were not previously evaluated. We report the overall survival and healthcare costs associated with precision oncology in these patients with advanced cancer. Building on a matched cohort study of 44 patients with metastatic cancer who received all of their care within a single institution, we evaluated the overall survival and healthcare costs for each patient. We analyzed the outcomes of 22 patients who received genomic testing and targeted therapy (precision oncology) between July 1, 2013 and January 31, 2015, and compared to 22 historically controlled patients (control) who received standard chemotherapy (N = 17) or best supportive care (N = 5). The median overall survival was 51.7 weeks for the targeted treatment group and 25.8 weeks for the control group (P = 0.008) when matching on age, gender, histological diagnosis and previous treatment lines. Average costs over the entire period were $2,720 per week for the targeted treatment group and $3,453 per week for the control group, (P = 0.036). A separate analysis of 1,814 patients with late-stage cancer diagnoses found that those who received a targeted cancer treatment (N = 93) had 6.9% lower costs in the last 3 months of life compared with those who did not. These findings suggest that precision oncology may improve overall survival for refractory cancer patients while lowering average per-week healthcare costs, resource utilization and end-of-life costs. PMID:29552312

  6. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan K; Russell, Nigel H; Hills, Robert K

    2012-01-01

    PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved...

  7. Hepatocyte transplantation improves early survival after partial hepatic resection and irradiation

    International Nuclear Information System (INIS)

    Guha, C.; Sharma, A.; Alfieri, A.; Guha, U.; Sokhi, R.; Gagandeep, S.; Gupta, S.; Vikram, B.; RoyChowdhury, J.

    1997-01-01

    Purpose: Radiation therapy (RT) is limited in its role as an adjuvant therapy of intrahepatic malignancies because of lower tolerance of human liver to irradiation (TD (5(5)) -TD (50(5)) ∼ 30-40 Gy). Although, surgical resection of primary or metastatic hepatic tumors has been shown to prolong survival, it is often limited by the presence of residual disease. RT could potentially improve survival of patients with positive surgical margins. However, radiation damage to the liver may be enhanced by hepatocellular proliferation induced by partial hepatic (PH) resection. We hypothesize that hepatocyte transplantation would be able to provide metabolic support and modulate the development of radiation-induced liver disease post-resection. The present study was designed to test the potential of hepatocyte transplantation in modifying the outcome of hepatocellular damage induced by PH and RT. Methods: Adult male Fischer 344 rats (Charles River) received hepatic irradiation of 50 Gy in a single fraction, after surgical exposure and shielding of the stomach and intestine, using a 320 MGC Philips orthovoltage unit. Immediately following irradiation, a two-third partial hepatectomy was performed. Four days post-radiation, the treatment group was injected with 5 x 10 6 syngeneic hepatocytes into the splenic pulp after a left subcostal incision, which allows homogeneous liver engraftment of the transplanted hepatocytes. Hematoxylin and eosin stains of liver biopsies, performed at various time points (3 days, 1, 2, 3 weeks or, anytime when animals died) were used for histologic evaluation. Time-adjusted survival was calculated from the date of irradiation by the product-limit Kaplan-Meier method, adjusting the denominator at every time point for the number of rats at risk. Results: Eight weeks after RT, 30% (n = 11) of the control animals (PH + 50 Gy) were alive compared to 100% (n = 9) of the transplant recipients (p <0.05). The median survival of the control group was 15

  8. Improving survival of culture bacteria in frozen desserts by microentrapment.

    Science.gov (United States)

    Sheu, T Y; Marshall, R T; Heymann, H

    1993-07-01

    Lactobacillus bulgaricus cells were entrapped in beads of calcium alginate and evaluated for their ability to survive freezing processes. Cells survived freezing (without agitation) in ice milk mix much better than in distilled water, and more entrapped cells survived than did cells that were not entrapped. Glycerol and mannitol were cryoprotective, but glucose was not, when each was added (6%) separately to the beads. Entrapment protected the lactobacilli in batch frozen and continuously frozen ice milk mixes. The percentage of survival for entrapped and unentrapped cells in continuously frozen ice milk approximated 90 and 40%, respectively. Lactobacilli survived better in beads with mean diameters > 30 microns than in those averaging 15 microns. Addition of entrapped lactobacilli had no measurable effect on the sensory characteristics of the ice milk.

  9. Radiation therapy and patient age in the survival from early-stage breast cancer

    International Nuclear Information System (INIS)

    Joslyn, Sue A.

    1999-01-01

    Purpose: To analyze the use of radiation therapy following local excision of invasive localized breast cancer and subsequent survival by 5-year age category. Methods: Data for 27,399 women diagnosed with localized stage of breast cancer and treated with local excision surgery from 1983 through 1992 were collected and provided by the national Surveillance, Epidemiology, and End Results (SEER) program. Use of radiation therapy was analyzed by race, ethnic background, geographic location, and age at diagnosis. Survival for women treated with local excision plus radiation therapy was compared to that of women treated with local excision alone for each 5-year age category. Results: Subjects in older age groups were significantly less likely (p < 0.001) to receive radiation following local excision compared to younger age groups. Statistically significant survival advantages were conferred on women receiving radiation therapy in each 5-year age category from age 35 to 84 years (ranging from p = 0.02 to p < 0.0001). Conclusion: While the use of radiation therapy following local excision of early-stage breast tumors drops significantly in older age groups, women aged 35-84 years receiving radiation therapy had significant reductions in mortality. These results did not appear to be influenced by the presence of mortal comorbid conditions. These results strongly suggest the need to consider carefully patient characteristics other than age in deciding the course of treatment for early-stage breast cancer

  10. Temozolomide during radiotherapy of glioblastoma multiforme. Daily administration improves survival

    Energy Technology Data Exchange (ETDEWEB)

    Nachbichler, Silke Birgit; Schupp, Gabi; Ballhausen, Hendrik; Niyazi, Maximilian; Belka, Claus [LMU Munich, Department of Radiation Oncology, Munich (Germany)

    2017-11-15

    Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week. From 2002-2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m{sup 2}) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60 Gy. Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1-year survival rates were 33, 52, and 64%, respectively. Kaplan-Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept. Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration. (orig.) [German] Eine Temozolomid-(TMZ-)basierte Radiochemotherapie ist der gegenwaertige Goldstandard in der Behandlung von neu diagnostizierten Glioblastomen. Daten bezueglich des Einflusses der TMZ-Dosisdichte waehrend der Radiochemotherapie sind derzeit nicht vorhanden. Wir haben retrospektiv die Ergebnisse von Patienten verglichen, die entweder kein TMZ, TMZ zur Strahlentherapie nur an Bestrahlungstagen oder TMZ konstant 7 Tage/Woche erhalten hatten. Von 2002-2012 bekamen insgesamt 432 Patienten mit

  11. Shock Wave Therapy Promotes Cardiomyocyte Autophagy and Survival during Hypoxia

    Directory of Open Access Journals (Sweden)

    Ling Du

    2017-06-01

    Full Text Available Background: Autophagy plays an important role in cardiovascular disease. Controversy still exists regarding the effect of autophagy on ischemic/hypoxic myocardium. Cardiac shock wave therapy (CSWT is an effective alternative treatment for refractory ischemic heart disease. Whether CSWT can regulate cardiomyocyte autophagy under hypoxic conditions is not clear. We established a myocardial hypoxia model using the H9c2 cell line and performed shock waves (SWs treatment to evaluate the effect of SW on autophagy. Methods: The H9c2 cells were incubated under hypoxic conditions, and SW treatment was then performed at energies of 0.02, 0.05, or 0.10 mJ/mm2. The cell viability and intracellular ATP level were examined. Western blot analysis was used to assess the expression of LC3B, AMPK, mTOR, Beclin-1, Sirt1, and HIF-1α. Autophagic vacuoles were visualized by monodansylcadaverine staining. Results: After the 24-hour hypoxic period, cardiomyocyte viability and ATP levels were decreased and autophagy was significantly increased in H9c2 cells. SW treatment with an energy of 0.05 mJ/mm2 significantly increased the cellular viability, ATP level, LC3B-II/I, and number of autophagic vacuoles. In addition, phosphorylated AMPK and Sirt1 were increased and phosphorylated mTOR and HIF-1α were decreased after SW treatment. Conclusion: SW treatment can potentially promote cardiomyocyte autophagy during hypoxia and protect cardiomyocyte function by regulating the AMPK/mTOR pathway.

  12. Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up.

    Science.gov (United States)

    Parmar, S; Kongtim, P; Champlin, R; Dinh, Y; Elgharably, Y; Wang, M; Bashir, Q; Shah, J J; Shah, N; Popat, U; Giralt, S A; Orlowski, R Z; Qazilbash, M H

    2014-08-01

    Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

  13. Determinants of survival in adult HIV patients on antiretroviral therapy in Oromiyaa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Andinet Worku Alemu

    2010-10-01

    Full Text Available Background: The antiretroviral treatment (ART scale-up service has been a recent development in Ethiopia, but its impact on mortality has not been well investigated. The aim of this study was to assess the early survival outcome of the scale-up service by utilizing routine hospital data. Methods: All adult HIV/AIDS patients who started on antiretroviral treatment in Shashemene and Assela hospitals from January 1, 2006 to May 31, 2006 were included and followed up for 2 years. Data were extracted from standard patient medical registrations. Kaplan–Meier curves were used to estimate survival probability and the Cox proportional hazard model was applied to determine predictors of mortality. Two alterative assumptions (real case and worst case were made in determining predictors of mortality. Results: The median age of patients was 33 years and 57% were female. Eighty-five percent had CD4 <200 cells/µL with a median CD4 count of 103 cells/µL. The median survival time was 104.4 weeks. A total of 28 (10.3% deaths were observed during the 2-year period and 48 patients (18% were lost to follow up. The majority of deaths occurred in the first 4 months of treatment. In multivariate analysis, 2-year survival was significantly associated with the clinical stage of the disease, baseline hemoglobin, and cotrimoxazole prophylaxis therapy (CPT at or before ART initiation in both assumptions. The median CD4 count and body weight showed a marked improvement during the first 6 months of treatment, followed by stagnation thereafter. Conclusion: The study has shown an overall low mortality but a high loss to follow-up rate of the cohort. Advanced clinical stage, anemia, low body weight, and lack of CPT initiation were independent predictors of mortality – but not gender. CPT initiation should be encouraged in routine HIV care services, and patient retention mechanisms have to be strengthened. Stagnation in immunological and weight recovery after the first 6

  14. Improved survival using specialized multidisciplinary board in sarcoma patients.

    Science.gov (United States)

    Blay, J-Y; Soibinet, P; Penel, N; Bompas, E; Duffaud, F; Stoeckle, E; Mir, O; Adam, J; Chevreau, C; Bonvalot, S; Rios, M; Kerbrat, P; Cupissol, D; Anract, P; Gouin, F; Kurtz, J-E; Lebbe, C; Isambert, N; Bertucci, F; Toumonde, M; Thyss, A; Piperno-Neumann, S; Dubray-Longeras, P; Meeus, P; Ducimetière, F; Giraud, A; Coindre, J-M; Ray-Coquard, I; Italiano, A; Le Cesne, A

    2017-11-01

    Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Radium-223 Improves Survival in Patients with Advanced Prostate Cancer

    Science.gov (United States)

    ... This well-executed study shows a clear survival benefit in patients who had received the treatments that were available when the study was conducted, including standard chemotherapy,” said Bhupinder Mann, MBBS, of NCI’s Division of ...

  16. Audit in radiation therapy: long-term survival and cost of treatment

    International Nuclear Information System (INIS)

    Stevens, G.; Firth, I.

    1997-01-01

    In order to determine the cost of radiation treatment and the survival rate of a cohort of patients treated in a 6 month period in 1988, estimates of the capital and recurrent costs of this service were made for the calendar year 1988, expressed as $A(1988). Data collected prospectively included workload statistics (including number of attendances), field treated and complexity of treatment. Patient and tumour-related data included tumour site, intent of treatment and survival. The survival rate of patients during this period was determined in June 1995. The cost per field in 1988 was estimated at $A44.32. The 1988 costs of courses of definitive, adjuvant and palliative radiation therapy were estimated at $A2545, $A2482 and $A929, respectively. The major contributor to the cost of salaries and consumables within the Radiation Oncology Department (81.6%), with capital costs accounting for 13.5%, overheads accounting for 4.5% of the costs and planned admissions accounting for 0.2%. The median survival time of 580 patients with malignant disease treated during this period in 1988 was 12.4 months. The overall 5 year survival rate was 27%. For 105 patients treated definitively with radiation therapy, the median and 5 year survival rate figures were 26.0 months and 40%. For 149 patients treated with adjuvant radiation therapy, the 5 year survival rate was 62% (median survival rate not reached). For 279 patients treated palliatively, median and 5 year survival rate figures were 5.2 months and 3%. The cost per month of survival for all patients with malignancy was $A67; the figures for definitive , adjuvant and palliative treatments being $A74, $A48 and $A105, respectively. A sensitivity analysis indicated that these figures were robust. The cost of radiation treatment per field was comparable to reports for other centres and emphasizes the utility of radiation therapy as a cost-effective cancer treatment modality. 7 refs., 6 tabs., 2 figs

  17. Hibernation Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2016-06-01

    leaks extravascularly • Necrosis and inflammation involving the ear tip is considered to be a more severe manifestation of vascular damage associated...similar lesions to the 2M test solution, it appears that 2M test solution is more likely to cause vascular necrosis and inflammation (noted at 24 hours...injections • Although DMSO induced similar lesions to the 4M test solution, it appears that 4M test solution is more likely to cause vascular necrosis and

  18. Overall Survival Benefit From Postoperative Radiation Therapy for Organ-Confined, Margin-Positive Prostate Cancer

    International Nuclear Information System (INIS)

    Dillman, Robert O.; Hafer, Russell; Cox, Craig; McClure, Stephanie E.

    2011-01-01

    Purpose: Radical prostatectomy for invasive prostate cancer is associated with positive margin rates in 10% to 50% of resected specimens. Postoperative radiation therapy may benefit patients who have organ-confined prostate cancer with positive margins. Methods and Materials: We performed a retrospective analysis to examine whether adjunctive radiation therapy enhanced long-term survival for prostate cancer patients who underwent prostatectomy for localized prostate cancer but with positive margins. We used the Hoag Cancer Center database to identify patients diagnosed with invasive prostate cancer. Relative and overall survival rates were calculated. Results: Among 1,474 patients diagnosed with localized invasive prostate cancer during the years 1990 to 2006 and undergoing prostatectomy, 113 (7.7%) were identified who had positive margins and did not have local extension of disease, positive lymph nodes, or distant metastases. A total of 17 patients received adjunctive radiation therapy (Group A), whereas 96 did not (Group B; 3 received hormonal therapy). Both groups had a median age of 64 years and median follow-up of 7.5 years. In Group A, no patients have died as of last follow-up, but in Group B, 18 have died. Estimated 10-year and 15-year overall survival rates were both 100% for Group A compared with 85% and 57% respectively for Group B (p 2 = 0.050, log rank). Relative 10- and 15 year survival rates were both 100% for Group A compared with 100% and 79% respectively for Group B. Conclusions: This retrospective analysis suggests that prostate cancer patients with localized disease but positive margins do derive a survival benefit from adjuvant radiation therapy.

  19. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    International Nuclear Information System (INIS)

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-01-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer

  20. Early-Stage Classic Hodgkin Lymphoma: The Utilization of Radiation Therapy and Its Impact on Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Rahul R., E-mail: rparikh@chpnet.org [Department of Radiation Oncology, Mount Sinai Beth Israel Medical Center and Mount Sinai St. Luke' s-Roosevelt Hospitals, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, New York (United States); Grossbard, Michael L. [Division of Hematology-Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York (United States); Harrison, Louis B. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Yahalom, Joachim [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2015-11-01

    Purpose: To examine the association between radiation therapy (RT) utilization and overall survival (OS) for patients with early-stage Hodgkin lymphoma (HL). Methods and Materials: Using the National Cancer Database, we evaluated clinical features and survival outcomes among patients diagnosed with stage I/II HL from 1998 to 2011. The association between RT use, covariables, and outcome was assessed in a Cox proportional hazards regression model. Propensity score matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. Results: Among the 41,943 patients in the National Cancer Database with stage I/II HL, 29,752 patients were analyzed for this study. Radiation therapy use was associated with younger age (≤40 years), favorable insured status, higher socioeconomic status (income, education), and treatment at comprehensive community cancer centers (all P<.05). Five-year OS for patients receiving RT was 94.5%, versus 88.9% for those not receiving RT (P<.01). Radiation therapy use was a significant predictor of OS in the “As-Treated” cohort (hazard ratio 0.53, 95% confidence interval 0.49-0.58, P<.01) and intention-to-treat analysis (P<.01). After propensity score matching based on clinicopathologic characteristics, RT use remained associated with improved OS (hazard ratio 0.46, 95% confidence interval 0.38-0.56, P<.01). Over the study period, RT utilization for this cohort decreased from 55% to 44%, most commonly because it was not part of the planned initial treatment strategy. Conclusions: Consolidation RT was associated with improved OS for patients with early-stage classic HL. We also have identified patient-specific variations in the use of RT that may be targeted to improve patient access to care.

  1. Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

    International Nuclear Information System (INIS)

    Beyer, David C.; McKeough, Timothy; Thomas, Theresa

    2005-01-01

    Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] 70 years (p = 0.0013), Gleason score ≥ 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade, PSA, age) on multivariate analysis. The leading causes of death were cardiovascular, prostate cancer, and other cancers with no obvious discrepancy between the two groups. This finding is unexpected and requires confirmation from other centers

  2. Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

    Science.gov (United States)

    Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

    2016-09-01

    To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. ZTI-01 Treatment Improves Survival of Animals Infected with Multidrug Resistant Pseudomonas aeruginosa

    Science.gov (United States)

    Lawrenz, Matthew B; denDekker, Ashley Eb; Cramer, Daniel E; Gabbard, Jon D; Lafoe, Kathryn M; Pfeffer, Tia L; Sotsky, Julie B; Vanover, Carol D; Ellis-Grosse, Evelyn J; Warawa, Jonathan M

    2017-01-01

    Abstract Background ZTI-01 (fosfomycin, FOS, for injection) is currently under US development to treat complicated urinary tract infections. ZTI-01 is unique compared with other antimicrobials in that it inhibits an early step in cell wall synthesis via covalent binding to MurA. ZTI-01 demonstrates broad in vitro activity against Gram-negative (GN) and -positive (GP) bacteria, including multidrug-resistant (MDR) organisms. Our study goals were to determine the efficacy of ZTI-01 as a monotherapy or in combination with meropenem against MDR Pseudomonas aeruginosa in a preclinical model of pulmonary infection. Methods 8 week old neutropenic mice were infected with a MDR strain of P. aeruginosa via intubation-mediated intratracheal (IMIT) instillation. 3 hours after instillation, mice received treatment with ZTI-01, meropenem, or ZTI-01 plus meropenem (combination therapy) q8h for 5 days. Mice were monitored every 8 hours for 7 days for development of disease and moribund animals were humanely euthanized. Lungs and spleens were harvested at euthanasia, or at 7 days for survivors, and processed for bacterial enumeration and development of pathology. Results Mice were challenged with a lethal dose of P. aeruginosa UNC-D. Mock treated animals succumbed to infection within 36 hours post-infection. Animals that received 6 g/kg/day ZTI-01 showed an increase in the MTD (52 hours) and 25% of the cohort were protected from lethal disease. Combining ZTI-01 with meropenem resulted in a significant increase in survival (≥75% of cohorts survived infection). Combination therapy also significantly decreased bacterial numbers in the lungs and inhibited dissemination to the spleens. Furthermore, animals receiving combination therapy were protected from significant inflammation in the lungs and the development of pneumonia. Conclusion Here we report that combination therapy with ZTI-01 and meropenem provides significant improvements in all disease manifestations over treatment with

  4. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Adam J., E-mail: adam_olszewski@brown.edu; Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  5. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    International Nuclear Information System (INIS)

    Olszewski, Adam J.; Desai, Amrita

    2014-01-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas

  6. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

    Science.gov (United States)

    Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

  7. Single Agent Polysaccharopeptide Delays Metastases and Improves Survival in Naturally Occurring Hemangiosarcoma

    Directory of Open Access Journals (Sweden)

    Dorothy Cimino Brown

    2012-01-01

    Full Text Available The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. Clear evidence of clinically relevant benefits of PSP in cancer patients, however, is lacking. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality.

  8. Association Between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas.

    Science.gov (United States)

    Venigalla, Sriram; Nead, Kevin T; Sebro, Ronnie; Guttmann, David M; Sharma, Sonam; Simone, Charles B; Levin, William P; Wilson, Robert J; Weber, Kristy L; Shabason, Jacob E

    2018-03-15

    Soft tissue sarcomas (STS) are rare malignancies that require complex multidisciplinary management. Therefore, facilities with high sarcoma case volume may demonstrate superior outcomes. We hypothesized that STS treatment at high-volume (HV) facilities would be associated with improved overall survival (OS). Patients aged ≥18 years with nonmetastatic STS treated with surgery and radiation therapy at a single facility from 2004 through 2013 were identified from the National Cancer Database. Facilities were dichotomized into HV and low-volume (LV) cohorts based on total case volume over the study period. OS was assessed using multivariable Cox regression with propensity score-matching. Patterns of care were assessed using multivariable logistic regression analysis. Of 9025 total patients, 1578 (17%) and 7447 (83%) were treated at HV and LV facilities, respectively. On multivariable analysis, high educational attainment, larger tumor size, higher grade, and negative surgical margins were statistically significantly associated with treatment at HV facilities; conversely, black race and non-metropolitan residence were negative predictors of treatment at HV facilities. On propensity score-matched multivariable analysis, treatment at HV facilities versus LV facilities was associated with improved OS (hazard ratio, 0.87, 95% confidence interval, 0.80-0.95; P = .001). Older age, lack of insurance, greater comorbidity, larger tumor size, higher tumor grade, and positive surgical margins were associated with statistically significantly worse OS. In this observational cohort study using the National Cancer Database, receipt of surgery and radiation therapy at HV facilities was associated with improved OS in patients with STS. Potential sociodemographic disparities limit access to care at HV facilities for certain populations. Our findings highlight the importance of receipt of care at HV facilities for patients with STS and warrant further study into improving access to

  9. Improving Child survival through enhancing Prevention of Mother to ...

    African Journals Online (AJOL)

    0655711075

    Background: Although highly effective prevention interventions exist, the ... highly prioritized for the PMTCT programme to achieve its potential. .... Drug costs, VCT costs, natural history MTCT rate, adherence to therapy, drug efficacy, .... settings, PMTCT programmes helped to create the environment for the later roll-out of.

  10. Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xi-Mei [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Ye-Xiong, E-mail: yexiong@yahoo.com [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Zhou, Li-Qiang [Department of Medical Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Liu, Xin-Fan; Yu, Zi-Hao [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China)

    2013-03-15

    Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.

  11. Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

    International Nuclear Information System (INIS)

    Zhang, Xi-Mei; Li, Ye-Xiong; Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua; Zhou, Li-Qiang; Liu, Xin-Fan; Yu, Zi-Hao

    2013-01-01

    Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival

  12. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Christensen, Ib J

    2015-01-01

    BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non......-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised...... disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised...

  13. Growth and Survival of Bagged Lucilia sericata Maggots in Wounds of Patients Undergoing Maggot Debridement Therapy

    OpenAIRE

    Čičková, Helena; Čambal, Marek; Kozánek, Milan; Takáč, Peter

    2013-01-01

    Maggot debridement therapy (MDT) is an established method of debridement of nonhealing wounds. Despite intense clinical research about its efficacy and effects of substances produced by the larvae, growth and development of maggots in the wounds remain largely unexplored. In the present study, the bags with larvae (n = 52), which had been used to debride traumatic, ischemic, diabetic and venous ulcers, were collected and examined. Survival, length, width and larval instar of the maggots withi...

  14. Improvement of cycloid psychosis following electroconvulsive therapy.

    Science.gov (United States)

    Holm, Jonas; Brus, Ole; Båve, Ullvi; Landen, Mikael; Lundberg, Johan; Nordanskog, Pia; von Knorring, Lars; Nordenskjöld, Axel

    2017-08-01

    The treatment of choice for cycloid psychosis has traditionally been electroconvulsive therapy (ECT), but there is a lack of studies on its effectiveness. The primary aim of this register study was to determine the rates of remission and response after ECT for cycloid psychosis. The secondary aim was to examine possible predictors of outcome. Data were obtained from the National Quality Register for ECT in Sweden. The study population was patients (n = 42) who received ECT for acute polymorphic psychotic disorder without symptoms of schizophrenia or for cycloid psychosis between 2011-2015 in 13 hospitals. Remission and response rates were calculated using Clinical Global Impression-Severity (CGI-S) and -Improvement scores, respectively. Variables with possible predictive value were tested using Chi-square and Fisher's exact test. The response rate was 90.5%. The remission rate was 45.2%. Of 42 patients, 40 improved their CGI-S score after ECT (p < 0.001). The mean number of ECT treatments was 2.5 for non-responders and 7.0 for responders (p = 0.010). The mean number of ECT treatments did not differ significantly between remitters and non-remitters (7.2 vs 6.1, p = 0.31). None of the other investigated potential predictors was statistically significantly associated with outcome. ECT is an effective treatment for cycloid psychosis. Future studies need to compare the outcome of ECT to that of other treatment strategies. The high response rate with ECT indicates that cycloid psychosis is a clinically useful diagnosis.

  15. [Determinants of survival in HIV patients receiving antiretroviral therapy in Goma, Democratic Republic of Congo].

    Science.gov (United States)

    Akilimali, P Z; Mutombo, P B; Kayembe, P K; Kaba, D K; Mapatano, M A

    2014-06-01

    The study aimed to identify factors associated with the survival of patients receiving antiretroviral therapy. A historic cohort of HIV patients from two major hospitals in Goma (Democratic Republic of Congo) was followed from 2004 to 2012. The Kaplan-Meier method was used to describe the probability of survival as a function of time since inclusion into the cohort. The log-rank test was used to compare survival curves based on determinants. The Cox regression model identified the determinants of survival since treatment induction. The median follow-up time was 3.56 years (IQR=2.22-5.39). The mortality rate was 40 deaths per 1000 person-years. Male gender (RR: 2.56; 95 %CI 1.66-4.83), advanced clinical stage (RR: 2.12; 95 %CI 1.15-3.90), low CD4 count (CD4 < 50) (RR: 2.05; 95 %CI : 1.22-3.45), anemia (RR: 3.95; 95 %CI 2.60-6.01), chemoprophylaxis with cotrimoxazole (RR: 4.29, 95 % CI 2.69-6.86) and period of treatment initiation (2010-2011) (RR: 3.34; 95 %CI 1.24-8.98) were statistically associated with short survival. Initiation of treatment at an early stage of the disease with use of less toxic molecules and an increased surveillance especially of male patients are recommended to reduce mortality. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Disease-specific survival in de novo metastatic renal cell carcinoma in the cytokine and targeted therapy era.

    Directory of Open Access Journals (Sweden)

    Sumanta K Pal

    Full Text Available Recent phase III studies of targeted agents for metastatic renal cell carcinoma (mRCC have generated median survival estimates that far exceed those observed during the cytokine era. However, substantial population-based data does not exist to confirm this trend. We sought to determine whether survival has improved for patients with mRCC diagnosed in the era of targeted therapies, as compared to the era of immunotherapy.The Surveillance, Epidemiology, and End Results (SEER Registry was used to identify patients aged 18 and older diagnosed stage IV RCC between 1992 and 2009. Patients had documented clear cell, papillary or chromophobe histology. The Kaplan Meier method and log-rank test were used to compare disease-specific survival (DSS for patients diagnosed from 1992-2004 (i.e., the cytokine era and 2005-2009 (i.e., the targeted therapy era. Univariate and multivariate analyses of relevant clinicopathologic characteristics were also performed.Of 5,176 patients identified using the above characteristics, 2,392 patients were diagnosed from 1992-2004 and 2,784 from 2005-2009. Median DSS was improved in those patients diagnosed from 2005-2009 (16 months vs 13 months; P<0.0001. A similar temporal trend towards improving survival was noted in patients with clear cell (P = 0.0006, but not in patients with non-clear cell disease (P = 0.32. Notable findings on multivariate analysis include an association between shorter DSS and the following characteristics: (1 diagnosis from 1992-2004, (2 advanced age (80+, and (3 absence of cytoreductive nephrectomy.These data reflect progress in the management of mRCC, specifically in the era of targeted therapies. Notably, it was inferred that certain treatment strategies were employed during pre-specified time periods, representing a major caveat of the current analysis. Further studies related to the influence of age and race/ethnicity are warranted, as are studies exploring the role of cytoreductive nephrectomy

  17. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Directory of Open Access Journals (Sweden)

    Angela M Poff

    Full Text Available INTRODUCTION: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. METHODS: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week. Tumor growth was monitored by in vivo bioluminescent imaging. RESULTS: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. CONCLUSIONS: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  18. Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!

    DEFF Research Database (Denmark)

    Hailer, N. P.; Lazarinis, S.; MaKela, K. T.

    2015-01-01

    Background and purpose - It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients and m...

  19. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease

    NARCIS (Netherlands)

    Lutgens, M. W. M. D.; Oldenburg, B.; Siersema, P. D.; van Bodegraven, A. A.; Dijkstra, G.; Hommes, D. W.; de Jong, D. J.; Stokkers, P. C. F.; van der Woude, C. J.; Vleggaar, F. P.

    2009-01-01

    Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. The aim of this study was to compare tumour stage and survival of IBD

  20. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention

    DEFF Research Database (Denmark)

    Vestergaard, P; Hermann, A P; Gram, J

    1997-01-01

    To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.......To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule....

  1. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS mouse model.

    Directory of Open Access Journals (Sweden)

    Csilla Ari

    Full Text Available Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG, the main ingredient of the DP, and the ketogenic diet (KD, would increase motor function and survival in a mouse model of ALS (SOD1-G93A. ALS mice were fed standard rodent diet (SD, KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001 and 4.2% (p = 0.006, respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which

  2. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model.

    Science.gov (United States)

    Ari, Csilla; Poff, Angela M; Held, Heather E; Landon, Carol S; Goldhagen, Craig R; Mavromates, Nicholas; D'Agostino, Dominic P

    2014-01-01

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong

  3. Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

    2016-09-01

    We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

  4. Constitutive STAT5 Activation Correlates With Better Survival in Cervical Cancer Patients Treated With Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Helen H.W. [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Chou, Cheng-Yang [Department of Obstetrics and Gynecology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Wu, Yuan-Hua; Hsueh, Wei-Ting; Hsu, Chiung-Hui [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Guo, How-Ran [Department of Environmental and Occupational Health, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Lee, Wen-Ying, E-mail: 7707@so-net.net.tw [Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan (China) and Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Wu-Chou, E-mail: sunnysu@mail.ncku.edu.tw [Department of Internal Medicine, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China)

    2012-02-01

    Purpose: Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. Methods and Materials: A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. Results: Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor ({>=}4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. Conclusions: This is the first report to provide the overall expression patterns and prognostic significance of

  5. Overall survival after prostate-specific-antigen-detected recurrence following conformal radiation therapy

    International Nuclear Information System (INIS)

    Sandler, Howard M.; Dunn, Rodney L.; McLaughlin, P. William; Hayman, James A.; Sullivan, Molly A.; Taylor, Jeremy M.G.

    2000-01-01

    Purpose: To study the significance, in terms of overall and cause-specific survival, of biochemical failure after conformal external-beam radiation therapy (RT) for prostate cancer. Methods and Materials: Of the 1844 patients in the Radiation Oncology prostate cancer database, 718 were deemed eligible. Patients excluded were those with N1 or M1 disease, those treated after radical prostatectomy, those who received hormone therapy before radiation therapy, and those who died, failed clinically, or had no PSA response in the first 6 months after RT. Patients included were required to have a minimum of 2 post-RT PSAs separated by at least 1 week. Biochemical relapse was defined as 3 consecutive PSA rises. This resulted in 154 patients with biochemical failure. Survival was calculated from the third PSA elevation. The rate of rise of PSA was calculated by fitting a regression line to the four rising PSAs on a ln PSA vs. time plot. Results: There were 41 deaths among the 154 patients with failure in 23 of the 41 due to prostate cancer. The overall survival after failure was 58% at 5 years, while the cause-specific failure was 73% at 5 years. Among the 154 failures, several factors were evaluated for an association with overall survival: age at failure, pre-RT PSA, PSA at second rise, PSA nadir, time from RT to failure, time to nadir, Gleason score, T-stage, and rate of rise, both from the nadir and from the beginning of the rise. None of these factors were significantly associated with an increased risk of death. As expected, the group of patients with biochemical failure have significantly worse prognostic factors than those without biochemical failure: median pre-RT PSA 15.9 vs. 9.0 (p < 0.001), and Gleason score of 7 or greater for 48% of subjects vs. 40% (p 0.1). Relative PSA rise and slope of ln PSA vs. time were associated with cause-specific mortality (p < 0.001 and p = 0.007, respectively). Conclusion: Overall survival after conformal radiotherapy for prostate

  6. Growth and Survival of Bagged Lucilia sericata Maggots in Wounds of Patients Undergoing Maggot Debridement Therapy

    Directory of Open Access Journals (Sweden)

    Helena Čičková

    2013-01-01

    Full Text Available Maggot debridement therapy (MDT is an established method of debridement of nonhealing wounds. Despite intense clinical research about its efficacy and effects of substances produced by the larvae, growth and development of maggots in the wounds remain largely unexplored. In the present study, the bags with larvae (n=52, which had been used to debride traumatic, ischemic, diabetic and venous ulcers, were collected and examined. Survival, length, width and larval instar of the maggots within each bag were recorded and analyzed with respect to the wound type and duration of the treatment. Survival of maggots after a 48-h cycle of MDT ranged between 63.6 and 82.7%. Maggots in venous ulcers had on average 9–19% higher mortality than maggots within traumatic, ischemic, and diabetic ulcers. Length of larvae after 48 h cycle of MDT reached on average 7.09–9.68 mm, and average width varied between 1.77 and 2.26 mm. Larvae in venous ulcers were significantly smaller after 48 h, but not after 72 h treatment compared to the other wound types. Further studies should be aimed to identify other patient-associated factors which might influence growth and survival of the larvae during maggot debridement therapy.

  7. Growth and Survival of Bagged Lucilia sericata Maggots in Wounds of Patients Undergoing Maggot Debridement Therapy.

    Science.gov (United States)

    Cičková, Helena; Cambal, Marek; Kozánek, Milan; Takáč, Peter

    2013-01-01

    Maggot debridement therapy (MDT) is an established method of debridement of nonhealing wounds. Despite intense clinical research about its efficacy and effects of substances produced by the larvae, growth and development of maggots in the wounds remain largely unexplored. In the present study, the bags with larvae (n = 52), which had been used to debride traumatic, ischemic, diabetic and venous ulcers, were collected and examined. Survival, length, width and larval instar of the maggots within each bag were recorded and analyzed with respect to the wound type and duration of the treatment. Survival of maggots after a 48-h cycle of MDT ranged between 63.6 and 82.7%. Maggots in venous ulcers had on average 9-19% higher mortality than maggots within traumatic, ischemic, and diabetic ulcers. Length of larvae after 48 h cycle of MDT reached on average 7.09-9.68 mm, and average width varied between 1.77 and 2.26 mm. Larvae in venous ulcers were significantly smaller after 48 h, but not after 72 h treatment compared to the other wound types. Further studies should be aimed to identify other patient-associated factors which might influence growth and survival of the larvae during maggot debridement therapy.

  8. Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

    Science.gov (United States)

    Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

    2014-01-01

    Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

  9. Improved survival of newborns receiving leukocyte transfusions for sepsis

    International Nuclear Information System (INIS)

    Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

    1984-01-01

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions

  10. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    . Data on patients with stage III colonic cancer operated between January 1, 2005 and August 31, 2012 were retrieved. Perioperative variables, surgical modality, and time to adjuvant therapy (8 weeks) were evaluated and Cox regression was performed to identify factors influencing survival...

  11. Metformin use and improved response to therapy in rectal cancer

    International Nuclear Information System (INIS)

    Skinner, Heath D.; Crane, Christopher H.; Garrett, Christopher R.; Eng, Cathy; Chang, George J.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Kelly, Patrick; Sandulache, Vlad C.; Delclos, Marc E.; Krishnan, Sunil; Das, Prajnan

    2013-01-01

    Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision (TME). Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy. In this study, we examined the effect of metformin use on pathologic complete response (pCR) rates and outcomes in rectal cancer. The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was 50.4 Gy (range 19.8–63). Nearly, all patients were treated with concurrent 5-fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%). Patients were categorized as nondiabetic (422), diabetic not taking metformin (40), or diabetic taking metformin (20). No significant differences between groups were found in clinical tumor classification, nodal classification, tumor distance from the anal verge or circumferential extent, pretreatment carcinoembryonic antigen level, or pathologic differentiation. pCR rates were 16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for diabetics taking metformin, with metformin users having significantly higher pCR rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P = 0.007). Metformin use was significantly associated with pCR rate on univariate (P = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking metformin had significantly increased disease-free (P = 0.013) and overall survival (P = 0.008) compared with other diabetic patients. Metformin use is associated with significantly higher pCR rates as well as improved survival. These promising data warrant further prospective study

  12. Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Xing, Minzhi; Sakaria, Sonali; Dhanasekaran, Renumathy; Parekh, Samir; Spivey, James; Knechtle, Stuart J.; Zhang, Di; Kim, Hyun S.

    2017-01-01

    Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

  13. Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Minzhi [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Sakaria, Sonali [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Dhanasekaran, Renumathy [Stanford University School of Medicine, Division of Gastroenterology and Hepatology (United States); Parekh, Samir; Spivey, James [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Knechtle, Stuart J. [Duke University School of Medicine, Division of Transplant Surgery, Department of Surgery (United States); Zhang, Di [University of Pittsburgh, Department of Biostatistics, Graduate School of Public Health (United States); Kim, Hyun S., E-mail: kevin.kim@yale.edu [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States)

    2017-03-15

    Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

  14. A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study

    International Nuclear Information System (INIS)

    Gu, Ran; Long, Meijun; Chen, Kai; Chen, Lili; Xiao, Qiaozhen; Wu, Mei; Song, Erwei; Su, Fengxi; Jia, Weijuan; Zeng, Yunjie; Rao, Nanyan; Hu, Yue; Li, Shunrong; Wu, Jiannan; Jin, Liang; Chen, Lijuan

    2012-01-01

    In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. Toremifene may be a valid and

  15. Autologous cytokine-induced killer cell immunotherapy may improve overall survival in advanced malignant melanoma patients.

    Science.gov (United States)

    Zhang, Yong; Zhu, Yu'nan; Zhao, Erjiang; He, Xiaolei; Zhao, Lingdi; Wang, Zibing; Fu, Xiaomin; Qi, Yalong; Ma, Baozhen; Song, Yongping; Gao, Quanli

    2017-11-01

    Our study was conducted to explore the efficacy of autologous cytokine-induced killer (CIK) cells in patients with advanced malignant melanoma. Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients among which 68 patients received CIK cell immunotherapy alone, while 45 patients accepted CIK cell therapy combined with chemotherapy. Results: We found that the median survival time in CIK cell group was longer than the combined therapy group (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as monocyte proportion and lymphocyte count were associated with patients' survival time. These indicated that CIK cell immunotherapy might extend survival time in advanced malignant melanoma patients. Furthermore, serum hemoglobin level, monocyte proportion and lymphocyte count could be prognostic indicators for melanoma.

  16. Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

    NARCIS (Netherlands)

    Ritfeld, G.J.; Nandoe Tewarie, R.D.S.; Rahiem, S.T.; Hurtado, A.; Roos, R.A.; Grotenhuis, A.; Oudega, M.

    2010-01-01

    We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in

  17. Hypofractionated radiation therapy for invasive thyroid carcinoma in dogs: a retrospective analysis of survival

    International Nuclear Information System (INIS)

    Brearley, M.J.; Hayes, A.M.; Murphy, S.

    1999-01-01

    Thirteen dogs with invasive thyroid carcinoma (WHO classification T2b or T3b) seen between January 1991 and October 1997 were treated by external beam Irradiation. Four once-weekly fractions of 9 gray of 4 MeV X-rays were administered. Four of the dogs died of progression of the primary disease and four from metastatic spread. Of the remaining dogs, three died of unrelated problems, although two were still alive at the time of the censor. Kaplan-Meier analysis of the survival time from first dose to death from either primary or metastatic disease gave a median survival time of 96 weeks (mean 85 weeks, range six to 247 weeks). Radiographic evidence of pulmonary metastatic disease at presentation had no prognostic value whereas crude growth rate was a highly significant factor. The present series Indicates that radiation therapy should be considered an important modality for the control of invasive thyroid carcinoma in the dog

  18. Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?

    International Nuclear Information System (INIS)

    Poulsen, Michael G.; Rischin, Danny; Porter, Ian; Walpole, Euan; Harvey, Jennifer; Hamilton, Chris; Keller, Jacqui; Tripcony, Lee

    2006-01-01

    Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m 2 i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For

  19. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    International Nuclear Information System (INIS)

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-01-01

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

  20. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Bollen, Laurens; Dijkstra, Sander P. [Department of Orthopedic Surgery, Leiden University Medical Center (Netherlands); Steen-Banasik, Elzbieta M. van der [ARTI Institute for Radiation Oncology Arnhem, Arnhem (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is

  1. Role of TIPS in Improving Survival of Patients with Decompensated Liver Disease

    Directory of Open Access Journals (Sweden)

    Sundeep J. Punamiya

    2011-01-01

    Full Text Available Liver cirrhosis is associated with higher morbidity and reduced survival with appearance of portal hypertension and resultant decompensation. Portal decompression plays a key role in improving survival in these patients. Transjugular intrahepatic portosystemic shunts are known to be efficacious in reducing portal venous pressure and control of complications such as variceal bleeding and ascites. However, they have been associated with significant problems such as poor shunt durability, increased encephalopathy, and unchanged survival when compared with conservative treatment options. The last decade has seen a significant improvement in these complications, with introduction of covered stents, better selection of patients, and clearer understanding of procedural end-points. Use of TIPS early in the period of decompensation also appears promising in further improvement of survival of cirrhotic patients.

  2. Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

    Science.gov (United States)

    Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

    2007-09-01

    In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

  3. Improved survival in HIV-infected persons: consequences and perspectives

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Hansen, Ann-Brit Eg; Gerstoft, Jan

    2007-01-01

    -infected individual to be 39 years. The prospect of a near-normal life expectancy has implications for the HIV-infected persons as well as for the handling of the disease in the healthcare system. The patients can now on a long-term perspective plan their professional career, join a pension plan and start a family....... Further, they may expect to be treated equally with other members of society with respect to access to mortgage, health insurance and life insurance. As the infected population ages, more patients will contract age-related diseases, and the disease burden on some individuals may even come to be dominated......, improved drug adherence, prevention and treatment of HIV-unrelated co-morbidity and collaboration with other medical specialists to treat an ageing co-morbidity-acquiring HIV population....

  4. Does Music Therapy Improve Anxiety and Depression in Alzheimer's Patients?

    Science.gov (United States)

    de la Rubia Ortí, José Enrique; García-Pardo, María Pilar; Iranzo, Carmen Cabañés; Madrigal, José Joaquin Cerón; Castillo, Sandra Sancho; Rochina, Mariano Julián; Gascó, Vicente Javier Prado

    2018-01-01

    To evaluate the effectiveness of the implementation of a short protocol of music therapy as a tool to reduce stress and improve the emotional state in patients with mild Alzheimer's disease. A sample of 25 patients with mild Alzheimer's received therapy based on the application of a music therapy session lasting 60 min. Before and after the therapy, patient saliva was collected to quantify the level of salivary cortisol using the Enzyme-Linked ImmunoSorbent Assay (ELISA) immunoassay technique and a questionnaire was completed to measure anxiety and depression (Hospital Anxiety and Depression Scale). The results show that the application of this therapy lowers the level of stress and decreases significantly depression and anxiety, establishing a linear correlation between the variation of these variables and the variation of cortisol. A short protocol of music therapy can be an alternative medicine to improve emotional variables in Alzheimer patients.

  5. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    Science.gov (United States)

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  6. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Bayanzay K

    2016-08-01

    Full Text Available Karim Bayanzay, Lama Alzoebie Department of Hematology, Gulf Medical University, Ajman, United Arab Emirates Abstract: Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. Keywords: hematology, chelators, deferoxamine, deferiserox, deferiprone, liver iron concentration, iron overload, serum ferritin concentration, hepatic iron storage, iron chelation therapy

  7. Improvement of child survival in Mexico: the diagonal approach.

    Science.gov (United States)

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Oláiz, Gustavo; Partida, Virgilio; García-García, Lourdes; Valdespino, José Luis

    2006-12-02

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  8. [Improvement of child survival in Mexico: the diagonal approach].

    Science.gov (United States)

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Olaiz, Gustavo; Partida, Virgilio; García-García, Ma de Lourdes; Valdespino, José Luis

    2007-01-01

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  9. Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

    International Nuclear Information System (INIS)

    Lim, Yu Jin; Kim, Eunji; Kim, Hak Jae; Wu, Hong-Gyun; Yan, Jinchun; Liu, Qin; Patel, Shilpen

    2016-01-01

    Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

  10. Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yu Jin; Kim, Eunji [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Yan, Jinchun [Department of Radiation Oncology, Dalian Medical University, Liaoning (China); Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Liu, Qin [The Wistar Institute, Philadelphia, Pennsylvania (United States); Patel, Shilpen [Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States)

    2016-04-01

    Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

  11. Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

    Directory of Open Access Journals (Sweden)

    Leeman Jonathan E

    2012-07-01

    Full Text Available Abstract Background Brainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS of brainstem metastases. Methods We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28–89. Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44% had received whole brain radiation therapy (WBRT prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%. The median tumor volume was 0.94 cm3 (range: 0.01-4.2 with a median prescription dose of 17 Gy (range: 12–24 delivered in 1–5 fractions. Results Median follow-up for the cohort was 3.2 months (range: 0.4-20.6. Nineteen patients (52% had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79% experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40% had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of

  12. Pioglitazone Improves Survival In Patients With Cancer: The Hypothesis

    Directory of Open Access Journals (Sweden)

    Banshi Saboo

    2015-12-01

    Full Text Available Pioglitazone is currently the only thiazolidinedione approved by regulatory agencies worldwide for the treatment of type 2 diabetes mellitus (T2DM. The use of pioglitazone in patients with T2DM has been limited because earlier studies showed moderate weight gain and an increased incidence of heart failure, osteoporotic fractures, and bladder cancer. However, new studies have shown that pioglitazone improves both systolic and diastolic left ventricular function and that there is no association between pioglitazone and bladder cancer. Furthermore, pioglitazone is associated with a reduced risk of all-cause mortality in patients with T2DM. Pioglitazone was also found to reduce the incidence of lung, head and neck, breast, colorectal, and hepatocellular cancer. There is tremendous preclinical evidence that links thiazolidinediones with anti-cancer effects. Three possible mechanisms of anti-proliferative effects induced by peroxisome proliferator activated receptor gamma (PPARG agonists emerge: 1 activation of PPARG and epidermal growth factor receptor, which actives several intracellular pathways involved in carcinogenesis; 2 increase in serum adiponectin levels and decrease in serum leptin levels, which are associated with lower cancer risk and more favorable outcomes in patients with cancer; 3 modulate insulin-like growth factor 1 (IGF-1 receptor signaling by decreasing IGF-1 levels and increasing the expression of IGF binding protein 1. To date, there are no prospective, placebo-controlled trials that have analyzed the efficacy of pioglitazone in chemotherapy and chemoprevention. Only one ongoing study has shown that pioglitazone has an excellent capability of eradicating quiescent leukemia stem cells in patients with chronic myeloid leukemia and achieving a complete molecular response. Current evidence supports our theory that future case-control studies examining pioglitazone as chemotherapy, or adjuvant chemotherapy, should be performed in

  13. Metabolomics has the potential to improve drug therapy

    DEFF Research Database (Denmark)

    Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder

    2014-01-01

    Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even more...

  14. Scoring system predictive of survival for patients undergoing stereotactic body radiation therapy for liver tumors

    Directory of Open Access Journals (Sweden)

    Kress Marie-Adele S

    2012-09-01

    Full Text Available Abstract Background Stereotactic body radiation therapy (SBRT is an emerging treatment option for liver tumors. This study evaluated outcomes after SBRT to identify prognostic variables and to develop a novel scoring system predictive of survival. Methods The medical records of 52 patients with a total of 85 liver lesions treated with SBRT from 2003 to 2010 were retrospectively reviewed. Twenty-four patients had 1 lesion; 27 had 2 or more. Thirteen lesions were primary tumors; 72 were metastases. Fiducials were placed in all patients prior to SBRT. The median prescribed dose was 30 Gy (range, 16 – 50 Gy in a median of 3 fractions (range, 1–5. Results With median follow-up of 11.3 months, median overall survival (OS was 12.5 months, and 1 year OS was 50.8%. In 42 patients with radiographic follow up, 1 year local control was 74.8%. On univariate analysis, number of lesions (p = 0.0243 and active extralesional disease (p  Conclusions SBRT offers a safe and feasible treatment option for liver tumors. A prognostic scoring system based on the number of liver lesions, activity of extralesional disease, and KPS predicts survival following SBRT and can be used as a guide for prospective validation and ultimately for treatment decision-making.

  15. Improve T Cell Therapy in Neuroblastoma

    Science.gov (United States)

    2012-07-01

    Savoldo B, Vigouroux S et al. T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte...Natl Acad Sci U S A. 2004;101(suppl 2):14622–14626. 8. Eghtesad S, Morel PA, Clemens PR. The companions : regulatory T cells and gene therapy...were euthanized and examined for NKT cell localiza- tion to the tumor tissues. Animals treated with anti-CCL2 or anti- CCL20 mAb had lower frequency

  16. Increasing Winter Maximal Metabolic Rate Improves Intrawinter Survival in Small Birds.

    Science.gov (United States)

    Petit, Magali; Clavijo-Baquet, Sabrina; Vézina, François

    Small resident bird species living at northern latitudes increase their metabolism in winter, and this is widely assumed to improve their chances of survival. However, the relationship between winter metabolic performance and survival has yet to be demonstrated. Using capture-mark-recapture, we followed a population of free-living black-capped chickadees (Poecile atricapillus) over 3 yr and evaluated their survival probability within and among winters. We also measured the size-independent body mass (M s ), hematocrit (Hct), basal metabolic rate (BMR), and maximal thermogenic capacity (Msum) and investigated how these parameters influenced survival within and among winters. Results showed that survival probability was high and constant both within (0.92) and among (0.96) winters. They also showed that while M s , Hct, and BMR had no significant influence, survival was positively related to Msum-following a sigmoid relationship-within but not among winter. Birds expressing an Msum below 1.26 W (i.e., similar to summer levels) had a winter. Our data therefore suggest that black-capped chickadees that are either too slow or unable to adjust their phenotype from summer to winter have little chances of survival and thus that seasonal upregulation of metabolic performance is highly beneficial. This study is the first to document in an avian system the relationship between thermogenic capacity and winter survival, a proxy of fitness.

  17. NanOx, a new model to predict cell survival in the context of particle therapy

    Science.gov (United States)

    Cunha, M.; Monini, C.; Testa, E.; Beuve, M.

    2017-02-01

    Particle therapy is increasingly attractive for the treatment of tumors and the number of facilities offering it is rising worldwide. Due to the well-known enhanced effectiveness of ions, it is of utmost importance to plan treatments with great care to ensure tumor killing and healthy tissues sparing. Hence, the accurate quantification of the relative biological effectiveness (RBE) of ions, used in the calculation of the biological dose, is critical. Nevertheless, the RBE is a complex function of many parameters and its determination requires modeling. The approaches currently used have allowed particle therapy to thrive, but still show some shortcomings. We present herein a short description of a new theoretical framework, NanOx, to calculate cell survival in the context of particle therapy. It gathers principles from existing approaches, while addressing some of their weaknesses. NanOx is a multiscale model that takes the stochastic nature of radiation at nanometric and micrometric scales fully into account, integrating also the chemical aspects of radiation-matter interaction. The latter are included in the model by means of a chemical specific energy, determined from the production of reactive chemical species induced by irradiation. Such a production represents the accumulation of oxidative stress and sublethal damage in the cell, potentially generating non-local lethal events in NanOx. The complementary local lethal events occur in a very localized region and can, alone, lead to cell death. Both these classes of events contribute to cell death. The comparison between experimental data and model predictions for the V79 cell line show a good agreement. In particular, the dependence of the typical shoulders of cell survival curves on linear energy transfer are well described, but also the effectiveness of different ions, including the overkill effect. These results required the adjustment of a number of parameters compatible with the application of the model in

  18. Are global and regional improvements in life expectancy and in child, adult and senior survival slowing?

    Directory of Open Access Journals (Sweden)

    Ryan J Hum

    Full Text Available Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health-primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest.

  19. Stem Cell Therapy to Improve Burn Wound Healing

    Science.gov (United States)

    2017-03-01

    Award Number: W81XWH-13-2-0024 TITLE: Stem Cell Therapy to Improve Burn Wound Healing PRINCIPAL INVESTIGATOR: Carl Schulman, MD, PhD, MSPH...NUMBER Stem Cell Therapy to Improve Burn Wound Healing 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Carl Schulman, MD, PhD, MSPH...treatments, steroid injections, and compression garments. Mesenchymal stem cells (MSC’s) have been used in a variety of clinical applications to repair

  20. Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury PRINCIPAL...TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord...care. However, despite these drastic interventions, the cervical injured patient is still susceptible to death due to respiratory complications

  1. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension rates-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.24 Improved pension...

  2. Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

    Science.gov (United States)

    Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

    2017-08-01

    To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p 12 g/dl was a factor with an average association with the overall survival (p cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

  3. Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology, and Survival in the Mouse Model of Bubonic Plague.

    Science.gov (United States)

    Levy, Yinon; Vagima, Yaron; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Gur, David; Fogel, Itay; Chitlaru, Theodor; Flashner, Yehuda; Mamroud, Emanuelle

    2016-09-15

    Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of antiplague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague. Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-Y. pestis antibodies alone or in combination with the corticosteroid methylprednisolone. The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase 9 in the tissues, and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs. Corticosteroids induce an unexpectedly effective antibacterial response apart from their antiinflammatory properties, thereby improving treatment efficacy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Promising survival with three-dimensional conformal radiation therapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Armstrong, John; Raben, Adam; Zelefsky, Michael; Burt, Michael; Leibel, Steve; Burman, Chandra; Kutcher, Gerard; Harrison, Louis; Hahn, Cathy; Ginsberg, Robert; Rusch, Valerie; Kris, Mark; Fuks, Zvi

    1997-01-01

    Purpose: Local failure is a major obstacle to the cure of locally advanced non small-cell lung cancer. Three-dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially representing an enhancement of the therapeutic ratio of radiation therapy for lung cancer. We performed this analysis of 45 non-small cell lung cancer patients treated with 3-DCRT alone, to evaluate the ability of computer derived lung dose volume histograms to predict serious pulmonary toxicity, to assess the feasibility of this approach, and to examine the resulting survival. Methods: There were 28 males (62%) and 17 females (38%). The median age was 65 (range: 38-82). Tumor stage was Stage I/II in 13%, IIIa in 42%, and IIIb in 44%. The histology was squamous in 44%, adenocarcinoma in 36%, and other non-small cell histologies in the others. Only 47% of patients. had combined favorable prognostic factors (i.e. KPS ≤ 80, and ≤5% wt. loss). The median dose of radiation to gross disease was 70.2 Gy (range: 52.2-72 Gy) delivered in fractions of 1.8 Gy, 5 days per week. Results: Seven patients did not complete 3-DCRT due to disease progression outside the port. Follow-up data are mature: the median follow up of the 6 survivors is 43.5 months (35-59). Thoracic progression occurred in 46%. Median survival (all 45 patients.) is 15.7 months and survival is 32% at 2 years and 12% at 59 months. Pulmonary toxicity ≥grade 3 occurred in 9% of patients. Dose volume histograms were available in 31 patients and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% ((3(8))) of patients with >30% of lung volume receiving ≥25 Gy, versus 4% ((1(23))) of patients with ≤30% lung receiving ≥25 Gy (P = 0.04). Grade 3 or higher pulmonary toxicity occurred in 29% ((4(14))) of patients with a predicted pulmonary normal tissue

  5. Improving village poultry’s survival rate through community-based poultry health management

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto D.

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of “poultry interest groups” in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due...... to the fact that village poultry farming is practiced in a total or partial scavenging system which gives the impression that all the birds in the village belong to the same flock. Accordingly, actions that target all farmers of the same village may have a larger impact on the village poultry’s survival rate...... than actions that target individual producers. The objective of this study is to assess the impact of CBM on the survival rate of village poultry. Based on data collected on 353 poultry keepers, the study shows that CBM significantly improves the survival rate of village poultry. The adoption...

  6. Improving village poultry's survival rate through community-based poultry health management

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto Delphin

    2012-01-01

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of “poultry interest groups” in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due...... to the fact that village poultry farming is practiced in a total or partial scavenging system which gives the impression that all the birds in the village belong to the same flock. Accordingly, actions that target all farmers of the same village may have a larger impact on the village poultry's survival rate...... than actions that target individual producers. The objective of this study is to assess the impact of CBM on the survival rate of village poultry. Based on data collected on 353 poultry keepers, the study shows that CBM significantly improves the survival rate of village poultry. The adoption...

  7. Kinetic therapy improves oxygenation in critically ill pediatric patients.

    Science.gov (United States)

    Schultz, Theresa Ryan; Lin, Richard; Francis, Barbara A; Hales, Roberta L; Colborn, Shawn; Napoli, Linda A; Helfaer, Mark A

    2005-07-01

    To compare changes in oxygenation after manual turning and percussion (standard therapy) and after automated rotation and percussion (kinetic therapy). Randomized crossover trial. General and cardiac pediatric intensive care units. Intubated and mechanically ventilated pediatric patients who had an arterial catheter and no contraindications to using a PediDyne bed. Patients were placed on a PediDyne bed (Kinetic Concepts) and received 18 hrs blocks of standard and kinetic therapy in an order determined by randomization. Arterial blood gases were measured every 2 hrs during each phase of therapy. Oxygenation index and arterial-alveolar oxygen tension difference [P(A-a)O(2)] were calculated. Indexes calculated at baseline and after each 18-hr phase of therapy were analyzed. Fifty patients were enrolled. Data from 15 patients were either not collected or not used due to reasons that included violation of protocol and inability to tolerate the therapies in the study. Indexes of oxygenation were not normally distributed and were compared using Wilcoxon signed rank testing. Both therapies led to improvements in oxygenation, but only those from kinetic therapy achieved statistical significance. In patients receiving kinetic therapy first, median oxygenation index decreased from 7.4 to 6.19 (p = .015). The median P(A-a)O(2) decreased from 165.2 to 126.4 (p = .023). There were continued improvements in oxygenation after the subsequent period of standard therapy, with the median oxygenation index decreasing to 5.52 and median P(A-a)O(2) decreasing to 116.0, but these changes were not significant (p = .365 and .121, respectively). When standard therapy was first, the median oxygenation index decreased from 8.83 to 8.71 and the median P(a-a)o(2) decreased from 195.4 to 186.6. Neither change was significant. Median oxygenation index after the subsequent period of kinetic therapy was significantly lower (7.91, p = .044) and median P(A-a)O(2) trended lower (143.4, p = .077

  8. Delayed Posthypoxic Leukoencephalopathy: Improvement with Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Franklin King

    2015-12-01

    Full Text Available Introduction: Delayed posthypoxic leukoencephalopathy (DPHL may result from a variety of hypoxic insults, including respiratory depression from an opiate overdose. The underlying pathophysiological mechanism of DPHL remains uncertain. We describe a patient with a typical case of DPHL who responded clinically to antioxidant treatment. Methods: Clinical, serological, and radiographic investigations were undertaken in the evaluation of the patient. Results: A 63-year-old man developed altered mental status 10 days following recovery from an opiate overdose and aspiration pneumonia that required intubation. The clinical course and brain imaging were consistent with DPHL. Initiation of antioxidant therapy with vitamin E, vitamin C, B-complex vitamins, and coenzyme Q10 coincided with the prompt reversal of clinical deterioration. Conclusions: The potential therapeutic effect of antioxidants on DPHL needs to be explored in future cases. If this relationship indeed holds true, it would be consistent with the hypothesis that formation of reactive oxygen species during reperfusion plays a role in the pathophysiology of this disorder.

  9. Improved survival for rectal cancer compared to colon cancer: the four cohort study.

    Science.gov (United States)

    Buchwald, Pamela; Hall, Claire; Davidson, Callum; Dixon, Liane; Dobbs, Bruce; Robinson, Bridget; Frizelle, Frank

    2018-03-01

    Colorectal cancer (CRC) is the third most common cancer worldwide. This study was undertaken to evaluate survival outcomes and changes of disease outcomes of CRC patients over the last decades. A retrospective analysis of CRC patients in Christchurch was performed in four patient cohorts at 5 yearly intervals; 1993-94, 1998-99, 2004-05 and 2009. Data on cancer location, stage, surgical and oncological treatment and survival were collected. Univariate, multivariate and Kaplan-Meier survival analysis were performed. There were 1391 patients (355, 317, 419 and 300 per cohort), 1037 colon and 354 rectal cancers, respectively. For colon cancer, right-sided cancers appeared more common in later cohorts (P = 0.01). There was a significant decrease in the number of permanent stomas for colon cancer patients (P = 0.001). There was an analogous trend for rectal cancers (P = 0.075). More CRC patients with stage IV disease were treated surgically (P = 0.001) and colon cancer stages I and II tended to have increased survival if operated by a colorectal surgeon (P = 0.06). Oncology referrals have increased remarkably (P = 0.001). Overall 56% of patients were alive at 5 years however rectal cancer patients had significantly better 5-year survival than those with colon cancer (P rectal cancer patients have a better 5-year survival than colon cancer patients. The improved survival with early stage colon cancers operated on by specialist colorectal surgeons needs further exploration. © 2016 Royal Australasian College of Surgeons.

  10. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  11. Trophic factors as modulators of motor neuron physiology and survival: implications for ALS therapy

    Directory of Open Access Journals (Sweden)

    Luis B Tovar-y-Romo

    2014-02-01

    Full Text Available Motor neuron physiology and development depend on a continuous and tightly regulated trophic support from a variety of cellular sources. Trophic factors guide the generation and positioning of motor neurons during every stage of the developmental process. As well, they are involved in axon guidance and synapse formation. Even in the adult spinal cord an uninterrupted trophic input is required to maintain neuronal functioning and protection from noxious stimuli. Among the trophic factors that have been demonstrated to participate in motor neuron physiology are vascular endothelial growth factor (VEGF, glial-derived neurotrophic factor (GDNF, ciliary neurotrophic factor (CNTF and insulin-like growth factor 1 (IGF-1. Upon binding to membrane receptors expressed in motor neurons or neighboring glia, these trophic factors activate intracellular signaling pathways that promote cell survival and have protective action on motor neurons, in both in vivo and in vitro models of neuronal degeneration. For these reasons these factors have been considered a promising therapeutic method for amyotrophic lateral sclerosis (ALS and other neurodegenerative diseases, although their efficacy in human clinical trials have not yet shown the expected protection. In this review we summarize experimental data on the role of these trophic factors in motor neuron function and survival, as well as their mechanisms of action. We also briefly discuss the potential therapeutic use of the trophic factors and why these therapies may have not been yet successful in the clinical use.

  12. SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kotti, Angeliki, E-mail: angkotti@yahoo.gr; Holmqvist, Annica; Albertsson, Maria; Sun, Xiao-Feng, E-mail: xiao-feng.sun@liu.se

    2014-04-01

    Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  13. Improving Islet Engraftment by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2011-01-01

    Full Text Available Islet cell transplantation is currently the only feasible long-term treatment option for patients with type 1 diabetes. However, the majority of transplanted islets experience damage and apoptosis during the isolation process, a blood-mediated inflammatory microenvironment in the portal vein upon islet infusion, hypoxia induced by the low oxygenated milieu, and poor-revascularization-mediated lack of nutrients, and impaired hormone modulation in the local transplanted site. Strategies using genetic modification methods through overexpression or silencing of those proteins involved in promoting new formation of blood vessels or inhibition of apoptosis may overcome these hurdles and improve islet engraftment outcomes.

  14. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

    Science.gov (United States)

    Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

    2015-08-01

    We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Survival in pediatric medulloblastoma: a population-based observational study to improve prognostication.

    Science.gov (United States)

    Weil, Alexander G; Wang, Anthony C; Westwick, Harrison J; Ibrahim, George M; Ariani, Rojine T; Crevier, Louis; Perreault, Sebastien; Davidson, Tom; Tseng, Chi-Hong; Fallah, Aria

    2017-03-01

    Medulloblastoma is the most common form of brain malignancy of childhood. The mainstay of epidemiological data regarding childhood medulloblastoma is derived from case series, hence population-based studies are warranted to improve the accuracy of survival estimates. To utilize a big-data approach to update survival estimates in a contemporary cohort of children with medulloblastoma. We performed a population-based retrospective observational cohort study utilizing the Surveillance, Epidemiology, and End Results Program database that captures all children, less than 20 years of age, between 1973 and 2012 in 18 geographical regions representing 28% of the US population. We included all participants with a presumed or histologically diagnosis of medulloblastoma. The main outcome of interest is survivors at 1, 5 and 10 years following diagnosis. A cohort of 1735 children with a median (interquartile range) age at diagnosis of 7 (4-11) years, with a diagnosis of medulloblastoma were identified. The incidence and prevalence of pediatric medulloblastoma has remained stable over the past 4 decades. There is a critical time point at 1990 when the overall survival has drastically improved. In the contemporary cohort (1990 onwards), the percentage of participants alive was 86, 70 and 63% at 1, 5 and 10 years, respectively. Multivariate Cox-Regression model demonstrated Radiation (HR 0.37; 95% CI 0.30-0.46, p < 0.001) and Surgery (HR 0.42; 95% CI 0.30-0.58, p < 0.001) independently predict survival. The probability of mortality from a neurological cause is <5% in patients who are alive 8 years following diagnosis. The SEER cohort analysis demonstrates significant improvements in pediatric medulloblastoma survival. In contrast to previous reports, the majority of patients survive in the modern era, and those alive 8 years following initial diagnosis are likely a long-term survivor. The importance of minimizing treatment-related toxicity is increasingly apparent given

  16. Primary Tumour Resection Could Improve the Survival of Unresectable Metastatic Colorectal Cancer Patients Receiving Bevacizumab-Containing Chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhiming Wang

    2016-09-01

    Full Text Available Background: The effect of primary tumour resection (PTR among metastatic colorectal cancer (mCRC patients remains controversial. Combination chemotherapy with bevacizumab could improve the clinical outcomes of these patients, which might change the importance of PTR in the multi-disciplinary treatment pattern. Methods: We performed a non-randomized prospective controlled study of mCRC pts whose performance status (PS scored ≤2 and who received bevacizumab combination chemotherapy (FOLFOX/XELOX/FOLFIRI as a first-line therapy. These patients were classified into the PTR group and the IPT (intact primary tumour group according to whether they underwent PTR before receiving the systemic therapy. The progression free survival (PFS time and overall survival (OS time, which were recorded from the start of the primary diagnosis until disease progression and death or last follow-up, were analysed. We also compared severe clinical events (such as emergency surgery, radiation therapy, and stent plantation between the two groups. Results: One hundred and nighty-one mCRC pts (108 male patients and 93 female patients were entered in this prospective observational study. The median age was 57.5 years old. The clinical characteristics (age, gender, performance status, primary tumour site, RAS status, and the number of metastatic organs did not significantly differ between the two groups. The median PFS and OS times of the PTR group were superior than those of the IPT group (10.0 vs 7.8 months, p Conclusions: The mCRC patients who received PTR and bevacizumab combination chemotherapy had better clinical outcomes than patients who did not receive PTR. PTR also decreased the incidence of severe clinical events and improved quality of life.

  17. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    Science.gov (United States)

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  18. Improved survival after an out-of-hospital cardiac arrest using new guidelines

    DEFF Research Database (Denmark)

    Steinmetz, Jacob; Barnung, S.; Nielsen, S.L.

    2008-01-01

    BACKGROUND: An out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis. We hypothesized that the implementations of 2005 European Resuscitation Council resuscitation guidelines were associated with improved 30-day survival after OHCA. METHODS: We prospectively recorded data on all....... Treatment after implementation was confirmed as a significant predictor of better 30-day survival in a logistic regression analysis. CONCLUSION: The implementation of new resuscitation guidelines was associated with improved 30-day survival after OHCA Udgivelsesdato: 2008/8...... patients with OHCA treated by the Mobile Emergency Care Unit of Copenhagen in two periods: 1 June 2004 until 31 August 2005 (before implementation) and 1 January 2006 until 31 March 2007 (after implementation), separated by a 4-month period in which the above-mentioned change took place. RESULTS: We found...

  19. Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

    Directory of Open Access Journals (Sweden)

    Lisa Y. Pang

    2016-01-01

    Full Text Available Cyclooxygenase-2 (COX-2 is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2, a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2 release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

  20. Health care factors associated with survival among women with breast cancer on hormone therapy in Rio de Janeiro, Brazil, 2004 – 2010

    Directory of Open Access Journals (Sweden)

    Cláudia de Brito

    Full Text Available ABSTRACT Objectives To better understand the role that health care plays in breast cancer survival by investigating the effects that hormone therapy adherence and other select health care variables, adjusted for clinical and sociodemographic factors, had among a population of women in Rio de Janeiro, Brazil. Methods This was a longitudinal study based on secondary data of 5 861 women treated with hormone therapy (tamoxifen or aromatase inhibitors at the National Cancer Institute of Brazil (INCA, from 1 January 2004 – 29 October 2010. Four different sources of data were integrated for analysis: INCA Pharmacy Sector Dispensation System; Hospital-based Cancer Registry; Integrated Hospital System and INCA Absolute System; and Mortality Information System. Analyses explored the effects of adherence to hormone therapy, disease care aspects, and sociodemographic, behavioral, and clinical variables, on the time of survival, using Kaplan-Meier and Cox proportional hazards models. Results The general survival rate was 94% in the first year after initiation of hormone therapy, and 71% in the fifth year. The Cox model indicated a higher hazard of death among women smokers, with more hospitalizations, more exams, and, among those who used, who used only aromatase inhibitors, as hormone therapy modality. The hazard was lower among women with a partner (stable relationship, a high school or college education a family history of cancer, and those who were treated by a mastologist, oncologist, and/or psychotherapist, who underwent surgery, and who adhered to hormone therapy. Conclusions The study indicated more vulnerable sub-groups and the aspects of care that provide best results, bringing new knowledge to improve assistance to this group of women.

  1. Animal-Assisted Therapy for Improving Human Health

    Directory of Open Access Journals (Sweden)

    Sibel Cevizci

    2009-06-01

    Full Text Available ABSTRACT Animal Assisted Therapy (AAT or Pet Therapy is an adjunctive therapy by taking advantage of human and animal interaction, activate the physiological and psychological mechanisms, initiate positive changes improving health in metabolism. In recent years, this interaction are in use to treat psychological and psychiatric disorders such as stress, depression, loneliness, pervasive developmental disorders affect negatively to human health. Furthermore, AAT has been increasingly used to improve quality of life, hypertension, cardiovascular diseases, chronic illnesses such as cancer and AIDS. The aim of this paper is to identify AAT by reviewing human and animal interaction, evaluate how AAT has a scientific background from past to now. Also, we aim to give some information about the risks, institutional applications, some factors referring AAT’s mechanism of action and chronic diseases, psychological and physical improvements provided with animal assisted therapies. The therapy results will be evaluated more advisable providing AAT is being applied with public health specialist, veterinarian, physician, psychologist, psychiatrist and veterinary public health experts who are monitor applications. Especially, the psychosomatic effects result from physical, emotional and play mechanism of action of HDT can be used for improving quality of life in individuals with chronic diseases. In Turkey, there is no any investigation which have been performed in this scientific field. It is quitely important to evaluate the benefits of this therapy accurately and to select various methods proper to diseases. Consequently, it is obvious that AAT will be considered by the healthcare services as a supportive therapy process for improving human health in Turkey and needs further studies. [TAF Prev Med Bull 2009; 8(3.000: 263-272

  2. Witnessed arrest, but not delayed bystander cardiopulmonary resuscitation improves prehospital cardiac arrest survival.

    Science.gov (United States)

    Vukmir, R B

    2004-05-01

    This study correlated the effect of witnessing a cardiac arrest and instituting bystander CPR (ByCPR), as a secondary end point in a study evaluating the effect of bicarbonate on survival. This prospective, randomised, double blinded clinical intervention trial enrolled 874 prehospital cardiopulmonary arrest patients encountered in a prehospital urban, suburban, and rural regional emergency medical service (EMS) area. This group underwent conventional advanced cardiac life support intervention followed by empiric early administration of sodium bicarbonate (1 mEq/l), monitoring conventional resuscitation parameters. Survival was measured as presence of vital signs on emergency department (ED) arrival. Data were analysed using chi(2) with Pearson correlation and odds ratio where appropriate. The overall survival rate was 13.9% (110 of 792) of prehospital cardiac arrest patients. The mean (SD) time until provision of bystander cardiopulmonary resuscitation (ByCPR) by laymen was 2.08 (2.77) minutes, and basic life support (BLS) by emergency medical technicians was 6.62 (5.73) minutes. There was improved survival noted with witnessed cardiac arrest-a 2.2-fold increase in survival, 18.9% (76 of 402) versus 8.6% (27 of 315) compared with unwitnessed arrests (ptwo minutes (p = 0.3752). Survival after prehospital cardiac arrest is more likely when witnessed, but not necessarily when ByCPR was performed by laymen.

  3. Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy

    International Nuclear Information System (INIS)

    Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A. M.S.; Adamovich, Edward

    2006-01-01

    Purpose: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. Methods and Materials: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. Conclusions: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death

  4. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease

    NARCIS (Netherlands)

    Lutgens, M. W. M. D.; Oldenburg, B.; Siersema, P. D.; van Bodegraven, A. A.; Dijkstra, G.; Hommes, D. W.; de Jong, D. J.; Stokkers, P. C. F.; van der Woude, C. J.; Vleggaar, F. P.

    2009-01-01

    BACKGROUND: Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. METHOD: The aim of this study was to compare tumour stage and

  5. Improved survival of colorectal cancer in Denmark during 2001-2012

    DEFF Research Database (Denmark)

    Iversen, Lene Hjerrild; Green, Anders; Ingeholm, Peter

    2016-01-01

    cancer and 15 213 patients with rectal cancer were included. The stage distribution was almost stable over time. The mortality rate per 100 patient year within one year decreased from 32 to 26 in colon cancer and from 26 to 19 in rectal cancer with associated improvements in absolute survival from 73......% to 78% in colon cancer and from 78% to 83% in rectal cancer. The five-year relative survival of colon cancer improved from 58% to 63% and in rectal cancer from 59% to 65%. Comorbidity had major negative impact on outcome. Irrespective of tumor location, outcome improved relatively more in patients...... with stage III and IV disease. The proportion of patients who were spared surgery increased from 8% to 15% in colon cancer and from 13% to 19% in rectal cancer, and these changes were associated with improved outcome for rectal cancer patients, whereas outcome worsened for colon cancer patients. Conclusion...

  6. Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers.

    Science.gov (United States)

    Lechner, Melissa G; Vyas, Chirag M; Hamnvik, Ole-Petter R; Alexander, Erik K; Larsen, P Reed; Choueiri, Toni K; Angell, Trevor E

    2018-04-01

    Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction is recognized as a common adverse effect of treatment, but the importance of incident hypothyroidism during TKI therapy remains unclear. This study analyzed the prognostic significance of hypothyroidism during TKI therapy in cancer patients. This was a retrospective cohort study of adult patients with advanced nonthyroidal cancer treated with TKI and available thyroid function testing at three affiliated academic hospitals from 2000 to 2017. Patients with preexisting thyroid disease were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid status with TKI treatment was determined from thyroid function testing and initiation of thyroid medication, and classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement). Multivariate models were used to evaluate the effect of TKI-related hypothyroidism on overall survival (OS). Of 1120 initial patients, 538 remained after exclusion criteria. SCH occurred in 72 (13%) and OH in 144 (27%) patients with TKI therapy. Patients with hypothyroidism had significantly longer OS, with median OS in euthyroid patients of 685 days [confidence interval (CI) 523-851] compared to 1005 days [CI 634-1528] in SCH and 1643 days [CI 1215-1991] in OH patients (p hypothyroid patients (SCH and OH) with TSH >5 and hypothyroidism in cancer patients treated with TKI is associated with significantly improved OS, should not necessitate TKI dose reduction or discontinuation, and may provide independent prognostic information.

  7. Edaravone improves survival and neurological outcomes after CPR in a ventricular fibrillation model of rats.

    Science.gov (United States)

    Qin, Tao; Lei, Ling-Yan; Li, Nuo; Shi, Fangying Ruan; Chen, Meng-Hua; Xie, Lu

    2016-10-01

    Overproduction of free radicals is a main factor contributing to cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). We sought to evaluate the impact of edaravone on the survival and neurological outcomes after CA/CPR in rats. Rats were subjected to CA following CPR. For survival study, the rats with restoration of spontaneous circulation (ROSC) were randomly allocated to one of the two groups (edaravone and saline group, n=20/each group) to received Edaravone (3 mg/kg) or normal saline. Another 10 rats without experiencing CA and CPR served as the sham group. Survival was observed for 72 hours and the neurological deficit score (NDS) was calculated at 12, 24, 48, and 72 hours after ROSC. For the neurological biochemical analysis study, rats were subjected to the same experimental procedures. Then, edaravone group (n=24), saline group (n=24) and sham group (n=16) were further divided into 4 subgroups according to the different time intervals (12, 24, 48, and 72 hours following ROSC). Brain tissues were harvested at relative time intervals for evaluation of oxidative stress, TUNEL staining and apoptotic gene expression. Edaravone improved postresuscitative survival time and neurological deficit, decreased brain malonylaldehyde level, increased superoxide dismutase activities, decreased proapoptotic gene expression of capase-8, capase-3, and Bax, and increased antiapoptotic Bcl-2 expression at 12, 24, 48, and 72 hours after ROSC. Edaravone improves survival and neurological outcomes following CPR via antioxidative and antiapoptotic effects in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Interact to survive: Phyllobacterium brassicacearum improves Arabidopsis tolerance to severe water deficit and growth recovery.

    Directory of Open Access Journals (Sweden)

    Justine Bresson

    Full Text Available Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm, was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture.

  9. Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

    Science.gov (United States)

    Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

    2018-02-01

    The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

  10. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

    Science.gov (United States)

    Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

    2011-06-03

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. 2011 Elsevier B.V. All rights reserved.

  11. Survival After Conservative Management Versus External Beam Radiation Therapy in Elderly Patients With Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dell' Oglio, Paolo, E-mail: paolo.delloglio@gmail.com [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan (Italy); Boehm, Katharina [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg (Germany); Trudeau, Vincent [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Department of Urology, University of Montreal Health Center, Montreal, Québec (Canada); Tian, Zhe [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec (Canada); Larcher, Alessandro [Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan (Italy); Leyh-Bannurah, Sami-Ramzi [Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Québec (Canada); Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg (Germany); Moschini, Marco; Capitanio, Umberto [Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan (Italy); Shariat, Shahrokh F. [Department of Urology, Medical University of Vienna and General Hospital, Vienna (Austria); and others

    2016-12-01

    Purpose: To compare survival in elderly men with clinically localized prostate cancer (PCa) according to treatment type, defined as radiation therapy (RT) with or without androgen deprivation therapy (ADT) versus conservative management (observation). Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database, we identified 23,790 patients aged 80 years or more with clinically localized PCa treated with either RT or observation between 1991 and 2009. Competing risks analyses focused on cancer-specific mortality and other-cause mortality, after accounting for confounders. All analyses were repeated after stratification according to grade (well-differentiated vs moderately differentiated vs poorly differentiated disease), race, and United States region, in patients with no comorbidities and in patients with at least 1 comorbidity. Analyses were repeated within most contemporary patients, namely those treated between 2001 and 2009. Results: Radiation therapy was associated with more favorable cancer-specific mortality rates than observation in patients with moderately differentiated disease (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.66-0.94; P=.009) and in patients with poorly differentiated disease (HR 0.58; 95% CI 0.49-0.69; P<.001). Conversely, the benefit of RT was not observed in well-differentiated disease. The benefit of RT was confirmed in black men (HR 0.54; 95% CI 0.35-0.83; P=.004), across all United States regions (all P≤.004), in the subgroups of the healthiest patients (HR 0.67; 95% CI 0.57-0.78; P<.001), in patients with at least 1 comorbidity (HR 0.69; 95% CI 0.56-0.83; P<.001), and in most contemporary patients (HR 0.55; 95% CI 0.46-0.66; P<.001). Conclusions: Radiation therapy seems to be associated with a reduction in the risk of death from PCa relative to observation in elderly patients with clinically localized PCa, except for those with well-differentiated disease.

  12. Survival After Conservative Management Versus External Beam Radiation Therapy in Elderly Patients With Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Dell'Oglio, Paolo; Boehm, Katharina; Trudeau, Vincent; Tian, Zhe; Larcher, Alessandro; Leyh-Bannurah, Sami-Ramzi; Moschini, Marco; Capitanio, Umberto; Shariat, Shahrokh F.

    2016-01-01

    Purpose: To compare survival in elderly men with clinically localized prostate cancer (PCa) according to treatment type, defined as radiation therapy (RT) with or without androgen deprivation therapy (ADT) versus conservative management (observation). Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database, we identified 23,790 patients aged 80 years or more with clinically localized PCa treated with either RT or observation between 1991 and 2009. Competing risks analyses focused on cancer-specific mortality and other-cause mortality, after accounting for confounders. All analyses were repeated after stratification according to grade (well-differentiated vs moderately differentiated vs poorly differentiated disease), race, and United States region, in patients with no comorbidities and in patients with at least 1 comorbidity. Analyses were repeated within most contemporary patients, namely those treated between 2001 and 2009. Results: Radiation therapy was associated with more favorable cancer-specific mortality rates than observation in patients with moderately differentiated disease (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.66-0.94; P=.009) and in patients with poorly differentiated disease (HR 0.58; 95% CI 0.49-0.69; P<.001). Conversely, the benefit of RT was not observed in well-differentiated disease. The benefit of RT was confirmed in black men (HR 0.54; 95% CI 0.35-0.83; P=.004), across all United States regions (all P≤.004), in the subgroups of the healthiest patients (HR 0.67; 95% CI 0.57-0.78; P<.001), in patients with at least 1 comorbidity (HR 0.69; 95% CI 0.56-0.83; P<.001), and in most contemporary patients (HR 0.55; 95% CI 0.46-0.66; P<.001). Conclusions: Radiation therapy seems to be associated with a reduction in the risk of death from PCa relative to observation in elderly patients with clinically localized PCa, except for those with well-differentiated disease.

  13. Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

    Science.gov (United States)

    Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

    2018-01-01

    To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have

  14. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

  15. Superior metastasis-free survival for patients with high-risk prostate cancer treated with definitive radiation therapy compared to radical prostatectomy: A propensity score-matched analysis

    Directory of Open Access Journals (Sweden)

    Stephanie Markovina, MD, PhD

    2018-04-01

    Full Text Available Purpose: For high-risk prostate cancer (HR-PCa in men with a life expectancy of at least 10 years, the National Comprehensive Cancer Network recommends radiation therapy (RT plus androgen deprivation therapy (ADT with category 1 evidence or radical prostatectomy (RP as an acceptable initial therapy. Randomized evidence regarding which therapy is optimal for disease control is lacking for men with HR-PCa. We performed a propensity-score-matched comparison of outcomes for men with localized HR-PCa treated with primary RT or RP. Methods and materials: The medical records of patients with localized HR-PCa who were treated at our institution between 2002 and 2011 were reviewed. Patient and disease characteristics, treatment details, and outcomes were collected. A combination of nearest-neighbor propensity score matching on age, Adult Comorbidity Evaluation-27 comorbidity index, prostate-specific antigen, biopsy Gleason scores, and clinical T-stage as well as exact matching on prostate-specific antigen, biopsy Gleason scores, and clinical T-stage was performed. Outcomes were measured from diagnosis. Multivariate Cox proportional hazards regression was used to compare metastasis-free and overall survival. Results: A total of 246 patients were identified with 62 propensity-score-matched pairs. ADT was administered to 6.5% and 80.6% of patients receiving RP and RT, respectively. Five-year rates of metastasis for RP and RT were 33% and 8.9%, respectively (P = .003. Overall survival was not different. Delay of salvage therapy was longer for patients undergoing primary RT (P < .001. Findings were similar when only those patients who did not receive ADT were compared. Conclusions: At our institution, treatment with primary RT resulted in superior metastasis-free survival over RP. This was not accompanied by an improvement in OS.

  16. Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

    Directory of Open Access Journals (Sweden)

    Steve R. Martinez

    2013-02-01

    Full Text Available The intact parathyroid hormone (iPTH assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa. We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I and 1997 to 2006 (era II, when the iPTH assay was in standard use. We estimated overall survival (OS and disease-specific survival (DSS using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with dis- tant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.

  17. Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

    1997-01-01

    Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

  18. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    International Nuclear Information System (INIS)

    Boda-Heggemann, J.; Schneider, V.; Weiss, C.

    2013-01-01

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  19. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, J.; Schneider, V. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Radiation Oncology; Weiss, C. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Biomathematics and Medical Statistics] [and others

    2013-05-15

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  20. CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

    International Nuclear Information System (INIS)

    Ke, Chien-Chih; Liu, Ren-Shyan; Yang, An-Hang; Liu, Ching-Sheng; Chi, Chin-Wen; Tseng, Ling-Ming; Tsai, Yi-Fan; Ho, Jennifer H.; Lee, Chen-Hsen; Lee, Oscar K.

    2013-01-01

    131 I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133 + cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133 + cells and higher radioresistance. After γ-irradiation of the cells, the CD133 + population was enriched due to the higher apoptotic rate of CD133 - cells. In vivo 131 I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133 + cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133 + cells. (orig.)

  1. Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer trials with preoperative therapy: Literature-based meta-analysis.

    Science.gov (United States)

    Kataoka, K; Nakamura, K; Mizusawa, J; Kato, K; Eba, J; Katayama, H; Shibata, T; Fukuda, H

    2017-10-01

    There have been no reports evaluating progression-free survival (PFS) as a surrogate endpoint in resectable esophageal cancer. This study was conducted to evaluate the trial level correlations between PFS and overall survival (OS) in resectable esophageal cancer with preoperative therapy and to explore the potential benefit of PFS as a surrogate endpoint for OS. A systematic literature search of randomized trials with preoperative chemotherapy or preoperative chemoradiotherapy for esophageal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane Library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R 2 ) within PFS and OS. The primary analysis included trials in which the HR for both PFS and OS was reported. The sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. Of 614 articles, 10 trials were selected for the primary analysis and 15 for the sensitivity analysis. The primary analysis did not show a correlation between treatment effects on PFS and OS (R 2 0.283, 95% CI [0.00-0.90]). The sensitivity analysis did not show an association between PFS and OS (R 2 0.084, 95% CI [0.00-0.70]). Although the number of randomized controlled trials evaluating preoperative therapy for esophageal cancer is limited at the moment, PFS is not suitable for primary endpoint as a surrogate endpoint for OS. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  2. Improving access to psychological therapies in voice disorders: a cognitive behavioural therapy model.

    Science.gov (United States)

    Miller, Tracy; Deary, Vincent; Patterson, Jo

    2014-06-01

    The improving access to psychological therapies initiative has highlighted the importance of managing mental health problems effectively, and research has shown excellent outcomes from cognitive behavioural therapy (CBT) interventions. Patients presenting with functional dysphonia will often also describe psychological distress including anxiety, depression and reduced general well-being, and it is felt that effective voice therapy needs to include the management of psychological well-being. The evidence for the use of CBT enhanced voice therapy is limited to date. Recent research has only started to identify the benefits of this approach and questions regarding how to achieve and maintain competence are essential. Voice therapy outcomes are positive and patients receiving CBT with voice therapy have shown more improvement in their general well-being and distress. CBT is a very well evidenced therapy and recommended by The National Institute for Health and Care Excellence (NICE) as the treatment of choice for mental health difficulties and medically unexplained symptoms. Allied health professionals are increasingly being trained to use CBT skills in the management of a number of symptoms/illnesses, and this should be considered for the management of functional dysphonia. However, there is a need for more research and detailed consideration of how therapists should be trained and supervised and how cost-effective this approach may be.

  3. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Dominguez, Jessica A; Vithayathil, Paul J; Khailova, Ludmila; Lawrance, Christopher P; Samocha, Alexandr J; Jung, Enjae; Leathersich, Ann M; Dunne, W Michael; Coopersmith, Craig M

    2011-10-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

  4. Patient-centric Blood Pressure–targeted Cardiopulmonary Resuscitation Improves Survival from Cardiac Arrest

    Science.gov (United States)

    Friess, Stuart H.; Naim, Maryam Y.; Lampe, Joshua W.; Bratinov, George; Weiland, Theodore R.; Garuccio, Mia; Nadkarni, Vinay M.; Becker, Lance B.; Berg, Robert A.

    2014-01-01

    Rationale: Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. Objectives: To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF). Methods: After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure–targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival. Measurements and Main Results: The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9–13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0–12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0–3] vs. 2 [range, 2–2]; P = 0.003). Conclusions: Blood pressure–targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest. PMID:25321490

  5. Patient-centric blood pressure-targeted cardiopulmonary resuscitation improves survival from cardiac arrest.

    Science.gov (United States)

    Sutton, Robert M; Friess, Stuart H; Naim, Maryam Y; Lampe, Joshua W; Bratinov, George; Weiland, Theodore R; Garuccio, Mia; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A

    2014-12-01

    Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF). After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure-targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival. The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9-13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0-12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0-3] vs. 2 [range, 2-2]; P = 0.003). Blood pressure-targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest.

  6. Macrophages improve survival, proliferation and migration of engrafted myogenic precursor cells into MDX skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Pierre-François Lesault

    Full Text Available Transplantation of muscle precursor cells is of therapeutic interest for focal skeletal muscular diseases. However, major limitations of cell transplantation are the poor survival, expansion and migration of the injected cells. The massive and early death of transplanted myoblasts is not fully understood although several mechanisms have been suggested. Various attempts have been made to improve their survival or migration. Taking into account that muscle regeneration is associated with the presence of macrophages, which are helpful in repairing the muscle by both cleansing the debris and deliver trophic cues to myoblasts in a sequential way, we attempted in the present work to improve myoblast transplantation by coinjecting macrophages. The present data showed that in the 5 days following the transplantation, macrophages efficiently improved: i myoblast survival by limiting their massive death, ii myoblast expansion within the tissue and iii myoblast migration in the dystrophic muscle. This was confirmed by in vitro analyses showing that macrophages stimulated myoblast adhesion and migration. As a result, myoblast contribution to regenerating host myofibres was increased by macrophages one month after transplantation. Altogether, these data demonstrate that macrophages are beneficial during the early steps of myoblast transplantation into skeletal muscle, showing that coinjecting these stromal cells may be used as a helper to improve the efficiency of parenchymal cell engraftment.

  7. Relationship between spermatogonial stem cell survival and testis function after cytotoxic therapy

    International Nuclear Information System (INIS)

    Meistrich, M.L.

    1986-01-01

    This review, with substantial bibliography, concludes that the acute effects of radiation and cytotoxic drugs are a result of toxicity to the most sensitive of the germ cells, which in most cases are the differentiating spermatogonia. Long-term sterility or reduction in sperm production depends directly on killing of spermatogonial stem cells. For a variety of cytotoxic agents, the same relationship holds between the stem cell survival index and the prompt recovery level of sperm production (at 56 days), the maximal recovered level of sperm production, and the time required for fertility to return. It also appears that the spermatogonial stem cell is the target for long-term sterility in man following cytotoxic therapy. It is not known whether the delay in recovery is a result of this direct damage to the stem cell or an effect on another target cell in the tissue. Data obtained in both experimental animals and man indicate very little direct changes in the secretory cells and other stromal cells of the testis, and there is no evidence as yet that any alterations in these cells adversely affect sperm production or reproductive performance. (UK)

  8. Results and survival after photodynamic therapy in early-stage esophageal carcinoma

    Science.gov (United States)

    Spinelli, Pasquale; Mancini, Andrea; dal Fante, Marco; Meroni, Emmanuele; Jasinskas, Algirdas

    1996-01-01

    From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.

  9. Survival prediction algorithms miss significant opportunities for improvement if used for case selection in trauma quality improvement programs.

    Science.gov (United States)

    Heim, Catherine; Cole, Elaine; West, Anita; Tai, Nigel; Brohi, Karim

    2016-09-01

    Quality improvement (QI) programs have shown to reduce preventable mortality in trauma care. Detailed review of all trauma deaths is a time and resource consuming process and calculated probability of survival (Ps) has been proposed as audit filter. Review is limited on deaths that were 'expected to survive'. However no Ps-based algorithm has been validated and no study has examined elements of preventability associated with deaths classified as 'expected'. The objective of this study was to examine whether trauma performance review can be streamlined using existing mortality prediction tools without missing important areas for improvement. We conducted a retrospective study of all trauma deaths reviewed by our trauma QI program. Deaths were classified into non-preventable, possibly preventable, probably preventable or preventable. Opportunities for improvement (OPIs) involve failure in the process of care and were classified into clinical and system deviations from standards of care. TRISS and PS were used for calculation of probability of survival. Peer-review charts were reviewed by a single investigator. Over 8 years, 626 patients were included. One third showed elements of preventability and 4% were preventable. Preventability occurred across the entire range of the calculated Ps band. Limiting review to unexpected deaths would have missed over 50% of all preventability issues and a third of preventable deaths. 37% of patients showed opportunities for improvement (OPIs). Neither TRISS nor PS allowed for reliable identification of OPIs and limiting peer-review to patients with unexpected deaths would have missed close to 60% of all issues in care. TRISS and PS fail to identify a significant proportion of avoidable deaths and miss important opportunities for process and system improvement. Based on this, all trauma deaths should be subjected to expert panel review in order to aim at a maximal output of performance improvement programs. Copyright © 2016 Elsevier

  10. 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.

  11. Pulmonary functions of children with asthma improve following massage therapy.

    Science.gov (United States)

    Fattah, Mohammed Abdel; Hamdy, Basant

    2011-11-01

    This study aimed at evaluating the effect of massage therapy on the pulmonary functions of stable Egyptian children with asthma. This study was an open, randomized, controlled trial. The study was conducted in pediatric allergy and chest unit of the New Children's Hospital of Cairo University, Egypt. Sixty (60) children with asthma were divided randomly into two equal groups: massage therapy group and control group. Subjects in the massage therapy group received a 20-minute massage therapy by their parents at home before bedtime every night for 5 weeks in addition to the standard asthma treatment. The control group received the standard asthma treatment alone for 5 weeks. Spirometry was performed for all children on the first and last days of the study. Forced expiratory flow in first second (FEV1), forced vital capacity (FVC), FEV1/FVC and peak expiratory flow (PEF) were recorded. At the end of the study, mean FEV1 of the massage therapy group was significantly higher than controls (2.3-0.8 L versus 1.9-0.9 L, p=0.04). There was no significant difference in FVC (2.5-0.8 L versus 2.7-0.7 L, p=0.43). However, FEV1/FVC ratio showed a significant improvement in the massage therapy group (92.3-21.5 versus 69.5-17, pmassage therapy in pediatric asthma is suggested. It improved the key pulmonary functions of the children, namely, FEV1 and FEV1/FVC ratio. However, further research on a larger scale is warranted. © Mary Ann Liebert, Inc.

  12. Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Maklad AM

    2016-10-01

    Full Text Available Ahmed Marzouk Maklad,1,2 Yasser Bayoumi,2,3 Mohamed Abdalazez Senosy Hassan,2,4 AbuSaleh A Elawadi,5,6 Hussain AlHussain,2 Ashraf Elyamany,7,8 Saleh F Aldhahri,9 Khalid Hussain Al-Qahtani,10 Mubarak AlQahtani,11 Mutahir A Tunio12 1Clinical Oncology, Sohag University, Sohag, Egypt; 2Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 3Radiation Oncology, NCI, Cairo University, Cairo, 4Radiation Oncology, Minia Oncology Center, Minia, 5Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 6Medical Physics, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 7Medical Oncology, SECI-Assiut University, Assiut, Egypt; 8Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, 9Department of Otolaryngology, Head and Neck Surgery, King Saud University, 10Department of Otolaryngology-Head and Neck Surgery, College of Medicine, King Saud University, 11Department of ENT, King Fahad Medical City, 12Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia Background: We aimed to investigate the patterns of failure (locoregional and distant metastasis, associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT combined with chemotherapy. Patients and methods: From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results: The median follow-up time was 52.2 months (range: 11–87 months. Epstein–Barr virus infection was positive in 63.2% of

  13. PD-1 and PD-L1 inhibitors after platinum-based chemotherapy or in first-line therapy in cisplatin-ineligible patients: Dramatic improvement of prognosis and overall survival after decades of hopelessness in patients with metastatic urothelial cancer.

    Science.gov (United States)

    Resch, Irene; Shariat, Shahrokh F; Gust, Kilian M

    2018-01-01

    Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control. Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. All five CPI are FDA-approved as second-line therapy with atezolizumab and pembrolizumab also being approved for first-line therapy in cisplatin-ineligible patients. The rapid acceptance in the treatment algorithm of UC is based on the impressive clinical efficacy of these agents in some patients, combined with their excellent safety profile. These new agents are indeed the most important advancement in UC care. However, the challenge in the age of precision medicine is to identify the patients who are most likely to benefit from CPIs, as the majority of patients do not respond to CPI. Toward this goal, validation of clinical, molecular and imaging biomarkers that serve for prediction and monitoring of treatment response are of central necessity.

  14. Adipose stem cells from chronic pancreatitis patients improve mouse and human islet survival and function.

    Science.gov (United States)

    Song, Lili; Sun, Zhen; Kim, Do-Sung; Gou, Wenyu; Strange, Charlie; Dong, Huansheng; Cui, Wanxing; Gilkeson, Gary; Morgan, Katherine A; Adams, David B; Wang, Hongjun

    2017-08-30

    from the adipose of chronic pancreatitis patients improved islet survival and islet function after transplantation. The effects are in part mediated by paracrine secretion of IGF-1, suppression of inflammation, and promotion of angiogenesis. ASCs from chronic pancreatitis patients have the potential to be used as a synergistic therapy to enhance the efficacy of islet transplantation following pancreatectomy.

  15. Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis.

    Science.gov (United States)

    Winny, Markus; Paroglou, Vagia; Bektas, Hüseyin; Kaltenborn, Alexander; Reichert, Benedikt; Zachau, Lea; Kleine, Moritz; Klempnauer, Jürgen; Schrem, Harald

    2014-02-01

    This retrospective, single-center, observational study on postoperative long-term results aims to define yet unknown factors for long-term outcome after operation for chronic pancreatitis. We analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to 2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long-term survival data were provided by the German citizen registration authorities for all patients. A quality-of-life questionnaire was sent to surviving patients after a mean follow-up of 5.7 years. Surgical principles were resection (n = 86; 59%), decompression (n = 29; 20%), and hybrid procedures (n = 32; 21%). No significant influences of different surgical principles and operative procedures on survival, long-term quality of life and pain control could be detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year survival 90.8%. Multivariate Cox regression analysis revealed that only postoperative insulin dependence at the time of hospital discharge (P = .027; Exp(B) = 2.111; 95% confidence interval [CI], 1.089-4.090) and the absence of pancreas enzyme replacement therapy at the time of hospital discharge (P = .039; Exp(B) = 2.102; 95% CI, 1.037-4.262) were significant, independent risk factors for survival with significant hazard ratios for long-term survival. Long-term improvement in quality of life was reported by 55 of 76 long-term survivors (73%). Pancreatic enzyme replacement should be standard treatment after surgery for chronic pancreatitis at the time of hospital discharge, even when no clinical signs of exocrine pancreatic failure exist. This study underlines the potential importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present. Copyright © 2014 Mosby, Inc. All rights reserved.

  16. Survival comparison of the Ross procedure and mechanical valve replacement with optimal self-management anticoagulation therapy: propensity-matched cohort study.

    Science.gov (United States)

    Mokhles, M Mostafa; Körtke, Heinrich; Stierle, Ulrich; Wagner, Otto; Charitos, Efstratios I; Bogers, Ad J J C; Gummert, Jan; Sievers, Hans-Hinrich; Takkenberg, Johanna J M

    2011-01-04

    It is suggested that in young adults the Ross procedure results in better late patient survival compared with mechanical prosthesis implantation. We performed a propensity score-matched study that assessed late survival in young adult patients after a Ross procedure versus that after mechanical aortic valve replacement with optimal self-management anticoagulation therapy. We selected 918 Ross patients and 406 mechanical valve patients 18 to 60 years of age without dissection, aneurysm, or mitral valve replacement who survived an elective procedure (1994 to 2008). With the use of propensity score matching, late survival was compared between the 2 groups. Two hundred fifty-three patients with a mechanical valve (mean follow-up, 6.3 years) could be propensity matched to a Ross patient (mean follow-up, 5.1 years). Mean age of the matched cohort was 47.3 years in the Ross procedure group and 48.0 years in the mechanical valve group (P=0.17); the ratio of male to female patients was 3.2 in the Ross procedure group and 2.7 in the mechanical valve group (P=0.46). Linearized all-cause mortality rate was 0.53% per patient-year in the Ross procedure group compared with 0.30% per patient-year in the mechanical valve group (matched hazard ratio, 1.86; 95% confidence interval, 0.58 to 5.91; P=0.32). Late survival was comparable to that of the general German population. In comparable patients, there is no late survival difference in the first postoperative decade between the Ross procedure and mechanical aortic valve implantation with optimal anticoagulation self-management. Survival in these selected young adult patients closely resembles that of the general population, possibly as a result of highly specialized anticoagulation self-management, better timing of surgery, and improved patient selection in recent years.

  17. Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis.

    Science.gov (United States)

    Alcayaga-Miranda, Francisca; Cuenca, Jimena; Martin, Aldo; Contreras, Luis; Figueroa, Fernando E; Khoury, Maroun

    2015-10-16

    Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection. Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells (MSCs) derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstrual derived MSCs (MenSCs) emerge as an attractive candidate because they present important advantages over other sources, including improved proliferation rates and paracrine response under specific stress conditions. Here, we evaluate their therapeutic effect in a polymicrobial severe sepsis model. The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides (AMPs) by quantitative reverse transcription-polymerase chain reaction. The therapeutic effect of MenSCs was determined in the cecal ligation and puncture (CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone or in combination. The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry. MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model, MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced bacterial clearance in the peritoneal fluids and blood; (c) reduced organ injuries evaluated by lower concentrations of the liver enzymes alanine aminotransferase and aspartate aminotransferase; and (d) modulated the inflammatory response through reduction of pro- and anti-inflammatory cytokines without significant loss of T and B lymphocytes. We conclude that MenSCs in combination with AB

  18. Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites

    Science.gov (United States)

    Liu, Da-Quan; Gao, Qiao-Ying; Liu, Hong-Bin; Li, Dong-Hua; Wu, Shang-Wei

    2013-01-01

    AIM: To investigate the benefits of probiotics treatment in septic rats. METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P probiotics treated group compared with septic model group (33.3% vs 100.0%, P probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P Probiotics improve survival of septic rats by suppressing these conditioned pathogens. PMID:23840152

  19. Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice

    International Nuclear Information System (INIS)

    Itasaka, Satoshi; Komaki, Ritsuko; Herbst, Roy S.; Shibuya, Keiko; Shintani, Tomoaki D.D.S.; Hunter, Nancy R. M.S.; Onn, Amir; Bucana, Corazon D.; Milas, Luka; Ang, K. Kian; O'Reilly, Michael S.

    2007-01-01

    Purpose: Clinical trials of antiangiogenic agents used alone for advanced malignancy have been disappointing but preclinical studies suggest that the addition of radiation therapy could improve antitumor efficacy. To test the hypothesis that antiangiogenic therapy combined with radiation therapy can overcome the limitations of antiangiogenic monotherapy, we studied the effects of endostatin combined with radiation on the growth and vascularization of A431 human epidermoid carcinomas growing intramuscularly in the legs of mice. Methods and Materials: Mice with established A431 human epidermoid leg tumors were treated with radiation, endostatin, both radiation and endostatin, or vehicle control. The experiment was repeated and mice from each group were killed at 2, 7, and 10 days after irradiation so that tumor tissue could be obtained to further analyze the kinetics of the antitumor, antivascular, and antiangiogenic response to therapy. Results: Endostatin enhanced the antitumor effects of radiation, and prolonged disease-free survival was observed in the combined treatment group. Endothelial cell proliferation was increased in tumors after irradiation but was blocked by the concurrent administration of endostatin, and the combination of endostatin with radiation enhanced endothelial cell apoptosis within 48 h after irradiation. Expression of vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 were increased in tumors after irradiation, and this increase was blocked by concurrent administration of endostatin. Conclusion: These data indicate that endostatin can block tumor revascularization after radiation therapy and thereby augment radioresponse

  20. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jill P Smith

    2010-03-01

    Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

  1. Virally delivered, constitutively active NFκB improves survival of injured retinal ganglion cells.

    Science.gov (United States)

    Dvoriantchikova, Galina; Pappas, Steve; Luo, Xueting; Ribeiro, Marcio; Danek, Dagmara; Pelaez, Daniel; Park, Kevin K; Ivanov, Dmitry

    2016-12-01

    As axon damage and retinal ganglion cell (RGC) loss lead to blindness, therapies that increase RGC survival and axon regrowth have direct clinical relevance. Given that NFκB signaling is critical for neuronal survival and may regulate neurite growth, we investigated the therapeutic potential of NFκB signaling in RGC survival and axon regeneration. Although both NFκB subunits (p65 and p50) are present in RGCs, p65 exists in an inactive (unphosphorylated) state when RGCs are subjected to neurotoxic conditions. In this study, we used a phosphomimetic approach to generate DNA coding for an activated (phosphorylated) p65 (p65mut), then employed an adeno-associated virus serotype 2 (AAV2) to deliver the DNA into RGCs. We tested whether constitutive p65mut expression prevents death and facilitates neurite outgrowth in RGCs subjected to transient retinal ischemia or optic nerve crush (ONC), two models of neurotoxicity. Our data indicate that RGCs treated with AAV2-p65mut displayed a significant increase in survival compared to controls in ONC model (77 ± 7% vs. 25 ± 3%, P-value = 0.0001). We also found protective effect of modified p65 in RGCs of ischemic retinas (55 ± 12% vs. 35 ± 6%), but not to a statistically significant degree (P-value = 0.14). We did not detect a difference in axon regeneration between experimental and control animals after ONC. These findings suggest that increased NFκB signaling in RGCs attenuates retinal damage in animal models of neurodegeneration, but insignificantly impacts axon regeneration. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    International Nuclear Information System (INIS)

    Herbert, Christopher; Liu, Mitchell; Tyldesley, Scott; Morris, W. James; Joffres, Michel; Khaira, Mandip; Kwan, Winkle; Moiseenko, Vitali; Pickles, Thomas

    2012-01-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51–176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%–94.1%) and 62.1% (95% CI 52.9%–71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%–100%) and 79.8% (95% CI 68.0%–91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p 90%.

  3. The Effectiveness of Gestalt Therapy and Cognitive Therapy on Improvement of Life Quality of War Veterans

    Directory of Open Access Journals (Sweden)

    S Sadeghi

    2012-02-01

    Full Text Available Background & Aim: The imposed war burdened a lot of problems on the society of Iran during the past few years. In this course, veterans didn’t immune from its harmful effects. The aim of the present study was to determine the effectiveness of integrated group gestalt therapy and cognitive therapy on improvement of quality of life of veterans of city of Jahrom, Iran. Methods: The present clinical trial study was conducted on thirty veterans of Jahrom in 2010. The subjects included all the war veterans of Jahrom, 820 with 25-69 percent physical damage. Random sampling was executed and the world Health Organization life quality questionnaire (WHOQOL-BREF was given to 150 of them. Fifteen people in each group were replaced by another fifteen people. The test group received eight sessions of group consultation in Gestalt therapy and cognition therapy ways, but the control group received no therapy. The gathered data was analyzed using ANOVA test. Results: The result of this study showed that-there is a significant difference between the life quality dimensions (physical health, mental health, life environment and social relations between the test and control group (p=0.001. Conclusion: The results of this study showed that the integrated of group counseling by gestalt therapy and cognitive therapy had an influence on increasing the veteran’s life qualifications in aspects of physical health, mental health, life environment and social relations.

  4. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  5. Does Surgical Repair of Moderate Ischemic Mitral Regurgitation Improve Survival? A Systematic Review.

    Science.gov (United States)

    Chatterjee, Saurav; Tripathi, Byomesh; Virk, Hafeez Ul Hassan; Ahmed, Mohammed; Bavishi, Chirag; Krishnamoorthy, Parasuram; Sardar, Partha; Giri, Jay; Omidvari, Karan; Chikwe, Joanna

    2016-03-01

    Mitral regurgitation (MR) is one of the common complications in myocardial infarction (MI) patients. Almost half of the post MI patients have MR (ischemic MR)(17) which is moderate to severe (grade II-IV). Whether there is a mortality benefit of performing mitral valve repair (MVR) along with coronary artery bypass grafting (CABG) in patients with post MI moderate MR remains inconclusive. Literature search was done from PubMed, Google scholar, Ovid, and Medline databases. Studies which included post MI patients with moderate ischemic MR and reported mortality outcomes of performing CABG and MVR were chosen for the systematic review. Our preliminary literature search identified 194 studies, of which 11 studies met our inclusion criteria. Nine studies showed no survival benefit of performing simultaneous MVR and CABG. One study demonstrated survival benefit of performing CABG plus MVR only in the New York Heart Association (NYHA) class III-IV, and one study suggested survival benefit of performing CABG plus MVR as compared to CABG alone in patient with ischemic MR irrespective of preoperative NYHA functional class. Review of current literature showed mixed results in terms of improvement in functional status but failed to show any survival benefit of performing MVR along with CABG. Limitations of studies include small sample size, difference in baseline demographic variables, and short follow-up period which might influence the outcome of the study. Prospective randomized studies are required to establish clear benefit of performing MVR simultaneously with CABG.

  6. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

    Science.gov (United States)

    Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

  7. Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

    International Nuclear Information System (INIS)

    Zeliadt, Steven B.; Potosky, Arnold L.; Penson, David F.; Etzioni, Ruth

    2006-01-01

    Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease

  8. Rac1 selective activation improves retina ganglion cell survival and regeneration.

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

    Full Text Available In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

  9. Androgen Deprivation Therapy Does Not Impact Cause-Specific or Overall Survival in High-Risk Prostate Cancer Managed With Brachytherapy and Supplemental External Beam

    International Nuclear Information System (INIS)

    Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A.; Adamovich, Edward; Lief, Jonathan

    2007-01-01

    Purpose: To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score ≥8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage ≥T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA ≤0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. Results: The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT ≤6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS

  10. Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

    2014-11-15

    Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

  11. Nicotinamide augments the survival and incidence of apoptosis in glioma cells following photodynamic therapy in vitro

    Science.gov (United States)

    Bisland, Stuart K.; Modi, Nayan; Wilson, Brian C.

    2004-10-01

    The ability to customize photodynamic therapy (PDT) parameters with regards to timing and dosing of administered drug and light can be beneficial in determining target specificity and mode of cell death. Sustained, low level PDT or metronomic PDT (mPDT) may afford enhanced apoptotic cell death. This is of particular importance when considering PDT for the treatment of brain tumors as unlike apoptosis, necrotic cell death often leads to inflammation with increased intracranial pressure. The ability, therefore, to 'fine tune' PDT in favour of apoptosis is paramount. We have studied both acute (one time treatment) PDT (aPDT) and mPDT delivery strategies in combination with nicotinamide (NA) in an attempt to maximize the number of tumor cells dieing by apoptosis. Using several different glioma cell lines (9L, U87-MG and CNS-1) we now confirm that NA provides a dose-dependent (0.1-0.5 mM) increase in apoptotic cells following d-aminolevulinic acid-mediated aPDT or mPDT. Furthermore, using the 9L cell line stably transfected with the luciferase gene, NA was shown to delay the depletion of bioluminscence signal in aPDT and mPDT treated cells, inferring that adenosine triphosphate levels are maintained for longer following NA treatment. NA has previously been reported as promoting neuronal and vascular cell survival in normal brain following a number of neurological insults in which reactive oxygen species are implicated including, stroke, Alzheimer's disease and toxin-induced lesions. It is likely that the effects of NA reflect its capacity as an antioxidant as well as its ability to inhibit poly (adenosine diphosphate-ribose) polymerase-mediated depletion of ATP. Our results indicate that NA may prove therapeutically advantageous when used in combination with PDT treatment of brain tumors.

  12. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  13. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Trickey, Adam; May, Margaret T; Vehreschild, Jorg-Janne

    2016-01-01

    OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro......OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing...... to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. RESULTS: During 50,593 person...... years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict...

  14. Improved survival of macroencapsulated islets of Langerhans by preimplantation of the immunoisolating device: a morphometric study.

    Science.gov (United States)

    Rafael, E; Wu, G S; Hultenby, K; Tibell, A; Wernerson, A

    2003-01-01

    Encapsulation of cells in a semipermeable membrane may in the future provide an opportunity to treat a variety of endocrine and neurological disorders, without the need for lifelong immunosuppression. The physiological conditions in the device are crucial factors for graft survival. Previously, we have shown that the exchange across the immunoisolating membrane and the microcirculation around the TheraCyte device increase around 3 months after implantation. The aim of this study was to determine whether preimplantation of the TheraCyte device would improve the survival of a later transplanted islet graft. A TheraCyte device was implanted SC on one side of the back of a nondiabetic SD rat. After 3 months, 1500 islets isolated from SD rats were transplanted via the device port. At the same time, another device, loaded with the same number of islets, was implanted on the other side of the back. Both devices were explanted 2 weeks after islet transplantation (i.e., 3.5 months and 0.5 month after device implantation, respectively). Six pairs of devices were evaluated by morphometery. The volume densities of viable islets were 0.22 +/- 0.04 in the preimplanted device vs. 0.06 +/- 0.03 in the nonpreimplanted one (p TheraCyte device seems to improve the survival of an encapsulated islet graft and reduce fibroblast outgrowth in the device.

  15. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Directory of Open Access Journals (Sweden)

    Saher Hamed

    Full Text Available BACKGROUND: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF-treated and phosphate-buffered saline (PBS-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  16. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Science.gov (United States)

    Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

    2010-11-15

    Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  17.  Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.

    Science.gov (United States)

    Hilscher, Moira; Enders, Felicity B; Carey, Elizabeth J; Lindor, Keith D; Tabibian, James H

    2016-01-01

     Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.

  18. Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

    Science.gov (United States)

    Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun

    2012-11-01

    Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

  19. Long-Term Survival and Improved Quality of Life following Multiple Repeat Gamma Knife Radiosurgeries for Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Erik W. Larson

    2013-01-01

    Full Text Available The management of glioblastoma multiforme (GBM is in most cases complex and must be specifically tailored to the needs of the patient with the goals of extended survival and improved quality of life. Despite advancements in therapy, treatment outcomes remain almost universally poor. Salvage treatment options for the recurrence of the disease is an area of intense study. The following case highlights the utility of Gamma Knife Radiosurgery (GKRS as a salvage treatment. In this clinical situation, three sequential GKRS treatments led to prolonged survival (beyond four years after diagnosis and improved quality of life in a patient who was unable to receive further chemotherapy regimens and was unwilling to undergo further aggressive resection. To date, there have been few reports of three or more sequential GKRS treatment sessions utilized as salvage therapy for recurrent GBM in patients who can no longer tolerate chemotherapy. This report provides evidence that aggressive local treatment with GKRS at the time of recurrence may be appropriate, depending on a patient’s individual clinical situation, and can lead to prolonged survival and improved quality of life.

  20. Community-Based Multidisciplinary Computed Tomography Screening Program Improves Lung Cancer Survival.

    Science.gov (United States)

    Miller, Daniel L; Mayfield, William R; Luu, Theresa D; Helms, Gerald A; Muster, Alan R; Beckler, Vickie J; Cann, Aaron

    2016-05-01

    cancer specific survival was 71% in the screened patients, whereas nonscreened lung cancer patients during that time in WHS had an overall survival of only 19% (p < 0.001). A community-based multidisciplinary lung cancer screening program can improve survival of patients with lung cancer outside of a large multicenter study. This survival advantage was caused by a significant stage shift to earlier disease. Lung cancer CT screening may also benefit patients not meeting the National Lung Screening Trial criteria who are at moderate or high risk for lung cancer. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer - An updated retrospective study on local failure and survival rates

    International Nuclear Information System (INIS)

    Jeppesen, Stefan S.; Schytte, Tine; Hansen, Olfred; Jensen, Henrik R.; Brink, Carsten

    2013-01-01

    Introduction: Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single-institutional report is to describe survival outcome for medically inoperable patients with early stage NSCLC treated with SBRT compared with high dose conventional RT. Material and methods: From August 2005 to June 2012, 100 medically inoperable patients were treated with SBRT at Odense Univ. Hospital. The thoracic RT consisted of 3 fractions (F) of 15-22 Gy delivered in nine days. For comparison a group of 32 medically inoperable patients treated with conventional RT with 80 Gy/35-40 F (5 F/week) in the period of July 1998 to August 2011 were analyzed. All tumors had histological or cytological proven NSCLC T1-2N0M0. Results: The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT, respectively (p = 0.015). Local failure-free survival rates at one year were in SBRT group 93 % versus 89 % in the conventional RT group and at five years 69 % versus 66 %, SBRT and conventional RT respectively (p = 0.99). On multivariate analysis, female gender and performance status of 0-1 and SBRT predicted improved prognosis. Conclusion: In a cohort of patients with NSCLC there was a significant difference in overall survival favoring SBRT. Performance status of 0-1, female gender and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients

  2. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  4. IMPROVING FUNCTIONAL INDEPENDENCE OF PATIENTS WITH MULTIPLE SCLEROSIS BY PHYSICAL THERAPY AND OCCUPATIONAL THERAPY

    Directory of Open Access Journals (Sweden)

    Ana-Maria Ticărat

    2011-06-01

    Full Text Available Introduction. Patients with multiple sclerosis can have a normal life despite of their real or possible disability and of the progressive nature of it. Scope. Patients who follow physical therapy and occupational therapy will have an increased quality of life and a greater functional independence.Methods. The randomized study was made on 7 patients with multiple sclerosis, from Oradea Day Centre, 3 times/week, ages between 35 – 55 years, functional level between mild and sever. Assessment and rehabilitation methods: inspection, BARTHEL Index. Frenkel method, brething exercises, weights exercises, gait exercises, writind exercises and games were used in the rehabilitation process. Group therapies: sociotherapy, arttherapy, music therapy. Results analysis consisted of the comparison of baseline and final means.Results. By analizing baseline and final means for Barthel Index for each functon separately, it was shown a mild improvement of functional independence for almost assessed functions, with at least 1-1,5 points.Conclusions. Persons with multiple sclerosis who follow physical therapy and occupational therapy presents a better functional independence after the treatment.

  5. ESC guidelines adherence is associated with improved survival in patients from the Norwegian Heart Failure Registry.

    Science.gov (United States)

    De Blois, Jonathan; Fagerland, Morten Wang; Grundtvig, Morten; Semb, Anne Grete; Gullestad, Lars; Westheim, Arne; Hole, Torstein; Atar, Dan; Agewall, Stefan

    2015-01-01

    To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry. The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival (P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality. Published on behalf of the European Society of Cardiology. All rights reserved. ©The Author 2015. For permissions please email: journals.permissions@oup.com.

  6. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Patient-reported distress and survival among patients receiving definitive radiation therapy

    Directory of Open Access Journals (Sweden)

    Yacob Habboush, MD

    2017-04-01

    Conclusions: PRD before or during RT is a prognostic factor associated with decreased survival. Distress screening guidelines and interventions should be implemented for patients receiving definitive RT.

  8. Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy.

    Science.gov (United States)

    Tong, Luqing; Yi, Li; Liu, Peidong; Abeysekera, Iruni Roshanie; Hai, Long; Li, Tao; Tao, Zhennan; Ma, Haiwen; Xie, Yang; Huang, Yubao; Yu, Shengping; Li, Jiabo; Yuan, Feng; Yang, Xuejun

    2018-07-01

    Glioblastoma multiforme (GBM) is a fatal cancer with varying life expectancy, even for patients undergoing the same standard therapy. Identification of differentially expressed genes in GBM patients with different survival rates may benefit the development of effective therapeutic strategies. In the present study, key pathways and genes correlated with survival in GBM patients were screened with bioinformatic analysis. Included in the study were 136 eligible patients who had undertaken surgical resection of GBM followed by temozolomide (TMZ) chemoradiation and long-term therapy with TMZ. A total of 383 differentially expressed genes (DEGs) related to GBM survival were identified. Gene Ontology and pathway enrichment analysis as well as hub gene screening and module analysis were performed. As expected, angiogenesis and migration of GBM cells were closely correlated with a poor prognosis. Importantly, the results also indicated that cell dormancy was an essential contributor to the reduced survival of GBM patients. Given the lack of specific targeted genes and pathways known to be involved in tumour cell dormancy, we proposed enriched candidate genes related to the negative regulation of cell proliferation, signalling pathways regulating pluripotency of stem cells and neuroactive ligand-receptor interaction, and 3 hub genes (FTH1, GRM1 and DDIT3). Maintaining persistent cell dormancy or preventing tumour cells from entering dormancy during chemoradiation should be a promising therapeutic strategy.

  9. Sleep Quality Improvement During Cognitive Behavioral Therapy for Anxiety Disorders.

    Science.gov (United States)

    Ramsawh, Holly J; Bomyea, Jessica; Stein, Murray B; Cissell, Shadha H; Lang, Ariel J

    2016-01-01

    Despite the ubiquity of sleep complaints among individuals with anxiety disorders, few prior studies have examined whether sleep quality improves during anxiety treatment. The current study examined pre- to posttreatment sleep quality improvement during cognitive behavioral therapy (CBT) for panic disorder (PD; n = 26) or generalized anxiety disorder (GAD; n = 24). Among sleep quality indices, only global sleep quality and sleep latency improved significantly (but modestly) during CBT. Sleep quality improvement was greater for treatment responders, but did not vary by diagnosis. Additionally, poor baseline sleep quality was independently associated with worse anxiety treatment outcome, as measured by higher intolerance of uncertainty. Additional intervention targeting sleep prior to or during CBT for anxiety may be beneficial for poor sleepers.

  10. Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    McDowell, Lachlan J.; Huang, Shao Hui [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Xu, Wei; Che, Jiahua [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Wong, Rebecca K.S.; Brierley, James; Kim, John; Cummings, Bernard; Waldron, John; Bayley, Andrew [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Hansen, Aaron [Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Department of Otolaryngology–Head and Neck Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Ringash, Jolie, E-mail: jolie.ringash@rmp.uhn.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2017-05-01

    Purpose: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). Conclusions: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

  11. Improved survival with combined modality treatment for Stage IV breast cancer

    International Nuclear Information System (INIS)

    Nervi, C.; Arcangeli, G.; Concolino, F.; Cortese, M.

    1979-01-01

    Between 1974 and 1977, 85 patients with breast cancer at first postmastectomy relapse were irradiated (Radiation 3500 to 6000 rad--3/5 weeks) to all clinically evident lesions. Radiation fields were properly shaped to include a maximum 40% active bone marrow. After 3 to 4 weeks rest, chemotherapy was started as adjuvant therapy for residual or subclinical disease (ADR 30 mg/M 2 Day 1 and 8, 5-FU 400 mg/M 2 Day 1 and 8, CY 100 mg/M 2 Day 1 through 14: repeated after 14 days). ADR was discontinued at 500/M 2 and substituted by MTX 30 mg/M 2 Day 1 and 8 for a total of 2 years. Irradiated sites were chest wall in 35, supraclavicular and internal mammary nodes in 22, bone in 56, single lung lesions in 12, brain in 24. Controls were 52 comparable but non-randomized patients treated with chemotherapy only. Forty days after x-irradiation 68 patients (80%) were free of disease (NED) while in 17 cases (20%) some residual was still present (RED). In 28 of 68 cases (41%) NED after x-irradiation and 13 of 17 (76%) in RED group developed second relapse after a median interval of 26 and 20 mos., respectively. Four of 52 patients (8%) in the control group had complete regression with a median interval to second relapse of 7 mos. Median survival was 30 mos., 24 mos., and 13 mos., respectively, for NED, RED and chemotherapy only. Eighteen patients (26%) are free of disease after 36 to 48 mos. in the combined modality group; none in the chemotherapy group. Combined treatment cases did not show untolerable myelodepression. In 10 long-surviving patients a marked subcutaneous and skin fibrosis developed because of drug additive effect. Stage IV breast cancers rendered clinically free of disease with x-irradiation and subsequently treated with chemotherapy survive significantly longer than with chemotherapy alone

  12. Gene transfer strategies for improving radiolabeled peptide imaging and therapy

    International Nuclear Information System (INIS)

    Rogers, B.E.; Buchsbaum, D.J.; Zinn, K.R.

    2000-01-01

    Utilization of molecular biology techniques offers attractive options in nuclear medicine for improving cancer imaging and therapy with radiolabeled peptides. Two of these options include utilization of phage-panning to identify novel tumor specific peptides or single chain antibodies and gene transfer techniques to increase the antibodies and gene transfer techniques to increase the number of antigen/receptor sites expressed on malignant cells. The group has focused on the latter approach for improving radiolabeled peptide imaging and therapy. The most widely used gene transfer vectors in clinical gene therapy trials include retrovirus, cationic lipids and adenovirus. It has been utilized adenovirus vectors for gene transfer because of their ability to accomplish efficient in vivo gene transfer. Adenovirus vectors encoding the genes for a variety of antigens/receptors (carcinoembryonic antigen, gastrin-releasing peptide receptor, somatostatin receptor subtype 2 (SSTr2) have all shown that their expression is increased on cancer cells both in vitro and in vivo following adenovirus infection. Of particular interest has been the adenovirus encoding for SSTr2 (AdCMVSSTr2). Various radioisotopes have been attached to somatostatin analogues for imaging and therapy of SSTr2-positive tumors both clinically and in animal models. The use of these analogues in combination with AdCMVSSTr2 is a promising approach for improving the detection sensitivity and therapeutic efficacy of these radiolabeled peptides against solid tumors. In addition, it has been proposed the use of SSTr2 as a marker for imaging the expression of another cancer therapeutic transgene (e.g. cytosine deaminase, thymidine kinase) encoded within the same vector. This would allow for non-invasive monitoring of gene delivery to tumor sites

  13. Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.

    Science.gov (United States)

    Brenner, Hermann; Jansen, Lina

    2016-02-01

    Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates; Adenocarcinoma gastrico avancado. Analise da toxicidade e da influencia da radioterapia pre-operatoria nos indices de sobrevivencia a longo prazo

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1996-12-31

    The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author) 112 refs., 34 tabs.

  15. Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates; Adenocarcinoma gastrico avancado. Analise da toxicidade e da influencia da radioterapia pre-operatoria nos indices de sobrevivencia a longo prazo

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1997-12-31

    The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author) 112 refs., 34 tabs.

  16. Phosphodiesterase type 4 inhibitor rolipram improves survival of spiral ganglion neurons in vitro.

    Directory of Open Access Journals (Sweden)

    Katharina Kranz

    Full Text Available Sensorineural deafness is caused by damage of hair cells followed by degeneration of the spiral ganglion neurons and can be moderated by cochlear implants. However, the benefit of the cochlear implant depends on the excitability of the spiral ganglion neurons. Therefore, current research focuses on the identification of agents that will preserve their degeneration. In this project we investigated the neuroprotective effect of Rolipram as a promising agent to improve the viability of the auditory neurons. It is a pharmaceutical agent that acts by selective inhibition of the phosphodiesterase 4 leading to an increase in cyclic AMP. Different studies reported a neuroprotective effect of Rolipram. However, its significance for the survival of SGN has not been reported so far. Thus, we isolated spiral ganglion cells of neonatal rats for cultivation with different Rolipram concentrations and determined the neuronal survival rate. Furthermore, we examined immunocytologically distinct proteins that might be involved in the neuroprotective signalling pathway of Rolipram and determined endogenous BDNF by ELISA. When applied at a concentration of 0.1 nM, Rolipram improved the survival of SGN in vitro. According to previous studies, our immunocytological data showed that Rolipram application induces the phosphorylation and thereby activation of the transcription factor CREB. This activation can be mediated by the cAMP-PKA-signalling pathway as well as via ERK as a part of the MAP-kinase pathway. However, only in cultures pre-treated with BDNF, an endogenous increase of BDNF was detected. We conclude that Rolipram has the potential to improve the vitality of neonatal auditory nerve cells in vitro. Further investigations are necessary to prove the effect of Rolipram in vivo in the adult organism after lesion of the hair cells and insertion of cochlear implants.

  17. Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden.

    Science.gov (United States)

    Strömsöe, A; Afzelius, S; Axelsson, C; Södersved Källestedt, M L; Enlund, M; Svensson, L; Herlitz, J

    2013-06-01

    In a review based on estimations and assumptions, to report the estimated number of survivors after out-of-hospital cardiac arrest (OHCA) in whom cardiopulmonary resuscitation (CPR) was started and to speculate about possible future improvements in Sweden. An observational study. All ambulance organisations in Sweden. Patients included in the Swedish Cardiac Arrest Registry who suffered an OHCA between January 1, 2008 and December 31, 2010. Approximately 80% of OHCA cases in Sweden in which CPR was started are included. None In 11 005 patients, the 1-month survival rate was 9.4%. There are approximately 5000 OHCA cases annually in which CPR is started and 30-day survival is achieved in up to 500 patients yearly (6 per 100 000 inhabitants). Based on findings on survival in relation to the time to calling for the Emergency Medical Service (EMS) and the start of CPR and defibrillation, it was estimated that, if the delay from collapse to (i) calling EMS, (ii) the start of CPR, and (iii) the time to defibrillation were reduced to <2 min, <2 min, and <8 min, respectively, 300-400 additional lives could be saved. Based on findings relating to the delay to calling for the EMS and the start of CPR and defibrillation, we speculate that 300-400 additional OHCA patients yearly (4 per 100 000 inhabitants) could be saved in Sweden. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  18. The Green Roof Microbiome: Improving Plant Survival for Ecosystem Service Delivery

    Directory of Open Access Journals (Sweden)

    Roberta Fulthorpe

    2018-02-01

    Full Text Available Plants are key contributors to ecosystem services delivered by green roofs in cities including stormwater capture, temperature regulation, and wildlife habitat. As a result, current research has primarily focused on their growth in relationship to extensive green roof (e.g., substrates <15 cm depth ecosystem services. Green roofs are exposed to a variety of harsh abiotic factors such as intense solar radiation, wind, and isolation from ground-level habitats, making survival exceedingly difficult. Plants in natural habitats benefit from a variety of interactions with fungi and bacteria. These plant-microbial interactions improve mechanisms of survival and productivity; however, many green roof substrates are sterilized prior to installation and lack microbial communities with unstudied consequences for green roof plant health and subsequent survival and performance. In this paper, we present six hypotheses on the positive role of microbes in green roof applications. In natural and experimental systems, microbial interactions have been linked to plant (1 drought tolerance, (2 pathogen protection, (3 nutrient availability, (4 salt tolerance, (5 phytohormone production, and (6 substrate stabilization, all of which are desirable properties of green roof ecosystems. As few studies exist that directly examine these relationships on green roofs, we explore the existing ecological literature on these topics to unravel the mechanisms that could support more complex green roof ecosystem and lead to new insight into the design, performance, and broader applications in green infrastructure.

  19. Stereotactic radiosurgery improves the survival in patients with solitary brain metastasis: a reasonable alternative to surgery

    International Nuclear Information System (INIS)

    Kwan, H. Cho; Hall, Walter A.; Lee, Andrew K.; Gerbi, Bruce J.; Higgins, Patrick D.; Nussbaum, Eric S.; Chung, K.K. Lee; Bohen, Marva; Clark, H. Brent

    1996-01-01

    (Group 3) (p=0.69 by log-rank test). Conclusion: Although it is difficult to draw a definite conclusion from a retrospective analysis of an unbalanced number of patients among the Groups, our data suggest that SRS improves survival when compared to WBI only and is a reasonable alternative to surgery in the management of solitary brain metastases

  20. Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

    Science.gov (United States)

    Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

    2014-04-01

    Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, J.L.; Wang, F.L.; Yi, X.M.; Qin, W.J.; Wu, G.J. [Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China); Huan, Y. [Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, L.J.; Zhang, G.; Yu, L.; Zhang, Y.T.; Qin, R.L.; Tian, C.J. [Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China)

    2014-10-31

    Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

  2. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Atif J., E-mail: atif.j.khan@rutgers.edu [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Rafique, Raza [Suleman Dawood School of Business, Lahore University of Management Sciences, Lahore (Pakistan); Zafar, Waleed [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Shah, Chirag [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Haffty, Bruce G. [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Vicini, Frank [Michigan HealthCare Professionals, Farmington Hills, Michigan (United States); Jamshed, Arif [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Zhao, Yao [Rutgers University School of Business, Newark, New Jersey (United States)

    2017-02-01

    Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

  3. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

    International Nuclear Information System (INIS)

    Khan, Atif J.; Rafique, Raza; Zafar, Waleed; Shah, Chirag; Haffty, Bruce G.; Vicini, Frank; Jamshed, Arif; Zhao, Yao

    2017-01-01

    Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

  4. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation.

    Science.gov (United States)

    Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H

    2014-01-28

    ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.

  5. Invited review: Improving neonatal survival in small ruminants: science into practice.

    Science.gov (United States)

    Dwyer, C M; Conington, J; Corbiere, F; Holmøy, I H; Muri, K; Nowak, R; Rooke, J; Vipond, J; Gautier, J-M

    2016-03-01

    Neonatal mortality in small ruminant livestock has remained stubbornly unchanging over the past 40 years, and represents a significant loss of farm income, contributes to wastage and affects animal welfare. Scientific knowledge about the biology of neonatal adaptation after birth has been accumulating but does not appear to have had an impact in improving survival. In this paper, we ask what might be the reasons for the lack of impact of the scientific studies of lamb and kid mortality, and suggest strategies to move forward. Biologically, it is clear that achieving a good intake of colostrum, as soon as possible after birth, is crucial for neonatal survival. This provides fuel for thermoregulation, passive immunological protection and is involved in the development of attachment between the ewe and lamb. The behaviour of the lamb in finding the udder and sucking rapidly after birth is a key component in ensuring sufficient colostrum is ingested. In experimental studies, the main risk factors for lamb mortality are low birthweight, particularly owing to poor maternal nutrition during gestation, birth difficulty, litter size and genetics, which can all be partly attributed to their effect on the speed with which the lamb reaches the udder and sucks. Similarly, on commercial farms, low birthweight and issues with sucking were identified as important contributors to mortality. In epidemiological studies, management factors such as providing assistance with difficult births, were found to be more important than risk factors associated with housing. Social science studies suggest that farmers generally have a positive attitude to improving neonatal mortality but may differ in beliefs about how this can be achieved, with some farmers believing they had no control over early lamb mortality. Facilitative approaches, where farmers and advisors work together to develop neonatal survival strategies, have been shown to be effective in achieving management goals, such as

  6. Survival Following Radiation and Androgen Suppression Therapy for Prostate Cancer in Healthy Older Men: Implications for Screening Recommendations

    International Nuclear Information System (INIS)

    Nguyen, Paul L.; Chen, Ming-Hui; Renshaw, Andrew A.; Loffredo, Marian; Kantoff, Philip W.; D'Amico, Anthony V.

    2010-01-01

    Purpose: The U.S. Preventive Services Task Force has recommended against screening men over 75 for prostate cancer. We examined whether older healthy men could benefit from aggressive prostate cancer treatment. Methods and Materials: 206 men with intermediate to high risk localized prostate cancer randomized to 70 Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST) constituted the study cohort. Within subgroups stratified by Adult Comorbidity Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to determine whether treatment with RT+AST as compared with RT was associated with a decreased risk of death. Results: Among healthy men (i.e., with mild or no comorbidity), 78 were older than the median age of 72.4 years, and in this subgroup, RT+AST was associated with a significantly lower risk of death on multivariable analysis (adjusted hazard ratio = 0.36 (95% CI=0.13-0.98), p = 0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were older than the median age of 73, and in this subgroup, treatment with RT+AST was associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p = 0.018). Conclusion: In older men with mild or no comorbidity, treatment with RT+AST was associated with improved survival compared with treatment with RT alone, suggesting that healthy older men may derive the same benefits from prostate cancer treatment as younger men. We therefore suggest that prostate cancer screening recommendations should not be based on strict age cutoffs alone but should also take into account comorbidity.

  7. Survival during renal replacement therapy of patients previously treated with a very low-protein diet supplemented with ketoacids : the Italian experience.

    Directory of Open Access Journals (Sweden)

    A Cupisti

    2012-06-01

    In conclusion, prescription of sVLPD during the conservative phase of chronic renal failure does not worsen, or even improves, survival after starting RRT. This survival advantage is more evident in patients younger than 70 years.

  8. Propensity Score Matched Comparison of Intensity Modulated Radiation Therapy vs Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Survival Analysis from the National Cancer Database

    Directory of Open Access Journals (Sweden)

    Anthony Ricco

    2017-08-01

    Full Text Available PurposeNo direct comparisons between extreme hypofractionation and conventional fractionation have been reported in randomized trials for the treatment of localized prostate cancer. The goal of this study is to use a propensity score matched (PSM analysis with the National Cancer Database (NCDB for the comparison of stereotactic body radiation therapy (SBRT and intensity modulated radiation therapy (IMRT for organ confined prostate cancer.MethodsMen with localized prostate cancer treated with radiation dose ≥72 Gy for IMRT and ≥35 Gy for SBRT to the prostate only were abstracted from the NCDB. Men treated with previous surgery, brachytherapy, or proton therapy were excluded. Matching was performed to eliminate confounding variables via PSM. Simple 1–1 nearest neighbor matching resulted in a matched sample of 5,430 (2,715 in each group. Subset analyses of men with prostate-specific antigen (PSA > 10, GS = 7, and GS > 7 yielded matched samples of 1,020, 2,194, and 247, respectively.ResultsNo difference in survival was noted between IMRT and SBRT at 8 years (p = 0.65. Subset analyses of higher risk men with PSA > 10 or GS = 7 histology or GS > 7 histology revealed no difference in survival between IMRT and SBRT (p = 0.58, p = 0.68, and p = 0.62, respectively. Variables significant for survival for the matched group included: age (p < 0.0001, primary payor (p = 0.0001, Charlson/Deyo Score (p = 0.0002, PSA (p = 0.0013, Gleason score (p < 0.0001, and use of hormone therapy (p = 0.02.ConclusionUtilizing the NCDB, there is no difference in survival at 8 years comparing IMRT to SBRT in the treatment of localized prostate cancer. Subset analysis confirmed no difference in survival even for intermediate- and high-risk patients based on Gleason Score and PSA.

  9. Dose Dependent Survival Response in Chronic Myeloid Leukemia under Continuous and Pulsed Targeted Therapy

    International Nuclear Information System (INIS)

    Pizzolato, N.; Valenti, D.; Spagnolo, B.; Persano Adorno, D.

    2010-01-01

    A simulative study of cancer growth dynamics in patients affected by Chronic Myeloid Leukemia (CML), under the effect of a targeted dose dependent continuous or pulsed therapy, is presented. We have developed a model for the dynamics of CML in which the stochastic evolution of white blood cell populations are simulated by adopting a Monte Carlo approach. Several scenarios in the evolutionary dynamics of white blood cells, as a consequence of the efficacy of the different modelled therapies, pulsed or continuous, are described. The best results, in terms of a permanent disappearance of the leukemic phenotype, are achieved with a continuous therapy and higher dosage. However, our findings demonstrate that an intermittent therapy could represent a valid choice in patients with high risk of toxicity, when a long-term therapy is considered. A suitably tuned pulsed therapy can enhance the treatment efficacy and reduce the percentage of patients developing resistance. (authors)

  10. Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

    Directory of Open Access Journals (Sweden)

    Chunguang Chen

    Full Text Available Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

  11. Value-based contracting innovated Medicare advantage healthcare delivery and improved survival.

    Science.gov (United States)

    Mandal, Aloke K; Tagomori, Gene K; Felix, Randell V; Howell, Scott C

    2017-02-01

    In Medicare Advantage (MA) with its CMS Hierarchical Condition Categories (CMS-HCC) payment model, CMS reimburses private plans (Medicare Advantage Organizations [MAOs]) with prospective, monthly, health-based or risk-adjusted, capitated payments. The effect of this payment methodology on healthcare delivery remains debatable. How value-based contracting generates cost efficiencies and improves clinical outcomes in MA is studied. A difference in contracting arrangements between an MAO and 2 provider groups facilitated an intervention-control, preintervention-postintervention, difference-in-differences approach among statistically similar, elderly, community-dwelling MA enrollees within one metropolitan statistical area. Starting in 2009, for intervention-group MA enrollees, the MAO and a provider group agreed to full-risk capitation combined with a revenue gainshare. The gainshare was based on increases in the Risk Adjustment Factor (RAF), which modified the CMS-HCC payments. For the control group, the MAO continued to reimburse another provider group through fee-for-service. RAF, utilization, and survival were followed until December 31, 2012. The intervention group's mean RAF increased significantly (P based visits (P based care for these MA enrollees with multiple comorbidities, a 6% survival benefit with a 32.8% lower hazard of death (P Value-based contracting can drive utilization patterns and improve clinical outcomes among chronically ill, elderly MA members.

  12. Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer - Results from the prospective German TMK cohort study.

    Science.gov (United States)

    Fietz, Thomas; Tesch, Hans; Rauh, Jacqueline; Boller, Emil; Kruggel, Lisa; Jänicke, Martina; Marschner, Norbert

    2017-08-01

    Data on treatment and outcome of advanced breast cancer in routine practice are rare, especially concerning recurrent disease, but important to complement the results from clinical trials and to improve the standard of care. We present data on choice of systemic first-line treatment, number of treatment lines, and survival of patients treated by medical oncologists in Germany. 1395 patients recruited by 124 sites at start of first-line therapy into the ongoing, prospective German clinical cohort study TMK (Tumour Registry Breast Cancer) between February 2007 and October 2015 were analysed. The median OS was 33.8 months (95% CI 30.2-40.2) for HR-positive/HER2-negative, 38.2 months (95% CI 31.3-43.0) for HER2-positive and 16.8 months (95% CI 11.5-22.0) for triple negative breast cancer. Patients with triple negative tumours more often died before start of a third-line therapy than patients with HR-positive or HER2-positive tumours (44% vs. 25%). Use of taxane-based chemotherapies has increased since 2007, with 65% of all first-line chemotherapy-treatments containing taxanes in 2013-15 (60% HR-positive/HER2-negative, 75% HER2-positive, 56% triple negative). 52% of the patients with HR-positive/HER2-negative tumours received first-line endocrine therapy in 2013-15; when restricted to patients with only non-visceral metastases this percentage increased to 63%. To our knowledge, this is the first cohort study showing systemic first-line therapy for all subtypes of advanced breast cancer. Overall survival in the TMK is comparable to that reported by clinical trials despite the inclusion of older and comorbid patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Il Han, E-mail: ihkim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Byoung Hyuck [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Tae Min; Heo, Dae Seog [Department of Internal Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

  14. Additional survival benefit of involved-lesion radiation therapy after R-CHOP chemotherapy in limited stage diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kwon, Jeanny; Kim, Il Han; Kim, Byoung Hyuck; Kim, Tae Min; Heo, Dae Seog

    2015-05-01

    The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥ 7 cm); and 75.3% underwent ≥ 6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥ 6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level. Copyright © 2015. Published by Elsevier Inc.

  15. Application of bacterial lipopolysaccharide to improve survival of the black tiger shrimp after Vibrio harveyi exposure.

    Science.gov (United States)

    Rungrassamee, Wanilada; Maibunkaew, Sawarot; Karoonuthaisiri, Nitsara; Jiravanichpaisal, Pikul

    2013-10-01

    This study investigates an effect of bacterial lipopolysaccharide (LPS) as feed supplement to improve immunity of the black tiger shrimp (Penaeus monodon). LPS was coated to commercial feed pellets and given to the shrimp once or twice a day for 10 days before an exposure with shrimp pathogenic bacterium Vibrio harveyi. The growth rates, percent weight gains, total hemocyte and granulocyte counts and survival rates of shrimp between the LPS-coated pellet fed groups and a control group where shrimp fed with commercial feed pellets were compared. After 10 days of the feeding trials, growth rates were not significantly different in all groups, suggesting no toxicity from LPS supplement. To determine beneficial effect of LPS diets, each group was subsequently exposed to V. harveyi by immersion method and the survival rates were recorded for seven days after the immersion. Regardless of the dosages of LPS, the shrimp groups fed with LPS-coated pellets showed higher survival rates than the control group. There was no significant difference in survival rates between the two LPS dosages groups. In addition to survival under pathogen challenge, we also determine effect of LPS on immune-related genes after 10-day feeding trial. Gene expression analysis in the P. monodon intestines revealed that antilipopolysaccharide factor isoform 3 (ALF3), C-type lectin, and mucine-like peritrophin (mucin-like PM) were expressed significantly higher in a group fed with LPS supplemental diet once or twice a day than in a control group. The transcript levels of C-type lectin and mucin-like PM had increased significantly when LPS was given once a day, while significant induction of ALF3 transcripts was observed when shrimp were fed with LPS twice a day. The up-regulation of the immune gene levels in intestines and higher resistance to V. harveyi of the shrimp fed with LPS provide the evidence for potential application of LPS as an immunostimulant in P. monodon farming. Copyright © 2013

  16. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

    Science.gov (United States)

    Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

    2016-09-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

  17. Effect of therapy on five- and ten-year survival of malignant melanoma patients

    International Nuclear Information System (INIS)

    Siffnerova; Bustova; Zikmund

    1989-01-01

    The results are reported of five-year and ten-year survival of malignant melanoma patients treated postoperatively by actinotherapy. In patients where lymph flow was not apparent, 2.5 Gy of daily doses of electron irradiation from a 6-8 MeV betatron were used centred on the scar. The total dose was 60 Gy. Where the lymph flow could be identified, cobalt or cesium sources were used to deliver a total dose of 50 Gy in 2.5 Gy daily. Both five-year and ten-year survival was significantly better than in patients treated with surgery only, without irradiation. 55% of the patients on combined management survived for more than 5 years, 86% of them without relapses. 41% patients survived for 10 years, of which 92% without relapse. In contrast, the corresponding figures for the patients treated with surgery only were 42% and 71% respectively for the five-year survival, and 26% and 70% respectively for the ten-year survival. (L.O.). 3 figs., 2 tabs

  18. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  19. Long-term survival of bladder preservation therapy with radiation and chemotherapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

    Noguchi, Sumio; Takase, Kazunori; Kubota, Yoshinobu; Masuda, Mitsunobu; Yao, Masahiro; Hosaka, Masahiko

    1998-01-01

    The prognoses and prognostic factors of the 54 patients with locally invasive bladder cancer who underwent bladder preservation therapy at Yokohama City University Hospital between 1977 and 1995 were analyzed statistically. The therapeutic modalities of bladder preservation were mainly radiation or chemotherapy. The prognosis for the patients who underwent bladder preservation therapy was worse than that for the patients who underwent total cystectomy. The prognostic factors of these patients were size and grade of tumor, presence of hydronephrosis and performance status (PS) of the patients by univariate analysis. Tumor grade was the most predictable prognostic factor using multivariate analysis. Only 17 patients survived more than 5 years after treatment; 78% of the survivors had good PS (0 or 1). Five of them died of cancer and two patients were alive with cancer. All of them had G3 tumors. These results suggest that patients with locally invasive G2 tumor could be candiates for bladder preservation therapy and patients who underwent bladder preservation therapy should be evaluated at 10 years post-therapy. (author)

  20. Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival?

    NARCIS (Netherlands)

    Eggermont, Alexander M. M.; Punt, Cornelis J. A.

    2003-01-01

    The experience with interferon-alpha in malignant melanoma resembles, to some degree, the experience with various kinds of adjuvant immunotherapeutic agents where 25 years of phase III trials of adjuvant therapy in stage II-IIII melanoma have not defined a standard therapy. Most trials failed to

  1. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    Directory of Open Access Journals (Sweden)

    Enjae Jung

    Full Text Available World conditions place large populations at risk from ionizing radiation (IR from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA. While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01. Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01. These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

  2. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    Science.gov (United States)

    Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

  3. Interventions for weight reduction in obesity to improve survival in women with endometrial cancer.

    Science.gov (United States)

    Kitson, Sarah; Ryan, Neil; MacKintosh, Michelle L; Edmondson, Richard; Duffy, James Mn; Crosbie, Emma J

    2018-02-01

    Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival as well as a reduction in the risk of cardiovascular disease, a frequent cause of death in endometrial cancer survivors. To determine the impact of weight-loss interventions, in addition to standard management of endometrial cancer, on overall survival and the frequency of adverse events.Secondary objectives include an assessment of weight-loss interventions on endometrial cancer-specific survival, weight loss achieved, cardiovascular event frequency and quality of life both overall and stratified according to patient body mass index (BMI), where possible. This review searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase and reference lists of articles, trial registries, and international gynaecological oncology conference abstracts from inception to January 2018. Randomised controlled trials (RCTs) of interventions to facilitate weight loss in overweight or obese women undergoing treatment for, or previously treated for, endometrial cancer were selected. Two review authors independently selected studies, assessed trial quality, and extracted data with disagreements resolved by a third review author. Study authors were contacted to obtain missing data, including details of any adverse events. We included three RCTs in the review, randomising a total of 161 overweight and obese women with endometrial cancer. All studies compared combined behavioural and lifestyle interventions to facilitate weight loss

  4. Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion.

    Science.gov (United States)

    Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-02-01

    Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore

  5. Improved survival and neurodevelopmental outcomes among extremely premature infants born near the limit of viability.

    Science.gov (United States)

    Younge, Noelle; Smith, P Brian; Gustafson, Kathryn E; Malcolm, William; Ashley, Patricia; Cotten, C Michael; Goldberg, Ronald N; Goldstein, Ricki F

    2016-04-01

    Infants born near the limit of viability are at high risk for death or adverse neurodevelopmental outcomes. It is unclear whether these outcomes have improved over the past 15 years. To determine if death and neurodevelopmental impairment have declined over the past 15 years in infants born at 22 to 24 weeks' gestation. Retrospective cohort study. We identified infants born at 22 to 24 weeks' gestation in our center in two epochs: 1998-2004 (Epoch 1) and 2005-2011 (Epoch 2). The primary outcome, death or neurodevelopmental impairment, was evaluated at 17-25 months' corrected gestational age with neurologic exams and Bayley Scales of Infant Development. Perinatal characteristics, major morbidities, and outcomes were compared between epochs. Birth weight and gestational age were similar between 170 infants in Epoch 1 and 187 infants in Epoch 2. Mortality was significantly lower in Epoch 2, 55% vs. 42% (p=0.02). Among surviving infants, late-onset sepsis (pNeurodevelopmental impairment among surviving infants declined from 68% in Epoch 1 to 47% in Epoch 2, p=0.02. Odds of death or NDI were significantly lower in Epoch 2 vs. Epoch 1, OR=0.31 (95% confidence interval; 0.16, 0.58). Risk of death or neurodevelopmental impairment decreased over time in infants born at 22 to 24 weeks' gestation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Going the Extra Mile: Improved Survival for Pancreatic Cancer Patients Traveling to High-volume Centers.

    Science.gov (United States)

    Lidsky, Michael E; Sun, Zhifei; Nussbaum, Daniel P; Adam, Mohamed A; Speicher, Paul J; Blazer, Dan G

    2017-08-01

    This study compares outcomes following pancreaticoduodenectomy (PD) for patients treated at local, low-volume centers and those traveling to high-volume centers. Although outcomes for PD are superior at high-volume institutions, not all patients live in proximity to major medical centers. Theoretical advantages for undergoing surgery locally exist. The 1998 to 2012 National Cancer Data Base was queried for T1-3N0-1M0 pancreatic adenocarcinoma patients who underwent PD. Travel distances to treatment centers were calculated. Overlaying the upper and lower quartiles of travel distance with institutional volume established short travel/low-volume (ST/LV) and long travel/high-volume (LT/HV) cohorts. Overall survival was evaluated. Of 7086 patients, 773 ST/LV patients traveled ≤6.3 (median 3.2) miles to centers performing ≤3.3 PDs yearly, and 758 LT/HV patients traveled ≥45 (median 97.3) miles to centers performing ≥16 PDs yearly. LT/HV patients had higher stage disease (P travel to a high-volume center remained associated with reduced long-term mortality (hazard ratio 0.75, P travel burden, patients treated at high-volume centers had improved perioperative outcomes, short-term mortality, and overall survival. These data support ongoing efforts to centralize care for patients undergoing PD.

  7. Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

    Directory of Open Access Journals (Sweden)

    Golden Daniel W

    2012-09-01

    Full Text Available Abstract Background Unresectable pancreatic cancer (UPC has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT as definitive treatment for UPC and the CA 19–9 response to therapy have an impact on overall survival (OS. Methods From 1997–2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy. All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other and 24 received adjuvant chemotherapy. Results 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy. Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19–9 post-CRT Conclusions CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19–9

  8. Radiation therapy: A major factor in the five-year survival analysis of women with breast cancer in Lagos, Nigeria

    International Nuclear Information System (INIS)

    Makanjuola, Samira B.L.; Popoola, Abiodun O.; Oludara, Mobolaji A.

    2014-01-01

    Purpose: This retrospective study was carried out to examine five-year survival from breast cancer cases diagnosed between 2005 and May 2008 in Nigerian women. Material and methods: Two hundred and twenty-four patients were entered into the study. Five-year survival was evaluated using proportional hazard model proposed by Cox to assess variables such as age of diagnosis, menopausal status, and stage of the disease in the two treatment groups: surgery/chemotherapy or surgery/chemotherapy/radiotherapy. Results: Findings revealed that the different staging of disease and treatment are independent predictors of disease outcome whereas age of diagnosis and menopausal status although associated with low hazards, are not significant. TNM Stage I (Hazard Ratio = 0.153, 95% CI 0.45–0.51, P = 0.003), II (Hazard Ratio = 0.245, 95% CI 0.12–0.46, P = 0.0001), and III (Hazard Ratio = 0.449, 95% CI 0.31–0.46, P = 0.0001) showed significantly greater survival rates compared to TNM Stage IV for patients receiving surgery/chemotherapy. Similarly, for patients receiving surgery/chemotherapy/radiotherapy TNM Stage II (Hazard Ratio = 0.110, 95% CI 0.02–0.46, P = 0.003) and III (Hazard Ratio = 0.238, 95% CI 0.07–0.73, P = 0.012) also showed significantly greater survival rates compared to TNM Stage IV. Treatment had a significant impact on survival independent of stage, age, and menopausal status. Patients receiving surgery/chemotherapy/radiotherapy had a significant increase in survival outcome for TNM Stage (II, P = 0.045; III, P = 0.0001); age groups (40–49, P = 0.021; 50–59, P = 0.016; 60–69, P = 0.017; >70, P = 0.025); and menopausal status (premenopausal, P = 0.049; postmenopausal, P = 0.0001) compared to those receiving surgery/chemotherapy. Conclusion: The five-year breast cancer survival rate in Lagos, Nigeria 24.1% (54/224) is relatively poor compared to most countries in the world and needs to be improved. Poor survival rates are mainly attributed to late

  9. Improvements in breast cancer survival between 1995 and 2012 in Denmark

    DEFF Research Database (Denmark)

    Jensen, Maj-Britt; Ejlertsen, Bent; Mouridsen, Henning T

    2016-01-01

    Background Breast cancer mortality has declined from 1995 through 2012 which may be attributed to earlier diagnosis, changes in lifestyle risk factors, and improved treatments. To a large extent the relative contribution of these modalities are unknown. Mammography screening was introduced late...... was extended considerable. Methods A population-based study of 68 842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were...... in Denmark; in 1995 around 20% of the Danish female population aged 50-69 was covered by population-based screening, and this was in 2008 extended to the entire population. Breast conserving surgery gradually replaced mastectomy, and sentinel node biopsy was introduced. In the same period adjuvant treatment...

  10. Nutrition management for head and neck cancer patients improves clinical outcome and survival.

    Science.gov (United States)

    Müller-Richter, Urs; Betz, C; Hartmann, S; Brands, R C

    2017-12-01

    Up to 80% of patients with head and neck cancers are malnourished because of their lifestyle and the risk factors associated with this disease. Unfortunately, nutrition management systems are not implemented in most head and neck cancer clinics. Even worse, many head and neck surgeons as well as hospital management authorities disregard the importance of nutrition management in head and neck cancer patients. In addition, the often extensive resection and reconstruction required for tumors in the upper aerodigestive tract pose special challenges for swallowing and sufficient food intake, placing special demands on nutrition management. This article presents the basics of perioperative metabolism and nutrition management of head and neck cancer patients and makes recommendations for clinical practice. Implementing a nutrition management system in head and neck cancer clinics will improve the clinical outcome and the survival of the patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd; Fischer-Valuck, Benjamin W. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Mutch, David G.; Powell, Matthew A. [Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri (United States); Schwarz, Julie K. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Grigsby, Perry W., E-mail: pgrigsby@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2015-11-01

    Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Cox proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.

  12. Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

    International Nuclear Information System (INIS)

    Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd; Fischer-Valuck, Benjamin W.; Mutch, David G.; Powell, Matthew A.; Schwarz, Julie K.; Grigsby, Perry W.

    2015-01-01

    Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Cox proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.

  13. Combined intranasal nerve growth factor and ventricle neural stem cell grafts prolong survival and improve disease outcome in amyotrophic lateral sclerosis transgenic mice.

    Science.gov (United States)

    Zhong, Shi-Jiang; Gong, Yan-Hua; Lin, Yan-Chen

    2017-08-24

    Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively involves motor neurons. Neurotrophic factor supplementation and neural stem cell (NSC) alternative therapy have been used to treat ALS. The two approaches can affect each other in their pathways of action, and there is a possibility for synergism. However, to date, there have been no studies demonstrating the effects of combined therapy in the treatment of ALS. In this study, for the first time, we adopted a method involving the intranasal administration of nerve growth factor combined with lateral ventricle NSC transplantation using G93A-SOD1 transgenic mice as experimental subjects to explore the treatment effect of this combined therapy in ALS. We discover that the combined therapy increase the quantity of TrkA receptors, broaden the migration of exogenous NSCs, further promote active proliferation in neurogenic regions of the brain and enhance the preservation of motor neurons in the spinal cord. Regarding physical activity, the combined therapy improved motor functions, further postponed ALS onset and extended the survival time of the mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Can survival prediction be improved by merging gene expression data sets?

    Directory of Open Access Journals (Sweden)

    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  15. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Science.gov (United States)

    2010-07-01

    ... elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and... spouses of Spanish-American War veterans. (a) General. A surviving spouse of a Spanish-American War... and attendance. A surviving spouse of a Spanish-American War veteran who is receiving or entitled to...

  16. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    International Nuclear Information System (INIS)

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-01-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer

  17. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Eng-Yen [Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Chanchien, Chan-Chao; Lin, Hao [Department of Gynecologic Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Wang, Chung-Chi; Wang, Chong-Jong [Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Huang, Chao-Cheng, E-mail: huangcc@cgmh.org.tw [Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China)

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  18. Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

    International Nuclear Information System (INIS)

    Zheng, Xiangpeng; Schipper, Matthew; Kidwell, Kelley; Lin, Jules; Reddy, Rishindra; Ren, Yanping; Chang, Andrew; Lv, Fanzhen; Orringer, Mark; Spring Kong, Feng-Ming

    2014-01-01

    Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery

  19. Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xiangpeng [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Schipper, Matthew [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Kidwell, Kelley [Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Lin, Jules; Reddy, Rishindra [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Ren, Yanping [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Chang, Andrew [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Lv, Fanzhen [Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai (China); Orringer, Mark [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Spring Kong, Feng-Ming, E-mail: Fkong@gru.edu [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States)

    2014-11-01

    Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

  20. Association Between Use of Traditional Chinese Medicine Herbal Therapy and Survival Outcomes in Patients With Stage II and III Colorectal Cancer: A Multicenter Prospective Cohort Study.

    Science.gov (United States)

    Xu, Yun; Mao, Jun J; Sun, Lingyun; Yang, Lin; Li, Jie; Hao, Yingxu; Li, Huashan; Hou, Wei; Chu, Yuping; Bai, Yu; Jia, Xiaoqiang; Wang, Jinwan; Shen, Lin; Zhang, Ying; Wang, Jianbin; Liu, Jianping; Yang, Yufei

    2017-11-01

    Chinese cancer patients often use Traditional Chinese Medicine (TCM) herbal medicine during or after active cancer treatments. However, little is known about how TCM herbal medicine impacts cancer outcomes. This study aimed to evaluate the association between TCM herbal therapy and survival outcomes in patients with stage II or III colorectal cancer. We conducted an eight-center prospective cohort study in China among patients who had undergone radical resection for stage II and III colorectal cancer. All patients received comprehensive conventional treatments according to National Comprehensive Cancer Network (NCCN) guidelines, and follow-up visits were conducted over five years. We defined high exposure as a patient's use of TCM individualized herbs for more than one year, ascertained via clinical interviews. The primary outcome was disease-free survival (DFS), with overall survival (OS) as a secondary outcome. Between April 2007 and February 2009, we enrolled 312 patients into the cohort; 166 (53.2%) met the definition of high exposure to TCM herbs. Adjusting for covariates, high exposure to TCM was associated with both better DFS (hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.39 to 0.98) and OS (HR = 0.31, 95% CI = 0.14 to 0.68). In subgroup exploratory analysis, the effects demonstrated that the differences in outcomes were statistically significant in patients who had received chemotherapy. Longer duration of TCM herbal use is associated with improved survival outcomes in stage II and III colorectal cancer patients in China. More research is needed to evaluate the effects and underlying mechanisms of herbal medicine on colorectal cancer outcomes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated Systemic Capillary-Leak Syndrome.

    Science.gov (United States)

    Pineton de Chambrun, Marc; Gousseff, Marie; Mauhin, Wladimir; Lega, Jean-Christophe; Lambert, Marc; Rivière, Sophie; Dossier, Antoine; Ruivard, Marc; Lhote, François; Blaison, Gilles; Alric, Laurent; Agard, Christian; Saadoun, David; Graveleau, Julie; Soubrier, Martin; Lucchini-Lecomte, Marie-Josée; Christides, Christine; Bosseray, Annick; Levesque, Hervé; Viallard, Jean-François; Tieulie, Nathalie; Lovey, Pierre-Yves; Le Moal, Sylvie; Bibes, Béatrice; Malizia, Giuseppe; Abgueguen, Pierre; Lifermann, François; Ninet, Jacques; Hatron, Pierre-Yves; Amoura, Zahir

    2017-10-01

    Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first

  2. Survival Outcomes of Patients Treated with Hypofractionated Stereotactic Body Radiation Therapy for Parotid Gland Tumors: a Retrospective Analysis

    International Nuclear Information System (INIS)

    Karam, Sana D.; Snider, James W.; Wang, Hongkun; Wooster, Margaux; Lominska, Christopher; Deeken, John; Newkirk, Kenneth; Davidson, Bruce; Harter, K. William

    2012-01-01

    Background: to review a single-institution experience with the management of parotid malignancies treated by fractionated stereotactic body radiosurgery (SBRT). Findings: Between 2003 and 2011, 13 patients diagnosed with parotid malignancies were treated with adjuvant or definitive SBRT to a median dose of 33 Gy (range 25–40 Gy). There were 11 male and two female patients with a median age of 80. Ten patients declined conventional radiation treatment and three patients had received prior unrelated radiation therapy to neighboring structures with unavailable radiation records. Six patients were treated with definitive intent while seven patients were treated adjuvantly for adverse surgical or pathologic features. Five patients had clinical or pathologic evidence of lymph node disease. Conclusion: at a median follow-up of 14 months only one patient failed locally, and four failed distantly. The actuarial 2-year overall survival, progression-free survival, and local-regional control rates were 46, 84, and 47%, respectively. Statistical analysis revealed surgery as a positive predictor of overall survival while presence of gross disease was a negatively correlated factor (p < 0.05).

  3. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    International Nuclear Information System (INIS)

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  4. Renal transplant immunology in the last 20 years: A revolution towards graft and patient survival improvement.

    Science.gov (United States)

    Sá, Helena; Leal, Rita; Rosa, Manuel Santos

    2017-05-04

    To deride the hope of progress is the ultimate fatuity, the last word in poverty of spirit and meanness of mind. There is no need to be dismayed by the fact that we cannot yet envisage a definitive solution of our problems, a resting-place beyond which we need not try to go. -P.B. Medawar, 1969 * Thomas E. Starlz, also known as the Father of Clinical Transplantation, once said that organ transplantation was the supreme exception to the rule that most major advances in medicine spring from discoveries in basic science [Starzl T. The mystique of organ transplantation. J Am Coll Surg 2005 Aug;201(2):160-170]. In fact, the first successful identical-twin kidney transplantation performed by Murray's team in December 1954 (Murray J et al. Renal homotransplantations in identical twins. Surg Forum 1955;6:432-436) was the example of an upside down translation medicine: Human clinical transplantation began and researchers tried to understand the underlying immune response and how to control the powerful rejection pathways through experimental models. In the last 20 years, we have witnessed an amazing progress in the knowledge of immunological mechanisms regarding alloimmune response and an outstanding evolution on the identification and characterization of major and minor histocompatibility antigens. This review presents an historical and clinical perspective of those important advances in kidney transplantation immunology in the last 20 years, which contributed to the improvement in patients' quality of life and the survival of end-stage renal patients. In spite of these significant progresses, some areas still need substantial progress, such as the definition of non-invasive biomarkers for acute rejection; the continuous reduction of immunosuppression; the extension of graft survival, and finally the achievement of real graft tolerance extended to HLA mismatch donor: recipient pairs.

  5. Abandoning Peracetic Acid-Based Dialyzer Reuse Is Associated with Improved Survival

    Science.gov (United States)

    Wang, Weiling; Mooney, Ann; Ofsthun, Norma; Lazarus, J. Michael; Hakim, Raymond M.

    2011-01-01

    Summary Background and objectives Higher mortality risk reported with reuse versus single use of dialyzers is potentially related to reuse reagents that modify membrane surface characteristics and the blood-membrane interface. A key mechanism may involve stimulation of an inflammatory response. Design, setting, participants, & measurements In a prospective crossover design, laboratory markers and mortality from 23 hemodialysis facilities abandoning reuse with peracetic acid mixture were tracked. C-reactive protein (CRP), white blood cell (WBC) count, albumin, and prealbumin were measured for 2 consecutive months before abandoning reuse and subsequently within 3 and 6 months on single use. Survival models were utilized to compare the 6-month period before abandoning reuse (baseline) and the 6-month period on single use of dialyzers after a 3-month “washout period.” Results Patients from baseline and single-use periods had a mean age of approximately 63 years; 44% were female, 54% were diabetic, 60% were white, and the mean vintage was approximately 3.2 years. The unadjusted hazard ratio for death was 0.70 and after case-mix adjustment was 0.74 for single use compared with reuse. Patients with CRP ≥ 5 mg/L during reuse (mean CRP = 26.6 mg/ml in April) declined on single use to 20.2 mg/L by August and 20.4 mg/L by November. WBC count declined slightly during single use, but nutritional markers were unchanged. Conclusions Abandonment of peracetic-acid-based reuse was associated with improved survival and lower levels of inflammatory but not nutritional markers. Further study is needed to evaluate a potential link between dialyzer reuse, inflammation, and mortality. PMID:20947788

  6. Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

    Science.gov (United States)

    Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

    2016-09-01

    The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Postoperative radiotherapy improves local control and survival in patients with uterine leiomyosarcoma

    International Nuclear Information System (INIS)

    Wong, Philip; Han, Kathy; Sykes, Jenna; Catton, Charles; Laframboise, Stephane; Fyles, Anthony; Manchul, Lee; Levin, Wilfred; Milosevic, Michael

    2013-01-01

    To examine the role of radiotherapy (RT) in uterine leiomyosarcomas (LMS) and to determine the patient population who may benefit from RT. From 1998–2008, 69 patients with primary uterine LMS underwent hysterectomy with or without pelvic radiotherapy to a median dose of 45 Gy. Univariate analysis was performed using the Kaplan-Meier method and cumulative-incidence function, and multivariate analyses using Fine and Gray or Cox proportional hazard models. Following surgery, 32 out of 69 patients received RT. There was no evidence of any correlation between patient, disease and treatment characteristics and the use of RT. Median follow-up was 57 months. RT was associated with reduced local recurrence (3y LR 19% vs. 39%; Gray’s p = 0.019) and improved overall survival (3y OS 69% vs. 35%; log-rank p = 0.025) on univariate analysis. Multivariate analysis demonstrated that RT reduced LR (HR: 0.28, CI: 0.11-0.69, p = 0.006) and increased OS (HR: 0.44, CI: 0.23-0.85, p = 0.014) independent of other clinical and pathologic factors. Positive surgical margins increased the odds of LR (HR: 5.6, CI: 2.3-13.4, p = 0.00012). Large tumor size and advanced stage (II-IV) were associated with the development of distant metastases and inferior OS. Postoperative pelvic RT reduces LR and improves OS of patients with uterine LMS

  8. High hospital research participation and improved colorectal cancer survival outcomes: a population-based study.

    Science.gov (United States)

    Downing, Amy; Morris, Eva Ja; Corrigan, Neil; Sebag-Montefiore, David; Finan, Paul J; Thomas, James D; Chapman, Michael; Hamilton, Russell; Campbell, Helen; Cameron, David; Kaplan, Richard; Parmar, Mahesh; Stephens, Richard; Seymour, Matt; Gregory, Walter; Selby, Peter

    2017-01-01

    In 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals. Data for patients diagnosed with CRC in England in 2001-2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day postoperative mortality and 5-year survival and the level and duration of study participation. Most of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer 'centres of excellence', although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower postoperative mortality (presearch participation, with a reduction in postoperative mortality of 1.5% (6.5%-5%, pstudies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Improving breast cancer survival analysis through competition-based multidimensional modeling.

    Directory of Open Access Journals (Sweden)

    Erhan Bilal

    Full Text Available Breast cancer is the most common malignancy in women and is responsible for hundreds of thousands of deaths annually. As with most cancers, it is a heterogeneous disease and different breast cancer subtypes are treated differently. Understanding the difference in prognosis for breast cancer based on its molecular and phenotypic features is one avenue for improving treatment by matching the proper treatment with molecular subtypes of the disease. In this work, we employed a competition-based approach to modeling breast cancer prognosis using large datasets containing genomic and clinical information and an online real-time leaderboard program used to speed feedback to the modeling team and to encourage each modeler to work towards achieving a higher ranked submission. We find that machine learning methods combined with molecular features selected based on expert prior knowledge can improve survival predictions compared to current best-in-class methodologies and that ensemble models trained across multiple user submissions systematically outperform individual models within the ensemble. We also find that model scores are highly consistent across multiple independent evaluations. This study serves as the pilot phase of a much larger competition open to the whole research community, with the goal of understanding general strategies for model optimization using clinical and molecular profiling data and providing an objective, transparent system for assessing prognostic models.

  10. Characteristics and survival of young adults who started renal replacement therapy during childhood

    NARCIS (Netherlands)

    Kramer, Anneke; Stel, Vianda S.; Tizard, Jane; Verrina, Enrico; Rönnholm, Kai; Pálsson, Runólfur; Maxwell, Heather; Jager, Kitty J.

    2009-01-01

    BACKGROUND: Little is known about the group of children on renal replacement therapy (RRT) who reach the age of 18 years and are transferred from paediatric to adult nephrology services. The aim of this study was to describe patient demographics, primary renal diseases, treatment history and

  11. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    Science.gov (United States)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  12. Oral Effects and Early Implant Survival Results After Imatinib Discontinuation Therapy for Chronic Myelogenous Leukemia: A Case Report.

    Science.gov (United States)

    Dixon, Douglas R; Yassin, Alaa

    2017-08-01

    Little is known regarding the success, failure, or complication rates of advanced implant procedures in patients after discontinuation therapy of long-term medications for the treatment of chronic myelogenous leukemia (CML). This case report presents initial results of a case involving implant placement in the mandible and maxilla as well as reduction of palatal oral pigmentation in a patient discontinuing long-term tyrosine kinase inhibitor (TKI) therapy for CML. A 57-year-old male was referred to the Department of Periodontics, University of Washington, Seattle, Washington, for an assessment of edentulous areas (tooth sites #3 and #14) and failing tooth #19. Previous medical treatment included oral administration (>10 years) of TKI for the treatment of CML. Systemic complications arising from long-term TKI therapy were treated with discontinuation of this medication. Concurrently, after multispecialty dental and medical consultation, extraction of tooth #19 with immediate implant placement and bilateral sinus augmentation with simultaneous implant placement were successfully performed during three separate surgical appointments. Additionally, marked reduction of oral palatal pigmentation was observed during the surgical and restorative phases after TKI discontinuation. Patients with a history of long-term TKIs for CML are at risk for developing complications that result in discontinuation of therapy. Long-term benefits of therapy may allow these patients to enjoy remission with an extended and improved quality of life. Patients undergoing discontinuation therapy may seek dental care. Therefore, dental providers need to understand these systemic interactions and, with multispecialty consultation, may help effectively treat these individuals.

  13. Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Minatel, Emilio [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Di Maso, Matteo [Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Drigo, Annalisa; Barresi, Loredana [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Furlan, Carlo [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Pordenone (Italy); Bruschi, Gioia [Department of Pneumology, Pordenone General Hospital, Pordenone (Italy); Fontana, Paolo [Department of Thoracic Surgery, Mestre General Hospital, Mestre (Italy); Pagan, Vittore [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Franchin, Giovanni [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy)

    2015-11-01

    Purpose: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and

  14. Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Xinyu Qian

    Full Text Available Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer.From inception to January 2015, we searched for randomized, controlled trials (RCTs using the following databases: PubMed, ScienceDirect, the Cochrane Library, Clinicaltrials.gov and EBSCO. Eligible trials included RCTs that evaluated standard chemotherapy which was either followed or not followed by targeted maintenance in patients with ovarian cancer who had been previously receiving adjunctive treatments, such as cytoreductive surgery and standard chemotherapy. The outcome measures included progression-free survival (PFS, overall survival (OS and incidence of adverse events.A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria. The primary meta-analysis indicated that both PFS and OS were statistically and significantly improved in the targeted maintenance therapy group as compared to the control group (PFS: HR = 0.84, 95%CI: 0.75 to 0.95, p = 0.001; OS: HR = 0.91, 95%CI: 0.84 to 0.98, p = 0.02. When taking safety into consideration, the use of targeted agents was significantly correlated with increased risks of fatigue, diarrhea, nausea, vomiting, and hypertension. However, no significant differences were found in incidence rates of abdominal pain, constipation or joint pain.Our results indicate that targeted maintenance therapy clearly improves the survival of ovarian cancer patients but may also increase the incidence of adverse events. Additional randomized, double-blind, placebo-controlled, multicenter investigations will be required on a larger cohort of patients to verify our findings.

  15. Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease.

    Science.gov (United States)

    Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne

    2013-10-01

    There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.

  16. Assessing Community Based Improved Maternal Neonatal Child Survival (IMNCS Program in Rural Bangladesh.

    Directory of Open Access Journals (Sweden)

    Mahfuzar Rahman

    Full Text Available A community based approach before, during and after child birth has been proven effective address the burden of maternal, neonatal and child morbidity and mortality in the low and middle income countries. We aimed to examine the overall change in maternal and newborn health outcomes due the "Improved Maternal Newborn and Child Survival" (IMNCS project, which was implemented by BRAC in rural communities of Bangladesh.The intervention was implemented in four districts for duration of 5-years, while two districts served as comparison areas. The intervention was delivered by community health workers who were trained on essential maternal, neonatal and child health care services. A baseline survey was conducted in 2008 among 7, 200 women with pregnancy outcome in last year or having a currently alive child of 12-59 months. A follow-up survey was administered in 2012-13 among 4, 800 women of similar characteristics in the same villages.We observed significant improvements in maternal and essential newborn care in intervention areas over time, especially in health care seeking behaviors. The proportion of births taking place at home declined in the intervention districts from 84.3% at baseline to 71.2% at end line (P<0.001. Proportion of deliveries with skilled attendant was higher in intervention districts (28% compared to comparison districts (27.4%. The number of deliveries was almost doubled at public sector facility comparing with baseline (P<0.001. Significant improvement was also observed in healthy cord care practice, delayed bathing of the new-born and reduction of infant mortality in intervention districts compared to that of comparison districts.This study demonstrates that community-based efforts offer encouraging evidence and value for combining maternal, neonatal and child health care package. This approach might be considered at larger scale in similar settings with limited resources.

  17. Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

    DEFF Research Database (Denmark)

    Maddika, S; Ande, SR; Panigrahi, S

    2007-01-01

    )), and the Cip1/Waf1/Kip1-2-family (p21(Cip1/Waf1), p27(Kip1), p57(Kip2)) are shown both in the context of proliferation regulators and as contributors to the apoptotic machinery. Bcl2-family members (i.e. Bcl2, Bcl-X(L) Mcl-1(L); Bax, Bok/Mtd, Bak, and Bcl-X(S); Bad, Bid, Bim(EL), Bmf, Mcl-1(S)) are highlighted...... approaches that would involve redirecting over-active survival and proliferation pathways towards induction of apoptosis in cancer cells....

  18. Global survival in patients with glioblastoma treated with hypofractionated radiation therapy at Hospital Mexico of Costa Rica during the period from January 2010 to February 2013

    International Nuclear Information System (INIS)

    Ramirez Zamora, Juliana

    2014-01-01

    Survival is analyzed in patients with glioblastoma treated with hypofractionated radiation therapy at Hospital Mexico. The characteristics of the patients are determined within the study. Survival is stableshed in patients who have received hypofractionated regimen. Functional status according to ECOG scale and Karnofsky index is known prior to radiotherapy. The degree of resection to which these patients were submitted is diagnosed before being referred to radiotherapy. The RPA scale adapted from the EORTC of patients is related to overall survival. The mean survival time of the patients have been 5,8 months, and a greater overall survival in the first 6 months. Survival has been more favorable for patients with predicted RPA IV, those older than 60 years and with a degree of complete resection [es

  19. Clinical audit training improves undergraduates' performance in root canal therapy.

    Science.gov (United States)

    Fong, J Y M; Tan, V J H; Lee, J R; Tong, Z G M; Foong, Y K; Tan, J M E; Parolia, A; Pau, A

    2017-12-20

    To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates. Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test. Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001). Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    International Nuclear Information System (INIS)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

  1. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    International Nuclear Information System (INIS)

    Lee, Ching-Chih; Hung, Shih-Kai; Huang, Tze-Ta; Lee, Moon-Sing; Su, Yu-Chieh; Chou, Pesus; Hsiao, Shih-Hsuan; Chiou, Wen-Yen; Lin, Hon-Yi; Chien, Sou-Hsin

    2011-01-01

    Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001). Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate

  2. Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre-clinical study.

    Science.gov (United States)

    Abedinpour, Parisa; Baron, Véronique T; Chrastina, Adrian; Rondeau, Gaelle; Pelayo, Jennifer; Welsh, John; Borgström, Per

    2017-12-01

    Plumbagin is a candidate drug for the treatment of prostate cancer. Previous observations indicated that it may improve the efficacy of androgen deprivation therapy (ADT). This study evaluates the effectiveness of treatment with combinations of plumbagin and alternative strategies for ADT in mouse models of prostate cancer to support its clinical use. Plumbagin was administered per oral in a new sesame oil formulation. Standard toxicology studies were performed in rats. For tumor growth studies, mouse prostate cancer cell spheroids were placed on top of grafted prostate tissue in a dorsal chamber and allowed to form tumors. Mice were separated in various treatment groups and tumor size was measured over time by intra-vital microscopy. Survival studies were done in mice after injection of prostate cancer cells in the prostate of male animals. Androgen receptor (AR) levels were analyzed by Western blot from prostate cancer cells treated with plumbagin. Plumbagin caused a decrease in AR levels in vitro. In mice, plumbagin at 1 mg/kg in sesame oil displayed low toxicity and caused a 50% tumor regression when combined with castration. The combination of plumbagin with various forms of chemical ADT including treatment with a GnRH receptor agonist, a GnRH receptor antagonist, or CYP17A1 inhibitors, outperformed ADT alone, increasing mouse survival compared to the standard regimen of castration alone. In contrast, the combination of plumbagin with AR antagonists, such as bicalutamide and enzalutamide, showed no improvement over AR antagonists alone. Thus, plumbagin is effective in combination with drugs that prevent the synthesis of testosterone or its conversion to dihydrotestosterone, but not with drugs that bind to AR. Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice. © 2017 Wiley Periodicals, Inc.

  3. Pseudomonas aeruginosa Bacteremia among Immunocompetent and Immunocompromised Patients: Relation to Initial Antibiotic Therapy and Survival.

    Science.gov (United States)

    Migiyama, Yohei; Yanagihara, Katsunori; Kaku, Norihito; Harada, Yosuke; Yamada, Koichi; Nagaoka, Kentaro; Morinaga, Yoshitomo; Akamatsu, Norihiko; Matsuda, Junichi; Izumikawa, Koichi; Kohrogi, Hirotsugu; Kohno, Shigeru

    2016-01-01

    Pseudomonas aeruginosa bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of this study was to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki University Hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than in immunocompromised patients (7-day mortality, 8% vs. 30%, P antibiotic therapy (HR: 0.21, P immunocompromised, but not immunocompetent patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs. 66.7%, P < 0.01 by log-rank test).

  4. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

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    Michal Lotem

    2016-01-01

    Full Text Available Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p=0.0001 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2, MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p=0.007. Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.

  5. Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function

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    Pasque Michael K

    2007-01-01

    Full Text Available Abstract Objective Patients with severe left ventricular (LV dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF ≤25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+ in the post -operative period was compared to those without ICD (ICD-. Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5% patients received an ICD with a median of 2 (+/-2 years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT. There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.

  6. The Evaluation of More Lymph Nodes in Colon Cancer Is Associated with Improved Survival in Patients of All Ages.

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    Wouter B Aan de Stegge

    Full Text Available Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of ≥ 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer.In a population-based cohort study, all patients (N = 41,074 diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival.Over an eight years time period there was a 41.2% increase in patients with ≥ 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%. After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which ≥ 12 lymph nodes were removed compared to patients with 75: HR: 0.734 (95% CI, 0.700-0.771 and relative survival ( 75: RER: 0.621 (95% CI, 0.567-0.681 in all three age groups.The removal of ≥ 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification.

  7. Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax

    Science.gov (United States)

    Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S.

    2016-01-01

    The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. PMID:27431219

  8. Incorporating movement patterns to improve survival estimates for juvenile bull trout

    Science.gov (United States)

    Bowerman, Tracy; Budy, Phaedra

    2012-01-01

    Populations of many fish species are sensitive to changes in vital rates during early life stages, but our understanding of the factors affecting growth, survival, and movement patterns is often extremely limited for juvenile fish. These critical information gaps are particularly evident for bull trout Salvelinus confluentus, a threatened Pacific Northwest char. We combined several active and passive mark–recapture and resight techniques to assess migration rates and estimate survival for juvenile bull trout (70–170 mm total length). We evaluated the relative performance of multiple survival estimation techniques by comparing results from a common Cormack–Jolly–Seber (CJS) model, the less widely used Barker model, and a simple return rate (an index of survival). Juvenile bull trout of all sizes emigrated from their natal habitat throughout the year, and thereafter migrated up to 50 km downstream. With the CJS model, high emigration rates led to an extreme underestimate of apparent survival, a combined estimate of site fidelity and survival. In contrast, the Barker model, which allows survival and emigration to be modeled as separate parameters, produced estimates of survival that were much less biased than the return rate. Estimates of age-class-specific annual survival from the Barker model based on all available data were 0.218±0.028 (estimate±SE) for age-1 bull trout and 0.231±0.065 for age-2 bull trout. This research demonstrates the importance of incorporating movement patterns into survival analyses, and we provide one of the first field-based estimates of juvenile bull trout annual survival in relatively pristine rearing conditions. These estimates can provide a baseline for comparison with future studies in more impacted systems and will help managers develop reliable stage-structured population models to evaluate future recovery strategies.

  9. Improved Outcomes with Intensity Modulated Radiation Therapy Combined with Temozolomide for Newly Diagnosed Glioblastoma Multiforme

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    Noel J. Aherne

    2014-01-01

    Full Text Available Purpose. Glioblastoma multiforme (GBM is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months. We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  10. Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

    Science.gov (United States)

    Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

    2014-01-01

    Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  11. Survival Mediterranean Style: Lifestyle Changes to Improve the Health of the US Fire Service.

    Science.gov (United States)

    Korre, Maria; Sotos-Prieto, Mercedes; Kales, Stefanos N

    2017-01-01

    Cardiovascular disease (CVD) causes almost half of all on-duty deaths in US firefighters and is an important and costly cause of morbidity. In addition, cancer is a growing health concern in this population. Obesity and obesity-associated, cardiometabolic risk clustering are major, modifiable risk factors for fire service CVD and cancer risk. The Mediterranean diet (MedDiet) is proven effective in primary and secondary CVD prevention. It is also associated with a decreased risk of cancer and other chronic diseases. Moreover, it can be adapted into successful workplace interventions. Emerging data from our group regarding the US Fire Service show that greater compliance with the MedDiet is associated with improved CVD risk profiles and less weight gain among career firefighters. Moreover, the fact that career firefighters take a considerable number of meals communally on the job also represents an excellent opportunity for a workplace Mediterranean Diet Nutritional Intervention (MDNI). The devastating effects of obesity, CVD, and cancer on the US fire service are recognized, but currently few effective preventive programs exist. The consistently positive health benefits from following a MedDiet and promising preliminary data in the fire service justify translational research to determine the most effective means of delivering MDNIs to US firefighters. Therefore, a high priority should be assigned to efforts, which can help further disseminate and implement our program of novel behavior change strategies, "Survival Mediterranean Style," throughout the US fire service and eventually to other occupations.

  12. Survival Mediterranean Style: Lifestyle Changes to Improve the Health of the US Fire Service

    Directory of Open Access Journals (Sweden)

    Maria Korre

    2017-12-01

    Full Text Available Cardiovascular disease (CVD causes almost half of all on-duty deaths in US firefighters and is an important and costly cause of morbidity. In addition, cancer is a growing health concern in this population. Obesity and obesity-associated, cardiometabolic risk clustering are major, modifiable risk factors for fire service CVD and cancer risk. The Mediterranean diet (MedDiet is proven effective in primary and secondary CVD prevention. It is also associated with a decreased risk of cancer and other chronic diseases. Moreover, it can be adapted into successful workplace interventions. Emerging data from our group regarding the US Fire Service show that greater compliance with the MedDiet is associated with improved CVD risk profiles and less weight gain among career firefighters. Moreover, the fact that career firefighters take a considerable number of meals communally on the job also represents an excellent opportunity for a workplace Mediterranean Diet Nutritional Intervention (MDNI. The devastating effects of obesity, CVD, and cancer on the US fire service are recognized, but currently few effective preventive programs exist. The consistently positive health benefits from following a MedDiet and promising preliminary data in the fire service justify translational research to determine the most effective means of delivering MDNIs to US firefighters. Therefore, a high priority should be assigned to efforts, which can help further disseminate and implement our program of novel behavior change strategies, “Survival Mediterranean Style,” throughout the US fire service and eventually to other occupations.

  13. Survival prognostic factors for patients with synchronous brain oligometastatic non-small-cell lung carcinoma receiving local therapy

    Science.gov (United States)

    Bai, Hao; Xu, Jianlin; Yang, Haitang; Jin, Bo; Lou, Yuqing; Wu, Dan; Han, Baohui

    2016-01-01

    Introduction Clinical evidence for patients with synchronous brain oligometastatic non-small-cell lung carcinoma is limited. We aimed to summarize the clinical data of these patients to explore the survival prognostic factors for this population. Methods From September 1995 to July 2011, patients with 1–3 synchronous brain oligometastases, who were treated with stereotactic radiosurgery (SRS) or surgical resection as the primary treatment, were identified at Shanghai Chest Hospital. Results A total of 76 patients (22 patients underwent brain surgery as primary treatment and 54 patients received SRS) were available for survival analysis. The overall survival (OS) for patients treated with SRS and brain surgery as the primary treatment were 12.6 months (95% confidence interval [CI] 10.3–14.9) and 16.4 months (95% CI 8.8–24.1), respectively (adjusted hazard ratio =0.59, 95% CI 0.33–1.07, P=0.08). Among 76 patients treated with SRS or brain surgery, 21 patients who underwent primary tumor resection did not experience a significantly improved OS (16.4 months, 95% CI 9.6–23.2), compared with those who did not undergo resection (11.9 months, 95% CI 9.7–14.0; adjusted hazard ratio =0.81, 95% CI 0.46–1.44, P=0.46). Factors associated with survival benefits included stage I–II of primary lung tumor and solitary brain metastasis. Conclusion There was no significant difference in OS for patients with synchronous brain oligometastasis receiving SRS or surgical resection. Among this population, the number of brain metastases and stage of primary lung disease were the factors associated with a survival benefit. PMID:27471395

  14. Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model.

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    Zineb Belcaid

    Full Text Available Glioblastoma (GBM is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4 blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137 is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model.GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors.Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4+ and CD8+ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4+ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8+ T cells had no effect on the treatment response.Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in an orthotopic mouse

  15. Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

    Science.gov (United States)

    Pini, Maria; Rhodes, Davina H.; Castellanos, Karla J.; Cabay, Robert J.; Grady, Eileen F.; Fantuzzi, Giamila

    2012-01-01

    Obesity increases severity of acute pancreatitis (AP) by unclear mechanisms. We investigated the effect of the PPAR-gamma agonist rosiglitazone (RGZ, 0.01% in the diet) on severity of AP induced by administration of IL-12+ IL-18 in male C57BL6 mice fed a low fat (LFD) or high fat diet (HFD), under the hypothesis that RGZ would reduce disease severity in HFD-fed obese animals. In both LFD and HFD mice without AP, RGZ significantly increased body weight and % fat mass, with significant upregulation of adiponectin and suppression of erythropoiesis. In HFD mice with AP, RGZ significantly increased survival and hastened recovery from pancreatic inflammation, as evaluated by significantly improved pancreatic histology, reduced saponification of visceral adipose tissue and less severe suppression of erythropoiesis at Day 7 post-AP. This was associated with significantly lower circulating and pancreas-associated levels of IL-6, Galectin-3, osteopontin and TIMP-1 in HFD + RGZ mice, particularly at Day 7 post-AP. In LFD mice with AP, RGZ significantly worsened the degree of intrapancreatic acinar and fat necrosis as well as visceral fat saponification, without affecting other parameters of disease severity or inflammation. Induction of AP lead to major suppression of adiponectin levels at Day 7 in both HFD and HFD + RGZ mice. In conclusion, RGZ prevents development of severe AP in obese mice even though it significantly increases adiposity, indicating that obesity can be dissociated from AP severity by improving the metabolic and inflammatory milieu. However, RGZ worsens selective parameters of AP severity in LFD mice. PMID:22815875

  16. Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma.

    Science.gov (United States)

    Barone, Amy; Sengupta, Rajarshi; Warrington, Nicole M; Smith, Erin; Wen, Patrick Y; Brekken, Rolf A; Romagnoli, Barbara; Douglas, Garry; Chevalier, Eric; Bauer, Michael P; Dembowsky, Klaus; Piwnica-Worms, David; Rubin, Joshua B

    2014-10-30

    Glioblastoma recurrence involves the persistence of a subpopulation of cells with enhanced tumor-initiating capacity (TIC) that reside within the perivascular space, or niche (PVN). Anti-angiogenic therapies may prevent the formation of new PVN but have not prevented recurrence in clinical trials, suggesting they cannot abrogate TIC activity. We hypothesized that combining anti-angiogenic therapy with blockade of PVN function would have superior anti-tumor activity. We tested this hypothesis in an established intracranial xenograft model of GBM using a monoclonal antibody specific for murine and human VEGF (mcr84) and a Protein Epitope Mimetic (PEM) CXCR4 antagonist, POL5551. When doses of POL5551 were increased to overcome an mcr84-induced improvement in vascular barrier function, combinatorial therapy significantly inhibited intracranial tumor growth and improved survival. Anti-tumor activity was associated with significant changes in tumor cell proliferation and apoptosis, and a reduction in the numbers of perivascular cells expressing the TIC marker nestin. A direct effect on TICs was demonstrated for POL5551, but not mcr84, in three primary patient-derived GBM isolates. These findings indicate that targeting the structure and function of the PVN has superior anti-tumor effect and provide a strong rationale for clinical evaluation of POL5551 and Avastin in patients with GBM.

  17. Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Yang Haihua; Hu Wei; Wang Wei; Chen Peifang; Ding Weijun; Luo Wei

    2013-01-01

    Purpose: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Methods and Materials: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. Results: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). Conclusions: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

  18. Chronic obstructive pulmonary disease: getting it right. Does optimal management of chronic obstructive pulmonary disease alter disease progression and improve survival?

    Science.gov (United States)

    Russell, Richard E

    2014-03-01

    We live in a world where people live longer lives. The standardized mortality rate for many diseases is decreasing. Chronic obstructive pulmonary disease (COPD) is not following this trend. Over the last 10 years, interventions for COPD have been developed, but have any changed the prognosis or trajectory of this modern epidemic? We review the most recent and classical literature in order to answer this question. Recent analyses of data have clarified which interventions are effective in COPD and which are not. New studies have defined what is achievable with the current therapies. Only two interventions have been demonstrated to improve survival: smoking cessation and long-term oxygen therapy. Other treatments do reduce exacerbations, improve lung function and improve the patient's quality of life, but do not affect physiological disease progression or mortality. There is much work to do, not only to improve the treatments we have for this disease, but also to diagnose it early, intervene at the right time, reduce the treatment side-effects and most importantly understand the pathophysiology better. Moreover, we are duty bound to look at each patient and review what we are trying to achieve for each one through appropriate phenotyping as well as sometimes taking a more palliative approach.

  19. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

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    Marcos Perez-Basterrechea

    Full Text Available Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  20. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

    Science.gov (United States)

    Perez-Basterrechea, Marcos; Esteban, Manuel Martinez; Alvarez-Viejo, Maria; Fontanil, Tania; Cal, Santiago; Sanchez Pitiot, Marta; Otero, Jesus; Obaya, Alvaro Jesus

    2017-01-01

    Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  1. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

    Institute of Scientific and Technical Information of China (English)

    Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

    2004-01-01

    AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS <70 (P<0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

  2. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy.

    Science.gov (United States)

    Al-Zaidy, Samiah A; Sahenk, Zarife; Rodino-Klapac, Louise R; Kaspar, Brian; Mendell, Jerry R

    2015-09-02

    Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin.

  3. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  4. Narrative therapy for adults with major depressive disorder: improved symptom and interpersonal outcomes.

    Science.gov (United States)

    Vromans, Lynette P; Schweitzer, Robert D

    2011-01-01

    This study investigated depressive symptom and interpersonal relatedness outcomes from eight sessions of manualized narrative therapy for 47 adults with major depressive disorder. Post-therapy, depressive symptom improvement (d=1.36) and proportions of clients achieving reliable improvement (74%), movement to the functional population (61%), and clinically significant improvement (53%) were comparable to benchmark research outcomes. Post-therapy interpersonal relatedness improvement (d=.62) was less substantial than for symptoms. Three-month follow-up found maintenance of symptom, but not interpersonal gains. Benchmarking and clinical significance analyses mitigated repeated measure design limitations, providing empirical evidence to support narrative therapy for adults with major depressive disorder.

  5. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT)

    Energy Technology Data Exchange (ETDEWEB)

    Kong, G.; Thompson, M.; Johnston, V.; Eu, P. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); Collins, M.; Herschtal, A. [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne, VIC (Australia); Hofman, M.S.; Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Michael, M. [The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia)

    2014-10-15

    To review the response and outcomes of {sup 177}Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression. A total of 68 patients (39 men; 17 - 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression. Of those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 - 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival. A high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was

  6. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Zhang, Kai-Xin; Firus, Jessica; Prieur, Brenda; Jia, William; Rennie, Paul S.

    2011-01-01

    Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge

  7. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kai-Xin; Firus, Jessica; Prieur, Brenda [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Jia, William [Department of Surgery and Brain Research Centre, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Rennie, Paul S., E-mail: prennie@interchange.ubc.ca [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada)

    2011-03-24

    Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

  8. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    Directory of Open Access Journals (Sweden)

    Paul S. Rennie

    2011-03-01

    Full Text Available Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i the PI3K/Akt pathway, (ii receptor tyrosine kinases, (iii the p38 MAPK pathway, and (iv the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

  9. Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

    International Nuclear Information System (INIS)

    Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; Dam, Go van; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

    2014-01-01

    Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities

  10. Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival.

    Science.gov (United States)

    Löser, Anastassia; Schwarzenböck, Sarah M; Heuschkel, Martin; Willenberg, Holger S; Krause, Bernd J; Kurth, Jens

    2018-03-01

    Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is regarded as a safe treatment option with promising results for patients with neuroendocrine neoplasia (NEN). We aimed to study the absorbed organ and tumor doses, the renal and hematological toxicity as well as their mutual interaction. Another aim was the identification of adverse effects as possible predictors which may affect survival. A total of 30 (14 female and 16 male) patients with inoperable/metastatic NEN were treated with 7.4 GBq of Lu-DOTATATE. Occurrence of renal and hematological toxicity wasretrospectively studied. Morever, we examined the effects of hematological toxicity on survival after Lu-DOTATATE-PRRT. In 49 treatment cycles, the mean absorbed dose to the kidneys was 5.13±2.12, 4.49±2.49 Gy to the liver, and 14.44±8.97 Gy to the spleen, whereas tumor lesions absorbed a mean dose of 31.43±36.86 Gy. Comparing different localizations of metastases, no significant differences in absorbed dose were observed. Clinical response status revealed regressive disease in 47.6%, stable disease in 38.1%, and progressive disease in 14.3% of cases (n=21). Biochemically, 81.3% of patients showed reduced serotonin values (n=16; P<0.05) following Lu-DOTATATE-PRRT. No severe subacute renal or hematological toxicity occurred (one Common Terminology Criteria for Adverse Events-grade 3 for thrombocytopenia and another one for leukocytopenia). No statistically significant relation between baseline kidney function and post-therapeutic hematological changes was identified. The findings indicate that Lu-DOTATATE-PRRT is a safe and effective treatment method for patients with NEN. Moreover, these data strongly suggest that hematological parameters may affect survival so a further re-evaluation in prospective studies is warranted.

  11. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    Directory of Open Access Journals (Sweden)

    Chou Pesus

    2011-08-01

    Full Text Available Abstract Background Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Methods Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. Results As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p p = 0.001 after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p Conclusions Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.

  12. Positive end-expiratory pressure improves survival in a rodent model of cardiopulmonary resuscitation using high-dose epinephrine.

    LENUS (Irish Health Repository)

    McCaul, Conán

    2009-10-01

    Multiple interventions have been tested in models of cardiopulmonary resuscitation (CPR) to optimize drug use, chest compressions, and ventilation. None has studied the effects of positive end-expiratory pressure (PEEP) on outcome. We hypothesized that because PEEP can reverse pulmonary atelectasis, lower pulmonary vascular resistance, and potentially improve cardiac output, its use during CPR would increase survival.

  13. Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients.

    Science.gov (United States)

    Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

    2016-02-01

    The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors.Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann-Whitney U test and the Mantel-Cox log-rank sum test.A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P CRM status. Logistic regression analysis revealed that APR (P CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively).This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates.

  14. Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

    Science.gov (United States)

    Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-06-07

    Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

  15. Did professional attendance at home births improve early neonatal survival in Indonesia?

    Science.gov (United States)

    Hatt, Laurel; Stanton, Cynthia; Ronsmans, Carine; Makowiecka, Krystyna; Adisasmita, Asri

    2009-07-01

    BACKGROUND Early neonatal mortality has been persistently high in developing countries. Indonesia, with its national policy of home-based, midwife-assisted birth, is an apt context for assessing the effect of home-based professional birth attendance on early neonatal survival. METHODS We pooled four Indonesian Demographic and Health Surveys and used multivariate logistic regression to analyse trends in first-day and early neonatal mortality. We measured the effect of the context of delivery, including place and type of provider, and tested for changes in trend when the 'Midwife in the Village' programme was initiated. RESULTS Reported first-day mortality did not decrease significantly between 1986 and 2002, whereas early neonatal mortality decreased by an average of 3.2% annually. The rate of the decline did not change over the time period, either in 1989 when the Midwife in the Village programme was initiated, or in any year following when uptake of professional care increased. In simple and multivariate analyses, there were no significant differences in first-day or early neonatal death rates comparing home-based births with or without a professional midwife. Early neonatal mortality was higher in public facilities, likely due to selection. Biological determinants (twin births, male sex, short birth interval, previous early neonatal loss) were important for both outcomes. CONCLUSIONS Decreasing newborn death rates in Indonesia are encouraging, but it is not clear that these decreases are associated with greater uptake of professional delivery care at home or in health facilities. This may suggest a need for improved training in immediate newborn care, strengthened emergency referral, and continued support for family planning policies.

  16. Improving the survivability of Nb-encapsulated Ga targets for the production of 68Ge

    Science.gov (United States)

    Bach, H. T.; Claytor, T. N.; Hunter, J. F.; Olivas, E. R.; Kelsey, C. T., IV; Engle, J. W.; Connors, M. A.; Nortier, F. M.; Runde, W. H.; Moddrell, C.; Lenz, J. W.; John, K. D.

    2013-03-01

    At the Los Alamos Neutron Science Center (LANSCE) Isotope Production Facility (IPF), radioisotopes are produced for medical, scientific, and industrial applications by irradiating various targets with a 100 MeV, 230 μA proton beam. The medical isotope germanium-68 is produced by irradiating Nb capsules containing molten Ga target material. During irradiation, the Nb is subjected to intense radiation damage, corrosive attack by Ga, and mechanical and thermally-induced stresses for an extended period. Maintaining the structural integrity of the Nb target capsules during irradiation is crucial to contain the molten Ga target and the radioisotope product. In the present work, we focus on potential material related factors and assess the effect of the Nb stock material on target durability. We do so by comparing post-irradiation target mortality information to data collected during pre-irradiation ultrasound testing and X-ray imaging. We also explore possible failure mechanisms by using MCNP6 simulations and ANSYS codes to predict the induced atom displacement levels, hydrogen gas built-up, temperature distribution, and mechanical stresses. Our analysis, performed entirely in the context of an aggressive production program that allows for only limited diagnostic interference, suggests that using Nb stock with reasonably large and uniform grains is the most important factor in reducing early target failure at integrated beam current values <18 mAh and random failure at the face of the rear window at <60 mAh. We discuss possible failure mechanisms of failed targets that were fabricated using the same stock material and grain structure and then irradiated to integrated beam current values of up to 60 mAh and more. Based on these observations, we have enacted new specifications for Nb stock material quality, target design, and limits on integrated beam current. These changes have resulted in improved Nb capsule survivability.

  17. Colorectal cancers detected through screening are associated with lower stages and improved survival

    DEFF Research Database (Denmark)

    Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

    2014-01-01

    in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival. MATERIAL AND METHODS: All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences...... in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers...... detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...

  18. High procedure volume is strongly associated with improved survival after lung cancer surgery

    DEFF Research Database (Denmark)

    Lüchtenborg, Margreet; Riaz, Sharma P; Coupland, Victoria H

    2013-01-01

    Studies have reported an association between hospital volume and survival for non-small-cell lung cancer (NSCLC). We explored this association in England, accounting for case mix and propensity to resect....

  19. Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo.

    Science.gov (United States)

    Mangraviti, Antonella; Tzeng, Stephany Yi; Kozielski, Kristen Lynn; Wang, Yuan; Jin, Yike; Gullotti, David; Pedone, Mariangela; Buaron, Nitsa; Liu, Ann; Wilson, David R; Hansen, Sarah K; Rodriguez, Fausto J; Gao, Guo-Dong; DiMeco, Francesco; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Green, Jordan J

    2015-02-24

    Biodegradable polymeric nanoparticles have the potential to be safer alternatives to viruses for gene delivery; however, their use has been limited by poor efficacy in vivo. In this work, we synthesize and characterize polymeric gene delivery nanoparticles and evaluate their efficacy for DNA delivery of herpes simplex virus type I thymidine kinase (HSVtk) combined with the prodrug ganciclovir (GCV) in a malignant glioma model. We investigated polymer structure for gene delivery in two rat glioma cell lines, 9L and F98, to discover nanoparticle formulations more effective than the leading commercial reagent Lipofectamine 2000. The lead polymer structure, poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-modified with 1-(3-aminopropyl)-4-methylpiperazine, is a poly(β-amino ester) (PBAE) and formed nanoparticles with HSVtk DNA that were 138 ± 4 nm in size and 13 ± 1 mV in zeta potential. These nanoparticles containing HSVtk DNA showed 100% cancer cell killing in vitro in the two glioma cell lines when combined with GCV exposure, while control nanoparticles encoding GFP maintained robust cell viability. For in vivo evaluation, tumor-bearing rats were treated with PBAE/HSVtk infusion via convection-enhanced delivery (CED) in combination with systemic administration of GCV. These treated animals showed a significant benefit in survival (p = 0.0012 vs control). Moreover, following a single CED infusion, labeled PBAE nanoparticles spread completely throughout the tumor. This study highlights a nanomedicine approach that is highly promising for the treatment of malignant glioma.

  20. A prognostic scoring model for survival after locoregional therapy in de novo stage IV breast cancer.

    Science.gov (United States)

    Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ganti, Apar Kishor; Krishnamurthy, Jairam; Tandra, Pavan Kumar

    2018-05-02

    The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two "groups" [group 1 (0-7 points) and group 2 (7-17 points)]. Kaplan-Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p < 0.0001). The group 1 and group 2 in the training cohort showed a significant difference in the 3-year OS (p < 0.0001) (68 vs. 26%). On internal validation, comparable OS was seen between the respective groups in each cohort (p = 0.77). Our prognostic scoring system will help oncologists to predict the prognosis in de novo stage IV BC patients treated with LRT. Although firm treatment-related conclusions cannot be made due to the retrospective nature of the study, LRT appears to be associated with a better OS in specific subgroups.

  1. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    International Nuclear Information System (INIS)

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham; Kuk, Deborah; Zhang, Zhigang; Zelefsky, Michael J.

    2013-01-01

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy

  2. Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

    Science.gov (United States)

    Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

    2009-01-01

    renal transplantations, ATG-F induction therapy administered as a part of immunosuppressive therapy significantly improves patient survival and reduces the risk of graft failure and transplant rejections.

  3. Impact of biochemical failure on overall survival after radiation therapy for localized prostate cancer in the PSA era

    International Nuclear Information System (INIS)

    Kupelian, Patrick A.; Buchsbaum, Jeffrey C.; Patel, Chandrika; Elshaikh, Mohamed; Reddy, Chandana A.; Zippe, Craig; Klein, Eric A.

    2002-01-01

    Purpose: To study the impact of biochemical failure on overall survival rates during the first 10 years after definitive radiotherapy for localized prostate cancer. Methods and Materials: The analysis was performed on 936 cases treated at a single institution between 1986 and 1998 with definitive radiotherapy. The median age of treatment was 69 years (range: 46-86 years). Pretreatment PSA levels (iPSA) and biopsy Gleason scores (bGS) were available for all cases. The clinical stage was T1/T2A in 63%, T2B/C in 27%, and T3 in 10%. The median iPSA level was 9.6 ng/mL (range: 0.4-692.9 ng/mL). The iPSA was ≤10 in 53% and >10 in 47%. The bGS was ≤6 in 59% and ≥7 in 41%. Androgen deprivation (AD) was administered in 181 cases (19%) for a median duration of 6 months (range: 1-6 months). All 181 cases received AD neoadjuvantly, i.e., before and/or during the radiotherapy. No AD was delivered after the completion of radiation. The median radiation dose was 70 Gy (range: 60-78 Gy). The radiotherapy technique was conformal in 376 (40%) cases. The American Society of Therapeutic Radiology and Oncology definition of biochemical failure (bF) was used; 316 cases (34%) had failed biochemically, and 620 (66%) had not. The end point was overall survival (OS). Time to death was determined from the time of definitive radiotherapy. The median PSA follow-up was 58 months. The median follow-up times for bF vs. no-bF cases were 77 and 49 months, respectively. A multivariate analysis of factors affecting OS using the proportional hazards model was performed for all cases using the following variables: age (>65 vs. ≤65 years), race (African-American vs. Caucasian), clinical T stage (T1-2A vs. T2B-C vs. T3), bGS (≤6 vs. 7 vs. ≥8), iPSA (continuous variable), use of AD (yes vs. no), year of therapy (continuous variable), radiation dose (continuous variable), radiation technique (conformal vs. standard), and biochemical failure (yes vs. no). Results: The 5-year OS rate for the

  4. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken; Carstensen, Bendix

    2014-01-01

    OBJECTIVE: To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors ha...

  5. Early or Up-Front Radiotherapy Improved Survival of Localized Extranodal NK/T-Cell Lymphoma, Nasal-Type in the Upper Aerodigestive Tract

    International Nuclear Information System (INIS)

    Huang Meijuan; Jiang Yu; Liu Weiping; Li Zhiping; Li Mei; Zhou Lin; Xu Yong; Yu Chunhua; Li Qiu; Peng Feng; Liu Jiyan; Luo Feng; Lu You

    2008-01-01

    Purpose: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. Methods and Materials: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. Results: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving ≥54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). Conclusion: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease

  6. Role of ventricular assist therapy for patients with heart failure and restrictive physiology: Improving outcomes for a lethal disease.

    Science.gov (United States)

    Grupper, Avishay; Park, Soon J; Pereira, Naveen L; Schettle, Sarah D; Gerber, Yariv; Topilsky, Yan; Edwards, Brooks S; Daly, Richard C; Stulak, John M; Joyce, Lyle D; Kushwaha, Sudhir S

    2015-08-01

    Restrictive cardiomyopathy (RCM) patients have poor prognosis due to progressive heart failure characterized by impaired ventricular filling of either or both ventricles. The goal of this study was to evaluate the outcome of end-stage RCM patients after left ventricular assist device (LVAD) implantation and to determine factors that may be associated with improved survival. This investigation is a retrospective study of prospectively collected data that include 28 consecutive patients with end-stage RCM who received continuous-flow LVADs at the Mayo Clinic, Rochester, Minnesota. Outcome was assessed by survival with LVAD support until heart transplantation or all-cause mortality. The mean follow-up time post-LVAD implantation was 448 ± 425 days. The mean hospitalization time was 29 ± 19 days and was complicated mainly by post-operative right ventricular (RV) failure requiring short-term medical support. The short-term in-hospital mortality was 14%. Ten patients underwent heart transplantation with 100% survival post-transplant during the follow-up period. One-year survival for patients with LVADs without transplantation was 64%, and was not significantly different between amyloidosis and non-amyloidosis patients. Larger left ventricle (LV) end-diastolic and end-systolic dimensions were significantly associated with improved survival rates (RR = 0.94 and 0.95, p < 0.05, respectively), and left ventricular end-diastolic diameter (LVEDD) ≤46 mm was associated with increased mortality post-LVAD implantation. LVAD is a feasible, life-saving therapy for end-stage heart failure related to RCM, especially as a bridge to transplant and in patients with larger LV dimensions. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Wei [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nezolosky, Michelle [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Beard, Clair J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Den, Robert B. [Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States)

    2016-03-15

    Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95-0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test P=.0005; AHR: 0.91, 95% CI: 0.86-0.96, P=.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate

  8. Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

    2016-03-15

    Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

  9. Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

    International Nuclear Information System (INIS)

    Ruella, Marco; Filippi, Andrea Riccardo; Bruna, Riccardo; Di Russo, Anna; Magni, Michele; Caracciolo, Daniele; Passera, Roberto; Matteucci, Paola; Di Nicola, Massimo; Corradini, Paolo; Parvis, Guido; Gini, Guido; Olivieri, Attilio; Ladetto, Marco; Ricardi, Umberto; Tarella, Corrado; Devizzi, Liliana

    2016-01-01

    Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m"2, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

  10. Survival prognostic factors for patients with synchronous brain oligometastatic non-small-cell lung carcinoma receiving local therapy

    Directory of Open Access Journals (Sweden)

    Bai H

    2016-07-01

    Full Text Available Hao Bai,1,* Jianlin Xu,1,* Haitang Yang,2,* Bo Jin,1 Yuqing Lou,1 Dan Wu,3 Baohui Han1 1Department of Pulmonary, 2Department of Pathology, 3Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Introduction: Clinical evidence for patients with synchronous brain oligometastatic non-small-cell lung carcinoma is limited. We aimed to summarize the clinical data of these patients to explore the survival prognostic factors for this population. Methods: From September 1995 to July 2011, patients with 1–3 synchronous brain oligometastases, who were treated with stereotactic radiosurgery (SRS or surgical resection as the primary treatment, were identified at Shanghai Chest Hospital.Results: A total of 76 patients (22 patients underwent brain surgery as primary treatment and 54 patients received SRS were available for survival analysis. The overall survival (OS for patients treated with SRS and brain surgery as the primary treatment were 12.6 months (95% confidence interval [CI] 10.3–14.9 and 16.4 months (95% CI 8.8–24.1, respectively (adjusted hazard ratio =0.59, 95% CI 0.33–1.07, P=0.08. Among 76 patients treated with SRS or brain surgery, 21 patients who underwent primary tumor resection did not experience a significantly improved OS (16.4 months, 95% CI 9.6–23.2, compared with those who did not undergo resection (11.9 months, 95% CI 9.7–14.0; adjusted hazard ratio =0.81, 95% CI 0.46–1.44, P=0.46. Factors associated with survival benefits included stage I–II of primary lung tumor and solitary brain metastasis. Conclusion: There was no significant difference in OS for patients with synchronous brain oligometastasis receiving SRS or surgical resection. Among this population, the number of brain metastases and stage of primary lung disease were the factors associated with a survival benefit. Keywords: non-small-cell lung carcinoma

  11. The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression.

    Directory of Open Access Journals (Sweden)

    Li Bie

    Full Text Available Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001, and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67 labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time.

  12. Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study.

    Science.gov (United States)

    Elshaikh, Mohamed A; Ruterbusch, Julie; Cote, Michele L; Cattaneo, Richard; Munkarah, Adnan R

    2013-11-01

    To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC). Data were obtained from the SEER registry between 1988-2009. Inclusion criteria included women who underwent hysterectomy for stage I-II EC. Patients were divided into two birth cohorts: BB (women born between 1946 and 1964) and pre-boomers (PB) (born between 1926 and 1945). A total of 30,956 patients were analyzed. Considering that women in the PB group were older than those of the BB generation, the statistical analysis was limited to women 50-59 years of age at the time of diagnosis (n=11,473). Baby boomers had a significantly higher percentage of endometrioid histology (pgeneration compared to the PB generation (p=0.0003) with a trend for improved uterine cancer-specific survival (p=0.0752). On multivariate analysis, birth cohort (BB vs. PB) was not a significant predictor of survival end-points. Factors predictive of survival included: tumor grade, FIGO stage, African-American race, and increased number of dissected LN. Our study suggests that the survival of BB women between 50-60 years of age is better compared to women in the PB generation. As more BB patients are diagnosed with EC, further research is warranted.

  13. Improving the quality of survival for infants of birthweight Victorian Infant Collaborative Study Group.

    Science.gov (United States)

    1993-01-04

    To compare between eras the early care of extremely low birthweight (birthweight eras, 1979-1980 and 1985-1987. PATIENTS AND OUTCOMES: Mortality data to two years of age were available for all infants liveborn in non-level-III centres in the two eras (1979-1980, n = 106; 1985-1987, n = 129). In 1979-1980, 47 of 52 infants transferred to a level-III centre were transported by the Newborn Emergency Transport Service (NETS); in 1985-1987, all 49 infants transferred were transported by NETS. Data concerning the immediate care after birth and during transport to a level-III centre were available for all infants transferred by NETS. All survivors were assessed for sensorineural impairments and disabilities at two years of age, corrected for prematurity. In both eras, 18 children born outside and transferred to a level-III centre survived to two years of age. Survivors in both eras had almost identical mean birthweights and gestational ages. There were trends for more survivors to be referred by paediatricians--1979-1980, 61%; 1985-1987, 83%; odds ratio (OR), 2.94; 95% confidence interval (CI), 0.7-12.4--and for quicker referral times to NETS in 1985-1987 (1979-1980, median 34.5 minutes after birth; 1985-1987, median 21.5 minutes after birth; z = 1.91, P = 0.056). It was possible only during 1985-1987 to monitor transcutaneous PO2 during transport. Durations of transport were similar in both eras. However, only in 1985-1987 was it possible in survivors to reduce significantly the inspired oxygen concentration during transport (median reductions in inspired oxygen, 1979-1980 3.5%; 1985-1987 20%; P = 0.028). Neurological impairment rates were substantially lower in survivors transported in the latter era (1979-1980 72% impaired; 1985-1987 22% impaired; OR 0.14, 95% CI 0.04-0.52). Of the neurological impairments, fewer had severe developmental delay alone (1979-1980 22%; 1985-1987 0%; OR 0.09, 95% CI 0.018-0.46), and the rate of blindness was lower, but the latter difference

  14. Effectiveness of Cognitive-Behavioral Therapy in the Improvement of Coping Strategies and Addiction Symptoms in Drug-Dependent Patients

    Directory of Open Access Journals (Sweden)

    H BrockieMilan

    2014-12-01

    Full Text Available Objective: This study was carried out to determine the effectiveness of cognitive-behavioral therapy in improving coping strategies and symptoms of drug addiction patients. Method: In a quasi-experimental study, the number of 90drug-dependent patients referring to clinics to stop taking drugs existing in the city of Urmia were divided into two experimental (n=45 groups and control (n=45 using random sampling. The experimental group received 12 sessions of cognitive-behavioral treatment in Carroll style while the control group received only methadone and the physical pills. All the participants completed coping strategies questionnaire at the beginning, during (after three months, and three months after treatment (follow-up. As well, they were assessed for the rate of improvement in symptoms of addiction and process of addiction treatment using by Madzly’s addiction profile questionnaire. Findings: The results proved the effectiveness of cognitive-behavioral therapy and its survival. Conclusion: Cognitive behavioral therapy is very influential in the boost of coping strategies and the improvement of mental and physical health in drug-dependent patients.

  15. The Circadian Schedule for Childhood Acute Lymphoblastic Leukemia Maintenance Therapy does not Influence Event-Free Survival in the NOPHO ALL92 Protocol

    DEFF Research Database (Denmark)

    Clemmensen, Kim K. B.; Christensen, Regitse H.; Shabaneh, Diana N.

    2014-01-01

    BACKGROUND: The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning. PROCEDURE: In the ALL92 MT study we prospec...

  16. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dikken, Johan L. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Coit, Daniel G. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Baser, Raymond E.; Gönen, Mithat [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brennan, Murray F. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jansen, Edwin P.M. [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Boot, Henk [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Velde, Cornelis J.H. van de [Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Cats, Annemieke [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Verheij, Marcel, E-mail: m.verheij@nki.nl [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2014-03-01

    Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

  17. Survival Analysis of F98 Glioma Rat Cells Following Minibeam or Broad-Beam Synchrotron Radiation Therapy

    International Nuclear Information System (INIS)

    Gil, Silvia; Sarun, Sukhéna; Biete, Albert; Prezado, Yolanda; Sabés, Manel

    2011-01-01

    In the quest of a curative radiotherapy treatment for gliomas new delivery modes are being explored. At the Biomedical Beamline of the European Synchrotron Radiation Facility (ESRF), a new spatially-fractionated technique, called Minibeam Radiation Therapy (MBRT) is under development. The aim of this work is to compare the effectiveness of MBRT and broad-beam (BB) synchrotron radiation to treat F98 glioma rat cells. A dose escalation study was performed in order to delimit the range of doses where a therapeutic effect could be expected. These results will help in the design and optimization of the forthcoming in vivo studies at the ESRF. Two hundred thousand F98 cells were seeded per well in 24-well plates, and incubated for 48 hours before being irradiated with spatially fractionated and seamless synchrotron x-rays at several doses. The percentage of each cell population (alive, early apoptotic and dead cells, where either late apoptotic as necrotic cells are included) was assessed by flow cytometry 48 hours after irradiation, whereas the metabolic activity of surviving cells was analyzed on days 3, 4, and 9 post-irradiation by using QBlue test. The endpoint (or threshold dose from which an important enhancement in the effectiveness of both radiation treatments is achieved) obtained by flow cytometry could be established just before 12 Gy in the two irradiation schemes, whilst the endpoints assessed by the QBlue reagent, taking into account the cell recovery, were set around 18 Gy in both cases. In addition, flow cytometric analysis pointed at a larger effectiveness for minibeams, due to the higher proportion of early apoptotic cells. When the valley doses in MBRT equal the dose deposited in the BB scheme, similar cell survival ratio and cell recovery were observed. However, a significant increase in the number of early apoptotic cells were found 48 hours after the minibeam radiation in comparison with the seamless mode

  18. High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

    Science.gov (United States)

    Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

    2015-01-01

    Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence

  19. Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

    Directory of Open Access Journals (Sweden)

    Rui Guo

    Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

  20. Brazilian popular healers as effective promoters of oral rehydration therapy (ORT) and related child survival strategies.

    Science.gov (United States)

    Nations, M K; de Sousa, M A; Correia, L L; da Silva, D M

    1988-01-01

    In Ceara State in northeastern Brazil in 1986 infant mortality reached 110-139 per 1000 live births, and 50% of those deaths were due to diarrhea and dehydration. Diarrheal deaths can be prevented by oral rehydration therapy (ORT), which replaces lost fluids and electrolytes with oral rehydration salts (ORS) and water. ORT was known in the 1830s, but only in the 1960s was the importance of sugar, which increases the body's ability to absorb fluid some 25 times, realized. In northeastern Brazil access to ORT has been severely limited by poverty, official incompetence, and bureaucratic restrictions. In 1984 a 2-year research project was initiated in the village of Pacatuba to test the theory that mobilizing and training popular healers in ORT would 1) increase awareness and use of ORS, 2) promote continued feeding during diarrhea, 3) increase breast feeding, and 4) reduce the use of costly and nonindicated drugs. 46 popular healers, including rezadeiras and oradores (prayers), Umbandistas (priests), espiritas (mediums), an herbalist, and a lay doctor, were recruited and trained. Most of these people practiced a mixture of folk medicine and religion and were highly respected in the community. For purposes of survey, Pacatuba was divided into 3 groups, each containing houses at 4 different income levels. The mothers in 204 Group 1 homes were interviewed concerning ORT and diarrhea-related knowledge before intervention, and 226 households in Group 2 were interviewed after intervention. The healers were taught the basic biomedical concept of rehydration and how to mix the ORS -- 7 bottle cap-fulls of sugar and 1 of salt in a liter of unsweetened traditional tea. The healers were also taught how to use the World Health Organization's (WHO) ORS packets (2% glucose, 90 mmol/1 of sodium chloride, 1.5 gm potassium chloride, and 2.9 gm sodium bicarbonate) for cases of moderate to severe dehydration. In addition, the healers were taught the 5 basic health messages: give ORS

  1. Increased Lymph Node Yield Is Associated with Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment

    DEFF Research Database (Denmark)

    Lykke, Jakob; Jess, Per; Roikjaer, Ole

    2015-01-01

    patients in Denmark who were diagnosed with International Union Against Cancer stage I to III adenocarcinoma of the rectum and so treated in the period from 2003 to 2011 were included in the analysis. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: The observed percentages...

  2. Vaccinia scars associated with improved survival among adults in rural Guinea-Bissau.

    Directory of Open Access Journals (Sweden)

    Mette Lundsby Jensen

    Full Text Available BACKGROUND: In urban Guinea-Bissau, adults with a vaccinia scar had better survival but also a higher prevalence of HIV-2 infection. We therefore investigated the association between vaccinia scar and survival and HIV infection in a rural area of Guinea-Bissau. METHODOLOGY/PRINCIPAL FINDINGS: In connection with a study of HIV in rural Guinea-Bissau, we assessed vaccinia and BCG scars in 193 HIV-1 or HIV-2 infected and 174 uninfected participants. Mortality was assessed after 2(1/2-3 years of follow-up. The analyses were adjusted for age, sex, village, and HIV status. The prevalence of vaccinia scar was associated with age, village, and HIV-2 status but not with sex and schooling. Compared with individuals without any scar, individuals with a vaccinia scar had better survival (mortality rate ratio (MR = 0.22 (95% CI 0.08-0.61, the MR being 0.19 (95% CI 0.06-0.57 for women and 0.40 (95% CI 0.04-3.74 for men. Estimates were similar for HIV-2 infected and HIV-1 and HIV-2 uninfected individuals. The HIV-2 prevalence was higher among individuals with a vaccinia scar compared to individuals without a vaccinia scar (RR = 1.57 (95% CI 1.02-2.36. CONCLUSION: The present study supports the hypothesis that vaccinia vaccination may have a non-specific beneficial effect on adult survival.

  3. Special LOFT features for improved monitoring and survival of LOCA transients

    International Nuclear Information System (INIS)

    Goodrich, L.D.; Leach, L.P.; Klingler, T.B.; Morrow, J.C.; Phoenix, W.C.; Satterwhite, D.G.; Sumpter, K.C.; Rouhani, S.Z.; Welland, H.J.

    1980-01-01

    LOFT is designed to monitor and survive Loss-Of-Coolant-Accidents (LOCAs). This report presents the primary design difference from LPWRs that were required to accomplish this. These design differences may be of interest to the nuclear power generator industry. This report should be revised semi-annually or as developments in the LOFT Program require

  4. Considerations to improve the safety of cervical spine manual therapy.

    Science.gov (United States)

    Hutting, Nathan; Kerry, Roger; Coppieters, Michel W; Scholten-Peeters, Gwendolijne G M

    2018-02-01

    Manipulation and mobilisation of the cervical spine are well established interventions in the management of patients with headache and/or neck pain. However, their benefits are accompanied by potential, yet rare risks in terms of serious adverse events, including neurovascular insult to the brain. A recent international framework for risk assessment and management offers directions in the mitigation of this risk by facilitating sound clinical reasoning. The aim of this article is to critically reflect on and summarize the current knowledge about cervical spine manual therapy and to provide guidance for clinical reasoning for cervical spine manual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens.

    Science.gov (United States)

    Landsburg, Daniel J; Stadtmauer, Edward; Loren, Alison; Goldstein, Steven; Frey, Noelle; Nasta, Sunita D; Porter, David L; Tsai, Donald E; Perl, Alexander E; Hexner, Elizabeth O; Luger, Selina

    2013-08-01

    While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long-term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP- or hyperCVAD-based chemotherapy regimens from 2003-2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically-significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease-related characteristics including high-risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment-related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment-related toxicity experienced by these patients. Copyright © 2013 Wiley Periodicals, Inc.

  6. Deferasirox and vitamin D improves overall survival in elderly patients with acute myeloid leukemia after demethylating agents failure.

    Directory of Open Access Journals (Sweden)

    Etienne Paubelle

    Full Text Available The prognosis of acute myeloid leukemia (AML in elderly (≥65 years patients is poor and treatment remains non-consensual especially for those who are not eligible for intensive therapies. Our group has shown that in vitro the iron chelator deferasirox (DFX synergizes with vitamin D (VD to promote monocyte differentiation in primary AML cells. Herein, we present results from a retrospective case-control study in which the association of DFX (1-2 g/d and 25-hydroxycholecalciferol (100,000 IU/week (DFX/VD was proposed to patients following demethylating agents failure. Median survival of patients treated with DFX/VD combination (n = 17 was significantly increased in comparison with matched patients receiving best supportive care (BSC alone (n = 13 (10.4 versus 4 months respectively. In addition, the only factor associated to an increased overall survival in DFX/VD-treated patients was serum VD levels. We conclude that DFX/VD treatment correlated with increased overall survival of AML patients in this retrospective cohort of elderly patients.

  7. Factors associated with improved survival among older colorectal cancer patients in the US: a population-based analysis

    Directory of Open Access Journals (Sweden)

    Earle Craig C

    2009-07-01

    Full Text Available Abstract Background The purpose of this study was to estimate the relative impact of changes in demographics, stage at detection, treatment mix, and medical technology on 5-year survival among older colorectal cancer (CRC patients. Methods We selected older patients diagnosed with CRC between 1992 and 2000 from the SEER-Medicare database and followed them through 2005. Trends in demographic characteristics, stage at detection and initial treatment mix were evaluated descriptively. Separate multivariate logistic regression models for colon (CC and rectal cancer (RC patients were estimated to isolate the independent effects of these factors along with technological change (proxied by cohort year on 5-year survival. Results Our sample included 37,808 CC and 13,619 RC patients (combined mean ± SD age: 77.2 ± 7.0 years; 55% female; 87% white. In recent years, more CC patients were diagnosed at Stage I and fewer at Stages II and IV, and more RC patients were diagnosed at Stage I and fewer at Stages II and III. CC and RC patients diagnosed in later years were slightly older with somewhat better Charlson scores and were more likely to be female, from the Northeast, and from areas with higher average education levels. Surgery alone was more common in later years for CC patients while combined surgery, chemotherapy, and radiotherapy was more common for RC patients. Between 1992 and 2000, 5-year observed survival improved from 43.0% to 46.3% for CC patients and from 39.4% to 42.2% for RC patients. Multivariate logistic regressions indicate that patients diagnosed in 2000 had significantly greater odds of 5-year survival than those diagnosed in 1992 (OR: 1.35 for CC, 1.38 for RC. Our decomposition suggests that early detection had little impact on survival; rather, technological improvements (e.g., new medical technologies or more effective use of existing technologies and changing demographics were responsible for the largest share of the change in 5

  8. Do implantable cardioverter defibrillators improve survival in patients with severe left ventricular systolic dysfunction after coronary artery bypass graft surgery?

    Science.gov (United States)

    Fazal, Iftikhar A; Bates, Matthew G D; Matthews, Iain G; Turley, Andrew J

    2011-06-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether implantable cardioverter defibrillators (ICD) improve survival in patients with severe left ventricular systolic dysfunction (LVSD) after coronary artery bypass graft (CABG) surgery. ICDs are designed to terminate potentially fatal cardiac tachyarrhythmias. A right ventricular lead is mandatory for detection, pacing and defibrillation capabilities. Dual chamber ICDs have an additional right atrial lead and are used for patients with conventional atrioventricular pacing indications. More sophisticated, biventricular devices exist to provide cardiac resynchronisation therapy (CRT) in addition to defibrillation (CRT-D). ICDs have been extensively investigated in patients with LVSD post myocardial infarction and in patients with non-ischaemic cardiomyopathy for both secondary prevention (history of ventricular arrhythmias) and primary prevention (deemed high risk for ventricular arrhythmias). This best evidence topic aims to review the evidence and its applicability to patients post CABG. Nine hundred and sixteen papers were identified using the search method outlined. Eight randomised controlled trials, two meta-analyses, and one non-randomised trial, in addition to international guidelines presented the best evidence to answer the clinical question. The current evidence base and guidelines suggest that ICDs should be considered for all patients with LVSD [ejection fraction (EF) ≤30-40%] receiving optimal pharmacological management, who are ≥40 days post MI [four weeks for National Institute for Health and Clinical Excellence (NICE)] and in New York Heart Association (NYHA) class I-III. UK NICE guidelines require in addition; non-sustained ventricular tachycardia (NSVT) on a Holter monitor and inducible ventricular tachycardia at electrophysiological study for EF between 30 and 35%; or a QRS >120 ms if EF <30%. The North American guidelines

  9. Can low-intensity extracorporeal shockwave therapy improve erectile dysfunction?

    DEFF Research Database (Denmark)

    Olsen, Anne B; Persiani, Marie; Boie, Sidsel

    2015-01-01

    OBJECTIVE: The aim of this study was to investigate whether low-intensity extracorporeal shockwave therapy (LI-ESWT) can be used as a treatment for men with erectile dysfunction of organic origin. MATERIALS AND METHODS: This prospective, randomized, blinded, placebo-controlled study included 112 ...... are needed. KEYWORDS: Erectile dysfunction; extracorporeal shockwave; penis...

  10. Improvement of disfiguring skin conditions by laser therapy

    NARCIS (Netherlands)

    van Drooge, A.M.

    2014-01-01

    Since their introduction in dermatology, lasers became a welcome addition to the therapeutic armentarium for disfiguring skin conditions. In this thesis, we evaluated laser therapy for the treatment of scars, of benign dermal tumours, and of port-wine stains. For scars, many different laser devices

  11. Poly-β-hydroxybutyrate (PHB) accumulating Bacillus spp. improve the survival, growth and robustness of Penaeus monodon (Fabricius, 1798) postlarvae.

    Science.gov (United States)

    Laranja, Joseph Leopoldo Q; Ludevese-Pascual, Gladys L; Amar, Edgar C; Sorgeloos, Patrick; Bossier, Peter; De Schryver, Peter

    2014-10-10

    Low larval survival resulting from suboptimal culture conditions and luminous vibriosis poses a major problem for the larviculture of penaeid shrimp. In this study, a poly-β-hydroxybutyrate (PHB) accumulating mixed bacterial culture (mBC; 48.5% PHB on cell dry weight) and two PHB accumulating bacterial isolates, Bacillus sp. JL47 (54.7% PHB on cell dry weight) and Bacillus sp. JL1 (45.5% PHB on cell dry weight), were obtained from a Philippine shrimp culture pond and investigated for their capacity to improve growth, survival and robustness of Penaeus monodon postlarvae (PL). Shrimp PL1 and shrimp PL30 were provided with the PHB containing bacterial cultures in the feed for 30 days followed by, respectively, a challenge with pathogenic Vibrio campbellii and exposure to a lethal dose of ammonia. Prior to the pathogenic challenge or ammonia stress, growth and survival were higher for shrimp receiving the PHB accumulating bacteria as compared to shrimp receiving diets without bacterial additions. After exposure to the pathogenic challenge the shrimp fed PHB accumulating bacteria showed a higher survival as compared to non-treated shrimp, suggesting an increase in robustness for the shrimp. Similar effects were observed when shrimp PL30 were provided with the PHB accumulating bacterial cultures during a challenge with pathogenic V. campbellii through the water. The survival of shrimp exposed to lethal ammonia stress showed no significant difference between PHB accumulating bacteria-fed shrimp and non-PHB treated shrimp. The data illustrate that bacilli capable of accumulating PHB can provide beneficial effects to P. monodon post-larvae during culture in terms of growth performance, survival and resistance against pathogenic infection and ammonia stress. Further investigations are required to verify the PHB effect of the bacterial cultures on the shrimp. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Survival outcomes after radiation therapy for stage III non-small-cell lung cancer after adoption of computed tomography-based simulation.

    Science.gov (United States)

    Chen, Aileen B; Neville, Bridget A; Sher, David J; Chen, Kun; Schrag, Deborah

    2011-06-10

    Technical studies suggest that computed tomography (CT) -based simulation improves the therapeutic ratio for thoracic radiation therapy (TRT), although few studies have evaluated its use or impact on outcomes. We used the Surveillance, Epidemiology and End Results (SEER) -Medicare linked data to identify CT-based simulation for TRT among Medicare beneficiaries diagnosed with stage III non-small-cell lung cancer (NSCLC) between 2000 and 2005. Demographic and clinical factors associated with use of CT simulation were identified, and the impact of CT simulation on survival was analyzed by using Cox models and propensity score analysis. The proportion of patients treated with TRT who had CT simulation increased from 2.4% in 1994 to 34.0% in 2000 to 77.6% in 2005. Of the 5,540 patients treated with TRT from 2000 to 2005, 60.1% had CT simulation. Geographic variation was seen in rates of CT simulation, with lower rates in rural areas and in the South and West compared with those in the Northeast and Midwest. Patients treated with chemotherapy were more likely to have CT simulation (65.2% v 51.2%; adjusted odds ratio, 1.67; 95% CI, 1.48 to 1.88; P simulation. Controlling for demographic and clinical characteristics, CT simulation was associated with lower risk of death (adjusted hazard ratio, 0.77; 95% CI, 0.73 to 0.82; P simulation. CT-based simulation has been widely, although not uniformly, adopted for the treatment of stage III NSCLC and is associated with higher survival among patients receiving TRT.

  13. Sodium nitroprusside enhanced cardiopulmonary resuscitation improves short term survival in a porcine model of ischemic refractory ventricular fibrillation.

    Science.gov (United States)

    Yannopoulos, Demetris; Bartos, Jason A; George, Stephen A; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P

    2017-01-01

    Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. UK Renal Registry 15th annual report: Chapter 5 survival and causes of death of UK adult patients on renal replacement therapy in 2011: national and centre-specific analyses.

    Science.gov (United States)

    Steenkamp, Retha; Shaw, Catriona; Feest, Terry

    2013-01-01

    These analyses examine a) survival from the start of