Music Therapy and Music Therapy Research. Response

DEFF Research Database (Denmark)

Pedersen, Inge Nygaard

2002-01-01

This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

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Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

2014-08-01

Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Posttreatment assessment of response using FDG-PET/CT for patients treated with definitive radiation therapy for head and neck cancers

International Nuclear Information System (INIS)

Andrade, Regiane S.; Heron, Dwight E.; Degirmenci, Berna; Filho, Pedro A.A.; Branstetter, Barton F.; Seethala, Raja R.; Ferris, Robert L.; Avril, Norbert

2006-01-01

Purpose: The goal of this study was to evaluate coregistered [ 18 F] fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) for the detection of persistent disease after definitive radiation therapy in head and neck cancer. Methods and Materials: Posttreatment FDG-PET/CT was performed in 28 patients on average 8 weeks (range, 4 to 15.7 weeks) after completing definitive radiation therapy. FDG-PET/CT was visually analyzed for the entire patient group and at two time points (4-8 and >8 weeks) after treatment. The contrast-enhanced CT portion of PET/CT was separately analyzed blinded to the results of coregistered FDG-PET/CT and classified as negative or positive for residual locoregional disease. Pathologic findings and clinical follow-up served as the reference standard. Results: Follow-up data were available for all 28 patients (median, 17.6 months). Regarding the detection of residual disease, the overall sensitivity and specificity of FDG-PET/CT was 76.9% and 93.3%, respectively, compared with 92.3% and 46.7% for contrast-enhanced CT. The accuracy of FDG-PET/CT was 85.7%, compared with 67.9% for CT alone. All false-negative (n = 3) and false-positive (n = 1) FDG-PET/CT results occurred between 4 and 8 weeks after treatment. At 8 weeks or later after treatment, the specificity of CT was 28%, compared with 100% for FDG-PET/CT. Conclusions: The metabolic-anatomic information from coregistered FDG-PET/CT provided the most accurate assessment for treatment response when performed later than 8 weeks after the conclusion of radiation therapy. FDG-PET/CT excelled by a higher specificity and overall diagnostic performance than CT imaging alone. These results support a potential clinical role of FDG-PET/CT in the early assessment of therapy response after definitive radiation therapy

Patient predictors of response to cognitive behaviour therapy and schema therapy for depression.

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Carter, Janet D; McIntosh, Virginia Vw; Jordan, Jennifer; Porter, Richard J; Douglas, Katie; Frampton, Christopher M; Joyce, Peter R

2018-01-01

Few studies have examined differential predictors of response to psychotherapy for depression. Greater understanding about the factors associated with therapeutic response may better enable therapists to optimise response by targeting therapy for the individual. The aim of the current exploratory study was to examine patient characteristics associated with response to cognitive behaviour therapy and schema therapy for depression. Participants were 100 outpatients in a clinical trial randomised to either cognitive behaviour therapy or schema therapy. Potential predictors of response examined included demographic, clinical, functioning, cognitive, personality and neuropsychological variables. Individuals with chronic depression and increased levels of pre-treatment negative automatic thoughts had a poorer response to both cognitive behaviour therapy and schema therapy. A treatment type interaction was found for verbal learning and memory. Lower levels of verbal learning and memory impairment markedly impacted on response to schema therapy. This was not the case for cognitive behaviour therapy, which was more impacted if verbal learning and memory was in the moderate range. Study findings are consistent with the Capitalisation Model suggesting that therapy that focuses on the person's strengths is more likely to contribute to a better outcome. Limitations were that participants were outpatients in a randomised controlled trial and may not be representative of other depressed samples. Examination of a variety of potential predictors was exploratory and requires replication.

Self-assessment of professionalism in physical therapy education.

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Anderson, Deborah K; Irwin, Kent E

2013-01-01

With the physical therapy (PT) professions' advancement to the clinical doctorate degree and the promotion of autonomous practice, exemplary professional conduct is an expectation of the PT profession. PT education programs are being challenged to develop methods to teach and assess professional behavior. Forty-three PT students (11 male and 32 female, ages 20-28 years) completed the APTA Professionalism in Physical Therapy: Core Values Self-Assessment (PPTCVSA) after their first 3 week clinical experience and again after their final clinical experience. A mixed design ANOVA compared participants' total scores and individual Core Value scores on the Professionalism in Physical Therapy: Core Values Self-Assessment (PPTCVSA) after 3 and 33 weeks of clinical education. The effects of gender, age, and undergraduate area of study on growth in professionalism scores were also investigated. Total PPTCVSA scores and individual Core Value scores on professionalism (accountability, altruism, compassion/caring, excellence, integrity, professional duty, and social responsibility) were higher after 33 weeks compared to scores after 3 weeks of clinical education. Female student's total professionalism scores were higher than male student's scores on both the first and second self-assessments. In addition, female students scored themselves higher than their male peers on accountability, excellence, integrity, and professional duty. Improved scores on the PPTCVSA indicate that physical therapy education is playing an important role in the development of professional behavior, knowledge, and application in practice.

Alanine EPR dosimeter response in proton therapy beams

International Nuclear Information System (INIS)

Gall, K.; Serago, C.; Desrosiers, M.; Bensen, D.

1997-01-01

We report a series of measurements directed to assess the suitability of alanine as a mailable dosimeter for dosimetry quality assurance of proton radiation therapy beams. These measurements include dose-response of alanine at 140 MeV, and comparison of response vs energy with a parallel plate ionization chamber. All irradiations were made at the Harvard Cyclotron Laboratory, and the dosimeters were read at NIST. The results encourage us that alanine could be expected to serve as a mailable dosimeter with systematic error due to differential energy response no greater than 3% when doses of 25 Gy are used. (Author)

Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

International Nuclear Information System (INIS)

Schwarzenboeck, Sarah M.; Krause, Bernd J.; Eiber, Matthias; Schwaiger, Markus; Kundt, Guenther; Retz, Margitta; Treiber, Uwe; Nawroth, Roman; Gschwend, Juergen E.; Thalgott, Mark; Sakretz, Monique; Kurth, Jens; Rummeny, Ernst J.

2016-01-01

The aim of this study was to prospectively evaluate the value of [ 11 C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [ 11 C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [ 11 C] Choline uptake (SUV max , SUV mean ), CT derived Houndsfield units (HU max , HU mean ), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV max , SUV mean , HU max , HU mean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV max and SUV mean (early and late) and changes of PSA early and PSA late were evaluated. Prognostic value of initial SUV max and SUV mean was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV max and SUV mean were statistically significantly higher in nPD (applying clinical

A novel approach to assess the treatment response using Gaussian random field in PET

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Wang, Mengdie [Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China and Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Guo, Ning [Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Hu, Guangshu; Zhang, Hui, E-mail: hzhang@mail.tsinghua.edu.cn, E-mail: li.quanzheng@mgh.harvard.edu [Department of Biomedical Engineering, Tsinghua University, Beijing 100084 (China); El Fakhri, Georges; Li, Quanzheng, E-mail: hzhang@mail.tsinghua.edu.cn, E-mail: li.quanzheng@mgh.harvard.edu [Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 and Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115 (United States)

2016-02-15

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response

Development and validation of the functional assessment of cancer therapy-antiangiogenesis subscale.

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Kaiser, Karen; Beaumont, Jennifer L; Webster, Kimberly; Yount, Susan E; Wagner, Lynne I; Kuzel, Timothy M; Cella, David

2015-05-01

The Functional Assessment of Cancer Therapy (FACT)-Antiangiogenesis (AntiA) Subscale was developed and validated to enhance treatment decision-making and side effect management for patients receiving anti-angiogenesis therapies. Side effects related to anti-angiogenesis therapies were identified from the literature, clinician input, and patient input. Fifty-nine possible patient expressions of side effects were generated. Patient and clinician ratings of the importance of these expressions led us to develop a 24-item questionnaire with clinical and research potential. To assess the scale's reliability and validity, 167 patients completed the AntiA Subscale, the Functional Assessment of Cancer Therapy-general (FACT-G), the FACT-Kidney Symptom Index (FKSI), the FACIT-Fatigue Subscale, the Global Rating of Change Scale (GRC), and the PROMIS Global Health Scale. Patient responses to the AntiA were analyzed for internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness to change in clinical status. All tested scales were found to have good internal consistency reliability (Cronbach's alpha 0.70-0.92). Test-retest reliability was also good (0.72-0.88) for total and subscale scores and lower for individual items. The total score, subscale scores, and all single items (except nosebleeds) significantly differentiated between groups defined by level of side effect bother. Evaluation of responsiveness to change in this study was not conclusive, suggesting an area for further research. The AntiA is a reliable and valid measure of side effects from anti-angiogenesis therapy. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Prospective evaluation of [{sup 11}C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Schwarzenboeck, Sarah M.; Krause, Bernd J. [Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Rostock University Medical Centre, Department of Nuclear Medicine, Rostock (Germany); Eiber, Matthias; Schwaiger, Markus [Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kundt, Guenther [Rostock University Medical Centre, Department of Biostatistics and Informatics, Rostock (Germany); Retz, Margitta; Treiber, Uwe; Nawroth, Roman; Gschwend, Juergen E.; Thalgott, Mark [Technical University of Munich, Department of Urology, Klinikum rechts der Isar, Munich (Germany); Sakretz, Monique; Kurth, Jens [Rostock University Medical Centre, Department of Nuclear Medicine, Rostock (Germany); Rummeny, Ernst J. [Technical University of Munich, Institute of Radiology, Klinikum rechts der Isar, Munich (Germany)

2016-11-15

The aim of this study was to prospectively evaluate the value of [{sup 11}C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [{sup 11}C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [{sup 11}C] Choline uptake (SUV{sub max}, SUV{sub mean}), CT derived Houndsfield units (HU{sub max}, HU{sub mean}), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV{sub max}, SUV{sub mean}, HU{sub max}, HU{sub mean,} and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV{sub max} and SUV{sub mean} (early and late) and changes of PSA{sub early} and PSA{sub late} were evaluated. Prognostic value of initial SUV{sub max} and SUV{sub mean} was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV{sub max

Therapy of chronic hepatitis C: Virologic response monitoring

Directory of Open Access Journals (Sweden)

Kuljić-Kapulica Nada

2010-01-01

Full Text Available Background/Aim. Virological testing is considered to be essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, and, most importantly, as a quide for treatment decisions and assess the virological response to antiviral therapy. The aim of this study was to determine the rate of a sustained virological response (SVR and various factors associated with response rates in chronic hepatitis C infected patients treated with pegiinterferon alpha (PEGINF and ribavirin (RBV combination therapy. Methods. A total of 34 patients, treated with PEG-IFN and RBV were studied. Serum HCV-RNA was measured before the treatment, 12 weeks following the start of the therapy and 6 weeks after the treatment cessation. SVR was defined as undetectable serum HCV-RNA 6 months of post-treatment follow-up, virologic relapse (VR as relapse of HCV-RNA during the post-treatment follow-up. Serum HCV-RNA was measured with the Cobas Amplicor test. Results. At the end of post-treatment follow-up 19 (55.8% patients demonstrated a SVR. The majority of the patients were genotype 1 (27, and the other were genotype 3 (5 patients and genotype 4 (2 patients. There was VR in 6 patients 6 months after the therapy. In 9 patients HCV-RNA was positive after 12 weeks. Conclusion. We demonstrated that patients with chronic HCV infection can be successfully treated with combination of PEG-INF and RBV. This result emphasizes also that post-treatment follow-up to identify patients with SVR or VR could be important.

Responsiveness of migraine-ACT and MIDAS questionnaires for assessing migraine therapy.

Science.gov (United States)

García, María Luisa; Baos, Vicente; Láinez, Miguel; Pascual, Julio; López-Gil, Arturo

2008-10-01

Migraine is frequently undertreated. The 4-item Migraine Assessment of Current Therapy (Migraine-ACT) questionnaire is a simple and reliable tool to identify patients requiring a change in current acute migraine treatment. To investigate the responsiveness of the Migraine-ACT tool, and compare it with that of the Migraine Disability Assessment (MIDAS) questionnaire, for patients with migraine at 1100 primary care sites in Spain. Patients eligible for this open-label, 2-visit prospective study reported migraine for >1 year and >or=1 migraine attack per month and were new to the clinic or on follow-up care for MIDAS questionnaires were administered, and patient satisfaction with treatment was recorded, at baseline and at 3 months. A total of 3272 patients, 78% female, were enrolled, and 2877 (88%) returned for the 3-month visit. Investigators changed baseline migraine treatment for 72% of returning patients; 85% and 80% of these patients had improved Migraine-ACT and MIDAS scores at 3 months, respectively. Patients who reported being completely or very satisfied with migraine treatment numbered 492 (15%) at baseline and 1406 (49%) at 3 months. Migraine-ACT and MIDAS score agreement for improvement at 3 months was poor (kappa = 0.339). Both the mean MIDAS score and the distribution of Migraine-ACT scores improved over the course of 3 months; however, Migraine-ACT scores were significantly (P MIDAS scores. The area under the curve in the receiver-operating characteristic analysis was significantly (P MIDAS (0.70) questionnaire. These results suggest that the Migraine-ACT questionnaire can be used more reliably than the MIDAS questionnaire for detecting improvements in treatment of new and follow-up patients with migraine.

Response to microneedling treatment in men with androgenetic alopecia who failed to respond to conventional therapy

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Rachita Dhurat

2015-01-01

Full Text Available Introduction: The efficacy of conventional therapy viz. finasteride and minoxidil in androgenetic alopecia (AGA that is based on both preventing hair loss and promoting new hair growth, varies between 30% and 60%. This has led to a large number of patients unsatisfied who demand for a better cosmetic coverage over the scalp. Microneedling has recently been reported to be promising, effective and a safe treatment modality in the treatment of AGA. This augments the response of conventional therapy. Materials and Methods: Four men with AGA were on finasteride and 5% minoxidil solution since 2 to 5 years. Though there was no worsening in their respective AGA stages with the therapy, they showed no new hair growth. They were subjected to microneedling procedure over a period of 6 months along with their ongoing therapy. Patients were assessed with the use of the standardized 7-point evaluation scale and patients′ subjective hair growth assessment scale. The patients were followed up for 18 months post microneedling procedure to assess the sustainability of the response. Results: All patients showed a response of + 2 to + 3 on standardized 7-point evaluation scale. The response in the form of new hair growth started after 8-10 sessions. The patients′ satisfaction was more than 75% in three patients and more 50% in one patient, on patients′ subjective hair growth assessment scale. The obtained results were sustained post procedure during 18 months follow-up period. Conclusion : Treatment with microneedling showed an accelerated response with addition of microneedling procedure leading to significant scalp density. This is the first case series to report the boosting effect of microneedling with respect to new hair follicle stimulation in patients with androgenetic alopecia who were poor responders to conventional therapy.

Predictive value of early viriological response for sustained viriological response in chronic hepatitis c with conventional interferon therapy

International Nuclear Information System (INIS)

Awan, A.; Umar, M.; Khaar, H.T.B.; Kulsoom, A.; Minhas, Z.; Ambreen, S.; Habib, N.; Mumtaz, W.; Habib, F.

2016-01-01

Background: Hepatitis is a major public health problem in Pakistan due to its strong association with liver failure and hepatocellular carcinoma. In Pakistan, conventional interferon therapy along with Ribavirin is favoured especially in Government funded programs for treatment of Hepatitis C, over the more expensive Pegylated Interferon and Ribavirin combination therapy as recommended by Pakistan society of Gastroenterology and GI endoscopy due to its favourable results observed in genotype 3 which is the dominant genotype of this region. Objective of our study was to assess the viriological responses with standard interferon therapy and to determine the predictive values of early viriological response (EVR) for Sustained Viriological Response (SVR) in chronic hepatitis C patients treated with standard interferon therapy. Methods: A cross sectional study was conducted on patients with chronic hepatitis C having received standard interferon and ribavirin therapy for six months. EVR and SVR were noted for analysis. Positive and negative predictive values of EVR on SVR were calculated. Results: Out of the total sample (N=3075), 1946 (63.3 percentage) patients were tested for EVR. 1386 (71.2 percentage) were positive while 560 (28.8 percentage) were negative while 516 (16.8 percentage) were tested for SVR. Two hundred and eighty-five (55.2 percentage) were positive while 231 (44.8 percentage) were negative. EVR and SVR tested were N=117. Positive predictive value of EVR on SVR was 67.1 percentage and negative predictive value was 65.8 percentage. Statistically significant association between EVR and SVR was determined with Chi square statistic of 11.8 (p-value <0.0001). Conclusion: EVR is a good predictor of response of patients to standard interferon and ribavirin therapy. In the absence of an EVR, it seems imperative to stop further treatment. Virilogical responses with conventional interferon therapy are comparable to those of pegylated interferon therapy so

ASSESSMENT OF THE RESPONSE OF PATIENTS WITH CROHN'S DISEASE TO BIOLOGICAL THERAPY USING NEW NON-INVASIVE MARKERS: lactoferrin and calprotectin

Directory of Open Access Journals (Sweden)

Islaine Martins NOGUEIRA

2013-04-01

Full Text Available Context The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment. Objective To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin, colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI, as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. Methods Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8, and after maintenance (week 32. Results The calprotectin levels exhibited significant reductions (P = 0.04 between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P = 0.036, and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P<0.01. Conclusion Calprotectin and lactoferrin are not useful for monitoring inflammatory activity in Crohn's disease patients who are subjected to biological therapy.

Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

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Baum, R. P.; Przetak, C. [Zentralklinik Bad Berka, Clinic of Nuclear Medicine, Center for PET, Bad Berka (Germany)

2001-09-01

Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these.

Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

International Nuclear Information System (INIS)

Baum, R. P.; Przetak, C.

2001-01-01

Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these

18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start

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Seith, Ferdinand; Schmidt, Holger; Pfannenberg, Christina; Gueckel, Brigitte; Schwenzer, Nina [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Forschner, Andrea; Garbe, Claus [Eberhard Karls University, Department of Dermatology, Tuebingen (Germany); Nikolaou, Konstantin [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); German Cancer Consortium (DKTK), Heidelberg (Germany); La Fougere, Christian [German Cancer Consortium (DKTK), Heidelberg (Germany); Eberhard Karls University, Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Tuebingen (Germany)

2018-01-15

The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation. Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t{sub 0}, base-line), two weeks (t{sub 1}, study examination) and three months after treatment initiation (t{sub 2}, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients. Three patients with partial metabolic response in PET at t{sub 1} turned out to have complete response at t{sub 2}. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t{sub 2}, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t{sub 1}. OS in patients with PMD at t{sub 2} varied between 148 and 814 days. SMD at both t{sub 1} and t{sub 2} was seen in one patient, tumor progress was observed after 308 days. Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future. (orig.)

Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

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Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2013-06-01

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

Mental health consumer participation in undergraduate occupational therapy student assessment: No negative impact.

Science.gov (United States)

Logan, Alexandra; Yule, Elisa; Taylor, Michael; Imms, Christine

2018-05-28

Australian accreditation standards for occupational therapy courses require consumer participation in the design, delivery and evaluation of programs. This study investigated whether a mental health consumer - as one of two assessors for an oral assessment in a mental health unit - impacted engagement, anxiety states and academic performance of undergraduate occupational therapy students. Students (n = 131 eligible) self-selected into two groups but were blinded to the group differences (assessor panel composition) until shortly prior to the oral assessment. Control group assessors were two occupational therapy educators, while consumer group assessors included an occupational therapy educator and a mental health consumer. Pre- and post-assessment data were successfully matched for 79 students (overall response rate = 73.1%). No evidence was found of significant differences between the two groups for engagement, anxiety or academic performance (all P values >0.05). Including mental health consumers as assessors did not negatively impact student engagement and academic performance, nor increase student anxiety beyond that typically observed in oral assessment tasks. The findings provide support for expanding the role of mental health consumers in the education and assessment of occupational therapy students. Development of methods to determine the efficacy of consumer involvement remains an area for future research. © 2018 Occupational Therapy Australia.

Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy.

Science.gov (United States)

Kinahan, Paul E; Fletcher, James W

2010-12-01

The use of standardized uptake values (SUVs) is now common place in clinical 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG) position emission tomography-computed tomography oncology imaging and has a specific role in assessing patient response to cancer therapy. Ideally, the use of SUVs removes variability introduced by differences in patient size and the amount of injected FDG. However, in practice there are several sources of bias and variance that are introduced in the measurement of FDG uptake in tumors and also in the conversion of the image count data to SUVs. In this article the overall imaging process is reviewed and estimates of the magnitude of errors, where known, are given. Recommendations are provided for best practices in improving SUV accuracy. Copyright © 2010 Elsevier Inc. All rights reserved.

Neurophysiological and behavioural responses to music therapy in vegetative and minimally conscious states

Directory of Open Access Journals (Sweden)

Julian eO'Kelly

2013-12-01

Full Text Available Assessment of awareness for those with disorders of consciousness (DOC is a challenging undertaking, due to the complex presentation of the population, where misdiagnosis rates remain high. Music therapy may be effective in the assessment and rehabilitation with this population due to effects of musical stimuli on arousal, attention and emotion, irrespective of verbal or motor deficits, however, an evidence base is lacking. To address this, a neurophysiological and behavioural study was undertaken comparing EEG, heart rate variability, respiration and behavioural responses of 20 healthy subjects with 21 individuals in vegetative or minimally conscious states (VS or MCS. Subjects were presented with live preferred music and improvised music entrained to respiration (i.e., music therapy procedures, recordings of disliked music, white noise and silence. ANOVA tests indicated a range of significant responses (p ≤ 0.05 across healthy subjects corresponding to arousal and attention in response to preferred music including concurrent increases in respiration rate with globally enhanced EEG power spectra responses across frequency bandwidths. Whilst physiological responses were heterogeneous across patients, significant post hoc EEG amplitude increases for stimuli associated with preferred music were found for frontal midline theta in 6 VS and 4 MCS subjects, and frontal alpha in 3 VS and 4 MCS subjects (p = 0.05 - 0.0001. Furthermore, behavioural data showed a significantly increased blink rate for preferred music (p = 0.029 across the VS cohort. Two VS cases are presented with concurrent changes (p ≤ 0.05 across measures indicative of discriminatory responses to both music therapy procedures. A MCS case study highlights how more sensitive selective attention may distinguish MCS from VS. Further investigation is warranted to explore the use of music therapy for prognostic indicators, and its potential to support neuroplasticity in rehabilitation

Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy

Directory of Open Access Journals (Sweden)

Li Kuiyuan

2009-04-01

Full Text Available Abstract Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS status has emerged as a predictor of response to epidermal growth factor receptor (EGFR targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.

Videofluoroscopic assessment of dysphagia: A questionnaire survey of protocols, roles and responsibilities of radiology and speech and language therapy personnel

International Nuclear Information System (INIS)

Power, Maxine; Laasch, Hans-Ulrich; Kasthuri, Ram S.; Nicholson, David A.; Hamdy, Shaheen

2006-01-01

Videofluoroscopy (VF) is the 'gold standard' assessment for oropharyngeal dysphagia and radiographers are beginning to direct this examination independently, yet little is known about the roles and responsibilities of the core professions of radiology and speech and language therapy and their practice in this examination. Aim: To evaluate VF practice and identify the roles and responsibilities of radiology and speech and language therapy personnel. Materials and methods: A questionnaire was developed and distributed to speech and language therapists (SALT) and radiologists via national special interest networks. Information regarding protocols, test materials, supervision, radiation protection and training was obtained. Results: One hundred and thirteen questionnaires were completed, 83% of respondents had more than 5 years service. Most were carrying out VF on an 'ad hoc' basis with only 32% participating in more than 6 assessments per month. There was no consensus on protocol and 41% chose to thicken barium solutions by adding more barium sulphate powder, potentially predisposing patients to complications. Over 50% of SALTs had received one day post-graduate training in VF, whereas, only one radiologist had specific VF training. Conclusion: Despite its importance in determining the feeding route for patients, VF is carried out infrequently by most clinicians and protocols vary widely. Moreover, intra- and inter-disciplinary training and supervision is minimal. More work is needed to develop standard guidelines, to improve the quality of the examination and its reproducibility

Non-response to (statin) therapy

DEFF Research Database (Denmark)

Trompet, S; Postmus, I; Slagboom, P E

2016-01-01

PURPOSE: In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non-responders are truly biologically non-responsive......-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p levels (p ... that non-adherence is investigated instead of non-responsiveness....

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

Science.gov (United States)

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanoscale theranostics for physical stimulus-responsive cancer therapies.

Science.gov (United States)

Chen, Qian; Ke, Hengte; Dai, Zhifei; Liu, Zhuang

2015-12-01

Physical stimulus-responsive therapies often employing multifunctional theranostic agents responsive to external physical stimuli such as light, magnetic field, ultra-sound, radiofrequency, X-ray, etc., have been widely explored as novel cancer therapy strategies, showing encouraging results in many pre-clinical animal experiments. Unlike conventional cancer chemotherapy which often accompanies with severe toxic side effects, physical stimulus-responsive agents usually are non-toxic by themselves and would destruct cancer cells only under specific external stimuli, and thus could offer greatly reduced toxicity and enhanced treatment specificity. In addition, physical stimulus-responsive therapies can also be combined with other traditional therapeutics to achieve synergistic anti-tumor effects via a variety of mechanisms. In this review, we will summarize the latest progress in the development of physical stimulus-responsive therapies, and discuss the important roles of nanoscale theranostic agents involved in those non-conventional therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Response to combination antiretroviral therapy: variation by age

DEFF Research Database (Denmark)

Lundgren, Jens

2008-01-01

-naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

Metabolomics of Therapy Response in Preclinical Glioblastoma: A Multi-Slice MRSI-Based Volumetric Analysis for Noninvasive Assessment of Temozolomide Treatment

Science.gov (United States)

Arias-Ramos, Nuria; Ferrer-Font, Laura; Lope-Piedrafita, Silvia; Mocioiu, Victor; Julià-Sapé, Margarida; Pumarola, Martí; Arús, Carles; Candiota, Ana Paula

2017-01-01

Glioblastoma (GBM) is the most common aggressive primary brain tumor in adults, with a short survival time even after aggressive therapy. Non-invasive surrogate biomarkers of therapy response may be relevant for improving patient survival. Previous work produced such biomarkers in preclinical GBM using semi-supervised source extraction and single-slice Magnetic Resonance Spectroscopic Imaging (MRSI). Nevertheless, GBMs are heterogeneous and single-slice studies could prevent obtaining relevant information. The purpose of this work was to evaluate whether a multi-slice MRSI approach, acquiring consecutive grids across the tumor, is feasible for preclinical models and may produce additional insight into therapy response. Nosological images were analyzed pixel-by-pixel and a relative responding volume, the Tumor Responding Index (TRI), was defined to quantify response. Heterogeneous response levels were observed and treated animals were ascribed to three arbitrary predefined groups: high response (HR, n = 2), TRI = 68.2 ± 2.8%, intermediate response (IR, n = 6), TRI = 41.1 ± 4.2% and low response (LR, n = 2), TRI = 13.4 ± 14.3%, producing therapy response categorization which had not been fully registered in single-slice studies. Results agreed with the multi-slice approach being feasible and producing an inverse correlation between TRI and Ki67 immunostaining. Additionally, ca. 7-day oscillations of TRI were observed, suggesting that host immune system activation in response to treatment could contribute to the responding patterns detected. PMID:28524099

Metabolomics of Therapy Response in Preclinical Glioblastoma: A Multi-Slice MRSI-Based Volumetric Analysis for Noninvasive Assessment of Temozolomide Treatment

Directory of Open Access Journals (Sweden)

Nuria Arias-Ramos

2017-05-01

Full Text Available Glioblastoma (GBM is the most common aggressive primary brain tumor in adults, with a short survival time even after aggressive therapy. Non-invasive surrogate biomarkers of therapy response may be relevant for improving patient survival. Previous work produced such biomarkers in preclinical GBM using semi-supervised source extraction and single-slice Magnetic Resonance Spectroscopic Imaging (MRSI. Nevertheless, GBMs are heterogeneous and single-slice studies could prevent obtaining relevant information. The purpose of this work was to evaluate whether a multi-slice MRSI approach, acquiring consecutive grids across the tumor, is feasible for preclinical models and may produce additional insight into therapy response. Nosological images were analyzed pixel-by-pixel and a relative responding volume, the Tumor Responding Index (TRI, was defined to quantify response. Heterogeneous response levels were observed and treated animals were ascribed to three arbitrary predefined groups: high response (HR, n = 2, TRI = 68.2 ± 2.8%, intermediate response (IR, n = 6, TRI = 41.1 ± 4.2% and low response (LR, n = 2, TRI = 13.4 ± 14.3%, producing therapy response categorization which had not been fully registered in single-slice studies. Results agreed with the multi-slice approach being feasible and producing an inverse correlation between TRI and Ki67 immunostaining. Additionally, ca. 7-day oscillations of TRI were observed, suggesting that host immune system activation in response to treatment could contribute to the responding patterns detected.

177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

International Nuclear Information System (INIS)

Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar; Sahoo, Ranjit Kumar; Seth, Amlesh

2017-01-01

The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, 177 Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic 68 Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly 177 Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity. 177 Lu

Assessment in Cognitive Therapy

OpenAIRE

Brown, Gary P.; Clark, David A.

2015-01-01

This volume brings together leading experts to explore the state of the art of cognitive clinical assessment and identify cutting-edge approaches of interest to clinicians and researchers. The book highlights fundamental problems concerning the validity of assessments that are widely used in cognitive-behavioral therapy (CBT). Key directions for further research and development are identified. Updated cognitive assessment methods are described in detail, with particular attention to transdiag...

Therapy assessment in prostate cancer using choline and PSMA PET/CT

Energy Technology Data Exchange (ETDEWEB)

Ceci, Francesco; Castellucci, Paolo; Fanti, Stefano [University of Bologna, Nuclear Medicine Unit, S. Orsola-Malpighi University Hospital, Bologna (Italy); Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); University of California Los Angeles, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA (United States); Hadaschik, Boris [University Hospital Essen, Department of Urology, Essen (Germany)

2017-08-15

While PET with non-FDG tracers (mainly choline and Ga-PSMA) has commonly been used for restaging in men with biochemically recurrent prostate cancer, as well as for primary staging, it is only recently that a few preliminary studies have addressed the possible use of PET for monitoring the response to systemic therapy of metastatic disease, especially innovative treatments such as abiraterone and enzalutamide. This article aims to evaluate the role of PET imaging with different non-FDG radiotracers for assessment of therapy in advanced prostate cancer patients. (orig.)

{sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

Energy Technology Data Exchange (ETDEWEB)

Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Sahoo, Ranjit Kumar [All India Institute of Medical Sciences, Department of Medical Oncology, BR Ambedkar Rotary Cancer Hospital, New Delhi (India); Seth, Amlesh [All India Institute of Medical Sciences, Department of Urology, New Delhi (India)

2017-01-15

The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic{sup 68}Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly {sup 177}Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity

Tumor response and clinical outcome in metastatic gastrointestinal stromal tumors under sunitinib therapy: Comparison of RECIST, Choi and volumetric criteria

Energy Technology Data Exchange (ETDEWEB)

Schramm, N., E-mail: Nicolai.schramm@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Englhart, E., E-mail: Elisabeth.Englhart@gmx.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Schlemmer, M., E-mail: Marcus.Schlemmer@med.uni-muenchen.de [Department of Medicine III, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Hittinger, M., E-mail: Markus.Hittinger@uksh.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Übleis, C., E-mail: Christopher.Uebleis@med.uni-muenchen.de [Department of Nuclear Medicine, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Becker, C.R., E-mail: Christoph.becker@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Reiser, M.F., E-mail: Maximilian.Reiser@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Berger, F., E-mail: Frank.Berger@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany)

2013-06-15

Purpose: Purpose of the study was to compare radiological treatment response according to RECIST, Choi and volumetry in GIST-patients under 2nd-line-sunitinib-therapy and to correlate the results of treatment response assessment with disease-specific survival (DSS). Patients and methods: 20 patients (mean: 60.7 years; 12 male/8 female) with histologically proven GIST underwent baseline-CT of the abdomen under imatinib and follow-up-CTs 3 months and 1 year after change to sunitinib. 68 target lesions (50 hepatic, 18 extrahepatic) were investigated. Therapy response (partial response (PR), stable disease (SD), progressive disease (PD)) was evaluated according to RECIST, Choi and volumetric criteria. Response according to the different assessment systems was compared and correlated to the DSS of the patients utilizing Kaplan–Meier statistics. Results: The mean DSS (in months) of the response groups 3 months after therapy change was: RECIST: PR (0/20); SD (17/20): 30.4 (months); PD (3/20) 11.6. Choi: PR (10/20) 28.6; SD (8/20) 28.1; PD (2/20) 13.5. Volumetry: PR (4/20) 29.6; SD (11/20) 29.7; PD (5/20) 17.2. Response groups after 1 year of sunitinib showed the following mean DSS: RECIST: PR (3/20) 33.6; SD (9/20) 29.7; PD (8/20) 20.3. Choi: PR (10/20) 21.5; SD (4/20) 42.9; PD (6/20) 23.9. Volumetry: PR (6/20) 27.3; SD (5/20) 38.5; PD (9/20) 19.3. Conclusion: One year after modification of therapy, only partial response according to RECIST indicated favorable survival in patients with GIST. The value of alternate response assessment strategies like Choi criteria for prediction of survival in molecular therapy still has to be demonstrated.

Tumor response and clinical outcome in metastatic gastrointestinal stromal tumors under sunitinib therapy: Comparison of RECIST, Choi and volumetric criteria

International Nuclear Information System (INIS)

Schramm, N.; Englhart, E.; Schlemmer, M.; Hittinger, M.; Übleis, C.; Becker, C.R.; Reiser, M.F.; Berger, F.

2013-01-01

Purpose: Purpose of the study was to compare radiological treatment response according to RECIST, Choi and volumetry in GIST-patients under 2nd-line-sunitinib-therapy and to correlate the results of treatment response assessment with disease-specific survival (DSS). Patients and methods: 20 patients (mean: 60.7 years; 12 male/8 female) with histologically proven GIST underwent baseline-CT of the abdomen under imatinib and follow-up-CTs 3 months and 1 year after change to sunitinib. 68 target lesions (50 hepatic, 18 extrahepatic) were investigated. Therapy response (partial response (PR), stable disease (SD), progressive disease (PD)) was evaluated according to RECIST, Choi and volumetric criteria. Response according to the different assessment systems was compared and correlated to the DSS of the patients utilizing Kaplan–Meier statistics. Results: The mean DSS (in months) of the response groups 3 months after therapy change was: RECIST: PR (0/20); SD (17/20): 30.4 (months); PD (3/20) 11.6. Choi: PR (10/20) 28.6; SD (8/20) 28.1; PD (2/20) 13.5. Volumetry: PR (4/20) 29.6; SD (11/20) 29.7; PD (5/20) 17.2. Response groups after 1 year of sunitinib showed the following mean DSS: RECIST: PR (3/20) 33.6; SD (9/20) 29.7; PD (8/20) 20.3. Choi: PR (10/20) 21.5; SD (4/20) 42.9; PD (6/20) 23.9. Volumetry: PR (6/20) 27.3; SD (5/20) 38.5; PD (9/20) 19.3. Conclusion: One year after modification of therapy, only partial response according to RECIST indicated favorable survival in patients with GIST. The value of alternate response assessment strategies like Choi criteria for prediction of survival in molecular therapy still has to be demonstrated

The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy

NARCIS (Netherlands)

Kloosterman, Mariëlle; Damman, Kevin; Van Veldhuisen, Dirk J; Rienstra, Michiel; Maass, Alexander H

AimTo perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods and resultsWe searched MEDLINE/PubMed and Cochrane for all papers published up

Provider-patient in-office discussions of response to hepatitis C antiviral therapy and impact on patient comprehension.

Science.gov (United States)

Hamilton, Heidi E; Nelson, Meaghan; Martin, Paul; Cotler, Scott J

2006-04-01

Providers need to communicate projected response rates effectively to enable patients with hepatitis C virus to make informed decisions about therapy. This study used interactional sociolinguistics (1) to evaluate how gastroenterologists and allied health professionals communicate information regarding response rates to antiviral therapy, (2) to determine how these discussions relate to where the patient is in the continuum of evaluation and treatment, (3) to assess whether patients were aligned with providers in their perceptions of response rates after office visits, and (4) to identify factors that improve provider-patient alignment. Gastroenterologists, allied health professionals, and patients with hepatitis C virus were videotaped and audiotaped during regularly scheduled visits. Postvisit interviews were conducted separately with patients and providers. Visits and postvisits were transcribed and analyzed using validated sociolinguistic techniques. The phase of hepatitis C virus treatment shaped the benchmarks of response talk, although across the treatment continuum providers overwhelmingly made strategic use of positive statistics, providing motivation. In postvisit interviews, 55% of providers and patients were aligned on response rates. Patients with a favorable outcome and patients who asked response-related questions in the visit were more likely to be aligned with providers. Areas identified for improvement included the tendency to discuss response rates before an individualized assessment could be made, balancing motivation and accuracy, and assessing the patient's perspective before delivering any bad news, if necessary. Sociolinguistic analysis provides a powerful tool to evaluate provider-patient interactions and to identify ways to improve in-office communication regarding antiviral therapy.

Proton therapy radiation pneumonitis local dose–response in esophagus cancer patients

International Nuclear Information System (INIS)

Echeverria, Alfredo E.; McCurdy, Matthew; Castillo, Richard; Bernard, Vincent; Ramos, Natalia Velez; Buckley, William; Castillo, Edward; Liu, Ping; Martinez, Josue; Guerrero, Thomas

2013-01-01

Purpose: This study quantifies pulmonary radiation toxicity in patients who received proton therapy for esophagus cancer. Materials/methods: We retrospectively studied 100 esophagus cancer patients treated with proton therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were assessed using the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4). The interaction of the imaging response with dosimetric parameters and symptoms was evaluated. Results: The RP scores were: 0 grade 4/5, 7 grade 3, 20 grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly higher for the symptomatic group. The AIC winning models were 30 linear, 52 linear quadratic, and 18 linear logarithmic. There was no significant difference in the linear coefficient between models. The slope of the FDG vs. proton dose response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p = 0.014). Combining dosimetric parameters with the slope did not improve the sensitivity or accuracy in identifying symptomatic cases. Conclusions: The proton radiation dose response on FDG PET/CT imaging exhibited a predominantly linear dose response on modeling. Symptomatic patients had a higher dose response slope

Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

LENUS (Irish Health Repository)

Tobin, W O

2013-02-01

The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised \\'anti-coagulant\\' effects of dipyridamole in ischaemic CVD.

Feelings of Loss in Response to Divorce: Assessment and Intervention.

Science.gov (United States)

Huber, Charles H.

1983-01-01

Presents a cognitively based model, founded on rational emotive therapy, as a basis for assessment and intervention strategies for assisting individuals to cope with feelings of loss in response to divorce. The model is seen as a four-pane window through which persons might see their divorce. (Author/JAC)

Stage of readiness of patients with behavioral dysphonia in pre and post-group voice therapy assessments.

Science.gov (United States)

Costa, Bianca Oliveira Ismael da; Silva, Priscila Oliveira Costa; Pinheiro, Renata Serrano de Andrade; Silva, Hêmmylly Farias da; Almeida, Anna Alice Figueirêdo de

2017-08-10

To verify the efficacy of group voice therapy in the stage of readiness and identify which items of the URICA-Voice range are more sensitive to post-therapy change in patients with behavioral dysphonia. An intervention study was conducted on 49 patients with behavioral dysphonia. An eclectic approach to group therapy was implemented over eight sessions, the first and last sessions consisting of assessments. The URICA-Voice range was used to evaluate the stage of readiness at pre- and post-therapy assessments. A descriptive and inferential statistical analysis was implemented for the results. Most participants were female, did not make professional use of voice, and had membranous vocal fold lesions. Most of them were in the Contemplation stage at in both moments, pre- and post-therapy. There was no significant change in the comparison of pre- and post-therapy scores. The majority of patients showed a reduction in the stage of readiness and some advanced to a higher stage. In the comparison of URICA-V range items, seven questions had equal or inferior responses in the post-therapy assessment. There was no statistical difference when comparing the pre- and post-therapy total average score of the URICA-Voice range. There were significant changes in the stage of readiness of patients in pre- and post-group speech therapy assessments.

Ecology, Ethics, and Responsibility in Family Therapy.

Science.gov (United States)

Maddock, James W.

1993-01-01

Notes that working with marital and family problems complicates the concept of therapeutic responsibility. Discusses several societal contributors to ethical dilemmas in contemporary family therapy and summarizes an ecological framework for therapy on the basis of which a profile of the ethical family therapist is derived. (Author/NB)

3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

Science.gov (United States)

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-09-01

To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk

The Music Therapy assessment tool for Advanced Huntington's Disease

DEFF Research Database (Denmark)

O'Kelly, Julian; Bodak, R.

2013-01-01

is limited, is a challenging process. With awareness often masked by perceptual or motor impairments, misdiagnosis rates remain high. Music therapy assessment holds the potential to elicit responses despite damage to verbal or visual processing faculties, although robust empirical studies are lacking...... music conditions (live salient music & improvised music entrained to respiration), recordings of disliked music, white noise and silence. Neurophysiological and behavioral measures were recorded using a 32 channel XLTEK© video EEG system, with a piezoelectric respiratory belt, and analysed using MATLAB......, EEGLAB and BrainVision Analyzer 2 software. One way repeated measures ANOVA analysis of respiration, and power spectra analysis of EEG data indicated a range of significant responses (p≤0.05) across controls corresponding to arousal and attention in response to live music, including concurrent increases...

Spiritual Assessments in Occupational Therapy

Directory of Open Access Journals (Sweden)

Barbara Hemphill

2015-07-01

Full Text Available Spirituality is recognized as an important concept in the study and practice of medicine, including occupational therapy. This aligns with occupational therapy’s core value of treating people holistically—mind, body, and spirit. Currently, the Joint Commission for the Accreditation of Hospital Organizations ( JCAHO requires that a spiritual assessment be given to patients on admission. To conduct effective spiritual assessments, occupational therapists must distinguish between religion and spirituality. They also must be aware of their own spiritual beliefs and practices and how those might influence their clinical interactions. This article presents spiritual assessment tools that occupational therapists can use in clinical practice; they range from history taking, to questionnaires, to observation scales. Guidelines are presented for selecting among several spiritual assessments. A case study is presented in which a patient’s faith tradition is being challenged, which could affect the outcome of therapy. Finally, treatment and intervention planning and ethical considerations are discussed.

Radionuclide assessment of the effects of chest physical therapy on ventilation in cystic fibrosis

International Nuclear Information System (INIS)

DeCesare, J.A.; Babchyck, B.M.; Colten, H.R.; Treves, S.

1982-01-01

This study assesses the use of /sup 81m/Kr scintigraphy as a measurement tool in evaluating the effectiveness of bronchial drainage with percussion and vibration on peripheral ventilation in patients with cystic fibrosis. Ten patients with cystic fibrosis participated. Each patient underwent a /sup 81m/Kr ventilation study and traditional pulmonary function tests. Forty-five minutes later, these studies were repeated before and after a chest physical therapy treatment. Each patient acted as his own control. All /sup 81m/Kr scintiscans were recorded and analyzed visually and numerically using a digital computer to assess distribution of ventilation. Visual analysis of the scintiscans indicated individual variation in treatment response: in some patients ventilation improved with therapy; in others, no change was noted; still others had changes independent of treatment. Numerical data derived from the scintiscans and pulmonary function tests showed no important differences among the three studies of each patient. Airway abnormalities characteristic of cystic fibrosis, progression of the disease, sputum production, or a combination of these factors may account for the individual variation in response to treatment. /sup 81m/Kr scintigraphy is a reliable measure of regional ventilation and should be useful for assessing the efficacy of chest physical therapy because of the consistent, high quality visual data retrieved

Multi-modality imaging of tumor phenotype and response to therapy

Science.gov (United States)

Nyflot, Matthew J.

2011-12-01

Imaging and radiation oncology have historically been closely linked. However, the vast majority of techniques used in the clinic involve anatomical imaging. Biological imaging offers the potential for innovation in the areas of cancer diagnosis and staging, radiotherapy target definition, and treatment response assessment. Some relevant imaging techniques are FDG PET (for imaging cellular metabolism), FLT PET (proliferation), CuATSM PET (hypoxia), and contrast-enhanced CT (vasculature and perfusion). Here, a technique for quantitative spatial correlation of tumor phenotype is presented for FDG PET, FLT PET, and CuATSM PET images. Additionally, multimodality imaging of treatment response with FLT PET, CuATSM, and dynamic contrast-enhanced CT is presented, in a trial of patients receiving an antiangiogenic agent (Avastin) combined with cisplatin and radiotherapy. Results are also presented for translational applications in animal models, including quantitative assessment of proliferative response to cetuximab with FLT PET and quantification of vascular volume with a blood-pool contrast agent (Fenestra). These techniques have clear applications to radiobiological research and optimized treatment strategies, and may eventually be used for personalized therapy for patients.

Therapy assessment in multiple myeloma with PET

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Nanni, Cristina [Medicina Nucleare Metropolitana di Bologna, Bologna (Italy); Zamagni, Elena [Bologna University School of Medicine, Seragnoli Institute of Hematology, Bologna (Italy)

2017-08-15

Multiple myeloma is a plasma cell dyscrasia producing bone lytic lesions. In recent years, a wide spectrum of therapeutic approaches are available to treat the disease: an accurate therapy assessment has, therefore, become of utmost importance. In this field, imaging is becoming a cornerstone, especially in association with clinical parameters. Among imaging procedures, FDG PET/CT is recognized to provide reliable information, achieved in a very safe and fast procedure. The literature has produced very concordant results from different groups assessing the value of FDG PET/CT as a prognostic factor in general and in therapy assessment, but some issues remain regarding a standardization of image interpretation especially in borderline cases. So far, no data regarding nor other imaging compounds and the use of hybrid tomographs PET/MR are available to define therapy assessment in PET. (orig.)

First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

Directory of Open Access Journals (Sweden)

Johann von Felden

2016-11-01

Full Text Available Advanced hepatocellular carcinoma (HCC with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST is helpful to identify patients who do not benefit from sorafenib treatment.

Quality of life assessment in radionuclide therapy: a feasibility study of the EORTC QLQ-C30 questionnaire in palliative 131I-lipiodol therapy

International Nuclear Information System (INIS)

Brans, B.; Lambert, B.; De Beule, E.; De Winter, F.; Dierckx, R.A.; Van Belle, S.; Van Vlierberghe, H.; De Hemptinne, B.

2002-01-01

The good tolerance of radionuclide therapy has frequently been proposed as a major advantage. This study explored the feasibility of using the EORTC QLQ-C30 questionnaire in palliative iodine-131 lipiodol therapy for hepatocellular carcinoma. Questionnaires were completed during interviews in which all symptoms, co-morbidity and medication were assessed at baseline within 1 week before 131 I-lipiodol therapy, and subsequently after 1 and 3 months, in 20 patients treated with locoregional, intra-arterial 131 I-lipiodol therapy with or without cisplatin. Principal observations were that (1) a number of important scales, i.e. overall quality of life, physical functioning and pain, worsened between 0 and 3 months after 131 I-lipiodol therapy, irrespective of tumour response, and (2) the occurrence of clinical side-effects was associated with a negative impact on quality of life and physical functioning 1 and 3 months after 131 I-lipiodol. The QLQ-C30 can be regarded as a feasible method for quality of life assessment in 131 I-lipiodol therapy for hepatocellular carcinoma and possibly in other radionuclide therapies. These observations should be related to the impact of other treatment modalities on quality of life. (orig.)

Music therapy in the assessment and treatment of autistic spectrum disorder: clinical application and research evidence.

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Wigram, T; Gold, C

2006-09-01

Children and adolescents with autistic spectrum disorder (ASD) presenting with significant limitations in conventional forms of verbal and non-verbal communication are found to respond positively to music therapy intervention involving both active, improvizational methods and receptive music therapy approaches. Improvizational musical activity with therapeutic objectives and outcomes has been found to facilitate motivation, communication skills and social interaction, as well as sustaining and developing attention. The structure and predictability found in music assist in reciprocal interaction, from which tolerance, flexibility and social engagement to build relationships emerge, relying on a systematic approach to promote appropriate and meaningful interpersonal responses. Published reports of the value and effectiveness of music therapy as an intervention for children with ASD range from controlled studies to clinical case reports. Further documentation has emphasized the role music therapy plays in diagnostic and clinical assessment. Music therapy assessment can identify limitations and weaknesses in children, as well as strengths and potentials. Research evidence from a systematic review found two randomized controlled trials that examined short-term effects of structured music therapy intervention. Significant effects were found in these studies even with extremely small samples, and the findings are important because they demonstrate the potential of the medium of music for autistic children. Case series studies were identified that examined the effects of improvizational music therapy where communicative behaviour, language development, emotional responsiveness, attention span and behavioural control improved over the course of an intervention of improvizational music therapy.

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis.

Science.gov (United States)

Premkumar, Preethi; Fannon, Dominic; Sapara, Adegboyega; Peters, Emmanuelle R; Anilkumar, Anantha P; Simmons, Andrew; Kuipers, Elizabeth; Kumari, Veena

2015-03-30

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6-8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Material interaction in art therapy assessment

NARCIS (Netherlands)

Pénzes, I.J.N.J.; Hooren, S. van; Dokter, D.; Smeijsters, H.; Hutschemaekers, G.J.M.

2014-01-01

Diverse approaches to art therapy assessment agree that art materials should play a central role. However, relatively little research is done on the role of different art materials. This article describes the results of a qualitative study on the use of art materials by art therapists in art therapy

A pilot validation of a modified Illness Perceptions Questionnaire designed to predict response to cognitive therapy for psychosis.

Science.gov (United States)

Marcus, Elena; Garety, Philippa; Weinman, John; Emsley, Richard; Dunn, Graham; Bebbington, Paul; Freeman, Daniel; Kuipers, Elizabeth; Fowler, David; Hardy, Amy; Waller, Helen; Jolley, Suzanne

2014-12-01

Clinical responsiveness to cognitive behavioural therapy for psychosis (CBTp) varies. Recent research has demonstrated that illness perceptions predict active engagement in therapy, and, thereby, better outcomes. In this study, we aimed to investigate the psychometric properties of a modification of the Illness Perceptions Questionnaire (M-IPQ) designed to predict response following CBTp. Fifty-six participants with persistent, distressing delusions completed the M-IPQ; forty before a brief CBT intervention targeting persecutory ideation and sixteen before and after a control condition. Additional predictors of outcome (delusional conviction, symptom severity and belief inflexibility) were assessed at baseline. Outcomes were assessed at baseline and at follow-up four to eight weeks later. The M-IPQ comprised two factors measuring problem duration and therapy-specific perceptions of Cure/Control. Associated subscales, formed by summing the relevant items for each factor, were reliable in their structure. The Cure/Control subscale was also reliable over time; showed convergent validity with other predictors of outcome; predicted therapy outcomes; and differentially predicted treatment effects. We measured outcome without an associated measure of engagement, in a small sample. Findings are consistent with hypothesis and existing research, but require replication in a larger, purposively recruited sample. The Cure/Control subscale of the M-IPQ shows promise as a predictor of response to therapy. Specifically targeting these illness perceptions in the early stages of cognitive behavioural therapy may improve engagement and, consequently, outcomes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Effects of Music Therapy on the Physiological Response of Asthmatic Children Receiving Inhalation Therapy.

Science.gov (United States)

Roslita, Riau; Nurhaeni, Nani; Wanda, Dessie

The clinical manifestation of asthma in children can interfere with their daily activities. Music therapy may become one of the alternative approaches to making children feel comfortable during inhalation therapy. The aim of the study was to identify the effects of music therapy on the physiological response of asthmatic preschool and school-age children receiving inhalation therapy. This study used a quasi-experimental, nonequivalent control group with a pre-test-post-test design. The 44 respondents consisted of preschool and school-age children assigned to intervention and control groups. The results showed a significant difference in average oxygen saturation, heart rate, and respiratory rate between the control and intervention groups before and after intervention (p Music therapy can be used as a nursing intervention to improve the physiological response of children with breathing problems.

Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at the Heidelberg Ion Therapy Center Using the Raster Scanning Technique

Energy Technology Data Exchange (ETDEWEB)

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Haberer, Thomas [Heidelberg Ion Therapy Center, Heidelberg (Germany); Jaekel, Oliver [Heidelberg Ion Therapy Center, Heidelberg (Germany); Department of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Muenter, Marc W.; Welzel, Thomas; Debus, Juergen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Combs, Stephanie E., E-mail: Stephanie.Combs@med.uni-hedielberg.de [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany)

2011-12-01

Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.

Computer-assisted detection (CAD) methodology for early detection of response to pharmaceutical therapy in tuberculosis patients

Science.gov (United States)

Lieberman, Robert; Kwong, Heston; Liu, Brent; Huang, H. K.

2009-02-01

The chest x-ray radiological features of tuberculosis patients are well documented, and the radiological features that change in response to successful pharmaceutical therapy can be followed with longitudinal studies over time. The patients can also be classified as either responsive or resistant to pharmaceutical therapy based on clinical improvement. We have retrospectively collected time series chest x-ray images of 200 patients diagnosed with tuberculosis receiving the standard pharmaceutical treatment. Computer algorithms can be created to utilize image texture features to assess the temporal changes in the chest x-rays of the tuberculosis patients. This methodology provides a framework for a computer-assisted detection (CAD) system that may provide physicians with the ability to detect poor treatment response earlier in pharmaceutical therapy. Early detection allows physicians to respond with more timely treatment alternatives and improved outcomes. Such a system has the potential to increase treatment efficacy for millions of patients each year.

Immunotherapy Response Assessment in Neuro-Oncology (iRANO): A Report of the RANO Working Group

Science.gov (United States)

Okada, Hideho; Weller, Michael; Huang, Raymond; Finocchiaro, Gaetano; Gilbert, Mark R.; Wick, Wolfgang; Ellingson, Benjamin M.; Hashimoto, Naoya; Pollack, Ian F.; Brandes, Alba A.; Franceschi, Enrico; Herold-Mende, Christel; Nayak, Lakshmi; Panigrahy, Ashok; Pope, Whitney B.; Prins, Robert; Sampson, John H.; Wen, Patrick Y.; Reardon, David A.

2015-01-01

Immunotherapy represents a promising area of therapy among neuro-oncology patients. However, early phase studies reveal unique challenges associated with assessment of radiological changes reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumor regression, can still occur following initial apparent progression or appearance of new lesions. Refinement of response assessment criteria for neuro-oncology patients undergoing immunotherapy is therefore warranted. A multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describes immunotherapy response assessment for neuro-oncology (iRANO) criteria that are based on guidance for determination of tumor progression outlined by the immune-related response criteria (irRC) and the response assessment in neuro-oncology (RANO) working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease (PD) within six months of initiating immunotherapy including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for use of corticosteroids. The role of advanced imaging techniques and measurement of clinical benefit endpoints including neurologic and immunologic functions are reviewed. The iRANO guidelines put forth herein will evolve successively to improve their utility as further experience from immunotherapy trials in neuro-oncology accumulate. PMID:26545842

Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

Science.gov (United States)

Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Silberg, Debra G

2013-04-01

Approximately 20-30% of patients with gastroesophageal reflux disease (GERD) do not experience complete symptom resolution during proton pump inhibitor (PPI) therapy. The aim of this study was to determine the prevalence of esophageal mucosal breaks among patients who have a partial response to PPI therapy. This was an analysis of data from a phase 2b clinical trial carried out to assess the efficacy and safety of a reflux inhibitor, lesogaberan (AZD3355), as an add-on to PPI therapy in this patient population (clinicaltrials.gov reference: NCT01005251). A total of 661 patients with persistent GERD symptoms who had received a minimum of 4 weeks of PPI therapy were included in the study. The prevalence of esophageal mucosal breaks was assessed according to (i) the most recent endoscopy results from within the previous 24 months, if available ("historical" endoscopies), and (ii) the results of endoscopies performed at study baseline ("baseline" endoscopies). Baseline endoscopies were not carried out in patients who had a historical endoscopy showing an absence of esophageal mucosal breaks. Historical endoscopy results were available for 244 patients, of whom 48 (19.7%) had esophageal mucosal breaks. Baseline endoscopies were carried out in 465 patients, of whom 146 (31.4%) had esophageal mucosal breaks. Sensitivity analyses showed a prevalence of esophageal mucosal breaks of 20-30%. In both the historical and baseline endoscopies, most esophageal mucosal breaks were Los Angeles grades A or B. In patients with GERD symptoms partially responsive to PPI therapy, mild-to-moderate severity esophageal mucosal breaks are common (prevalence 20-30%), and may contribute to symptom etiology.

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.

Science.gov (United States)

Deuschl, Cornelius; Moenninghoff, Christoph; Goericke, Sophia; Kirchner, Julian; Köppen, Susanne; Binse, Ina; Poeppel, Thorsten D; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Herrmann, Ken; Hense, Joerg; Schlamann, Marc

2017-08-01

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study

Energy Technology Data Exchange (ETDEWEB)

Deuschl, Cornelius [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); Moenninghoff, Christoph; Goericke, Sophia; Forsting, Michael; Umutlu, Lale [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Kirchner, Julian [University Hospital Duesseldorf, Institute of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Koeppen, Susanne [University Hospital Essen, Department of Neurology, Essen (Germany); Binse, Ina; Poeppel, Thorsten D.; Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Hense, Joerg [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Schlamann, Marc [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Giessen, Department of Neuroradiology, Essen (Germany)

2017-08-15

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM. (orig.)

A Combined Pharmacokinetic and Radiologic Assessment of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Response to Chemoradiation in Locally Advanced Cervical Cancer

International Nuclear Information System (INIS)

Semple, Scott; Harry, Vanessa N. MRCOG.; Parkin, David E.; Gilbert, Fiona J.

2009-01-01

Purpose: To investigate the combination of pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging (MRI) as an early response indicator in women receiving chemoradiation for advanced cervical cancer. Methods and Materials: Twenty women with locally advanced cervical cancer were included in a prospective cohort study. Dynamic contrast-enhanced MRI was carried out before chemoradiation, after 2 weeks of therapy, and at the conclusion of therapy using a 1.5-T MRI scanner. Radiologic assessment of uptake parameters was obtained from resultant intensity curves. Pharmacokinetic analysis using a multicompartment model was also performed. General linear modeling was used to combine radiologic and pharmacokinetic parameters and correlated with eventual response as determined by change in MRI tumor size and conventional clinical response. A subgroup of 11 women underwent repeat pretherapy MRI to test pharmacokinetic reproducibility. Results: Pretherapy radiologic parameters and pharmacokinetic K trans correlated with response (p < 0.01). General linear modeling demonstrated that a combination of radiologic and pharmacokinetic assessments before therapy was able to predict more than 88% of variance of response. Reproducibility of pharmacokinetic modeling was confirmed. Conclusions: A combination of radiologic assessment with pharmacokinetic modeling applied to dynamic MRI before the start of chemoradiation improves the predictive power of either by more than 20%. The potential improvements in therapy response prediction using this type of combined analysis of dynamic contrast-enhanced MRI may aid in the development of more individualized, effective therapy regimens for this patient group.

Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI.

Science.gov (United States)

Nelson, Sarah J

2011-07-01

MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low-grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12-15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium-enhancing lesion on T(1) -weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T(2) lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti-angiogenic and anti

Anatomic, functional and molecular imaging in lung cancer precision radiation therapy: treatment response assessment and radiation therapy personalization

Science.gov (United States)

Everitt, Sarah; Schimek-Jasch, Tanja; Li, X. Allen; Nestle, Ursula; Kong, Feng-Ming (Spring)

2017-01-01

This article reviews key imaging modalities for lung cancer patients treated with radiation therapy (RT) and considers their actual or potential contributions to critical decision-making. An international group of researchers with expertise in imaging in lung cancer patients treated with RT considered the relevant literature on modalities, including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). These perspectives were coordinated to summarize the current status of imaging in lung cancer and flag developments with future implications. Although there are no useful randomized trials of different imaging modalities in lung cancer, multiple prospective studies indicate that management decisions are frequently impacted by the use of complementary imaging modalities, leading both to more appropriate treatments and better outcomes. This is especially true of 18F-fluoro-deoxyglucose (FDG)-PET/CT which is widely accepted to be the standard imaging modality for staging of lung cancer patients, for selection for potentially curative RT and for treatment planning. PET is also more accurate than CT for predicting survival after RT. PET imaging during RT is also correlated with survival and makes response-adapted therapies possible. PET tracers other than FDG have potential for imaging important biological process in tumors, including hypoxia and proliferation. MRI has superior accuracy in soft tissue imaging and the MRI Linac is a rapidly developing technology with great potential for online monitoring and modification of treatment. The role of imaging in RT-treated lung cancer patients is evolving rapidly and will allow increasing personalization of therapy according to the biology of both the tumor and dose limiting normal tissues. PMID:29218270

An Assessment of Early Response to Targeted Therapy via Molecular Imaging: A Pilot Study of 3′-deoxy-3′[(18F]-Fluorothymidine Positron Emission Tomography 18F-FLT PET/CT in Prostate Adenocarcinoma

Directory of Open Access Journals (Sweden)

Kalevi Kairemo

2017-04-01

Full Text Available Fluorothymidine is a thymidine analog labeled with fluorine-18 fluorothymidine for positron emission tomography (18F-FLT-PET imaging. Thymidine is a nucleic acid that is used to build DNA. Fluorine-18 fluorothymidine (18F-FLT utilizes the same metabolic pathway as does thymidine but has a very low incidence of being incorporated into the DNA (<1%. 18F-FLT-PET could have a role in the evaluation of response to targeted therapy. We present here a pilot study where we investigated cellular metabolism and proliferation in patients with prostate cancer before and after targeted therapy. Seven patients with Stage IV prostate adenocarcinoma, candidates for targeted therapy inhibiting the hepatocyte growth factor/tyrosine-protein kinase Met (HGF/C-MET pathway, were included in this study. The HGF/C-MET pathway is implicated in prostate cancer progression, and an evaluation of the inhibition of this pathway could be valuable. 18F-FLT was performed at baseline and within four weeks post-therapy. Tumor response was assessed semi-quantitatively and using visual response criteria. The range of SUVmax for 18F-FLT at baseline in the prostate varied from 2.5 to 4.2. This study demonstrated that 18F-FLT with positron emission tomography/computerized tomography (18F-FLT PET/CT had only limited applications in the early response evaluation of prostate cancer. 18F-FLT PET/CT may have some utility in the assessment of response in lymph node disease. However, 18F-FLT PET/CT was not found to be useful in the evaluation of the prostate bed, metastatic skeletal disease, and liver disease.

Revisiting the relationship between tumour volume and diameter in advanced NSCLC patients: An exercise to maximize the utility of each measure to assess response to therapy

International Nuclear Information System (INIS)

Nishino, M.; Jackman, D.M.; DiPiro, P.J.; Hatabu, H.; Jänne, P.A.; Johnson, B.E.

2014-01-01

Aim: To revisit the presumed relationship between tumour diameter and volume in advanced non-small-cell lung cancer (NSCLC) patients, and determine whether the measured volume using volume-analysis software and its proportional changes during therapy matches with the calculated volume obtained from the presumed relationship and results in concordant response assessment. Materials and methods: Twenty-three patients with stage IIIB/IV NSCLC with a total of 53 measurable lung lesions, treated in a phase II trial of erlotinib, were studied with institutional review board approval. Tumour volume and diameter were measured at baseline and at the first follow-up computed tomography (CT) examination using volume-analysis software. Using the measured diameter (2r) and the equation, calculated volume was obtained as (4/3)πr 3 at baseline and at the follow-up. Percent volume change was obtained by comparing to baseline for measured and calculated volumes, and response assessment was assigned. Results: The measured volume was significantly smaller than the calculated volume at baseline (median 11,488.9 mm 3 versus 17,148.6 mm 3 ; p < 0.0001), with a concordance correlation coefficient (CCC) of 0.7022. At follow-up, the measured volume was once again significantly smaller than the calculated volume (median 6573.5 mm 3 versus 9198.1 mm 3 ; p = 0.0022), with a CCC of 0.7408. Response assessment by calculated versus measured volume changes had only moderate agreement (weighted κ = 0.545), with discordant assessment results in 20% (8/40) of lesions. Conclusion: Calculated volume based on the presumed relationship significantly differed from the measured volume in advanced NSCLC patients, with only moderate concordance in response assessment, indicating the limitations of presumed relationship. - Highlights: • Response assessment by measured vs calculated values has only moderate agreement. • It is important to obtain the actual measured values for tumor response

The Initial Response To Corticosteroid Therapy in Childhood ...

African Journals Online (AJOL)

Background: Nephrotic syndrome (NS) in African children is associated with poor response to corticosteroids. There is disparity in treatment response on the African continent. The aim of this present study was to describe the initial response to corticosteroid therapy of childhood NS in Côte d'ivoire. Materials and methods: ...

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

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Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

International Nuclear Information System (INIS)

Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

2015-01-01

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted

[Application of decision curve on evaluation of MRI predictive model for early assessing pathological complete response to neoadjuvant therapy in breast cancer].

Science.gov (United States)

He, Y J; Li, X T; Fan, Z Q; Li, Y L; Cao, K; Sun, Y S; Ouyang, T

2018-01-23

Objective: To construct a dynamic enhanced MR based predictive model for early assessing pathological complete response (pCR) to neoadjuvant therapy in breast cancer, and to evaluate the clinical benefit of the model by using decision curve. Methods: From December 2005 to December 2007, 170 patients with breast cancer treated with neoadjuvant therapy were identified and their MR images before neoadjuvant therapy and at the end of the first cycle of neoadjuvant therapy were collected. Logistic regression model was used to detect independent factors for predicting pCR and construct the predictive model accordingly, then receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive model. Results: ΔArea(max) and Δslope(max) were independent predictive factors for pCR, OR =0.942 (95% CI : 0.918-0.967) and 0.961 (95% CI : 0.940-0.987), respectively. The area under ROC curve (AUC) for the constructed model was 0.886 (95% CI : 0.820-0.951). Decision curve showed that in the range of the threshold probability above 0.4, the predictive model presented increased net benefit as the threshold probability increased. Conclusions: The constructed predictive model for pCR is of potential clinical value, with an AUC>0.85. Meanwhile, decision curve analysis indicates the constructed predictive model has net benefit from 3 to 8 percent in the likely range of probability threshold from 80% to 90%.

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.

Progress of assessment and rehabilitation therapy of cognitive impairment

Directory of Open Access Journals (Sweden)

Yuan-yuan TAO

2017-07-01

Full Text Available  Cognitive impairment is one of major disorders after brain injury. With the rapid development of rehabilitation medicine in China, more and more attention was focused on it. The methods of assessment and rehabilitation therapy of cognitive impairment are more widely used in clinic. Based on traditional methods of assessment and rehabilitation therapy, driven by the development of computer, Internet and Internet of Things, more and more new methods emerged. This article intends to review the commonly used assessment and rehabilitation therapy of cognitive impairment and their progress. DOI: 10.3969/j.issn.1672-6731.2017.05.002

Supporting the Loewenstein occupational therapy cognitive assessment using distributed user interfaces.

Science.gov (United States)

Tesoriero, Ricardo; Gallud Lazaro, Jose A; Altalhi, Abdulrahman H

2017-02-01

Improve the quantity and quality of information obtained from traditional Loewenstein Occupational Therapy Cognitive Assessment Battery systems to monitor the evolution of patients' rehabilitation process as well as to compare different rehabilitation therapies. The system replaces traditional artefacts with virtual versions of them to take advantage of cutting edge interaction technology. The system is defined as a Distributed User Interface (DUI) supported by a display ecosystem, including mobile devices as well as multi-touch surfaces. Due to the heterogeneity of the devices involved in the system, the software technology is based on a client-server architecture using the Web as the software platform. The system provides therapists with information that is not available (or it is very difficult to gather) using traditional technologies (i.e. response time measurements, object tracking, information storage and retrieval facilities, etc.). The use of DUIs allows therapists to gather information that is unavailable using traditional assessment methods as well as adapt the system to patients' profile to increase the range of patients that are able to take this assessment. Implications for Rehabilitation Using a Distributed User Interface environment to carry out LOTCAs improves the quality of the information gathered during the rehabilitation assessment. This system captures physical data regarding patient's interaction during the assessment to improve the rehabilitation process analysis. Allows professionals to adapt the assessment procedure to create different versions according to patients' profile. Improves the availability of patients' profile information to therapists to adapt the assessment procedure.

Usefulness of 99mTc(V)-dimercaptosuccinic acid scintigraphy in the assessment of response to external radiation therapy in soft tissue sarcoma in Giant Schnauzer dog

International Nuclear Information System (INIS)

Chaudhari, P. R.; Mathe, D.; Balogh, L.; Andocs, G.; Janoki, G. A.

2005-01-01

A nine-year-old male black Giant Schnauzer dog was referred for the scintigraphic evaluation with a history of malignant fibrosarcoma with a rapidly growing non painful mass on the left shoulder region quite near to the site of an operation performed four months ago. We carried out oncological scintigraphy using pentavalent 99mT echnetium labelled dimercaptosuccinic acid [ 99mT c(V)-DMSA], a tumour localising radiopharmaceutical agent. The study was performed to assess the margins, vascularity of the tumour and response to the cancer therapy. Uniform intense radiopharmaceutical uptake was observed in the lesion indicating its margins, vascularity and malignant nature. The dog was subjected to external radiation therapy to control the growth of the cancer and to bring the tumour mass to an operable size. The dog was followed up with 99mT c(V)-DMSA scintigraphy pre-irradiation and post-irradiation. Immediately after the post-irradiation scintigraphy, the dog was operated on. During the surgery, resection of the tumour margins was performed carefully using a hand held gamma probe to assure that no tumour tissue was left inside. In conclusion, the authors would like to state that 99mT c(V)-DMSA oncoscintigraphy is valuable in the assessment and evaluation of therapy in canine soft tissue cancer. (author)

Assessment of adherence to visual correction and occlusion therapy in the Infant Aphakia Treatment Study

Directory of Open Access Journals (Sweden)

Carolyn Drews-Botsch

2016-08-01

Full Text Available Occlusion therapy throughout early childhood is believed to be efficacious in treating deprivation amblyopia but has not been rigorously assessed in clinical trials. Further, tools to assess adherence to such therapy over an extended period of time are lacking. Using data from the Infant Aphakia Treatment Study, a randomized clinical trial of treatment for unilateral congenital cataract, we examined the use of quarterly 48-h recall interviews and annual 7-day prospective diaries to assess reported hours of patching in 114 children throughout the first 5 years of life. Consistency of data reported was assessed using correlation coefficients and intraclass correlation coefficients. Both interview and diary data showed excellent consistency with Cronbach’s Alpha’s ranging from 0.69 to 0.88 for hours of patching and 0.60 to 0.73 for hours of sleep. However, caregivers reported somewhat more adherence in prospective diaries than retrospective interviews. Completion rates, on the other hand, were substantially higher for telephone interviews than prospective diaries. For example, four years after surgery response rates to telephone interviews exceeded 75% versus completion rates of only 54% for diaries. In situations where occlusion dose monitors cannot be used for assessing adherence to occlusion therapy, such as in infants or over an extended period of time, quantitative assessments of occlusion therapy can be obtained by parental report, either as a series of prospective diaries or a series of recall interviews.

Desmoid fibromatosis: MRI features of response to systemic therapy

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Sheth, Pooja J.; Subhawong, Ty K. [University of Miami Miller School of Medicine/Jackson Memorial Hospital, Department of Radiology, Miami, FL (United States); Del Moral, Spencer; Wilky, Breelyn A.; Trent, Jonathan C. [University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, Miami, FL (United States); Cohen, Jonathan [Oncology and Radiation Associates, Miami, FL (United States); Rosenberg, Andrew E. [University of Miami Miller School of Medicine, Department of Pathology, Miami, FL (United States); Temple, H.T. [Center for Orthopedic Innovations, Miami, FL (United States)

2016-10-15

Imaging criteria for measuring the response of desmoid fibromatosis to systemic therapy are not well established. We evaluated a series of patients with desmoids who underwent systemic therapy to document magnetic resonance imaging (MRI) features associated with a positive clinical response. This Institutional Review Board-approved retrospective study included 23 patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were categorized as progressive disease, stable, or partial response. Maximum tumor dimension (D{sub max}), approximate tumor volume (V{sub Tumor}), and quantitative tumor T2 hyperintensity and contrast enhancement (relative to muscle) for pre- and post-treatment MRIs were compared. Three lesions progressed, 5 lesions were stable, whereas 21 showed a clinical response. D{sub max} decreased more in responders (mean -11.0 %) than in stable/progressive lesions (mean -3.6 and 0 % respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 27 out of 29 lesions were ''stable,'' including the 3 progressive lesions. In responders, V{sub Tumor} change averaged -29.4 %, but -19.2 % and +32.5 % in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria 14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50-54 % in partial response/stable disease, but only by 10 % in progressive lesions (p = 0.049, t test). Changes in contrast enhancement ranged from -23 % to 0 %, but were not statistically significant among response groups (p = 0.37). Change in T2 hyperintensity showed a positive correlation with volumetric change (r = 0.40). Decreases in volume and T2 hyperintensity reflect the positive response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not sensitive to clinically

How does race/ethnicity influence pharmacological response to asthma therapies?

Science.gov (United States)

Cazzola, Mario; Calzetta, Luigino; Matera, Maria Gabriella; Hanania, Nicola A; Rogliani, Paola

2018-04-01

Our understanding of whether and/or how ethnicity influences pharmacological response to asthma therapies is still very scarce. A possible explanation for the increased asthma treatment failures observed in ethnic and racial minorities receiving asthma therapies is that some of these groups may have a pharmacogenomic predisposition to either nonresponse or to adverse response with a specific class of drugs. However, the effects of ethnicity on pharmacological response to asthma therapies are also, and mainly, determined by socioeconomic and environmental factors to a varying extent, depending on the ethnic groups. Areas covered: Genetic, socioeconomic and environmental factors that can affect the pharmacotherapeutic responses to asthma medications and their link(s) to race/ethnicity have been examined and critically discussed. Expert opinion: Differences in genetic ancestry are definitely non-modifiable factors, but socioeconomic and environmental disadvantages are all factors that can be modified. It is likely that improved outcomes may be achieved when tailored and multifaceted approaches that include home, school, and clinician-based interventions are implemented. Consequently, it is critical to determine if a clinical intervention programme combined with implementation strategies that attempt to reduce inequalities can reduce asthma disparities, including the influence of ethnicity and race on pharmacological response to asthma therapies.

3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

International Nuclear Information System (INIS)

Muruganandham, Manickam; Clerkin, Patrick P.; Smith, Brian J.; Anderson, Carryn M.; Morris, Ann; Capizzano, Aristides A.; Magnotta, Vincent; McGuire, Sarah M.; Smith, Mark C.; Bayouth, John E.; Buatti, John M.

2014-01-01

Purpose: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of

3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Muruganandham, Manickam; Clerkin, Patrick P. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Smith, Brian J. [Department of Biostatistics, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Anderson, Carryn M.; Morris, Ann [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Capizzano, Aristides A.; Magnotta, Vincent [Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); McGuire, Sarah M.; Smith, Mark C.; Bayouth, John E. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Buatti, John M., E-mail: john-buatti@uiowa.edu [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States)

2014-09-01

Purpose: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of

An audit about music therapy assessments and recommendations for adult patients suspected to be in a low awareness state.

Science.gov (United States)

Daveson, Barbara

2010-01-01

In neuro-rehabilitation, the role of music therapy is expanding to include assessment of patients with severely-altered states of consciousness. Diagnosis of these conditions is a complex task for all, and cases of misdiagnosis have been reported. Aggregated findings from 33 music therapy assessments of patients suspected of being in a low awareness state are described and discussed here. The Music Therapy Assessment Tool for Low Awareness States (MATLAS) was used during these assessments. All assessments were offered as part of a specialist multidisciplinary assessment package. A brief description of the patient group is supplied, along with details regarding the assessment tool and the recommendations that followed. In summary, a difference in the time it took to assess patients in vegetative state (VS) as compared to those in minimally conscious state (MCS) was found and, on average, the assessment of those in VS took less time to complete than for those in MCS. A greater range in session length was found for patients in VS, as compared to those in MCS. Generally after the assessments, patients in VS were likely to be admitted to a sensory regulation group administered by a music therapy assistant, supervised by a qualified music therapist, to enable the continued collection of behavioral responses to stimuli. Patients in MCS were admitted to a music therapy treatment program offered by a qualified music therapist. Ongoing work is recommended to advance the assessment and treatment of this patient population, and to consolidate the role of music therapy with this population.

Vectorization of ultrasound-responsive nanoparticles in placental mesenchymal stem cells for cancer therapy.

Science.gov (United States)

Paris, Juan L; de la Torre, Paz; Victoria Cabañas, M; Manzano, Miguel; Grau, Montserrat; Flores, Ana I; Vallet-Regí, María

2017-05-04

A new platform constituted by engineered responsive nanoparticles transported by human mesenchymal stem cells is here presented as a proof of concept. Ultrasound-responsive mesoporous silica nanoparticles are coated with polyethylenimine to favor their effective uptake by decidua-derived mesenchymal stem cells. The responsive-release ability of the designed nanoparticles is confirmed, both in vial and in vivo. In addition, this capability is maintained inside the cells used as carriers. The migration capacity of the nanoparticle-cell platform towards mammary tumors is assessed in vitro. The efficacy of this platform for anticancer therapy is shown against mammary tumor cells by inducing the release of doxorubicin only when the cell vehicles are exposed to ultrasound.

Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy.

Science.gov (United States)

Sabir, Adeel; Schor-Bardach, Rachel; Wilcox, Carol J; Rahmanuddin, Syed; Atkins, Michael B; Kruskal, Jonathan B; Signoretti, Sabina; Raptopoulos, Vassilios D; Goldberg, S Nahum

2008-07-01

The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

Assessment of response to anti-angiogenic targeted therapy in pulmonary metastatic renal cell carcinoma: R2* value as a predictive biomarker

Energy Technology Data Exchange (ETDEWEB)

Wu, Guangyu; Liu, Guiqin; Suo, Shiteng; Liu, Xiaosheng; Xu, Jianrong [Shanghai Jiao Tong University, Department of Radiology, Renji Hospital, School of Medicine, Shanghai (China); Kong, Wen; Zhang, Jin [Shanghai Jiao Tong University, Department of Urinary Surgery, Renji Hospital, School of Medicine, Shanghai (China); Qu, Jianxun [GE Healthcare, Shanghai (China)

2017-09-15

To evaluate the utility of MR R2*-mapping and the optimal time-point for assessing the response of pulmonary metastatic renal cell carcinoma (mRCC) to anti-angiogenic targeted therapy (aATT). The exploration-sample group and the validation-sample group consisted of 22 and 16 patients. The parameters of MR R2*-mapping, including the R2* value at each time-point (R2*{sub base}, R2*{sub 1cyc} and R2*{sub 2cyc}) and change between different time-points (R2*{sub (1cyc-base)/base}, R2*{sub (2cyc-base)/base} and R2*{sub (2cyc-1cyc)/1cyc}), were evaluated with a receiver-operating-characteristic analysis, and a cut-off value derived from the clinical outcome was applied to the Kaplan-Meier method to assess the value of R2* mapping and Response-Evaluation-Criteria in Solid Tumours (RECIST) during treatment evaluation. The inter-, intra-observer agreements and inter-scan consistency were excellent (p > 0.80). For the exploration-sample group, the areas under the curve for the parameters of MR R2* mapping were 0.55, 0.60, 0.83, 0.64, 0.88 and 0.83 for R2*{sub base}, R2*{sub 1cyc}, R2*{sub 2cyc}, R2*{sub (1cyc-base)/base}, R2*{sub (2cyc-base)/base} and R2*{sub (2cyc-1cyc)/1cyc.} For the validation-sample, R2*{sub (2cyc-base)/base} better predicted progression-free survival (p = 0.03) than RECIST and other R2* mapping parameters with a lower p value. Assessing aATT outcome based on changes in the R2* value between baseline and second treatment is more accurate than assessment at other time-points and assessment based on the RECIST. (orig.)

Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of response to therapy and patient outcomes.

Science.gov (United States)

Coutsouvelis, John; Avery, Sharon; Dooley, Michael; Kirkpatrick, Carl; Spencer, Andrew

2018-03-01

Defibrotide is an agent used to treat sinusoidal obstruction syndrome (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim of this study was to evaluate the effectiveness of defibrotide used within institutional guidelines for the treatment of SOS/VOD in patients undergoing haemopoietic stem cell transplantation (HSCT). Data for 23 patients was retrospectively reviewed to evaluate the effectiveness of defibrotide and the utility of response criteria to direct therapy as specified within institution guidelines. Patients met institutional criteria for a diagnosis of SOS/VOD based on predominantly Baltimore criteria and received defibrotide. Stabilisation or improvement in symptoms and biochemical markers was required for continuation of therapy with defibrotide. Overall, 14 patients responded to therapy. Survival at day 100 post HSCT was 70%. Median serum (total) bilirubin concentrations in all evaluable patients had decreased at days 5 and 10 (p defibrotide, there was a decrease in the proportion of patients exhibiting hepatomegaly (p = 0.02), ascites (p Defibrotide to treat SOS/VOD and continued based on attainment of early response was effective management of this condition. Defibrotide should be considered in any consensus protocol providing guidance on the management of SOS/VOD, with future studies considered to assess appropriate time points for response to therapy during treatment.

Theory and Practice of Positive Feminist Therapy: A Culturally Responsive Approach to Divorce Therapy with Chinese Women

Science.gov (United States)

Tzou, Jean Yuh-Jin; Kim, Eunha; Waldheim, Kim

2012-01-01

Positive Feminist Therapy (PFT) is a strength-based culturally responsive therapy model specifically designed for helping Chinese women facing marital conflicts and divorce, integrating Empowerment Feminist Therapy, systems theory, and positive psychology. To help clients become change agents, PFT uses clients' existing strengths to develop…

Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

International Nuclear Information System (INIS)

Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

2010-01-01

Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

Development of the Music Therapy Assessment Tool for Advanced Huntington's Disease: A Pilot Validation Study.

Science.gov (United States)

O'Kelly, Julian; Bodak, Rebeka

2016-01-01

Case studies of people with Huntington's disease (HD) report that music therapy provides a range of benefits that may improve quality of life; however, no robust music therapy assessment tools exist for this population. Develop and conduct preliminary psychometric testing of a music therapy assessment tool for patients with advanced HD. First, we established content and face validity of the Music Therapy Assessment Tool for Advanced HD (MATA-HD) through focus groups and field testing. Second, we examined psychometric properties of the resulting MATA-HD in terms of its construct validity, internal consistency, and inter-rater and intra-rater reliability over 10 group music therapy sessions with 19 patients. The resulting MATA-HD included a total of 15 items across six subscales (Arousal/Attention, Physical Presentation, Communication, Musical, Cognition, and Psychological/Behavioral). We found good construct validity (r ≥ 0.7) for Mood, Communication Level, Communication Effectiveness, Choice, Social Behavior, Arousal, and Attention items. Cronbach's α of 0.825 indicated good internal consistency across 11 items with a common focus of engagement in therapy. The inter-rater reliability (IRR) Intra-Class Coefficient (ICC) scores averaged 0.65, and a mean intra-rater ICC reliability of 0.68 was obtained. Further training and retesting provided a mean of IRR ICC of 0.7. Preliminary data indicate that the MATA-HD is a promising tool for measuring patient responses to music therapy interventions across psychological, physical, social, and communication domains of functioning in patients with advanced HD. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Predicting response to incretin-based therapy

Directory of Open Access Journals (Sweden)

Agrawal N

2011-04-01

Full Text Available Sanjay Kalra1, Bharti Kalra2, Rakesh Sahay3, Navneet Agrawal41Department of Endocrinology, 2Department of Diabetology, Bharti Hospital, Karnal, India; 3Department of Endocrinology, Osmania Medical College, Hyderabad, India; 4Department of Medicine, GR Medical College, Gwalior, IndiaAbstract: There are two important incretin hormones, glucose-dependent insulin tropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1. The biological activities of GLP-1 include stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. GLP-1 appears to have a number of additional effects in the gastrointestinal tract and central nervous system. Incretin based therapy includes GLP-1 receptor agonists like human GLP-1 analogs (liraglutide and exendin-4 based molecules (exenatide, as well as DPP-4 inhibitors like sitagliptin, vildagliptin and saxagliptin. Most of the published studies showed a significant reduction in HbA1c using these drugs. A critical analysis of reported data shows that the response rate in terms of target achievers of these drugs is average. One of the first actions identified for GLP-1 was the glucose-dependent stimulation of insulin secretion from islet cell lines. Following the detection of GLP-1 receptors on islet beta cells, a large body of evidence has accumulated illustrating that GLP-1 exerts multiple actions on various signaling pathways and gene products in the ß cell. GLP-1 controls glucose homeostasis through well-defined actions on the islet ß cell via stimulation of insulin secretion and preservation and expansion of ß cell mass. In summary, there are several factors determining the response rate to incretin therapy. Currently minimal clinical data is available to make a conclusion. Key factors appear to be duration of diabetes, obesity, presence of autonomic neuropathy, resting energy expenditure, plasma glucagon levels and

Response of melanoma to heat and radiation therapy--a review of the literature and experience from The Prince of Wales Hospital, Sydney.

Science.gov (United States)

Mameghan, H; Knittel, T

1988-11-07

Our review of the literature indicates that radiotherapy and/or heat therapy can provide local control of recurrent or metastatic melanoma in a large proportion of patients. This has undoubted value in the local palliation of symptoms and, in the absence of disseminated disease, can be curative. At The Prince of Wales Hospital, Sydney, we have studied the response of melanoma lesions to heat and radiation therapy and have assessed the reaction in the adjacent normal skin. Thirty-two melanoma lesions that were measurable in 12 patients received radiotherapy and heat therapy in different combinations and dose schedules (15 lesions received radiotherapy alone, six lesions received heat therapy alone, and 11 lesions received combined radiation and heat therapy). The acute normal skin reaction was compared between lesions that received single modality radiation or heat therapy and those that received the combination of heat and radiation therapy. A moderate or severe reaction developed at six of the 21 sites that were treated by a single modality, and at four of the 11 sites that received combined heat and radiation therapy (P = 0.7), and all healed within a few days. Evaluation of the melanoma response to therapy was possible only in 26 of the 32 lesions that were treated because two patients died soon after therapy and the response of their six lesions was not evaluable. A complete response occurred in 14 (54%) of 26 lesions and a partial response occurred in 10 (38%) of 26 lesions. The objective response by treatment modality was 10 of 15 lesions for radiotherapy, six of six lesions for heat therapy and eight of 11 lesions for both therapies combined. We conclude that radiotherapy and heat therapy, separately or combined, produce acceptably-low damage to normal tissue and highly-satisfactory local control of melanoma.

Ultrasound Assessment of Carotid Plaque Echogenicity Response to Statin Therapy: A Systematic Review and Meta-Analysis

Science.gov (United States)

Ibrahimi, Pranvera; Jashari, Fisnik; Bajraktari, Gani; Wester, Per; Henein, Michael Y.

2015-01-01

Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS). Results: Nine out of 580 identified studies including 566 patients’ carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%–36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months. Conclusions: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL. PMID:25984600

Electroconvulsive Therapy: A Comprehensive Assessment

Directory of Open Access Journals (Sweden)

Tayfun Zeren

2003-08-01

Full Text Available Electroconvulsive therapy (ECT is one of the most important discoveries of psychiatric treatments. This article comprehensively assesses historical progress, mechanism of actions, practical methods, indications, side effects, complications, drug interactions of ECT and attitudes towards ECT. [Archives Medical Review Journal 2003; 12(4.000: 340-377

Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders

Directory of Open Access Journals (Sweden)

Loftis Jennifer M

2007-01-01

Full Text Available Abstract Background Individuals with substance use disorders (SUDs are at increased risk for hepatitis C viral infection (HCV, and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20 of the Veterans Healthcare Administration (VHA between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN or combination therapy (IFN and ribavirin who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group and patients without a history of SUD (SUD- Group. Results Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%, and if they had genotypes 1 and 4 (39.5% vs. 39.9%. Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8% and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%. Conclusion Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

CT halo sign as an imaging marker for response to adoptive cell therapy in metastatic melanoma with pulmonary metastases

Energy Technology Data Exchange (ETDEWEB)

Shrot, Shai; Apter, Sara [Department of Diagnostic Imaging, Sheba Medical Center, Tel-Hashomer (Israel); Schachter, Jacob; Shapira-Frommer, Ronnie [Sheba Medical Center, The Ella Institute for Melanoma Research and Treatment, Tel Hashomer (Israel); Besser, Michal J. [Sheba Medical Center, The Ella Institute for Melanoma Research and Treatment, Tel Hashomer (Israel); Sackler School of Medicine, Tel Aviv University, Department of Clinical Microbiology and Immunology, Tel Aviv (Israel)

2014-06-15

The halo sign refers to a zone of ground-glass attenuation surrounding a pulmonary nodule. Pulmonary metastatic nodules exhibiting a halo sign are seen mainly in hypervascular tumours. We describe the appearance of a halo sign following treatment of adoptive transfer of autologous tumour-infiltrating lymphocytes (TIL) to melanoma patients with lung metastases. The study included 29 melanoma patients with pulmonary metastases who received TIL therapy. Pre- and post-treatment chest CTs were retrospectively reviewed for the presence of a halo sign and its correlation with therapeutic response. A pulmonary halo sign was not seen in any pre-treatment CT. It was observed in four of 12 patients who responded to the therapy but not in those who failed to respond. Significant differences were found between response ratio in patients in whom post-TIL halo sign appeared compared with those without the halo sign (p = 0.02). The appearance of a CT halo sign in melanoma with lung metastases following TIL therapy may indicate antitumoral effect and a good response to therapy. Our findings emphasize the importance of applying new assessment criteria for immunological anticancer therapies. (orig.)

Assessments in outcome evaluation in aphasia therapy

DEFF Research Database (Denmark)

Isaksen, Jytte; Brouwer, Catherine E.

2015-01-01

Abstract Outcomes of aphasia therapy in Denmark are documented in evaluation sessions in which both the person with aphasia and the speech-language therapist take part. The participants negotiate agreements on the results of therapy. By means of conversation analysis, we study how such agreements...... on therapy outcome are reached interactionally. The sequential analysis of 34 video recordings focuses on a recurrent method for reaching agreements in these outcome evaluation sessions. In and through a special sequence of conversational assessment it is claimed that the person with aphasia has certain...

Inadequate Response to Therapy as a Predictor of Suicide.

Science.gov (United States)

Dahlsgaard, Katherine K.; Beck, Aaron T.; Brown, Gregory K.

1998-01-01

The role of response to cognitive therapy as a predictor of suicide was investigated by comparing 17 outpatients with mood disorders who committed suicide with 17 matched patients who did not commit suicide. Significant differences were found on several variables including higher levels of hopelessness at termination of therapy. (Author/EMK)

Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

Directory of Open Access Journals (Sweden)

Ahmed R

2014-03-01

Full Text Available Rafay Ahmed,1 Matthew J Oborski,2 Misun Hwang,1 Frank S Lieberman,3 James M Mountz11Department of Radiology, 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Neurology and Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies

Importance of Heart Rate During Exercise for Response to Cardiac Resynchronization Therapy

NARCIS (Netherlands)

Maass, Alexander H.; Buck, Sandra; Nieuwland, Wybe; Bruegemann, Johan; Van Veldhuisen, Dirk J.; Van Gelder, Isabelle C.

Background: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. Objectives: To study exercise-related factors predicting response to CRT. Methods: We retrospectively

The advantages and challenges of using FDG PET/CT for response assessment in melanoma in the era of targeted agents and immunotherapy

Energy Technology Data Exchange (ETDEWEB)

Wong, Annie N.M.; McArthur, Grant A. [The Peter MacCallum Cancer Centre, Cancer Medicine, Melbourne (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Hofman, Michael S. [The Peter MacCallum Cancer Centre, Cancer Imaging, Melbourne, VIC (Australia); Hicks, Rodney J. [The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); The Peter MacCallum Cancer Centre, Cancer Imaging, Melbourne, VIC (Australia)

2017-08-15

The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably. In this review, we discuss the mode of action of these emerging therapies and their toxicities to provide a framework for the use of FDG PET/CT in therapeutic response assessment. We propose that the greatest utility of PET in assessment of response to agents that abrogate signalling related to BRAF mutation is for early assessment of resistance, while in anti-CTLA4 therapy, immunological flare can compromise early assessment of response but can identify potentially life-threatening autoimmune reactions. For anti-PD1/PDL1 therapy, the role of FDG PET/CT is more akin to its use in other solid malignancies undergoing treatment with conventional chemotherapy. However, further research is required to optimise the timing of scans and response criteria in this disease. (orig.)

The advantages and challenges of using FDG PET/CT for response assessment in melanoma in the era of targeted agents and immunotherapy

International Nuclear Information System (INIS)

Wong, Annie N.M.; McArthur, Grant A.; Hofman, Michael S.; Hicks, Rodney J.

2017-01-01

The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably. In this review, we discuss the mode of action of these emerging therapies and their toxicities to provide a framework for the use of FDG PET/CT in therapeutic response assessment. We propose that the greatest utility of PET in assessment of response to agents that abrogate signalling related to BRAF mutation is for early assessment of resistance, while in anti-CTLA4 therapy, immunological flare can compromise early assessment of response but can identify potentially life-threatening autoimmune reactions. For anti-PD1/PDL1 therapy, the role of FDG PET/CT is more akin to its use in other solid malignancies undergoing treatment with conventional chemotherapy. However, further research is required to optimise the timing of scans and response criteria in this disease. (orig.)

Optimal dose-response relationships in voice therapy.

Science.gov (United States)

Roy, Nelson

2012-10-01

Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal dose-response relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible "overdosing".

Oral beta-glucan adjuvant therapy converts nonprotective Th2 response to protective Th1 cell-mediated immune response in mammary tumor-bearing mice.

Directory of Open Access Journals (Sweden)

Gordon D Ross

2007-06-01

Full Text Available Beta (1-3-D-glucans were identified almost 40 years ago as biological response modifiers that stimulated tumor rejection. In vitro studies have shown that beta-glucans bind to a lectin domain within complement receptor type 3 (CR3, or to, more recently described dectin-1 a beta-glucan specific receptor, acting mainly on phagocytic cells. In this study, we assessed the intracellular cytokine profiles of peripheral blood lymphocytes from mice bearing mammary tumors receiving i.v. anti-tumor mAbs combined or not with whole glucan particle suspension given orally (WGP, 400 microg every 24 hours. The proportions of T cells producing IL-4 and IFNgamma were determined by flow cytometry. The proportion of T cells producing IL-4 was significantly higher in tumor-bearing mice not receiving beta-glucan-enhanced therapy. Conversely, T cells from mice undergoing beta-glucan-enhanced therapy showed increased production of the Th1 cytokine IFNgamma. The switch from a Th2 to a Th1 response after WGP therapy was possibly mediated by intestinal mucosal macrophages releasing IL-12.

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

Science.gov (United States)

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

Dermatomyositis Leading to Necrotizing Vasculitis: A Perfect Response to Applied Therapy.

Science.gov (United States)

Akbaryan, Mahmood; Darabi, Farideh; Soltani, Zahra

2016-12-01

Dermatomyositis is an idiopathic inflammatory myopathy that cause skin and muscle complications. The ethiology is not understood well yet. Released cytokines including interferon and interleukins are suggested to make inflammatory responses in the skin or muscle. Muscle weakness and skin lesions including heliotrope rash, shawl sign and Gottron's papules are the most common symptoms. A biopsy (muscle or skin) is always the most reliable method for diagnosis. Corticosteroids in association with immunosuppressive agents are used as standard treatment. The patient was a 30 years old woman who got involved with dermatomyositis for 10 years. She has been under therapy with Methotrexate, Prednisolon and Azathioprine until she came to us suffering from progressive skin lesions. Experiments and examinations were normal except the lesions and detected lipoatrophy. Because of immune cells infiltration and observations necrotizing vasculitis was diagnosed. After three month of high dose prednisolon and intravenous cyclophosphamide therapy the lesions vanished remarkable. True and immediate diagnosis gives physicians the chance not only to assess the best treatment but have adequate time to apply the procedure. However shortening the therapy and diminishing morbidity of the disease need more investigations and efforts.

Influence of Immune Responses in Gene/Stem Cell Therapies for Muscular Dystrophies

Directory of Open Access Journals (Sweden)

Andrea Farini

2014-01-01

Full Text Available Muscular dystrophies (MDs are a heterogeneous group of diseases, caused by mutations in different components of sarcolemma, extracellular matrix, or enzymes. Inflammation and innate or adaptive immune response activation are prominent features of MDs. Various therapies under development are directed toward rescuing the dystrophic muscle damage using gene transfer or cell therapy. Here we discussed current knowledge about involvement of immune system responses to experimental therapies in MDs.

Idiopathic lymphocytic pleuritis: radiographic and high-resolution CT appearances and changes in response to therapy in two adults.

LENUS (Irish Health Repository)

O' Donnell, David H

2012-02-01

Inflammatory conditions of the pleura characterized by a predominantly lymphocytic infiltrate are described in several disorders. The commonest underlying aetiologies include tuberculous infection, autoimmune disorders (particularly Sjogren\\'s syndrome), and post coronary artery bypass graft surgery. Idiopathic lymphocytic pleuritis (ILP) is a rare form of diffuse pleural inflammation characterized by extensive lymphocytic infiltration for which no cause is found. Radiological descriptions of ILP are limited. We describe the radiographic and high-resolution computed tomography (HRCT) imaging features and response to corticosteroid therapy of ILP in two adults. Both patients presented with bilateral diffuse pleural thickening of >10 mm thickness extending >10 cm craniocaudally with small focal areas of atelectasis. Both cases demonstrated marked improvement in the degree and extent of pleural thickening and rounded atelectasis following corticosteroid therapy. HRCT provided a useful noninvasive method of assessing disease response to therapy.

Difference of protein 53 expression based on radiation therapy response in cervical cancer

Science.gov (United States)

Pasaribu, H. P.; Lubis, L. I.; Dina, S.; Simanjuntak, R. Y.; Siregar, H. S.; Rivany, R.

2018-03-01

Cervical cancer is one of most common gynecological cancer in women and the leading cause of death in developing countries. An analytic study with the case-control design was conducted to determine the difference of p53 expression based on radiation therapy response in cervical cancer. The study was performed in Obstetric and Gynecology Department and Pathology Department of Adam Malik General Hospital Medan from January to February 2017. 15 paraffin blocks of acervical cancer patient with incomplete response were obtained as study samples, and 15 paraffin blocks of acervical cancer patient with complete response were obtained as control samples, The samples were collected by consecutive sampling, andan immunohistochemical assessment of p53 expression was done to assessapoptosis count and radiation response. Data were analyzed using Kruskal-Wallis with confidence interval 83.5% and pcervical cancer.

Therapy response evaluation with positron emission tomography-computed tomography.

Science.gov (United States)

Segall, George M

2010-12-01

Positron emission tomography-computed tomography with F-18-fluorodeoxyglucose is widely used for evaluation of therapy response in patients with solid tumors but has not been as readily adopted in clinical trials because of the variability of acquisition and processing protocols and the absence of universal response criteria. Criteria proposed for clinical trials are difficult to apply in clinical practice, and gestalt impression is probably accurate in individual patients, especially with respect to the presence of progressive disease and complete response. Semiquantitative methods of determining tissue glucose metabolism, such as standard uptake value, can be a useful descriptor for levels of tissue glucose metabolism and changes in response to therapy if technical quality control measures are carefully maintained. The terms partial response, complete response, and progressive disease are best used in clinical trials in which the terms have specific meanings and precise definitions. In clinical practice, it may be better to use descriptive terminology agreed upon by imaging physicians and clinicians in their own practice. Copyright © 2010. Published by Elsevier Inc.

Comparison of PET metabolic indices for the early assessment of tumour response in metastatic colorectal cancer patients treated by polychemotherapy

Energy Technology Data Exchange (ETDEWEB)

Maisonobe, Jacques-Antoine; Necib, Hatem; Buvat, Irene [IMNC UMR 8165 CNRS - Paris 7 and Paris 11 Universities, Orsay Cedex (France); Garcia, Camilo A.; Vanderlinden, Bruno; Flamen, Patrick [Universite Libre de Bruxelles, Department of Nuclear Medicine, Institut Jules Bordet, Brussels (Belgium); Hendlisz, Alain [Universite Libre de Bruxelles, Department of Gastroenterology, Institut Jules Bordet, Brussels (Belgium)

2013-02-15

To compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. Forty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for PVE, a metabolic volume (MV) and a total lesion glycolysis (TLG). The relative change in each index between the two scans was calculated for each lesion. Lesions were also classified as responding and nonresponding lesions using the Response Evaluation Criteria In Solid Tumours (RECIST) 1.0 measured by contrast-enhanced CT at baseline and 6-8 weeks after starting therapy. Bland-Altman analyses were performed to compare the various indices. Based on the RECIST classification, ROC analyses were used to determine how accurately the indices predicted lesion response to therapy later seen with RECIST. RECIST showed 27 responding and 74 nonresponding lesions. Bland-Altman analyses showed that the four SUV indices uncorrected for PVE could not be used interchangeably, nor could the two SUV corrected for PVE. The areas under the ROC curves (AUC) were not significantly different between the SUV indices not corrected for PVE. The mean SUV change in a lesion better predicted lesion response without than with PVE correction. The AUC was significantly higher for SUV uncorrected for PVE than for the MV, but change in MV provided some information regarding the lesion response to therapy (AUC >0.5). In these mCRC patients, all SUV uncorrected for PVE accurately predicted the tumour response on day 14 after starting therapy as assessed 4 to 6 weeks later (i.e. 6 to 8 weeks after therapy initiation) using the RECIST criteria. Neither correcting SUV for PVE nor measuring TLG improved the assessment of tumour

Therapy evaluation and diagnostic accuracy in neuroendocrine tumours: assessment of radiological methods

International Nuclear Information System (INIS)

Elvin, A.

1993-01-01

The diagnostic accuracy of ultrasonically guided biopsy-gun biopsies was assessed in a group of 47 patients with suspected pancreatic carcinoma. A correct diagnosis was obtained in 44 of the 47 patients (94%). Biopsy-gun biopsy of the pancreas is considered a useful, reliable and non-traumatic method for the diagnosis of pancreatic malignancy. Twenty-five patients with known neuroendocrine tumour disease were biopsied with 1.2 mm and 0.9 mm biopsy-gun needles. The influence of treatment-related fibrosis was also evaluated. The overall diagnostic accuracy with the 0.9 mm needle was 69% as compared to 92% with the 1.2 mm needle. In order to assess the diagnostic accuracy rate for radiologists with different experience of biopsy procedures 175 cases of renal biopsy-gun biopsies were evaluated. No statistical significant difference was found between the different operators. The role of duplex Doppler ultrasound in monitoring interferon treatment-related changes in carcinoid metastases was evaluated. It present duplex Doppler ultrasound does not seem to play a role in the evaluation of tumour therapy in carcinoid patients. Therapy response evaluation was performed with MR imaging in a group of 17 patients with neuroendocrine liver metastases. A significant difference was found between patients responding to and patients with failure of treatment in terms of tumour T1, contrast enhancement and signal intensity ratio. This indicates that MR investigation may be used in therapy monitoring of patients with neuroendocrine metastases. The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 mice to establish a tumour/animal model that would allow the monitoring of changes with MR imaging induced by interferon therapy and to evaluate whether the therapeutic response could be modulated by different interferon dosages. Interferon does not seem to have any prolonged anti-proliferative effect on the LCC-18 tumour cell line when transplanted to

Isotretinoin therapy: Any need for laboratory assessment? | Tallab ...

African Journals Online (AJOL)

Background: Recently studies showed the no need for laboratory follow up of patients on isotretinoin therapy. The aim of this study is to assess this issue. Patients and methods: A retrospective study on 400 patients was performed to analyze the laboratory data before and after isotretinoin therapy of acne vulgaris patients.

FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.

Science.gov (United States)

Horn, Kevin P; Yap, Jeffrey T; Agarwal, Neeraj; Morton, Kathryn A; Kadrmas, Dan J; Beardmore, Britney; Butterfield, Regan I; Boucher, Kenneth; Hoffman, John M

2015-09-03

Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using (18) F-fluorodeoxyglucose (FDG) and (18) F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment. Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy. While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed

Predictors and Moderators of Response to Cognitive Behavioral Therapy and Medication for the Treatment of Binge Eating Disorder

Science.gov (United States)

Grilo, Carlos M.; Masheb, Robin M.; Crosby, Ross D.

2012-01-01

Objective: To examine predictors and moderators of response to cognitive behavioral therapy (CBT) and medication treatments for binge-eating disorder (BED). Method: 108 BED patients in a randomized double-blind placebo-controlled trial testing CBT and fluoxetine treatments were assessed prior, throughout, and posttreatment. Demographic factors,…

Immune response to Taenia solium cysticerci after anti-parasitic therapy.

Science.gov (United States)

Singh, Aloukick K; Singh, Satyendra K; Singh, Amrita; Gupta, Kamlesh K; Khatoon, Jahanarah; Prasad, Amit; Rai, Ravi P; Gupta, Rakesh K; Tripathi, Mukesh; Husain, Nuzhat; Prasad, Kashi N

2015-10-01

Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Integrating Occupational Therapy Specific Assessments in Practice: Exploring Practitioner Experiences

Directory of Open Access Journals (Sweden)

Eric Asaba

2017-01-01

Full Text Available Background. Occupational therapists sometimes find it challenging to integrate client-centered and occupational therapy specific assessments in practice. The aim of this study was to explore the use of occupational therapy specific assessments such as the Assessment of Motor and Process Skills (AMPS among occupational therapists in Sweden and Japan. Methods. Interviews and qualitative thematic analyses were utilized. Findings. Four themes are reported: (1 use it or lose it, (2 simply no space until after hours, (3 biggest barriers can be colleagues, and (4 being more specific: communication. Conclusion. In keeping with previous studies, occupational therapists often find it challenging to implement client-centered and occupation-based assessment tools into practice. However, more work is needed to understand how best practices can be incorporated into a changing occupational therapy daily practice.

Progress of assessment and rehabilitation therapy of cognitive impairment

OpenAIRE

Yuan-yuan TAO; Rong SUN; Lu-ping SONG

2017-01-01

 Cognitive impairment is one of major disorders after brain injury. With the rapid development of rehabilitation medicine in China, more and more attention was focused on it. The methods of assessment and rehabilitation therapy of cognitive impairment are more widely used in clinic. Based on traditional methods of assessment and rehabilitation therapy, driven by the development of computer, Internet and Internet of Things, more and more new methods emerged. This article intends to revie...

Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

International Nuclear Information System (INIS)

Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

2006-01-01

Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma

International Nuclear Information System (INIS)

Gennatas, Spyridon; Stanway, Susana J; Thomas, Robert; Min, Toon; Shah, Riyaz; O’Brien, Mary ER; Popat, Sanjay

2013-01-01

Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy. A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal. Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea

Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

Energy Technology Data Exchange (ETDEWEB)

Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S. [Department of Radiology-JPP 3889, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52246 (United States); Luisiri, A. [Cardinal Glennon Children' s Hospital, St. Louis, Missouri (United States); Garibaldi, L.R. [Children' s Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey (United States); St. Barnabas Medical Center, Livingston, New Jersey (United States)

2000-07-01

Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

International Nuclear Information System (INIS)

Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S.; Luisiri, A.; Garibaldi, L.R.

2000-01-01

Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

Implant therapy in the esthetic zone: smile line assessment.

Science.gov (United States)

Kourkouta, Stella

2011-04-01

Assessment of the smile or lip line is imperative when implant therapy is carried out in the esthetic zone. The smile is generally defined as high, average, or low. Females are reported to have higher lip lines than males, which means that they are at greater risk when placing and restoring implants in the esthetic zone. Maximum upper lip elevation, usually observed during a strained posed smile, should be assessed. This paper discusses some clinical observations and concepts in relation to smile line assessment for implant therapy in the esthetic zone. (Int J Periodontics Restorative Dent 2011;31:195-201.).

Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

National Research Council Canada - National Science Library

Johnson, Leigh G; Rohan, Kelly J

2005-01-01

...), group cognitive-behavioral therapy (CBT), or combination therapy (CBT+LT). Atypical and typical symptoms were assessed using subscales of the Structured Interview Guide for the Hamilton Rating Scale for Depression - SAD Version (SIGH-SAD...

Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids

Science.gov (United States)

2008-08-01

SUBJECT TERMS Cancer therapy by localized immune response, Magneto -rehological Fluids 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...Metastasized Breast Cancer by Localized Therapy utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit Evrensel...2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy utilizing

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

DEFF Research Database (Denmark)

Appelt, A. L.; Ploen, J.; Vogelius, I. R.

2013-01-01

estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...... of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly...

A model for predicting lung cancer response to therapy

International Nuclear Information System (INIS)

Seibert, Rebecca M.; Ramsey, Chester R.; Hines, J. Wesley; Kupelian, Patrick A.; Langen, Katja M.; Meeks, Sanford L.; Scaperoth, Daniel D.

2007-01-01

Purpose: Volumetric computed tomography (CT) images acquired by image-guided radiation therapy (IGRT) systems can be used to measure tumor response over the course of treatment. Predictive adaptive therapy is a novel treatment technique that uses volumetric IGRT data to actively predict the future tumor response to therapy during the first few weeks of IGRT treatment. The goal of this study was to develop and test a model for predicting lung tumor response during IGRT treatment using serial megavoltage CT (MVCT). Methods and Materials: Tumor responses were measured for 20 lung cancer lesions in 17 patients that were imaged and treated with helical tomotherapy with doses ranging from 2.0 to 2.5 Gy per fraction. Five patients were treated with concurrent chemotherapy, and 1 patient was treated with neoadjuvant chemotherapy. Tumor response to treatment was retrospectively measured by contouring 480 serial MVCT images acquired before treatment. A nonparametric, memory-based locally weight regression (LWR) model was developed for predicting tumor response using the retrospective tumor response data. This model predicts future tumor volumes and the associated confidence intervals based on limited observations during the first 2 weeks of treatment. The predictive accuracy of the model was tested using a leave-one-out cross-validation technique with the measured tumor responses. Results: The predictive algorithm was used to compare predicted verse-measured tumor volume response for all 20 lesions. The average error for the predictions of the final tumor volume was 12%, with the true volumes always bounded by the 95% confidence interval. The greatest model uncertainty occurred near the middle of the course of treatment, in which the tumor response relationships were more complex, the model has less information, and the predictors were more varied. The optimal days for measuring the tumor response on the MVCT images were on elapsed Days 1, 2, 5, 9, 11, 12, 17, and 18 during

CT in the assessment of early response to neoadjuvant therapy of colon

DEFF Research Database (Denmark)

Rafaelsen, Søren Rafael; Dam, Claus; Lund-Rasmussen, Vera

tumour invasion and number and size of enlarged lymph nodes were measured before and after the therapy. Results: Mean tumour length was 7.8 cm (95% CI: 5.3–10.4) at baseline and 4.34 cm (95%, CI: 4.0–4.9) after therapy. Mean extramural tumour invasion was 10.6 mm (95% CI: 9.5–11.8) at baseline and 5.7 mm...

Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Kabolizadeh, Peyman, E-mail: peyman.kabolizadeh@beaumont.org [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Chen, Yen-Lin; Liebsch, Norbert [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Hornicek, Francis J.; Schwab, Joseph H. [Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Choy, Edwin [Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Rosenthal, Daniel I. [Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Niemierko, Andrzej; DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

2017-02-01

Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

International Nuclear Information System (INIS)

Kabolizadeh, Peyman; Chen, Yen-Lin; Liebsch, Norbert; Hornicek, Francis J.; Schwab, Joseph H.; Choy, Edwin; Rosenthal, Daniel I.; Niemierko, Andrzej; DeLaney, Thomas F.

2017-01-01

Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

Science.gov (United States)

Peng, Cheng-Liang; Lin, Hua-Ching; Chiang, Wei-Lun; Shih, Ying-Hsia; Chiang, Ping-Fang; Luo, Tsai-Yueh; Cheng, Chun-Chia; Shieh, Ming-Jium

2018-06-09

Photodynamic therapy (PDT) is a new treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. Copyright © 2018. Published by Elsevier B.V.

Application of the cognitive therapy model to initial crisis assessment.

Science.gov (United States)

Calvert, Patricia; Palmer, Christine

2003-03-01

This article provides a background to the development of cognitive therapy and cognitive therapeutic skills with a specific focus on the treatment of a depressive episode. It discusses the utility of cognitive therapeutic strategies to the model of crisis theory and initial crisis assessment currently used by the Community Assessment & Treatment Team of Waitemata District Health Board on the North Shore of Auckland, New Zealand. A brief background to cognitive therapy is provided, followed by a comprehensive example of the use of the Socratic questioning method in guiding collaborative assessment and treatment of suicidality by nurses during the initial crisis assessment.

Pre-treatment amygdala volume predicts electroconvulsive therapy response

NARCIS (Netherlands)

ten Doesschate, Freek; van Eijndhoven, Philip; Tendolkar, Indira; van Wingen, Guido A.; van Waarde, Jeroen A.

2014-01-01

Electroconvulsive therapy (ECT) is an effective treatment for patients with severe depression. Knowledge on factors predicting therapeutic response may help to identify patients who will benefit most from the intervention. Based on the neuroplasticity hypothesis, volumes of the amygdala and

Interim assessment of the experience of fast neutron therapy in Edinburgh

International Nuclear Information System (INIS)

Duncan, W.; Arnott, S.J.

1982-01-01

Clinical studies of fast neutron therapy were started in Edinburgh in March 1977. The treatment facility has an isocentric machine and a fixed horizontal beam. The neutron beam is produced by 15 MeV deuterons on a thick beryllium target. Six hundred and forty-one patients have been included in these studies in the four-year period to March 1981. Randomly controlled trials have been conducted since May 1977 and 376 patients have been recruited in this period. The local tumor response rates and morbidity observed is given for trials of patients with cerebral gliomass, squamous carcinoma of the head and neck region, transitional cell carcinoma of the bladder and adenocarcinoma of the rectum. This interim evaluation does not demonstrate any advantage of fast neutron radiotherapy as compared with photon therapy. However, greater numbers of patients require to be studied and followed-up for longer intervals. A definitive assessment of the randomly controlled clinical trials in Edinburgh should be possible at the end of 1982

Efficacy of multiple anticancer therapies may depend on host immune response

Directory of Open Access Journals (Sweden)

Kritika Karri

2017-06-01

Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

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Hall, Victoria; Johnson, Douglas; Torresi, Joseph

2018-01-01

Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

The Role of 18F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

International Nuclear Information System (INIS)

Choi, Jiyoun; Kim, Hyun Jeong; Jeong, Yong Hyu; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Yong Bae; Kim, Young Tae; Kang, Won Jun

2014-01-01

To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Preand post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/posttreatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5±0.8 and 7.2±4.2/1.9±0.7 for complete responders and 5.7±2.6 and 12.8±6.9/3.7±0.7 for patients with residual tumor (p 18 F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria for cervical cancer in post-CCRT PET/CT might help to detect residual tumor

Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer.

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Glaser, Rebecca L; Dimitrakakis, Constantine

2014-06-01

Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting. To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later. By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone. This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

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Ren, Jun; Gwin, William R; Zhou, Xinna; Wang, Xiaoli; Huang, Hongyan; Jiang, Ni; Zhou, Lei; Agarwal, Pankaj; Hobeika, Amy; Crosby, Erika; Hartman, Zachary C; Morse, Michael A; H Eng, Kevin; Lyerly, H Kim

2017-01-01

Purpose : Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy. Patients and Methods : We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results : Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR β sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients. Conclusions : Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

The reverse remodeling response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

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Martens, Pieter; Beliën, Hanne; Dupont, Matthias; Vandervoort, Pieter; Mullens, Wilfried

2018-05-17

Major classes of medical therapy for heart failure with reduced ejection fraction (HFrEF) induce reverse remodeling. The revere remodeling response to sacubitril/valsartan remains unstudied. We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients with a class I indication (New York heart Association [NYHA]-class II-IV, Left ventricular ejection fraction [LVEF] sacubitril/valsartan were optimized to individual tolerance. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. One-hundred-twenty-five HFrEF patients (66 ± 10 years) were prospectively included. The amount of RAS-blocker before and after switch to sacubitril/valsartan was similar(P = .290), indicating individual optimal dosing of sacubitril/valsartan. Over a median(IQR) follow-up of 118(77-160) days after initiation of sacubitril/valsartan, LVEF improved (29.6 ± 6% vs 34.8 ± 6%; P sacubitril/valsartan leading to more reverse remodeling. Switching therapy in eligible HFrEF patients from a RAS-blocker to sacubitril/valsartan induces beneficial reverse remodeling of both metrics of systolic as diastolic function. © 2018 John Wiley & Sons Ltd.

Lymphocytic Colitis: Pathologic predictors of response to therapy.

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Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

2018-02-13

While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

Science.gov (United States)

Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

2017-09-10

Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

Approach of combined cancer gene therapy and radiation: response of promoters to ionizing radiation

International Nuclear Information System (INIS)

Anstett, A.

2005-09-01

Gene therapy is an emerging cancer treatment modality. We are interested in developing a radiation-inducible gene therapy system to sensitize the tumor vasculature to the effects of ionizing radiation (IR) treatment. An expression system based on irradiation-inducible promoters will drive the expression of anti-tumor genes in the tumor vasculature. Solid tumors are dependent on angio genesis, a process in which new blood vessels are formed from the pre-existing vasculature. Vascular endothelial cells are un transformed and genetically stable, thus avoiding the problem of resistance to the treatments. Vascular endothelial cells may therefore represent a suitable target for this therapeutic gene therapy strategy.The identification of IR-inducible promoters native to endothelial cells was performed by gene expression profiling using cDNA micro array technology. We describe the genes modified by clinically relevant doses of IR. The extension to high doses aimed at studying the effects of total radiation delivery to the tumor. The radio-inductiveness of the genes selected for promoter study was confirmed by RT-PCR. Analysis of the activity of promoters in response to IR was also assessed in a reporter plasmid. We found that authentic promoters cloned onto a plasmid are not suitable for cancer gene therapy due to their low induction after IR. In contrast, synthetic promoters containing repeated sequence-specific binding sites for IR-activated transcription factors such as NF-κB are potential candidates for gene therapy. The activity of five tandemly repeated TGGGGACTTTCCGC elements for NF-κB binding in a luciferase reporter was increased in a dose-dependent manner. Interestingly, the response to fractionated low doses was improved in comparison to the total single dose. Thus, we put present evidence that a synthetic promoter for NF-κB specific binding may have application in the radio-therapeutic treatment of cancer. (author)

PIRATE: pediatric imaging response assessment and targeting environment

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Glenn, Russell; Zhang, Yong; Krasin, Matthew; Hua, Chiaho

2010-02-01

By combining the strengths of various imaging modalities, the multimodality imaging approach has potential to improve tumor staging, delineation of tumor boundaries, chemo-radiotherapy regime design, and treatment response assessment in cancer management. To address the urgent needs for efficient tools to analyze large-scale clinical trial data, we have developed an integrated multimodality, functional and anatomical imaging analysis software package for target definition and therapy response assessment in pediatric radiotherapy (RT) patients. Our software provides quantitative tools for automated image segmentation, region-of-interest (ROI) histogram analysis, spatial volume-of-interest (VOI) analysis, and voxel-wise correlation across modalities. To demonstrate the clinical applicability of this software, histogram analyses were performed on baseline and follow-up 18F-fluorodeoxyglucose (18F-FDG) PET images of nine patients with rhabdomyosarcoma enrolled in an institutional clinical trial at St. Jude Children's Research Hospital. In addition, we combined 18F-FDG PET, dynamic-contrast-enhanced (DCE) MR, and anatomical MR data to visualize the heterogeneity in tumor pathophysiology with the ultimate goal of adaptive targeting of regions with high tumor burden. Our software is able to simultaneously analyze multimodality images across multiple time points, which could greatly speed up the analysis of large-scale clinical trial data and validation of potential imaging biomarkers.

Noninferior response in BRAF{sup V600E} mutant nonmetastatic papillary thyroid carcinoma to radioiodine therapy

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Li, Jiao; Zhao, Teng; Lin, Yansong [Peking Union Medical College Hospital, Department of Nuclear Medicine, Beijing (China); Liang, Jun [Peking University International Hospital, Department of Oncology, Beijing (China)

2016-06-15

As the most frequent and specific genetic alteration in papillary thyroid carcinoma (PTC), BRAF{sup V600E} has an intimate relationship with more invasive tumour and higher postoperative recurrence risk in PTC patients. We investigate the effect of radioactive iodine (RAI) therapy on the clinical outcome in PTC patients with the BRAF{sup V600E} mutation without distant metastases. This retrospective study included PTC 228 patients without distant metastases who underwent total or near-total thyroidectomy and RAI treatment in our hospital from January 2011 to July 2014. The BRAF{sup V600E} status of the primary lesions was determined and the patients were divided into two groups according to the presence of the mutation. Serological and imaging data were collected at a median follow-up of 2.34 years after RAI administration. Suppressed and stimulated thyroglobulin (Tg), Tg antibody, diagnostic whole-body scintigraphy, and other imaging examinations were used to assess clinical outcome, which was defined as excellent response, indeterminate response, biochemical incomplete response and structural incomplete response. The BRAF{sup V600E} mutation was observed in 153 of the 228 patients (67.1 %). The clinicopathological features did not differ between the BRAF{sup V600E} mutatation and wild-type groups except age at diagnosis (P = 0.000), tumour size (P = 0.023) and TNM stage (P = 0.003). Older age and more advanced TNM stage were prevalent in the BRAF{sup V600E} mutatation group, whereas tumours were slightly larger in the BRAF{sup V600E} wild-type group. The response to RAI therapy was evaluated in both the entire series and the patients with a high recurrence risk, and no significant difference in response was found between the BRAF{sup V600E} mutatation and the wild-type groups (P = 0.881 and P = 0.851, respectively). The clinical response to timely postsurgical RAI therapy is not inferior in BRAF{sup V600E} mutation PTC patients without distant metastases, which

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

A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy

Science.gov (United States)

Wangerin, Kristen A.; Muzi, Mark; Peterson, Lanell M.; Linden, Hannah M.; Novakova, Alena; Mankoff, David A.; E Kinahan, Paul

2017-05-01

We developed a method to evaluate variations in the PET imaging process in order to characterize the relative ability of static and dynamic metrics to measure breast cancer response to therapy in a clinical trial setting. We performed a virtual clinical trial by generating 540 independent and identically distributed PET imaging study realizations for each of 22 original dynamic fluorodeoxyglucose (18F-FDG) breast cancer patient studies pre- and post-therapy. Each noise realization accounted for known sources of uncertainty in the imaging process, such as biological variability and SUV uptake time. Four definitions of SUV were analyzed, which were SUVmax, SUVmean, SUVpeak, and SUV50%. We performed a ROC analysis on the resulting SUV and kinetic parameter uncertainty distributions to assess the impact of the variability on the measurement capabilities of each metric. The kinetic macro parameter, K i , showed more variability than SUV (mean CV K i   =  17%, SUV  =  13%), but K i pre- and post-therapy distributions also showed increased separation compared to the SUV pre- and post-therapy distributions (mean normalized difference K i   =  0.54, SUV  =  0.27). For the patients who did not show perfect separation between the pre- and post-therapy parameter uncertainty distributions (ROC AUC  dynamic imaging outperformed SUV in distinguishing metabolic change in response to therapy, ranging from 12 to 14 of 16 patients over all SUV definitions and uptake time scenarios (p  PET imaging.

Automatic multi-modal MR tissue classification for the assessment of response to bevacizumab in patients with glioblastoma

International Nuclear Information System (INIS)

Liberman, Gilad; Louzoun, Yoram; Aizenstein, Orna; Blumenthal, Deborah T.; Bokstein, Felix; Palmon, Mika; Corn, Benjamin W.; Ben Bashat, Dafna

2013-01-01

Background: Current methods for evaluation of treatment response in glioblastoma are inaccurate, limited and time-consuming. This study aimed to develop a multi-modal MRI automatic classification method to improve accuracy and efficiency of treatment response assessment in patients with recurrent glioblastoma (GB). Materials and methods: A modification of the k-Nearest-Neighbors (kNN) classification method was developed and applied to 59 longitudinal MR data sets of 13 patients with recurrent GB undergoing bevacizumab (anti-angiogenic) therapy. Changes in the enhancing tumor volume were assessed using the proposed method and compared with Macdonald's criteria and with manual volumetric measurements. The edema-like area was further subclassified into peri- and non-peri-tumoral edema, using both the kNN method and an unsupervised method, to monitor longitudinal changes. Results: Automatic classification using the modified kNN method was applicable in all scans, even when the tumors were infiltrative with unclear borders. The enhancing tumor volume obtained using the automatic method was highly correlated with manual measurements (N = 33, r = 0.96, p < 0.0001), while standard radiographic assessment based on Macdonald's criteria matched manual delineation and automatic results in only 68% of cases. A graded pattern of tumor infiltration within the edema-like area was revealed by both automatic methods, showing high agreement. All classification results were confirmed by a senior neuro-radiologist and validated using MR spectroscopy. Conclusion: This study emphasizes the important role of automatic tools based on a multi-modal view of the tissue in monitoring therapy response in patients with high grade gliomas specifically under anti-angiogenic therapy

78 FR 70307 - Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy...

Science.gov (United States)

2013-11-25

...] Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products... Assessment of Investigational Cellular and Gene Therapy Products'' dated November 2013. The guidance document... products reviewed by the Office of Cellular, Tissue and Gene Therapies (OCTGT). The product areas covered...

Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

Science.gov (United States)

Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

2017-05-25

Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre

Research into the Development of Voice Assessment in Music Therapy

DEFF Research Database (Denmark)

Storm, Sanne

This study was a research into the development of a voice assessment profile (VOIAS). Already a preliminary literature search showed that no such profile within music therapy existed, and only very sparse research within music therapy focusing on and involving the human voice. The development...

Quantitative Multi-Parametric Magnetic Resonance Imaging of Tumor Response to Photodynamic Therapy.

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Tom J L Schreurs

Full Text Available The aim of this study was to characterize response to photodynamic therapy (PDT in a mouse cancer model using a multi-parametric quantitative MRI protocol and to identify MR parameters as potential biomarkers for early assessment of treatment outcome.CT26.WT colon carcinoma tumors were grown subcutaneously in the hind limb of BALB/c mice. Therapy consisted of intravenous injection of the photosensitizer Bremachlorin, followed by 10 min laser illumination (200 mW/cm2 of the tumor 6 h post injection. MRI at 7 T was performed at baseline, directly after PDT, as well as at 24 h, and 72 h. Tumor relaxation time constants (T1 and T2 and apparent diffusion coefficient (ADC were quantified at each time point. Additionally, Gd-DOTA dynamic contrast-enhanced (DCE MRI was performed to estimate transfer constants (Ktrans and volume fractions of the extravascular extracellular space (ve using standard Tofts-Kermode tracer kinetic modeling. At the end of the experiment, tumor viability was characterized by histology using NADH-diaphorase staining.The therapy induced extensive cell death in the tumor and resulted in significant reduction in tumor growth, as compared to untreated controls. Tumor T1 and T2 relaxation times remained unchanged up to 24 h, but decreased at 72 h after treatment. Tumor ADC values significantly increased at 24 h and 72 h. DCE-MRI derived tracer kinetic parameters displayed an early response to the treatment. Directly after PDT complete vascular shutdown was observed in large parts of the tumors and reduced uptake (decreased Ktrans in remaining tumor tissue. At 24 h, contrast uptake in most tumors was essentially absent. Out of 5 animals that were monitored for 2 weeks after treatment, 3 had tumor recurrence, in locations that showed strong contrast uptake at 72 h.DCE-MRI is an effective tool for visualization of vascular effects directly after PDT. Endogenous contrast parameters T1, T2, and ADC, measured at 24 to 72 h after PDT, are

Rapid and Quantitative Assessment of Cancer Treatment Response Using In Vivo Bioluminescence Imaging

Directory of Open Access Journals (Sweden)

Alnawaz Rehemtulla

2000-01-01

Full Text Available Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating antineoplastic therapies [1 ]. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal [2], subcutaneous, and intravascular [3] cancer models. However, use of this approach for evaluating orthotopic tumor models has not been demonstrated. In this report, the ability of BLI to noninvasively quantitate the growth and therapeuticinduced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luciferase (9LLuc was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryogenically cooled CCD camera and magnetic resonance imaging (MRI, respectively. There was excellent correlation (r=0.91 between detected photons and tumor volume. A quantitative comparison of tumor cell kill determined from serial MRI volume measurements and BLI photon counts following 1,3-bis(2-chloroethyl-1-nitrosourea (BCNU treatment revealed that both imaging modalities yielded statistically similar cell kill values (P=.951. These results provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.

Taming the green-eyed monster: temporal responsivity to cognitive behavioural and cognitive analytic therapy for morbid jealousy.

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Kellett, Stephen; Totterdell, Peter

2013-03-01

Credible evaluations of the psychological treatment of morbid jealousy are rare. The aim of this study was to evaluate temporal responsivity to cognitive behavioural therapy (CBT) and cognitive analytic therapy (CAT) for morbid jealousy. The methodology involved matched A/B single-case experimental designs (SCED) with extended follow-up, in which two patients and their partners completed daily jealousy target symptom items across the phases of the study. Patients also completed traditional psychometric outcome measures at assessment, post-therapy, and at final follow-up. Both patients received the same number of assessment (n = 3), treatment (n = 13), and follow-up (n = 1) sessions.  Autoregressive Integrated Moving Average (ARIMA) models of the patients' daily target symptom jealousy SCED data indicate the effectiveness of the CAT intervention and the ineffectiveness of the CBT intervention, but both therapies produced large effect sizes. The partner of the CBT patient felt less controlled following therapy, whilst the partner of CAT patient did not perceive any change to his partner. The discussion calls for a stronger evidence base for the psychological treatment of morbid jealousy to be constructed and debates the routine measurement of outcomes for partners of morbidly jealous patients. Measuring outcomes for partners of jealous patients is indicated.   CAT shows promise as an intervention for morbid jealousy. The evidence base for the treatment of morbid jealousy requires further development. © 2011 The British Psychological Society.

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.

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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

Neurocysticercosis as an important differential of paradoxical response during antituberculosis therapy in HIV-negative patient

Directory of Open Access Journals (Sweden)

Rivonirina Andry Rakotoarivelo

2011-12-01

Full Text Available Neurocysticercosis can simulate a paradoxical response during antituberculosis therapy with neurological ailments. We report the case of a 31 year-old-man, treated for tuberculous meningitis who developed neurological deficit after nine weeks of early antituberculous therapy. The diagnosis of neurocysticercosis was confirmed by CT scan and cerebrospinal fluid analysis. Neurocysticercosis should be sought as an important differential of paradoxical response during antituberculosis therapy.

Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

Directory of Open Access Journals (Sweden)

Ahmed A Alkhateeb

Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

Socioeconomic status and response to antiretroviral therapy in high-income countries: a literature review.

Science.gov (United States)

Burch, Lisa S; Smith, Colette J; Phillips, Andrew N; Johnson, Margaret A; Lampe, Fiona C

2016-05-15

It has been shown that socioeconomic factors are associated with the prognosis of several chronic diseases; however, there is no recent systematic review of their effect on HIV treatment outcomes. We aimed to review the evidence regarding the existence of an association of socioeconomic status with virological and immunological response to antiretroviral therapy (ART). We systematically searched the current literature using the database PubMed. We identified and summarized original research studies in high-income countries that assessed the association between socioeconomic factors (education, employment, income/financial status, housing, health insurance, and neighbourhood-level socioeconomic factors) and virological response, immunological response, and ART nonadherence among people with HIV-prescribed ART. A total of 48 studies met the inclusion criteria (26 from the United States, six Canadian, 13 European, and one Australian), of which 14, six, and 35 analysed virological, immunological, and ART nonadherence outcomes, respectively. Ten (71%), four (67%), and 23 (66%) of these studies found a significant association between lower socioeconomic status and poorer response, and none found a significant association with improved response. Several studies showed that adjustment for nonadherence attenuated the association between socioeconomic status and ART response. Our review provides strong support that socioeconomic disadvantage is associated with poorer response to ART. However, most studies have been conducted in settings such as the United States without universal free healthcare access. Further study in settings with free access to ART could help assess the impact of socioeconomic status on ART outcomes and the mechanisms by which it operates.

Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

International Nuclear Information System (INIS)

Chapiro, Julius; Savic, Lynn Jeanette; Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois; Lin, MingDe; Lesage, David

2015-01-01

This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

Energy Technology Data Exchange (ETDEWEB)

Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

2015-07-15

This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

A responsive evaluation of mental health treatment in Cambodia: Intentionally addressing poverty to increase cultural responsiveness in therapy.

Science.gov (United States)

Seponski, Desiree M; Lewis, Denise C; Megginson, Maegan C

2014-01-01

Mental health issues are significant contributors to the global burden of disease with the highest incidence in resource poor countries; 90% of those in need of mental health treatment reside in low resource countries but receive only 10% of the world's resources. Cambodia, the eighth least developed country in the world, serves as one example of the need to address mental health concerns in low-income, resource poor countries. The current study utilises responsive evaluation methodology to explore how poverty-stricken Cambodian clients, therapists and supervisors experience Western models of therapy as culturally responsive to their unique needs. Quantitative and qualitative data were triangulated across multiple stakeholders using numerous methods including a focus group, interviews, surveys, case illustrations and live supervision observation and analysed using constant comparative analysis. Emerging findings suggest that poverty, material needs, therapy location and financial situations greatly impact the daily lives and mental health conditions of Cambodians and hinder clients' therapeutic progress. The local community needs and context of poverty greatly hinder clients' therapeutic progress in therapy treatment and when therapy does not directly address the culture of poverty, clients did not experience therapy as valuable despite some temporary decreases in mental health symptoms.

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

International Nuclear Information System (INIS)

Appelt, Ane L.; Pløen, John; Vogelius, Ivan R.; Bentzen, Søren M.; Jakobsen, Anders

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D 50,i , and the normalized dose-response gradient, γ 50,i . Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D 50,TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), γ 50,TRG1 = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D 50,TRG1 and 2 = 72.1 Gy (CI 65.3-94.0 Gy), γ 50,TRG1 and 2 = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

Use of molecular markers for predicting therapy response in cancer patients.

LENUS (Irish Health Repository)

Duffy, Michael J

2012-02-01

Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

Science.gov (United States)

Gravis, Gwenaelle; Faure, Marjorie; Rybikowski, Stanislas; Dermeche, Slimane; Tyran, Marguerite; Calderon, Benoit; Thomassin, Jeanne; Walz, Jochen; Salem, Naji

2015-11-01

Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.

Targeted Proteomics to Assess the Response to Anti-Angiogenic Treatment in Human Glioblastoma (GBM).

Science.gov (United States)

Demeure, Kevin; Fack, Fred; Duriez, Elodie; Tiemann, Katja; Bernard, Amandine; Golebiewska, Anna; Bougnaud, Sébastien; Bjerkvig, Rolf; Domon, Bruno; Niclou, Simone P

2016-02-01

Glioblastoma (GBM) is a highly aggressive primary brain tumor with dismal outcome for affected patients. Because of the significant neo-angiogenesis exhibited by GBMs, anti-angiogenic therapies have been intensively evaluated during the past years. Recent clinical studies were however disappointing, although a subpopulation of patients may benefit from such treatment. We have previously shown that anti-angiogenic targeting in GBM increases hypoxia and leads to a metabolic adaptation toward glycolysis, suggesting that combination treatments also targeting the glycolytic phenotype may be effective in GBM patients. The aim of this study was to identify marker proteins that are altered by treatment and may serve as a short term readout of anti-angiogenic therapy. Ultimately such proteins could be tested as markers of efficacy able to identify patient subpopulations responsive to the treatment. We applied a proteomics approach based on selected reaction monitoring (SRM) to precisely quantify targeted protein candidates, selected from pathways related to metabolism, apoptosis and angiogenesis. The workflow was developed in the context of patient-derived intracranial GBM xenografts developed in rodents and ensured the specific identification of human tumor versus rodent stroma-derived proteins. Quality control experiments were applied to assess sample heterogeneity and reproducibility of SRM assays at different levels. The data demonstrate that tumor specific proteins can be precisely quantified within complex biological samples, reliably identifying small concentration differences induced by the treatment. In line with previous work, we identified decreased levels of TCA cycle enzymes, including isocitrate dehydrogenase, whereas malectin, calnexin, and lactate dehydrogenase A were augmented after treatment. We propose the most responsive proteins of our subset as potential novel biomarkers to assess treatment response after anti-angiogenic therapy that warrant future

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

Science.gov (United States)

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

77 FR 71194 - Draft Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy...

Science.gov (United States)

2012-11-29

...] Draft Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy... Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products,'' dated November... Evaluation (CBER), Office of Cellular, Tissue, and Gene Therapies (OCTGT). The product areas covered by this...

Effectiveness, response, and dropout of dialectical behavior therapy for borderline personality disorder in an inpatient setting.

Science.gov (United States)

Kröger, Christoph; Harbeck, Susanne; Armbrust, Michael; Kliem, Sören

2013-08-01

To examine the effectiveness of dialectical behavior therapy for inpatients with borderline personality disorder (BPD), small sample sizes and, predominantly, tests of statistical significance have been used so far. We studied 1423 consecutively admitted individuals with BPD, who were seeking a 3-month inpatient treatment. They completed the Borderline Symptom List (BSL) as the main outcome measure, and other self-rating measures at pre- and post-treatment. Therapy outcome was defined in three ways: effect size (ES), response based on the reliable change index, and remission compared to the general population symptom level. Non-parametric conditional inference trees were used to predict dropouts. In the pre-post comparison of the BSL, the ES was 0.54 (95% CI: 0.49-0.59). The response rate was 45%; 31% remained unchanged, and 11% deteriorated. Approximately 15% showed a symptom level equivalent to that of the general population. A further 10% of participants dropped out. A predictive impact on dropout was demonstrated by substance use disorders and a younger age at pre-treatment. In future research, follow-up assessments should be conducted to investigate the extent to which response and remission rates at post-treatment remain stable over time. A consistent definition of response appears to be essential for cross-study and cross-methodological comparisons. Copyright © 2013 Elsevier Ltd. All rights reserved.

SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

International Nuclear Information System (INIS)

Campos, D; Peeters, W; Nickel, K; Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M

2015-01-01

Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response

SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

Energy Technology Data Exchange (ETDEWEB)

Campos, D [University of Wisconsin Madison, Madison, WI (United States); Peeters, W [Radboud University Medical Center, Nijmegen, GA (United States); Nickel, K [University of Wisconsin, Madison, WI (United States); Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M [University of Wisconsin, Madison, Wisconsin (United States)

2015-06-15

Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response.

Construction of an Occupational Therapy Screenings Assessment for elderly medical patients

DEFF Research Database (Denmark)

Holsbæk, Jonas

there for demands a validated Occupational Therapy Screening Assessment, that fast and easy can tell if more Occupational Therapy is needed. Aim: The aim of the study is to develop a Screening Assessment which can be used in the Occupational Therapist practice screening Hospitalized Elderly medical inpatients...... by means of the Content Validity Index (CVI) – Questionaire. Result: The result was a Screening Assessment and a Manual, which was built up using ICF and the ADL-Taxonomy as References. The Screening Instrument should be a support for the working Occupational Therapist in their Clinical Reasoning. CVI...

Changes in stimulus and response AC/A ratio with vision therapy in Convergence Insufficiency.

Science.gov (United States)

Singh, Neeraj Kumar; Mani, Revathy; Hussaindeen, Jameel Rizwana

To evaluate the changes in the stimulus and response Accommodative Convergence to Accommodation (AC/A) ratio following vision therapy (VT) in Convergence Insufficiency (CI). Stimulus and response AC/A ratio were measured on twenty five CI participants, pre and post 10 sessions of VT. Stimulus AC/A ratio was measured using the gradient method and response AC/A ratio was calculated using modified Thorington technique with accommodative responses measured using WAM-5500 open-field autorefractor. The gradient stimulus and response AC/A cross-link ratios were compared with thirty age matched controls. Mean age of the CI and control participants were 23.3±5.2 years and 22.7±4.2 years, respectively. The mean stimulus and response AC/A ratio for CI pre therapy was 2.2±0.72 and 6.3±2.0 PD/D that changed to 4.2±0.9 and 8.28±3.31 PD/D respectively post vision therapy and these changes were statistically significant (paired t-test; paccommodation parameters in subjects with convergence insufficiency. This represents the plasticity of the AC/A crosslink ratios that could be achieved with vision therapy in CI. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

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

Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

Science.gov (United States)

Feletar, Marie; Hall, Stephen; Bird, Paul

2016-01-01

To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

Therapy response evaluation of malignant lymphoma in a multicenter study. Comparison of manual and semiautomatic measurements in CT

International Nuclear Information System (INIS)

Wessling, J.; Schuelke, C.; Koch, R.

2014-01-01

Purpose: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. Materials and Methods: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. Results: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. Conclusion: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. (orig.)

Therapy response evaluation of malignant lymphoma in a multicenter study. Comparison of manual and semiautomatic measurements in CT

Energy Technology Data Exchange (ETDEWEB)

Wessling, J.; Schuelke, C. [Muenster Univ. (Germany). Dept. of Clinical Radiology; Koch, R. [Muenster Univ. (Germany). Dept. of Medical Informatics and Biomathematics; and others

2014-08-15

Purpose: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. Materials and Methods: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. Results: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. Conclusion: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. (orig.)

Image Guidance and Assessment of Radiation Induced Gene Therapy

National Research Council Canada - National Science Library

Pelizzari, Charles

2004-01-01

Image guidance and assessment techniques are being developed for combined radiation/gene therapy, which utilizes a radiation-inducible gene promoter to cause expression of tumor necrosis factor alpha...

Pelvic floor muscle assessment outcomes in women with and without provoked vestibulodynia and the impact of a physical therapy program.

Science.gov (United States)

Gentilcore-Saulnier, Evelyne; McLean, Linda; Goldfinger, Corrie; Pukall, Caroline F; Chamberlain, Susan

2010-02-01

Physical therapy (PT) may reduce the pain associated with provoked vestibulodynia (PVD) based on previous findings that pelvic floor muscle dysfunction (PFMD) is associated with PVD symptoms. The goals of this study were: (i) to determine whether women with and without PVD differ on measures of pelvic floor muscle (PFM) behavior; and (ii) to assess the impact of PT treatment for women with PVD on these measures. Eleven women with PVD and 11 control women completed an assessment evaluating PFM behavior using surface electromyography (SEMG) recordings and a digital intravaginal assessment. Women with PVD repeated the assessment after they had undergone eight PT treatment sessions of manual therapy, biofeedback, electrical stimulation, dilator insertions, and home exercises. Superficial and deep PFM SEMG tonic activity and phasic activity in response to a painful pressure stimulus, PFM digital assessment variables (tone, flexibility, relaxation capacity, and strength). At pretreatment, women with PVD had higher tonic SEMG activity in their superficial PFMs compared with the control group, whereas no differences were found in the deep PFMs. Both groups demonstrated contractile responses to the painful pressure stimulus that were significantly higher in the superficial as compared with the deep PFMs, with the responses in the PVD group being higher than those in control women. Women with PVD had higher PFM tone, decreased PFM flexibility and lower PFM relaxation capacity compared with control women. Posttreatment improvements included less PFM responsiveness to pain, less PFM tone, improved vaginal flexibility, and improved PFM relaxation capacity, such that women with PVD no longer differed from controls on these measures. Women with PVD demonstrated altered PFM behavior when compared with controls, providing empirical evidence of PFMD, especially at the superficial layer. A PT rehabilitation program specifically targeting PFMD normalized PFM behavior in women with PVD.

Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

International Nuclear Information System (INIS)

Bernal-Estévez, David; Sánchez, Ramiro; Tejada, Rafael E.; Parra-López, Carlos

2016-01-01

Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells. T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy. We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy. Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in

SU-F-R-56: Early Assessment of Treatment Response During Radiation Therapy Delivery for Esophageal Cancer Using Quantitative CT

Energy Technology Data Exchange (ETDEWEB)

Li, D [Henan Province Tumor Hospital, Zhengzhou, Henan (China); Chen, X; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States); Wu, H [Medical college of Wisconsin, Milwaukee, WI (United States); Wang, J [Henan province Tumor hospital, Zhengzhou, Henan (China)

2016-06-15

Purpose: To investigate the feasibility of assessing treatment response using CTs during delivery of radiation therapy (RT) for esophageal cancer. Methods: Daily CTs acquired using a CT-on-Rails during the routine CT-guided RT for 20 patients with stage II to IV esophageal cancers were analyzed. All patients were treated with combined chemotherapy and IMRT of 45–50 Gy in 25 fractions, and were followed up for two years. Contours of GTV, spinal cord, and non-specified tissue (NST) irradiated with low dose were generated on each daily CT. A series of CT-texture metrics including Hounsfield Unit (HU) histogram, mean HU, standard derivation (STD), entropy, and energy were obtained in these contours on each daily CT. The changes of these metrics and GTV volume during RT delivery were calculated and correlated with treatment outcome. Results: Changes in CT texture (e.g., HU histogram) in GTV and spinal cord (but not in NST) were observed during RT delivery and were consistently increased with radiation dose. For the 20 cases studied, the mean HU in GTV was reduced on average by 4.0HU from the first to the last fractions, while 8 patients (responders) had larger reductions in GTV mean HU (average 7.8 HU) with an average GTV reduction of 51% and had increased consistently in GTV STD and entropy with radiation dose. The rest of 12 patients (non-responders) had lower reductions in GTV mean HU (average 1.5HU) and almost no change in STD and entropy. For the 8 responders, 2 experienced complete response, 7 (88%) survived and 1 died. In contrast, for the 12 non-responders, 4 (33%) survived and 8 died. Conclusion: Radiation can induce changes in CT texture in tumor (e.g., mean HU) during the delivery of RT for esophageal cancer. If validated with more data, such changes may be used for early prediction of RT response for esophageal cancer.

Interstitial brachytherapy for liver metastases and assessment of response by positron emission tomography: a case report

Directory of Open Access Journals (Sweden)

Goura Kishor Rath

2010-10-01

Full Text Available For liver metastases (LM, image guided percutaneous ablative procedures such as radiofrequency ablation (RFA, laser induced thermal therapy (LITT and trans-arterial chemo-embolisation (TACE are increasingly being used because they are relatively safer, less invasive and equally effective. CT scan guided interstitial brachytherapy (IBT with a single large dose of radiation by high dose rate (HDR brachytherapy is a novel technique of treating LM and has shown good results. Positron emission tomography (PET scan may provide better information for assessing the response toIBT procedures. We hereby report a case of LM that was treated by HDR IBT and PET scan was done in addition to CT scan for assessing the response.

Response to pediatric physical therapy in infants with positional preference and skull deformation

NARCIS (Netherlands)

Wijk, R.M. van; Pelsma, M.; Groothuis-Oudshoorn, C.G.; IJzerman, M.J.; Vlimmeren, L.A. van; Boere-Boonekamp, M.M.

2014-01-01

BACKGROUND: Pediatric physical therapy seems to reduce skull deformation in infants with positional preference. However, not all infants show improvement. OBJECTIVE: The study objective was to determine which infant and parent characteristics were related to responses to pediatric physical therapy

The host immunological response to cancer therapy: An emerging concept in tumor biology

International Nuclear Information System (INIS)

Voloshin, Tali; Voest, Emile E.; Shaked, Yuval

2013-01-01

Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome

The host immunological response to cancer therapy: An emerging concept in tumor biology

Energy Technology Data Exchange (ETDEWEB)

Voloshin, Tali [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel); Voest, Emile E. [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Shaked, Yuval, E-mail: yshaked@tx.technion.ac.il [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel)

2013-07-01

Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome.

ANTIPLATELET THERAPY IN THE PREVENTION OF CEREBROVASCULAR ACCIDENTS

Directory of Open Access Journals (Sweden)

O. V. Rodionova

2017-01-01

Full Text Available Currently the problem of preventing cerebrovascular disorders, in which antiplatelet therapy takes one of the leading places, remains relevant. The efficiency of the therapy depends on a large number of modifiable and non-modifiable factors. There are many methods to assess the severity of the response to antiplatelet therapy, but there is no common approach to the assessment of the results and their prognostic significance. Further studies of this issue are essential with the aim of individualization of antiplatelet therapy thereby increasing its efficiency and safety.

Remodeling of Tumor Stroma and Response to Therapy

Energy Technology Data Exchange (ETDEWEB)

Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

2012-03-27

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

Remodeling of Tumor Stroma and Response to Therapy

International Nuclear Information System (INIS)

Johansson, Anna; Ganss, Ruth

2012-01-01

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

Prediction of electroconvulsive therapy response and remission in major depression: Meta-analysis

NARCIS (Netherlands)

Van Diermen, L. (Linda); Van Den Ameele, S. (Seline); A.M. Kamperman (Astrid); Sabbe, B.C.G. (Bernard C.G.); Vermeulen, T. (Tom); Schrijvers, D. (Didier); T.K. Birkenhäger (Tom)

2018-01-01

textabstractElectroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate

Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis Express Increased Inflammatory Responses After Antimony Therapy.

Science.gov (United States)

Costa, Rúbia S; Carvalho, Lucas P; Campos, Taís M; Magalhães, Andréa S; Passos, Sara T; Schriefer, Albert; Silva, Juliana A; Lago, Ednaldo; Paixão, Camilla S; Machado, Paulo; Scott, Phillip; Carvalho, Edgar M

2018-02-14

Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure. A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects. A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

International Nuclear Information System (INIS)

Koritzinsky, Marianne

2015-01-01

Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers

Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

2015-10-01

Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.

Microanalysis on selected video clips with focus on communicative response in music therapy

DEFF Research Database (Denmark)

Ridder, Hanne Mette Ochsner

2007-01-01

This chapter describes a five-step procedure for video analysis where the topic of investigation is the communicative response of clients in music therapy. In this microanalysis procedure only very short video clips are used, and in order to select these clips an overview of each music therapy...... session is obtained with the help of a session-graph that is a systematic way of collecting video observations from one music therapy session and combining the data in one figure. The systematic procedures do not demand sophisticated computer equipment; only standard programmes such as Excel and a media...... player. They are based on individual music therapy work with a population who are difficult to engage in joint activities and who show little response (e.g. persons suffering from severe dementia). The video analysis tools might be relevant to other groups of clients where it is important to form a clear...

Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography

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Schabel, Christoph; Horger, Marius; Kum, Sara [Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Weisel, Katja [Department of Internal Medicine II – Hematology & Oncology, Eberhard-Karls-University Tuebingen, Otfried-Müller-Str. 5, 72076 Tuebingen (Germany); Fritz, Jan [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Baltimore, MD 21287 (United States); Ioanoviciu, Sorin D. [Department of Internal Medicine, Clinical Municipal Hospital Timisoara, Gheorghe Dima Str. 5, 300079 Timisoara (Romania); Bier, Georg, E-mail: georg.bier@med.uni-tuebingen.de [Department of Neuroradiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

2016-12-15

Highlights: • A simplified method for response monitoring of multiple myeloma is proposed. • Medullary bone lesions of all limbs were included and analysed. • Diameters of ≥2 medullary bone lesions are sufficient for therapy monitoring. - Abstract: Introduction: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its time consumption for proper evaluation. Objective: To establish simplified response criteria by correlating size and CT attenuation changes of medullary multiple myeloma lesions in the appendicular skeleton with the course of lytic bone lesions in the entire skeleton. Furthermore to evaluate these criteria with respect to established hematological myeloma-specific parameters for the prediction of treatment response to bortezomib or lenalidomide. Materials and methods: Non-enhanced reduced-dose whole-body CT examinations of 78 consecutive patients (43 male, 35 female, mean age 63.69 ± 9.2 years) with stage III multiple myeloma were retrospectively re-evaluated. On per patient basis, size and mean CT attenuation of 2–4 representative lesions in the limbs were measured at baseline and at a follow-up after a mean of 8 months. Results were compared with the course of lytical bone lesions as well with that of specific hematological biomarkers. Myeloma response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Testing for correlation between response of medullary lesions (Resp

Gender difference in response predictors after 1-year exenatide therapy twice daily in type 2 diabetic patients: a real world experience.

Science.gov (United States)

Anichini, Roberto; Cosimi, Sabrina; Di Carlo, Alberto; Orsini, Paola; De Bellis, Alessandra; Seghieri, Giuseppe; Franconi, Flavia; Baccetti, Fabio

2013-01-01

To investigate whether gender affects therapeutic response by exenatide twice a day (BID) in type 2 diabetes by using a database concerning patients monitored by five outpatient clinics in Tuscany, Italy. We considered a cohort of 315 (154 male/161 female) patients experiencing therapeutic failure while on oral therapy (metformin, or combination therapy metformin + sulphonylureas), who were given exenatide (10 μg/BID) and who fully completed 4 months, 8 months, and 12 months of follow-ups. Among patients stratified by gender and well matched for age, body mass index, and hemoglobin A1c (HbA1c), it was found that the length of disease was longer in females than in males (12 ± 8 years versus 10 ± 7 years; P = 0.037), and the ratio of patients on metformin to those on combination therapy was higher in men (P = 0.018). Target glycemic response (1-year HbA1c ≤ 7%) was achieved in a significantly higher proportion of males than females (38% versus 27%; χ(2) = 4.66; P = 0.03). Target weight loss expressed as 1-year weight percent fall from baseline ≥ 75th percentile (8.5%) was significantly higher in females at 8 and 12 months (P < 0.05; for both). One-year glycemic target response was inversely related to baseline HbA1c levels and diabetes duration among males, while metformin therapy (compared to oral combination therapy) was a significant predictor of better glycemic targets among females. Homeostasis model assessment-B, measured in 117 patients, predicted hypoglycemic response only in women (P = 0.009). Target 1-year weight loss was predicted by longer diabetes duration among males and by lower baseline HbA1c among females. Finally, no significant difference between genders was noted as to gastrointestinal side effects after exenatide therapy. According to this "real world" experience, predictors of glycemic control and body weight loss after 12 months of exenatide BID therapy are different between genders in type 2 diabetes.

Use of regularized principal component analysis to model anatomical changes during head and neck radiation therapy for treatment adaptation and response assessment

International Nuclear Information System (INIS)

Chetvertkov, Mikhail A.; Siddiqui, Farzan; Chetty, Indrin; Kumarasiri, Akila; Liu, Chang; Gordon, J. James; Kim, Jinkoo

2016-01-01

Purpose: To develop standard (SPCA) and regularized (RPCA) principal component analysis models of anatomical changes from daily cone beam CTs (CBCTs) of head and neck (H&N) patients and assess their potential use in adaptive radiation therapy, and for extracting quantitative information for treatment response assessment. Methods: Planning CT images of ten H&N patients were artificially deformed to create “digital phantom” images, which modeled systematic anatomical changes during radiation therapy. Artificial deformations closely mirrored patients’ actual deformations and were interpolated to generate 35 synthetic CBCTs, representing evolving anatomy over 35 fractions. Deformation vector fields (DVFs) were acquired between pCT and synthetic CBCTs (i.e., digital phantoms) and between pCT and clinical CBCTs. Patient-specific SPCA and RPCA models were built from these synthetic and clinical DVF sets. EigenDVFs (EDVFs) having the largest eigenvalues were hypothesized to capture the major anatomical deformations during treatment. Results: Principal component analysis (PCA) models achieve variable results, depending on the size and location of anatomical change. Random changes prevent or degrade PCA’s ability to detect underlying systematic change. RPCA is able to detect smaller systematic changes against the background of random fraction-to-fraction changes and is therefore more successful than SPCA at capturing systematic changes early in treatment. SPCA models were less successful at modeling systematic changes in clinical patient images, which contain a wider range of random motion than synthetic CBCTs, while the regularized approach was able to extract major modes of motion. Conclusions: Leading EDVFs from the both PCA approaches have the potential to capture systematic anatomical change during H&N radiotherapy when systematic changes are large enough with respect to random fraction-to-fraction changes. In all cases the RPCA approach appears to be more

Use of regularized principal component analysis to model anatomical changes during head and neck radiation therapy for treatment adaptation and response assessment

Energy Technology Data Exchange (ETDEWEB)

Chetvertkov, Mikhail A., E-mail: chetvertkov@wayne.edu [Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan 48201 and Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202 (United States); Siddiqui, Farzan; Chetty, Indrin; Kumarasiri, Akila; Liu, Chang; Gordon, J. James [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202 (United States); Kim, Jinkoo [Department of Radiation Oncology, Stony Brook University Hospital, Stony Brook, New York 11794 (United States)

2016-10-15

Purpose: To develop standard (SPCA) and regularized (RPCA) principal component analysis models of anatomical changes from daily cone beam CTs (CBCTs) of head and neck (H&N) patients and assess their potential use in adaptive radiation therapy, and for extracting quantitative information for treatment response assessment. Methods: Planning CT images of ten H&N patients were artificially deformed to create “digital phantom” images, which modeled systematic anatomical changes during radiation therapy. Artificial deformations closely mirrored patients’ actual deformations and were interpolated to generate 35 synthetic CBCTs, representing evolving anatomy over 35 fractions. Deformation vector fields (DVFs) were acquired between pCT and synthetic CBCTs (i.e., digital phantoms) and between pCT and clinical CBCTs. Patient-specific SPCA and RPCA models were built from these synthetic and clinical DVF sets. EigenDVFs (EDVFs) having the largest eigenvalues were hypothesized to capture the major anatomical deformations during treatment. Results: Principal component analysis (PCA) models achieve variable results, depending on the size and location of anatomical change. Random changes prevent or degrade PCA’s ability to detect underlying systematic change. RPCA is able to detect smaller systematic changes against the background of random fraction-to-fraction changes and is therefore more successful than SPCA at capturing systematic changes early in treatment. SPCA models were less successful at modeling systematic changes in clinical patient images, which contain a wider range of random motion than synthetic CBCTs, while the regularized approach was able to extract major modes of motion. Conclusions: Leading EDVFs from the both PCA approaches have the potential to capture systematic anatomical change during H&N radiotherapy when systematic changes are large enough with respect to random fraction-to-fraction changes. In all cases the RPCA approach appears to be more

Effect of cobalt-60 radiation on response to endodontic therapy in monkeys

International Nuclear Information System (INIS)

Matson, J.E.; Patterson, S.S.; Kafrawy, A.H.; Hornback, N.B.; Shidnia, H.

1978-01-01

Response of teeth that had received therapeutic doses of Cobalt-60 radiation to endodontic therapy were investigated in three monkeys. The results indicated no appreciable effect of the irradiation on the response to root canal treatment aside from reduction in osteoblastic activity

Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment.

Science.gov (United States)

2016-01-01

Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians' perception of patients' lived experience, and a modified grounded theory method to analyze information from the survey. For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85-5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14-3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46-212.44; abdominal cramping, relative risk 14.81, 95% CI 2.07-105.97) (GRADE: low). For

18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Eschmann, Susanne M.; Reimold, Matthias; Bares, Roland; Friedel, Godehard; Paulsen, Frank; Hehr, Thomas; Budach, Wilfried; Langen, Heinz-Jakob

2007-01-01

The aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy (NARCT) of advanced non-small cell lung cancer (NSCLC). Seventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NARCT. Changes in FDG uptake and PET findings after completion of NARCT were compared with (1) the histology of tumour samples obtained at surgery or repeat mediastinoscopy, and (2) treatment results in terms of achieved operability and long-term survival. The mean average FDG uptake of the primary tumours in the patient group decreased significantly during NARCT (p = 0.004). Sensitivity, specificity and overall accuracy of FDG-PET were 94.5%, 80% and 91%, respectively, for the detection of residual viable primary tumour, and 77%, 68% and 73%, respectively, for the presence of lymph node metastases. A negative PET scan or a reduction in the standardised uptake value (SUV) of more than 80% was the best predictive factor for a favourable outcome of further treatment. Progressive disease according to PET (new tumour manifestations or increasing SUV) was significantly correlated with an unfavourable outcome (p = 0.005). In this subgroup, survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery, whereas for the whole patient group, complete tumour resection had a significant influence on outcome. FDG-PET is suitable to assess response to NARCT in patients with stage III NSCLC accurately. It was highly predictive for treatment outcome and patient survival. PET may be helpful in improving restaging after NARCT by allowing reliable assessment of residual tumour viability. (orig.)

Response to ovarian stimulation in patients facing gonadotoxic therapy.

Science.gov (United States)

Johnson, Lauren N C; Dillon, Katherine E; Sammel, Mary D; Efymow, Brenda L; Mainigi, Monica A; Dokras, Anuja; Gracia, Clarisa R

2013-04-01

Chemotherapy naïve patients undergoing embryo/oocyte banking for fertility preservation (FP) were assessed for response to ovarian stimulation. Fifty FP patients facing gonadotoxic therapy were matched by age, race, cycle number, date of stimulation and fertilization method to patients undergoing IVF for infertility or oocyte donation. There were no differences in baseline FSH, anti-Müllerian hormone, antral follicle count and total gonadotrophin dose. FP patients had more immature oocytes (2.2 versus 1.1; P=0.03) and lower fertilization rates per oocyte retrieved (52% versus 70%; P=0.002). There were no differences in numbers of oocytes retrieved, mature oocytes or fertilized embryos. Subgroup analysis revealed that FP patients taking letrozole required higher gonadotrophin doses (3077IU versus 2259IU; P=0.0477) and had more immature oocytes (3.4 versus 1.2; P=0.03) than matched controls. There were no differences in gonadotrophin dose or oocyte immaturity among FP patients not taking letrozole. Overall, chemotherapy naïve FP patients had similar ovarian reserve, response to stimulation and oocyte and embryo yield compared to controls. Patients who received letrozole required higher gonadotrophin doses and produced more immature oocytes, suggesting that response to ovarian stimulation may be impaired in patients with hormone-sensitive cancers receiving letrozole. With improvement in cancer survival rates, there has been a shift in attention toward management of long-term consequences of cancer therapy, including infertility. Many young women with cancer, particularly those who will be treated with chemotherapy, pursue fertility preservation (FP) strategies for the purpose of banking oocytes or embryos for future use. We examined patients with no prior exposure to chemotherapy who underwent IVF to freeze embryos or oocytes for FP. Fifty FP patients were identified and matched to healthy controls by age, race, cycle number, date of stimulation and fertilization

A Virtual Clinical Trial of FDG-PET Imaging of Breast Cancer: Effect of Variability on Response Assessment1

OpenAIRE

Harrison, Robert L; Elston, Brian F; Doot, Robert K; Lewellen, Thomas K; Mankoff, David A; Kinahan, Paul E

2014-01-01

INTRODUCTION: There is growing interest in using positron emission tomography (PET) standardized uptake values (SUVs) to assess tumor response to therapy. However, many error sources compromise the ability to detect SUV changes. We explore relationships between these errors and overall SUV variability. METHODS: We used simulations in a virtual clinical trial framework to study impacts of error sources from scanning and analysis effects on assessment of SUV changes. We varied tumor diameter, s...

[Immune response in therapy with allergens and allergoids].

Science.gov (United States)

Kalveram, C M; Kalveram, K J; Kästner, H; Forck, G

1986-02-01

We report on the patterns of specific IgE, IgG, and IgA antibodies during different kinds of hyposensitization. Whereas sIgE antibodies may even be influenced by environmental stimulants, the production of sIgG antibodies depends on the amount of antigens injected for therapy. There is some evidence that patients who do not reveal sIgG response have increased sIgA antibody titers, instead.

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

Science.gov (United States)

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-12-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

International Nuclear Information System (INIS)

Schaefer, Inga-Marie; Hornick, Jason L.; Barysauskas, Constance M.; Raut, Chandrajit P.; Patel, Sagar A.; Royce, Trevor J.; Fletcher, Christopher D.M.; Baldini, Elizabeth H.

2017-01-01

Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score.

Science.gov (United States)

Schaefer, Inga-Marie; Hornick, Jason L; Barysauskas, Constance M; Raut, Chandrajit P; Patel, Sagar A; Royce, Trevor J; Fletcher, Christopher D M; Baldini, Elizabeth H

2017-06-01

To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

Energy Technology Data Exchange (ETDEWEB)

Schaefer, Inga-Marie; Hornick, Jason L. [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Barysauskas, Constance M. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Raut, Chandrajit P. [Division of Surgical Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Patel, Sagar A.; Royce, Trevor J. [Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Fletcher, Christopher D.M. [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

2017-06-01

Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy.

Directory of Open Access Journals (Sweden)

Sulggi A Lee

Full Text Available A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the "reservoir". We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART.We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR; integrated DNA (Alu PCR; unspliced RNA (rtPCR, multiply-spliced RNA (TILDA, residual plasma HIV RNA (single copy PCR, and replication-competent virus (outgrowth assay. We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR. Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables.Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years, the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004 and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003. However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results.Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV during treatment.

Influence of radiation therapy on oral Candida albicans colonization: a quantitative assessment

International Nuclear Information System (INIS)

Rossie, K.M.; Taylor, J.; Beck, F.M.; Hodgson, S.E.; Blozis, G.G.

1987-01-01

An increase in quantity of oral Candida albicans was documented in patients receiving head and neck radiation therapy during and after therapy, as assessed by an oral-rinse culturing technique. The amount of the increase was greater in denture wearers and directly related to increasing radiation dose and increasing volume of parotid gland included in the radiation portal. A significant number of patients who did not carry C. albicans prior to radiation therapy developed positive cultures by 1 month after radiation therapy. The percentage of patients receiving head and neck radiation therapy who carried C. albicans prior to radiation therapy did not differ significantly from matched dental patient controls

Predictors of response to cardiac resynchronization therapy in chronic heart failure patients

Directory of Open Access Journals (Sweden)

Mohamed Loutfi

2016-12-01

Full Text Available Cardiac resynchronization therapy (CRT is established in the management patients with moderate to severe symptoms due to left ventricular systolic dysfunction who present with signs of electrical dyssynchrony. There is wide variability in the clinical response and improvement in LVEF with CRT. Prediction of response to CRT is an important goal in order to tailor this therapy to patients most apt to derive benefit. Aim: The aim of the study was to assess and identify the best predictors of CRT response. Patients and methods: The study included 170 consecutive heart failure (HF patients in New York Heart Association (NYHA functional class III or IV and LVEF ⩽ 35%. Routine device and clinical follow-up, as well as CRT optimization, were performed at baseline and at 3-month intervals. Responders were defined as having an absolute reduction in left ventricular end-systolic diameter >15% and an improvement in LVEF >10%. Results: 170 patients were included [71.1% men; mean age 68.8 ± 9.7 years; 159 patients NYHA class III, 11 patients ambulatory NYHA class IV; 91 patients had non-ischemic cardiomyopathy (ICM – 79 patients had ICM; 55.3% of patients had LBBB; mean QRS duration 145 ± 25 ms; left ventricular ejection fraction 28.38 ± 7.2]. CRT-P was implanted in 65 patients and CRT-D was implanted in 105 patients. CRT response was achieved in 114 patients (67.1%. Mean LVEF improved from 28.38 ± 7.2% to 35.46 ± 9.3% (p = 0.001, mean LV end-diastolic diameter reduced from 67.91 ± 8.7 to 64.95 ± 8.9 mm (p 150 ms, non-ICM, TAPSE >15 mm, sinus rhythm, the absence of COPD and the absence of renal disease were the independent predictors of CRT response. We generated a new CRT score to predict responders to CRT. The score consists of maximum 9 points. The CRT response rate has been markedly different according to the CRT score: CRT response rate was 97.5% patients with CRT score >6 vs 40.7% if CRT score <6, p < 0

Evolution of nodule stiffness might predict response to local ablative therapy: A series of patients with hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Michael Praktiknjo

Full Text Available Early information on treatment response of HCC to local ablative therapy is crucial. Elastography as a non-invasive method has recently been shown to play a potential role in distinguishing between benign and malignant liver lesions. Elastography of hepatocellular carcinoma (HCC in early response to local ablative therapy has not been studied to date.We prospectively included a cohort of 14 patients with diagnosis of HCC who were treated with local ablative therapy (transarterial chemoembolization, TACE and/or radiofrequency ablation, RFA. We used 2D shear-wave elastography (RT 2D-SWE to examine stiffness of HCC lesion before and 3, 30 and 90 days after local ablative therapy. Contrast-enhanced imaging after 90 days was performed to evaluate treatment response. Primary endpoint was stiffness of HCC in response to local ablative therapy. Secondary end point was tumor recurrence.Stiffness of HCC nodules and liver showed no significant difference prior to local ablative therapy. As early as three days after treatment, stiffness of responding HCC was significantly higher compared to non-responding. Higher stiffness before treatment was significantly associated with tumor recurrence.Nodule stiffness in general and RT 2D-SWE in particular could provide a useful tool for early prediction of HCC response to local ablative therapy.

HBV Genotype B/C and Response to Lamivudine Therapy: A Systematic Review

Directory of Open Access Journals (Sweden)

Xiu-Li Chen

2013-01-01

Full Text Available A number of nucleoside analogues such as lamivudine (LAM, actually used for the treatment of chronic hepatitis B, can suppress HBV DNA replication, improve transaminase level and liver histology, and enhance the rate of hepatitis B e antigen (HBeAg clearance. The responses to LAM therapy involve HBeAg clearance and HBV DNA conversion of negative. However, the associations between HBV genotype B/C and response to LAM therapy remain ambiguous. The aim of this meta-analysis is to determine more precise estimations of the relationship. All the publications on the associations between HBV genotype B/C and response to LAM (HBeAg clearance and HBV DNA conversion of negative through June 2013 were collected. Relative risk (RR with 95% confidence intervals (95% CI was calculated in fixed or random model, was calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects with Stata 11 software. Overall, for HBeAg clearance and genotype B/C, the RR (95% CI was 1.27 (0.94–1.71, while for HBV DNA conversion of negative and genotype B/C, the RR (95% CI was 1.07 (0.98–1.17. HBV genotype B/C shows no significance associations with response to lamivudine therapy (HBeAg clearance and HBV DNA conversion of negative.

TH-E-202-00: PET for Radiation Therapy

International Nuclear Information System (INIS)

2016-01-01

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy. The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the

TH-E-202-00: PET for Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy. The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the

Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis.

Science.gov (United States)

Castaldo, Giuseppe; Galdo, Giovanna; Rotondi Aufiero, Felice; Cereda, Emanuele

2016-01-01

Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment

Science.gov (United States)

2016-01-01

Background Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). Methods We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians’ perception of patients’ lived experience, and a modified grounded theory method to analyze information from the survey. Results For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85–5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14–3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46–212.44; abdominal cramping, relative risk 14

Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients

Directory of Open Access Journals (Sweden)

Zhiming Lin

2015-01-01

Full Text Available Objectives. To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. Methods. Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. Results. Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P=0.005, CRP (AUC = 0.75; P=0.017, and ASDAS (AUC = 0.778, P=0.007 significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P=0.040 significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ2=6.87, P=0.009, and wald χ2=5.171, P=0.023. Conclusions. Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients.

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography

Energy Technology Data Exchange (ETDEWEB)

Paul, Jijo; Yang, Cungeng [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wu, Hui [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou (China); Tai, An [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Dalah, Entesar [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Department of Medical Diagnostic Imaging, College of Health Science, University of Sharjah (United Arab Emirates); Zheng, Cheng [Biostatistics, Joseph. J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin (United States); Johnstone, Candice [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Kong, Feng-Ming [Department of Radiation Oncology, Indiana University, Indianapolis, Indiana (United States); Gore, Elizabeth [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

2017-06-01

Purpose: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Methods and Materials: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. Results: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R{sup 2} > 0.99) and correlates weakly with the change in GTV (R{sup 2} = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Conclusion: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.

Childhood asthma clusters and response to therapy in clinical trials.

Science.gov (United States)

Chang, Timothy S; Lemanske, Robert F; Mauger, David T; Fitzpatrick, Anne M; Sorkness, Christine A; Szefler, Stanley J; Gangnon, Ronald E; Page, C David; Jackson, Daniel J

2014-02-01

Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial). In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Our Journal Unites Us: Global Responsibilities and Possibilities for Pediatric Physical Therapy.

Science.gov (United States)

Van Sant, Ann F

2018-04-01

This article was designed to describe personal and social responsibilities for strengthening the science of pediatric physical therapy and effective international research collaboration and communication. Common flaws in research design and analysis are reviewed with recommendations for developing research students' design and analytical skills. Our social responsibility to be informed by global knowledge is highlighted. Barriers to scientific collaboration and communication including international disparities in scientific development and language barriers are presented. Suggestions to reduce these barriers are outlined. The importance of free access to scientific literature in developing countries is reviewed. The journal should assume a leadership role in building a strong science of pediatric physical therapy through encouraging personal and social responsibility in research and serving as a model of international collaboration and communication. Treatment for children with movement disorders will be improved by stronger science, international collaboration, and communication.

A case study of occupational therapy managers in NSW: Roles, responsibilities and work satisfaction.

Science.gov (United States)

Gamble, Jane E; Lincoln, Michelle; Adamson, Barbara

2009-04-01

Job satisfaction has been shown to affect levels of staff retention and productivity, but few studies have been conducted on the work of occupational therapy managers and their job satisfaction. This study explores the roles and responsibilities of occupational therapy managers who are clinician-managers or manager-administrators, and sources of their work satisfaction. A collective case study involved telephone interviews with 16 occupational therapy managers. Semistructured interview questions were based on an earlier discussion with a separate group of occupational therapy managers. Interview transcripts were analysed for emerging themes. There were no clear differences in the roles and responsibilities of the two types of managers (manager-administrators and clinician-managers); however, manager-administrators tended to be responsible for larger numbers of staff. Managers reported that taking a clinical caseload is often at their own discretion. A common challenge for managers is the balancing of priorities as a clinician and a manager. Managing people was a common source of joy and sometimes a source of frustration. Mediating between staff and senior management and the need for budget control and efficiencies was an important aspect of managers' work, as was their autonomy to make decisions. Occupational therapy managers assume responsibilities consistent with clinician managers across disciplines. The main sources of work satisfaction related to people management particularly when staff were working effectively as a team and there was respect from senior management. Further research will confirm whether there are no obvious differences between clinician-manager and manager-administrators, and whether there are clear differences in work-related frustration across sectors.

Non-specific vaginitis: diagnostic features and response to imidazole therapy (metronidazole, ornidazole).

Science.gov (United States)

Meech, R J; Loutit, J

1985-05-22

Detailed quantitative aerobic, anaerobic, fungal and mycoplasma flora was obtained for 43 women presenting with complaints of vaginal discharge and malodour. Clinical response was associated with eradication of the abnormal anaerobic flora, despite persistence of G vaginalis in nine (26%). Topical imidazole therapy appeared to have some advantage over oral therapy. Gram stains of vaginal swabs were found to be the most useful laboratory investigation.

Factors affecting responses of infants with respiratory distress syndrome to exogenous surfactant therapy.

Science.gov (United States)

Ho, N K

1993-02-01

Approximately 20% to 30% of infants with respiratory distress syndrome (RDS) do not respond to surfactant replacement therapy. Unfortunately there is no uniform definition of 'response' or 'non-response' to surfactant therapy. Response was based on improvement in a/A PO2 and/or mean airway pressure (MAP) by some and on improvement in FIO2 and/or MAP by others. Even the point of time at which evaluation of response was done is different in various reports. There is an urgent need to adopt an uniform definition. Most premature babies are surfactant deficient which is the aetiological factor of RDS. Generally good antenatal care and perinatal management are essential in avoidance of premature birth. Babies with lung hypoplasia and who are extremely premature (less than 24 weeks of gestation) do not respond well to exogenous surfactant replacement because of structural immaturity. Prompt management of asphyxiated birth and shock are necessary as there may be negative response to surfactant replacement. Foetal exposure to glucocorticoids improves responsiveness to postnatal administration of surfactant. Antenatal steroid therapy has become an important part of management of RDS with surfactant replacement. The premature lungs with high alveolar permeability tend to develop pulmonary oedema. With the presence of plasma-derived surfactant inhibitors, the response to exogenous surfactant may be affected. These inhibitors may also be released following ventilator barotrauma. The standard of neonatal intensive care such as ventilatory techniques has an important bearing on the outcome of the RDS babies.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostate cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI

International Nuclear Information System (INIS)

Hoetker, Andreas M.; Mazaheri, Yousef; Zheng, Junting; Moskowitz, Chaya S.; Berkowitz, Joshua; Pei, Xin; Zelefsky, Michael J.; Lantos, Joshua E.; Hricak, Hedvig; Akin, Oguz

2015-01-01

To investigate the effects of androgen-deprivation therapy (ADT) on MRI parameters and evaluate their associations with treatment response measures. The study included 30 men with histopathologically confirmed prostate cancer who underwent MRI before and after initiation of ADT. Thirty-four tumours were volumetrically assessed on DW-MRI (n = 32) and DCE-MRI (n = 18), along with regions of interest in benign prostatic tissue, to calculate apparent diffusion coefficient (ADC) and transfer constant (K trans ) values. Changes in MRI parameters and correlations with clinical parameters (change in prostate-specific antigen [PSA], treatment duration, PSA nadir) were assessed. Prostate volume and PSA values decreased significantly with therapy (p < 0.001). ADC values increased significantly in tumours and decreased in benign prostatic tissue (p < 0.05). Relative changes in ADC and absolute post-therapeutic ADC values differed significantly between tumour and benign tissue (p < 0.001). K trans decreased significantly only in tumours (p < 0.001); relative K trans changes and post-therapeutic values were not significantly different between tumour and benign tissue. The relative change in tumour ADC correlated significantly with PSA decrease. No changes were associated with treatment duration or PSA nadir. Multi-parametric MRI shows significant measurable changes in tumour and benign prostate caused by ADT and may help in monitoring treatment response. (orig.)

Relationship between evaluation by quantitative fatty acid myocardial scintigraphy and response to {beta}-blockade therapy in patients with dilated cardiomyopathy

Energy Technology Data Exchange (ETDEWEB)

Ito, Tatsuo; Hoshida, Shiro; Nishino, Masami; Aoi, Toshiyuki; Egami, Yasuyuki; Takeda, Toshihiro; Kawabata, Masayoshi; Tanouchi, Jun; Yamada, Yoshio; Kamada, Takenobu [Div. of Cardiology, Osaka Rosai Hospital (Japan)

2001-12-01

Predicting the effect of {beta}-blockade therapy on the clinical outcome of patients with dilated cardiomyopathy (DCM) is difficult prior to the initiation of therapy. Myocardial fatty acid metabolism has been shown to be impaired in patients with DCM. We examined whether the extent of myocardial injury, as assessed by iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy, is related to the response of patients with DCM to {beta}-blockade therapy. Thirty-seven patients with DCM were examined using BMIPP myocardial scintigraphy before and after 6 months of treatment with metoprolol. Myocardial BMIPP uptake (%BM uptake) was estimated quantitatively as a percentage of the total injected count ratio. The left ventricular end-diastolic and end-systolic dimensions (LVDd, LVDs) and ejection fraction (LVEF) were also evaluated. The patients were divided into two groups according to their functional improvement (>10% elevation of LVEF) after 6 months of metoprolol therapy. Twenty-eight patients responded to the therapy, while nine did not. Prior to the therapy, no significant differences in LVDd, LVDs or LVEF were observed between the responders and non-responders. However, the %BM uptake was significantly lower in the non-responders than in the responders (1.0%{+-}0.2% vs 2.1%{+-}0.5%, P<0.001). The %BM uptake could be used to distinguish the responders from the non-responders with a sensitivity of 0.93 and a specificity of 1.00 at a threshold value of 1.4. After the metoprolol therapy, the %BM uptake improved significantly in the responders (2.5%{+-}0.5%, P<0.01) but did not change in the non-responders. These results indicate that myocardial BMIPP uptake could predict the response of DCM patients to {beta}-blockade therapy. (orig.)

Asthma: Effect of Genotype on Response to Therapy in the Emergency Department

Directory of Open Access Journals (Sweden)

Henderson, Sean

2007-08-01

Full Text Available Objective: We examined the effect of two β2-adrenoreceptor (β2AR polymorphisms (A46G and C79G in asthmatics presenting to the Emergency Department (ED in relation to their response to standard therapy measured by change in Forced Expiratory Volume at one second (FEV1. Our hypothesis was that the polymorphisms in the β2AR gene would predict clinical response to therapy with 46G and 79C displaying decreased response to inhaled therapy. Methods: This was a pilot feasibility study of a convenience sample of patients seen in the ED for acute exacerbation of asthma. Baseline data collected included: age, gender, ethnicity, vital signs, baseline FEV1, body mass index (BMI, smoking history and medications taken prior to arrival to the ED. Patients received standard ED care and FEV1 was measured after each treatment. Blood was taken and genotyped. Results: Fifty-three patients were enrolled over a three-month period. Using mean improvement in FEV1 from baseline to the first treatment as the primary outcome of interest, we performed multivariable linear regression analyses, with the FEV1 change as the dependent variable. When modeled as an ordinal covariate representing the number of G alleles present, there was a significant positive trend for the C79G locus (p=0.035. Those who were GG homozygotes had a 0.284 L/min improvement in FEV1 (31% after their initial albuterol treatment compared to 0.123 L/min (12% in those who were CC homozygotes. This represents a 2.5 times relative difference and a 19% actual difference. Genotypes at the A46G locus were not associated with FEV1 change. Conclusion: In this pilot study of ED patients with acute asthma exacerbation, there was a significant effect of genotype on response to therapy.

Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

Science.gov (United States)

Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

2014-01-01

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

The internal and external responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in patients with prostate cancer.

Science.gov (United States)

Choi, Edmond P H; Wong, Carlos K H; Wan, Eric Y F; Tsu, James H L; Chin, W Y; Kung, Kenny; Yiu, M K

2016-09-01

To examine the responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in prostate cancer patients because there is a lack of evidence to support their responsiveness in this patient population. One hundred sixty-eight subjects with prostate cancer were surveyed at baseline and at 6 months using the SF-12 v2 and FACT-P version 4. Internal responsiveness was assessed using paired t test and generalized estimating equation. External responsiveness was evaluated using receiver operating characteristic curve analysis. The internal responsiveness of the FACT-P and SF-12 v2 to detect positive change was satisfactory. The FACT-P and SF-12 v2 could not detect negative change. The FACT-P and the SF-12 v2 performed the best in distinguishing between improved general health and worsened general health. The FACT-P performed better in distinguishing between unchanged general health and worsened general health. The SF-12 v2 performed better in distinguishing between unchanged general health and improved general health. Positive change detected by these measures should be interpreted with caution as they might be too responsive to detect "noise," which is not clinically significant. The ability of the FACT-P and the SF-12 v2 to detect negative change was disappointing. The internal and external responsiveness of the social well-being of the FACT-P cannot be supported, suggesting that it is not suitable to longitudinally monitor the social component of HRQOL in prostate cancer patients. The study suggested that generic and disease-specific measures should be used together to complement each other.

Prediction of electroconvulsive therapy response and remission in major depression : meta-analysis

OpenAIRE

Diermen, van, Linda; Ameele, van den, Seline; Kamperman, Astrid M.; Sabbe, Bernard G.C.; Vermeulen, Tom; Schrijvers, Didier; Birkenhager, Tom K.

2018-01-01

Abstract: Background Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression. Method A meta-analysis was conducted according to t...

Pretreatment with betamethasone of patients with Graves' disease given radioiodine therapy: thyroid autoantibody responses and outcome of therapy

International Nuclear Information System (INIS)

Gamstedt, A.; Karlsson, A.

1991-01-01

The effects of betamethasone on thyroid autoantibody responses and outcome of radioiodine therapy were determined over a period of 1 yr in a prospective randomized study of 40 patients with Graves' disease. Twenty patients were given placebo tablets, and 20 patients were treated with betamethasone from 3 weeks before until 4 weeks after 131 I therapy. At the time of inclusion in the study, the mean serum concentrations of TSH receptor antibodies, thyroid peroxidase antibodies, and thyroglobulin antibodies (TgAb) were increased in both groups. Three weeks of treatment with betamethasone reduced the thyroid peroxidase antibody and TgAb titers as well as the serum concentrations of thyroid hormones. A decrease in the TSH receptor antibody level was not statistically significant. After radioiodine therapy, transient increases in thyroid autoantibody levels were observed. The titers of the different antibodies generally changed in parallel. In some patients a detectable level of a given antibody was found only after the radioiodine treatment, and in two cases, TgAb did not appear at all, although the two other antibodies increased temporarily. Betamethasone delayed, but did not abolish, the 131 I-induced antibody peaks. Betamethasone also caused a reduction in the total serum immunoglobulin G, a reduction which persisted throughout the study period. When the study ended, 17 patients given placebo and 9 patients given betamethasone were receiving replacement therapy due to the development of hypothyroidism. These patients at this point in time had lower antibody levels than those not requiring T4. The results of this study demonstrate that betamethasone reduces and modifies the thyroid autoantibody responses as well as the outcome of radioiodine therapy in patients with Graves' disease

Music therapy, emotions and the heart: a pilot study.

Science.gov (United States)

Raglio, Alfredo; Oasi, Osmano; Gianotti, Marta; Bellandi, Daniele; Manzoni, Veronica; Goulene, Karine; Imbriani, Chiara; Badiale, Marco Stramba

2012-01-01

The autonomic nervous system plays an important role in the control of cardiac function. It has been suggested that sound and music may have effects on the autonomic control of the heart inducing emotions, concomitantly with the activation of specific brain areas, i.e. the limbic area, and they may exert potential beneficial effects. This study is a prerequisite and defines a methodology to assess the relation between changes in cardiac physiological parameters such as heart rate, QT interval and their variability and the psychological responses to music therapy sessions. We assessed the cardiac physiological parameters and psychological responses to a music therapy session. ECG Holter recordings were performed before, during and after a music therapy session in 8 healthy individuals. The different behaviors of the music therapist and of the subjects have been analyzed with a specific music therapy assessment (Music Therapy Checklist). After the session mean heart rate decreased (p = 0.05), high frequency of heart rate variability tended to be higher and QTc variability tended to be lower. During music therapy session "affect attunements" have been found in all subjects but one. A significant emotional activation was associated to a higher dynamicity and variations of sound-music interactions. Our results may represent the rational basis for larger studies in diferent clinical conditions.

Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

Science.gov (United States)

Geres, Alejandra E; Mereshian, Paula Szafryk; Fernández, Silvia; Rey Caro, Daniel Gonzalo; Castro, Ricardo; Podio, Ricardo; Ojeda, Silvia

2015-12-01

To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT. Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi). Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands. Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Moderators and predictors of response to behavior therapy for tics in Tourette syndrome.

Science.gov (United States)

Sukhodolsky, Denis G; Woods, Douglas W; Piacentini, John; Wilhelm, Sabine; Peterson, Alan L; Katsovich, Lily; Dziura, James; Walkup, John T; Scahill, Lawrence

2017-03-14

To examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders. Data from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9-69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression-Improvement score assessed by masked evaluators. The presence of tic medication significantly moderated response to CBIT vs PST ( p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity ( p = 0.005) and positive participant expectancy ( p = 0.01) predicted greater tic improvement. Anxiety disorders ( p = 0.042) and premonitory urge severity ( p = 0.005) predicted lower tic reduction. Presence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication. The child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respectively). This study provides Class I evidence that

Auditory evoked potentials: predicting speech therapy outcomes in children with phonological disorders

Directory of Open Access Journals (Sweden)

Renata Aparecida Leite

2014-03-01

Full Text Available OBJECTIVES: This study investigated whether neurophysiologic responses (auditory evoked potentials differ between typically developed children and children with phonological disorders and whether these responses are modified in children with phonological disorders after speech therapy. METHODS: The participants included 24 typically developing children (Control Group, mean age: eight years and ten months and 23 children clinically diagnosed with phonological disorders (Study Group, mean age: eight years and eleven months. Additionally, 12 study group children were enrolled in speech therapy (Study Group 1, and 11 were not enrolled in speech therapy (Study Group 2. The subjects were submitted to the following procedures: conventional audiological, auditory brainstem response, auditory middle-latency response, and P300 assessments. All participants presented with normal hearing thresholds. The study group 1 subjects were reassessed after 12 speech therapy sessions, and the study group 2 subjects were reassessed 3 months after the initial assessment. Electrophysiological results were compared between the groups. RESULTS: Latency differences were observed between the groups (the control and study groups regarding the auditory brainstem response and the P300 tests. Additionally, the P300 responses improved in the study group 1 children after speech therapy. CONCLUSION: The findings suggest that children with phonological disorders have impaired auditory brainstem and cortical region pathways that may benefit from speech therapy.

3D-MR Spectroscopic Imaging at 3Tesla for Early Response Assessment of Glioblastoma Patients during External Beam Radiation Therapy

Science.gov (United States)

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-01-01

Purpose To evaluate the utility of 3D-MR proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium enhanced MR images at simulation and at boost treatment planning after 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. MRSI images obtained at initial simulation were analyzed for choline / N-acetylaspartate ratios (Cho/NAA) on a voxel by voxel basis with abnormal activity defined as Cho/NAA ≥ 2. These images were compared on anatomically matched MRSI data collected after 3 weeks of radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. PMID:24986746

A Pilot Study of Mindfulness-based Exposure Therapy in OEF/OIF Combat Veterans with PTSD: Altered Medial Frontal Cortex and Amygdala Responses in Social-Emotional Processing

Directory of Open Access Journals (Sweden)

Anthony King

2016-09-01

Full Text Available Combat-related PTSD is common among returning veterans, and is a serious and debilitating disorder. While highly effective treatments involving trauma exposure exist, difficulties with engagement and early drop may lead to sub-optimal outcomes. Mindfulness training may provide a method for increasing emotional regulation skills that may improve engagement in trauma-focused therapy. Here we examine potential neural correlates of mindfulness training and in vivo exposure (non-trauma focused using a novel group therapy (Mindfulness-based Exposure Therapy in Afghanistan (OEF or Iraq (OIF combat veterans with PTSD. OEF/OIF combat veterans with PTSD (N=23 were treated with MBET (N = 14 or a comparison group therapy (Present-centered group therapy [PCGT], N = 9. PTSD symptoms were assessed at pre- and post-therapy with Clinician Administered PTSD scale (CAPS. Functional neuroimaging (3 Tesla fMRI before and after therapy examined responses to emotional faces (angry, fearful, and neutral faces. Patients treated with MBET had reduced PTSD symptoms (effect size d = .92 but effect was not significantly different from PCGT (d = .43. Improvement in PTSD symptoms from Pre- to Post treatment in both treatment groups was correlated with increased activity in rostral ACC, dorsal medial PFC, and left amygdala. The MBET group showed greater increases in amygdala and fusiform gyrus responses to Angry faces, as well as increased response in left medial PFC to Fearful faces. These preliminary findings provide intriguing evidence that MBET group therapy for PTSD may lead to changes in neural processing of social-emotional threat related to symptom reduction.

Music Therapy Assessment and Development of Parental Competences in Families Where Children Have Experienced Emotional Neglect

DEFF Research Database (Denmark)

Jacobsen, Stine Lindahl

2012-01-01

In trying to aid difficulties within social services of assessing families at risk, the thesis sat out to strengthen, further develop, and test a music therapy assessment tool, Assessment of Parenting Competencies (APC). The study also aimed to examine the effect of music therapy on parenting...

Immunological Response of Hiv-Infected Children to Highly Active Antiretoviral Therapy at Gondar University Hospital, North-Western Ethiopia.

Science.gov (United States)

Kokeb, Mehretie; Degu, Getu

2016-01-01

The effectiveness of highly active antiretroviral therapy (HAART) in children has not been well studied specially in developing countries where the burden of HIV is high. This study was aimed to assess the immunologic response of HIV-infected children to HAART at Pediatric ART Clinic Gondar University Hospital. Institution based cross-sectional study was conducted at the Pediatric ART Clinic Gondar University Hospital from March 01-April 30, 2014. The study included 283 HIV-infected children who were on HAART for 6 months and above. Medical records of HIV-infected children were reviewed using pre-tested questionnaire. CD4 count/percent was collected every 6 months retrospectively. For all statistical significance tests, the cut-off value was pimmunological response. The study revealed that there was good Immunological response to ART, and that the maximum response was in the 1(st) 6 months of ART. Low CD4 count at initiation, undisclosed HIV status and lack of good adherence were found to cause low immunological response to HAART.

Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review.

Science.gov (United States)

García-Castellano, José M; Atallah Yordi, Nagib; Reyes, Carolina; Healey, John H

2012-01-01

Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into "good" and "poor" responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

The Role of {sup 18}F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Choi, Jiyoun; Kim, Hyun Jeong; Jeong, Yong Hyu; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Yong Bae; Kim, Young Tae; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

2014-06-15

To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Preand post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/posttreatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5±0.8 and 7.2±4.2/1.9±0.7 for complete responders and 5.7±2.6 and 12.8±6.9/3.7±0.7 for patients with residual tumor (p < 0.05). The pre-treatment SUVmax and pre-/post-treatment serum SCC levels of the complete responders tended to be lower than those of patients with residual tumor, but this did not have statistical significance. Using ROC analysis, an optimal cutoff SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and 99 %, respectively (p <0.001). Persistent cervical FDG uptake in {sup 18}F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy

Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

Directory of Open Access Journals (Sweden)

Coventry BJ

2012-05-01

Full Text Available Brendon J Coventry, Martin L AshdownDiscipline of Surgery, University of Adelaide, Royal Adelaide Hospital and Faculty of Medicine, University of Melbourne, AustraliaAbstract: Over 50 years of cancer therapy history reveals complete clinical responses (CRs from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained?Over some 20 years, realization that (1 chronic inflammation is intricately associated with cancer, and (2 the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of "final common pathways" of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This "missing" aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer

Contrast-Enhanced Spectral Mammography is Comparable to MRI in the Assessment of Residual Breast Cancer Following Neoadjuvant Systemic Therapy.

Science.gov (United States)

Patel, Bhavika K; Hilal, Talal; Covington, Matthew; Zhang, Nan; Kosiorek, Heidi E; Lobbes, Marc; Northfelt, Donald W; Pockaj, Barbara A

2018-05-01

To evaluate the performance of contrast-enhanced spectral mammography (CESM) compared to MRI in the assessment of tumor response in breast cancer patients undergoing neoadjuvant systemic therapy (NST). The institutional review board approved this study. From September 2014 to June 2017, we identified patients with pathologically confirmed invasive breast cancer who underwent NST. All patients had both CESM and MRI performed pre- and post-NST with pathological assessment after surgical management. Size of residual malignancy on post-NST CESM and MRI was compared with surgical pathology. Lin concordance and Pearson correlation coefficient were used to assess agreement. Bland-Altman plots were used to visualize the differences between tumor size on imaging and pathology. Sixty-five patients were identified. Mean age was 52.7 (range 30-76) years. Type of NST included chemotherapy in 53 (82%) and endocrine therapy in 12 (18%). Mean tumor size after NST was 14.6 (range 0-105) mm for CESM and 14.2 mm (range 0-75 mm) for MRI compared with 19.6 (range 0-100) mm on final surgical pathology. Equivalence tests demonstrated that mean tumor size measured by CESM (p = 0.009) or by MRI (p = 0.01) was equivalent to the mean tumor size measured by pathology within - 1 and 1-cm range. Comparing CESM versus MRI for assessment of complete response, the sensitivity was 95% versus 95%, specificity 66.7% versus 68.9%, positive predictive value 55.9% versus 57.6%, and negative predictive value 96.7% versus 96.9% respectively. CESM was comparable to MRI in assessing residual malignancy after completion of NST.

Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy.

Science.gov (United States)

Williams, Ross; Hudson, John M; Lloyd, Brendan A; Sureshkumar, Ahthavan R; Lueck, Gordon; Milot, Laurent; Atri, Mostafa; Bjarnason, Georg A; Burns, Peter N

2011-08-01

To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US). The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected. In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome. © RSNA, 2011.

Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

Directory of Open Access Journals (Sweden)

Fernanda Vaisman

2011-01-01

Full Text Available BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14. The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up. Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014. The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

Cortisol as a predictor of psychological therapy response in depressive disorders: systematic review and meta-analysis.

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Fischer, Susanne; Strawbridge, Rebecca; Vives, Andres Herane; Cleare, Anthony J

2017-02-01

Many patients with depressive disorders demonstrate resistance to psychological therapy. A frequent finding is hypothalamic-pituitary-adrenal (HPA) axis alterations. As cortisol is known to modulate cognitive processes, those patients may be less likely to profit from psychological therapy. To conduct a systematic review and meta-analysis on cortisol as a predictor of psychological therapy response. The Cochrane Library, EMBASE, MEDLINE and PsycINFO databases were searched. Records were included if they looked at patients with any depressive disorder engaging in psychological therapy, with a pre-treatment cortisol and a post-treatment symptom measure. Eight articles satisfied our selection criteria. The higher the cortisol levels before starting psychological therapy, the more symptoms patients with depression experienced at the end of treatment and/or the smaller their symptom change. Our findings suggest that patients with depression with elevated HPA functioning are less responsive to psychological therapy. © The Royal College of Psychiatrists 2017.

Diabetic foot ulcers. Pathophysiology, assessment, and therapy.

OpenAIRE

Bowering, C. K.

2001-01-01

OBJECTIVE: To review underlying causes of diabetic foot ulceration, provide a practical assessment of patients at risk, and outline an evidence-based approach to therapy for diabetic patients with foot ulcers. QUALITY OF EVIDENCE: A MEDLINE search was conducted for the period from 1979 to 1999 for articles relating to diabetic foot ulcers. Most studies found were case series or small controlled trials. MAIN MESSAGE: Foot ulcers in diabetic patients are common and frequently lead to lower limb...

Fluoride therapy for osteoporosis: characterization of the skeletal response by serial measurements of serum alkaline phosphatase activity.

Science.gov (United States)

Farley, S M; Wergedal, J E; Smith, L C; Lundy, M W; Farley, J R; Baylink, D J

1987-03-01

Optimum use of fluoride therapy for osteoporosis requires a sensitive and convenient index of the skeletal response to fluoride. Since previous studies had shown that serum alkaline phosphatase activity (SALP) was increased in response to fluoride therapy, we examined serial measurements of SALP in 53 osteoporotics treated with 66 to 110 mg of sodium fluoride (NaF) for 12 to 91 months. SALP was increased in 87% of the subjects during therapy with fluoride. The increase in SALP was thought to reflect the osteogenic action of fluoride based on the findings that SALP correlated with both trabecular bone area (r = .81, P less than .001) and osteoid length (r = .67, P less than .01) in iliac crest biopsies, predicted increased bone density on spinal radiographs in response to fluoride therapy with an 87% accuracy, and predicted decreased back pain in response to fluoride with a 91% accuracy. In addition, the SALP response to fluoride was seen earlier than other therapeutic responses as indicated by the findings that the tau 1/2 for the SALP response (ie, time for 1/2 of the patients to show a significant response) was significantly less (1.2 +/- 0.3 yr) than that for the pain response (1.6 +/- 0.3 yr, P less than .05) or that for the radiographic response (3.7 +/- 0.5 yr, P less than .001). Although most patients responded to fluoride with an increase in SALP, evaluation of the kinetics of the SALP response to fluoride revealed marked interpatient variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular responses to radiotherapy and androgendeprivation therapy in experimental prostate cancer

LENUS (Irish Health Repository)

2012-05-23

AbstractBackgroundRadiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC.MethodsUsing mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI.ResultsCompared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after

MRI assessment of early response to certolizumab pegol in rheumatoid arthritis

DEFF Research Database (Denmark)

Østergaard, Mikkel; Jacobsson, L T H; Schaufelberger, C

2015-01-01

OBJECTIVES: To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). METHODS: Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400...

Gallium-67 scintigraphy for monitoring therapy response and follow-up of paracoccidioidomycosis

International Nuclear Information System (INIS)

Yamaga, L.Y.; Watanabe, T.; Hironaka, F.; Buchpiguel, C.; Cerri, G.; Benard, G.; Shikanai-Yasuda, M.A.

2002-01-01

Objectives: The current tools to evaluate patients' therapy response in paracoccidioidomycosis (PCM) are based on clinical, immunological and radiological data. However, these criteria may be of limited value in the follow-up of asymptomatic lesions, negative pre-treatment serological tests and in severe pulmonary involvement whose chest radiography usually doesn't differentiate active from fibrotic lesions. The purpose of this study was to determine the value of Ga imaging for monitoring therapy response and follow-up of PCM patients. Methods: We studied 45 patients with confirmed PCM. Each patient underwent 2 to 7 Ga scintigraphies (total:147 scans) during a follow-up period of 4 months to 8,5 years. The Ga findings were compared to the clinical outcome and serum specific antibody levels. Results: Most patients showed improvement in the sequential Ga scans during the treatment with progressive decrease in number and intensity of sites with active infectious process. Ga scan was performed in nine patients with clinical cure and negative or persistently low levels of serum antibody following prolonged treatment. The scintigraphy confirmed the absence of inflammatory disease in all of these cases. Three patients with clinically suspected recurrence after irregular treatment showed positive Ga scans, confirming disease reactivation. Conclusion: Ga imaging is helpful in monitoring therapy response of PCM patients. Moreover, this method may be used to evaluate disease activity by confirming apparent cure and clinical recurrence

Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

International Nuclear Information System (INIS)

Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

2015-01-01

Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a

Emotional responses to music: towards scientific perspectives on music therapy.

Science.gov (United States)

Suda, Miyuki; Morimoto, Kanehisa; Obata, Akiko; Koizumi, Hideaki; Maki, Atsushi

2008-01-08

Neurocognitive research has the potential to identify the relevant effects of music therapy. In this study, we examined the effect of music mode (major vs. minor) on stress reduction using optical topography and an endocrinological stress marker. In salivary cortisol levels, we observed that stressful conditions such as mental fatigue (thinking and creating a response) was reduced more by major mode music than by minor mode music. We suggest that music specifically induces an emotional response similar to a pleasant experience or happiness. Moreover, we demonstrated the typical asymmetrical pattern of stress responses in upper temporal cortex areas, and suggested that happiness/sadness emotional processing might be related to stress reduction by music.

Genome-wide association study of response to cognitive–behavioural therapy in children with anxiety disorders

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Coleman, Jonathan R. I.; Lester, Kathryn J.; Keers, Robert; Roberts, Susanna; Curtis, Charles; Arendt, Kristian; Bögels, Susan; Cooper, Peter; Creswell, Cathy; Dalgleish, Tim; Hartman, Catharina A.; Heiervang, Einar R.; Hötzel, Katrin; Hudson, Jennifer L.; In-Albon, Tina; Lavallee, Kristen; Lyneham, Heidi J.; Marin, Carla E.; Meiser-Stedman, Richard; Morris, Talia; Nauta, Maaike H.; Rapee, Ronald M.; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Wergeland, Gro Janne; Breen, Gerome; Eley, Thalia C.

2016-01-01

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5 × 10−8) in either analysis. Four variants met criteria for suggestive significance (P<5 × 10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts. PMID:26989097

Prostate cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI

Energy Technology Data Exchange (ETDEWEB)

Hoetker, Andreas M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Universitaetsmedizin Mainz, Department of Diagnostic and Interventional Radiology, Mainz (Germany); Mazaheri, Yousef [Memorial Sloan-Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Zheng, Junting; Moskowitz, Chaya S. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Berkowitz, Joshua; Pei, Xin; Zelefsky, Michael J. [Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States); Lantos, Joshua E.; Hricak, Hedvig; Akin, Oguz [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States)

2015-09-15

To investigate the effects of androgen-deprivation therapy (ADT) on MRI parameters and evaluate their associations with treatment response measures. The study included 30 men with histopathologically confirmed prostate cancer who underwent MRI before and after initiation of ADT. Thirty-four tumours were volumetrically assessed on DW-MRI (n = 32) and DCE-MRI (n = 18), along with regions of interest in benign prostatic tissue, to calculate apparent diffusion coefficient (ADC) and transfer constant (K{sup trans}) values. Changes in MRI parameters and correlations with clinical parameters (change in prostate-specific antigen [PSA], treatment duration, PSA nadir) were assessed. Prostate volume and PSA values decreased significantly with therapy (p < 0.001). ADC values increased significantly in tumours and decreased in benign prostatic tissue (p < 0.05). Relative changes in ADC and absolute post-therapeutic ADC values differed significantly between tumour and benign tissue (p < 0.001). K{sup trans} decreased significantly only in tumours (p < 0.001); relative K{sup trans} changes and post-therapeutic values were not significantly different between tumour and benign tissue. The relative change in tumour ADC correlated significantly with PSA decrease. No changes were associated with treatment duration or PSA nadir. Multi-parametric MRI shows significant measurable changes in tumour and benign prostate caused by ADT and may help in monitoring treatment response. (orig.)

Physiological responses of preterm newborn infants submitted to classical music therapy.

Science.gov (United States)

da Silva, Camila Mendes; Cação, Jessica Marcelle R; Silva, Karin Cristina dos S; Marques, Cassia Fernandes; Merey, Leila Simone F

2013-01-01

To evaluate the physiological effects of music therapy on hospitalized preterm newborns. A noncontrolled clinical trial including 12 newborn infants with gestational age classical music therapy twice a day (morning and afternoon) for three consecutive days. The variables: heart and respiratory rates, oxygen saturation, diastolic and systolic arterial pressures, and body temperature were analyzed before and immediately after each music therapy session. There was a decrease in the heart rate after the second session of music therapy (paired t-test; p=0.002), and an increase at the end of the third session (paired t-test; p=0.005). Respiratory rate decreased during the fourth and fifth sessions (paired t-test; p=0.01 and 0.03, respectively). Regarding oxygen saturation, there was an increase after the fifth session (p=0.008). Comparison of physiological parameters among sessions, for the six studied sessions, showed only that the gain in oxygen saturation during the fifth session was significantly higher than during the sixth one (Tukey's test after variance analysis; p=0.04). Music therapy may modify short-term physiological responses of hospitalized preterm newborn infants.

Study on the effectiveness of Responsive Aggression Regulation Therapy (Re-ART)

NARCIS (Netherlands)

Hoogsteder, L.M.; Kuijpers, N.; Stams, G.J.J.M.; van Horn, J.E.; Hendriks, J.; Wissink, I.B.

2014-01-01

This article describes a pre-test/post-test quasi-experimental study of the effectiveness of Responsive Aggression Regulation Therapy (Re-ART), a Dutch intervention for 16- to 21-year-old juveniles. Re-ART aims to decrease severe aggressive behavior using a cognitive behavioral approach combined

Study on the Effectiveness of Responsive Aggression Regulation Therapy (Re-ART)

NARCIS (Netherlands)

Hoogsteder, L.; Kuijpers, N N; Stams, G.J.J.M.; van Horn, J.; Hendriks, J.; Wissink, I.B.

2014-01-01

This article describes a pre-test/post-test quasi-experimental study of the effectiveness of Responsive Aggression Regulation Therapy (Re-ART), a Dutch intervention for 16- to 21-year-old juveniles. Re-ART aims to decrease severe aggressive behavior using a cognitive behavioral approach combined

Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

Directory of Open Access Journals (Sweden)

Carl K Edwards

2012-12-01

Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

Stimuli-Responsive NO Release for On-Demand Gas-Sensitized Synergistic Cancer Therapy.

Science.gov (United States)

Fan, Wenpei; Yung, Bryant C; Chen, Xiaoyuan

2018-03-08

Featuring high biocompatibility, the emerging field of gas therapy has attracted extensive attention in the medical and scientific communities. Currently, considerable research has focused on the gasotransmitter nitric oxide (NO) owing to its unparalleled dual roles in directly killing cancer cells at high concentrations and cooperatively sensitizing cancer cells to other treatments for synergistic therapy. Of particular note, recent state-of-the-art studies have turned our attention to the chemical design of various endogenous/exogenous stimuli-responsive NO-releasing nanomedicines and their biomedical applications for on-demand NO-sensitized synergistic cancer therapy, which are discussed in this Minireview. Moreover, the potential challenges regarding NO gas therapy are also described, aiming to advance the development of NO nanomedicines as well as usher in new frontiers in this fertile research area. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treating Women Drug Abusers: Action Therapy and Trauma Assessment

Science.gov (United States)

Uhler, Ann S.; Parker, Olga V.

2002-01-01

The authors suggest that action therapy, a group of techniques including psychodrama, drama therapy, and role training, warrants research attention to determine whether it is well suited to the special characteristics and needs of women clients. In addition, the authors call on researchers to develop a new standardized tool for counselors to use during initial interviews to determine whether women presenting for drug abuse treatment also have significant issues related to trauma. The authors believe the use of unassisted clinical judgment for trauma assessment in first interviews may drive patients away by probing for painful information that clients are not yet ready to confront or divulge. PMID:18567963

Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer’s disease cohort

Directory of Open Access Journals (Sweden)

Wattmo Carina

2012-11-01

Full Text Available Abstract Background Activities of daily living (ADL are an essential part of the diagnostic criteria for Alzheimer’s disease (AD. A decline in ADL affects independent living and has a strong negative impact on caregiver burden. Functional response to cholinesterase inhibitor (ChEI treatment and factors that might influence this response in naturalistic AD patients need investigating. The aim of this study was to identify the socio-demographic and clinical factors that affect the functional response after 6 months of ChEI therapy. Methods This prospective, non-randomised, multicentre study in a routine clinical setting included 784 AD patients treated with donepezil, rivastigmine or galantamine. At baseline and after 6 months of treatment, patients were assessed using several rating scales, including the Instrumental Activities of Daily Living (IADL scale, Physical Self-Maintenance Scale (PSMS and Mini-Mental State Examination (MMSE. Demographic and clinical characteristics were investigated at baseline. The functional response and the relationships of potential predictors were analysed using general linear models. Results After 6 months of ChEI treatment, 49% and 74% of patients showed improvement/no change in IADL and in PSMS score, respectively. The improved/unchanged patients exhibited better cognitive status at baseline; regarding improved/unchanged PSMS, patients were younger and used fewer anti-depressants. A more positive functional response to ChEI was observed in younger individuals or among those having the interaction effect of better preserved cognition and lower ADL ability. Patients with fewer concomitant medications or those using NSAIDs/acetylsalicylic acid showed a better PSMS response. Conclusions Critical characteristics that may influence the functional response to ChEI in AD were identified. Some predictors differed from those previously shown to affect cognitive response, e.g., lower cognitive ability and older age

Continuing competence assessment and maintenance in occupational therapy: Scoping review with stakeholder consultation.

Science.gov (United States)

Myers, Christine T; Schaefer, Nancy; Coudron, Ashley

2017-12-01

Continuing competence activities hold the promise of improving health-care service quality, especially given concerns about system inefficiencies and fragmentation. The aim of this scoping review was to describe the assessment and maintenance of occupational therapists' continuing competence and identify knowledge gaps for future research. A secondary aim was comparing scoping review findings with those from other health-care fields and considering possible impact of varying international regulations. A series of database searches retrieved peer-reviewed and grey literature on assessment and maintenance of occupational therapy continuing competence from 1995 to 2015. Themes were developed and findings shared with stakeholders, whose comments drove a second phase: searching for reviews related to continuing competence from allied health, medicine, and nursing, and reviewing websites and documents concerning regulatory requirements for occupational therapy continuing competence in seven English-speaking nations. Twenty-seven sources from the scoping review search met inclusion criteria. Stakeholder consultation validated the themes and preliminary knowledge gaps. Research into other health-care specialties corresponded to findings from the scoping review. The website/document review of occupational therapy regulatory requirements revealed wide variation on both the state/province and national levels. This scoping review highlights gaps in research on effective methods and assessment of occupational therapy continuing competence. Findings suggest a need for research on approaches to continuing competence that incorporate the translation of evidence to practice and address the influence of external factors. Regulatory agencies may address the quality of occupational therapy services by incorporating a variety of professional development options into requirements. © 2017 Occupational Therapy Australia.

Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review

Directory of Open Access Journals (Sweden)

José M. García-Castellano

2012-01-01

Full Text Available Ewing’s sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing’s sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing’s sarcoma into “good” and “poor” responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing’s sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

Science.gov (United States)

Bagby, R Michael; Quilty, Lena C; Segal, Zindel V; McBride, Carolina C; Kennedy, Sidney H; Costa, Paul T

2008-01-01

Objective Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result Four personality traits—the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness—were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. PMID:18616856

SU-F-R-54: CT-Texture Based Early Tumor Treatment Response Assessment During Radiation Therapy Delivery: Small Cell Versus Non-Small Cell Lung Cancers

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Paul, J; Gore, E; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2016-06-15

Purpose: Tumor treatment response may potentially be assessed during radiation therapy (RT) by analyzing changes in CT-textures. We investigated the different early RT-responses between small cell (SCLC) and non-small cell lung cancer (NSCLC) as assessed by CT-texture. Methods: Daily diagnostic-quality CT acquired during routine CT-guided RT using a CT-on-Rails for 13-NSCLC and 5-SCLC patients were analyzed. These patient had ages ranging from 45–78 and 38–63 years, respectively, for NSCLC and SCLC groups, and tumor-stages ranging from T2-T4, and were treated with either RT or chemotherapy and RT with 45–66Gy/ 20–34 fractions. Gross-tumor volume (GTV) contour was generated on each daily CT by populating GTV contour from simulation to daily CTs with manual editing if necessary. CT-texture parameters, such as Hounsfield Unit (HU) histogram, mean HU, skewness, kurtosis, entropy, and short-run high-gray level emphasis (SRHGLE), were calculated in GTV from each daily CT-set using an in house software tool. Difference in changes of these texture parameters during RT between NSCLC and SCLC was analyzed and compared with GTV volume changes. Results: Radiation-induced changes in CT-texture were different between SCLC and NSCLC. Average changes from first to the last fractions for NSCLC and SCLC in GTV were 28±10(12–44) and 30±15(11–47) HU (mean HU reduction), 12.7% and 18.3% (entropy), 50% and 55% (SRHGLE), 19% and 22% (kurtosis), and 5.2% and 22% (skewness), respectively. Good correlation in kurtosis changes and GTV was seen (R{sup 2}=0.8923) for SCLC, but not for NSCLC (R{sup 2}=0.4748). SCLC had better correlations between GTV volume reduction and entropy (SCLC R{sup 2}=0.847; NSCLC R{sup 2}=0.6485), skewness (SCLC R{sup 2}=0.935; NSCLC R{sup 2}=0.7666), or SRHGLE (SCLC R{sup 2}=0.9619; NSCLC R{sup 2}=0.787). Conclusion: NSCLC and SCLC exhibited different early RT-responses as assessed by CT-texture changes during RT-delivery. The observed larger changes in

Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

International Nuclear Information System (INIS)

Coventry, Brendon J; Ashdown, Martin L

2012-01-01

Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained? Over some 20 years, realization that (1) chronic inflammation is intricately associated with cancer, and (2) the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of “final common pathways” of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This “missing” aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer therapy. This aspect has been somewhat obscured and has been “lost in translation” to date

Multisurface Interpersonal Assessment in a Cognitive-Behavioral Therapy Context.

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Dawood, Sindes; Pincus, Aaron L

2016-01-01

The interpersonal paradigm of personality assessment provides a rich nomological net for describing and assessing constructs of interpersonal functioning. The aim of this article is to demonstrate for clinicians how the use of a multisurface interpersonal assessment (MSIA) battery can augment psychotherapy (e.g., cognitive-behavioral therapy). We present 2 clinical case examples and specify interpretative guidelines for MSIA that integrate multiple circumplex profiles (e.g., problems, traits, sensitivities, strengths, values, and efficacies) for each patient. Subsequently, we demonstrate how this approach provides a context to better understand patient symptoms and difficulties, and discuss how it can inform case conceptualization, treatment planning, and intervention.

Response of the oral mucosa to porphyrin mediated boron neutron capture therapy

International Nuclear Information System (INIS)

Morris, G.M.

2003-01-01

Pre-clinical studies are now in progress to develop boron neutron capture therapy (BNCT) modalities for the treatment of head and neck carcinomas. BNCT is a bimodal therapy which involves the administration of a boron-10 enriched compound, that accumulates preferentially in tumours, prior to irradiation with low energy neutrons. These neutrons are captured by boron-10 atoms to produce a highly localised radiation exposure. More recently, it has been demonstrated that various boronated porphyrins can target a variety of tumours. Of the porphyrins evaluated to date, copper tetracarboranylphenyl porphyrin (CuTCPH) is a strong candidate for potential clinical evaluation. It has extremely high specificity for a variety of tumour models. Therapeutic efficacy of CuTCPH mediated BNCT has been demonstrated in pre-clinical studies using the murine EMT-6 carcinoma model. In the present investigation the response of the oral mucosa to CuTCPH mediated boron neutron capture (BNC) irradiation was assessed using a standard rat model (ventral tongue). Single exposure irradiation was carried out on the thermal neutron beam at the Brookhaven Medical Research Reactor, at 3 days after the final injection of the boronated porphyrin. The impact of CuTCPH mediated BNC irradiation on oral mucosa at therapeutically effective exposure times, assessed using the ventral tongue model, was minimal. This was primarily due to the fact that blood boron levels (from CuTCPH) were very low at the time of irradiation. Analysis of the dose-effect data for CuTCPH gave a compound biological effectiveness (CBE) factor of 2.5. It can be concluded that, although, the CBE factor (calculated using blood boron concentrations) was relatively high, CuTCPH mediated BNC irradiation should not cause significant damage at clinically relevant radiation doses. This is because blood boron levels would be very low at the time of irradiation

Delayed response after repeated {sup 177}Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer

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Rahbar, Kambiz; Schaefers, Michael [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Boegeman, Martin [University Hospital Muenster, Department of Urology, Muenster (Germany); Yordanova, Anna; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Eveslage, Maria [University Hospital Muenster, Institute for Biostatistics, Muenster (Germany)

2018-02-15

Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA. Seventy-one patients (median age: 72 years; range 44-87) received 3 cycles of RLT with Lu-PSMA (mean administered activity: 6.016 ± 0.543 GBq) every 8 weeks. Response was evaluated using serum PSA levels and a PSA decline ≥50% was considered as biochemical response. Additionally, any PSA decline after the first cycle was evaluated for further therapy effects after the second and third cycle. A total of 213 cycles were performed in 71 patients. Data for response and adverse events were available for all patients. A PSA decline ≥50% and some PSA decline occurred in 56% and 66% of the patients. Of 30 patients with a PSA response after the first cycle, 28 remained responders and 12/41 of non-responders responded to further therapy cycles. RLT with Lu-177-PSMA-617 shows respectable response rates. In this retrospective analysis, a relevant number of patients showed a delayed response, even if they did not respond to the first cycle of the therapy. (orig.)

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

Science.gov (United States)

Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

2016-01-01

Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize

Predicting fitness-to-drive following stroke using the Occupational Therapy - Driver Off Road Assessment Battery.

Science.gov (United States)

Unsworth, Carolyn A; Baker, Anne; Lannin, Natasha; Harries, Priscilla; Strahan, Janene; Browne, Matthew

2018-02-28

It is difficult to determine if, or when, individuals with stroke are ready to undergo on-road fitness-to-drive assessment. The Occupational Therapy - Driver Off Road Assessment Battery was developed to determine client suitability to resume driving. The predictive validity of the Battery needs to be verified for people with stroke. Examine the predictive validity of the Occupational Therapy - Driver Off Road Assessment Battery for on-road performance among people with stroke. Off-road data were collected from 148 people post stroke on the Battery and the outcome of their on-road assessment was recorded as: fit-to-drive or not fit-to-drive. The majority of participants (76%) were able to resume driving. A classification and regression tree (CART) analysis using four subtests (three cognitive and one physical) from the Battery demonstrated an area under the curve (AUC) of 0.8311. Using a threshold of 0.5, the model correctly predicted 98/112 fit-to-drive (87.5%) and 26/36 people not fit-to-drive (72.2%). The three cognitive subtests from the Occupational Therapy - Driver Off Road Assessment Battery and potentially one of the physical tests have good predictive validity for client fitness-to-drive. These tests can be used to screen client suitability for proceeding to an on-road test following stroke. Implications for Rehabilitation: Following stroke, drivers should be counseled (including consideration of local legislation) concerning return to driving. The Occupational Therapy - Driver Off Road Assessment Battery can be used in the clinic to screen people for suitability to undertake on road assessment. Scores on four of the Occupational Therapy - Driver Off Road Assessment Battery subtests are predictive of resumption of driving following stroke.

Multiple bony metastases of breast cancer. Role of CA 15.3 and response to hormone therapy

International Nuclear Information System (INIS)

Lopez C, Nayara; Ramon G, Natividad; Sanchez M, Jose Ignacio; De Santiago G, Javier

2012-01-01

Bone metastases are involved in a 65-75% of advanced metastatic breast cancer cases. Tumoral markers (CEA, CA 15.3) are useful in the follow-up and evaluation of response to treatment. Hormonal therapy is the optimal treatment option in low grade metastatic breast cancer due to low toxicity and general long term good response. We present a breast cancer case treated with surgery, chemotherapy and radiotherapy. The patient was asymptomatic during the follow-up and multiple bone metastases were diagnosed as a result of an increased CA 15.3 marker found. Hormone therapy was the recommended initial treatment with good response and tolerance. Bone lesions remained stabilized for 7 years but after treatment suspension new bone lesions appeared. CA 15.3 marker had increased again. Reintroduction of hormonal therapy achieved again the stabilization of the lesions

Assessment of the psychopathological effects of a horticultural therapy program in patients with schizophrenia.

Science.gov (United States)

Oh, Yun-Ah; Park, Sin-Ae; Ahn, Byung-Eun

2018-02-01

This study assessed the psychopathological effects of participation in a 10-session horticultural therapy program in patients with schizophrenia. The study design was pre and post test design of experimental and control groups. Twenty-eight Korean patients with schizophrenia, recruited from a mental health clinic and two mental health rehabilitation centers in Suwon, South Korea, were voluntarily assigned to either a control group (average age: 33.4±9.4years) or a horticultural therapy group (average age: 42.1±13.0years). The participants in the horticultural therapy group participated in a 10-session horticultural therapy program designed around various plant cultivating activities. The horticultural therapy program involved sessions once a week from April 2017 to June 2017. A psychiatrist evaluated the psychopathological symptoms of schizophrenic patients in both groups. To assess the clinical psychopathological effects, the Korean version of the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used. The horticultural therapy group significantly improved in terms of positive, negative, and general symptoms on the PANSS after the 10-session horticultural therapy program. Moreover, the horticultural therapy group significantly improved in terms of clinical symptoms of schizophrenia in BPRS after the 10-session horticultural therapy program. However, there was no change in the PANSS and BPRS scores in the control group. This study showed the potential of horticultural therapy in improving psychopathological symptoms in psychiatric patients. Future studies should investigate the effects of long-term horticultural therapy program on the chronic symptoms of patients with schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pitfalls in the Neuroimaging of Glioblastoma in the Era of Antiangiogenic and Immuno/Targeted Therapy - Detecting Illusive Disease, Defining Response

Directory of Open Access Journals (Sweden)

Raymond Yi-Kun Huang

2015-02-01

Full Text Available Glioblastoma, the most common malignant primary brain tumor in adults is a devastating diagnosis with an average survival of 14-16 months using the current standard of care treatment. The determination of treatment response and clinical decision making is based on the accuracy of radiographic assessment. Notwithstanding, challenges exist in the neuroimaging evaluation of patients undergoing treatment for malignant glioma.Differentiating treatment response from tumor progression is problematic and currently combines long-term follow-up using standard MRI, with clinical status and corticosteroid-dependency assessments. In the clinical trial setting, treatment with gene therapy, vaccines, immunotherapy, and targeted biologicals similarly produces MRI changes mimicking disease progression. A neuroimaging method to clearly distinguish between pseudoprogression and tumor progression has unfortunately not been found to date. With the incorporation of antiangiogenic therapies, a further pitfall in imaging interpretation is pseudoresponse. The Macdonald Criteria that correlate tumor burden with contrast enhanced imaging proved insufficient and misleading in the context of rapid blood brain barrier normalization following antiangiogenic treatment that is not accompanied by expected survival benefit. Even improved criteria, such as the RANO criteria, that incorporate non-enhancing disease, clinical status, and need for corticosteroid use, fall short of definitively distinguishing tumor progression, pseudoresponse, and pseudoprogression.This review focuses on advanced imaging techniques including perfusion MRI, diffusion MRI, MR spectroscopy, and new PET imaging tracers. The relevant image analysis algorithms and interpretation methods of these promising techniques are discussed in the context of determining response and progression during treatment of glioblastoma both in the standard of care as well as clinical trial context.

Acyclovir Therapy Reduces the CD4+ T Cell Response against the Immunodominant pp65 Protein from Cytomegalovirus in Immune Competent Individuals.

Directory of Open Access Journals (Sweden)

Annette Pachnio

Full Text Available Cytomegalovirus (CMV infects the majority of the global population and leads to the development of a strong virus-specific immune response. The CMV-specific CD4+ and CD8+ T cell immune response can comprise between 10 and 50% of the T cell pool within peripheral blood and there is concern that this may impair immunity to other pathogens. Elderly individuals with the highest magnitude of CMV-specific immune response have been demonstrated to be at increased risk of mortality and there is increasing interest in interventions that may serve to moderate this. Acyclovir is an anti-viral drug with activity against a range of herpes viruses and is used as long term treatment to suppress reactivation of herpes simplex virus. We studied the immune response to CMV in patients who were taking acyclovir to assess if therapy could be used to suppress the CMV-specific immune response. The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir. This effect was seen within one year of therapy and was observed primarily within the CD4+ response. Acyclovir treatment only modestly influenced the immune response to the IE-1 target protein. These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

Material interaction and art product in art therapy assessment in adult mental health

NARCIS (Netherlands)

Pénzes, I.J.N.J.; Hooren, S. van; Dokter, D.; Smeijsters, H.; Hutschemaekers, G.J.M.

2016-01-01

Background: Art materials have a central role in art therapy. The way a client interacts with art materials - material interaction - is an important source of information in art therapy assessment in adult mental health. The aim of this study was to develop the categories of material interaction and

Pilot study using technetium-99m pertechnetate sequential radionuclide-sialography for assessing salivary gland function of nasopharyngeal cancer patients on radiation therapy

International Nuclear Information System (INIS)

Ng, K.S.; Sundram, F.; Somanesan, S.; Tan, H.S.K.; Gao, F.; Chung, B.; Machin, D.

2003-01-01

Nasopharyngeal carcinoma (NPC) is mainly treated by radiation therapy. A common complication of radiotherapy is xerostomia. Direct measurements of the amount of saliva produced using suction cups and volumetric assessments are cumbersome and time consuming. Sequential radionuclide sialography is a reproducible and convenient method of measuring salivary function. Patients with newly diagnosed NPC underwent a pilot study using technetium-99m pertechnetate sequential radionuclide sialography to assess their salivary function before and at 3 months post radiation therapy. From the sialography, time-activity-curves were obtained for analysis of salivary function. The shape of the time-activity-curve with citric acid stimulation was classified into 4 types according to the degree of radiation-induced dysfunction. All 14 patients had worse time-activity curves for both parotids and submandibular glands after radiation therapy. The P values for the change in time-activity-curves for all the salivary glands were less than 0.005. All patients with abnormal type of curves before radiation therapy presented type IV(non-functioning) curve after radiation therapy. A ratio (Rc) of pre- and post-stimulation counts allowed for quantification of the degree of stimulatory response. We found a significant decrease in Rc before and after radiation therapy for all the salivary glands (P < 0.001). The salivary gland to background ratio, which is a reflection of the degree of salivary gland functional uptake, also had a significant reduction after radiation. It is feasible to use technetium 99m pertechnetate in the measurement of salivary gland function in nasopharyngeal cancer patients treated with radiation therapy

Gender Differences in the Maintenance of Response to Cognitive Behavior Therapy for Posttraumatic Stress Disorder

Science.gov (United States)

Felmingham, Kim L.; Bryant, Richard A.

2012-01-01

Objective: To examine potential differential responses in men and women to cognitive behavior therapy for posttraumatic stress disorder (PTSD). Method: Fifty-two men and 56 women diagnosed with PTSD participated in randomized controlled trials of cognitive behavior therapy for PTSD. Participants were randomly allocated to either (a) exposure-only…

Genetic predictors for the response to therapy in colorectal cancer cells

NARCIS (Netherlands)

de Bruijn, M.T.

2011-01-01

The general goal of this thesis is to create a better insight into the genes and signaling proteins that influence the response of colorectal cancer cells to MEK-targeted therapy and chemotherapy (5-FU and oxaliplatin). In chapter 2 of this thesis we set out to explore the mechanisms of resistance

Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

Science.gov (United States)

Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

2017-07-01

Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

Molecular genetics of Turner syndrome: correlation with clinical phenotype and response to growth hormone therapy.

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Tsezou, A; Hadjiathanasiou, C; Gourgiotis, D; Galla, A; Kavazarakis, E; Pasparaki, A; Kapsetaki, M; Sismani, C; Theodoridis, C; Patsalis, P C; Moschonas, N; Kitsiou, S

1999-12-01

To correlate the origin of the retained X in Turner syndrome with phenotype, pre-treatment height and response to recombinant human growth hormone (rhGH) therapy, systematic clinical assessment and molecular studies were carried out in 33 Greek children with Turner syndrome and their parents including 18 children with 45,X and 15 with X-mosaicism. Microsatellite markers on X chromosomes (DXS101 and DXS337) revealed that the intact X was paternal (Xp) in 15/30 and maternal (Xm) in 15/30 children, while 3/33 families were non-informative. No significant relationship was found between parental origin of the retained X and birth weight/length/gestational age, blepharoptosis, pterygium colli, webbed neck, low hairline, abnormal ears, lymphoedema, short 4th metacarpal, shield chest, widely spaced nipples, cubitus valgus, pigmented naevi, streak gonads, and cardiovascular/renal anomalies. With regard to the children's pre-treatment height, there was a significant correlation with maternal height and target height in both Xm and Xp groups. No differences were found between Xm and Xp groups and the improvement of growth velocity (GV) during the first and second year of rhGH administration, while for both groups GV significantly improved with rhGH by the end of the first and the second year. To our knowledge, this is the first attempt to correlate the parental origin of Turner syndrome with the response to rhGH therapy.

Nutritional therapy and effect assessment of infants with primary intestinal lymphangiectasia

Science.gov (United States)

Li, Suyun; Liu, Xiaoqian; He, Yuan; Li, Qianyu; Ji, Linlin; Shen, Wenbin; Tong, Guansheng

2017-01-01

Abstract Rationale: Intestinal lymphangiectasia (IL) is a rare enteropathy involving the expansion and rupture of intestinal lymphatic channels. Although several reports have studied cases of primary IL (PIL), this condition is very rare, and is even less commonly encountered in infants. This study aimed to investigate the nutritional therapy and effect assessment of chylous reflux disorder caused by PIL in infants. Patient concerns: Infantile patients were enrolled in the Affiliated Beijing Shijitan Hospital of the Capital Medical University between January 2012 and March 2014. The minimum age of onset was 4 months and the maximum age of onset was 16 months, with an average age of 4.9 months. Diagnoses: All children were inpatient who had been diagnosed with chylous reflux syndrome (chylothorax and/or chylic abdomen) caused by PIL. Interventions: Retrospective analysis and individualized nutrition therapy of these cases were carried out. Finally, nutritional therapy and prognosis of PIL were assessed and summarized. Outcomes: All the children survived, showed improvement in the serum total protein, albumin, and HGB levels after nutritional therapy. After comprehensive nutritional therapy, we were able to achieve diarrhea control for all the 9 patients, and after treatment, the children passed soft, yellow stools 1 to 2 times/d. After treatment, the height and weight of all patients increased to within the normal ranges of the World Health Organization standard chart. The mean serum albumin level reached 41.3 g/L. All nutrition-related indicators were found to have significant improvement compared with the baseline levels. Lessons: The results revealed that nutritional therapy for the 9 children with PIL was effective, and it may be able to improve the clinical syndromes and symptoms of children with PIL and promote recovery. PMID:29390480

Prospective, Multicenter Validation Study of Magnetic Resonance Volumetry for Response Assessment After Preoperative Chemoradiation in Rectal Cancer: Can the Results in the Literature be Reproduced?

Energy Technology Data Exchange (ETDEWEB)

Martens, Milou H., E-mail: mh.martens@hotmail.com [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Heeswijk, Miriam M. van [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Broek, Joris J. van den [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Rao, Sheng-Xiang [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Radiology, Fudan University, Shanghai (China); Vandecaveye, Vincent [Department of Radiology, University Hospital Leuven, Leuven (Belgium); Vliegen, Roy A. [Department of Radiology, Atrium Medical Center, Heerlen (Netherlands); Schreurs, Wilhelmina H. [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Beets, Geerard L. [Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Lambregts, Doenja M.J. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Beets-Tan, Regina G.H. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands)

2015-12-01

Purpose: To review the available literature on tumor size/volume measurements on magnetic resonance imaging for response assessment after chemoradiotherapy, and validate these cut-offs in an independent multicenter patient cohort. Methods and Materials: The study included 2 parts. (1) Review of the literature: articles were included that assessed the accuracy of tumor size/volume measurements on magnetic resonance imaging for tumor response assessment. Size/volume cut-offs were extracted; (2) Multicenter validation: extracted cut-offs from the literature were tested in a multicenter cohort (n=146). Accuracies were calculated and compared with reported results from the literature. Results: The review included 14 articles, in which 3 different measurement methods were assessed: (1) tumor length; (2) 3-dimensonial tumor size; and (3) whole volume. Study outcomes consisted of (1) complete response (ypT0) versus residual tumor; (2) tumor regression grade 1 to 2 versus 3 to 5; and (3) T-downstaging (ypTtherapy) and a volume reduction of Δ80% to 86.6%. Accuracies for whole-volume measurements to assess tumor regression grade 1 to 2 were 52% to 61%, and for T-downstaging 51% to 57%. Overall accuracies for tumor length ranged between 48% and 53% and for 3D size measurement between 52% and 56%. Conclusions: Magnetic resonance volumetry using whole-tumor volume measurements can be helpful in rectal cancer response assessment with selected cut-off values. Measurements of tumor length or 3-dimensional tumor size are not helpful. Magnetic resonance volumetry is mainly accurate to assess a complete tumor response (ypT0) after chemoradiation therapy (accuracies up to 80%).

Gender difference in response predictors after 1-year exenatide therapy twice daily in type 2 diabetic patients: a real world experience

Directory of Open Access Journals (Sweden)

Anichini R

2013-04-01

Full Text Available Roberto Anichini,1 Sabrina Cosimi,2 Alberto Di Carlo,3 Paola Orsini,4 Alessandra De Bellis,1 Giuseppe Seghieri,1 Flavia Franconi,5 Fabio Baccetti6 1Diabetes Unit, Spedali Riuniti, Pistoia, Italy; 2Diabetes Unit, Hospital of Versilia, Camaiore (LU, Italy; 3Diabetes Unit, Hospital of Lucca, Italy; 4Diabetes Unit, Hospital of Livorno, Italy; 5Department of Biochemical Sciences, University of Sassari, Italy; 6Diabetes Unit, Hospital of Massa, Italy Purpose: To investigate whether gender affects therapeutic response by exenatide twice a day (BID in type 2 diabetes by using a database concerning patients monitored by five outpatient clinics in Tuscany, Italy. Patients and methods: We considered a cohort of 315 (154 male/161 female patients experiencing therapeutic failure while on oral therapy (metformin, or combination therapy metformin + sulphonylureas, who were given exenatide (10 µg/BID and who fully completed 4 months, 8 months, and 12 months of follow-ups. Results: Among patients stratified by gender and well matched for age, body mass index, and hemoglobin A1c (HbA1c, it was found that the length of disease was longer in females than in males (12 ± 8 years versus 10 ± 7 years; P = 0.037, and the ratio of patients on metformin to those on combination therapy was higher in men (P = 0.018. Target glycemic response (1-year HbA1c ≤ 7% was achieved in a significantly higher proportion of males than females (38% versus 27%;Χ2 = 4.66; P = 0.03. Target weight loss expressed as 1-year weight percent fall from baseline ≥ 75th percentile (8.5% was significantly higher in females at 8 and 12 months (P < 0.05; for both. One-year glycemic target response was inversely related to baseline HbA1c levels and diabetes duration among males, while metformin therapy (compared to oral combination therapy was a significant predictor of better glycemic targets among females. Homeostasis model assessment-B, measured in 117 patients, predicted hypoglycemic

Coupled multiple-response versus free-response conceptual assessment: An example from upper-division physics

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Bethany R. Wilcox

2014-10-01

Full Text Available Free-response research-based assessments, like the Colorado Upper-division Electrostatics Diagnostic (CUE, provide rich, fine-grained information about students’ reasoning. However, because of the difficulties inherent in scoring these assessments, the majority of the large-scale conceptual assessments in physics are multiple choice. To increase the scalability and usability of the CUE, we set out to create a new version of the assessment that preserves the insights afforded by a free-response format while exploiting the logistical advantages of a multiple-choice assessment. We used our extensive database of responses to the free-response CUE to construct distractors for a new version where students can select multiple responses and receive partial credit based on the accuracy and consistency of their selections. Here, we describe the development of this modified CUE format, which we call coupled multiple response (CMR, and present data from direct comparisons of both versions. We find that the two formats have the same average score and perform similarly on multiple measures of validity and reliability, suggesting that the new version is a potentially viable alternative to the original CUE for the purpose of large-scale research-based assessment. We also compare the details of student responses on each of the two versions. While the CMR version does not capture the full scope of potential student responses, nearly three-quarters of our students’ responses to the free-response version contained one or more elements that matched options provided on the CMR version.

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

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Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

2017-01-01

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

Longitudinal Changes in Depressive Circuitry in Response to Neuromodulation Therapy

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Yagna Pathak

2016-07-01

Full Text Available Background: Major Depressive Disorder (MDD is a public health problem worldwide. There is increasing interest in using non-invasive therapies such as repetitive transcranial magnetic stimulation (rTMS to treat MDD. However, the changes induced by rTMS on neural circuits remain poorly characterized. The present study aims to test whether the brain regions previously targeted by deep brain stimulation (DBS in the treatment of MDD respond to rTMS, and whether functional connectivity measures can predict clinical response.Methods: rTMS (20 sessions was administered to five MDD patients at the left-dorsolateral prefrontal cortex (L-DLPFC over 4 weeks. Magnetoencephalography (MEG recordings and Montgomery-Asberg Depression Rating Scale (MADRS assessments were acquired before, during and after treatment. Our primary measures, obtained with MEG source imaging, were changes in power spectral density (PSD and changes in functional connectivity as measured using coherence.Results: Of the five patients, four met the clinical response criterion (40% or greater decrease in MADRS after four weeks of treatment. An increase in gamma power at the L-DLPFC was correlated with improvement in symptoms. We also found that increases in delta band connectivity between L-DLPFC/amygdala and L-DLPFC/pregenual anterior cingulate cortex (pACC, and decreases in gamma band connectivity between L-DLPFC/subgenual anterior cingulate cortex (sACC, were correlated with improvements in depressive symptoms. Conclusions: Our results suggest that non-invasive intervention techniques, such as rTMS, modulate the ongoing activity of depressive circuits targeted for DBS, and that MEG can capture these changes. Gamma oscillations may originate from GABA-mediated inhibition, which increases synchronization of large neuronal populations, possibly leading to increased long-range functional connectivity. We postulate that responses to rTMS could provide valuable insights into early evaluation

Item Response Theory for Peer Assessment

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Uto, Masaki; Ueno, Maomi

2016-01-01

As an assessment method based on a constructivist approach, peer assessment has become popular in recent years. However, in peer assessment, a problem remains that reliability depends on the rater characteristics. For this reason, some item response models that incorporate rater parameters have been proposed. Those models are expected to improve…

Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer.

Science.gov (United States)

Janjigian, Yelena Y; Sanchez-Vega, Francisco; Jonsson, Philip; Chatila, Walid K; Hechtman, Jaclyn F; Ku, Geoffrey Y; Riches, Jamie C; Tuvy, Yaelle; Kundra, Ritika; Bouvier, Nancy; Vakiani, Efsevia; Gao, Jianjiong; Heins, Zachary J; Gross, Benjamin E; Kelsen, David P; Zhang, Liying; Strong, Vivian E; Schattner, Mark; Gerdes, Hans; Coit, Daniel G; Bains, Manjit; Stadler, Zsofia K; Rusch, Valerie W; Jones, David R; Molena, Daniela; Shia, Jinru; Robson, Mark E; Capanu, Marinela; Middha, Sumit; Zehir, Ahmet; Hyman, David M; Scaltriti, Maurizio; Ladanyi, Marc; Rosen, Neal; Ilson, David H; Berger, Michael F; Tang, Laura; Taylor, Barry S; Solit, David B; Schultz, Nikolaus

2018-01-01

The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability-high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein-Barr virus-positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance. Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49-58. ©2017 AACR. See related commentary by Sundar and Tan, p. 14 See related article by Pectasides et al., p. 37 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

Antibody production in response to staphylococcal MS-1 phage cocktail in patients undergoing phage therapy

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Maciej Żaczek

2016-10-01

Full Text Available In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiphage antibodies to a staphylococcal phage cocktail in patients undergoing experimental phage therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, Poland. We also evaluated whether occurring antiphage antibodies had neutralizing properties towards applied phages (K rate. Among 20 examined patients receiving the MS-1 phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiphage antibodies in their sera during phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiphage antibodies did not translate into unsatisfactory clinical results of phage therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiphage antibodies before and during treatment. This may imply that possible induction of antiphage antibodies is not an obstacle to the implementation of phage therapy and support our assumption that the outcome of the phage treatment does not primarily depend on the appearance of antiphage antibodies in sera of patients during therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of phage therapy in humans.

Antibody Production in Response to Staphylococcal MS-1 Phage Cocktail in Patients Undergoing Phage Therapy.

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Żaczek, Maciej; Łusiak-Szelachowska, Marzanna; Jończyk-Matysiak, Ewa; Weber-Dąbrowska, Beata; Międzybrodzki, Ryszard; Owczarek, Barbara; Kopciuch, Agnieszka; Fortuna, Wojciech; Rogóż, Paweł; Górski, Andrzej

2016-01-01

In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiphage antibodies) to a staphylococcal phage cocktail in patients undergoing experimental phage therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, Poland. We also evaluated whether occurring antiphage antibodies had neutralizing properties toward applied phages (K rate). Among 20 examined patients receiving the MS-1 phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiphage antibodies in their sera during phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiphage antibodies did not translate into unsatisfactory clinical results of phage therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiphage antibodies before and during treatment. This may imply that possible induction of antiphage antibodies is not an obstacle to the implementation of phage therapy and support our assumption that the outcome of the phage treatment does not primarily depend on the appearance of antiphage antibodies in sera of patients during therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of phage therapy in humans.

Association between brain natriuretic peptide, markers of inflammation and the objective and subjective response to cardiac resynchronization therapy

DEFF Research Database (Denmark)

Brouwers, Corline; Versteeg, Henneke; Meine, Mathias

2014-01-01

Introduction: Studies suggest that cardiac resynchronization therapy (CRT) can induce a decrease in brain natriuretic peptide (BNP) and systemic inflammation, which may be associated with CRT-response. However, the evidence is inconclusive. We examined levels of BNP and inflammatory markers from...... ventricular end systolic volume; subjective CRT-response was defined as an improvement of ⩾10 points in patient-reported health status assessed with the Kansas City Cardiomyopathy Questionnaire. Plasma BNP and markers of inflammation (CRP, IL-6, TNFα, sTNFr1 and sTNFr2) were measured at three time points...... is not automatically related to a stronger overall decrease in inflammation. Large-scale studies are warranted that further examine the relation between the clinical effects of CRT on inflammatory markers, as the latter have been associated with poor prognosis in heart failure....

METHODS OF ASSESSMENT OF THE RELATIVE BIOLOGICAL EFFECTIVENESS OF NEUTRONS IN NEUTRON THERAPY

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V. A. Lisin

2017-01-01

Full Text Available The relative biological effectiveness (RBE of fast neutrons is an important factor influencing the quality of neutron therapy therefore, the assessment of RBE is of great importance. Experimental and clinical studies as well as different mathematical and radiobiological models are used for assessing RBE. Research is conducted for neutron sources differing in the method of producing particles, energy and energy spectrum. Purpose: to find and analyze the dose-dependence of fast neutron RBE in neutron therapy using the U-120 cyclotron and NG-12I generator. Material and methods: The optimal method for assessing the relative biological effectiveness of neutrons for neutron therapy was described. To analyze the dependence of the RBE on neutron dose, the multi-target model of cell survival was applied. Results: The dependence of the RBE of neutrons produced from the U-120 cyclotron and NG-120 generator on the dose level was found for a single irradiation of biological objects. It was shown that the function of neutron dose was consistent with similar dependencies found by other authors in the experimental and clinical studies.

Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

International Nuclear Information System (INIS)

Røe, Kathrine; Mikalsen, Lars TG; Kogel, Albert J van der; Bussink, Johan; Lyng, Heidi; Ree, Anne H; Marignol, Laure; Olsen, Dag R

2012-01-01

Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC. Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI. Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density (VD), and vessel area fraction (VF) from qIHC. Although total hypoxic fractions (HF) did not change, estimated acute hypoxia scores (AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve (AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size (VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after pharmacokinetic modeling. Interestingly, such

Assessment of patients' knowledge of their drug therapy in a ...

African Journals Online (AJOL)

Patients' knowledge of their medications is an important factor in ensuring adherence. Medication adherence is essential for rational drug use and derivation of optimal therapy. This study was conducted to assess knowledge of outpatients regarding their medications. A well structured questionnaire was administered to 200 ...

Subjective and objective assessment of patients' compression therapy skills as a predicator of ulcer recurrence.

Science.gov (United States)

Mościcka, Paulina; Szewczyk, Maria T; Jawień, Arkadiusz; Cierzniakowska, Katarzyna; Cwajda-Białasik, Justyna

2016-07-01

To verify whether the subjectively and objectively assessed patient's skills in applying compression therapy constitute a predicting factor of venous ulcer recurrence. Systematic implementation of compression therapy by the patient is a core of prophylaxis for recurrent ulcers. Therefore, patient education constitutes a significant element of care. However, controversies remain if all individuals benefit equally from education. A retrospective analysis. The study included medical records of patients with venous ulcers (n = 351) treated between 2001 and 2011 at the Clinic for Chronic Wounds at Bydgoszcz Clinical Hospital. We compared two groups of patients, (1) with at least one episode of recurrent ulcer during the five-year observation period, and (2) without recurrences throughout the analysed period in terms of their theoretical skills and knowledge on compression therapy recorded at baseline and after one month. Very good self-assessment of a patient's compression therapy skills and weak assessment of these skills by a nurse proved significant risk factors for recurrence of the ulcers on univariate analysis. The significance of these variables as independent risk factors for recurrent ulcers has been also confirmed on multivariate analysis, which also took into account other clinical parameters. Building up proper compression therapy skills among the patients should be the key element of a properly construed nurse-based prophylactic program, as it is the most significant modifiable risk factor for recurrent ulcers. Although the development of compression skills is undeniably important, also other factors should be considered, e.g. surgical correction of superficial reflux. Instruction on compression therapy should be conducted by properly trained nursing personnel - the nurses should have received both content and psychological training. The compression therapy training should contain practical instruction with guided exercises and in-depth objective

Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia.

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Akin, M; Sarbay, H; Guler, S; Balci, Y I; Polat, A

2016-04-01

We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65-70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. © 2016 John Wiley & Sons Ltd.

Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy.

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Schmidt, M; Hochhaus, A; König-Merediz, S A; Brendel, C; Proba, J; Hoppe, G J; Wittig, B; Ehninger, G; Hehlmann, R; Neubauer, A

2000-10-01

Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-alpha) treatment in CML. Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro-stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-alpha therapy and in 47 additional CML samples taken during IFN-alpha therapy. IRF4 expression was then correlated with cytogenetic response to IFN-alpha. IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-alpha therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-alpha therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-alpha, a good response was associated with high IRF4 expression. IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-alpha therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-alpha in CML.

Tics as signs of catatonia: electroconvulsive therapy response in 2 men.

Science.gov (United States)

Dhossche, Dirk M; Reti, Irving M; Shettar, Shashidhar M; Wachtel, Lee E

2010-12-01

Tics have rarely been described in catatonia although tics are sudden and nonrhythmic variants of stereotypic or repetitive movement abnormalities that are considered cardinal symptoms of catatonia. We describe 2 men with tics and self-injurious behavior, who met criteria for catatonia. One patient met criteria for autism. We reported 2 new cases and performed a literature review using PubMed to identify other cases of tics that were treated with electroconvulsive therapy. Tics along with other catatonic symptoms and self-injurious behavior responded to electroconvulsive therapy in 2 men. Eight other patients with tics that were treated with electroconvulsive therapy were found in the literature. Catatonia was recognized in 4 of the 8 patients. Two patients met criteria for autism. Tics, with or without self-injurious behavior, may be signs of catatonia. Patients with tics or Tourette syndrome warrant assessment for catatonia. If catatonia is present, electroconvulsive therapy provides a safe but rarely used alternative to pharmacotherapy, psychosurgery, or invasive brain stimulation in the treatment of tics and Tourette syndrome. © 2010 Lippincott Williams & Wilkins, Inc.

Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

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Curtis L Cooper

2010-01-01

Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.

Science.gov (United States)

MacLean, Joanna E; Cohen, Eyal; Weinstein, Michael

2002-06-01

Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.

Value of PET and PET-CT for monitoring tumor therapy

International Nuclear Information System (INIS)

Chen Xiang; Zhao Jinhua

2007-01-01

18 F-fluorodeoxyglucose ( 18 F-FDG) PET or PET-CT is an accurate test for differentiating residual viable tumor tissue from therapy-induced changes in tumor. Furthermore, quantitative assessment of therapy-induced changes in tumor 18 F-FDG uptake may allow the prediction of tumor response. Treatment may be adjusted according to tumor response. So it is increasingly used to monitor tumor response in patients undergoing chemotherapy and chemoradiotherapy. Here we focused on practical aspects of 18 F-FDG PET or PET-CT for treatment monitoring and on the existing advantages and challenges. (authors)

Pattern analysis of defecography in patients with chronic functional constipation: is it predictable for the responsiveness of biofeedback therapy?

Energy Technology Data Exchange (ETDEWEB)

Yang, Hye Rin; Kim, Ah Young; Hong, Seong Sook; Byun, Jae Ho; Myung Seung Jae; Ha, Hyun Kwon [University of Ulsan of Medicine, Seoul (Korea, Republic of)

2005-08-15

To determine of pattern analysis of defecography can predict the responsiveness of biofeedback therapy in patients with chronic functional constipation. Over a two-year period, 104 patients with chronic functional constipation underwent defecography and biofeedback therapy. Two blinded readers analyzed the defecographic findings and classified them into six types; I = normal defecation, II = hypertonic lower anal sphincter (poor anal opening due to a persistent contraction of the lower anal sphincter), III dyskinetic puborectal sling (inadequate laxity of the puborectal sling), IV spastic pelvic floor syndrome (persistent contraction of both the puborectal sling and the lower and sphincter), V unclassified (including paradoxical contraction of the anal sphincter), VI anatomical obstruction. In addition, the degree of rectal contraction during defecation was scored (grade 0 to 3). After biofeedback therapy, the differences in the defecography patterns or rectal contraction between the two groups, the responsive or non-responsive group, were analyzed. The defecograms revealed that the type IV of the spastic pelvic floor syndrome was most common (50 of 104 patients, 48%), followed by II (21/104, 20%), III (12/104, 11.5%), V (9/104, 9%) and VI (12/104, 11.5%). Biofeedback therapy showed a therapeutic response in 71 out of 104 patients (68%) but failed in 33 patients (32%). However, there were no significant differences in the defecographic pattern between the responsive and non-responsive groups ({rho} = 0.630). The defecograms revealed contractions in 78 patients (75%) and moderate to vigorous contractions (more than grade 2) in 66 patients. Most of the biofeedback-responsive group showed rectal contractions (66 of 71 patients, 93%, {rho} < 0.001). In patients with chronic functional constipation, there was no significant difference in the morphological patterns of the defecogram between the responsive and non-responsive biofeedback groups. However, the presence of

Pattern analysis of defecography in patients with chronic functional constipation: is it predictable for the responsiveness of biofeedback therapy?

International Nuclear Information System (INIS)

Yang, Hye Rin; Kim, Ah Young; Hong, Seong Sook; Byun, Jae Ho; Myung Seung Jae; Ha, Hyun Kwon

2005-01-01

To determine of pattern analysis of defecography can predict the responsiveness of biofeedback therapy in patients with chronic functional constipation. Over a two-year period, 104 patients with chronic functional constipation underwent defecography and biofeedback therapy. Two blinded readers analyzed the defecographic findings and classified them into six types; I = normal defecation, II = hypertonic lower anal sphincter (poor anal opening due to a persistent contraction of the lower anal sphincter), III dyskinetic puborectal sling (inadequate laxity of the puborectal sling), IV spastic pelvic floor syndrome (persistent contraction of both the puborectal sling and the lower and sphincter), V unclassified (including paradoxical contraction of the anal sphincter), VI anatomical obstruction. In addition, the degree of rectal contraction during defecation was scored (grade 0 to 3). After biofeedback therapy, the differences in the defecography patterns or rectal contraction between the two groups, the responsive or non-responsive group, were analyzed. The defecograms revealed that the type IV of the spastic pelvic floor syndrome was most common (50 of 104 patients, 48%), followed by II (21/104, 20%), III (12/104, 11.5%), V (9/104, 9%) and VI (12/104, 11.5%). Biofeedback therapy showed a therapeutic response in 71 out of 104 patients (68%) but failed in 33 patients (32%). However, there were no significant differences in the defecographic pattern between the responsive and non-responsive groups (ρ = 0.630). The defecograms revealed contractions in 78 patients (75%) and moderate to vigorous contractions (more than grade 2) in 66 patients. Most of the biofeedback-responsive group showed rectal contractions (66 of 71 patients, 93%, ρ < 0.001). In patients with chronic functional constipation, there was no significant difference in the morphological patterns of the defecogram between the responsive and non-responsive biofeedback groups. However, the presence of rectal

FDG PET/CT in initial staging and early response to chemotherapy assessment of paediatric rhabdomyosarcomas

International Nuclear Information System (INIS)

Eugene, T.; Ansquer, C.; Oudoux, A.; Carlier, T.; Kraeber-Bodere, T.; Bodet-Milin, C.; Corradini, N.; Thomas, C.; Dupas, B.

2010-01-01

Purpose: The objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma. Patients and methods: Prior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years). Results: PET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years). Conclusion: This study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment. (authors)

Metabolic and clinical assessment of efficacy of cryoablation therapy on skeletal masses by 18F-FDG positron emission tomography/computed tomography (PET/CT) and visual analogue scale (VAS): initial experience

International Nuclear Information System (INIS)

Masala, Salvatore; Bartolucci, Alberto D.; Mammucari, Matteo; Simonetti, Giovanni; Schillaci, Orazio; Calabria, Ferdinando

2011-01-01

Various therapy modalities have been proposed as standard treatments in management of bone metastases. Radiation therapy remains the standard of care for patients with localized bone pain, but up to 30% of them do not experience notable pain relief. Percutaneous cryoablation is a minimally invasive technique that induces necrosis by alternately freezing and thawing a target tissue. This technique is successfully used to treat a variety of malignant and benign diseases in different sites. 18 F-FDG positron emission tomography/computed tomography ( 18 F-FDG PET/CT) is a single technique of imaging that provides in a ''single step'' both morphological and metabolic features of neoplastic lesions of the bone. The aim of this study was to evaluate the efficacy of the cryosurgical technique on secondary musculoskeletal masses according to semi-quantitative PET analysis and clinical-test evaluation with the visual analogue scale (VAS). We enrolled 20 patients with painful bone lesions (score pain that exceeded 4 on the VAS) that were non-responsive to treatment; one lesion per patient was treated. All patients underwent a PET-CT evaluation before and 8 weeks after cryotherapy; maximum standardized uptake value (SUV max ) was measured before and after treatment for metabolic assessment of response to therapy. After treatment, 18 patients (90%) showed considerable reduction in SUV max value (>50%) suggestive of response to treatment; only 2 patients did not show meaningful reduction in metabolic activity. Our preliminary study demonstrates that quantitative analysis provided by PET correlates with response to cryoablation therapy as assessed by CT data and clinical VAS evaluation. (orig.)

Concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy.

Science.gov (United States)

Lee, Dong Hyun; Kim, Moo Hyun; Guo, Long Zhe; De Jin, Cai; Cho, Young Rak; Park, Kyungil; Park, Jong Sung; Park, Tae-Ho; Serebruany, Victor

2016-01-15

Despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (DAPT) in patients undergoing percutaneous coronary interventions (PCI). There is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. Sustained released nitrates (SRN) are commonly used together with clopidogrel in post-PCI setting for mild vasodilatation and nitric oxide-induced platelet inhibition. We prospectively enrolled 458 patients (64.5 ± 9.6 years old, and 73.4% males) following PCI undergoing DAPT with clopidogrel and aspirin. Platelet reactivity was assessed by the VerifyNow™ P2Y12 assay at the maintenance outpatient setting. Concomitant SRN (n=266) significantly (p=0.008) enhanced platelet inhibition after DAPT (251.6 ± 80.9PRU) when compared (232.1 ± 73.5PRU) to the SRN-free (n=192) patients. Multivariate logistic regression analysis with the cut-off value of 253 PRU for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during DAPT and use of SRN (Relative risk=1.675; Odds ratio [1.059-2.648]; p=0.027). In contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ACE-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following DAPT. The synergic ability of SRN to enhance response during DAPT may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ergonomics work assessment in rural industrial settings: a student occupational therapy project.

Science.gov (United States)

Bowman, Peter J

2012-01-01

This case study describes a student occupational therapy (OT) program, the creation of a worksite assessment project as a part of a Community Connections: Partners for Learning and Service grant funded by Health Resources and Services Administration. The primary goals were to design occupation-based community learning experiences in a variety of rural community settings, so that students might benefit from participating in the community based learning and: based on the results, embed occupation-based learning into existing occupational therapy curriculum. The components of the project and the ergonomics content of the OT education program are described; details of the work assessment are presented with analysis of data from the student evaluation of this project.

Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids. Addendum

Science.gov (United States)

2009-08-01

Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit A. Evrensel...AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible... Magneto -rheological Fluid (MRF) iron nano-particles were synthesized using the reverse micelle technique and coated with poly(NIPAAm). The size

em>In vivoem> biological response to extracorporeal shockwave therapy in human tendinopathy

DEFF Research Database (Denmark)

Waugh, C. M.; Morrissey, D.; Jones, E.

2015-01-01

Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session...

WE-H-202-02: Biomechanical Modeling of Anatomical Response Over the Course of Therapy

Energy Technology Data Exchange (ETDEWEB)

Brock, K. [University of Michigan (United States)

2016-06-15

Deformable image registration has now been commercially available for several years, with solid performance in a number of sites and for several applications including contour and dose mapping. However, more complex applications have arisen, such as assessing response to radiation therapy over time, registering images pre- and post-surgery, and auto-segmentation from atlases. These applications require innovative registration algorithms to achieve accurate alignment. The goal of this session is to highlight emerging registration technology and these new applications. The state of the art in image registration will be presented from an engineering perspective. Translational clinical applications will also be discussed to tie these new registration approaches together with imaging and radiation therapy applications in specific diseases such as cervical and lung cancers. Learning Objectives: To understand developing techniques and algorithms in deformable image registration that are likely to translate into clinical tools in the near future. To understand emerging imaging and radiation therapy clinical applications that require such new registration algorithms. Research supported in part by the National Institutes of Health under award numbers P01CA059827, R01CA166119, and R01CA166703. Disclosures: Phillips Medical systems (Hugo), Roger Koch (Christensen) support, Varian Medical Systems (Brock), licensing agreements from Raysearch (Brock) and Varian (Hugo).; K. Brock, Licensing Agreement - RaySearch Laboratories. Research Funding - Varian Medical Systems; G. Hugo, Research grant from National Institutes of Health, award number R01CA166119.; G. Christensen, Research support from NIH grants CA166119 and CA166703 and a gift from Roger Koch. There are no conflicts of interest.

[Partial response of solar urticaria to omalizumab therapy].

Science.gov (United States)

Kowalzick, L; Thiel, W; C Bielfeld; Ziegler, H; Eickenscheidt, L

2017-06-01

The treatment of solar urticaria is regarded as difficult. In some cases good responses to the anti-IgE antibody omalizumab (Xolair®), approved for treatment of chronic spontaneous urticaria, have been reported. We report on a 50-year-old Caucasian woman who for the last 5 years has developed localized itching and stinging erythemas following exposure to sunlight accompanied sometimes by anaphylactic reactions. Oral antihistamines in three- to four-fold doses and a topical sun screen had been only partially effective in long-term use. Positive immediate-type reactions with whealing appeared in phototesting with low doses of UVB and UVA. Three weeks after s. c. injection of 300 mg omalizumab, the minimal urticarial dose (MUD) for UVB was increased at least 20-fold (from omalizumab administration to 14 points in weeks two and three. Overall, a partial response of solar urticaria to omalizumab therapy could be observed in the present case.

Assessing Patients’ Cognitive Therapy Skills: Initial Evaluation of the Competencies of Cognitive Therapy Scale

Science.gov (United States)

Strunk, Daniel R.; Hollars, Shannon N.; Adler, Abby D.; Goldstein, Lizabeth A.; Braun, Justin D.

2014-01-01

In Cognitive Therapy (CT), therapists work to help patients develop skills to cope with negative affect. Most current methods of assessing patients’ skills are cumbersome and impractical for clinical use. To address this issue, we developed and conducted an initial psychometric evaluation of self and therapist reported versions of a new measure of CT skills: the Competencies of Cognitive Therapy Scale (CCTS). We evaluated the CCTS at intake and post-treatment in a sample of 67 patients participating in CT. The CCTS correlated with a preexisting measure of CT skills (the Ways of Responding Questionnaire) and was also related to concurrent depressive symptoms. Across CT, self-reported improvements in CT competencies were associated with greater changes in depressive symptoms. These findings offer initial evidence for the validity of the CCTS. We discuss the CCTS in comparison with other measures of CT skills and suggest future research directions. PMID:25408560

Meta-Analysis of the Relation of Baseline Right Ventricular Function to Response to Cardiac Resynchronization Therapy.

Science.gov (United States)

Sharma, Abhishek; Bax, Jerome J; Vallakati, Ajay; Goel, Sunny; Lavie, Carl J; Kassotis, John; Mukherjee, Debabrata; Einstein, Andrew; Warrier, Nikhil; Lazar, Jason M

2016-04-15

Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (β = 0.005, p = 0.989); baseline RVEF (β = 0.270, p = 0.493); baseline RVFAC (β = -0.367, p = 0.06); baseline basal strain (β = -0.342, p = 0.462) after a mean follow-up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF. Copyright © 2016 Elsevier Inc. All rights reserved.

A music therapy tool for assessing parent-child interaction in cases of emotional neglect

DEFF Research Database (Denmark)

Jacobsen, Stine Lindahl; H. McKinney, Cathy

2015-01-01

Using a music therapy approach to assess emotional communication and parent–child interaction is new to the field of child protection. However, musical improvisations in music therapy has long been known as an analogue to affect attunement and early non-verbal communication between parent and inf...

Interpersonal Subtypes and Therapy Response in Patients Treated for Posttraumatic Stress Disorder.

Science.gov (United States)

König, Julia; Onnen, Margarete; Karl, Regina; Rosner, Rita; Butollo, Willi

2016-01-01

Interpersonal traits may influence psychotherapy success. One way of conceptualizing such traits is the interpersonal circumplex model. In this study, we analyse interpersonal circumplex data, assessed with the Inventory of Interpersonal Problems (Horowitz, Strauß, & Kordy, 1994) from a randomized study with 138 patients suffering from posttraumatic stress disorder after trauma in adulthood. The study compared cognitive processing therapy and dialogical exposure therapy, a Gestalt-based intervention. We divided the interpersonally heterogeneous sample according to the quadrants of the interpersonal circumplex. The division into quadrants yielded subgroups that did not differ in their general psychological distress, but the cold-submissive quadrant tended to exhibit higher posttraumatic stress disorder symptom severity and interpersonal distress than the other three. There was also a trend for patients in different quadrants to be affected differently by the treatments. Correlation analyses supported these results: in cognitive processing therapy, more dominant patients had more successful therapies, while in dialogical exposure therapy, success was not correlated with interpersonal style. Results indicate that especially patients with cold interpersonal styles profited differentially from the two treatments offered. Dividing samples according to the interpersonal circumplex quadrants seems promising. Interpersonal traits may contribute to psychotherapy outcome. Dividing the sample according to the quadrants of the interpersonal circumplex, as opposed to cluster analysis, yielded promising results. Patients higher in dominance fared better with cognitive processing therapy, while interpersonal style had no correlations with therapy success in dialogical exposure therapy. Copyright © 2015 John Wiley & Sons, Ltd.

HElmet therapy Assessment in infants with Deformed Skulls (HEADS: protocol for a randomised controlled trial

Directory of Open Access Journals (Sweden)

van Wijk Renske M

2012-07-01

Full Text Available Abstract Background In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly. However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed Skulls aims to determine the effects and costs of helmet therapy compared to no helmet therapy in infants with moderate to severe skull deformation. Methods/design Pragmatic randomised controlled trial (RCT nested in a cohort study. The cohort study included infants with a positional preference and/or skull deformation at two to four months (first assessment. At 5 months of age, all children were assessed again and infants meeting the criteria for helmet therapy were asked to participate in the RCT. Participants were randomly allocated to either helmet therapy or no helmet therapy. Parents of eligible infants that do not agree with enrolment in the RCT were invited to stay enrolled for follow up in a non-randomisedrandomised controlled trial (nRCT; they were then free to make the decision to start helmet therapy or not. Follow-up assessments took place at 8, 12 and 24 months of age. The main outcome will be head shape at 24 months that is measured using plagiocephalometry. Secondary outcomes will be satisfaction of parents and professionals with the appearance of the child, parental concerns about the future, anxiety level and satisfaction with the treatment, motor development and quality of life of the infant. Finally, compliance and costs will also be determined. Discussion HEADS will be the first study presenting data from an RCT on the effectiveness of helmet therapy. Outcomes will be important for affected children and their parents, health care professionals and future treatment policies. Our findings are likely to influence the reimbursement policies of health insurance companies. Besides these health outcomes, we will be able to

The study of correlation between HBV genotype and the response to transcatheter arterial chemoembolization therapy in hepatocellular carcinoma patients

International Nuclear Information System (INIS)

Huang Keyao; Yang Weizhu; Jiang Na; Zheng Qubing

2004-01-01

Objective: To evaluate the influence of hepatitis B virus(HBV) genotype on response to transcatheter arterial embolization therapy in patients with HBV-related HCC. Methods: Transcatheter arterial chemoem-bolization therapy was conducted in patients with HBV-related HCC and response to embolization therapy were observed according to the tumor necrosis rate, the HCC recurrence rate, the cumulative incidence of survival rate and the change of AFP. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. The response of HCC to embolization therapy was compared between patients who were infected with different genotypic HBV. Results: The tumor necrosis rate of genotype C patients was similar to that of genotype B patients (P=0.099). The HCC recurrence rate of genotype B was lower than that of genotype C patients (P=0.036). The cumulative incidence of survival rates of 2 and 3 years were significantly higher in the genotype B patients (P=0.036 and P=0.013). There was no difference between the two genotypes, patients in the change of AFP (P>0.05). Conclusions: HBV genotype B patients seem to have a better response to embolization therapy as compared to genotype C patients. Determination of HBV genotype may be useful in predicting the outcomes of TACE therapy in HBV-related HCC. (authors)

Importance of heart rate during exercise for response to cardiac resynchronization therapy.

Science.gov (United States)

Maass, Alexander H; Buck, Sandra; Nieuwland, Wybe; Brügemann, Johan; van Veldhuisen, Dirk J; Van Gelder, Isabelle C

2009-07-01

Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. To study exercise-related factors predicting response to CRT. We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months. We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO2 significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P exercise (OR 15.8 [3.3-76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0-5.7], P = 0.04) as predictive for response. Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.

SU-F-J-178: A Computer Simulation Model Observer for Task-Based Image Quality Assessment in Radiation Therapy

International Nuclear Information System (INIS)

Dolly, S; Mutic, S; Anastasio, M; Li, H; Yu, L

2016-01-01

Purpose: Traditionally, image quality in radiation therapy is assessed subjectively or by utilizing physically-based metrics. Some model observers exist for task-based medical image quality assessment, but almost exclusively for diagnostic imaging tasks. As opposed to disease diagnosis, the task for image observers in radiation therapy is to utilize the available images to design and deliver a radiation dose which maximizes patient disease control while minimizing normal tissue damage. The purpose of this study was to design and implement a new computer simulation model observer to enable task-based image quality assessment in radiation therapy. Methods: A modular computer simulation framework was developed to resemble the radiotherapy observer by simulating an end-to-end radiation therapy treatment. Given images and the ground-truth organ boundaries from a numerical phantom as inputs, the framework simulates an external beam radiation therapy treatment and quantifies patient treatment outcomes using the previously defined therapeutic operating characteristic (TOC) curve. As a preliminary demonstration, TOC curves were calculated for various CT acquisition and reconstruction parameters, with the goal of assessing and optimizing simulation CT image quality for radiation therapy. Sources of randomness and bias within the system were analyzed. Results: The relationship between CT imaging dose and patient treatment outcome was objectively quantified in terms of a singular value, the area under the TOC (AUTOC) curve. The AUTOC decreases more rapidly for low-dose imaging protocols. AUTOC variation introduced by the dose optimization algorithm was approximately 0.02%, at the 95% confidence interval. Conclusion: A model observer has been developed and implemented to assess image quality based on radiation therapy treatment efficacy. It enables objective determination of appropriate imaging parameter values (e.g. imaging dose). Framework flexibility allows for incorporation

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

Science.gov (United States)

Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Marchesiello, Anna; Tolino, Ersilia; Zuber, Sara; La Torre, Giuseppe; Potenza, Concetta

2017-01-01

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score. PMID:29067277

Emotional, motivational and interpersonal responsiveness of children with autism in improvisational music therapy

DEFF Research Database (Denmark)

Kim, Jinah; Wigram, Tony; Gold, Christian

2009-01-01

Through behavioural analysis, this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional, motivational and interpersonal responsiveness in children with autism during joint attention ep...

Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

Science.gov (United States)

Wang, Sheng; Zhang, Lei; Dong, Chunhong; Su, Lin; Wang, Hanjie; Chang, Jin

2015-01-01

A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy.

Science.gov (United States)

Pritzker, Kenneth; Pritzker, Laura; Generali, Daniele; Bottini, Alberto; Cappelletti, Maria Rosa; Guo, Baoqing; Parissenti, Amadeo; Trudeau, Maureen

2015-05-01

As there is now evidence that switching clinical nonresponders early in primary systemic therapy to alternate treatment regimens can enhance survival in some breast cancer patients, the need for a robust intermediate endpoint that can guide treatment response across all tumor subtypes is urgent. Recently, chemotherapy drugs have been shown to induce a decrease in RNA quality in tumor cells from breast cancer biopsies in some patients at midtherapy, and that this has been associated with subsequent achievement of pathological complete response (pCR). The decrease in RNA quality has been shown to be associated with RNA disruption; aberrant RNA bands visualized by RNA electrophoresis have been associated with subsequent tumor cell death. The objectives of these studies are to show that a new assay based on induction of RNA disruption in tumor cells by chemotherapy can stratify at midtherapy, pCR responders from non-pCR responders irrespective of clinical response and to present early evidence that clinically useful RNA disruption can be detected as early as 14 days after initiation of treatment. RNA disruption in tumor cells was quantified by analysis of the RNA electrophoresis banding pattern and expressed as an RNA disruption index (RDI). To develop the RNA disruption assay (RDA), RDI was correlated with clinical outcome (pCR) from the NCIC-CTG MA.22 breast cancer clinical trial (ClinicalTrials.gov NCT00066443). RDA Zones were established by stratifying patients using RDI values into Zone 1, Zone 2, and Zone 3. Zone 3 included seven out of eight pCR responders, whereas Zone 1 contained no pCR responders. An intermediate zone (Zone 2) was established which contained one pCR. Subsequently, to determine early drug response, RNA disruption was examined by RDI after 14 days exposure to trastuzumab, zoledronic acid, or letrozole + cyclophosphamide ± sorafenib therapy. In MA.22, RDA stratified 23 of 85 patients in Zone 1 as pCR nonresponders, 24 patients in Zone 2, an

An adaptive randomized trial of dialectical behavior therapy and cognitive behavior therapy for binge-eating.

Science.gov (United States)

Chen, E Y; Cacioppo, J; Fettich, K; Gallop, R; McCloskey, M S; Olino, T; Zeffiro, T A

2017-03-01

Early weak treatment response is one of the few trans-diagnostic, treatment-agnostic predictors of poor outcome following a full treatment course. We sought to improve the outcome of clients with weak initial response to guided self-help cognitive behavior therapy (GSH). One hundred and nine women with binge-eating disorder (BED) or bulimia nervosa (BN) (DSM-IV-TR) received 4 weeks of GSH. Based on their response, they were grouped into: (1) early strong responders who continued GSH (cGSH), and early weak responders randomized to (2) dialectical behavior therapy (DBT), or (3) individual and additional group cognitive behavior therapy (CBT+). Baseline objective binge-eating-day (OBD) frequency was similar between DBT, CBT+ and cGSH. During treatment, OBD frequency reduction was significantly slower in DBT and CBT+ relative to cGSH. Relative to cGSH, OBD frequency was significantly greater at the end of DBT (d = 0.27) and CBT+ (d = 0.31) although these effects were small and within-treatment effects from baseline were large (d = 1.41, 0.95, 1.11, respectively). OBD improvements significantly diminished in all groups during 12 months follow-up but were significantly better sustained in DBT relative to cGSH (d = -0.43). At 6- and 12-month follow-up assessments, DBT, CBT and cGSH did not differ in OBD. Early weak response to GSH may be overcome by additional intensive treatment. Evidence was insufficient to support superiority of either DBT or CBT+ for early weak responders relative to early strong responders in cGSH; both were helpful. Future studies using adaptive designs are needed to assess the use of early response to efficiently deliver care to large heterogeneous client groups.

Is response-guided therapy being applied in the clinical setting? The hepatitis C example.

Science.gov (United States)

Harris, Jennifer B; Ward, Melea A; Schwab, Phil

2015-02-01

Response-guided therapy (RGT) is a treatment model that bases adjustments to therapeutic regimens on individualized patient physiologic response. This approach is applied to patients with chronic hepatitis C virus (HCV) infection who are treated with a triple therapy regimen of boceprevir or telaprevir in combination with pegylated interferon and ribavirin. As RGT expands in other pharmacologic regimens, including the treatment of breast cancer and acute myeloid leukemia, a measurement of how this approach is applied in clinical practice is important to determine whether the benefits of RGT are being optimized. To measure adherence to the RGT guidelines and to the treatment futility rules based on the drug labeling information for boceprevir and for telaprevir in the treatment of patients with chronic HCV infection. A retrospective observational cohort study was conducted using the large Humana research database, which includes pharmacy, medical, and laboratory claims, as well as enrollment data for more than 1.5 million fully insured commercial members, 1.9 million Medicare Advantage members, and 2.4 million Medicare Part D members from all 50 states. The study population included patients aged ≥18 years to <90 years who were fully insured with commercial or Medicare Advantage coverage. A pharmacy claim for boceprevir or telaprevir was used to identify patients receiving triple therapy for HCV infection. Medical, pharmacy, and laboratory claims were reviewed from the date of the first boceprevir or telaprevir pharmacy claim between May 2011 and February 2012 through a 32-week follow-up period, during which patients were required to have continuous health plan enrollment eligibility. This time period allowed for the occurrences of required HCV RNA laboratory monitoring and the assessment of treatment patterns. The use of RGT for boceprevir and telaprevir includes the monitoring of HCV RNA levels at routine intervals to determine how to proceed with therapy

Comparison of (18)F-FET and (18)F-FLT small animal PET for the assessment of anti-VEGF treatment response in an orthotopic model of glioblastoma

DEFF Research Database (Denmark)

Nedergaard, Mette Kjoelhede; Michaelsen, Signe Regner; Perryman, Lara

2016-01-01

was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts. METHODS: Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow....... Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time. CONCLUSION: FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET...

Magnetic resonance imaging assessment of intraventricular dyssynchrony and delayed enhancement as predictors of response to cardiac resynchronization therapy in patients with heart failure of ischaemic and non-ischaemic etiologies

International Nuclear Information System (INIS)

Petryka, Joanna; Miśko, Jolanta; Przybylski, Andrzej; Śpiewak, Mateusz; Małek, Łukasz A.; Werys, Konrad; Mazurkiewicz, Łukasz; Gepner, Katarzyna; Croisille, Pierre; Demkow, Marcin; Rużyłło, Witold

2012-01-01

Purpose: To assess the value of dyssynchrony and myocardial viability assessment by cardiac magnetic resonance (CMR) in prediction of response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) of both ischaemic and non-ischaemic etiologies. Materials and methods: Patients scheduled for CRT in NYHA class II–IV, left ventricular ejection fraction <35%, QRS ≥ 120 ms were included. Tagged cine and late gadolinium enhancement (LGE) images were performed. Dyssynchrony was assessed with inTag toolbox and LGE was quantified using cutoff value at half of maximal signal in the scar. Cardiopulmonary exercise test, echocardiography and blood testing for NT-proBNP levels were done at baseline and 6 months after CRT. Results: 52 patients (age 60.3 ± 13 years) were included. 26 patients (50%) met response criteria. The ischaemic etiology of HF was more frequent (69% vs. 31%, p = 0.002), the percent of LGE was higher (7.7% [0–13.5%] vs. 19.0% (0–31.9%], p = 0.013), regional vector of circumferential strain variance (RVV) was lower (0.27 ± 0.08 vs. 0.34 ± 0.09, p = 0.009) and uniformity of radial strain was higher (0.72 ± 0.25 vs. 0.56 ± 0.29, p = 0.046) in non-responders vs. responders. Multivariate logistic regression showed that RVV predicted response to CRT (HR 2.3, 95% CI 1.02–5.02, p = 0.0430) independently of LGE and the etiology of heart failure. In the subgroup of patients with ischaemic HF the extend of transmural scar within myocardium was higher in non-responders vs. responders (26.3% vs. 15.0% respectively, p = 0.01) and was a predictor of response to CRT in univariable analysis (HR 0.87, 95% CI 0.77–0.98, p = 0.025) providing the sensitivity of 76% and specificity of 75% at the cutoff point of 18% in the prediction of poor response to CRT. In patients with non-ischaemic HF QRS was wider (162 ms vs. 140 ms, p = 0.04), regional vector of strain variance (RVV) was higher (0.39 vs. 0.25, p = 0.002) and uniformity of radial

Magnetic resonance imaging assessment of intraventricular dyssynchrony and delayed enhancement as predictors of response to cardiac resynchronization therapy in patients with heart failure of ischaemic and non-ischaemic etiologies

Energy Technology Data Exchange (ETDEWEB)

Petryka, Joanna, E-mail: joannapetryka@hotmail.com [Department of Coronary Artery Disease and Structural Heart Diseases, Institute of Cardiology, Warsaw (Poland); Cardiovascular Magnetic Resonance Unit, Institute of Cardiology, Warsaw (Poland); Miśko, Jolanta [Cardiovascular Magnetic Resonance Unit, Institute of Cardiology, Warsaw (Poland); Department of Radiology, Institute of Cardiology, Warsaw (Poland); Przybylski, Andrzej [Department of Arrhythmia, Institute of Cardiology, Warsaw (Poland); Śpiewak, Mateusz [Department of Coronary Artery Disease and Structural Heart Diseases, Institute of Cardiology, Warsaw (Poland); Cardiovascular Magnetic Resonance Unit, Institute of Cardiology, Warsaw (Poland); Małek, Łukasz A. [Cardiovascular Magnetic Resonance Unit, Institute of Cardiology, Warsaw (Poland); Department of Cardiology and Interventional Angiology, Institute of Cardiology, Warsaw (Poland); Werys, Konrad [Cardiovascular Magnetic Resonance Unit, Institute of Cardiology, Warsaw (Poland); Mazurkiewicz, Łukasz [Cardiovascular Magnetic Resonance Unit, Institute of Cardiology, Warsaw (Poland); Department of Cardiomyopathy, Institute of Cardiology, Warsaw (Poland); Gepner, Katarzyna [Department of Coronary Artery Disease, Institute of Cardiology, Warsaw (Poland); Croisille, Pierre [Creatis Laboratory, UMR CNRS 5515, INSERM, U1044, CHU Saint-Etienne, Universite de Lyon (France); Demkow, Marcin [Department of Coronary Artery Disease and Structural Heart Diseases, Institute of Cardiology, Warsaw (Poland); Rużyłło, Witold [Institute of Cardiology, Warsaw (Poland)

2012-10-15

Purpose: To assess the value of dyssynchrony and myocardial viability assessment by cardiac magnetic resonance (CMR) in prediction of response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) of both ischaemic and non-ischaemic etiologies. Materials and methods: Patients scheduled for CRT in NYHA class II–IV, left ventricular ejection fraction <35%, QRS ≥ 120 ms were included. Tagged cine and late gadolinium enhancement (LGE) images were performed. Dyssynchrony was assessed with inTag toolbox and LGE was quantified using cutoff value at half of maximal signal in the scar. Cardiopulmonary exercise test, echocardiography and blood testing for NT-proBNP levels were done at baseline and 6 months after CRT. Results: 52 patients (age 60.3 ± 13 years) were included. 26 patients (50%) met response criteria. The ischaemic etiology of HF was more frequent (69% vs. 31%, p = 0.002), the percent of LGE was higher (7.7% [0–13.5%] vs. 19.0% (0–31.9%], p = 0.013), regional vector of circumferential strain variance (RVV) was lower (0.27 ± 0.08 vs. 0.34 ± 0.09, p = 0.009) and uniformity of radial strain was higher (0.72 ± 0.25 vs. 0.56 ± 0.29, p = 0.046) in non-responders vs. responders. Multivariate logistic regression showed that RVV predicted response to CRT (HR 2.3, 95% CI 1.02–5.02, p = 0.0430) independently of LGE and the etiology of heart failure. In the subgroup of patients with ischaemic HF the extend of transmural scar within myocardium was higher in non-responders vs. responders (26.3% vs. 15.0% respectively, p = 0.01) and was a predictor of response to CRT in univariable analysis (HR 0.87, 95% CI 0.77–0.98, p = 0.025) providing the sensitivity of 76% and specificity of 75% at the cutoff point of 18% in the prediction of poor response to CRT. In patients with non-ischaemic HF QRS was wider (162 ms vs. 140 ms, p = 0.04), regional vector of strain variance (RVV) was higher (0.39 vs. 0.25, p = 0.002) and uniformity of radial

High cortisol awakening response is associated with an impairment of the effect of bright light therapy

DEFF Research Database (Denmark)

Martiny, Klaus Per Juul; Lunde, Marianne Anita; Undén, M

2009-01-01

OBJECTIVE: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non-seasonal major depression. METHOD: Patients were treated with sertraline in combination with bright or dim light therapy for a 5-week period. Saliva cortisol levels were measured in 63...... patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time-points: awakening and 20 and 60 min after awakening. RESULTS: Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas...... patients with a high CAR had no effect of bright light therapy compared with dim light therapy. CONCLUSION: High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from...

Complete pathological response after neoadjuvant therapy in patients with rectal adenocarcinoma

Directory of Open Access Journals (Sweden)

E.A. Sánchez-Pérez

2017-10-01

Full Text Available Background: Colorectal cancer is the fourth most common cancer and the second leading cause of death from cancer in the United States. Preoperative neoadjuvant therapy (chemotherapy and radiotherapy is the gold standard in the management of rectal cancer before surgical resection. The literature includes reports of absence of neoplastic cells after neoadjuvant therapy. There are no reports on complete pathological response to this type of therapy in Mexico. Objectives: Determine the percentage of patients with rectal adenocarcinoma with complete pathological response after neoadjuvant therapy. All patients were treated in a colorectal surgery department of a tertiary care hospital. Materials and methods: A total of 64 patients with rectal adenocarcinoma diagnosed by biopsy were treated from January 2010 to December 2015. Demographic data, tumour localisation, pathological report, TNM stage, neoadjuvant therapy, surgical procedure and postoperative pathological report were collected from patient records. Results: Mean patient age was 52.8 years (range of 26–73; 31 were women and 33 men. Twenty-seven patients (27 were stage II and 27 stage III. The preoperative biopsy results were classified as: well differentiated (10; moderately differentiated (48; and poorly differentiated/undifferentiated adenocarcinoma (6. Twenty patients received neoadjuvant therapy (31.2%. In these, 2 tumours were localised in the upper third of the rectum, 6 in the middle third, and 12 in the lower third. Six patients underwent abdominoperineal resection, 10 total mesorectal excision, and four posterior pelvic exenteration. Six patients undergoing neoadjuvant therapy had a complete pathological response. Conclusions: The percentage of patients with a complete pathological response is similar to that in other literature reports. More evidence is needed to define good prognosis factors in patients who might not require surgery after neoadjuvant therapy. Resumen

Therapy assessment of bone metastatic disease in the era of {sup 223}radium

Energy Technology Data Exchange (ETDEWEB)

Etchebehere, Elba; Brito, Ana Emilia [The University of Campinas, Division of Nuclear Medicine, Campinas (Brazil); Rezaee, Alireza; Langsteger, Werner [St. Vincent' s Hospital, Department of Nuclear Medicine and Endocrinology, PET - CT Center LINZ, Ordensklinikum, Linz (Austria); Beheshti, Mohsen [St. Vincent' s Hospital, Department of Nuclear Medicine and Endocrinology, PET - CT Center LINZ, Ordensklinikum, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine and Endocrinology, Salzburg (Austria)

2017-08-15

Defining an optimal imaging modality for assessment of therapy and the best time of evaluation are pivotal for ideal patient's management. {sup 223}Ra (Xofigo registered, formerly Alpharadin) has been approved by the FDA and European Medicines Agency for treatment of metastatic castration-resistant prostate cancer with painful osseous involvement. PET/CT imaging using various radiotracers such as {sup 18}F-FDG, {sup 18}F-FCH, {sup 68}Ga-PSMA and {sup 18}F-NaF have been investigated to mitigate the limitations of conventional imaging modalities. Diagnostic radiotracers that have properties similar to a therapeutic radiotracer will precisely assess of the possibility and efficacy of a treatment; this is the theranostic concept. An example of a diagnostic test employed for selecting targeted therapy is the combined use of {sup 18}F-fluoride PET/CT for evaluation of possible therapy with {sup 223}Ra. This review examines the most recent publications related to this topic. (orig.)

Approach of combined cancer gene therapy and radiation: response of promoters to ionizing radiation; Approche de therapie genique anti-cancereuse combinee a l'irradiation: etude de la reponse de promoteurs aux radiations ionisantes

Energy Technology Data Exchange (ETDEWEB)

Anstett, A

2005-09-15

Gene therapy is an emerging cancer treatment modality. We are interested in developing a radiation-inducible gene therapy system to sensitize the tumor vasculature to the effects of ionizing radiation (IR) treatment. An expression system based on irradiation-inducible promoters will drive the expression of anti-tumor genes in the tumor vasculature. Solid tumors are dependent on angio genesis, a process in which new blood vessels are formed from the pre-existing vasculature. Vascular endothelial cells are un transformed and genetically stable, thus avoiding the problem of resistance to the treatments. Vascular endothelial cells may therefore represent a suitable target for this therapeutic gene therapy strategy.The identification of IR-inducible promoters native to endothelial cells was performed by gene expression profiling using cDNA micro array technology. We describe the genes modified by clinically relevant doses of IR. The extension to high doses aimed at studying the effects of total radiation delivery to the tumor. The radio-inductiveness of the genes selected for promoter study was confirmed by RT-PCR. Analysis of the activity of promoters in response to IR was also assessed in a reporter plasmid. We found that authentic promoters cloned onto a plasmid are not suitable for cancer gene therapy due to their low induction after IR. In contrast, synthetic promoters containing repeated sequence-specific binding sites for IR-activated transcription factors such as NF-{kappa}B are potential candidates for gene therapy. The activity of five tandemly repeated TGGGGACTTTCCGC elements for NF-{kappa}B binding in a luciferase reporter was increased in a dose-dependent manner. Interestingly, the response to fractionated low doses was improved in comparison to the total single dose. Thus, we put present evidence that a synthetic promoter for NF-{kappa}B specific binding may have application in the radio-therapeutic treatment of cancer. (author)

Federal Radiological Monitoring and Assessment Center: Phase I Response

International Nuclear Information System (INIS)

Riland, C.; Bowman, D.R.; Lambert, R.; Tighe, R.

1999-01-01

A Federal Radiological Monitoring and Assessment Center (FRMAC) is established in response to a Lead Federal Agency (LFA) or State request when a radiological emergency is anticipated or has occurred. The FRMAC coordinates the off-site monitoring, assessment, and analysis activities during such an emergency. The FRMAC response is divided into three phases. FRMAC Phase 1 is a rapid, initial-response capability that can interface with Federal or State officials and is designed for a quick response time and rapid radiological data collection and assessment. FRMAC Phase 1 products provide an initial characterization of the radiological situation and information on early health effects to officials responsible for making and implementing protective action decisions

Face Validity of the Functional Assessment of Cancer Therapy-Breast Symptom Index (FACT- B into Formal Arabic

Directory of Open Access Journals (Sweden)

Loulou Kobeissi

2014-06-01

Full Text Available Background: Breast cancer affects over one million women annually and is the most common global malignancy among women. Extensive improvements have taken place in the management of breast cancer in recent years and a higher percentage of women are cured from this disease. A proper assessment of the quality of life of women with breast cancer is an essential component in disease management. The Functional Assessment of Cancer Therapy- Breast Symptom Index has been commonly used and well-validated among English speaking populations as well as other populations. To date, no formal translation and evaluation of the Functional Assessment of Cancer Therapy-Breast System Index exists in Arabic. Therefore, this study intends to translate, adapt and face-validate the Functional Assessment of Cancer Therapy-Breast System Index into Arabic, specifically in the context of the Lebanese culture. Methods: We conducted forward and backward translation in Arabic, combined with face validity by clinicians. This was followed by pre-testing to ensure the instrument’s adequacy and cultural sensitivity conducted by the administration of face-to-face interviews with individual breast cancer patients (n=33 and two focus groups (4 women/group to evaluate the relevance and appropriateness of each item and words used in the questionnaire. Results: Study results reinforced the value of the Arabic translated version of the Functional Assessment of Cancer Therapy-Breast System Index in capturing the quality of life of women with breast cancer in Lebanon. Conclusion: The instrument was perceived to be adequate, appropriate for use, culturally sensitive, simple as well as exhaustive. Suggestions have been made to enrich the instruments’ ability to incorporate other quality of life dimensions not captured, as well to enhance the cultural specificity of the Functional Assessment of Cancer Therapy-Breast System Index, when administered among Lebanese women diagnosed with

Physiological and psychological effects of walking in stay-in forest therapy.

Science.gov (United States)

Park, Bum-Jin; Tsunetsugu, Yuko; Morikawa, Takeshi; Kagawa, Takahide; Lee, Juyoung; Ikei, Harumi; Song, Chorong; Miyazaki, Yoshifumi

2014-01-01

To provide scientific evidence of the physiological and psychological effects of forest and urban environments on 47 young male adults undergoing stay-in forest therapy. Field experiments were conducted at four sites in Japan. At each site, 12 subjects participated in the experiment. The experiments were conducted in forest and urban environments, and the subjects' physiological and psychological responses to these environments were compared. On the first day, six subjects were sent to a forest area, and the other six were sent to an urban area as controls. The groups were switched the next day. Heart rate variability and heart rate were measured to assess physiological responses. The semantic differential method for assessing emotions, the reports of "refreshed" feeling, and the Profile of Mood States (POMS) were used to assess psychological responses. The physiological and psychological responses of each subject were recorded during and after walking, and the differences in indices were compared between the two environments. The forest environment was associated with a higher parasympathetic nervous activity, a lower sympathetic nervous activity, and a lower heart rate than the urban environment. The subjective evaluation scores were generally in accordance with the physiological reactions and were significantly higher in the forest environment than in the urban environment. POMS measurements showed that the forest environment was psychologically relaxing and enhanced psychological vigor. This study provided clear scientific evidence of the physiological effects of forest therapy. The results will contribute to the development of forest therapy research and support the inclusion of forest therapy in preventive medicine.

Alcohol-Aversion Therapy: Relation Between Strength of Aversion and Abstinence.

Science.gov (United States)

Cannon, Dale S.; And Others

1986-01-01

Assessed degree of alcohol aversion in 60 alcoholics who received emetic alcohol-aversion therapy. Results revealed changes in response to alcoholic, but not to nonalcoholic, flavors, including decreased consumption in taste tests, more negative flavor ratings, overt behavioral indicants of aversion and increased tachycardiac response. (Author/NB)

Therapeutic responses in systematic targeted alpha therapy trial for melanoma

International Nuclear Information System (INIS)

Raja, C.; Rizvi, S.M.A.; Song, E.Y.; Graham, P.; Kearsley, J.H.; Goldsmith, H.; Bosserhoff, A.; Morgenstern, A.; Apostolidis, C.; Reisfeld, R.

2006-01-01

Full text: The therapeutic response of melanoma patients after systemic alpha therapy has been investigated in an open-labeled Phase 1 dose escalation study to establish the effective dose of alpha-immunoconjugate 2l3 Bi-cDTPA-9.2.27 mAb (AIC). The tools used to investigate the effects were physical examination; the images of the tumours, pathology comparisons over 12 weeks; CT comparisons and changes in tumour marker over 8 weeks. The physical examination indicated varied tumour responses. One patient showed complete response at 12 weeks post-TAT, with 20 of 21 tumours completely regressing, the last reduced by 80%. The tumour beds were biopsied for staining; S l OO was negative and no viable cells were observed. Most patients showed stable disease at 2 weeks. In one patient the CT comparison of 8 weeks with baseline showed marked reduction in three lung lesions. At least 4/21 patients showed partial response at 4 to 8 weeks and the same number showed stable disease. The disease progressed in 7 patients. The tumour marker melanoma inhibitory activity protein (MIA) showed reductions over 8 weeks, and was consistent with observations in most patients. Complete and partial responses were observed in systemic TAT for stage IV melanoma, but there was no dose-response relationship

Proteomic approaches in cancer risk and response assessment.

Science.gov (United States)

Petricoin, Emanuel F; Liotta, Lance A

2004-02-01

Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy.

Assessment of Mobile Accident Response Capability

International Nuclear Information System (INIS)

1983-03-01

This report presents the results of a DOE-sponsored assessment of nuclear accident response resources. It identifies the mobile resources that could be required to respond to different types of nuclear accidents including major ones like TMI-2, identifies the resources currently available and makes recommendations for the design and construction of additional mobile accident response resources to supplement those already in existence. This project is referred to as the Mobile Accident Response Capability (MARC) program

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

Energy Technology Data Exchange (ETDEWEB)

Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

2014-04-01

Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

DEFF Research Database (Denmark)

Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

TH-E-202-03: PET for Tumor Response Evaluation

International Nuclear Information System (INIS)

Lu, W.

2016-01-01

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy. The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the

TH-E-202-03: PET for Tumor Response Evaluation

Energy Technology Data Exchange (ETDEWEB)

Lu, W. [University of Maryland School of Medicine (United States)

2016-06-15

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy. The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the

The host immunological response to cancer therapy: An emerging concept in tumor biology.

Science.gov (United States)

Voloshin, Tali; Voest, Emile E; Shaked, Yuval

2013-07-01

Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction-both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Rheumatoid Arthritis Risk Allele PTPRC Is Also Associated With Response to Anti–Tumor Necrosis Factor α Therapy

Science.gov (United States)

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2013-01-01

Objective Anti–tumor necrosis factor α (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (ΔDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ΔDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39–0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41–1.99). Conclusion Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections

Emotional, Motivational and Interpersonal Responsiveness of Children with Autism in Improvisational Music Therapy

Science.gov (United States)

Kim, Jinah; Wigram, Tony; Gold, Christian

2009-01-01

Through behavioural analysis, this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional, motivational and interpersonal responsiveness in children with autism during joint engagement episodes. The randomized controlled study (n = 10)…

Childhood maltreatment and the response to cognitive behavior therapy for chronic fatigue syndrome.

NARCIS (Netherlands)

Heins, M.J.; Knoop, H.; Lobbestael, J.; Bleijenberg, G.

2011-01-01

Objective: To examine the relationship between a history of childhood maltreatment and the treatment response to cognitive behavior therapy for chronic fatigue syndrome (CFS). Methods: A cohort study in a tertiary care clinic with a referred sample of 216 adult patients meeting the Centers for

Neurophysiological and behavioral responses to music therapy in vegetative and minimally conscious states

DEFF Research Database (Denmark)

O'Kelly, Julian; James, L.; Palaniappan, R.

2013-01-01

for preferred music (p = 0.029) across the VS cohort. Two VS cases are presented with concurrent changes (p ≤ 0.05) across measures indicative of discriminatory responses to both music therapy procedures. A MCS case study highlights how more sensitive selective attention may distinguish MCS from VS. Further...... of musical stimuli on arousal, attention and emotion, irrespective of verbal or motor deficits, however, an evidence base is lacking. To address this, a neurophysiological and behavioural study was undertaken comparing EEG, heart rate variability, respiration and behavioural responses of 20 healthy subjects...... responses (p ≤ 0.05) across healthy subjects corresponding to arousal and attention in response to preferred music including concurrent increases in respiration rate with globally enhanced EEG power spectra responses across frequency bandwidths. Whilst physiological responses were heterogeneous across...

Metabolic and clinical assessment of efficacy of cryoablation therapy on skeletal masses by {sup 18}F-FDG positron emission tomography/computed tomography (PET/CT) and visual analogue scale (VAS): initial experience

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Masala, Salvatore; Bartolucci, Alberto D.; Mammucari, Matteo; Simonetti, Giovanni [University Hospital Tor Vergata, Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, Rome (Italy); Schillaci, Orazio; Calabria, Ferdinando [University Hospital Tor Vergata, Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, Rome (Italy); I.R.C.C.S. Neuromed, Department of Nuclear Medicine and Neuroradiology, Pozzilli (Italy); Policlinico Tor Vegata, Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, Rome (Italy)

2011-02-15

Various therapy modalities have been proposed as standard treatments in management of bone metastases. Radiation therapy remains the standard of care for patients with localized bone pain, but up to 30% of them do not experience notable pain relief. Percutaneous cryoablation is a minimally invasive technique that induces necrosis by alternately freezing and thawing a target tissue. This technique is successfully used to treat a variety of malignant and benign diseases in different sites. {sup 18}F-FDG positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) is a single technique of imaging that provides in a ''single step'' both morphological and metabolic features of neoplastic lesions of the bone. The aim of this study was to evaluate the efficacy of the cryosurgical technique on secondary musculoskeletal masses according to semi-quantitative PET analysis and clinical-test evaluation with the visual analogue scale (VAS). We enrolled 20 patients with painful bone lesions (score pain that exceeded 4 on the VAS) that were non-responsive to treatment; one lesion per patient was treated. All patients underwent a PET-CT evaluation before and 8 weeks after cryotherapy; maximum standardized uptake value (SUV{sub max}) was measured before and after treatment for metabolic assessment of response to therapy. After treatment, 18 patients (90%) showed considerable reduction in SUV{sub max} value (>50%) suggestive of response to treatment; only 2 patients did not show meaningful reduction in metabolic activity. Our preliminary study demonstrates that quantitative analysis provided by PET correlates with response to cryoablation therapy as assessed by CT data and clinical VAS evaluation. (orig.)

Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

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Reinhard Meier

Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

Sustained Complete Response after Maintenance Therapy with Topotecan and Erlotinib for Recurrent Cervical Cancer with Distant Metastases

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Donato Callegaro-Filho

2014-01-01

Full Text Available Introduction: Recurrent cervical cancer is associated with a poor prognosis. Most treatment responses are partial and of short duration. The development of new therapies is vital to improve treatment for recurrent disease. Epidermal growth factor receptor (EGFR inhibitors may have a role in this setting. Case Description: A 53-year-old woman with stage IB2 squamous cell carcinoma of the cervix was initially treated with chemoradiation. Six months after completing treatment, she developed a recurrence in the common iliac and para-aortic lymph nodes above the previous radiation field and was treated with additional radiation therapy. Two years later, she developed recurrent disease in the left supraclavicular lymph nodes and was treated with chemoradiation followed by 3 cycles of adjuvant cisplatin and topotecan. She had a complete response and was placed on maintenance therapy with topotecan and erlotinib, which was well tolerated and produced minimal side effects. After 20 months of maintenance therapy, it was discontinued given the long interval without evidence of disease. The patient is currently without evidence of disease 5 years after completing the topotecan-erlotinib treatment. Conclusion: We noted a sustained response in a patient with recurrent metastatic cervical cancer treated with radiotherapy, cisplatin, and topotecan followed by maintenance therapy with topotecan and erlotinib. Further evaluation of the role of EGFR inhibitors in this setting should be considered given their favorable toxicity profile and biological relevance.

Assessing the relationship between the WNSSP and therapeutic participation in adolescents in low response states following severe traumatic brain injury.

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Patrick, Peter D; Wamstad, Julia Buch; Mabry, Jennifer L; Smith-Janik, Shannan; Gurka, Matthew J; Buck, Marcia L; Blackman, James A

2009-06-01

This study examines the relationship between scores on the Western Neuro Sensory Stimulation Profile (WNSSP) and therapeutic participation as it relates to rehabilitation readiness (RR) in adolescents with low response following severe traumatic brain injury (TBI). This is a serial observational design using multiple measures of clinical status and participation. Ten children, mean age 16.7 years, who remained in a low response state (30 days or more) were assessed with the WNSSP and videotaped during physical and occupational therapy sessions. Associations were evaluated between WNSSP scores and participation scores related to arousal, awareness and communication. The WNSSP was only associated with the communication score (p < 0.0001). The arousal and awareness scores had no significant impact on the WNSSP score. These results suggest that scores on the WNSSP may be related to the return of communication skills in adolescents in low response states as one part of assessing their therapeutic participation and ultimate rehabilitation readiness. This ability may assist in making decisions regarding care planning.

[Therapy-resistant and therapy-refractory arterial hypertension].

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Wallbach, M; Koziolek, M J

2018-05-02

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

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Chu, Michael Kok Loon

Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

Qualitative assessment of awake nasopharyngoscopy for prediction of oral appliance treatment response in obstructive sleep apnoea.

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Sutherland, Kate; Chan, Andrew S L; Ngiam, Joachim; Darendeliler, M Ali; Cistulli, Peter A

2018-01-23

Clinical methods to identify responders to oral appliance (OA) therapy for obstructive sleep apnoea (OSA) are needed. Awake nasopharyngoscopy during mandibular advancement, with image capture and subsequent processing and analysis, may predict treatment response. A qualitative assessment of awake nasopharyngoscopy would be simpler for clinical practice. We aimed to determine if a qualitative classification system of nasopharyngoscopic observations reflects treatment response. OSA patients were recruited for treatment with a customised two-piece OA. A custom scoring sheet was used to record observations of the pharyngeal airway (velopharynx, oropharynx, hypopharynx) during supine nasopharyngoscopy in response to mandibular advancement and performance of the Müller manoeuvre. Qualitative scores for degree ( 75%), collapse pattern (concentric, anteroposterior, lateral) and diameter change (uniform, anteroposterior, lateral) were recorded. Treatment outcome was confirmed by polysomnography after a titration period of 14.6 ± 9.8 weeks. Treatment response was defined as (1) Treatment AHI  50% AHI reduction and (3) > 50% AHI reduction. Eighty OSA patients (53.8% male) underwent nasopharyngoscopy. The most common naspharyngoscopic observation with mandibular advancement was a small ( 75% velopharyngeal collapse on performance of the Müller manoeuvre. Mandibular advancement reduced the observed level of pharyngeal collapse at all three pharyngeal regions (p < 0.001). None of the nasopharyngoscopic qualitative scores differed between responder and non-responder groups. Qualitative assessment of awake nasopharyngoscopy appears useful for assessing the effect of mandibular advancement on upper airway collapsibility. However, it is not sensitive enough to predict oral appliance treatment outcome.

Approach of combined cancer gene therapy and radiation: response of promoters to ionizing radiation; Approche de therapie genique anti-cancereuse combinee a l'irradiation: etude de la reponse de promoteurs aux radiations ionisantes

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Anstett, A

2005-09-15

Gene therapy is an emerging cancer treatment modality. We are interested in developing a radiation-inducible gene therapy system to sensitize the tumor vasculature to the effects of ionizing radiation (IR) treatment. An expression system based on irradiation-inducible promoters will drive the expression of anti-tumor genes in the tumor vasculature. Solid tumors are dependent on angio genesis, a process in which new blood vessels are formed from the pre-existing vasculature. Vascular endothelial cells are un transformed and genetically stable, thus avoiding the problem of resistance to the treatments. Vascular endothelial cells may therefore represent a suitable target for this therapeutic gene therapy strategy.The identification of IR-inducible promoters native to endothelial cells was performed by gene expression profiling using cDNA micro array technology. We describe the genes modified by clinically relevant doses of IR. The extension to high doses aimed at studying the effects of total radiation delivery to the tumor. The radio-inductiveness of the genes selected for promoter study was confirmed by RT-PCR. Analysis of the activity of promoters in response to IR was also assessed in a reporter plasmid. We found that authentic promoters cloned onto a plasmid are not suitable for cancer gene therapy due to their low induction after IR. In contrast, synthetic promoters containing repeated sequence-specific binding sites for IR-activated transcription factors such as NF-{kappa}B are potential candidates for gene therapy. The activity of five tandemly repeated TGGGGACTTTCCGC elements for NF-{kappa}B binding in a luciferase reporter was increased in a dose-dependent manner. Interestingly, the response to fractionated low doses was improved in comparison to the total single dose. Thus, we put present evidence that a synthetic promoter for NF-{kappa}B specific binding may have application in the radio-therapeutic treatment of cancer. (author)

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

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