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  1. Nitrite therapy improves survival postexposure to chlorine gas

    Science.gov (United States)

    Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis

    2014-01-01

    Exposure to relatively high levels of chlorine (Cl2) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl2 exposure, could prevent Cl2 gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl2 gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl2 exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl2-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl2 gas exposure that is amenable to administration in mass-casualty scenarios. PMID:25326579

  2. Nitrite therapy improves survival postexposure to chlorine gas.

    Science.gov (United States)

    Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis; Patel, Rakesh P

    2014-12-01

    Exposure to relatively high levels of chlorine (Cl₂) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl₂ exposure, could prevent Cl₂ gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl₂ gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl₂ exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl₂-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl₂ gas exposure that is amenable to administration in mass-casualty scenarios. Copyright © 2014 the American Physiological Society.

  3. Does ifosfamide therapy improve survival of patients with dedifferentiated chondrosarcoma?

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    Kawaguchi, Satoshi; Sun, Tao; Lin, Patrick P; Deavers, Michael; Harun, Nusrat; Lewis, Valerae O

    2014-03-01

    Dedifferentiated chondrosarcoma remains a significant therapeutic challenge. Studies performed to date have not identified efficacious chemotherapy regimens for this disease. We sought to (1) evaluate the disease-specific survival at 2 and 5 years of patients with dedifferentiated chondrosarcoma; (2) assess the prognostic variables (both patient- and treatment-related), including the use of chemotherapy with ifosfamide, that relate to survivorship; and (3) assess specific toxicities associated with ifosfamide use. Data from 41 patients with dedifferentiated chondrosarcoma diagnosed and treated at the University of Texas MD Anderson Cancer Center from 1986 to 2010 were analyzed for demographics, treatments, oncologic outcomes, and prognostic variables. There were 14 women and 27 men. The mean age at diagnosis was 58 years (range, 26-86 years). Seven patients presented with metastasis. Surgical resection alone was performed in 11 patients; resection and chemotherapy in 26 patients; resection and radiotherapy in two patients; and resection, chemotherapy, and radiotherapy in two patients. Ifosfamide-based regimens were used for 16 patients. In general, ifosfamide was used when the tumor was located in the trunk or if cisplatin was discontinued as a result of toxicity. Minimum followup was 8 months (median, 68 months; range, 8-281 months). Survival was estimated using Kaplan-Meier plots and analyzed by using the Cox proportional hazards model. Disease-specific survival rates at 2 and 5 years were 33% and 15%, respectively. Multivariate analysis revealed that treatment without ifosfamide-based chemotherapy was the only independent negative prognostic factor for disease-specific survival (hazard ratio, 0.4; 95% confidence interval, 0.17-0.92; p = 0.03). Ifosfamide was discontinued in a patient as a result of renal dysfunction and was decreased in dose in another patient who developed encephalopathy. In this small retrospective study, it appeared that ifosfamide

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

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    Coventry BJ

    2015-04-01

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

  5. Adjuvant radiation therapy is associated with improved survival for adenoid cystic carcinoma of the breast.

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    Coates, Jodi M; Martinez, Steve R; Bold, Richard J; Chen, Steven L

    2010-09-15

    The role of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast remains unclear. We queried the Surveillance, Epidemiology, and End Results database for patients with breast ACC resected between 1988 and 2005, and divided patients based on the receipt of RT. Univariate and multivariate survival comparisons were made for overall and disease-specific survival. Three hundred seventy six patients met criteria for inclusion. Demographics and staging were similar between groups. Univariate analysis revealed an absolute overall and cause-specific survival benefit of 21% and 7% at 10 years (P = 0.005 and P = 0.12 respectively). In the multivariate analysis, RT was a significant predictor of overall and cause-specific survival with hazard ratios of 0.44 (95% Confidence interval (CI) = 0.22-0.88) and 0.1 (95% CI: 0.01-0.88), respectively. RT after local surgical therapy for ACC of the breast improved both cause-specific and overall survival. Use of RT in this rare tumor should be considered in patients otherwise eligible for RT. (c) 2010 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2017-12-01

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

  7. Do Increased Doses to Stem-Cell Niches during Radiation Therapy Improve Glioblastoma Survival?

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    Sebastian Adeberg

    2016-01-01

    Full Text Available Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS and overall survival (OS in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n=54 who received higher doses (Dmean ≥ 40 Gy to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p=0.013. Furthermore, higher doses (Dmean ≥ 30 Gy to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p=0.025. Conclusion. Moderate higher IL SVZ doses (≥40 Gy and CL SVZ doses (≥30 Gy are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial.

  8. Adjuvant chemotherapy is associated with improved survival after esophagectomy without induction therapy for node-positive adenocarcinoma.

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    Speicher, Paul J; Englum, Brian R; Ganapathi, Asvin M; Mulvihill, Michael S; Hartwig, Matthew G; Onaitis, Mark W; D'Amico, Thomas A; Berry, Mark F

    2015-01-01

    This study investigated adjuvant chemotherapy (AC) use after esophagectomy without induction therapy for node-positive (pN+) adenocarcinoma using the National Cancer Database, including the impact of complications related to surgery (CRS) on outcomes. Predictors of AC use in 1694 patients in the National Cancer Data Base who underwent R0 esophagectomy from 2003-2011 without induction therapy for pN+ adenocarcinoma of the middle or lower esophagus and survived more than 30 days were identified with multivariable logistic regression. The impact of AC on survival was estimated using Kaplan-Meier and Cox-proportional hazards methods. AC was given to 874 of 1694 (51.6%) patients; 618 (70.7%) AC patients received radiation. Older age (adjusted odds ratio [AOR] 0.58/decade, p improved survival in multivariate analysis (hazard ratio 0.67, p = 0.008). Receiving radiation in addition to AC did not improve survival (p = 0.35). Although CRS was associated with worse survival, patients who had CRS but received AC had superior survival compared to patients who did not have CRS or get AC (p = 0.016). AC after esophagectomy is associated with improved survival but was only used in half of patients with pN+ esophageal adenocarcinoma. We also found that the addition of radiation to AC was not associated with a survival benefit. CRS predict worse long-term survival and lower the chance of getting AC, but even patients with CRS had improved survival when given AC.

  9. Pediatric-protocol of multimodal therapy is associated with improved survival in AYAs and adults with rhabdomyosarcoma.

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    Fischer, Trevan D; Gaitonde, Shrawan G; Bandera, Bradley C; Raval, Mehul V; Vasudevan, Sanjeev A; Gow, Kenneth W; Beierle, Elizabeth A; Doski, John J; Goldin, Adam B; Langer, Monica; Nuchtern, Jed G; Stern, Stacey; Foshag, Leland J; Goldfarb, Melanie

    2018-02-01

    Multimodal therapy is the standard treatment for pediatric rhabdomyosarcoma, but for adolescents and young adults (AYAs: ages 15-39) and older adults with rhabdomyosarcoma, the use of adjuvant therapy is variable, and survival is greatly decreased compared with younger patients. All patients with rhabdomyosarcoma who had a curative operative were identified from the 1998-2012 National Cancer Database. Regression analyses identified independent factors relating to receipt of multimodal therapy (resection + chemotherapy + radiation) and the influence of multimodal therapy on 5-year overall survival. Of 2,312 patients, 44% were pediatric (age multimodal therapy least often (pediatric: 62%, AYA: 46%, adults: 24%; P multimodal therapy was associated with a decreased risk of death within 5 years (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.84), with similar findings after stratification by age (pediatric: HR 0.64, 95% CI 0.48-0.85; AYA: HR 0.72, 95% CI 0.55-0.95; adult: HR 0.74, 95% CI 0.58-0.93). In AYAs only, black and Hispanic patients had an increased risk of death within 5 years (black patients: HR 1.64, 95% CI 1.14-2.37; Hispanic patients: HR 1.62, 95% CI 1.11-2.36). This first large national study suggests that multimodal therapy is independently associated with improved survival for both AYAs and adults with rhabdomyosarcoma, similar to pediatric patients, but multimodal therapy is appreciably underused. Implementation of multimodal therapy for all patients could potentially improve overall outcomes of patients with rhabdomyosarcoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Improved survival of cardiac transplantation candidates with implantable cardioverter defibrillator therapy: role of beta-blocker or amiodarone treatment.

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    Ermis, Cengiz; Zadeii, Gino; Zhu, Alan X; Fabian, William; Collins, Joanne; Lurie, Keith G; Sakaguchi, Scott; Benditt, David G

    2003-06-01

    Survival in patients awaiting cardiac transplantation is poor due to the severity of left ventricular dysfunction and the susceptibility to ventricular arrhythmia. The potential role of implantable cardioverter defibrillators (ICDs) in this group of patients has been the subject of increasing interest. The aims of this study were to ascertain whether ICDs improve the survival rate of patients on the waiting list for cardiac transplantation and whether any improvement is independent of concomitant beta-blocker or amiodarone therapy. Data comprised findings from 310 consecutive patients at a single center who were evaluated and deemed suitable for cardiac transplantation and placed on the waiting list. Kaplan-Meier actuarial approach was used for survival analysis. Survival analysis censored patients at time of transplantation or death. Of the 310 patients, 111 (35.8%) underwent successful cardiac transplantation and 164 (52.9%) died while waiting; 35 patients remain on the waiting list. Fifty-nine (19%) patients had ICD placement for ventricular arrhythmias prior to or after being listed. Twenty-nine (49.1%) ICD patients survived until cardiac transplantation, 13 (22%) patients died, and 17 (28.8%) remain on the waiting list. Among non-ICD patients, 82 (32.7%) received transplants, 151 (60.2%) died, and 18 (7.2%) remain on the waiting list. Survival rates at 6 months and 1, 2, 3, and 4 years were better for all ICD patients compared to non-ICD patients (log-rank x2, P = 0.0001). By multivariate analysis, ICD therapy and beta-blocker treatment were the strongest predictors of survival. Further, ICD treatment was associated with improved survival independent of concomitant treatment with beta-blocker or amiodarone. Among ICD and non-ICD patients treated with a beta-blocker or amiodarone, survivals at the 1 and 4 years were 93% vs 69% and 57% vs 32%, respectively (log-rank x2, P = 0.003). ICD therapy is associated with improved survival in high-risk cardiac transplant

  11. Inflammation, apoptosis, and necrosis induced by neoadjuvant fas ligand gene therapy improves survival of dogs with spontaneous bone cancer.

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    Modiano, Jaime F; Bellgrau, Donald; Cutter, Gary R; Lana, Susan E; Ehrhart, Nicole P; Ehrhart, Ej; Wilke, Vicki L; Charles, J Brad; Munson, Sibyl; Scott, Milcah C; Pozniak, John; Carlson, Cathy S; Schaack, Jerome; Duke, Richard C

    2012-12-01

    Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas.

  12. The Addition of Postoperative Chemotherapy is Associated with Improved Survival in Patients with Pancreatic Cancer Treated with Preoperative Therapy.

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    Roland, Christina L; Katz, Matthew H G; Tzeng, Ching-Wei D; Lin, Heather; Varadhachary, Gauri R; Shroff, Rachna; Javle, Milind; Fogelman, David; Wolff, Robert A; Vauthey, Jean N; Crane, Christopher H; Lee, Jeffrey E; Fleming, Jason B

    2015-12-01

    Preoperative/neoadjuvant therapy (NT) is increasingly utilized for the treatment of pancreatic ductal adenocarcinoma (PDAC). However, little data exist regarding information on the use of additional postoperative therapy following NT. The lymph node ratio (LNR) is a prognostic marker of oncologic outcomes after NT and resection. In this study, we evaluated the effectiveness of postoperative therapy following NT, stratified by LNR. A prospective tumor registry database was queried to identify patients with PDAC who underwent resection following NT from 1990 to 2008. Clinicopathologic factors were compared to identify associations with overall survival (OS) and time to recurrence (TTR) based on postoperative chemotherapy status. Thirty-six (14 %) of the 263 patients received additional postoperative therapy. No differences were observed in the pathologic characteristics between patients who received postoperative chemotherapy and those who did not. The median LNR was 0.12 for patients with N + disease. Following NT, the administration of postoperative therapy was associated with improved median OS (72 vs. 33 months; p = 0.008) for patients with an LNR chemotherapy and OS for patients with LNR ≥ 0.15. Multivariate analysis demonstrated that the administration of postoperative systemic therapy in patients with a low LNR was associated with a reduced risk of death (hazard ratio 0.49; p = 0.02). Postoperative chemotherapy after NT in patients with low LNR is associated with improved oncologic outcomes.

  13. Antibody/doxycycline combined therapy for pulmonary ricinosis: Attenuation of inflammation improves survival of ricin-intoxicated mice

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    Yoav Gal

    2014-01-01

    Full Text Available Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biological warfare due to its high availability and ease of preparation. Pulmonary exposure to ricin results in the generation of an acute edematous inflammation followed by respiratory insufficiency and death. Passive immunization with polyclonal anti-ricin antibodies conferred protection against pulmonary ricinosis, however, at clinically-relevant time points for treatment, survival rates were limited. In this study, intranasal instillation of a lethal dose of ricin to mice, served as a lung challenge model for the evaluation and comparison of different therapeutic modalities against pulmonary ricinosis. We show that treatment with doxycycline resulted in a significant reduction of pro-inflammatory cytokines, markers of oxidative stress and capillary permeability in the lungs of the mice. Moreover, survival rates of mice intoxicated with ricin and treated 24 h later with anti-ricin antibody were significantly improved by co-administration of doxycycline. In contrast, co-administration of the steroid drug dexamethasone with anti-ricin antibodies did not increase survival rates when administered at late hours after intoxication, however dexamethasone did exert a positive effect on survival when applied in conjunction with the doxycycline treatment. These studies strongly suggest that combined therapy, comprised of neutralizing anti-ricin antibodies and an appropriate anti-inflammatory agent, can promote high-level protection against pulmonary ricinosis at clinically-relevant time points post-exposure.

  14. Continuous Renal Replacement Therapy Improves Survival in Severely Burned Military Casualties With Acute Kidney Injury

    National Research Council Canada - National Science Library

    Chung, Kevin K; Juncos, , Luis A; Wolf, Steven E; Mann, Elizabeth E; Renz, Evan M; White, Christopher E; Barillo, David J; Clark, Richard A; Jones, John A; Edgecombe, Harcourt P

    2007-01-01

    .... We wondered whether early use of continuous renal replacement therapy (CRRT) changes outcomes in severely burned military casualties with predetermined criteria for acute kidney injury. Methods...

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

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

    2016-03-15

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

  16. Metastatic lung cancer in the age of targeted therapy: improving long-term survival

    OpenAIRE

    Del Rivero, Jaydira; Enewold, Lindsey; Thomas, Anish

    2016-01-01

    Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term surviva...

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

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

    2017-06-01

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

  18. Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma.

    Science.gov (United States)

    Hosry, Jeff; Mahale, Parag; Turturro, Francesco; Miranda, Roberto N; Economides, Minas P; Granwehr, Bruno P; Torres, Harrys A

    2016-12-01

    Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non-Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV-infected patients with diffuse large B-cell lymphoma (DLBCL) is unclear. We therefore analyzed AVT's impact on oncologic outcomes of HCV-infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004-May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon-based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p = 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement. Cases never given AVT had DLBCL more refractory to first-line chemotherapy than that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% vs. 32%; p = 0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse 5-year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01-5.3]; p = 0.04). Furthermore, AVT improved 5-year OS rates among cases in both univariate (median [Interquartile range]: 39 [26-56] vs. 16 [6-41] months, p = 0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06-0.69]; p = 0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5-year OS. © 2016 UICC.

  19. Overall survival of patients with advanced pancreatic cancer improved with an increase in second-line chemotherapy after gemcitabine-based therapy.

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    Zhang, Yuan Dong; Yang, Qiong; Jiang, Zhi Min; Ma, Wen; Zhou, Si Wei; Xie, De Rong

    2011-03-09

    In the last decade, gemcitabine-based regimen as first-line therapy has demonstrated low efficacy regarding overall survival benefit for patients with advanced pancreatic cancer. The purpose of this study was to explore a new strategy, such as an increased second-line chemotherapy rate, in order to improve overall survival. Retrospective data analysis. The data in the literature on gemcitabine-based therapy for patients with advanced pancreatic cancer were collected by searching databases, such as MEDLINE, EMBASE, the Chinese Biomedical Literature Analysis and Retrieval System, and EBM Reviews (Cochrane Database of Systematic Reviews). Linear regression was used to explore the relationship between overall survival and second-line chemotherapy. The primary endpoint was overall survival. The secondary endpoints were progression-free survival and residual survival. Ten randomized controlled trials, involving 2,679 patients, were included in the present study. The results indicated that overall survival was positively correlated with a combination of chemotherapy, stage of disease and second-line chemotherapy in patients with advanced pancreatic cancer (r = 0.753; P = 0.003). Meanwhile median overall survival would be prolonged about 1.56 days if second-line chemotherapy was increased by 1% (t = 4.33; P = 0.001). Progression-free survival was not significantly correlated with second-line chemotherapy (r = 0.092; P = 0.701); in contrast, residual survival was positively correlated with second-line chemotherapy (r = 0.717; P chemotherapy in patients with advanced pancreatic cancer; more attention should be paid after first-line therapy which must be administered skillfully in order to improve overall survival, and this is worthy of further study.

  20. Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival.

    Science.gov (United States)

    Powe, Desmond G; Voss, Melanie J; Zänker, Kurt S; Habashy, Hany O; Green, Andrew R; Ellis, Ian O; Entschladen, Frank

    2010-11-01

    Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary.

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

    LENUS (Irish Health Repository)

    2011-04-01

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

  2. Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base.

    Science.gov (United States)

    Pezzi, Todd A; Mohamed, Abdallah S R; Sheu, Tommy; Blanchard, Pierre; Sandulache, Vlad C; Lai, Stephen Y; Cabanillas, Maria E; Williams, Michelle D; Pezzi, Christopher M; Lu, Charles; Garden, Adam S; Morrison, William H; Rosenthal, David I; Fuller, Clifton D; Gunn, G Brandon

    2017-05-01

    The outcomes of patients with unresected anaplastic thyroid carcinoma (ATC) from the National Cancer Data Base (NCDB) were assessed, and potential correlations were explored between radiation therapy (RT) dose and overall survival (OS). The study cohort was comprised of patients who underwent either no surgery or grossly incomplete resection. Correlates of OS were explored using univariate analysis and multivariable analysis (MVA). In total, 1288 patients were analyzed. The mean patient age was 70.2 years, 59.7% of patients were women, and 47.6% received neck RT. The median OS was 2.27 months, and 11% of patients remained alive at 1 year. A positive RT dose-survival correlation was observed for the entire study cohort, for those who received systemic therapy, and for those with stage IVA/IVB and IVC disease. On MVA, older age (hazard ratio [HR], 1.317; 95% confidence interval [CI], 1.137-1.526), ≥ 1 comorbidity (HR, 1.587; 95% CI, 1.379-1.827), distant metastasis (HR, 1.385; 95% CI, 1.216-1.578), receipt of systemic therapy (HR, 0.637; 95% CI, 0.547-0.742), and receipt of RT compared with no RT (Cancer 2017;123:1653-1661. © 2017 American Cancer Society. © 2016 American Cancer Society.

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

  5. Does beta-blocker therapy improve the survival of patients with metastatic non-small cell lung cancer?

    Science.gov (United States)

    Aydiner, Adnan; Ciftci, Rumeysa; Karabulut, Senem; Kilic, Leyla

    2013-01-01

    To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (±2.87) months (95%CI: 13.62-24.88) in the BB group and 13.20 (±2.37) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.

  6. Prolongation of Off-Cycle Interval by Finasteride Is Not Associated with Survival Improvement in Intermittent Androgen Deprivation Therapy in LNCaP Tumor Model

    Science.gov (United States)

    Wang, Yujuan; Gupta, Shubham; Hua, Vi; Ramos-Garcia, Raquel; Shevrin, Daniel; Jovanovic, Borko D.; Nelson, Joel B

    2009-01-01

    BACKGROUND We have previously reported that finasteride administration in intermittent androgen deprivation therapy (IADT) can improve survival of nude mice bearing LNCaP xenograft tumors when the duration of off-cycle in IADT was fixed. A recent retrospective study showed that addition of finasteride doubled the duration of the off-cycle, without changing progression to castration resistance. In view of the above difference, we attempted to investigate the relationship of 5α-reductase inhibition with the off-cycle interval and overall survival in a murine model. METHODS Subcutaneous LNCaP tumors were established in nude mice (Balb/C-Nu). After the tumors reached a size of 0.5 cm in diameter, the mice were castrated and followed up for 2 weeks after which they were randomized to continuous androgen deprivation (CAD), CAD plus finasteride, IADT, and IADT plus finasteride. The off-cycle was discontinued when the tumor volume was doubled. Subsequent cycles were carried out similarly. RESULTS Use of finasteride during the off-cycle of IADT doubled the first off-cycle duration. However, prolongation of the off-cycle by finasteride did not translate into an increase in overall survival. CONCLUSIONS The survival advantage of IADT+F over IADT that we previously reported was lost when the off-cycle prolongation by finasteride was allowed. Maximum possible lengthening of the off-cycle by 5α-reductase inhibition is not associated with survival improvement in this animal model. PMID:19739129

  7. Granulocyte-colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acute-on-chronic liver failure.

    Science.gov (United States)

    Duan, Xue-Zhang; Liu, Fang-Fang; Tong, Jing-Jing; Yang, Hao-Zhen; Chen, Jing; Liu, Xiao-Yan; Mao, Yuan-Li; Xin, Shao-Jie; Hu, Jin-Hua

    2013-02-21

    To evaluate the safety and efficacy of granulocyte-colony stimulating factor (G-CSF) therapy in patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF). Fifty-five patients with HBV-associated ACLF were randomized into two groups: the treatment group and the control group. Twenty-seven patients in the treatment group received G-CSF (5 μg/kg per day, six doses) treatment plus standard therapy, and 28 patients in the control group received standard therapy only. The peripheral CD34(+) cell count was measured consecutively by flow cytometry. Circulating white blood cell count, biochemical parameters, and other clinical data of these patients were recorded and analyzed. All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate. The peripheral neutrophil and CD34(+) cell counts in the G-CSF group increased on day 3 from the onset of therapy, continued to rise on day 7, and remained elevated on day 15 compared to those of the control group. Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy, compared to that in the controls (P = 0.041). Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7 (P = 0.004) and remained high on day 30 from the onset of G-CSF therapy (P liver function and the survival rate of these patients.

  8. Improving Survival in Decompensated Cirrhosis

    Directory of Open Access Journals (Sweden)

    Amar Nath Mukerji

    2012-01-01

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

  9. Adding the implantable cardioverter-defibrillator to cardiac resynchronization therapy is associated with improved long-term survival in ischaemic, but not in non-ischaemic cardiomyopathy

    DEFF Research Database (Denmark)

    Witt, Christoffer Tobias; Kronborg, Mads Brix; Nohr, Ellen Aagaard

    2015-01-01

    AIMS: Cardiac resynchronization therapy (CRT) improves symptoms, left ventricular function, and survival in patients with heart failure (HF) and wide QRS. The benefit of adding implantable cardioverter-defibrillator (ICD) backup is debated. We analysed the long-term outcome of patients with HF due...... to ischaemic cardiomyopathy (ICM) or non-ischaemic cardiomyopathy (NICM) treated with a CRT device with or without defibrillator backup. METHODS AND RESULTS: In this observational study, consecutive patients with an ejection fraction ≤35% and QRS width ≥120 ms receiving a CRT device at Aarhus University...

  10. Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria.

    Science.gov (United States)

    Martins, Yuri C; Clemmer, Leah; Orjuela-Sánchez, Pamela; Zanini, Graziela M; Ong, Peng Kai; Frangos, John A; Carvalho, Leonardo J M

    2013-04-24

    Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. In the experimental model of cerebral malaria (ECM) by Plasmodium berghei ANKA, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ECM. However, the dose and administration route used is associated with cardiovascular side effects such as hypotension and bradycardia in humans and mice, which could preclude its potential use as adjunctive treatment in HCM. In the present study, alternative delivery systems for nimodipine during late-stage ECM in association with artesunate were searched to define optimal protocols to achieve maximum efficacy in increasing survival in rescue therapy while causing the least cardiac side effects. The baseline electrocardiogram (ECG) and arterial pressure characteristics of uninfected control animals and of mice with ECM and its response upon rescue treatment with artesunate associated or not with nimodipine is also analysed. Nimodipine, given at 0.5 mg/kg/day via a slow and continuous delivery system by osmotic pumps, increases survival of mice with ECM when used as adjunctive treatment to artesunate. Mice with ECM showed hypotension and ECG changes, including bradycardia and increases in PR, QRS, QTc and ST interval duration. ECM mice also show increased QTc dispersion, heart rate variability (HRV), RMSSD, low frequency (LF) and high frequency (HF) bands of the power spectrum. Both sympathetic and parasympathetic inputs to the heart were increased, but there was a predominance of sympathetic tone as demonstrated by an increased LF/HF ratio. Nimodipine potentiated bradycardia when given by bolus injection, but not when via osmotic pumps. In addition, nimodipine shortened PR duration and improved HRV, RMSSD, LF and HF powers in mice with ECM. In addition, nimodipine did not increased

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

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Graham D. [University of Western Ontario, London, Ontario (Canada); Pickles, Tom [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Crook, Juanita [Department of Radiation Oncology, Kelowna General Hospital, Kelowna, British Columbia (Canada); Martin, Andre-Guy; Vigneault, Eric [Department of Radiation Oncology, L' Hotel Dieu de Quebec, Quebec City, Quebec (Canada); Cury, Fabio L. [Department of Radiation Oncology, Montreal General Hospital, Montreal, Quebec (Canada); Morris, Jim [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Catton, Charles [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Lukka, Himu [Department of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario (Canada); Warner, Andrew [Department of Radiation Oncology, London Health Sciences Center, London, Ontario (Canada); Yang, Ying [University of Waterloo, Waterloo, Ontario (Canada); Rodrigues, George, E-mail: George.Rodrigues@lhsc.on.ca [University of Western Ontario, London, Ontario (Canada); Department of Radiation Oncology, London Health Sciences Center, London, Ontario (Canada)

    2015-03-01

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

  12. Adding the implantable cardioverter-defibrillator to cardiac resynchronization therapy is associated with improved long-term survival in ischaemic, but not in non-ischaemic cardiomyopathy.

    Science.gov (United States)

    Witt, Christoffer Tobias; Kronborg, Mads Brix; Nohr, Ellen Aagaard; Mortensen, Peter Thomas; Gerdes, Christian; Jensen, Henrik Kjærulf; Nielsen, Jens Cosedis

    2016-03-01

    Cardiac resynchronization therapy (CRT) improves symptoms, left ventricular function, and survival in patients with heart failure (HF) and wide QRS. The benefit of adding implantable cardioverter-defibrillator (ICD) backup is debated. We analysed the long-term outcome of patients with HF due to ischaemic cardiomyopathy (ICM) or non-ischaemic cardiomyopathy (NICM) treated with a CRT device with or without defibrillator backup. In this observational study, consecutive patients with an ejection fraction ≤35% and QRS width ≥120 ms receiving a CRT device at Aarhus University Hospital, Denmark from 2000 to 2010 were included. Baseline characteristics were retrieved from patient files and survival data were obtained from the Danish Civil Registration System. The primary outcome was all-cause mortality. The effect of ICD backup was estimated using Cox proportional hazards model, and the multivariate analyses were adjusted for a priori selected variables. We included 917 HF patients, 427 with NICM, and 490 with ICM. Median follow-up was 4.0 years. Adjusted hazard ratio (aHR) for all-cause mortality was 0.76 [95% confidence interval (95% CI), 0.60-0.97; P = 0.03] in all patients; 0.96 (95% CI, 0.60-1.51; P = 0.85) in patients with NICM, and 0.74 (95% CI, 0.56-0.97; P = 0.03) in patients with ICM. In patients with NICM, ICD backup seemed to be associated with improved survival among non-responders to CRT (P = 0.08), but not among responders (P = 0.61). Adding an ICD backup is associated with better survival in CRT recipients. This effect was evident among patients with ICM, but not in patients with NICM. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Sarah E. Sinnett

    2017-06-01

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

  14. Increasing Radiation Therapy Dose Is Associated With Improved Survival in Patients Undergoing Stereotactic Body Radiation Therapy for Stage I Non–Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koshy, Matthew, E-mail: mkoshy@radonc.uchicago.edu [Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois (United States); Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois (United States); Malik, Renuka [Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois (United States); Weichselbaum, Ralph R. [Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois (United States); Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois (United States); Sher, David J. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States)

    2015-02-01

    Purpose: To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non–small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. Methods and Materials: The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/β ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Results: The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log–rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I non–small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors.

  15. Marked improvements in survival of patients with rectal cancer in the Netherlands following changes in therapy, 1989-2006.

    NARCIS (Netherlands)

    Elferink, M.A.; Steenbergen, L.N. van; Krijnen, P.; Lemmens, V.E.; Rutten, H.J.; Marijnen, C.A.; Nagtegaal, I.D.; Karim-Kos, H.E.; Vries, E. de; Siesling, S.

    2010-01-01

    BACKGROUND: Since the 1990s, treatment of patients with rectal cancer has changed in the Netherlands. Aim of this study was to describe these changes in treatment over time and to evaluate their effects on survival. METHODS: All patients in the Netherlands Cancer Registry with invasive primary

  16. Avoiding radical surgery improves early survival in elderly patients with rectal cancer, demonstrating complete clinical response after neoadjuvant therapy: results of a decision-analytic model.

    Science.gov (United States)

    Smith, Fraser McLean; Rao, Christopher; Oliva Perez, Rodrigo; Bujko, Krzysztof; Athanasiou, Thanos; Habr-Gama, Angelita; Faiz, Omar

    2015-02-01

    In elderly and comorbid patients with rectal cancer, radical surgery is associated with significant perioperative mortality. Data suggest that a watch-and-wait approach where a complete clinical response is obtained after neoadjuvant chemoradiotherapy might be oncologically safe. This study aimed to determine whether patient age and comorbidity should influence surgeon and patient decision making where a complete clinical response is obtained. Decision-analytic modeling consisting of a decision tree and Markov chain simulation was used. Modeled outcome parameters were elicited both from comprehensive literature review and from a national patient outcomes database. Outcomes for 3 patient cohorts treated with neoadjuvant therapy were modeled after either surgery or watch and wait. Patients included 60-year-old and 80-year-old men with mild comorbidities (Charlson score 3). Absolute survival, disease-free survival, and quality-adjusted life years were measured. The model found that absolute survival was similar in 60-year-old patients but was significantly improved in fit and comorbid 80-year-old patients at 1 year after treatment where watch and wait was implemented instead of radical surgery, with a survival advantage of 10.1% (95% CI, 7.9-12.6) and 13.5% (95% CI, 10.2-16.9). At all of the other time points, absolute survival was equivalent for both techniques. There were no short- or long-term differences among any patient groups managed either by radical surgery or watch and wait in terms of either disease-free survival or quality-adjusted life years. Oncologic data for the watch-and-wait approach used for this study is derived from only a small number of studies pertaining to a highly selected group of patients. The 90-day postoperative mortality rate derived from the United Kingdom population-based study might be lower in other countries or individual institutions. This study suggests competing effects of oncologic and surgical risk when using watch

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  19. Can early initiation of continuous renal replacement therapy improve patient survival with septic acute kidney injury when enrolled in early goal-directed therapy?

    Science.gov (United States)

    Oh, Hyung Jung; Kim, Min Hyung; Ahn, Jin Young; Ku, Nam Su; Park, Jung Tak; Han, Sang Hoon; Choi, Jun Yong; Han, Seung Hyeok; Yoo, Tae-Hyun; Song, Young Goo; Kang, Shin-Wook; Kim, June Myung

    2016-10-01

    The purpose of our study was to investigate the timing of continuous renal replacement therapy (CRRT) application, based on the interval between the start of early goal-directed therapy (EGDT) and CRRT initiation, to ascertain whether the timing was an independent predictor of mortality in patients with septic acute kidney injury (AKI). An observational retrospective cohort study was conducted of 60 patients (>18 years old) who had been admitted to the emergency department and received resuscitation according to the standard EGDT algorithm for severe sepsis and septic shock, and who were treated with CRRT due to septic AKI, between June 2008 and February 2013 at a tertiary hospital in Seoul, Korea. The patients were divided into 2 groups based on the median interval between the start of EGDT and the commencement of CRRT. The main outcome was 28-day all-cause mortality, and a multivariate Cox analysis for mortality was used to evaluate the independent impact of the early CRRT treatment. The mean patient age was 66.3 years, and 52 (86.7%) were male. The most common comorbid disease was diabetes mellitus (35.0%) followed by malignancy (26.7%). The median interval between the start of EGDT and commencement of CRRT was 26.4 hours. During the study period, 28-day mortality was 43.3% (26 of 60 patients). The 28-day all-cause mortality rate was significantly higher in the late CRRT group than in the early CRRT group (56.7 vs 30.0%, P= .037). Furthermore, the higher mortality risk in the late group remained significant even after adjusting for diabetes mellitus, liver failure, and Acute Physiology and Chronic Health Evaluation II scores (hazard ratio, 2.461; 95% confidence interval, 1.044-5.800; P= .026). Early initiation of CRRT may be of benefit. Given the complex nature of this intervention and the ongoing controversy regarding early vs late initiation of therapy in acute and chronic situations, it is vital to develop accurate clinical trials to find definitive answers

  20. VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH ≤ 150 pg/mL: results of the Italian FARO Survey.

    Science.gov (United States)

    Cozzolino, Mario; Brancaccio, Diego; Cannella, Giuseppe; Messa, Piergiorgio; Gesualdo, Loreto; Marangella, Martino; LoDeserto, Cosimo; Pozzato, Marco; Rombolà, Giuseppe; Costanzo, Anna Maria; di Luzio Paparatti, Umberto; Mazzaferro, Sandro

    2012-09-01

    Chronic kidney disease (CKD) patients affected by mineral bone disorders (MBD) have higher rates of all-cause and cardiovascular-related mortality. Approximately, one-third of dialysis patients have low serum parathyroid hormone (PTH) levels (≤ 150 pg/mL). However, the reason why these patients have higher mortality compared to patients with normal PTH levels has not yet been fully elucidated. The FARO study was performed on 2453 Italian patients followed prospectively from 28 dialysis centres over a 2-year period. Data were collected every 6 months and end points included time-to-death cumulative probability in patients with serum intact PTH (iPTH) ≤ 150 pg/mL and the effect of vitamin D receptor activation (VDRA) therapy. Kaplan-Meier curves and proportional hazards regression models stratified by PTH levels (i.e. ≤ 150 and >150 pg/mL) were used to determine cumulative probability of time-to-death and adjusted hazard ratios (HRs) for demographic, clinical and CKD-MBD treatment characteristics. The cumulative probability of death was higher (P < 0.01) for patients with serum iPTH levels ≤ 150 pg/mL [25.1%, 95% confidence interval (CI): 22.1-28.5 at 18 months] versus those with serum iPTH levels within the normal range (18.0%, 95% CI: 16.1-20.1). In a model with time-dependent covariates restricted to time periods when patients had iPTH levels ≤ 150 pg/mL, lower mortality was observed in patients treated with VDRA [i.e. HR = 0.62, 95% CI: 0.42-0.92 for oral or intravenous (IV) calcitriol; HR = 0.18, 95% CI: 0.04-0.8 for IV paricalcitol] versus those not receiving any VDRA (P < 0.01) independently of other variables. Patients who received IV paricalcitol, compared with either oral or IV calcitriol, showed reduced mortality, but this was not statistically significant (HR = 0.3, 95% CI: 0.07-1.31, P = 0.11). Results from this observational study suggest that VDRA therapy was associated with improved survival in dialysis patients, even with low serum i

  1. Palliative photodynamic therapy for biliary tract carcinoma may improve survival and has a similar outcome to attempted curative surgery with positive resection margins

    Science.gov (United States)

    Pereira, Stephen P.; Matull, W. Rudiger; Dhar, Dipok K.; Ayaru, Laskshmana; Sandanayake, Neomal S.; Chapman, Michael H.

    2009-06-01

    There is a need for better management strategies to improve survival and quality of life in patients with biliary tract cancer (BTC). We compared treatment outcomes in 321 patients (median age 65 years, range 29-102; F:M; 1:1) with a final diagnosis of BTC (cholangiocarcinoma n=237, gallbladder cancer n=84) seen in a tertiary referral cancer centre between 1998-2007. Of 89 (28%) patients who underwent surgical intervention with curative intent, 38% had R0 resections and had the most favourable outcome, with a 3 year survival of 57%. Even though PDT patients had more advanced clinical T-stages, their survival was similar to those treated with attempted curative surgery which resulted in R1/2 resections (median survival 12 vs. 13 months, ns). In a subgroup of 36 patients with locally advanced BTC treated with PDT as part of a prospective phase II study, the median survival was 12 (range 2-51) months, compared with 5 months in matched historical controls treated with stenting alone (p Palliative PDT resulted in similar survival to those with curatively intended R1/R2 resections.

  2. Survival Outcomes for Combined Modality Therapy for Sinonasal Undifferentiated Carcinoma.

    Science.gov (United States)

    Kuo, Phoebe; Manes, R Peter; Schwam, Zachary G; Judson, Benjamin L

    2017-01-01

    Objective Sinonasal undifferentiated carcinoma is a rare and aggressive malignancy of the nasal cavity and paranasal sinuses. Multi-institutional studies examining outcomes of combined modality treatment versus other treatment modalities have not been performed. The objective of our study was to present outcomes for multimodality therapy through use of the National Cancer Database. Study Design Retrospective cohort study. Setting National Cancer Database. Methods A total of 435 cases of SNUC diagnosed between 2004 and 2012 were identified. Kaplan-Meier analyses were performed to find 5-year cumulative survival rates. Multivariate Cox regression evaluated overall survival based on treatment when adjusting for other prognostic factors (age, primary site, sex, race, comorbidity, insurance, and TNM stage). Within the surgery + chemoradiotherapy group, survival analysis was also performed to compare outcomes for induction and adjuvant chemotherapy. Results The cumulative 5-year survival rate was 41.5%, and 36.1% of patients received surgery with chemoradiotherapy. In multivariate analysis, surgery + chemoradiotherapy was associated with significantly improved overall survival versus surgery + radiotherapy and radiotherapy but not significantly different from chemoradiotherapy. Within the surgery + chemoradiotherapy group, induction and adjuvant chemotherapy groups did not have associated differences in survival. Conclusion Combined modality therapy (chemoradiotherapy or surgery + chemoradiotherapy) is associated with improved survival outcomes versus other treatment modalities in patients with sinonasal undifferentiated carcinoma.

  3. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy.

    Science.gov (United States)

    Wang, H M; Liao, Z X; Komaki, R; Welsh, J W; O'Reilly, M S; Chang, J Y; Zhuang, Y; Levy, L B; Lu, C; Gomez, D R

    2013-05-01

    Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.

  4. Complementary Chinese Herbal Medicine Therapy Improves Survival of Patients With Pancreatic Cancer in Taiwan: A Nationwide Population-Based Cohort Study.

    Science.gov (United States)

    Kuo, Yi-Ting; Liao, Hou-Hsun; Chiang, Jen-Huai; Wu, Mei-Yao; Chen, Bor-Chyuan; Chang, Ching-Mao; Yeh, Ming-Hsien; Chang, Tung-Ti; Sun, Mao-Feng; Yeh, Chia-Chou; Yen, Hung-Rong

    2017-08-01

    Pancreatic cancer is a difficult-to-treat cancer with a late presentation and poor prognosis. Some patients seek traditional Chinese medicine (TCM) consultation. We aimed to investigate the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. We included all patients with pancreatic cancer who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 1997 and 2010. We used 1:1 frequency matching by age, sex, the initial diagnostic year of pancreatic cancer, and index year to enroll 386 CHM users and 386 non-CHM users. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. According to the Cox hazard ratio model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity, and treatments, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.67, 95% CI = 0.56-0.79). Those who received CHM therapy for more than 90 days had significantly lower hazard ratios of mortality risk than non-CHM users (90- to 180-day group: adjusted HR = 0.56, 95% CI = 0.42-0.75; >180-day group: HR = 0.33, 95% CI = 0.24-0.45). The survival probability was higher for patients in the CHM group. Bai-hua-she-she-cao (Herba Oldenlandiae; Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum Combination) were the most commonly used single herb and Chinese herbal formula, respectively. Complementary Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trial is warranted.

  5. Statin therapy is associated with improved survival in patients with non-serous-papillary epithelial ovarian cancer: a retrospective cohort analysis.

    Directory of Open Access Journals (Sweden)

    Mohammed Habis

    Full Text Available AIM: To determine whether statin use is associated with improved epithelial ovarian cancer (OvCa survival. METHODS: This is a single-institution retrospective cohort review of patients treated for OvCa between 1992 and 2013. Inclusion criteria were International Federation of Gynecology and Obstetrics (FIGO stage I-IV OvCa. The primary exposures analyzed were hyperlipidemia and statin use. The primary outcomes were progression-free survival (PFS and disease-specific survival (DSS. RESULTS: 442 patients met inclusion criteria. The cohort was divided into three groups: patients with hyperlipidemia who used statins (n = 68, patients with hyperlipidemia who did not use statins (n = 28, and patients without hyperlipidemia (n = 346. OvCa outcomes were evaluated. When we analyzed the entire cohort, we found no significant differences in PFS or DSS among the groups. The median PFS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 21.7, 13.6, and 14.7 months, respectively (p = 0.69. Median DSS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 44.2, 75.7, and 41.5 months, respectively (p = 0.43. These findings did not change after controlling for confounders. However, a secondary analysis revealed that, among patients with non-serous-papillary subtypes of OvCa, statin use was associated with a decrease in hazards of both disease recurrence (adjusted HR = 0.23, p = 0.02 and disease-specific death (adjusted HR = 0.23, p = 0.04. To augment the findings in the retrospective cohort, the histology-specific effects of statins were also evaluated in vitro using proliferation assays. Here, statin treatment of cell lines resulted in a variable level of cytotoxicity. CONCLUSION: Statin use among patients with non-serous-papillary OvCa was associated with improvement in both PFS and DSS.

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

    Science.gov (United States)

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

    2017-03-06

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

  7. Improved survival after rectal cancer in Denmark

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  8. Racial disparities in survival among patients with advanced renal cell carcinoma in the targeted therapy era.

    Science.gov (United States)

    Rose, Tracy L; Deal, Allison M; Krishnan, Bhavani; Nielsen, Matthew E; Smith, Angela B; Kim, William Y; Milowsky, Matthew I

    2016-10-01

    Historically, African American (AA) patients with renal cell carcinoma (RCC) have had inferior survival compared with Caucasian patients. Recent studies suggest that the survival disparity between races may be worsening since the advent of targeted therapies for RCC. In this study, survival rates among AA and Caucasian patients with advanced RCC are examined over time to determine whether a disparity in survival persists in the targeted therapy era. The authors identified patients with stage IV RCC in the National Cancer Data Base and compared survival between AA and Caucasian patients during the periods before (1998-2004) and after (2006-2011) the advent of targeted therapy. In total, 48,846 patients were identified, and 10% were AA. Three-year survival among both AA and Caucasian patients improved between the 2 periods (P therapy era, which was unchanged from the pretargeted therapy era (adjusted HR, 1.10; 95% confidence interval, 1.04-1.15). The adjusted HR was similar when the analysis was restricted to those who received systemic therapy. Both AA and Caucasian patients with advanced RCC have had a significant improvement in survival since the advent of targeted therapy. However, AA patients maintain a survival disadvantage compared with Caucasians independent of treatment received, potentially related to unmeasured comorbidities, disease burden, or tumor biology. Cancer 2016;122:2988-2995. © 2016 American Cancer Society. © 2016 American Cancer Society.

  9. Does Oral Beta-Blocker Therapy Improve Long-Term Survival in ST-Segment Elevation Myocardial Infarction With Preserved Systolic Function? A Meta-Analysis.

    Science.gov (United States)

    Misumida, Naoki; Harjai, Kishore; Kernis, Steven; Kanei, Yumiko

    2016-05-01

    The effect of oral beta-blocker therapy on long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) who are treated with primary percutaneous coronary intervention (PCI) and who have preserved left ventricular ejection fraction (LVEF) remains unclear. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for studies evaluating the effect of oral beta-blocker therapy in patients with STEMI who underwent primary PCI and who had preserved LVEF. The primary outcome was all-cause mortality. Randomized controlled trials and the observational studies that reported an adjusted hazard ratio (or hazard ratio in the propensity score-matched patients) with follow-up duration equal to or more than 6 months were included. Pooled hazard ratio with 95% confidence interval (CI) was calculated using a random effect model. No randomized controlled trials met the inclusion criteria. Seven observational studies totaling 10 857 patients met the inclusion criteria. Follow-up duration ranged from 6 months to 5.2 years. Preserved LVEF was defined as 40% in 4 studies and 50% in 3 studies. Based on the pooled estimate, oral beta-blocker therapy was associated with a reduction in all-cause mortality (combined hazard ratio 0.79, 95% CI 0.65-0.97). This meta-analysis demonstrates that oral beta-blocker therapy is associated with decreased all-cause mortality in patients with STEMI who are treated with primary PCI and who have preserved LVEF. This supports the current American College of Cardiology Foundation/American Heart Association 2013 Guideline for the Management of STEMI. © The Author(s) 2015.

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

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Felix Y., E-mail: ffeng@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan (United States); Blas, Kevin; Olson, Karin; Stenmark, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Sandler, Howard [Cedars Sinai Medical Center, Los Angeles, California (United States); Hamstra, Daniel A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-05-01

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

  11. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    Science.gov (United States)

    ... Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival For some women with breast cancer , taking adjuvant ... Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival was originally published by the National Cancer Institute.” ...

  12. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    Science.gov (United States)

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  13. Early diagnosis improves survival in kidney cancer.

    Science.gov (United States)

    Lewis, Gareth; Maxwell, Alexander P

    2012-02-01

    Kidney cancers account for 2-3% of all adult malignancies in the UK. Men are predominantly affected by renal cancer with an average age at diagnosis of 64 years. Renal (or clear) cell carcinoma (RCC) accounts for 90% of kidney cancers. Early diagnosis improves survival with five-year survival rates for renal cancer of 70-94% for localised tumours in the UK. RCC should be suspected in the presence of localising symptoms such as flank pain, a loin mass or haematuria; constitutional upset including weight loss, pyrexia and/or night sweats; or with unexplained laboratory tests. Smoking, obesity and hypertension are the most important and most common risk factors. Environmental exposure to asbestos, cadmium and trichloroethylene are less common risk factors. Patients on chronic dialysis and renal transplant recipients are at increased risk of RCC in their native kidneys. If kidney cancer is suspected on history, physical examination or initial screening tests then a red flag ultrasound examination of the renal tracts should be requested. Dipstick urinalysis is of great value as asymptomatic haematuria may be the only abnormal test in the presence of non-specific symptoms such as weight loss or loin pain. Visible or non-visible haematuria, in the absence of proteinuria, suggests an underlying structural abnormality is present in the kidneys, ureters or bladder. Surgical removal of RCCs, where feasible, may result in cure in up to 40-60% of cases. Individuals too frail for major surgery may benefit from thermal ablation and cryotherapy. Agents that target the VEGF and mTOR pathways are considered first line in the treatment of metastatic RCC. Sunitinib, recommended by NICE, is administered orally and acts by inhibiting the VEGF receptor.

  14. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

    Science.gov (United States)

    Hodi, F. Stephen; O’Day, Steven J.; McDermott, David F.; Weber, Robert W.; Sosman, Jeffrey A.; Haanen, John B.; Gonzalez, Rene; Robert, Caroline; Schadendorf, Dirk; Hassel, Jessica C.; Akerley, Wallace; van den Eertwegh, Alfons J.M.; Lutzky, Jose; Lorigan, Paul; Vaubel, Julia M.; Linette, Gerald P.; Hogg, David; Ottensmeier, Christian H.; Lebbé, Celeste; Peschel, Christian; Quirt, Ian; Clark, Joseph I.; Wolchok, Jedd D.; Weber, Jeffrey S.; Tian, Jason; Yellin, Michael J.; Nichol, Geoffrey M.; Hoos, Axel; Urba, Walter J.

    2013-01-01

    BACKGROUND An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. METHODS A total of 676 HLA-A⋆0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. RESULTS The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. CONCLUSIONS Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate

  15. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy.

    Science.gov (United States)

    Kopetz, Scott; Chang, George J; Overman, Michael J; Eng, Cathy; Sargent, Daniel J; Larson, David W; Grothey, Axel; Vauthey, Jean-Nicolas; Nagorney, David M; McWilliams, Robert R

    2009-08-01

    Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified. We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006. Landmark analysis evaluated the association of diagnosis year and liver resection with overall survival. Additional survival analysis of the Surveillance Epidemiology and End Results (SEER) database evaluated a similar population from 1990 through 2005. Two thousand four hundred seventy patients with metastatic CRC at diagnosis received their primary treatment at the two institutions during this time period. Median overall survival for those patients diagnosed from 1990 to 1997 was 14.2 months, which increased to 18.0, 18.6, and 29.3 months for patients diagnosed in 1998 to 2000, 2001 to 2003, and 2004 to 2006, respectively. Likewise, 5-year overall survival increased from 9.1% in the earliest time period to 19.2% in 2001 to 2003. Improved outcomes from 1998 to 2004 were a result of an increase in hepatic resection, which was performed in 20% of the patients. Improvements from 2004 to 2006 were temporally associated with increased utilization of new chemotherapeutics. In the SEER registry, overall survival for the 49,459 identified patients also increased in the most recent time period. Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients (1998 to 2006) and advancements in medical therapy (2004 to 2006).

  16. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Science.gov (United States)

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  17. Deep brain stimulation improves survival in severe Parkinson's disease.

    Science.gov (United States)

    Ngoga, Desire; Mitchell, Rosalind; Kausar, Jamilla; Hodson, James; Harries, Anwen; Pall, Hardev

    2014-01-01

    Levodopa and other dopaminergic treatments have not had the expected effect on survival in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor function, motor fluctuations, health-related quality of life, and to reduce medication usage and drug-induced dyskinesia in patients with severe PD refractory to medical therapy. Little however, has been described on the impact of STN-DBS on the survival of these patients. We aim in this study to examine the impact of STN-DBS on the survival of patients with severe PD. Patients who were eligible for STN-DBS were given the choice of undergoing surgery or continuing on medical treatment. Those who exercised patient choice and preferred to continue with medical treatment formed a control population. All eligible patients seen in a 10-year period are included in this study. Our primary outcome measure is a difference in mortality between the two groups with a secondary measure of admission rates to residential (nursing home) care. 106 patients underwent STN-DBS, and 41 patients exercised patient choice and declined the procedure. The two groups were matched for age, gender, ethnicity, duration of disease, rates of pre-existing depression and Levodopa equivalent doses of anti-Parkinson's medications taken. Patients undergoing STN-DBS had significantly longer survival and were significantly less likely to be admitted to a residential care home than those managed purely medically. The statistical significance of these findings persisted after adjusting for potential confounding factors (survival: p=0.002, HR 0.29 (0.13 to 0.64) (residential care home admission: OR: 0.1 (95% CI 0.0 to 0.3; padvanced PD. The effect of potential bias factors is examined. The survival advantage may arise for several postulated reasons, ranging from improvement in axial functions, such as swallowing, to some as yet unrecognised benefit of reduction in dopaminergic medication. These

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    . RESULTS: The final population included 1,827 patients scheduled for adjuvant chemotherapy. Adjuvant therapy started within 4 and 8 weeks improved survival when compared to start later than 8 weeks (HR [95%CI]: 1.7 [1.1-2.6]; P = 0.024 and 1.4 [1.07-1.8]; P = 0.013, respectively), whereas......BACKGROUND AND OBJECTIVES: In stage III colonic cancer, time from surgery to start of adjuvant chemotherapy may influence survival. In this study, we evaluated the effect of timing of adjuvant therapy on survival. METHODS: Database study from the Danish Colorectal Cancer Group's national database...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    . Further, they may expect to be treated equally with other members of society with respect to access to mortgage, health insurance and life insurance. As the infected population ages, more patients will contract age-related diseases, and the disease burden on some individuals may even come to be dominated......, with lifestyle factors potentially playing a pronounced role. Consequently, an effort to further increase survival must target risk factors for both HIV-related and -unrelated mortality. The continuation of the positive trend may be achieved by increased HIV testing, earlier initiation of antiretroviral therapy......, improved drug adherence, prevention and treatment of HIV-unrelated co-morbidity and collaboration with other medical specialists to treat an ageing co-morbidity-acquiring HIV population....

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    (43%) died, 497 (17%) had a thromboembolic event, and 536 (18%) had major bleeding. Postdischarge use of oral anticoagulation therapy among patients with indication for oral anticoagulation therapy was associated with a significant lower risk of death (adjusted hazard ratio, 0.59; 95% confidence...... inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  2. The Survival Benefits of Antiretroviral Therapy in South Africa

    OpenAIRE

    April, Michael D.; Wood, Robin; Berkowitz, Bethany K.; Paltiel, A. David; Anglaret, Xavier; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2013-01-01

    Background.  We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods.  We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), secon...

  3. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    Science.gov (United States)

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    Introduction Caffeine is consumed on a daily basis for its nervous system stimulant properties and is a global adenosine receptor antagonist. Since adenosine receptors have been found to play a major role in regulating the immune response to a septic insult, we investigated if caffeine consumption prior to a septic insult would alter immunological and physiological responses, as well as survival. Methods Two separate experimental designs were employed, both using outbred female ICR mice. In the first experiment mice were administered 20mg/kg of caffeine (equal to 2–3 cups of coffee for a human) or normal saline intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological parameters including cytokines and local cell recruitment measured. In the second experiment caffeine (10mg/kg/hr) was delivered continuously for 24 hours via a subcutaneous infusion pump placed the day prior to CLP and hemodynamic parameters were examined. In both experiments survival was followed for five days. Results A single dose of caffeine at the initiation of sepsis did not alter survival. This single dose of caffeine did significantly increase in plasma levels of the chemokine KC six hours after the onset of sepsis compared to septic mice given normal saline. There were no changes in IL-6 or IL-10 levels in the caffeine groups. Peritoneal lavages performed 24 hours post-CLP showed no difference in the levels of IL-6, TNF, KC, MIP-1, IL-10 or the IL-1 receptor antagonist between caffeine and normal saline treated mice. Additionally, the lavages yielded similar numbers of cells (4.1×106 vehicle vs. 6.9×106 caffeine) and bacterial colony forming units (CFU, 4.1 million CFU vehicle vs. 2.8 million CFU caffeine). In the infusion group, caffeine also did not alter survival. However, caffeine infusion did increase heart rate prior to CLP, and prevented the decline in heart rate after CLP. Conclusion Caffeine increased heart rate in mice but does not impact cytokine

  4. Implant survival rate after oral cancer therapy: a review.

    Science.gov (United States)

    Javed, Fawad; Al-Hezaimi, Khalid; Al-Rasheed, Abdulaziz; Almas, Khalid; Romanos, George E

    2010-12-01

    The overall impression regarding the success of dental implants (DI) in patients having undergone oral cancer therapy remains unclear. The aim of the present review study was to assess the implant survival rate after oral cancer therapy. Databases were explored from 1986 up to and including September 2010 using the following keywords in various combinations: "cancer", "chemotherapy", "dental implant", "oral", "osseointegration", "radiotherapy", "surgery" and "treatment". The eligibility criteria were: (1) original research articles; (2) clinical studies; (3) reference list of pertinent original and review studies; (4) intervention: patients having undergone radio- and chemotherapy following oral cancer surgery; and (5) articles published only in English. Twenty-one clinical studies were included. Results from 16 studies reported that DI can osseointegrate and remain functionally stable in patients having undergone radiotherapy following oral cancer surgery; whereas three studies showed irradiation to have negative effects on the survival of DI. Two studies reported that DI can osseointegrate and remain functionally stable in patients having undergone chemotherapy. It is concluded that DI can osseointegrate and remain functionally stable in patients having undergone oral cancer treatment. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  5. Pulmonary Physical Therapy Techniques to Enhance Survival in Amyotrophic Lateral Sclerosis: A Systematic Review.

    Science.gov (United States)

    Macpherson, Chelsea E; Bassile, Clare C

    2016-07-01

    Respiratory insufficiency is the primary cause of morbidity and mortality in individuals with amyotrophic lateral sclerosis (ALS). Although mechanical interventions are effective in prolonging survival through respiratory support, pulmonary physical therapy interventions are being investigated. The purpose of this systematic review was to examine the effectiveness of pulmonary physical therapy interventions across the progressive stages of ALS. Six databases were searched for articles from inception to December 2014 investigating pulmonary physical therapy interventions in the ALS population. The search strategy followed Cochrane Collaboration guidelines with replication per database. Effect sizes (ES) were calculated for primary outcome measures: forced vital capacity (FVC) and peak cough expiratory flow (PCEF). Seven studies met inclusion criteria. Four studies used control groups whereas the remainder used repeated measures. With the exception of diaphragmatic breathing, pulmonary physical therapy interventions were effective in improving multiple respiratory outcome measures in this population. Inspiratory muscle training (IMT) was shown to prolong respiratory muscle strength with a strong effect size (ES = 1.48) for FVC. In addition, mean length of survival increased by 12 months. Lung volume recruitment training (LVRT) strongly enhanced immediate cough efficacy with improved FVC (ES = 1.02) and PCEF (ES = 1.82). Manually assisted cough (MAC) only improved PCEF by a small amount (ES = 0.15, bulbar ALS; ES = 0.16, classical ALS groups). Specific pulmonary physical therapy interventions (IMT, LVRT, and MAC) have effectiveness in improving respiratory outcome measures and increasing survival. These should be routinely incorporated into the comprehensive management of individuals with ALS. More rigorous methodological investigations should be performed to replicate these findings.Video abstract available with brief technique demonstration of IMT and LVRT (see

  6. Interleukin-7 Ameliorates Immune Dysfunction and Improves Survival in a 2-Hit Model of Fungal Sepsis

    OpenAIRE

    Unsinger, Jacqueline; Burnham, Carey-Ann D.; McDonough, Jacquelyn; Morre, Michel; Prakash, Priya S.; Caldwell, Charles C.; Dunne, W. Michael; Hotchkiss, Richard S.

    2012-01-01

    Background. Secondary hospital-acquired fungal infections are common in critically-ill patients and mortality remains high despite antimicrobial therapy. Interleukin-7 (IL-7) is a potent immunotherapeutic agent that improves host immunity and has shown efficacy in bacterial and viral models of infection. This study examined the ability of IL-7, which is currently in multiple clinical trials (including hepatitis and human immunodeficiency virus), to improve survival in a clinically relevant 2-...

  7. Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial.

    Science.gov (United States)

    Miles, David; Vukelja, Svetislava; Moiseyenko, Vladimir; Cervantes, Guadalupe; Mauriac, Louis; Van Hazel, Guy; Liu, Wing-Yiu; Ayoub, Jean-Pierre; O'Shaughnessy, Joyce A

    2004-10-01

    In a large phase III trial of 511 patients with anthracycline-pretreated advanced/metastatic breast cancer, capecitabine/docetaxel combination therapy was shown to have significantly superior efficacy compared with single-agent docetaxel, including superior progression-free and overall survival and objective response rate. An updated survival analysis with >/= 27 months follow-up shows that patients receiving combination therapy maintained significantly superior survival (hazard ratio [HR], 0.777 [95% CI, 0.645-0.942]; P < 0.01; median survival, 14.5 months vs. 11.5 months) compared with those receiving single-agent docetaxel. Following the failure of docetaxel monotherapy, 35% of patients did not receive additional cytotoxic chemotherapy. Among patients randomized to single-agent docetaxel, only those given poststudy single-agent capecitabine had significantly prolonged survival compared with those given any other poststudy chemotherapy (HR, 0.500; P = 0.0046; median survival, 21.0 months vs. 12.3 months, respectively). By contrast, poststudy vinorelbine-containing chemotherapy did not affect survival following progression on single-agent docetaxel compared with other poststudy chemotherapy regimens (HR, 1.014; P = 0.94; median survival, 13.5 months vs. 12.6 months, respectively). Among patients randomized to combination therapy, discontinuing docetaxel of capecitabine has a similar effect on survival (HR, 0.720; P = 0.20; median survival, 15.8 months vs. 18.3 months, respectively). Median survival was 18.3 months in patients who discontinued docetaxel and continued to receive capecitabine versus 15.8 months in patients who discontinued capecitabine and continued to receive docetaxel, with a trend toward improved survival in patients continuing to receive capecitabine. Although this is a retrospective analysis, these data suggest that the sequential administration of docetaxel followed by capecitabine is associated with prolonged survival in patients who are

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

    Science.gov (United States)

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

    1996-09-01

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

  9. Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.

    Science.gov (United States)

    Turapov, Obolbek; Waddell, Simon J; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A; Tudo, Griselda; Labesse, Gilles; Young, Danielle I; Young, Michael; Andrew, Peter W; Butcher, Philip D; Cohen-Gonsaud, Martin; Mukamolova, Galina V

    2014-05-01

    Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis.

  10. Improving lung cancer survival; time to move on

    NARCIS (Netherlands)

    M.E. Heuvers (Marlies); J.P.J.J. Hegmans (Joost); B.H.Ch. Stricker (Bruno); J.G.J.V. Aerts (Joachim)

    2012-01-01

    textabstractBackground: During the past decades, numerous efforts have been made to decrease the death rate among lung cancer patients. Nonetheless, the improvement in long-term survival has been limited and lung cancer is still a devastating disease.Discussion: With this article we would like to

  11. Multiagent induction chemotherapy followed by chemoradiation is associated with improved survival in locally advanced pancreatic cancer.

    Science.gov (United States)

    Torgeson, Anna; Lloyd, Shane; Boothe, Dustin; Tao, Randa; Whisenant, Jonathan; Garrido-Laguna, Ignacio; Cannon, George M

    2017-10-01

    The role of chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) is uncertain after multiple randomized clinical trials have yielded mixed results. The authors used the National Cancer Data Base (NCDB) to determine whether CRT yields a survival benefit compared with chemotherapy alone (CT). Patients with nonmetastatic LAPC diagnosed during 2004 through 2014 were identified in the NCDB. Patients who received CT were compared with those who received CRT using chi-square analysis. Univariate and multivariate Cox regression analyses were used to compare demographic, clinical, and treatment characteristics that were predictive of survival. Propensity score matching and shared frailty analysis were done. Subgroup analyses were undertaken to examine patients who underwent pancreatectomy and cohorts of patients who received different CT or CRT regimens. In total, 8689 patients with LAPC were identified. CRT was associated with improved survival (median survival [MS], 13.5 months) compared with CT (MS, 10.6 months) on multivariate analysis (hazard ratio [HR], 0.80; P chemotherapy before CRT (HR, 0.67; P chemotherapy (HR, 0.72; P chemotherapy had superior MS and pancreatectomy rates (MS, 17.5 months; HR, 0.70; P improved survival (MS, 22 vs 10.6 months; HR, 0.39; P chemotherapy before CRT improved survival compared with CT alone in patients with LAPC. Continued analysis of CRT in properly selected patients after maximized systemic therapy is needed. Cancer 2017;123:3816-24. © 2017 American Cancer Society. © 2017 American Cancer Society.

  12. Does Statin or ASA Affect Survival When Prostate Cancer Is Treated with External Beam Radiation Therapy?

    Directory of Open Access Journals (Sweden)

    J. Caon

    2014-01-01

    Full Text Available Background. Prior studies evaluating the effect of statins or acetylsalicylic acid (ASA on the survival of men receiving prostate cancer were treatment have reported conflicting results, and have not adjusted for comorbidity. Our aim is to investigate the influence of statins and ASA on prostate cancer survival, when comorbidity is adjusted for, in men treated with external beam radiation therapy (EBRT for prostate cancer. Methods. A cohort of 3851 patients with prostate cancer treated with curative EBRT ± androgen deprivation therapy (ADT between 2000 and 2007. Stage, treatment, medication use, and Charlson comorbidity index (CCI scores were analyzed. Results. Median followup was 8.4 years. Mean age was 70.3 years. Neoadjuvant ADT was used in 67%. Statins were used in 23%, ASA in 24%, and both in 11%. Comorbidity scores were 0 in 65%, 1 in 25%, and ≥2 in 10% of patients. Statin and ASA use were associated with increased age and comorbidity. Although statin and ASA use were significantly associated with improved prostate cancer specific survival (PCSS on univariate analysis, neither were on multivariate analysis. Conclusion. Neither statin nor ASA use impacted PCSS on multivariate competing risks analysis. Survival was impacted by increased comorbidity as well as statin and ASA use.

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

    Directory of Open Access Journals (Sweden)

    R. A. Snyder

    2012-01-01

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

  14. Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis.

    Science.gov (United States)

    Unsinger, Jacqueline; Burnham, Carey-Ann D; McDonough, Jacquelyn; Morre, Michel; Prakash, Priya S; Caldwell, Charles C; Dunne, W Michael; Hotchkiss, Richard S

    2012-08-15

    Secondary hospital-acquired fungal infections are common in critically-ill patients and mortality remains high despite antimicrobial therapy. Interleukin-7 (IL-7) is a potent immunotherapeutic agent that improves host immunity and has shown efficacy in bacterial and viral models of infection. This study examined the ability of IL-7, which is currently in multiple clinical trials (including hepatitis and human immunodeficiency virus), to improve survival in a clinically relevant 2-hit model of fungal sepsis. Mice underwent cecal ligation and puncture to induce peritonitis. Four days later, surviving mice had intravenous injection with Candida albicans. Following Candida infection, mice were treated with IL-7 or saline control. The effect of IL-7 on host immunity and survival was recorded. IL-7 ameliorated the loss of immune effector cells and increased lymphocyte functions, including activation, proliferation, expression of adhesion molecules, and interferon-γ production. These beneficial effects of IL-7 were associated with an increase in global immunity as reflected by an enhanced delayed type hypersensitivity response and a 1.7-fold improvement in survival. The present findings showing that IL-7 improves survival in fungal sepsis, together with its previously reported efficacy in bacterial and viral infectious models, further supports its use as a novel immunotherapeutic in sepsis.

  15. Strong anti-Epstein Barr virus (EBV or cytomegalovirus (CMV cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy

    Directory of Open Access Journals (Sweden)

    Tumaini Nagu

    2017-03-01

    Conclusions: Increased cellular immune responses to CMV and EBV antigens at the time of diagnosis of pulmonary tuberculosis are associated with increased survival after a standard six months anti-TB therapy. CVM and EBV antigens may represent “intrinsic markers for immune fitness” and guide improved TB therapies including host-directed therapies.

  16. Interdisciplinary ICU Cardiac Arrest Debriefing Improves Survival Outcomes

    Science.gov (United States)

    Wolfe, Heather; Zebuhr, Carleen; Topjian, Alexis A.; Nishisaki, Akira; Niles, Dana E.; Meaney, Peter A.; Boyle, Lori; Giordano, Rita T.; Davis, Daniela; Priestley, Margaret; Apkon, Michael; Berg, Robert A.; Nadkarni, Vinay M.; Sutton, Robert M.

    2014-01-01

    Objective In-hospital cardiac arrest is an important public health problem. High-quality resuscitation improves survival but is difficult to achieve. Our objective is to evaluate the effectiveness of a novel, interdisciplinary, postevent quantitative debriefing program to improve survival outcomes after in-hospital pediatric chest compression events. Design, Setting, and Patients Single-center prospective interventional study of children who received chest compressions between December 2008 and June 2012 in the ICU. Interventions Structured, quantitative, audiovisual, interdisciplinary debriefing of chest compression events with front-line providers. Measurements and Main Results Primary outcome was survival to hospital discharge. Secondary outcomes included survival of event (return of spontaneous circulation for ≥ 20 min) and favorable neurologic outcome. Primary resuscitation quality outcome was a composite variable, termed “excellent cardiopulmonary resuscitation,” prospectively defined as a chest compression depth ≥ 38 mm, rate ≥ 100/min, ≤ 10% of chest compressions with leaning, and a chest compression fraction > 90% during a given 30-second epoch. Quantitative data were available only for patients who are 8 years old or older. There were 119 chest compression events (60 control and 59 interventional). The intervention was associated with a trend toward improved survival to hospital discharge on both univariate analysis (52% vs 33%, p = 0.054) and after controlling for confounders (adjusted odds ratio, 2.5; 95% CI, 0.91–6.8; p = 0.075), and it significantly increased survival with favorable neurologic outcome on both univariate (50% vs 29%, p = 0.036) and multivariable analyses (adjusted odds ratio, 2.75; 95% CI, 1.01–7.5; p = 0.047). Cardiopulmonary resuscitation epochs for patients who are 8 years old or older during the debriefing period were 5.6 times more likely to meet targets of excellent cardiopulmonary resuscitation (95% CI, 2.9–10

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-01

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

  18. Survival times for canine intranasal sarcomas treated with radiation therapy: 86 cases (1996-2011).

    Science.gov (United States)

    Sones, Evan; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Taylor, Kathryn; Haney, Siobhan; Wypij, Jackie; Keyerleber, Michele; Arthur, Jennifer; Hamilton, Terrance; Lawrence, Jessica; Gieger, Tracy; Sellon, Rance; Wright, Zack

    2013-01-01

    Sarcomas comprise approximately one-third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily-fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily-fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily-fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits. © 2012 Veterinary Radiology & Ultrasound.

  19. Association of Compliance With Process-Related Quality Metrics and Improved Survival in Oral Cavity Squamous Cell Carcinoma.

    Science.gov (United States)

    Graboyes, Evan M; Gross, Jennifer; Kallogjeri, Dorina; Piccirillo, Jay F; Al-Gilani, Maha; Stadler, Michael E; Nussenbaum, Brian

    2016-05-01

    Quality metrics for patients with head and neck cancer are available, but it is unknown whether compliance with these metrics is associated with improved patient survival. To identify whether compliance with various process-related quality metrics is associated with improved survival in patients with oral cavity squamous cell carcinoma who receive definitive surgery with or without adjuvant therapy. A retrospective cohort study was conducted at a tertiary academic medical center among 192 patients with previously untreated oral cavity squamous cell carcinoma who underwent definitive surgery with or without adjuvant therapy between January 1, 2003, and December 31, 2010. Data analysis was performed from January 26 to August 7, 2015. Surgery with or without adjuvant therapy. Compliance with a collection of process-related quality metrics possessing face validity that covered pretreatment evaluation, treatment, and posttreatment surveillance was evaluated. Association between compliance with these quality metrics and overall survival, disease-specific survival, and disease-free survival was calculated using univariable and multivariable Cox proportional hazards analysis. Among 192 patients, compliance with the individual quality metrics ranged from 19.7% to 93.6% (median, 82.8%). No pretreatment or surveillance metrics were associated with improved survival. Compliance with the following treatment-related quality metrics was associated with improved survival: elective neck dissection with lymph node yield of 18 or more, no unplanned surgery within 14 days of the index surgery, no unplanned 30-day readmissions, and referral for adjuvant radiotherapy for pathologic stage III or IV disease. Increased compliance with a "clinical care signature" composed of these 4 metrics was associated with improved overall survival, disease-specific survival, and disease-free survival on univariable analysis (log-rank test; P metrics was associated with improved overall survival (100

  20. Exsanguination protocol improves survival after major hepatic trauma.

    Science.gov (United States)

    Zaydfudim, Victor; Dutton, William D; Feurer, Irene D; Au, Brigham K; Pinson, C Wright; Cotton, Bryan A

    2010-01-01

    Hepatic injury remains an important cause of exsanguination after major trauma. Recent studies have noted a dramatic reduction in mortality amongst severely injured patients when trauma exsanguinations protocols (TEP) are employed. We hypothesised that utilisation of our institution's TEP at the initiation of hospital resuscitation would improve survival in patients with significant hepatic trauma. All patients who (1) sustained intra-abdominal haemorrhage with Grades III-V hepatic injury and (2) underwent immediate operative intervention between February 2004 and January 2008 were included in the study. TEP was instituted in February 2006, and all subsequent patients who met inclusion criteria and were treated with TEP constituted the study group. Patients who met inclusion criteria, were treated before introduction of TEP, and received at least 10 units packed red blood cells in the first 24h constituted pre-TEP comparison group. Univariate and multivariate analyses evaluated the effects of TEP on the study population. Seventy-five patients were included in the study: 39 in the pre-TEP cohort (31% 30-day survival) and 36 in the TEP cohort (53% 30-day survival). There were no differences in demographics, extent of hepatic injury, or operative approach between the patient groups (all p > or = 0.27). Injury Severity Scores were significantly higher in the TEP group (41+/-18 vs. 28+/-15, p<0.01). TEP patients received more plasma and platelets during operative intervention and significantly less crystalloid (all p<0.01). Occurrence of cardiac dysfunction and abdominal compartment syndrome was significantly lower in TEP patients who survived 24-h post-injury (both p < or = 0.04). After adjusting for the significant negative effects of Grade V injury and involvement of major hepatic vasculature (both p < or = 0.02), TEP significantly improved 30-day survival: OR=0.22, 95% CI: 0.06-0.81, p=0.02. TEP allows for an effective use of plasma and platelets during intra

  1. Effect of Induction Therapy on Graft Survival in Primary Pediatric Heart Transplantation: A Propensity Score Analysis of the UNOS Database.

    Science.gov (United States)

    Butts, Ryan; Davis, Melanie; Savage, Andrew; Burnette, Ali; Kavarana, Minoo; Bradley, Scott; Atz, Andrew; Nietert, Paul J

    2017-06-01

    The use of induction therapy in pediatric heart transplantation has increased. The aim of this study was to investigate the effects of induction therapy on graft survival. The United Network for Organ Sharing database was queried for isolated pediatric heart transplants from January 1, 1994, to December 31, 2013. Propensity scores for induction treatment were calculated by estimating probability of induction using a logistic regression model. Transplants were then matched between induction treatment groups based on the propensity score, reducing potential biases. Using only propensity score matched transplants, the effect of induction therapy on graft survival was investigated using Cox-proportional hazards. Subgroup analyses were performed based on age, race, recipient cardiac diagnosis, HLA, and recipient panel-reactive antibody (PRA). Of 4565 pediatric primary heart transplants from 1994 to 2013, 3741 had complete data for the propensity score calculation. There were 2792 transplants successfully matched (induction, n = 1396; no induction, n = 1396). There were no significant differences in transplant and pretransplant covariates between induction and no induction groups. In the Cox-proportional hazards model, the use of induction of was not associated with graft loss (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.75-1.01; P = 0.07). In subgroup analyses, induction therapy may be associated with improved survival in patients with PRA greater than 50% (HR, 0.57; 95% CI, 0.34-0.97) and congenital heart disease (HR, 0.78; 95% CI, 0.64-0.96). Induction therapy is not associated with improved graft survival in primary pediatric heart transplantation. However, in pediatric heart transplant recipients with PRA greater than 50% or congenital heart disease, induction therapy is associated with improved survival.

  2. Tobacco Cessation May Improve Lung Cancer Patient Survival.

    Science.gov (United States)

    Dobson Amato, Katharine A; Hyland, Andrew; Reed, Robert; Mahoney, Martin C; Marshall, James; Giovino, Gary; Bansal-Travers, Maansi; Ochs-Balcom, Heather M; Zevon, Michael A; Cummings, K Michael; Nwogu, Chukwumere; Singh, Anurag K; Chen, Hongbin; Warren, Graham W; Reid, Mary

    2015-07-01

    This study characterizes tobacco cessation patterns and the association of cessation with survival among lung cancer patients at Roswell Park Cancer Institute: an NCI Designated Comprehensive Cancer Center. Lung cancer patients presenting at this institution were screened with a standardized tobacco assessment, and those who had used tobacco within the past 30 days were automatically referred to a telephone-based cessation service. Demographic, clinical information, and self-reported tobacco use at last contact were obtained via electronic medical records and the Roswell Park Cancer Institute tumor registry for all lung cancer patients referred to the service between October 2010 and October 2012. Descriptive statistics and Cox proportional hazards models were used to assess whether tobacco cessation and other factors were associated with lung cancer survival through May 2014. Calls were attempted to 313 of 388 lung cancer patients referred to the cessation service. Eighty percent of patients (250 of 313) were successfully contacted and participated in at least one telephone-based cessation call; 40.8% (102 of 250) of persons contacted reported having quit at the last contact. After controlling for age, pack year history, sex, Eastern Cooperative Oncology Group performance status, time between diagnosis and last contact, tumor histology, and clinical stage, a statistically significant increase in survival was associated with quitting compared with continued tobacco use at last contact (HR = 1.79; 95% confidence interval: 1.14-2.82) with a median 9 month improvement in overall survival. Tobacco cessation among lung cancer patients after diagnosis may increase overall survival.

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

    Directory of Open Access Journals (Sweden)

    Xi Zhao

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

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

    Science.gov (United States)

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

    2014-01-01

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

  5. Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

    Science.gov (United States)

    Lindsay, Robert M.; Cuerden, Meaghan S.; Garg, Amit X.; Port, Friedrich; Austin, Peter C.; Moist, Louise M.; Pierratos, Andreas; Chan, Christopher T.; Zimmerman, Deborah; Lockridge, Robert S.; Couchoud, Cécile; Chazot, Charles; Ofsthun, Norma; Levin, Adeera; Copland, Michael; Courtney, Mark; Steele, Andrew; McFarlane, Philip A.; Geary, Denis F.; Pauly, Robert P.; Komenda, Paul; Suri, Rita S.

    2012-01-01

    Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5–5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34–0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown. PMID:22362910

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

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2015-12-15

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

  7. Taking out the JNK: A window of opportunity to improve cancer therapy.

    Science.gov (United States)

    Ferrao, Petranel T

    2016-05-01

    c-JUN-N-terminal kinase (JNK) signaling is a stress-induced response that enables survival of normal cells and is also utilized by cancer cells to evade therapy. Combining JNK inhibitors with standard therapies provides a potential strategy for overcoming drug resistance. Use of the optimal combination dosing and scheduling may substantially improve outcomes for cancer patients.

  8. Have Changes in Systemic Treatment Improved Survival in Patients with Breast Cancer Metastatic to the Brain?

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2008-01-01

    Full Text Available Newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases. In order to examine this hypothesis, a matched pairs analysis was performed that involved one group of patients, which were treated after these new drugs were introduced, and one group of patients, which were treated approximately 10 years earlier. The two groups were well balanced for the known prognostic factors age, KPS, extracranial disease status, and recursive partitioning analysis class, as well as for the extent of brain treatment. The results show that the use of systemic chemotherapy has increased over time, both before and after the diagnosis of brain metastases. However, such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups. Survival after whole-brain radiotherapy has remained unchanged in patients without further active treatment. It has improved in prognostically better patients and especially patients that received active treatment, where the 1-year survival rates have almost doubled. As these patient groups were small, confirmation of the results in other series should be attempted. Nevertheless, the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer.

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

    Science.gov (United States)

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

    2010-01-01

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

  10. Hypothyroidism improves random-pattern skin flap survival in rats.

    Science.gov (United States)

    Rahimpour, Sina; Nezami, Behtash Ghazi; Karimian, Negin; Sotoudeh-Anvari, Maryam; Ebrahimi, Farzad; Taleb, Shayandokht; Mirazi, Naser; Dehpour, Ahmad Reza

    2012-11-01

    The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps. Dorsal flaps with caudal pedicles were elevated at midline and flap survival was measured at the seventh day after surgery. The first group, as control, received 1 mL of 0.9% saline solution in the flap before flap elevation. In groups 2 and 3, hypothyroidism was induced by administration of either PTU 0.05% or MMI 0.04% in drinking water. The next four groups received local injections of MMI (10, 20, 50, or 100 μg/flap) before flap elevation. Local PTU injection was ignored due to insolubility of the agent. Hypothyroidism was induced in chronic PTU- and MMI-treated groups, and animals in these groups showed significant increase in their flap survival, compared to control euthyroid rats (79.47% ± 10.49% and 75.48% ± 12.93% versus 52.26% ± 5.75%, respectively, P hypothyroidism improves survival of random-pattern skin flaps in rats. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2013-12-15

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

  12. Improving long-term survival of patients with acute myocardial infarction from 1977-1988 in a region of Denmark

    DEFF Research Database (Denmark)

    Torp-Pedersen, C; Hildebrandt, P; Køber, L

    1995-01-01

    The aim of this investigation was to study secular trends in long-term survival following myocardial infarction (MI). Five thousand one hundred and fifty-seven consecutive cases of MI in 3942 patients were recorded in a well-defined region in the study period 1977-1988. The study period ended....... Year of infarction was without importance in the high risk group but highly significant in the low risk group. Long-term survival following MI gradually improved prior to the introduction of thrombolytic therapy. The improvement was confined to low risk patients without cardiac arrest or congestive...... before thrombolytic therapy was introduced in the hospital. One and 5-year survival (+/- 95% confidence limits) was 61 +/- 2% and 42 +/- 2% in 1977-1980. These figures changed to 61 +/- 2% and 44 +/- 2% in 1981-1984, and to 64 +/- 2 and 46 +/- 2% in 1985-1988. The improvement with time was statistically...

  13. Survival outcomes for first-line antiretroviral therapy in India's ART program.

    Science.gov (United States)

    Dandona, Rakhi; Rewari, Bharat B; Kumar, G Anil; Tanwar, Sukarma; Kumar, S G Prem; Vishnumolakala, Venkata S; Duber, Herbert C; Gakidou, Emmanuela; Dandona, Lalit

    2016-10-11

    Little is known about survival outcomes of HIV patients on first-line antiretroviral therapy (ART) on a large-scale in India, or facility level factors that influence patient survival to guide further improvements in the ART program in India. We examined factors at the facility level in addition to patient factors that influence survival of adult HIV patients on ART in the publicly-funded ART program in a high- and a low-HIV prevalence state. Retrospective chart review in public sector ART facilities in the combined states of Andhra Pradesh and Telangana (APT) before these were split in 2014 and in Rajasthan (RAJ), the high- and a low-HIV prevalence states, respectively. Records of adults initiating ART between 2007-12 and 2008-13 in APT and RAJ, respectively, were reviewed and facility-level information collected at all ART centres and a sample of link ART centres. Survival probability was estimated using Kaplan-Meier method, and determinants of mortality explored with facility and patient-level factors using Cox proportional hazard model. Based on data from 6581 patients, the survival probability of ART at 60 months was 76.3 % (95 % CI 73.0-79.2) in APT and 78.3 % (74.4-81.7) in RAJ. The facilities with cumulative ART patient load above the state average had lower mortality in APT (Hazard ratio [HR] 0.74, 0.57-0.95) but higher in RAJ (HR 1.37, 1.01-1.87). Facilities with higher proportion of lost to follow-up patients in APT had higher mortality (HR 1.47, 1.06-2.05), as did those with higher ART to pre-ART patient ratio in RAJ (HR 1.62, 1.14-2.29). In both states, there was higher hazard for mortality in patients with CD4 count 100 cells/mm 3 or less at ART initiation, males, and in patients with TB co-infection. These data from the majority of facilities in a high- and a low-HIV burden state of India over 5 years reveal reasonable and similar survival outcomes in the two states. The facilities with higher ART load in the longer established ART program in

  14. Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

    Science.gov (United States)

    Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

    2017-02-01

    Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p = .0001) and thienopyridine treatment (27% vs. 3%; p = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. © AlphaMed Press 2017.

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

    Science.gov (United States)

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

    2017-05-01

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

  16. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma : a prospective randomized phase 3 study

    NARCIS (Netherlands)

    Segeren, CM; Sonneveld, P; van der Holt, B; Vellenga, E; Croockewit, AJ; Verhoef, GEG; Cornelissen, JJ; van Oers, MHJ; Wijermans, PW; Fibbe, WE; Wittebol, S; Kooy, MV; Biesma, DH; Baars, JW; Slater, R; Steijaert, MMC; Buijt, [No Value; Lokhorst, HM; Schaafsma, M.R.

    2003-01-01

    We compared the efficacy of intensified chemotherapy followed by myeloablative therapy and autologous stem cell rescue with intensified chemotherapy alone in patients newly diagnosed with multiple myeloma. There were 261 eligible patients younger than 66 years with stage II/III multiple myeloma who

  17. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study

    NARCIS (Netherlands)

    Segeren, Christine M.; Sonneveld, Pieter; van der Holt, Bronno; Vellenga, Edo; Croockewit, Alexandra J.; Verhoef, Gregor E. G.; Cornelissen, Jan J.; Schaafsma, Martijn R.; van Oers, Marinus H. J.; Wijermans, Pierre W.; Fibbe, Wim E.; Wittebol, Shulamit; Schouten, Harry C.; van Marwijk Kooy, Marinus; Biesma, Douwe H.; Baars, Joke W.; Slater, Rosalyn; Steijaert, Monique M. C.; Buijt, Ivon; Lokhorst, Henk M.

    2003-01-01

    We compared the efficacy of intensified chemotherapy followed by myeloablative therapy and autologous stem cell rescue with intensified chemotherapy alone in patients newly diagnosed with multiple myeloma. There were 261 eligible patients younger than 66 years with stage II/III multiple myeloma who

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

    Science.gov (United States)

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

    2009-09-01

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

  19. How to improve survival in geriatric peritoneal dialysis patients.

    Science.gov (United States)

    Hiramatsu, Makoto

    2007-06-01

    Recently, more elderly patients who are independent or able to live at home with the support of family are opting for continuous ambulatory peritoneal dialysis (CAPD). At the end of 2005, the annual statistical survey conducted by the Japanese Society for Dialysis Therapy indicated that the mean age of patients at initiation of dialysis treatment is 66.2 years. Only 3.6% of the overall end-stage renal disease population were treated with CAPD, and this small number of elderly patients was treated with CAPD despite the many merits of peritoneal dialysis (PD) for the elderly. In the present study, we reviewed our experience with patients 65 years of age and older at the start of PD and the results from two multicenter studies on PD treatment in elderly patients in Japan. Study 1: Of 313 PD patients at Okayama Saiseikai General Hospital between January 1991 and June 2006, 166 patients 65 years of age and older were studied. The characteristics of these elderly PD patients were reviewed to determine which elderly patients can continue PD for more than 5 years, and what the causes of death and the effects of icodextrin were in elderly PD patients. Study 2: A multicenter study of 421 patients introduced to PD from April 2000 to December 2004 in Japan was carried out by the Japanese Society for Elderly Patients on Peritoneal Dialysis to retrospectively analyze patient survival and technique survival and to find factors that have the potential to influence prognosis in these patients. Study 3: A review of the PD management and nursing-care insurance system (long-term care insurance) targeted patients 65 years of age and older who were initiated onto PD from January 2000 to June 2002 at 82 centers in Japan. The review found 765 patients under the age of 65 years (62.6%), and 458 patients 65 years of age and over (37.4%). Data on 409 elderly PD patients from 73 centers were analyzed. Study 1: In 166 elderly patients, 27 (16.3%; 18 women, 9 men) continued PD for more than 5

  20. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Science.gov (United States)

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, phypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  1. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Directory of Open Access Journals (Sweden)

    Stéphanie Rimbaud

    Full Text Available Heart failure (HF is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT. Resveratrol (18 mg/kg/day; HS-RSV was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition. Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001, and prevented the 25% reduction in body weight in HS-NT (P<0.001. Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  2. Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

    Science.gov (United States)

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening −34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium–dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

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

    Directory of Open Access Journals (Sweden)

    Lena Serghides

    2014-03-01

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

  4. Gender differences in retention and survival on antiretroviral therapy ...

    African Journals Online (AJOL)

    Abstract. Background. There is currently a dearth of knowledge on gender differences in mortality among patients on ART in Africa. Methods. Using data from the national ART monitoring and evaluation system, a survival analysis of all healthcare workers, teachers, and police/army personnel who accessed ART in Malawi ...

  5. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity.

    Science.gov (United States)

    Schmidt, Barbara; Anderson, Peter J; Doyle, Lex W; Dewey, Deborah; Grunau, Ruth E; Asztalos, Elizabeth V; Davis, Peter G; Tin, Win; Moddemann, Diane; Solimano, Alfonso; Ohlsson, Arne; Barrington, Keith J; Roberts, Robin S

    2012-01-18

    Very preterm infants are prone to apnea and have an increased risk of death or disability. Caffeine therapy for apnea of prematurity reduces the rates of cerebral palsy and cognitive delay at 18 months of age. To determine whether neonatal caffeine therapy has lasting benefits or newly apparent risks at early school age. Five-year follow-up from 2005 to 2011 in 31 of 35 academic hospitals in Canada, Australia, Europe, and Israel, where 1932 of 2006 participants (96.3%) had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between 1999 and 2004. A total of 1640 children (84.9%) with birth weights of 500 to 1250 g had adequate data for the main outcome at 5 years. Combined outcome of death or survival to 5 years with 1 or more of motor impairment (defined as a Gross Motor Function Classification System level of 3 to 5), cognitive impairment (defined as a Full Scale IQcaffeine from that for the 807 children assigned to placebo (21.1% vs 24.8%; odds ratio adjusted for center, 0.82; 95% CI, 0.65-1.03; P = .09). The rates of death, motor impairment, behavior problems, poor general health, deafness, and blindness did not differ significantly between the 2 groups. The incidence of cognitive impairment was lower at 5 years than at 18 months and similar in the 2 groups (4.9% vs 5.1%; odds ratio adjusted for center, 0.97; 95% CI, 0.61-1.55; P = .89). Neonatal caffeine therapy was no longer associated with a significantly improved rate of survival without disability in children with very low birth weights who were assessed at 5 years.

  6. Survival benefits of antiretroviral therapy in Brazil: a model-based analysis

    Science.gov (United States)

    Luz, Paula M; Girouard, Michael P; Grinsztejn, Beatriz; Freedberg, Kenneth A; Veloso, Valdilea G; Losina, Elena; Struchiner, Claudio J; MacLean, Rachel L; Parker, Robert A; Paltiel, A David; Walensky, Rochelle P

    2016-01-01

    Objective In Brazil, universal provision of antiretroviral therapy (ART) has been guaranteed free of charge to eligible HIV-positive patients since December 1996. We sought to quantify the survival benefits of ART attributable to this programme. Methods We used a previously published microsimulation model of HIV disease and treatment (CEPAC-International) and data from Brazil to estimate life expectancy increase for HIV-positive patients initiating ART in Brazil. We divided the period of 1997 to 2014 into six eras reflecting increased drug regimen efficacy, regimen availability and era-specific mean CD4 count at ART initiation. Patients were simulated first without ART and then with ART. The 2014-censored and lifetime survival benefits attributable to ART in each era were calculated as the product of the number of patients initiating ART in a given era and the increase in life expectancy attributable to ART in that era. Results In total, we estimated that 598,741 individuals initiated ART. Projected life expectancy increased from 2.7, 3.3, 4.1, 4.9, 5.5 and 7.1 years without ART to 11.0, 17.5, 20.7, 23.0, 25.3, and 27.0 years with ART in Eras 1 through 6, respectively. Of the total projected lifetime survival benefit of 9.3 million life-years, 16% (or 1.5 million life-years) has been realized as of December 2014. Conclusions Provision of ART through a national programme has led to dramatic survival benefits in Brazil, the majority of which are still to be realized. Improvements in initial and subsequent ART regimens and higher CD4 counts at ART initiation have contributed to these increasing benefits. PMID:27029828

  7. Improving Patient Acceptance of Insulin Therapy by Improving Needle Design

    OpenAIRE

    Norman, James J.; Prausnitz, Mark R.

    2012-01-01

    Improved needle designs could increase patient compliance with insulin therapy. In this issue of Journal of Diabetes Science and Technology, Hirsch and colleagues assessed patient pain and preference for a 5-bevel needle design among diabetes patients. A blinded comparison with traditional 3-bevel needles yielded no significant difference, but patients preferred the 5-bevel needle in unblinded home injection and clinical insertion studies. This suggests that important subjective/contextual fa...

  8. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Du, Zhongli [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Wencheng [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Xiao, Zefen, E-mail: xiaozefen@sina.com [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Tan, Wen, E-mail: tanwen@cicams.ac.cn [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

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

    OpenAIRE

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

    2013-01-01

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

  10. Evaluation of three definitions of progression-free survival in preoperative cancer therapy (JCOG0801-A).

    Science.gov (United States)

    Nakamura, Kenichi; Shibata, Taro; Takashima, Atsuo; Yamamoto, Seiichiro; Fukuda, Haruhiko

    2012-10-01

    Progression-free survival is an often-used endpoint in clinical trials comparing preoperative therapy and surgery-first therapy. Because the surgery date is always later in the preoperative arm than in the surgery-first arm, it is difficult to define progression-free survival optimally. We evaluated three progression-free survival definitions that used different methods to handle incomplete resection. The three definitions specify the event date of incomplete resection (IR) as follows: 'IR = event' method, date of surgery; 'IR not event' method, date of radiological or clinical progression after incomplete resection; landmark method, landmark time. According to these definitions, the theoretical strengths and weaknesses of the three definitions are investigated. Three patterns of progression-free survival and overall survival were estimated using the data of the Japan Clinical Oncology Group studies. Theoretically, 'IR = event' inflates alpha error while 'IR not event' method and landmark method reduce the statistical power under the alternative hypothesis. In JCOG9907, hazard ratios for the three definitions were: 'IR = event', 0.80 (95% confidence interval, 0.59-1.07; P = 0.13); 'IR not event', 0.81 (95% confidence interval, 0.60-1.09; P = 0.16); landmark, 0.80 (95% confidence interval, 0.59-1.07; P = 0.15). No P value of any methods corresponded with the positive result for overall survival (P = 0.03). In the preoperative arms of the four studies, maximum differences in median and percentage of 1 year progression-free survival among the three definitions were 0-6.4 months and 1.2-5.2%. Progression-free survival sometimes fails as a surrogate of overall survival, and differences among results obtained with various progression-free survival definitions can be large. Overall survival should be used as primary endpoint in studies evaluating preoperative therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chun-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China); Lai, Chyong-Huey [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Huang, Yi-Ting [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chao, Angel; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China)

    2012-11-15

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

  12. Update: improvement strategies for peptide receptor scintigraphy and radionuclide therapy.

    Science.gov (United States)

    de Visser, Monique; Verwijnen, Suzanne M; de Jong, Marion

    2008-04-01

    Somatostatin receptor-targeting peptides are widely used for the imaging and therapy of neuroendocrine tumors. Peptide-receptor radionuclide therapy (PRRT) in neuroendocrine tumor patients with radiolabeled somatostatin analogs has resulted in symptomatic improvement, prolonged survival, and enhanced quality of life. The side-effects of PRRT are few and mostly mild, certainly when using kidney protective agents. If a more widespread use of PRRT is possible, such therapy might become the therapy of first choice in patients with metastasized or inoperable neuroendocrine gastroenteropancreatic tumors. Yet, much profit can be gained from improving the receptor-targeting strategies available and developing new strategies. This review presents an overview of several options to optimize receptor-targeted imaging and radionuclide therapy. These include the optimization of peptide analogs, increasing the number of receptors on the tumor site, and combining PRRT with other treatment strategies. The development of new peptide analogs with increased receptor-binding affinity and improved stability might lead to a higher accumulation of radioactivity inside tumor cells. Analogs of somatostatin have been widely studied. However, much profit can be gained in improving peptide analogs targeting other tumor-related receptors, including gastrin-releasing peptide (GRP) receptors, neurotensin (NT) receptors, cholecystokinin (CCK) receptors, and glucagon-like peptide-1 (GLP-1) receptors. Several peptide analogs targeting these receptors are well on their way to clinical utilization. The literature shows that it is possible to increase the receptor density on tumor cells by using different methods, which results in higher binding and internalization rates and thus a higher contrast during peptide-receptor scintigraphy. In PRRT treatment, this would enable the administration of higher therapeutic doses to tumors, which might lead to a higher cure rate in patients. Combinations of

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-01

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

  14. Survival prognosis after the start of a renal replacement therapy in the Netherlands: A retrospective cohort study

    NARCIS (Netherlands)

    A.C. Hemke (Aline); M.B.A. Heemskerk (Martin); M. van Diepen (Merel); W. Weimar (Willem); F.W. Dekker (Friedo); A.J. Hoitsma (Andries)

    2013-01-01

    textabstractBackground: There is no single model available to predict the long term survival for patients starting renal replacement therapy (RRT). The available models either predict survival on dialysis until transplantation, survival on the transplant waiting list, or survival after

  15. Survival, bacterial clearance and thrombocytopenia are improved in polymicrobial sepsis by targeting nuclear transport shuttles.

    Directory of Open Access Journals (Sweden)

    Ruth Ann Veach

    Full Text Available The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple organ failure in sepsis are attributed to a "genomic storm" resulting from changes in microbial and host genomes encoding virulence factors and endogenous inflammatory mediators, respectively. This storm is mediated by stress-responsive transcription factors that are ferried to the nucleus by nuclear transport shuttles importins/karyopherins. We studied the impact of simultaneously targeting two of these shuttles, importin alpha 5 (Imp α5 and importin beta 1 (Imp β1, with a cell-penetrating Nuclear Transport Modifier (NTM in a mouse model of polymicrobial sepsis. NTM reduced nuclear import of stress-responsive transcription factors nuclear factor kappa B, signal transducer and activator of transcription 1 alpha, and activator protein 1 in liver, which was also protected from sepsis-associated metabolic changes. Strikingly, NTM without antimicrobial therapy improved bacterial clearance in blood, spleen, and lungs, wherein a 700-fold reduction in bacterial burden was achieved while production of proinflammatory cytokines and chemokines in blood plasma was suppressed. Furthermore, NTM significantly improved thrombocytopenia, a prominent sign of microvascular injury in sepsis, inhibited neutrophil infiltration in the liver, decreased L-selectin, and normalized plasma levels of E-selectin and P-selectin, indicating reduced microvascular injury. Importantly, NTM combined with antimicrobial therapy extended the median time to death from 42 to 83 hours and increased survival from 30% to 55% (p = 0.022 as compared to antimicrobial therapy alone. This study documents the fundamental role of nuclear signaling mediated by Imp α5 and Imp β1 in the mechanism of polymicrobial sepsis and highlights the

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-01

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

  17. Effects of hemoperfusion and continuous renal replacement therapy on patient survival following paraquat poisoning.

    Directory of Open Access Journals (Sweden)

    Yadong Wang

    Full Text Available Mortality in patients with paraquat (PQ poisoning is related to plasma PQ levels. Concentrations lower than 5,000 ng/mL are considered critical but curable. This study assessed the effects of hemoperfusion (HP and continuous renal replacement therapy (CRRT on the survival of PQ-poisoned patients with plasma PQ levels below 5,000ng/mL. We analyzed the records of 164 patients with PQ poisoning who were treated at the First Affiliated Hospital of Wenzhou Medical University in China between January 2011 and May 2015. We divided these patients into six sub-groups based on baseline plasma PQ levels and treatment, compared their clinical characteristics, and analyzed their survival rates. Patient sub-groups did not differ in terms of age, sex, time between poisoning and hospital admission, or time to first gavage. Biochemical indicators improved over time in all sub-groups following treatment, and the combined HP and CRRT treatment yielded better results than HP or CRRT alone. Fatality rates in the three treatment sub-groups did not differ among patients with baseline plasma PQ levels of 50-1,000 ng/mL, but in patients with 1,000-5,000 ng/mL levels, the mortality rate was 59.2% (HP treatment group, 48% (CRRT treatment group, and 37.9% (combined treatment group. Mortality rates were higher 10-30 days after hospitalization than in the first 10 days after admission. In the early stages of PQ poisoning, CRRT is effective in reducing patient fatality rates, particularly when combined with HP. Our data could be useful in increasing survival in acute PQ poisoning patients.

  18. Effects of hemoperfusion and continuous renal replacement therapy on patient survival following paraquat poisoning

    Science.gov (United States)

    Wang, Yadong; Chen, Yao; Mao, Lu; Zhao, Guangju; Hong, Guangliang; Li, Mengfang; Wu, Bin; Chen, Xiaorong; Tan, Meng; Wang, Na

    2017-01-01

    Mortality in patients with paraquat (PQ) poisoning is related to plasma PQ levels. Concentrations lower than 5,000 ng/mL are considered critical but curable. This study assessed the effects of hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the survival of PQ-poisoned patients with plasma PQ levels below 5,000ng/mL. We analyzed the records of 164 patients with PQ poisoning who were treated at the First Affiliated Hospital of Wenzhou Medical University in China between January 2011 and May 2015. We divided these patients into six sub-groups based on baseline plasma PQ levels and treatment, compared their clinical characteristics, and analyzed their survival rates. Patient sub-groups did not differ in terms of age, sex, time between poisoning and hospital admission, or time to first gavage. Biochemical indicators improved over time in all sub-groups following treatment, and the combined HP and CRRT treatment yielded better results than HP or CRRT alone. Fatality rates in the three treatment sub-groups did not differ among patients with baseline plasma PQ levels of 50–1,000 ng/mL, but in patients with 1,000–5,000 ng/mL levels, the mortality rate was 59.2% (HP treatment group), 48% (CRRT treatment group), and 37.9% (combined treatment group). Mortality rates were higher 10–30 days after hospitalization than in the first 10 days after admission. In the early stages of PQ poisoning, CRRT is effective in reducing patient fatality rates, particularly when combined with HP. Our data could be useful in increasing survival in acute PQ poisoning patients. PMID:28704509

  19. Survival of patients discharged after acute myocardial infarction and evidence-based drug therapy.

    Science.gov (United States)

    Gouya, Ghazaleh; Reichardt, Berthold; Ohrenberger, Gerald; Wolzt, Michael

    2007-01-01

    There is consensus that patients should be treated with antiplatelet agents, beta-blockers, ACE-inhibitors/ARBs, and lipid lowering drugs for secondary prevention after acute myocardial infarction (AMI), but this evidence-based pharmacotherapy is underutilized. A quality improvement program was conducted in the Austrian county of Burgenland to emphasize the importance of cardiovascular drug therapy at hospital discharge in patients with AMI. In this prospective cohort study 250 members of a regional health insurance company, Burgenländische Gebietskrankenkasse (BGKK), with AMI during the year 2003 were identified using BGKK database. Discharge prescriptions and pharmacy reimbursement data of all included patients were determined. Overall prescription rate for patients discharged from hospital after AMI (n = 207) was 86% for platelet aggregation inhibitors, 77% for ACE-inhibitors or ARBs, 72% for beta-blockers, and 68% for a lipid lowering agent including statins. The all-cause mortality rate during a mean follow-up period of 552 days was 20%. Hazard ratio (HR) for death of patients with maximum 2 medications vs. those receiving 3 or 4 medications was 2.23 (95% CI: 1.19-4.18; p = 0.012). These data demonstrate that use of evidence-based drug treatment for prevention of mortality in patients with AMI is associated with risk reduction and survival benefit. Continuous quality improvement initiatives serve to improve outcome after AMI.

  20. Improving Patient Acceptance of Insulin Therapy by Improving Needle Design

    Science.gov (United States)

    Norman, James J.; Prausnitz, Mark R.

    2012-01-01

    Improved needle designs could increase patient compliance with insulin therapy. In this issue of Journal of Diabetes Science and Technology, Hirsch and colleagues assessed patient pain and preference for a 5-bevel needle design among diabetes patients. A blinded comparison with traditional 3-bevel needles yielded no significant difference, but patients preferred the 5-bevel needle in unblinded home injection and clinical insertion studies. This suggests that important subjective/contextual factors contribute to preference in conjunction with the fundamental needle design change. While 5-bevel needles may increase patient acceptance, more dramatic changes of needle design, such as microneedles, could enable still greater patient acceptance through reduced pain as well as improved insulin pharmacokinetics. PMID:22538143

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

    Science.gov (United States)

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

    2014-08-01

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

  2. Immunosuppression of allogenic mesenchymal stem cells transplantation after spinal cord injury improves graft survival and beneficial outcomes.

    Science.gov (United States)

    Torres-Espín, Abel; Redondo-Castro, Elena; Hernandez, Joaquim; Navarro, Xavier

    2015-03-15

    Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Mesenchymal stem cells (MSC) have demonstrated beneficial effects following transplantation in animal models of SCI. However, despite the immunoprivilege properties of the MSC, their survival in the injured spinal cord is reduced due to the detrimental milieu in the damaged tissue and immune rejection of the cells. The limited survival of the engrafted cells may determine the therapy success. Therefore, we compared two strategies to increase the presence of the cells in the injured spinal cord in rats: increasing the amount of MSC transplants and using immunosuppressive treatment with FK506 after transplantation. Functional outcomes for locomotion and electrophysiological responses were assessed. The grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that immunosuppression improved grafted cells survival. A cell-dose effect was found regarding locomotion recovery and tissue protection independent of immunosuppression. Nevertheless, immunosuppression enhanced the electrophysiological outcomes and allowed filling of the cavity formed after injury by new regenerative tissue and axons. These results indicate that MSC transplantation combined with immunosuppression prolongs the survival of engrafted cells and improves functional and morphological outcomes after SCI.

  3. Improving pacemaker therapy in congenital heart disease: contractility and resynchronization.

    Science.gov (United States)

    Karpawich, Peter P

    2015-01-01

    Designed as effective therapy for patients with symptomatic bradycardia, implantable cardiac pacemakers initially served to improve symptoms and survival. With initial applications to the elderly and those with severe myocardial disease, extended longevity was not a major concern. However, with design technology advances in leads and generators since the 1980s, pacemaker therapy is now readily applicable to all age patients, including children with congenital heart defects. As a result, emphasis and clinical interests have advanced beyond simply quantity to quality of life. Adverse cardiac effects of pacing from right ventricular apical or epicardial sites with resultant left bundle branch QRS configurations have been recognized. As a result, and with the introduction of newer catheter-delivered pacing leads, more recent studies have focused on alternative or select pacing sites such as septal, outflow tract, and para-bundle of His. This is especially important in dealing with pacemaker therapy among younger patients and those with congenital heart disease, with expected decades of artificial cardiac stimulation, in which adverse myocellular changes secondary to pacing itself have been reported. As a correlate to these alternate or select pacing sites, applications of left ventricular pacing, either via the coronary sinus, intraseptal or epicardial, alone or in combination with right ventricular pacing, have gained interest for patients with heart failure. Although cardiac resynchronization pacing has, to date, had limited clinical applications among patients with congenital heart disease, the few published reports do indicate potential benefits as a bridge to cardiac transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Hydroxocobalamin and epinephrine both improve survival in a swine model of cyanide-induced cardiac arrest.

    Science.gov (United States)

    Bebarta, Vikhyat S; Pitotti, Rebecca L; Dixon, Patricia S; Valtier, Sandra; Esquivel, Luis; Bush, Anneke; Little, Charles M

    2012-10-01

    To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (Pcyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased

  5. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Science.gov (United States)

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  6. Working to improve survival and health for babies born very preterm: the WISH project protocol.

    Science.gov (United States)

    Crowther, Caroline A; Middleton, Philippa F; Bain, Emily; Ashwood, Pat; Bubner, Tanya; Flenady, Vicki; Morris, Jonathan; McIntyre, Sarah

    2013-12-19

    Babies born very preterm (before 30 weeks gestation) are at high risk of dying in their first weeks of life, and those who survive are at risk of developing cerebral palsy in childhood. Recent high-quality evidence has shown that giving women magnesium sulphate immediately prior to very early birth can significantly increase the chances of their babies surviving free of cerebral palsy. In 2010 Australian and New Zealand clinical practice guidelines recommended this therapy. The WISH (Working to Improve Survival and Health for babies born very preterm) Project aims to bi-nationally improve and monitor the use of this therapy to reduce the risk of very preterm babies dying or having cerebral palsy. The WISH Project is a prospective cohort study. The 25 Australian and New Zealand tertiary level maternity hospitals will be provided with a package of active implementation strategies to guide the introduction and local adaptation of guideline recommendations. Surveys will be conducted at individual hospitals to evaluate outcomes related to local implementation progress and the use and value of the WISH implementation strategies. For the hospitals participating in the 'WISH audit of uptake and health outcomes data collection', the primary health outcomes (assessed through case note review, and 24 month corrected age questionnaires) will be: the proportion of eligible women receiving antenatal magnesium sulphate; and rates of death prior to primary hospital discharge and cerebral palsy at two years corrected age in infants born to eligible mothers. For hospitals wishing to assess factors influencing translation locally, barriers and facilitators will be measured through interviews with health care professionals, to further guide implementation strategies. Study outcomes for the early phase of the project (Year 1) will be compared with the later intervention phase (Years 2 and 3). The WISH Project will offer insight into the effectiveness of a multifaceted implementation

  7. Method of freezing living cells and tissues with improved subsequent survival

    Science.gov (United States)

    Senkan, Selim M.; Hirsch, Gerald P.

    1980-01-01

    This invention relates to an improved method for freezing red blood cells, ther living cells, or tissues with improved subsequent survival, wherein constant-volume freezing is utilized that results in significantly improved survival compared with constant-pressure freezing; optimization is attainable through the use of different vessel geometries, cooling baths and warming baths, and sample concentrations.

  8. Inhibition of the Mitochondrial Fission Protein Drp1 Improves Survival in a Murine Cardiac Arrest Model

    Science.gov (United States)

    Sharp, Willard W.; Beiser, David G.; Fang, Yong Hu; Han, Mei; Piao, Lin; Varughese, Justin; Archer, Stephen L.

    2015-01-01

    Objectives Survival following sudden cardiac arrest is poor despite advances in cardiopulmonary resuscitation (CPR) and the use of therapeutic hypothermia. Dynamin related protein 1 (Drp1), a regulator of mitochondrial fission, is an important determinant of reactive oxygen species generation, myocardial necrosis, and left ventricular function following ischemia/reperfusion injury, but its role in cardiac arrest is unknown. We hypothesized that Drp1 inhibition would improve survival, cardiac hemodynamics, and mitochondrial function in an in vivo model of cardiac arrest. Design Laboratory investigation. Setting University laboratory Interventions Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent an 8-min KCl induced cardiac arrest followed by 90 seconds of CPR. Mice were then blindly randomized to a single intravenous injection of Mdivi-1 (0.24 mg/kg), a small molecule Drp1 inhibitor or vehicle (DMSO). Measurements and Main Results Following resuscitation from cardiac arrest, mitochondrial fission was evidenced by Drp1 translocation to the mitochondrial membrane and a decrease in mitochondrial size. Mitochondrial fission was associated with increased lactate and evidence of oxidative damage. Mdivi-1 administration during CPR inhibited Drp1 activation, preserved mitochondrial morphology, and decreased oxidative damage. Mdivi-1 also reduced the time to return of spontaneous circulation (ROSC) 116±4 vs. 143±7 sec (pcardiac arrest. Conclusions Post cardiac arrest inhibition of Drp1 improves time to ROSC and myocardial hemodynamics resulting in improved survival and neurological outcomes in a murine model of cardiac arrest. Pharmacological targeting of mitochondrial fission may be a promising therapy for cardiac arrest. PMID:25599491

  9. Survival of patients with metastatic leiomyosarcoma: the MD Anderson Clinical Center for targeted therapy experience.

    Science.gov (United States)

    Wang, Zhijie; Shi, Naiyi; Naing, Aung; Janku, Filip; Subbiah, Vivek; Araujo, Dejka M; Patel, Shreyaskumar R; Ludwig, Joseph A; Ramondetta, Lois M; Levenback, Charles F; Ramirez, Pedro T; Piha-Paul, Sarina A; Hong, David; Karp, Daniel D; Tsimberidou, Apostolia M; Meric-Bernstam, Funda; Fu, Siqing

    2016-12-01

    Advanced stage leiomyosarcoma (LMS) is incurable with current systemic antitumor therapies. Therefore, there is clinical interest in exploring novel therapeutic regimens to treat LMS. We reviewed the medical records of 75 consecutive patients with histologically confirmed metastatic LMS, who had been referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. To lay the foundation for potential phase I trials for the treatment of advanced LMS, we analyzed tumor response and survival outcome data. The frequent hotspot gene aberrations that we observed were the TP53 mutation (65%) and RB1 loss/mutation (45%) detected by Sequenom or next-generation sequencing. Among patients treated with gene aberration-related phase I trial therapy, the median progression-free survival was 5.8 months and the median overall survival was 15.9 months, significantly better than in patients without therapy (1.9 months, P = 0.001; and 8.7 months, P = 0.013, respectively). Independent risk factors that predicted shorter overall survival included hemoglobin <10 g/dL, body mass index <30 kg/m(2) , serum albumin <3.5 g/dL, and neutrophil above upper limit of normal. The median survivals were 19.9, 7.6, and 0.9 months for patients with 0, 1 or 2, and ≥3 of the above risk factors, respectively (P < 0.001). A prognostic scoring system that included four independent risk factors might predict survival in patients with metastatic LMS who were treated in a phase I trial. Gene aberration-related therapies led to significantly better clinical benefits, supporting that further exploration with novel mechanism-driven therapeutic regimens is warranted. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. Temoporfin improves efficacy of photodynamic therapy in advanced biliary tract carcinoma: A multicenter prospective phase II study

    NARCIS (Netherlands)

    Wagner, Andrej; Denzer, Ulrike W.; Neureiter, Daniel; Kiesslich, Tobias; Puespoeck, Andreas; Rauws, Erik A. J.; Emmanuel, Klaus; Degenhardt, Nora; Frick, Ulrich; Beuers, Ulrich; Lohse, Ansgar W.; Berr, Frieder; Wolkersdörfer, Gernot W.

    2015-01-01

    Photodynamic therapy using porfimer (P-PDT) improves palliation and survival in nonresectable hilar bile duct cancer. Tumoricidal penetration depth of temoporfin-PDT (T-PDT) is twice that of P-PDT. In a single-arm phase II study we investigated the safety, efficacy, survival time, and adverse events

  11. Targeted Therapies Improve Survival for Patients with Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    In 2011, based on initial findings from two clinical trials, the Food and Drug Administration approved sunitinib and everolimus for patients with pancreatic neuroendocrine tumors. Updated results from the everolimus trial were published in September 2016.

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

    Science.gov (United States)

    2016-06-01

    lateral liver lobe, thyroid gland , small intestine, large intestine, stomach gall bladder, adrenal glands , thymus pancreas, mesenteric lymph node...includes both an alternate fuel source for cells (D- beta hydroxybutyrate) and a powerful anti-oxidant, melatonin, to protect cells against damage...75.1-241) G 0.0009 High-dose M 31.9 (-20.4- 84.2) 84.0 (31.1- 136.9) 196.2 (142.3- 250.0) 136.2 (82.0- 190.5) 152.6 (87.8- 217.4) T <.0001 Low

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

    Directory of Open Access Journals (Sweden)

    Ling Du

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Andinet Worku Alemu

    2010-10-01

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

  15. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  16. Periodontal therapy improves gastric Helicobacter pylori eradication.

    Science.gov (United States)

    Zaric, S; Bojic, B; Jankovic, Lj; Dapcevic, B; Popovic, B; Cakic, S; Milasin, J

    2009-10-01

    The oral cavity has been proposed as a reservoir for H. pylori that could be responsible for the refractoriness of gastric infection to triple therapy (antibiotics, antimicrobials, and proton pump inhibitors). The aim of this study was to evaluate the efficiency of combined periodontal and triple therapy vs. triple therapy alone, in gastric H. pylori eradication in persons with H. pylori in the subgingival biofilm. Individuals positive for H. pylori in their gastric and oral samples, as determined by nested PCR, were treated either with periodontal and triple therapy or with triple therapy alone. Our results indicate that 77.3% of those treated with the combined therapy exhibited successful eradication of gastric H. pylori, compared with 47.6% who underwent only triple therapy. Analysis of these data suggests that periodontal treatment in combination with systemic therapy could be a promising approach to increasing the therapy's efficacy and decreasing the risk of infection recurrence.

  17. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times.

    Science.gov (United States)

    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Marshall, Karen; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Senthilnathan, Seanthan; Baker, Talia; Gates, Vanessa L; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2011-08-01

    It is not clear whether survival times of patients with hepatocellular carcinoma (HCC) are associated with their response to therapy. We analyzed the association between tumor response and survival times of patients with HCC who were treated with locoregional therapies (LRTs) (chemoembolization and radioembolization). Patients received LRTs over a 9-year period (n = 463). Patients with metastases, portal venous thrombosis, or who had received transplants were excluded; 159 patients with Child-Pugh B7 or lower were analyzed. Response (based on European Association for the Study of the Liver [EASL] and World Health Organization [WHO] criteria) was associated with survival times using the landmark, risk-of-death, and Mantel-Byar methodologies. In a subanalysis, survival times of responders were compared with those of patients with stable disease and progressive disease. Based on 6-month data, in landmark analysis, responders survived longer than nonresponders (based on EASL but not WHO criteria: P = .002 and .0694). The risk of death was also lower for responders (based on EASL but not WHO criteria: P = .0463 and .707). Landmark analysis of 12-month data showed that responders survived longer than nonresponders (P < .0001 and .004, based on EASL and WHO criteria, respectively). The risk of death was lower for responders (P = .0132 and .010, based on EASL and WHO criteria, respectively). By the Mantel-Byar method, responders had longer survival than nonresponders, based on EASL criteria (P < .0001; P = .596 with WHO criteria). In the subanalysis, responders lived longer than patients with stable disease or progressive disease. Radiographic response to LRTs predicts survival time. EASL criteria for response more consistently predicted survival times than WHO criteria. The goal of LRT should be to achieve a radiologic response, rather than to stabilize disease. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Heat adaptation towards improve survival of Bifidobacterium longum ...

    African Journals Online (AJOL)

    This study examined the survival of Bifidobacterium longum BB 536 following the spray drying and during the storage of Medida, a fermented Sudanese cereal porridge. Medida was produced using 225 g flour of two days malted brown rice; blended in 0.405 L distilled water and cooked in 1 L boiling water. 150 g skim milk ...

  19. Heat adaptation towards improve survival of Bifidobacterium longum ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-04-20

    Apr 20, 2009 ... 150 g skim milk was added followed by sterilization; and the mixture was inoculated with B. longum. BB536 and incubated until the biomass reached approximately 9 Log CFU/ml. Spray drying inlet temperature was regulated at 160oC. The strain BB536 survivability at different outlet temperatures (95,.

  20. Gene Tests May Improve Therapy for Endometrial Cancer

    Science.gov (United States)

    ... Special Issues Subscribe June 2013 Print this issue Gene Tests May Improve Therapy for Endometrial Cancer Send us your comments By analyzing genes in hundreds of endometrial tumors, scientists identified details ... therapies for some patients. Endometrial cancer affects the lining ...

  1. Survival Patterns in Elderly Head and Neck Squamous Cell Carcinoma Patients Treated With Definitive Radiation Therapy.

    Science.gov (United States)

    Sommers, Linda W; Steenbakkers, Roel J H M; Bijl, Henk P; Vemer-van den Hoek, Johanna G M; Roodenburg, Jan L N; Oosting, Sjoukje F; Halmos, Gyorgy B; de Rooij, Sophia E; Langendijk, Johannes A

    2017-07-15

    We sought to assess the effect of age on overall survival (OS), cancer-specific survival (CSS), and non-cancer-related death (NCRD) in elderly (aged ≥70 years) head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radiation therapy. The results were compared with those of younger patients, and the most important prognostic factors for survival endpoints were determined. Treatments may be better justified based on identification of the main differences in survival between young and elderly patients. Data were analyzed from all consecutive HNSCC patients treated with definitive radiation therapy (66-70 Gy) in our department between April 2007 and December 2014. A total of 674 patients, including 168 elderly patients (24.9%), were included in the study. Multivariate association models were constructed to assess the effect of age on survival endpoints. Multivariate analysis was performed to identify potential prognostic factors for survival in elderly patients. A total of 674 consecutive patients, including 168 elderly patients, were analyzed. The 5-year OS and NCRD rates were significantly worse for elderly patients than for young patients: 45.5% versus 58.2% (P=.007) and 39.0% versus 20.7% (Pelderly patient group. Of the elderly patients, 80 (47%) died during follow-up; 45% of these deaths were ascribed to the index tumor. For elderly patients, radiation therapy combined with systemic forms of treatment was significantly associated with adverse NCRD rate (hazard ratio, 8.02; 95% confidence interval, 2.36-27.2; P=.001) after we performed a multivariate association analysis. Elderly HNSCC patients have worse survival outcomes than young HNSCC patients. Age is an independent prognostic factor for OS, mainly due to an increase in non-cancer-related mortality and comorbid diseases. The differences in CSS between young and elderly patients are negligible. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    2017-09-01

    This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing after cervical spinal...complications. This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing after...training as cervical SCI is a complicated and difficult surgery and much practice is needed in order to produce consistent injury outcomes

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-01

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

  4. Membrane based macroencapsulation devices for improved pancreatic islet survival and function

    NARCIS (Netherlands)

    Skrzypek, Katarzyna

    2017-01-01

    The research presented in this thesis is about the development of novel membrane based macroencapsulation devices for improved pancreatic islet survival and function. To improve pancreatic islets functionality by avoiding their aggregation within macroencapsulation devices, we developed a novel

  5. Multimodal and sequential treatment improves survival in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Göbel, Thomas; Graf, Dirk; Hosnowsky, Christina; Blondin, Dirk; Knoefel, Wolfram Trudo; Häussinger, Dieter; Erhardt, Andreas

    2017-03-01

    Background and aims  Therapy of hepatocellular carcinoma (HCC) mainly depends on tumor stage and liver function. The aim of this study was to identify additional predictors of overall survival in HCC patients with a particular attention to multimodal therapies. Methods  Six hundred and seven consecutive HCC-patients treated in a tertiary center between 1988 and 2011 were retrospectively analyzed. Multivariate analysis was performed by logistic and Cox-regression, overall survival was analyzed by Kaplan Meier statistics. Results  In comparison to unimodal therapies, multimodal treatment increased overall survival in BCLC-A patients from 16 to 26 months (p multimodal therapy irrespective of alfa-fetoprotein levels. Comparing the time span 1988 - 1999 with 2000 - 2011, the rate of multimodal/sequential treatment increased from 12.3 % to 30 % (p multimodal treatment was shown to be an independent predictor for overall survival besides elevated alfa-fetoprotein, Child Pugh score, and BCLC stage. Conclusion  Multimodal therapies increase overall survival in HCC patients and should be considered in patients with HCC if practicable. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival

    DEFF Research Database (Denmark)

    Witt, Christoffer Tobias; Kronborg, Mads Brix; Nohr, Ellen Aagaard

    2015-01-01

    AIMS: Treatment with evidence-based heart failure (HF) medication reduces morbidity and mortality, yet they remain underused and underdosed. Cardiac resynchronization therapy (CRT) improves haemodynamics, and might allow for optimization of HF medication. We analysed treatment with HF medication......HR 0.55 (0.38-0.80); P = 0.002). CONCLUSION: After CRT implantation, optimization of HF treatment is possible, and long-term adherence to HF medication remains high. Higher doses of BB and ACEi/ARB were associated with prolonged survival....

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

    Directory of Open Access Journals (Sweden)

    Dorothy Cimino Brown

    2012-01-01

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

  8. Retrospective Study of the Survival Rates of Indirect Pulp Therapy Versus Different Pulpotomy Medicaments.

    Science.gov (United States)

    Wunsch, Patrice Barsamian; Kuhnen, Marissa M; Best, Al M; Brickhouse, Tegwyn H

    2016-10-15

    The purposes of this retrospective chart review were to determine: (1) how primary molars in need of vital pulp therapy (VPT) have been treated over a period of four years at a university-based pediatric dental practice (UBP); and which treatments-indirect pulp therapy (IPT), formocresol pulpotomy (FCP), and ferric sulfate pulpotomy (FSP)-have been successful. Electronic patient records (axiUm) that contained the procedure codes D3120 (pulp cap-indirect) or D3220 (therapeutic pulpotomy) were totaled by year. Visit records were queried again to identify treatment failures (i.e., extractions [D7140] or pulpectomy [D3221/D3240]). A total of 2,001 primary molar teeth were included in the study. Success was compared using a Kaplan-Meier analysis. At the three-year follow-up, IPT had a 96.2 percent survival rate, FCP had a 65.8 percent survival rate, and FSP had a 62.9 percent survival rate (P<.0001). Over a four-year period of time, IPT became the more commonly used vital pulp therapy treatment at a university-based pediatric dental practice and had a significantly better survival rate than FCP or FSP.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    African Journals Online (AJOL)

    0655711075

    strategies are needed for the Prevention of Mother-To-Child Transmission of HIV (PMTCT). The complete PMTCT ... obstetric practices, antiretroviral therapy and infant feeding counseling and support. Aim: This article .... proposed for developing countries each with different resource requirements and levels of associated ...

  11. Thrombopoietin Receptor Agonist Mitigates Hematopoietic Radiation Syndrome and Improves Survival after Whole-Body Ionizing Irradiation Followed by Wound Trauma

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2017-01-01

    Full Text Available Ionizing radiation combined with trauma tissue injury (combined injury, CI results in greater mortality and H-ARS than radiation alone (radiation injury, RI, which includes thrombocytopenia. The aim of this study was to determine whether increases in numbers of thrombocytes would improve survival and mitigate H-ARS after CI. We observed in mice that WBC and platelets remained very low in surviving RI animals that were given 9.5 Gy 60Co-γ-photon radiation, whereas only lymphocytes and basophils remained low in surviving CI mice that were irradiated and then given skin wounds. Numbers of RBC and platelets, hemoglobin concentrations, and hematocrit values remained low in surviving RI and CI mice. CI induced 30-day mortality higher than RI. Radiation delayed wound healing by approximately 14 days. Treatment with a thrombopoietin receptor agonist, Alxn4100TPO, after CI improved survival, mitigated body-weight loss, and reduced water consumption. Though this therapy delayed wound-healing rate more than in vehicle groups, it greatly increased numbers of platelets in sham, wounded, RI, and CI mice; it significantly mitigated decreases in WBC, spleen weights, and splenocytes in CI mice and decreases in RBC, hemoglobin, hematocrit values, and splenocytes and splenomegaly in RI mice. The results suggest that Alxn4100TPO is effective in mitigating CI.

  12. Cytoreductive nephrectomy for metastatic renal cell carcinoma: inequities in access exist despite improved survival.

    Science.gov (United States)

    Patel, Manish I; Beattie, Kieran; Bang, Albert; Gurney, Howard; Smith, David P

    2017-10-01

    The use of cytoreductive nephrectomy (CRN) in the targeted therapy era is still debated. We aimed to determine factors associated with reduced use of CRN and determine the effect of CRN on overall survival in patients with metastatic renal cell carcinoma (RCC). All advanced RCC diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. Follow-up was to the end of 2011. Multivariable logistic regression analysis was used to determine factors associated with the receipt of CRN. Cox proportional hazards model was used to determine factors associated with survival. A total of 1062 patients were identified with metastatic RCC of whom 289 (27%) received CRN. There was no difference in the use of CRN over the time period of the study. Females (OR 0.68 (95% CI: 0.48-0.96)), unmarried individuals (OR 0.68 (95% CI: 0.48-0.96)), treatment in a nonteaching hospital (OR 0.26 (95% CI: 0.18-0.36)) and individuals without private insurance (OR 0.29 (95% CI: 0.20-0.41)) all had reduced likelihood of receiving CRN. On multivariable analysis, not receiving CRN resulted in a 90% increase in death (HR 1.90 (95% CI: 1.61-2.25)). In addition, increasing age (P < 0.001), increasing Charlson comorbidity status (P = 0.002) and female gender also had a significant independent association with death. Despite a strong association with improved survival, individuals who are elderly, female, have treatment in a nonteaching facility or have no private insurance have a reduced likelihood of receiving CRN. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Pal, Sumanta K; Nelson, Rebecca A; Vogelzang, Nicholas

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    National Cancer Research Institute trials showed significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002) and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02). CONCLUSION Adding GO (3 mg/m(2)) to induction chemotherapy reduces relapse risk and improves survival with little increase......PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved...... survival for the majority of patients when adding gemtuzumab ozogamicin (GO) to induction chemotherapy. PATIENTS AND METHODS Untreated patients with AML or high-risk myelodysplastic syndrome (median age, 67 years; range, 51 to 84 years) were randomly assigned to receive induction chemotherapy with either...

  16. Psoriasis: improving adherence to topical therapy.

    NARCIS (Netherlands)

    Feldman, S.R.; Horn, E.J.; Balkrishnan, R.; Basra, M.K.; Finlay, A.Y.; McCoy, D.; Menter, A.; Kerkhof, P.C.M. van de

    2008-01-01

    Topical therapy has an important role in psoriasis treatment. It is efficacious and has a favorable safety profile as demonstrated in clinical trials. However, poor treatment outcomes from topical therapy regimens likely result from poor adherence and ineffective use of the medication. The

  17. Chemotherapy and targeted therapy for patients with initially unresectable colorectal liver metastases, focusing on conversion hepatectomy and long-term survival.

    Science.gov (United States)

    Beppu, Toru; Miyamoto, Yuji; Sakamoto, Yasuo; Imai, Katsunori; Nitta, Hidetoshi; Hayashi, Hiromitsu; Chikamoto, Akira; Watanabe, Masayuki; Ishiko, Takatoshi; Baba, Hideo

    2014-06-01

    Eight years have passed since the introduction of chemotherapy (chemo) and targeted therapy regimens for colorectal liver metastases (CRLM). This study aimed to clarify the effectiveness of chemo and targeted therapy in facilitating conversion hepatectomy and improving long-term survival in Japanese patients with CRLM. A total of 199 patients with CRLM were treated between May 2005 and August 2012. Initial therapies for these patients included straightforward hepatic resection (n = 48; 24 %), induction chemotherapy (n = 148; 74 %), and radiofrequency ablation (n = 3; 2 %). In 56 of 137 patients (40.1 %) with initially unresectable CRLM, 7.5 courses of chemo and targeted therapy downsized and converted tumors to resectable tumors. The 5-year cumulative overall survival (OS) rate and the median survival time were significantly higher for the resectable CRLM than for the unresectable CRLM (54.6 vs. 5.3 % and 77.3 vs. 21.3 months, respectively; P conversion hepatectomy (hazard ratio [HR] 0.19; P therapy (HR 0.46; P therapy (OR 6.1; P conversion hepatectomy. A chemo and targeted therapy can facilitate conversion hepatectomy and allow for an excellent prognosis in patients with initially unresectable CRLM.

  18. Analysis of Survival After Initiation of Continuous Renal Replacement Therapy in a Surgical Intensive Care Unit.

    Science.gov (United States)

    Tatum, James M; Barmparas, Galinos; Ko, Ara; Dhillon, Navpreet; Smith, Eric; Margulies, Daniel R; Ley, Eric J

    2017-10-01

    Continuous renal replacement therapy (CRRT) benefits patients with renal failure who are too hemodynamically unstable for intermittent hemodialysis. The duration of therapy beyond which continued use is futile, particularly in a population of patients admitted to and primarily cared for by a surgical service (hereinafter referred to as surgical patients), is unclear. To analyze proportions of and independent risk factors for survival to discharge after initiation of CRRT among patients in a surgical intensive care unit (SICU). This retrospective cohort study included all patients undergoing CRRT from July 1, 2012, through January 31, 2016, in an SICU of an urban tertiary medical center. The population included patients treated before or after general surgery and patients admitted to a surgical service during inpatient evaluation and care before liver transplant. The pretransplant population was censored from further survival analysis on receipt of a transplant. Continuous renal replacement therapy. Hospital mortality among patients in an SICU after initiation of CRRT. Of 108 patients (64 men [59.3%] and 44 women [40.7%]; mean [SD] age, 62.0 [12.7] years) admitted to the SICU, 53 were in the general surgical group and 55 in the pretransplant group. Thirteen of the 22 patients in the pretransplant group who required 7 or more days of CRRT died (in-hospital mortality, 59.1%); among the 12 patients in the general surgery group who required 7 or more days of CRRT, 12 died (in-hospital mortality, 100%). In the general surgical group, each day of CRRT was associated with an increased adjusted odds ratio of death of 1.39 (95% CI, 1.01-1.90; P = .04). Continuous renal replacement therapy is valuable for surgical patients with an acute and correctable indication; however, survival decreases significantly with increasing duration of CRRT. Duration of CRRT does not correlate with survival among patients awaiting liver transplant.

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

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  20. Club cell secretory protein improves survival in a murine obliterative bronchiolitis model.

    Science.gov (United States)

    Wendt, Christine; Tram, Kevin; Price, Andrew; England, Kristen; Stiehm, Andrew; Panoskaltsis-Mortari, Angela

    2013-11-01

    Club cell secretory protein (CCSP) is an indirect phospholipase A2 inhibitor with some immunosuppressive and antiproliferative properties that is expressed in bronchiolar Club cells. In our murine bone marrow transplant (BMT) model of obliterative bronchiolitis (OB), CCSP is diminished; however, its role is unknown. To determine the role of CCSP, B6 wild-type (WT) or CCSP-deficient (CCSP(-/-)) mice were lethally conditioned and given allogeneic bone marrow with a sublethal dose of allogeneic splenic T cells to induce OB. We found that CCSP(-/-) mice demonstrated a higher mortality following BMT-induced OB compared with WT mice. Mice were analyzed 60 days post-BMT for protein expression, pulmonary function, and histology. CCSP levels were reduced in WT mice with BMT-induced OB, and lower levels correlated to decreased lung compliance. CCSP(-/-) had a higher degree of injury and fibrosis as measured by hydroxy proline, along with an increased lung resistance and the inflammatory markers, leukotriene B4 and CXCL1. Replacement with recombinant intravenous CCSP partially reversed the weight loss and improved survival in the CCSP(-/-) mice. In addition, CCSP replacement improved histology and decreased inflammatory cells and markers. These findings indicate that CCSP has a regulatory role in OB and may have potential as a preventive therapy.

  1. Filial cannibalism improves survival and development of beaugregory damselfish embryos.

    Science.gov (United States)

    Payne, Adam G; Smith, Carl; Campbell, Andrew C

    2002-01-01

    Cannibalism of small numbers of offspring by a parent has been proposed as an adaptive parental strategy, by providing energy to support parental care. However, there are few empirical studies to support this hypothesis. We conducted field and laboratory experiments to investigate partial filial cannibalism in Stegastes leucostictus, a coral reef fish with paternal care. Partial cannibalism was shown to be common, and males were found to remove developing embryos from throughout a clutch in a random pattern, rather than in the more aggregated pattern seen during embryo predation. Males that received a diet supplement grew faster than control males, but did not engage in less cannibalism. Also, males did not concentrate cannibalism on early embryonic stages with the highest energetic value. Experimental reduction of embryo densities was found to significantly increase embryo development rate and survival from egg deposition to hatching, and experimental reduction of oxygen levels significantly increased rates of partial filial cannibalism by males. Artificial spawning sites with low oxygen levels were avoided by spawning females, and cannibalism rates by males were higher. We propose that partial filial cannibalism serves as an adaptive parental strategy to low oxygen levels in S. leucostictus by increasing the hatching success of embryos. PMID:12396483

  2. Improving child survival: Malnutrition Task Force and the paediatrician's responsibility

    Science.gov (United States)

    Jackson, A A; Ashworth, A; Khanum, S

    2006-01-01

    Malnutrition (underweight) contributes to approximately 60% of all child deaths, yet health professionals, policy makers, and donor agencies often fail to recognise its relevance to child survival. There is a need for the paediatric community to champion the importance of adequate nutrition for normal growth and development, and of placing sufficient emphasis on the prevention and treatment of malnutrition. Many severely malnourished children die from inappropriate treatment. Case fatality rates of 25–30% are commonly found and in some hospitals as many as 50–70% will die. Many of these deaths are avoidable. Weaknesses in health systems, inappropriate training of doctors and nurses, inadequate supervision, and lack of support for staff all contribute to compromised quality of care. The International Union of Nutritional Sciences, with support from the International Pediatric Association, Launched a global Malnutrition Task Force in 2005. The main objective is to ensure that an integrated system of prevention and treatment of malnutrition is actively supported as a fundamental aspect of care, and becomes an integral part of all training programmes. PMID:16861489

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

    Directory of Open Access Journals (Sweden)

    Sumanta K Pal

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

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

    Science.gov (United States)

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

    2014-06-01

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

  5. Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.

    Science.gov (United States)

    Weijer, Ruud; Clavier, Séverine; Zaal, Esther A; Pijls, Maud M E; van Kooten, Robert T; Vermaas, Klaas; Leen, René; Jongejan, Aldo; Moerland, Perry D; van Kampen, Antoine H C; van Kuilenburg, André B P; Berkers, Celia R; Lemeer, Simone; Heger, Michal

    2017-03-01

    Photodynamic therapy (PDT) is an established palliative treatment for perihilar cholangiocarcinoma that is clinically promising. However, tumors tend to regrow after PDT, which may result from the PDT-induced activation of survival pathways in sublethally afflicted tumor cells. In this study, tumor-comprising cells (i.e., vascular endothelial cells, macrophages, perihilar cholangiocarcinoma cells, and EGFR-overexpressing epidermoid cancer cells) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). The post-PDT survival pathways and metabolism were studied following sublethal (LC50) and supralethal (LC90) PDT. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly HIF-1-, NF-кB-, AP-1-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. PDT-subjected SK-ChA-1 cells downregulated proteins associated with EGFR signaling, particularly at LC90. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor-associated cell types that transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, tumor cells sublethally afflicted by PDT are a major therapeutic culprit. Our multi-omic analysis further unveiled multiple druggable targets for pharmacological co-intervention.

  6. Recombinant factor VIIa is associated with an improved 24-hour survival without an improvement in inpatient survival in massively transfused civilian trauma patients

    Directory of Open Access Journals (Sweden)

    Bartolomeu Nascimento

    2011-01-01

    Full Text Available OBJECTIVE: To determine whether recombinant factor VIIa (rFVIIa is associated with increased survival and/or thromboembolic complications. INTRODUCTION: Uncontrollable hemorrhage is the main cause of early mortality in trauma. rFVIIa has been suggested for the management of refractory hemorrhage. However, there is conflicting evidence about the survival benefit of rFVIIa in trauma. Furthermore, recent reports have raised concerns about increased thromboembolic events with rFVIIa use. METHODS: Consecutive massively transfused (> 8 units of red blood cells within 12 h trauma patients were studied. Data on demographics, injury severity scores, baseline laboratory values and use of rFVIIa were collected. Rate of transfusion in the first 6 h was used as surrogate for bleeding. Study outcomes included 24-hour and in-hospital survival, and thromboembolic events. A multivariable logistic regression analysis was used to determine the impact of rFVIIa on 24-hour and in-hospital survival. RESULTS: Three-hundred and twenty-eight patients were massively transfused. Of these, 72 patients received rFVIIa. As expected, patients administered rFVIIa had a greater degree of shock than the non-rFVIIa group. Using logistic regression to adjust for predictors of death in the regression analysis, rFVIIa was a significant predictor of 24-hour survival (odds ratio (OR = 2.65; confidence interval 1.26-5.59; p = 0.01 but not of in-hospital survival (OR = 1.63; confidence interval 0.79-3.37; p = 0.19. No differences were seen in clinically relevant thromboembolic events. CONCLUSIONS: Despite being associated with improved 24-hour survival, rFVIIa is not associated with a late survival to discharge in massively transfused civilian trauma patients.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  8. Orbital rhabdomyosarcoma: improved survival with combined pulsed chemotherapy and irradiation.

    OpenAIRE

    Ghafoor, S Y; Dudgeon, J

    1985-01-01

    Three cases of embryonal orbital rhabdomyosarcoma are presented in which two cases had intracranial extension. All three are alive and well on follow-up several years after completing a 12-month course of combined pulsed chemotherapy and irradiation. The improved prognosis even in parameningeal involvement is emphasised.

  9. Restricted mean survival time over 15 years for patients starting renal replacement therapy.

    Science.gov (United States)

    Couchoud, Cécile; Dantony, Emmanuelle; Elsensohn, Mad-Hélénie; Villar, Emmanuel; Vigneau, Cécile; Moranne, Olivier; Rabilloud, Muriel; Ecochard, René

    2017-04-01

    The restricted mean survival time (RMST) estimates life expectancy up to a given time horizon and can thus express the impact of a disease. The aim of this study was to estimate the 15-year RMST of a hypothetical cohort of incident patients starting renal replacement therapy (RRT), according to their age, gender and diabetes status, and to compare it with the expected RMST of the general population. Using data from 67 258 adult patients in the French Renal Epidemiology and Information Network (REIN) registry, we estimated the RMST of a hypothetical patient cohort (and its subgroups) for the first 15 years after starting RRT (cRMST) and used the general population mortality tables to estimate the expected RMST (pRMST). Results were expressed in three different ways: the cRMST, which calculates the years of life gained under the hypothesis of 100% death without RRT treatment, the difference between the pRMST and the cRMST (the years lost), and a ratio expressing the percentage reduction of the expected RMST: (pRMST - cRMST)/pRMST. Over their first 15 years of RRT, the RMST of end-stage renal disease (ESRD) patients decreased with age, ranging from 14.3 years in patients without diabetes aged 18 years at ESRD to 1.8 years for those aged 90 years, and from 12.7 to 1.6 years, respectively, for those with diabetes; expected RMST varied from 15.0 to 4.1 years between 18 and 90 years. The number of years lost in all subgroups followed a bell curve that was highest for patients aged 70 years. After the age of 55 years in patients with and 70 years in patients without diabetes, the reduction of the expected RMST was >50%. While neither a clinician nor a survival curve can predict with absolute certainty how long a patient will live, providing estimates on years gained or lost, or percentage reduction of expected RMST, may improve the accuracy of the prognostic estimates that influence clinical decisions and information given to patients.

  10. Survival of women with gestational trophoblastic neoplasia and liver metastases: is it improving?

    Science.gov (United States)

    Ahamed, Eliyaz; Short, Dee; North, Bernard; Savage, Philip M; Seckl, Michael J

    2012-01-01

    To determine whether survival outcomes of women with liver metastases from gestational trophoblastic neoplasia (GTN) have improved from the previous finding of 27% at 5 years. The Charing Cross GTN database was searched for patients with liver metastases treated between 1975 and 2007. Prognostic variables were recorded and analyzed for effect on survival. Thirty-eight (1.8%) of 2,100 GTN patients had liver metastases. One patient with placental site trophoblastic tumor was excluded. In the remaining 37 cases the overall survival was 48% at 5 years. Seven patients with very advanced disease died survival was 68%. No prognostic variable was significant on univariate analysis. However, patients presenting >2.8 years and survival, respectively. The prognosis of patients with liver metastases from GTN has improved. Outcome may be best in those patients presenting within 2.8 years of the causative pregnancy and without very large volumes of disease.

  11. Advancements in cardiopulmonary resuscitation: increasing circulation and improving survival.

    Science.gov (United States)

    Ramsay, Philip T; Maxwell, Robert A

    2009-05-01

    Clinicians, as well as lay people, have realized the importance of resuscitative maneuvers throughout recorded history. Cardiopulmonary resuscitation has evolved from a relatively primitive technique to one now dictated by data from evidence based medicine. Recent advancements include changes in life support guidelines, the development of an impedance threshold device, and the initiation of therapeutic hypothermia. We can only expect continued advancements in cardiopulmonary resuscitation through new technology with resultant improved outcomes.

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

    Science.gov (United States)

    Poff, Angela M; Ari, Csilla; Seyfried, Thomas N; D'Agostino, Dominic P

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Angela M Poff

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

  14. The impact of repeated surgery and adjuvant therapy on survival for patients with recurrent glioblastoma.

    Science.gov (United States)

    De Bonis, Pasquale; Fiorentino, Alba; Anile, Carmelo; Balducci, Mario; Pompucci, Angelo; Chiesa, Silvia; Sica, Gigliola; Lama, Gina; Maira, Giulio; Mangiola, Annunziato

    2013-07-01

    Treatment of glioblastoma recurrence can have a palliative aim, after considering risks and potential benefits. The aim of this study is to verify the impact of surgery and of palliative adjuvant treatments on survival after recurrence. From January 2002 to June 2008, we treated 76 consecutive patients with recurrent glioblastoma. Treatment was: 1-surgery alone--17 patients; 2-adjuvant-therapy alone--24 patients; 3-surgery and adjuvant therapy--16 patients; no treatment--19 patients. The impact on median overall-survival (OS-time between recurrence and death/last follow-up) of age, Karnofsky performance scale (KPS), resection extent and adjuvant treatment scheme (Temozolomide alone vs low-dose fractionated radiotherapy vs others) was determined. Survival curves were obtained through the Kaplan-Meier method. Cox proportional-hazards was used for multivariate analyses. Significance was set at p<0.05. Median OS was 7 months. At univariate analysis, patients with a KPS≥70 had a longer OS (9 months vs 5 months--p<0.0001). OS was 6 months for patients treated with surgery alone, 5 months for patients that received no treatment, 8 months for patients treated with chemotherapy alone, 14 months for patients treated with surgery and adjuvant therapy--p=0.01. Patients with a KPS<70 were significantly at risk for death - HR 2.8 - p=0.001. Subgroup analysis showed no significant differences between patients receiving gross total or partial tumor resection and among patients receiving different adjuvant therapy schemes. Major surgical morbidity at tumor recurrence occurred in 16 out of 33 patients (48%). It is fundamental, before deciding to operate patients for recurrence, to carefully consider the impact of surgical morbidity on outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.

    Science.gov (United States)

    Srivastava, Amit K; Bulte, Camille A; Shats, Irina; Walczak, Piotr; Bulte, Jeff W M

    2016-01-01

    Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (ptransplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (pcells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Csilla Ari

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

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

    Science.gov (United States)

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

    2016-09-01

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

  18. Can Shockwave Therapy Improve Tendon Metabolism?

    NARCIS (Netherlands)

    Zwerver, Johannes; Waugh, Charlotte; van der Worp, Henk; Scott, Alex; Ackermann, PW; Hart, DA

    2016-01-01

    Shockwave treatments are commonly used in the management of tendon injuries and there is increasing evidence for its clinical effectiveness. There is a paucity of fundamental (in vivo) studies investigating the biological action of shockwave therapy. Destruction of calcifications, pain relief and

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

    Directory of Open Access Journals (Sweden)

    Helena Čičková

    2013-01-01

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

  20. Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients: four cases

    Science.gov (United States)

    2014-01-01

    Background and importance Recurrent malignant gliomas (RMGs) are very difficult to control, and no standard treatments have been established for them. We performed boron neutron capture therapy (BNCT) for patients with RMG. BNCT enables high-dose particle radiation to be applied selectively to tumor cells. However, RMG cases generally receive nearly 60 Gy X-ray irradiation prior to re-irradiation by BNCT. Therefore, even with tumor-selective particle radiation BNCT, radiation necrosis in the brain and symptomatic pseudoprogression may develop. In four of our recent patients with RMG after BNCT, we applied the anti-VEGF antibody bevacizumab to treat two pathological entities. This approach appeared to prolong survival. Here we present the case reports of these four consecutive patients with RMG and discuss the novel use of bevacizumab in this context. Clinical presentation Four patients with RMGs were treated with BNCT at our institutes. Upon the referral for BNCT, they were assessed as belonging to the recursive partitioning analysis (RPA) class 3 (n = 3 patients) or RPA class 4 (n = 1 patient) (the RPA classification for RMG was advocated by Carson et al. in 2007). The estimated median survival times for RPA classes 3 and 4 were 3.8 and 10.8 months, respectively, after some treatment at the recurrence. We applied BNCT for these four patients and administered bevacizumab when the lesions were considered radiation necrosis or symptomatic pseudoprogression. The class 3 patients survived after the BNCT for 14, 16.5 and > 23 months, and the class 4 patient survived > 26 months, with favorable improvements in clinical symptoms. Conclusion BNCT with the addition of bevacizumab for radiation necrosis or symptomatic pseudoprogression improved the clinical symptoms and prolonged the survival in RMG patients. PMID:24387301

  1. In vitro study of cell survival following dynamic MLC intensity-modulated radiation therapy dose delivery.

    Science.gov (United States)

    Moiseenko, Vitali; Duzenli, Cheryl; Durand, Ralph E

    2007-04-01

    The possibility of reduced cell kill following intensity-modulated radiation therapy (IMRT) compared to conventional radiation therapy has been debated in the literature. This potential reduction in cell kill relates to prolonged treatment times typical of IMRT dose delivery and consequently increased repair of sublethal lesions. While there is some theoretical support to this reduction in cell kill published in the literature, direct experimental evidence specific to IMRT dose delivery patterns is lacking. In this study we present cell survival data for three cell lines: Chinese hamster V79 fibroblasts, human cervical carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for 2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time 75 s, which served as a reference; regular seven-field IMRT, irradiation time 5 min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization after three fields were delivered, irradiation time 10 min. An actual seven-field dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC. Survival data were also collected for doses 1X, 2X, 3X, 4X, and 5x 2.1 Gy to establish parameters of the linear-quadratic equation describing survival following acute dose delivery. Cells were irradiated inside an acrylic cylindrical phantom specifically designed for this study. Doses from both IMRT and POP were validated using ion chamber measurements. A reproducible increase in cell survival was observed following IMRT dose delivery. This increase varied from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420 following uninterrupted IMRT, to very pronounced for SiHa, with a surviving fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared to IMRT or IMRT with a break for MLC initialization, cell survival following acute dose delivery was

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-03-15

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

  3. Improved Survival Among Children with Spina Bifida in the United States

    Science.gov (United States)

    Shin, Mikyong; Kucik, James E.; Siffel, Csaba; Lu, Chengxing; Shaw, Gary M.; Canfield, Mark A.; Correa, Adolfo

    2015-01-01

    Objective To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. Study design A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. Results During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. Conclusions The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival. PMID:22727874

  4. Interleukin 7 immunotherapy improves host immunity and survival in a two-hit model of Pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Shindo, Yuichiro; Fuchs, Anja G; Davis, Christopher G; Eitas, Tim; Unsinger, Jacqueline; Burnham, Carey-Ann D; Green, Jonathan M; Morre, Michel; Bochicchio, Grant V; Hotchkiss, Richard S

    2017-02-01

    Patients with protracted sepsis develop impaired immunity, which predisposes them to acquiring secondary infections. One of the most common and lethal secondary infections is Pseudomonas aeruginosa pneumonia. Immunoadjuvant therapy is a promising approach to reverse sepsis-induced immunosuppression and improve morbidity and mortality from secondary infections. Interleukin-7 is an immunoadjuvant that improves survival in clinically relevant animal models of polymicrobial peritonitis and in fungal sepsis. This study investigated the effect of recombinant human interleukin-7 (rhIL-7) on survival in a 2-hit model of sublethal cecal ligation and puncture followed by P. aeruginosa pneumonia. Potential immunologic mechanisms responsible for the rhIL-7 putative beneficial effect were also examined, focusing on IL-17, IL-22, IFN-γ, and TNF-α, cytokines that are critical in the control of sepsis and pulmonary Pseudomonas infections. Results showed that rhIL-7 was highly effective in preventing P. aeruginosa-induced death, i.e., 92% survival in rhIL-7-treated mice versus 56% survival in control mice. rhIL-7 increased absolute numbers of immune effector cells in lung and spleen and ameliorated the sepsis-induced loss of lung innate lymphoid cells (ILCs). rhIL-7 also significantly increased IL-17-, IFN-γ-, and TNF-α-producing lung ILCs and CD8 T cells as well as IFN-γ- and TNF-α-producing splenic T cell subsets and ILCs. Furthermore, rhIL-7 enhanced NF-κB and STAT3 signaling in lungs during sepsis and pneumonia. Given the high mortality associated with secondary P. aeruginosa pneumonia, the ability of rhIL-7 to improve immunity and increase survival in multiple animal models of sepsis, and the remarkable safety profile of rhIL-7, clinical trials with rhIL-7 should be considered. © Society for Leukocyte Biology.

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

    Science.gov (United States)

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

    2018-01-01

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

  6. Breast conserving therapy versus mastectomy in T1-2N2 stage breast cancer : a population based study on 10-year overall, relative and distant metastasis-free survival in 3,071 patients

    NARCIS (Netherlands)

    van Maaren, M.C.; de Munck, L.; Jobsen, J.J.; Poortmans, P.; de Bock, G.H.; Siesling, S.; Strobbe, L.J.A.

    2016-01-01

    Background: Recent observational studies showed improved survival after breast conserving therapy (surgery with radiation therapy, BCT) compared to mastectomy (MAST) in T1−2N0−2 stage breast cancer. However, N2 stage is described to affect patients’ prognosis dramatically compared to N0−1 stage, and

  7. Vibroacoustic sound therapy improves pain management and more.

    Science.gov (United States)

    Boyd-Brewer, Chris; McCaffrey, Ruth

    2004-01-01

    Vibroacoustic therapy is a new sound technology that uses audible sound vibrations to reduce symptoms, invoke relaxation, and alleviate stress. This technology is developed based on the recognition that external vibration can influence body function. Research demonstrates the effectiveness of vibroacoustic therapy. Implications for nurses include investigating the possibilities of vibroacoustic therapy in various nursing settings to promote patient well-being and improve the therapeutic environment.

  8. Animal-Assisted Therapy for Improving Human Health

    OpenAIRE

    Sibel Cevizci; Ethem Erginoz; Zuhal Baltas

    2009-01-01

    ABSTRACT Animal Assisted Therapy (AAT) or Pet Therapy is an adjunctive therapy by taking advantage of human and animal interaction, activate the physiological and psychological mechanisms, initiate positive changes improving health in metabolism. In recent years, this interaction are in use to treat psychological and psychiatric disorders such as stress, depression, loneliness, pervasive developmental disorders affect negatively to human health. Furthermore, AAT has been increasingly used to ...

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bayanzay K

    2016-08-01

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

  11. Artificial insemination technology for the emu--improving sperm survival.

    Science.gov (United States)

    Malecki, Irek A; Sood, Sushil; Tawang, Alene; Martin, Graeme B

    2011-12-01

    For the emu, where monogamous mating is normal, artificial insemination (AI) promises much faster genetic improvement and a considerable reduction in production costs by reducing the number of male birds needed for mating. Semen collection is now a routine procedure so the next step is to develop successful protocols for sperm storage. In this paper, we briefly overview our recent progress on the development of protocols for liquid storage and cryopreservation of emu spermatozoa. We have shown that emu semen can be stored at 10 °C for up to 48 h with a minimal loss of viability, and that cryopreservation with dimethylacetamide (DMA) as a cryoprotectant is feasible because we have observed no adverse effects of this cryoprotectant on the emu sperm membrane integrity, morphology and motility. We now need to establish the predictability of the various tests in vivo, but the proportions of live normal and motile sperm with good egg membrane penetration potential suggest that acceptable numbers of competent sperm are preserved and that this will be sufficient for AI.

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2006-12-02

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

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

    Science.gov (United States)

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

    1999-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Leeman Jonathan E

    2012-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Banshi Saboo

    2015-12-01

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

  17. Metabolomics has the potential to improve drug therapy

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  18. The impact of pamidronate and chemotherapy on survival times in dogs with appendicular primary bone tumors treated with palliative radiation therapy.

    Science.gov (United States)

    Oblak, Michelle L; Boston, Sarah E; Higginson, Geraldine; Patten, Steven G; Monteith, Gabrielle J; Woods, J Paul

    2012-04-01

    To assess survival times in dogs that received palliative radiation therapy (RT) alone, and in combination with chemotherapy, pamidronate, or both for primary appendicular bone tumors and determine whether the addition of these adjunctive therapies affects survival. Retrospective case series. Dogs (n = 50) with primary appendicular bone tumors. Dogs were divided into the following treatment groups: RT alone, RT + chemotherapy, RT+ pamidronate, and RT+ chemotherapy + pamidronate. Dogs were considered for analysis if they had a known euthanasia date or follow-up data were available for at least 120 days from the time of diagnosis. Survival time was defined as the time from admission to euthanasia. Cox proportional hazard models and Kaplan-Meier survival functions were used. A P value of less than .05 was considered significant. Fifty dogs were considered for survival analysis. Median survival times (MSTs) were longest for dogs receiving RT and chemotherapy (307 days; 95% CI: 279, 831) and shortest in dogs receiving RT and pamidronate (69 days; 95% CI: 47, 112 days). The difference in MST between dogs who received pamidronate and those who did not in this population was statistically significant in a univariate (P = .039) and multivariate analysis (P = .0015). The addition of chemotherapy into any protocol improved survival (P Chemotherapy should be recommended in addition to a palliative RT protocol to improve survival of dogs with primary appendicular bone tumors. When combined with RT ± chemotherapy, pamidronate decreased MST and should not be included in a standard protocol. © Copyright 2012 by The American College of Veterinary Surgeons.

  19. Metformin and improved treatment outcomes in radiation therapy - A review.

    Science.gov (United States)

    Samsuri, Nur Atiqah Binte; Leech, Michelle; Marignol, Laure

    2017-04-01

    Metformin, a primary treatment for diabetes mellitus (DM) patients, is associated with improved outcomes for diabetic cancer patients fuelling further investigation on its mechanisms of action. The radiosensitising properties of metformin are increasingly reported in pre-clinical studies. This review discusses whether metformin should be offered to radiotherapy (RT) cancer patients as a means to improve their treatment outcomes. A database search was conducted for articles published with metformin as the main intervention between 2010 and 2016. Three groups of RT cancer patients were analysed: diabetic patients using metformin, diabetic patients not using metformin and non-diabetic patients not using metformin. Data on survival and recurrence metrics were extracted. Thirteen studies were included. Conflicting evidence exists with regards to the impact of metformin administration on recurrence and survival outcomes following radiotherapy. Three studies reported improved tumour response determined by recurrence rates while five studies did not observe differences or metformin use was not the associated reason. One study revealed inconsistent tumour response results. Metformin was reported as improving survival outcomes in 2 studies and not improving outcomes in 5 studies. 4 studies showed indefinite results. Although metformin may improve tumour response in the non-randomized, retrospective studies analysed, it may not necessarily confer survival benefits. Future prospective and randomised trials are required to translate the positive impact of metformin documented in pre-clinical and retrospective studies into improve management of RT cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Long-term survival in stage IV melanoma after repetitive surgical therapy.

    Science.gov (United States)

    Tomov, Tsvetomir; Siegel, Robert; Bembenek, Andreas

    2008-05-01

    Surgical therapy in patients with stage IV melanoma is controversial and always an individual decision. We report the case of a young melanoma patient, who underwent resection of 5 distant metastases from 4 different organ systems. Thereby, the patient achieved a stable state of disease and a good quality of life for up to now 67 months without any evidence for further tumor manifestations at present. A systemic chemo- or immunotherapy was never applied. In selected patients with stage IV melanoma, surgery alone can provide long-term survival with good quality of life. (c) 2008 S. Karger AG, Basel

  1. Consideration of treatment fidelity to improve manual therapy research

    National Research Council Canada - National Science Library

    Karas, Steve; Plankis, Laura

    2016-01-01

    The purpose of this paper was to define treatment fidelity, review its use in health care research and suggest how it may be utilized in manual therapy research to improve the reliability and validity of the literature...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-15

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

  3. Are Global and Regional Improvements in Life Expectancy and in Child, Adult and Senior Survival Slowing?

    Science.gov (United States)

    Hum, Ryan J.; Verguet, Stéphane; Cheng, Yu-Ling; McGahan, Anita M.; Jha, Prabhat

    2015-01-01

    Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health–primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest. PMID:25992949

  4. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Science.gov (United States)

    2010-07-01

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

  5. Consideration of treatment fidelity to improve manual therapy research.

    Science.gov (United States)

    Karas, Steve; Plankis, Laura

    2016-09-01

    The purpose of this paper was to define treatment fidelity, review its use in health care research and suggest how it may be utilized in manual therapy research to improve the reliability and validity of the literature. We offer an outline and a table of how manual therapy research may benefit from the concept of treatment fidelity. While treatment fidelity is a newer concept, and has not been integrated into Physical Therapy or Manual Therapy research, when utilized, it can have positive effects on the reliability and validity of the techniques we evaluate.

  6. Clinical Characteristics, Response to Therapy, and Survival of African American Patients Diagnosed With Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Falchi, Lorenzo; Keating, Michael J.; Wang, Xuemei; Coombs, Catherine C.; Lanasa, Mark C.; Strom, Sara; Wierda, William G.; Ferrajoli, Alessandra

    2015-01-01

    Background Little is known regarding racial disparities in characteristics and outcomes among patients with chronic lymphocytic leukemia (CLL). Methods The characteristics and outcomes of untreated African American (AA) patients with CLL (n=84) were analyzed and compared with a reference nonblack (NB) patient population (n=1571). Results At the time of presentation, AA patients had lower median hemoglobin levels (12.9 g/dL vs 13.7 g/dL), higher β2 microglobulin levels (2.7 mg/dL vs 2.4 mg/dL), greater frequency of constitutional symptoms (27% vs 10%), unmutated immunoglobulin heavy-chain variable region (IGHV) mutation status (65% vs 47%), ζ-chain-associated protein kinase 70 (ZAP70) expression (58% vs 32%), and deletion of chromosome 17p or chromosome 11q (28% vs 17%; P ≤ 02 for each comparison). Fifty-one percent of AA patients and 39% of NB patients required first-line therapy and 91% and 88%, respectively, received chemoimmunotherapy. Overall response rates to treatment were 85% for AA patients and 94% for NB patients (P=.06); and the complete response rates were 56% and 58%, respectively (P=.87). The median survival of AA patients was shorter compared with that of NB patients (event-free survival: 36 months vs 61 months; P=.007; overall survival: 152 months vs not reached; P=.0001). AA race was an independent predictor of shorter event-free and overall survival in multivariable regression models. Conclusions The current results indicated that AA patients with CLL have more unfavorable prognostic characteristics and shorter survival compared with their NB counterparts. PMID:24022787

  7. Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis

    NARCIS (Netherlands)

    van Tuyl, Lilian H. D.; Boers, Maarten; Lems, Willem F.; Landewé, Robert B.; Han, Huub; van der Linden, S.; van de Laar, Mart; Westhovens, Rene; van Denderen, J. Christiaan; Westedt, Marie-Louise; Peeters, André J.; Jacobs, Piet; Huizinga, Tom W. J.; van de Brink, Hans; Dijkmans, Ben A. C.; Voskuyl, Alexandre E.

    2010-01-01

    COBRA (for 'COmbinatie therapie Bij Rheumatoide Artritis') combination therapy is effective for the treatment of rheumatoid arthritis (RA), but long-term safety is unknown. This study evaluates survival, comorbidities and joint damage in the original COBRA trial cohort. In the COBRA trial, 155

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-01

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

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

    Science.gov (United States)

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

    2016-09-15

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

  10. A national survey of teachers on antiretroviral therapy in Malawi: access, retention in therapy and survival.

    Directory of Open Access Journals (Sweden)

    Simon D Makombe

    Full Text Available BACKGROUND: HIV/AIDS is having a devastating effect on the education sector in sub-Saharan Africa. A national survey was conducted in all public sector and private sector facilities in Malawi providing antiretroviral therapy (ART to determine the uptake of ART by teachers and their outcomes while on treatment. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was carried out based on patient follow-up records from ART Registers and treatment master cards in all 138 ART clinics in Malawi; observations were censored on September 30(th 2006. By this date, Malawi's 102 public sector and 36 private sector ART clinics had registered a total of 72,328 patients for treatment. Of these, 2,643 (3.7% were teachers. Adjusting for double-registration caused by clinic transfers, it is estimated that 2,380 individual teachers had ever accessed ART. There were 15% of teachers starting ART in WHO clinical stage 1 or 2 with a CD4-lymphocyte count of

  11. Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer.

    Science.gov (United States)

    Melhem-Bertrandt, Amal; Chavez-Macgregor, Mariana; Lei, Xiudong; Brown, Erika N; Lee, Richard T; Meric-Bernstam, Funda; Sood, Anil K; Conzen, Suzanne D; Hortobagyi, Gabriel N; Gonzalez-Angulo, Ana-Maria

    2011-07-01

    To examine the association between beta-blocker (BB) intake, pathologic complete response (pCR) rates, and survival outcomes in patients with breast cancer treated with neoadjuvant chemotherapy. We retrospectively reviewed 1,413 patients with breast cancer who received neoadjuvant chemotherapy between 1995 and 2007. Patients taking BBs at the start of neoadjuvant therapy were compared with patients with no BB intake. Rates of pCR between the groups were compared using a χ² test. Cox proportional hazards models were fitted to determine the association between BB intake, relapse-free survival (RFS), and overall survival (OS). Patients who used BBs (n = 102) were compared with patients (n = 1,311) who did not. Patients receiving BBs tended to be older and obese (P cancer (TNBC; n = 377), BB intake was associated with improved RFS (HR, 0.30; 95% CI, 0.10 to 0.87;P = .027) but not OS (HR, 0.35; 95% CI, 0.12 to 1.00;P = .05). In this study, BB intake was associated with improved RFS in all patients with breast cancer and in patients with TNBC. Additional studies evaluating the potential benefits of beta-adrenergic blockade on breast cancer recurrence with a focus on TNBC are warranted.

  12. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-02-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6-9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  13. Autophagy Contributes to the Death/Survival Balance in Cancer PhotoDynamic Therapy

    Directory of Open Access Journals (Sweden)

    Luciana Dini

    2012-08-01

    Full Text Available Autophagy is an important cellular program with a “double face” role, since it promotes either cell survival or cell death, also in cancer therapies. Its survival role occurs by recycling cell components during starvation or removing stressed organelles; when damage becomes extensive, autophagy provides another programmed cell death pathway, known as Autophagic Cell Death (ACD. The induction of autophagy is a common outcome in PhotoDynamic Therapy (PDT, a two-step process involving the irradiation of photosensitizer (PS-loaded cancer cells. Upon tissue oxygen interaction, PS provokes immediate and direct Reactive Oxygen Species (ROS-induced damage to Endoplasmic Reticulum (ER, mitochondria, plasma membrane, and/or lysosomes. The main biological effects carried out in cancer PDT are direct cytotoxicity to tumor cells, vasculature damage and induction of inflammatory reactions stimulating immunological responses. The question about the role of autophagy in PDT and its putative immunological impact is hotly controversial and largely studied in recent times. This review deals with the induction of autophagy in PDT protocols and its dual role, also considering its interrelationship with apoptosis, the preferential cell death program triggered in the photodynamic process.

  14. Association of aging and survival in a large HIV-infected cohort on antiretroviral therapy.

    Science.gov (United States)

    Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Ford, Nathan; Cooper, Curtis L; Au-Yeung, Christopher; Chan, Keith; Nachega, Jean B; Wood, Evan; Hogg, Robert S; Dybul, Mark; Mills, Edward J

    2011-03-13

    To examine if there is a significant difference in survival between elderly (>50 years) and nonelderly adult patients receiving combination antiretroviral therapy in Uganda between 2004 and 2010. Prospective observational study. Patients 18-49 years of age (nonelderly) and 50 years of age and older enrolled in the AIDS Support Organization Uganda HIV/AIDS national programme were assessed for time to all-cause mortality. We applied a Weibull multivariable regression. Among the 22 087 patients eligible for analyses, 19 657 (89.0%) were aged between 18 and 49 years and 2430 (11.0%) were aged 50 years or older. These populations differed in terms of the distributions of sex, baseline CD4 cell count and death. The age group 40-44 displayed the lowest crude mortality rate [31.4 deaths per 1000 person-years; 95% confidence interval (CI) 28.1, 34.7) and the age group 60-64 displayed the highest crude mortality rate (58.9 deaths per 1000 person-years; 95% CI 42.2, 75.5). Kaplan-Meier survival estimates indicated that nonelderly patients had better survival than elderly patients (P age status was importantly associated (adjusted hazard ratio 1.23, 95% CI 1.08-1.42) with mortality, when controlling for sex, baseline CD4 cell count and year of therapy initiation. As antiretroviral treatment cohorts mature, the proportion of patients who are elderly will inevitably increase. Elderly patients may require focused clinical care that extends beyond HIV treatment.

  15. Improving survival of children with cancer worldwide: the St. Jude International Outreach Program approach.

    Science.gov (United States)

    Ribeiro, Raul C

    2012-01-01

    The mission of the St. Jude International Outreach Program (IOP) is to improve the survival rate of children with cancer and other catastrophic diseases worldwide, through the sharing of knowledge, technology, and organizational skills. There are an estimated 160,000 newly diagnosed cases of childhood cancer worldwide each year, and cancer is emerging as a major cause of childhood death in the developing regions of Asia, South and Central America, northwest Africa, and the Middle East. Over the past 30 years improved therapy has dramatically increased survival rates for children with cancer, but still more than 70% of the world's children with cancer lack access to modern treatment. Although sick children from around the world have traveled to our hospital in Memphis, Tennessee, since its inception, treating children in their own countries is more efficient and less disruptive for them and their families. In the context of St. Jude's culture of sharing knowledge about the management of children with cancer, we now use modern technology to reach far more children than would ever be able to come to St. Jude Children's Research Hospital. St. Jude strives to address the needs of those children in countries that lack sufficient resources and to help them manage their own burden of cases effectively. By sharing knowledge and technology with the local governments, health care providers, and the private sector in these countries, St. Jude is improving diagnoses and treatments to increase the survival rates of children all across the globe. In addition to training medical teams locally, St. Jude Children's Research Hospital hosts many visiting fellows at our campus in Memphis. St. Jude helps partner medical institutions develop tailored evidence-based protocols for treating children with cancer and other catastrophic diseases. St. Jude physicians serve as mentors to physicians at our partner sites and consult on difficult cases. Nurses are trained on best practices in

  16. Intraoperative radiation therapy in combination with conformation radiation therapy for localized unresectable pancreatic carcinoma; An analysis of 13 patients survived for more than one year

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, Atsutake; Tsuruta, Kohji; Tanaka, Yoshiaki (Tokyo Metropolitan Komagome Hospital (Japan)); Onodera, Tokio

    1992-04-01

    The present report is a retrospective analysis of the effect of intraoperative radiation therapy (IORT) for localized but unresectable pancreatic carcinoma. Thirteen of 30 patients treated by IORT in combination with external beam radiation therapy (EBRT) survived for more than one year. The longest survival period, attained by two patients, was 20 months. The 1, and 1.5-year survival rates were 46.5% and 20.8%, respectively, with a median survival of 11 months, whereas the 1-year survival rate was 0%, with a median survival of 6.2 months for the 16 patients treated by IORT alone (N=16). There was a statistically significant difference in survival rate between the two groups (p<0.01). Therefore, additional EBRT may be indispensable for prolongation of the survival period. Moreover, IORT conferred the palliative benefit of relief of pain in more than half of the patients with severe pain. In postmortem examination of seven patients who survived for more than one year, the tumors were replaced by fibrous and hyalinized tissue, as a result of the effect of IORT, and degeneration and necrosis of tumor cells were seen in the center of the tumor, while viable tumor cells remained in the periphery, spreading to the retroperitoneal tissues or neighboring organs. These histopathological findings are distinctive features of carcinoma of the pancreas treated by IORT. (author).

  17. Delayed Posthypoxic Leukoencephalopathy: Improvement with Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Franklin King

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

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

  19. A novel pharmacological strategy by PTEN inhibition for improving metabolic resuscitation and survival after mouse cardiac arrest

    Science.gov (United States)

    Li, Jing; Wang, Huashan; Zhong, Qiang; Zhu, Xiangdong; Chen, Sy-Jou; Qian, Yuanyu; Costakis, Jim; Bunney, Gabrielle; Beiser, David G.; Leff, Alan R.; Lewandowski, E. Douglas; ÓDonnell, J. Michael

    2015-01-01

    Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from 31P NMR), protein phosphorylation of Akt, GSK3β, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change in the left ventricular pressure, and Petco2 and improved 72 h neurological intact survival (50% vs. 10%; P cardiac phospholamban phosphorylation while reducing p-PDH. Moreover, VO improved cardiac bioenergetic recovery. We concluded that pharmacologic PTEN inhibition enhances Akt activation, improving metabolic, cardiovascular, and neurologic recovery with increased survival after SCA. PTEN inhibitors may be a novel pharmacologic strategy for treating SCA. PMID:25795713

  20. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy

    DEFF Research Database (Denmark)

    da Cunha-Bang, C; Simonsen, J; Rostgaard, K

    2016-01-01

    The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer...... diagnosed in 1978-1984 and 2006-2013, respectively. The improved survival corresponded to a decreasing risk of death from malignant hematological diseases, whereas the risk of death from infections was stable during the study period. These population-based data substantiate the improved survival...

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

    Science.gov (United States)

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

    2017-02-01

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

  2. Occurrence of complications and survival rates in elderly with neurological disorders undergoing enteral nutrition therapy.

    Science.gov (United States)

    Martins, Aline Stangherlin; Rezende, Nilton Alves de; Torres, Henrique Oswaldo da Gama

    2012-01-01

    To evaluate the occurrence of complications, as well as the survival rates, in elderly people having neurological diseases and undergoing enteral nutrition therapy (ENT). Patients aged over 60 years, assisted by a home medical service from a healthcare plan in the city of Belo Horizonte, MG, Brazil, were thoroughly evaluated. The mentioned evaluation occurred at their homes after hospital discharge with enteral nutrition (EN) after a three-month period, a six-month period, and at the end of the study. A nutritional assessment was performed along with data collection performed on the patients' electronic medical records, and interviews performed with patients' family members and caregivers. Seventy-nine patients aged 82.9 ± 10.4 years old were evaluated; of these, 49.4% presented dementia, and 50.6% presented other neurological diagnoses. 100% of patients presented a high dependence level, assessed by the Katz index. The majority of patients (91.2%) presented some complications such as: pneumonia, catheter loss, diarrhea, constipation, vomiting, fluid leakage, periostotomy, tube obstruction, reflux, and myiasis. Pneumonia was the most frequent complication, occurring in 55.9% of cases. The mortality rates were 15.2% at a three-month period, 22.8% at a six-month period, and 43% at the end of study. The median survival after starting EN was 364 days. Differences among the mortality rate and neurological diagnosis, EN routes of access, and complications were not observed. The survival rate was lower in patients having inadequate nutritional status and albumin levels nutritional status according to the clinical assessment and albumin levels lower than 3.5 mg/dL significantly influenced the survival rates.

  3. Time to adjuvant chemotherapy following colorectal cancer resection is associated with an improved survival.

    Science.gov (United States)

    Day, A R; Middleton, G; Smith, R V P; Jourdan, I C; Rockall, T A

    2014-05-01

    Multicentre randomized trials have demonstrated equivalent long-term outcomes for open and laparoscopic resection of colon cancer. Some studies have indicated a possible survival advantage in certain patients undergoing laparoscopic resection. Patients who receive adjuvant chemotherapy in improved survival. Data were collated for patients having an elective laparoscopic or open resection for non-metastatic colorectal cancer between October 2003 and December 2010 and subsequently having adjuvant chemotherapy. Survival analysis was conducted. In all, 209 patients received adjuvant chemotherapy following open (n = 76) or laparoscopic (n = 133) surgery. Median length of stay was 3 days with laparoscopic resection and 6 days with open resection (P chemotherapy was 52 with laparoscopic resection and 58 with open resection (P = 0.008). The 5-year overall survival was 89.6% in patients receiving chemotherapy in chemotherapy chemotherapy. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  4. Improving Islet Engraftment by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

  6. No survival benefit with empirical vancomycin therapy for coagulase-negative staphylococcal bloodstream infections in infants.

    Science.gov (United States)

    Ericson, Jessica E; Thaden, Joshua; Cross, Heather R; Clark, Reese H; Fowler, Vance G; Benjamin, Daniel K; Cohen-Wolkowiez, Michael; Hornik, Christoph P; Smith, P Brian

    2015-04-01

    Coagulase-negative Staphylococcus (CoNS) is the most common cause of bloodstream infections (BSI) in hospitalized infants. CoNS BSI is most reliably treated with vancomycin; however, concerns about side effects and promoting resistance often delay empirical vancomycin therapy until culture results become available. All infants with CoNS BSI discharged from 348 neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2012 were identified. Empirical vancomycin therapy was defined as vancomycin exposure on the day of the first positive blood culture. Delayed vancomycin therapy was defined as vancomycin exposure 1-3 days after the first positive blood culture. We used multivariable logistic regression with random effects for site to evaluate the association between the use of empirical vancomycin therapy versus delayed vancomycin therapy and 30-day mortality, controlling for gestational age, small-for-gestational age status, postnatal age on the day of the first positive culture, oxygen requirement, ventilator support and inotropic support on the day the first positive culture was obtained. A total of 4364 infants with CoNS BSI were identified; 2848 (65%) were treated with empirical vancomycin. The median postnatal age at first positive culture was 14 days (interquartile range: 9, 21). Unadjusted 30-day mortality was similar for infants treated with empirical vancomycin and infants treated with delayed vancomycin therapy [166/2848 (6%) vs. 69/1516 (4%); P = 0.08]. There was no significant difference in 30-day mortality on multivariable analysis [odds ratio: 1.14 (0.84, 1.56)]. The median duration of bacteremia was 1 day longer for infants with delayed vancomycin therapy [4 days (interquartile range: 2, 6) vs. 3 days (2, 5); P empirical vancomycin therapy for CoNS BSI was not associated with improved mortality.

  7. Overall Survival and Response to Systemic Therapy in Metastatic Extrauterine Leiomyosarcoma.

    Science.gov (United States)

    Shoushtari, A N; Landa, J; Kuk, D; Sanchez, A; Lala, B; Schmidt, N; Okoli, C; Chi, P; Dickson, M A; Gounder, M M; Keohan, M L; Crago, A M; Tap, W D; D'Angelo, S P

    2016-01-01

    Background. Leiomyosarcomas (LMS) represent a heterogeneous subset of soft tissue sarcomas. Factors influencing prognosis for patients with metastatic extrauterine LMS (euLMS) are not well described. Limited data are available regarding responses to systemic therapy. Methods. We collected clinical and pathologic information for all patients with metastatic euLMS seen at Memorial Sloan Kettering Cancer Center between 1989 and 2012. Objective responses to first-line therapy were analyzed for a subset of patients with available baseline and on-treatment imaging using RECIST 1.1. Results. 215 patients with metastatic euLMS had a median overall survival (OS) of 2.6 years from the time of metastasis. Older age, male sex, and ≥3 initial sites of metastasis were associated with worse OS on multivariate analysis. Objective response rate (ORR) in N = 113 was 19% overall and 25%, 26%, and 25% for gemcitabine, gemcitabine plus docetaxel, and anthracycline-alkylator combinations. Patients whose tumors objectively responded to first-line therapy had a lower risk of death versus those who did not (Hazard Ratio 0.46; 95% CI: 0.26-0.79, p = 0.005). Conclusions. Anthracycline- and gemcitabine-based regimens have similar activity in this cohort of euLMS. Prognostic factors for OS include older age, male sex, and ≥3 initial sites.

  8. Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies.

    Science.gov (United States)

    Choong, Ee Siang; Lo, Serigne; Drummond, Martin; Fogarty, Gerald B; Menzies, Alexander M; Guminski, Alexander; Shivalingam, Brindha; Clarke, Kathryn; Long, Georgina V; Hong, Angela M

    2017-04-01

    With new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy. A total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted. OS was defined as time from SRS to death or last follow-up, and BC was defined as absence of any active intracranial disease during follow-up. Univariate and multivariate Cox proportional hazard analyses were performed on clinico-pathological prognostic features associated with OS and BC. The median age was 64.3 years, and the median follow-up was 8.6 months. Seventy-nine (73.1%) patients received systemic treatment. The median OS were as follows: anti-CTLA4 - 7.5 months (95% CI: 4.4-15.6), anti-PD1 - 20.4 months (95% CI: 8.8 - N/A) and BRAF inhibitor (BRAFi) ± MEK inhibitor (MEKi) - 17.8 months (95% CI: 11.8 - N/A). Median BC was as follows: anti-CTLA4 - 7.5 months (95% CI: 4.0-15.6), anti-PD1 - 12.7 months (95% CI: 5.5 - N/A) and BRAFi ± MEKi - 12.7 months (95% CI: 8.3-18.5). In multivariate analysis, age and type of systemic therapy were strongly associated with OS. Age, Eastern Cooperative Oncology Group performance status, Graded Prognostic Assessment (GPA) score, and presence of symptoms were associated with BC. Favourable outcomes are seen in patients treated with SRS and with the best survival seen in patients treated with anti-PD1. Known independent prognostic factors for survival such as age and performance status and GPA score remain relevant in this setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Spa adjuvant therapy improves diabetic lower extremity arterial disease.

    Science.gov (United States)

    Qiu, Yongbin; Zhu, Yi; Jia, Wei; Chen, Songhua; Meng, Qingzhou

    2014-08-01

    To investigate the effect of spa adjuvant therapy on diabetic lower extremity arterial disease (LEAD). 128 patients with type II diabetes were separated into three groups according to the degree of lower extremity vascular stenosis. Patients within each group were then randomly divided to receive no treatment (control) or spa adjuvant therapy (treatment). Clinical symptoms, blood pressure and hemodynamic analyses were compared between control and treatment groups by Chi square or t-test. After adjuvant therapy with spa, patients' pain, numbness, and cold sensation were significantly improved compared with control groups (PSpa adjuvant therapy also significantly increased the dorsalis pedis pulse and systolic peak velocity ratio of patients with mild lower extremity vascular stenosis compared with control groups (P0.05). Both in the spa and control groups, there were no significant differences before and after medication for fasting, 2-h postprandial blood glucose and glycosylated hemoglobin (HbA1C) analyses (P>0.05). Spa adjuvant therapy can significantly alleviate lower extremity pain, numbness, and cold sensory symptoms in diabetic LEAD patients with stenosis. Moreover, in LEAD patients with mild stenosis, spa adjuvant therapy also improves the dorsalis pedis pulse and systolic peak velocity ratio, suggesting a potential role for spa therapy as an early intervention strategy to treat the initial stages of disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Functionalized Scaffold-mediated Interleukin 10 Gene Delivery Significantly Improves Survival Rates of Stem Cells In Vivo

    Science.gov (United States)

    Holladay, Carolyn; Power, Karen; Sefton, Michael; O'Brien, Timothy; Gallagher, William M.; Pandit, Abhay

    2011-01-01

    While stem cell transplantation could potentially treat a variety of disorders, clinical studies have not yet demonstrated conclusive benefits. This may be partly because transplanted stem cells have low survival rates, potentially due to host inflammation. The system described herein used two different gene therapy techniques to improve retention of rat mesenchymal stem cells. In the first, stem cells were transfected with interleukin-10 (IL-10) before being loaded into a collagen scaffold. In the second, unmodified stem cells were loaded into a collagen scaffold along with polymer-complexed IL-10 plasmids. The scaffolds were surgically implanted into the dorsum of syngeneic rats. At each endpoint, the scaffolds were explanted and cell retention, IL-10 level and inflammatory response were quantified. All treatment groups had statistically significant increases in cell retention after 7 days, but the group treated with 2 µg of IL-10 polyplexes had a significant improvement even at 21 days. This cell retention was associated with increased IL-10 and decreased levels of proinflammatory cytokines and apoptosis. The primary effect on the inflammatory response appeared to be on macrophage differentiation, encouraging the regulatory phenotype over the cytotoxic lineage. Improving cell survival may be an important step toward realization of the therapeutic potential of stem cells. PMID:21266957

  11. Animal-Assisted Therapy for Improving Human Health

    Directory of Open Access Journals (Sweden)

    Sibel Cevizci

    2009-06-01

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

  12. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and...

  13. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    BACKGROUND: An out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis. We hypothesized that the implementations of 2005 European Resuscitation Council resuscitation guidelines were associated with improved 30-day survival after OHCA. METHODS: We prospectively recorded data on all...

  15. Does hydroxyapatite coating of uncemented cups improve long-term survival?

    DEFF Research Database (Denmark)

    Lazarinis, Stergios; Mäkelä, Keijo T; Eskelinen, Antti

    2017-01-01

    OBJECTIVE: It is unclear whether hydroxyapatite (HA) coating of uncemented cups used in primary total hip arthroplasty (THA) improves bone ingrowth and reduces the risk of aseptic loosening. We therefore investigated survival of different uncemented cups that were available with or without HA...

  16. Similar Survival With Breast Conservation Therapy or Mastectomy in the Management of Young Women With Early-Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, Usama, E-mail: usama.mahmood@gmail.com [Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States); Morris, Christopher; Neuner, Geoffrey [Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States); Koshy, Matthew [Department of Cellular and Radiation Oncology, University of Chicago, Chicago, Illinois (United States); Kesmodel, Susan; Buras, Robert [Department of Surgery, University of Maryland, Baltimore, Maryland (United States); Chumsri, Saranya; Bao Ting; Tkaczuk, Katherine [Department of Medicine, University of Maryland, Baltimore, Maryland (United States); Feigenberg, Steven [Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States)

    2012-08-01

    Purpose: To evaluate survival outcomes of young women with early-stage breast cancer treated with breast conservation therapy (BCT) or mastectomy, using a large, population-based database. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients, ages 20 to 39 years old, diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007, who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable and matched pair analyses were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. Results: A total of 14,764 women were identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range, 0.5-17.9 years). After we accounted for all patient and tumor characteristics, multivariable analysis found that BCT resulted in OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.83-1.04; p = 0.16) and CSS (HR, 0.93; CI, 0.83-1.05; p = 0.26) similar to that of mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5-, 10-, and15-year OS rates for BCT and mastectomy were 92.5%, 83.5%, and 77.0% and 91.9%, 83.6%, and 79.1%, respectively (p = 0.99), and the 5-, 10-, and 15-year CSS rates for BCT and mastectomy were 93.3%, 85.5%, and 79.9% and 92.5%, 85.5%, and 81.9%, respectively (p = 0.88). Conclusions: Our analysis of this population-based database suggests that young women with early-stage breast cancer have similar survival rates whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on the assumption of improved survival.

  17. Effects of highly active antiretroviral therapy on the survival of HIV-infected adult patients in urban slums of Kenya.

    Science.gov (United States)

    Muhula, Samuel Opondo; Peter, Memiah; Sibhatu, Biadgilign; Meshack, Ndirangu; Lennie, Kyomuhangi

    2015-01-01

    Recent improvements in access to Anti-Retroviral Therapy (ART) have radically reduced hospitalizations and deaths associated with HIV infection in both developed countries and sub-Saharan Africa. Not much is known about survival of patients on ART in slums. The objective of this study was to identify factors associated with mortality among adult patients on ART in resource poor, urban, sub-Saharan African setting. A prospective open cohort study was conducted with adult patients on ART at a clinic in Kibera slums, Nairobi, Kenya. The patients' enrollment to care was between March 2005 and November 2011. Descriptive statistics were computed and Kaplan-Meier (KM) methods used to estimate survival time while Cox's proportional hazards (CPH) model fitted to determine mortality predictors. A total of 2,011 adult patients were studied, 69% being female. Female gender (p=0.0016), zidovudine-based regimen patients (p351 patients (p<0.0001), WHO stage I patients (p<0.0001) and "Working" functional status patients recorded better survival probability on ART. In CPH analysis, the hazard of dying was higher in patients on Stavudine-based regimen(hazard ratio (HR)=.8; 95% CI, 1.5-2.2; p<0.0001),CD4 count<50 cells/µl (HR=1.6; 95% CI, 1.5-1.7;p<0.0001), WHO Stage IV at ART initiation (HR=1.3; 95% CI, 1.1-1.6; p=0.016) and bedridden patients (HR=2.7; 95% CI, 1.7-4.4;p<0.0001). There was increased mortality among the males, those with advanced Immunosuppression, late WHO stage and bedridden patients. The findings further justify the need to switch patients on Stavudine-based regimen as per the WHO recommendations.

  18. Prior Infection Does Not Improve Survival against the Amphibian Disease Chytridiomycosis

    Science.gov (United States)

    Cashins, Scott D.; Grogan, Laura F.; McFadden, Michael; Hunter, David; Harlow, Peter S.; Berger, Lee; Skerratt, Lee F.

    2013-01-01

    Many amphibians have declined globally due to introduction of the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Hundreds of species, many in well-protected habitats, remain as small populations at risk of extinction. Currently the only proven conservation strategy is to maintain species in captivity to be reintroduced at a later date. However, methods to abate the disease in the wild are urgently needed so that reintroduced and wild animals can survive in the presence of Bd. Vaccination has been widely suggested as a potential strategy to improve survival. We used captive-bred offspring of critically endangered booroolong frogs (Litoria booroolongensis) to test if vaccination in the form of prior infection improves survival following re exposure. We infected frogs with a local Bd isolate, cleared infection after 30 days (d) using itraconazole just prior to the onset of clinical signs, and then re-exposed animals to Bd at 110 d. We found prior exposure had no effect on survival or infection intensities, clearly showing that real infections do not stimulate a protective adaptive immune response in this species. This result supports recent studies suggesting Bd may evade or suppress host immune functions. Our results suggest vaccination is unlikely to be useful in mitigating chytridiomycosis. However, survival of some individuals from all experimental groups indicates existence of protective innate immunity. Understanding and promoting this innate resistance holds potential for enabling species recovery. PMID:23451076

  19. Interact to Survive: Phyllobacterium brassicacearum Improves Arabidopsis Tolerance to Severe Water Deficit and Growth Recovery

    Science.gov (United States)

    Bresson, Justine; Vasseur, François; Dauzat, Myriam; Labadie, Marc; Varoquaux, Fabrice; Touraine, Bruno; Vile, Denis

    2014-01-01

    Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR) are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm), was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture. PMID:25226036

  20. Prior infection does not improve survival against the amphibian disease Chytridiomycosis.

    Directory of Open Access Journals (Sweden)

    Scott D Cashins

    Full Text Available Many amphibians have declined globally due to introduction of the pathogenic fungus Batrachochytrium dendrobatidis (Bd. Hundreds of species, many in well-protected habitats, remain as small populations at risk of extinction. Currently the only proven conservation strategy is to maintain species in captivity to be reintroduced at a later date. However, methods to abate the disease in the wild are urgently needed so that reintroduced and wild animals can survive in the presence of Bd. Vaccination has been widely suggested as a potential strategy to improve survival. We used captive-bred offspring of critically endangered booroolong frogs (Litoria booroolongensis to test if vaccination in the form of prior infection improves survival following re exposure. We infected frogs with a local Bd isolate, cleared infection after 30 days (d using itraconazole just prior to the onset of clinical signs, and then re-exposed animals to Bd at 110 d. We found prior exposure had no effect on survival or infection intensities, clearly showing that real infections do not stimulate a protective adaptive immune response in this species. This result supports recent studies suggesting Bd may evade or suppress host immune functions. Our results suggest vaccination is unlikely to be useful in mitigating chytridiomycosis. However, survival of some individuals from all experimental groups indicates existence of protective innate immunity. Understanding and promoting this innate resistance holds potential for enabling species recovery.

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

    Directory of Open Access Journals (Sweden)

    Justine Bresson

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Background The Danish Colorectal Cancer Group (DCCG) established a national clinical database in 2001 with the aim to monitor and improve outcome of colorectal cancer patients. Since 2000 several national initiatives have been taken to improve cancer outcome. In the present study we used DCCG data...... The Danish efforts to improve outcome of cancer have succeeded with improved outcomes in patients with colorectal cancer....... to evaluate mortality and survival of CRC patients with focus on comorbidity, stage, and perioperative treatment. Material and methods Patients notified to the DCCG database from 2001 to 2012 were included. Patients with primary cancer of the colon and rectum were analyzed separately. Analyses were stratified...

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

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, Christopher, E-mail: cherbert@bccancer.bc.ca [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Liu, Mitchell; Tyldesley, Scott; Morris, W. James [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Joffres, Michel [Department of Health Sciences, Simon Fraser University, Surrey, BC (Canada); Khaira, Mandip; Kwan, Winkle [Department of Radiation Oncology, British Columbia Cancer Agency, Fraser Valley Centre, Surrey, BC (Canada); Moiseenko, Vitali [Department of Medical Physics, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Pickles, Thomas [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada)

    2012-05-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51-176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%-94.1%) and 62.1% (95% CI 52.9%-71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%-100%) and 79.8% (95% CI 68.0%-91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p < 0.001) were statistically significant. Conclusion: Biochemical control translates into improved overall survival in patients with high or intermediate risk disease and an estimated 10-year overall survival of >90%.

  4. Stem Cell Therapy to Improve Burn Wound Healing

    Science.gov (United States)

    2017-03-01

    Award Number: W81XWH-13-2-0024 TITLE: Stem Cell Therapy to Improve Burn Wound Healing PRINCIPAL INVESTIGATOR: Carl Schulman, MD, PhD, MSPH...NUMBER Stem Cell Therapy to Improve Burn Wound Healing 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Carl Schulman, MD, PhD, MSPH...ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Univ ersity of Miam i M Miller School of Medicine Ryder Trauma Center 1800 NW 10th Avenue, Suite 221

  5. Thrombolytic Therapy for Right-Sided Mechanical Pulmonic and Tricuspid Valves: The Largest Survival Analysis to Date.

    Science.gov (United States)

    Taherkhani, Maryam; Hashemi, Seyed Reza; Hekmat, Manouchehr; Safi, Morteza; Taherkhani, Adineh; Movahed, Mohammad Reza

    2015-12-01

    Data regarding thrombolytic treatment of right-sided mechanical valve thrombosis are almost nonexistent, and all current guidelines arise from very small case series. We retrospectively studied the in-hospital and long-term outcome data of a larger series of patients who had received, from September 2005 through June 2012, thrombolytic therapy for right-sided mechanical pulmonary valve or tricuspid valve thrombosis. We identified 16 patients aged 8-67 years who had undergone thrombolytic therapy for definite thrombotic mechanical valve obstruction in the tricuspid or pulmonary valve position (8 in each position). All study patients except one had subtherapeutic international normalized ratios. The 8 patients with pulmonary mechanical valve thrombosis had a 100% response rate to thrombolytic therapy, and their in-hospital survival rate was also 100%. The 8 patients with tricuspid mechanical valve thrombosis had a 75% response rate to thrombolytic therapy, with an in-hospital survival rate of 87.5%. The one-year survival rate for mechanical valve thrombosis treated with thrombolytic therapy (whether pulmonary or tricuspid) was 87.5%. On the basis of our data, we recommend that thrombolytic therapy remain the first-line therapy for right-sided mechanical valve thrombosis in adults or children-including children with complex congenital heart disease and patients with mechanical pulmonary valve thrombosis. Surgery should be reserved for patients in whom this treatment fails.

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

    Directory of Open Access Journals (Sweden)

    Luis B Tovar-y-Romo

    2014-02-01

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

  7. Early palliative radiation therapy in patients with newly diagnosed cancer: Reasons, clinical practice, and survival.

    Science.gov (United States)

    Nieder, Carsten; Haukland, Ellinor; Mannsåker, Bård; Pawinski, Adam; Dalhaug, Astrid

    2015-01-01

    To analyze indications for early palliative radiation therapy (RT) (ie, start within 1 month from cancer diagnosis), regimens used in clinical practice, rate of treatment completion and treatment in the last 30 days of life, and overall survival. Retrospective uni- and multivariate analyses covering a 4.5-year inclusion period. Seventeen percent of all palliative RT courses were administered in the specified time frame (n = 100 patients, 30 Gy in 10 fractions in 49%). Common indications were bone and brain metastases, whereas metastatic spinal cord compression or other emergencies comprised a minority. Only 14% of patients had no distant metastases. Most patients had non-small cell lung cancer (51%), whereas other high-incidence primary tumors such as breast, prostate, and colorectal cancer combined comprised 10%. Failure to complete RT occurred in 6%. Median survival was 3.6 months. A startling high rate of RT in the last 30 days of life was observed (19%). Risk correlated significantly with performance status and extent of metastatic disease. The study population of patients who received early palliative RT is not identical to the general population described in previous studies, which covered the entire disease trajectory. Median survival was relatively short and rate of RT in the last 30 days of life higher than expected. Need for early palliative RT might be caused by large symptom burden and/or contraindication(s) for other management options, and might in many cases also be associated with adverse prognostic features and aggressive disease. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-01

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

  9. Do evolving practices improve survival in operated lung cancer patients? A biobank may answer.

    Science.gov (United States)

    Vlastos, Fotis; Lacomme, Stéphanie; Wild, Pascal; Poulain, Stéphane; Siat, Joëlle; Grosdidier, Gilles; du Manoir, Stanislas; Monga, Ben; Hillas, Georgios; Varsovie, Roselyne; Claudot, Frédérique; Marie, Béatrice; Vignaud, Jean Michel; Szymanski, Nadine

    2009-04-01

    Biobanks may play a pivotal role in lung cancer patients' management, research, and health policy. The Nancy "Centre of Biologic Resources" analyzed the evolving profiles of operated lung cancer patients and their management over 20 years. A total of 1259 consecutive patients operated upon from 1988 till 2007 were included. Survival rates were statistically compared before and after 1997. The parameters associated with a significant improvement of survival were determined. After 1997, lung cancer was diagnosed at an earlier stage. For Squamous Cell Lung Cancer (SQCLC), stages IA increased from 5.4 to 19.5% and for Adenocarcinoma (ADC), stage IA increased from 9.9 to 24.7%. More women with stage I ADC were operated upon after 1997 (p = 0.01). More patients with Large Cell Lung Cancer were diagnosed recently. Recent patients received more adjuvant or neo-adjuvant chemotherapy (p < 0.001) and less radiotherapy (stage I SQCLC: p = 0.019, stage I ADC: p < 0.001). A longer overall patients' survival was observed after 1997 (chi test for SQLC and ADC independently p < or = 0.002). Among SQCLC long survivors, those at stage I-II, below 50 years, were more numerous. A longer survival was associated with early stage in ADC patients. Stage was the single constant factor for overall outcome. Overall and stage-adjusted survival of operated lung cancer patients has been improved in the last decade due mainly to earlier diagnosis. The generalized use of computed tomography scan, chemotherapy, and a collegial management improved patients' survival.

  10. A hemodynamic-directed approach to pediatric cardiopulmonary resuscitation (HD-CPR) improves survival.

    Science.gov (United States)

    Morgan, Ryan W; Kilbaugh, Todd J; Shoap, Wesley; Bratinov, George; Lin, Yuxi; Hsieh, Ting-Chang; Nadkarni, Vinay M; Berg, Robert A; Sutton, Robert M

    2017-02-01

    Most pediatric in-hospital cardiac arrests (IHCAs) occur in ICUs where invasive hemodynamic monitoring is frequently available. Titrating cardiopulmonary resuscitation (CPR) to the hemodynamic response of the individual improves survival in preclinical models of adult cardiac arrest. The objective of this study was to determine if titrating CPR to systolic blood pressure (SBP) and coronary perfusion pressure (CoPP) in a pediatric porcine model of asphyxia-associated ventricular fibrillation (VF) IHCA would improve survival as compared to traditional CPR. After 7min of asphyxia followed by VF, 4-week-old piglets received either hemodynamic-directed CPR (HD-CPR; compression depth titrated to SBP of 90mmHg and vasopressor administration to maintain CoPP ≥20mmHg); or Standard Care (compression depth 1/3 of the anterior-posterior chest diameter and epinephrine every 4min). All animals received CPR for 10min prior to the first defibrillation attempt. CPR was continued for a maximum of 20min. Protocolized intensive care was provided to all surviving animals for 4h. The primary outcome was 4-h survival. Survival rate was greater with HD-CPR (12/12) than Standard Care (6/10; p=0.03). CoPP during HD-CPR was higher compared to Standard Care (point estimate +8.1mmHg, CI95: 0.5-15.8mmHg; p=0.04). Chest compression depth was lower with HD-CPR than Standard Care (point estimate -14.0mm, CI95: -9.6 to -18.4mm; pCPR vs. Standard Care (median 5 vs. 2; pCPR improves short-term survival compared to standard depth-targeted CPR in a porcine model of pediatric asphyxia-associated VF IHCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Radioembolization for Hepatocellular Carcinoma: Statistical Confirmation of Improved Survival in Responders by Landmark Analyses.

    Science.gov (United States)

    Riaz, Ahsun; Gabr, Ahmed; Abouchaleh, Nadine; Ali, Rehan; Alasadi, Ali; Mora, Ronald; Kulik, Laura; Desai, Kush; Thornburg, Bartley; Mouli, Samdeep; Hickey, Ryan; Miller, Frank H; Yaghmai, Vahid; Ganger, Daniel; Lewandowski, Robert J; Salem, Riad

    2017-08-18

    Does imaging response predict survival in hepatocellular carcinoma (HCC)? We studied the ability of post-therapeutic imaging response to predict overall survival. Over 14 years, 948 HCC patients were treated with radioembolization. Patients with baseline metastases, vascular invasion, multifocal disease, Child-Pugh>B7 and transplanted/resected were excluded. This created our homogenous study cohort of 134 Child-Pugh≤B7 patients with solitary HCC. Response (using European Association for Study of the Liver [EASL] and Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1] criteria) was associated with survival using Landmark and risk-of-death methodologies after reviewing 960 scans. In a sub-analysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Uni/multivariate survival analyses were performed at each Landmark. At the 3-month Landmark, responders survived longer than nonresponders by EASL (HR:0.46; CI:0.26-0.82; P=0.002) but not RECIST 1.1 criteria (HR:0.70; CI:0.37-1.32; P=0.32). At the 6-month Landmark, responders survived longer than nonresponders by EASL (HR:0.32; CI:0.15-0.77; P<0.001) and RECIST 1.1 criteria (HR:0.50; CI:0.29-0.87; P=0.021). At the 12-month Landmark, responders survived longer than nonresponders by EASL (HR:0.34; CI:0.15-0.77; P<0.001) and RECIST 1.1 criteria (HR:0.52;CI 0.27-0.98; P=0.049). At 6 months, risk of death was lower for responders by EASL (P<0.001) and RECIST 1.1 (P=0.0445). In sub-analyses, responders lived longer than patients with SD or PD. EASL response was a significant predictor of survival at 3, 6, and 12 month Landmarks on uni/multivariate analyses. Response to radioembolization in patients with solitary HCC can prognosticate improved survival. EASL necrosis criteria outperformed RECIST 1.1 size criteria in predicting survival. The therapeutic objective of radioembolization should be radiologic response and not solely to prevent progression

  12. Heavy Charged Particle Radiobiology: Using Enhanced Biological Effectiveness and Improved Beam Focusing to Advance Cancer Therapy

    Science.gov (United States)

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

    2011-01-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. PMID:21376738

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

    Science.gov (United States)

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

    2011-06-03

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

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

    DEFF Research Database (Denmark)

    Hailer, Nils P; Lazarinis, Stergios; Mäkelä, Keijo T

    2015-01-01

    Background and purpose - It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients...... to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed...

  15. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    Directory of Open Access Journals (Sweden)

    Liangpeng Li

    2016-01-01

    Full Text Available Mesenchymal stem cell (MSC is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

  16. Reporting quality of survival analyses in medical journals still needs improvement. A minimal requirements proposal.

    Science.gov (United States)

    Abraira, Víctor; Muriel, Alfonso; Emparanza, José I; Pijoan, José I; Royuela, Ana; Plana, María Nieves; Cano, Alejandra; Urreta, Iratxe; Zamora, Javier

    2013-12-01

    We reviewed publications with two main objectives: to describe how survival analyses are reported across medical journal specialties and to evaluate changes in reporting across periods and journal specialties. Systematic review of clinical research articles published in 1991 and 2007, in 13 high-impact medical journals. The number of articles performing survival analysis published in 1991 (104) and 2007 (240) doubled (17% vs. 33.5%; P = 0.000), although not uniformly across specialties. The percentage of studies using regression models and the number of patients included also increased. The presentation of results improved, although only the reporting of precision of effect estimates reached satisfactory levels (53.1% in 1991 vs. 94.2% in 2007; P = 0.000). Quality of reporting also varied across specialties; for example, cardiology articles were less likely than oncology ones to discuss sample size estimation (odds ratio = 0.12; 95% confidence interval: 0.05, 0.30). We also detected an interaction effect between period and specialty regarding the likelihood of reporting precision of curves and precision of effect estimates. The application of survival analysis to medical research data is increasing, whereas improvement in reporting quality is slow. We propose a list of minimum requirements for improved application and description of survival analysis. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Can MRI-derived factors predict the survival in glioblastoma patients treated with postoperative chemoradiation therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Hideo Nakamura, Hideo [Dept. of Neurosurgery, Faculty of Life Sciences, Kumamoto Univ., Kumamoto, (Japan); Murakami, Ryuji [Dept. of Medical Imaging, Faculty of Life Sciences, Kumamoto Univ., Kumamoto (Japan)], e-mail: murakami@kumamoto-u.ac.jp; Hirai, Toshinori; Kitajima, Mika; Yamashita, Yasuyuki [Dept. of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto Univ., Kumamoto (Japan)

    2013-03-15

    Background: Advanced diagnostic and therapeutic developments may yield novel prognostic factors in patients with glioblastoma multiforme (GBM). Purpose: To validate the predictive values of pretreatment quantitative diffusion-weighted (DW) magnetic resonance imaging (MRI) and MRI performed within 72 h after surgery in patients with GBM. Material and Methods: Between January 2000 and September 2009, 138 patients with GBM underwent postoperative chemoradiation therapy (chemo-RT) and longitudinal MRI before surgery, in the early postoperative period, and at 1-month intervals thereafter. The role of the patient age, Karnofsky performance scale (KPS) score, minimum apparent diffusion coefficient (ADC) on pretreatment DW-MRI, and gross residual tumor on early postoperative MRI were assessed by factor analysis of overall survival (OS). Survival curves were calculated using the Kaplan-Meier method; the multivariate Cox's proportional hazards model was used to adjust for the influence of prognostic factors. Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) criteria were used to validate the predictive value of the MRI-derived factors. Results: Substantial independent prognostic factors were the KPS score (hazard ratio [HR], 1.812), minimum ADC (HR, 2.365), and gross residual tumor (HR, 1.777). Based on MRI-derived factors, we assigned the patients to different prognostic groups in the RTOG-RPA classification and grouped them according to the level of risk, i.e. a high-risk group with low minimum ADCs (<0.93 X 10{sup -3} mm{sup 2}/s) with gross residual tumor and a low-risk group with high minimum ADCs ({>=}0.93 X 10{sup -}3 mm{sup 2}/s) without gross residual tumor; the other patients were assigned to the intermediate-risk group. Median OS for the low-, intermediate-, and high-risk groups were 28.2, 14.7, and 10.8 months, respectively (P < 0.001). Conclusion: The minimum ADC on pretreatment DW-MRI and gross residual tumor on early

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

    Directory of Open Access Journals (Sweden)

    Lisa Y. Pang

    2016-01-01

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

  19. Intermittent hypoxia selects for genotypes and phenotypes that increase survival, invasion, and therapy resistance.

    Directory of Open Access Journals (Sweden)

    Daniel Verduzco

    Full Text Available Hypoxia in tumors correlates with greater risk of metastases, increased invasiveness, and resistance to systemic and radiation therapy. The evolutionary dynamics that links specific adaptations to hypoxia with these observed tumor properties have not been well investigated. While some tumor populations may experience fixed hypoxia, cyclical and stochastic transitions from normoxia to hypoxia are commonly observed in vivo. Although some phenotypic adaptations to this cyclic hypoxia are likely reversible, we hypothesize that some adaptations may become fixed through mutations promoted by hypoxia-induced genomic instability. Here we seek to identify genetic alterations and corresponding stable phenotypes that emerge following cyclic hypoxia. Although these changes may originate as adaptations to this specific environmental stress, their fixation in the tumor genome may result in their observation in tumors from regions of normoxia, a condition known as pseudohypoxia. We exposed several epithelial cell lines to 50 cycles of hypoxia-normoxia, followed by culture in normoxia over a period of several months. Molecular analyses demonstrated permanent changes in expression of several oncogenes and tumor-suppressors, including p53, E-cadherin, and Hif-1α. These changes were associated with increased resistance to multiple cytotoxins, increased survival in hypoxia and increased anchorage-independent growth. These results suggest cycles of hypoxia encountered in early cancers can select for specific and stable genotypic and phenotypic properties that persist even in normoxic conditions, which may promote tumor progression and resistance to therapy.

  20. Increased Lymph Node Yield Is Associated with Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment

    DEFF Research Database (Denmark)

    Lykke, Jakob; Jess, Per; Roikjaer, Ole

    2015-01-01

    BACKGROUND: It has been proposed that the lymph node yield achieved during rectal cancer resection is associated with survival. It is debated whether a high lymph node yield improves survival, per se, or whether it does so by diminishing the International Union Against Cancer stage drifting effect....... OBJECTIVE: The purpose of this study was to evaluate the prognostic implications of the lymph node yield in curative resected rectal cancer. DESIGN: This study was based on data from a prospectively maintained colorectal cancer database. SETTINGS: This was a national cohort study. PATIENTS: All 6793...... patients in Denmark who were diagnosed with International Union Against Cancer stage I to III adenocarcinoma of the rectum and so treated in the period from 2003 to 2011 were included in the analysis. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: The observed percentages...

  1. Does a third arterial conduit to the right coronary circulation improve survival?

    Science.gov (United States)

    Luthra, Suvitesh; Leiva-Juárez, Miguel M; Matuszewski, Maciej; Morgan, Ian S; Billing, John S

    2018-03-01

    The long-term benefits of a third arterial conduit to the right circulation in triple-vessel disease remain debatable. This retrospective, single-center, propensity-matched study investigates the impact of a third arterial conduit to the right circulation on early and intermediate survival after coronary artery bypass grafting. Data were retrospectively collected from 2004 to 2014 for all surgical revascularizations for triple-vessel disease with at least 2 arterial conduits to the left circulation and a third arterial or venous conduit to the right circulation. A total of 167 pairs were propensity matched to arterial versus venous third conduit to right circulation. Hazard functions were obtained with Cox multivariate regression and Kaplan-Meier survival curves were compared between the matched cohorts. Extracardiac arteriopathy, logistic euroSCORE, and left main stem disease were significant predictors of adverse survival. A third arterial conduit to the right circulation was not a significant predictor of improved survival in multivariate analysis (HR, 0.72; 95% CI, 0.34-1.55; P = .411). 30-day mortality was 0.6% in both groups. There was no significant difference in early or intermediate survival in the propensity-matched groups (venous vs arterial, 99.2% vs 99.2%; P = 1.000 at 1 year; 85.2% vs 88.8%; P = .248 at 5 years and 69.2% vs 88.8%; P = .297 at 7 years) CONCLUSIONS: The use of a third arterial versus a venous conduit to the right circulation does not improve early or intermediate survival up to 7 years in triple-vessel coronary artery disease in this study. Longer follow-up and larger cohorts may be needed for differences to emerge. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Steve R. Martinez

    2013-02-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

  4. Improving proton therapy by metal-containing nanoparticles : Nanoscale insights

    NARCIS (Netherlands)

    Schlathölter, Thomas; Eustache, Pierre; Porcel, Erika; Salado, Daniela; Stefancikova, Lenka; Tillement, Olivier; Lux, Francois; Mowat, Pierre; Biegun, Aleksandra; van Goethem, Marc-Jan; Remita, Hynd; Lacombe, Sandrine

    2016-01-01

    The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to

  5. Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved Chemotherapy

    National Research Council Canada - National Science Library

    Scott Kopetz; George J. Chang; Michael J. Overman; Cathy Eng; Daniel J. Sargent; David W. Larson; Axel Grothey; Jean-Nicolas Vauthey; David M. Nagorney; Robert R. McWilliams

    2009-01-01

    .... With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population...

  6. A Systematic Case Study of the Course, Offshore Survival Systems Training, To Improve the Practice of Marine Survival Training.

    Science.gov (United States)

    Zambon, Franco

    A major applied research project evaluated the effectiveness of a novel course, Offshore Survival Systems Training. The major course outcome that was evaluated was the increase in frequency with which offshore personnel correctly launched the covered powered survival craft on offshore drilling rigs. The evaluation methodology included the 628…

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of “poultry interest groups” in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due...... that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry...

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

    DEFF Research Database (Denmark)

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

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of “poultry interest groups” in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due...... that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Pierre-François Lesault

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

  11. Localized microbubble cavitation-based antivascular therapy for improving HCC treatment response to radiotherapy.

    Science.gov (United States)

    Daecher, Annemarie; Stanczak, Maria; Liu, Ji-Bin; Zhang, Jie; Du, Shisuo; Forsberg, Flemming; Leeper, Dennis B; Eisenbrey, John R

    2017-09-29

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and the fastest growing malignancy in the United States. With a 5-year survival rate below 12%, effective therapies for HCC are needed. Current treatments for HCC include microwave and radiofrequency ablation, high intensity focused ultrasound, liver transplant, surgical resection, and localized embolizations. However, each of these approaches has some limitation, making it imperative to develop improved methods for sensitizing tumors prior to therapy. We hypothesized that the use of ultrasound-triggered microbubble destruction (UTMD), which sensitizes tumors to radiotherapy by inducing vascular endothelial cell apoptosis, will selectively sensitize malignant tissue to radiotherapy and improve outcomes. To test this, 18 nude rats were inoculated in the right liver lobe with Hu7.5 HCC cells and after tumor formation, received 5 Gy radiotherapy, UTMD, or UTMD prior to radiotherapy. Compared to radiotherapy alone, there was a 170% reduction in tumor growth 7 days post treatment and a 3.2X improvement in median survival time when radiotherapy was combined with UTMD. These results indicate that UTMD is an effective adjunct when combined with radiotherapy to treat HCC. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Porphyrin modified trastuzumab improves efficacy of HER2 targeted photodynamic therapy of gastric cancer.

    Science.gov (United States)

    Korsak, Barbara; Almeida, Gabriela M; Rocha, Sara; Pereira, Carla; Mendes, Nuno; Osório, Hugo; Pereira, Patrícia M R; Rodrigues, João M M; Schneider, Rudolf J; Sarmento, Bruno; Tomé, João P C; Oliveira, Carla

    2017-10-01

    Gastric cancer (GC) is the 3rd deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in ∼20% of GC cases and anti-HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2-positive metastatic GC. This strategy improves GC patients' survival by 2-3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2-positive GC. Using mass spectrometry analysis, the lysine residues in the trastuzumab structure most prone for porphyrin conjugation were mapped. The in vitro data demonstrates that Trast:Porph specifically binds to HER2-positive cells, accumulates intracellularly, co-localizes with lysosomal marker LAMP1, and induces massive HER2-positive cell death upon cellular irradiation. The high selectivity and cytotoxicity of Trast:Porph based photoimmunotherapy is confirmed in vivo in comparison with trastuzumab alone, using nude mice xenografted with a HER2-positive GC cell line. In the setting of human disease, these data suggest that repetitive cycles of Trast:Porph photoimmunotherapy may be used as an improved treatment strategy in HER2-positive GC patients. © 2017 UICC.

  13. The effects of maitland orthopedic manual therapy on improving constipation.

    Science.gov (United States)

    Koo, Ja-Pung; Choi, Jung-Hyun; Kim, Nyeon-Jun

    2016-10-01

    [Purpose] This study aimed to examine the effects of interventions on constipation and to provide basic data for physical therapy in internal medicine. [Subjects and Methods] The colon transit times of 30 subjects were measured and after the interventions. Fifteen subjects were assigned to a Maitland orthopedic manual therapy group, and 15 subjects were assigned to a dietary fiber group. [Results] The analysis of changes in colon transit time showed statistically significant differences in left colon transit time, rectosigmoid colon transit time, and total colon transit time for the Maitland orthopedic manual therapy group and statistically significant differences in rectosigmoid colon transit time and total colon transit time for the dietary fiber group. An analysis of group differences in the effects of Maitland orthopedic manual therapy and dietary fiber showed that the Maitland orthopedic manual therapy group achieved statistically significantly larger declines in rectosigmoid colon transit time and total colon transit time compared with the dietary fiber group. [Conclusion] This study confirmed that Maitland orthopedic manual therapy can be an effective treatment method for internal conditions such as functional constipation by almost normalizing the colon transit time, not only by improving the symptoms of constipation but also by facilitating intestinal movements.

  14. Five-year survival rates of melanoma patients treated by diet therapy after the manner of Gerson: a retrospective review.

    Science.gov (United States)

    Hildenbrand, G L; Hildenbrand, L C; Bradford, K; Cavin, S W

    1995-09-01

    Compare 5-year melanoma survival rates to rates in medical literature. Retrospective. Hospital in Tijuana, Mexico. White adult patients (N = 153) with superficial spreading and nodular melanoma, aged 25-72 years. Gerson's diet therapy: lactovegetarian; low sodium, fat and (temporarily) protein; high potassium, fluid, and nutrients (hourly raw vegetable/fruit juices). Metabolism increased by thyroid; calorie supply limited to 2600-3200 calories per day. Coffee enemas as needed for pain and appetite. 5-year survival rates by stage at admission. Of 14 patients with stages I and II (localized) melanoma, 100% survived for 5 years, compared with 79% of 15,798 reported by Balch. Of 17 with stage IIIA (regionally metastasized) melanoma, 82% were alive at 5 years, in contrast to 39% of 103 from Fachklinik Hornheide. Of 33 with combined stages IIIA + IIIB (regionally metastasized) melanoma, 70% lived 5 years, compared with 41% of 134 from Fachklinik Hornheide. We propose a new stage division: IVA (distant lymph, skin, and subcutaneous tissue metastases), and IVB (visceral metastases). Of 18 with stage IVA melanoma, 39% were alive at 5 years, compared with only 6% of 194 from the Eastern Cooperative Oncology Group. Survival impact was not assessed for stage IVB. Male and female survival rates were identical for stages I-IIIB, but stage IVA women had a strong survival advantage. The 5-year survival rates reported here are considerably higher than those reported elsewhere. Stage IIIA/B males had exceptionally high survival rates compared with those reported by other centers.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro...

  17. The effect of timing of the first kidney transplantation on survival in children initiating renal replacement therapy

    DEFF Research Database (Denmark)

    Kramer, Anneke; Stel, Vianda S; Geskus, Ronald B

    2012-01-01

    Controversy exists concerning the timing of the first kidney transplantation for children who need to start renal replacement therapy (RRT). Our aim was to estimate the effect of timing of the first transplantation on patient survival in children, for the first time also taking into account...

  18. Improving survival and preventing recurrence of diffuse large B-cell lymphoma in younger patients: current strategies and future directions

    Directory of Open Access Journals (Sweden)

    Karlin L

    2013-03-01

    Full Text Available Lionel Karlin, Bertrand CoiffierHematology Department, Centre Hospitalier Lyon Sud, Pierre-Benite, FranceAbstract: Prognosis of diffuse large B-cell lymphoma (DLBCL has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience primary refractory disease or short-term relapses, conferring poor survival. Thus, achieving first-line complete remission is of major importance, especially in young and fit patients. Current strategies are based on the age-adapted International Prognostic Index, which separates patients into three prognostic subgroups (low-risk, intermediate-risk, and high-risk. However, it is based only on clinical variables, and we have learned from daily practice that there remains a marked heterogeneity within each subgroup. Recently, biological prognostic factors have emerged, and should now be part of initial evaluation to guide treatment. Among those, so-called double-hit DLBCL with deregulation of both MYC and BCL2 genes usually follows a particularly aggressive course and should be treated more intensively. But for many other patients, the indication of high-dose therapy rather than immunochemotherapy alone remains controversial. In these cases, the interest of an early 18F fluoro-2-deoxy-d-glucose positron emission tomography evaluation-based strategy is now being assessed in ongoing clinical trials. Moreover, other strategies to improve response and survival consist in adding novel agents to standard chemotherapy. In this field, newly developed anti-CD20 monoclonal antibodies and immunomodulatory drugs could be of particular interest during induction therapy to optimize the quality of response, but also in maintenance treatment, in order to decrease the risk of relapse. Only well-conducted clinical trials will be able to resolve all these issues. Therefore, physicians should be encouraged, as far as possible, to propose

  19. A prognostic model of therapy-related myelodysplastic syndrome for predicting survival and transformation to acute myeloid leukemia.

    Science.gov (United States)

    Quintás-Cardama, Alfonso; Daver, Naval; Kim, Hawk; Dinardo, Courtney; Jabbour, Elias; Kadia, Tapan; Borthakur, Gautam; Pierce, Sherry; Shan, Jianqin; Cardenas-Turanzas, Marylou; Cortes, Jorge; Ravandi, Farhad; Wierda, William; Estrov, Zeev; Faderl, Stefan; Wei, Yue; Kantarjian, Hagop; Garcia-Manero, Guillermo

    2014-10-01

    We evaluated the characteristics of a cohort of patients with myelodysplastic syndrome (MDS) related to therapy (t-MDS) to create a prognostic model. We identified 281 patients with MDS who had received previous chemotherapy and/or radiotherapy for previous malignancy. Potential prognostic factors were determined using univariate and multivariate analyses. Multivariate Cox regression analysis identified 7 factors that independently predicted short survival in t-MDS: age ≥ 65 years (hazard ratio [HR], 1.63), Eastern Cooperative Oncology Group performance status 2-4 (HR, 1.86), poor cytogenetics (-7 and/or complex; HR, 2.47), World Health Organization MDS subtype (RARs or RAEB-1/2; HR, 1.92), hemoglobin (HR, 2.24), platelets (HR, 2.01), and transfusion dependency (HR, 1.59). These risk factors were used to create a prognostic model that segregated patients into 3 groups with distinct median overall survival: good (0-2 risk factors; 34 months), intermediate (3-4 risk factors; 12 months), and poor (5-7 risk factors; 5 months) (P < .001) and 1-year leukemia-free survival (96%, 84%, and 72%, respectively, P = .003). This model also identified distinct survival groups according to t-MDS therapy. In summary, we devised a prognostic model specifically for patients with t-MDS that predicted overall survival and leukemia-free survival. This model might facilitate the development of risk-adapted therapeutic strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2013-07-07

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jill P Smith

    2010-03-01

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

  3. Nutrition and Hydration Status of Aircrew Members Consuming The Food Packet, Survival, General Purpose, Improved During A Simulated Survival Scenario

    Science.gov (United States)

    1992-11-01

    over hilly terrain without packs to identify edible plants, shelter sites, water sources, and other materials to be used for survival purposes. The...snake, squirrel, trout, frog , venison, snail and numerous plant foods. In order to give the survival school students the same amount of kilocalories...dishes, Chinese or other ethnic foods, other fruits or vegetables, as well as nutritional supplements (bran, etc.). Please take a look at the list of

  4. Modulating Wnt signaling to improve cell replacement therapy for Parkinson's disease.

    Science.gov (United States)

    Parish, Clare L; Thompson, Lachlan H

    2014-02-01

    Clinical trials have demonstrated the capacity for dopamine neurons, transplanted ectopically into the striatum, to structurally integrate, restore dopamine transmission, and induce long-term functional benefits for Parkinson's disease (PD) patients. Despite this proof of principle, a number of limitations have hindered the development of cell replacement therapy over the past 20 years, particularly tissue availability, graft survival, and adequate reinnervation of the host brain. With a greater understanding of failure in prior clinical trials, increased knowledge of midbrain dopamine development (now including Wnts), and the development of pluripotent stem cell technologies, we are better equipped than ever to re-address a number of these challenges. This review summarizes the trials, tribulations, and progress in cell replacement therapy for PD. We discuss the prospects of modulating canonical and non-canonical Wnt signaling to improve cell therapy based upon their roles in dopamine neural development and the adult brain. This will include the potential of Wnts to (i) expand fetally derived tissue in vitro and following transplantation, (ii) promote the differentiation of pluripotent stem cells, (iii) increase graft integration and restoration of neural circuitry, and finally (iv) enhance graft survival.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Chien-Chih [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Liu, Ren-Shyan [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, National PET/Cyclotron Center, Taipei (China); National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China); Yang, An-Hang [Taipei Veterans General Hospital, Department of Pathology and Laboratory Medicine, Taipei (China); National Yang-Ming University, Department of Pathology, School of Medicine, Taipei (China); Liu, Ching-Sheng [National Yang-Ming University Medical School, Department of Nuclear Medicine, School of Medicine, Taipei (China); Chi, Chin-Wen [National Yang-Ming University, Institute of Pharmacology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China); Tseng, Ling-Ming [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Tsai, Yi-Fan [Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Ho, Jennifer H. [Taipei Medical University, Graduate Institute of Clinical Medicine, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Department of Ophthalmology, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Center for Stem Cell Research, Taipei (China); Lee, Chen-Hsen [NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Lee, Oscar K. [Taipei Veterans General Hospital, Department of Orthopedics, Taipei (China); National Yang-Ming University, Stem Cell Research Center, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China)

    2013-01-15

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

  6. Challenges and Strategies for Improving the Regenerative Effects of Mesenchymal Stromal Cell-Based Therapies

    Directory of Open Access Journals (Sweden)

    Silvia Baldari

    2017-10-01

    Full Text Available Cell-based therapies have the potential to revolutionize current treatments for diseases with high prevalence and related economic and social burden. Unfortunately, clinical trials have made only modest improvements in restoring normal function to degenerating tissues. This limitation is due, at least in part, to the death of transplanted cells within a few hours after transplant due to a combination of mechanical, cellular, and host factors. In particular, mechanical stress during implantation, extracellular matrix loss upon delivery, nutrient and oxygen deprivation at the recipient site, and host inflammatory response are detrimental factors limiting long-term transplanted cell survival. The beneficial effect of cell therapy for regenerative medicine ultimately depends on the number of administered cells reaching the target tissue, their viability, and their promotion of tissue regeneration. Therefore, strategies aiming at improving viable cell engraftment are crucial for regenerative medicine. Here we review the major factors that hamper successful cell engraftment and the strategies that have been studied to enhance the beneficial effects of cell therapy. Moreover, we provide a perspective on whether mesenchymal stromal cell-derived extracellular vesicle delivery, as a cell-free regenerative approach, may circumvent current cell therapy limitations.

  7. Improving Therapy of Chronic Lymphocytic Leukemia (CLL) with Chimeric Antigen Receptor (CAR) T Cells

    Science.gov (United States)

    Fraietta, Joseph A.; Schwab, Robert D.; Maus, Marcela V.

    2016-01-01

    Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically-engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and re-directing the immune system against cancer. This review will briefly summarize T cell therapies in development for CLL disease. We discuss the role of T cell function and phenotype, T cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. PMID:27040708

  8. Enhancement of survival of 9L gliosarcoma bearing rats following intracerebral delivery of drugs in combination with microbeam radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Regnard, Pierrick [Biomedical Facility, 6, Rue Jules Horowitz, ESRF, BP220, F 38043 Grenoble (France); Braeuer-Krisch, Elke [Biomedical Beamline, ESRF, BP220, F 38043 Grenoble (France); Tropres, Irene [IFR1, Universite Joseph Fourier, 3T MRI unit, CHU A Michallon, BP217, F 38043 Grenoble (France); Keyrilaeinen, Jani; Bravin, Alberto [Biomedical Beamline, ESRF, BP220, F 38043 Grenoble (France); Le Duc, Geraldine [Biomedical Facility, 6, Rue Jules Horowitz, ESRF, BP220, F 38043 Grenoble (France)], E-mail: leduc@esrf.fr

    2008-12-15

    Microbeam radiation therapy (MRT) is a form of radiosurgery first dedicated to the treatment of brain tumors. It uses arrays of synchrotron generated X-rays microbeams of very high doses (typically 625 Gy). Microbeams are typically few micrometers large (25 {mu}m) and few hundred micrometers spaced (200 {mu}m). Previous experiments have shown that despite a good tumor eradication rate (5/11), a 100-{mu}m spacing unidirectional irradiation (skin dose 625 Gy, width 25 {mu}m) was too invasive for normal tissue. On the contrary, a 200-{mu}m spacing unidirectional irradiation preserved healthy tissue with a low tumor eradication rate (2/32). The purpose of this study was to enhance the potential of the 200 {mu}m spacing irradiation protocol. After diagnosis of the tumor by MRI, 9L tumor-bearing rats were laterally irradiated with 51 microbeams (625 Gy, 25 {mu}m, 200 {mu}m) 14 days after implantation. Three drugs (Gd-DTPA, CisPt, temozolomide) were tested, after intratumoral injection at the theoretical center of the tumor. Control rats displayed a median survival time of 19 days. There was no significant difference between drug-treated rats and control group. Irradiated animals showed an increase in life span (ILS) of 60.5%. Interestingly, the ILS increased to 131.6% and 1/6 rat survived more than 1 year in case of MRT combined with gadolinium injection. These results showed that the synergy between gadolinium injection (acting as a dose enhancer) and MRT improved significantly the life span of tumor bearing rats (more than a factor 2)

  9. Serum Derived Transfer Factor Stimulates the Innate Immune System to Improve Survival Traits in High Risk Pathogen Scenarios.

    Science.gov (United States)

    Willeford, Bridget V; Shapiro-Dunlap, Trudy; Willeford, Kenneth O

    2017-08-01

    Preclinical Research Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal to survive high-risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host's cytokine response profile. Mice mortally challenged with 5,000 colony-forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0.01). The splenic bacterial load in untreated mice was over 10,000 times higher than that in the TF treated mice. Twenty-four hours post-administration, the treated murine population expressed a rapid temporal increase in serum IL-6 (26-fold) and INF-γ (77-fold) concentrations. IL-6 can act as a critical signal regulating action against bacterial pathogens. A comparative double-blind study performed using dogs confirmed to be undergoing a canine parvovirus challenge showed that when conventional supportive therapy was supplemented with a single 5 mg TF dose there was a reduction (p ≤ 0.01) in group mortality (68% of the TF treated group survived versus 32% of the placebo group), an observation consistent with the observed increase in INF-γ, a cytokine associated with promoting antiviral activity. Drug Dev Res 78 : 189-195, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

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

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

    DEFF Research Database (Denmark)

    Obel, Niels

    2017-01-01

    survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013. METHODS: We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between...... 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after...... ART initiation in four calendar periods (1996-99, 2000-03 [comparator], 2004-07, 2008-10). We estimated life expectancy by calendar period of initiation of ART. FINDINGS: 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second...

  12. A specialized home care intervention improves survival among older post-surgical cancer patients.

    Science.gov (United States)

    McCorkle, R; Strumpf, N E; Nuamah, I F; Adler, D C; Cooley, M E; Jepson, C; Lusk, E J; Torosian, M

    2000-12-01

    intervention group, compared with 52 (28%) in the usual care group. Stage of disease at diagnosis differed between the two groups at baseline (38% late stage patients in the intervention group compared with 26% in the control group, P = .01), so stratified analysis was performed. Overall, the specialized home care intervention group was found to have increased survival (P = .002 using stratified log-rank test). Among early stage patients only, there was no difference in survival between the intervention and control groups. Among late stage patients, there was improved survival in the intervention group. For example, 2-year survival among late stage intervention group cases was 67% compared with 40% among control cases. When Cox's proportional hazard model was used to adjust for significant baseline covariates, the relative hazard of death in the usual care group was 2.04 (CI: 1.33 to 3.12; P = .001) after adjusting for stage of disease and surgical hospitalization length of stay. This is the first empirical study of post-surgical cancer patients to link a specialized home care intervention by advanced practice nurses with improved survival. Additional research is needed to test home care interventions aimed at maintaining quality of life outcomes and their effects on survival of post-surgical cancer patients.

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

    Science.gov (United States)

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

    2017-11-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Erik W. Larson

    2013-01-01

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

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

    DEFF Research Database (Denmark)

    Hailer, Nils P; Lazarinis, Stergios; Mäkelä, Keijo T

    2015-01-01

    Background and purpose - It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients...... and methods - We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due...... to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed...

  19. Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease.

    Science.gov (United States)

    Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne

    2013-10-01

    There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate therapy failed to show a survival advantage over conservative management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.

  20. Dose-painted intensity modulated radiation therapy improves local control for locally advanced pancreas cancer.

    Science.gov (United States)

    Tunceroglu, Ahmet; Park, Joo Han; Balasubramanian, Sairam; Poppe, Matthew; Anker, Christopher J; Poplin, Elizabeth; Moss, Rebecca A; Yue, Ning J; Carpizo, Darren; Gannon, Christopher J; Haffty, Bruce G; Jabbour, Salma K

    2012-01-01

    Background. To evaluate the outcomes, adverse events, and therapeutic role of Dose-Painted Intensity-Modulated Radiation Therapy (DP-IMRT) for locally advanced pancreas cancer (LAPC). Methods. Patients with LAPC were treated with induction chemotherapy (n = 25) and those without metastasis (n = 20) received DP-IMRT consisting of 45 Gy to Planning Treatment Volume 1 (PTV1) including regional lymph nodes with a concomitant boost to the PTV2 (gross tumor volume + 0.5 cm) to either 50.4 Gy (n = 9) or 54 Gy (n = 11) in 25 fractions. DP-IMRT cases were compared to three-dimensional conformal radiation therapy (3D-CRT) plans to assess the potential relationship of radiation dose to adverse events. Kaplan-Meier and Cox regression analyses were used to calculate survival probabilities. The Fisher exact test and t-test were utilized to investigate potential prognostic factors of toxicity and survival. Results. Median overall and progression-free survivals were 11.6 and 5.9 months, respectively. Local control was 90%. Post-RT CA-19-9 levels following RT were predictive of survival (P = 0.02). Grade 2 and ≥grade 3 GI toxicity were 60% and 20%, respectively. In comparison to 3D-CRT, DP-IMRT plans demonstrated significantly lower V45 values of small bowel (P = 0.0002), stomach (P = 0.007), and mean liver doses (P = 0.001). Conclusions. Dose-escalated DP-IMRT offers improved local control in patients treated with induction chemotherapy for LAPC. Radiation-related morbidity appears reduced with DP-IMRT compared to 3D-CRT techniques, likely due to reduction in RT doses to organs at risk.

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age Improved and clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, chemotherapy regimen, even after adjustment for covariates and propensity score weighting (hazard ratio, 0.76; Pchemotherapy regimens. In what to the authors' knowledge is the largest group of patients with stage II colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

  3. Prior exercise improves survival, infarct healing, and left ventricular function after myocardial infarction.

    Science.gov (United States)

    de Waard, Monique C; Duncker, Dirk J

    2009-09-01

    We investigated the effects of voluntary wheel running before an acute myocardial infarction (MI) on survival, left ventricular (LV) remodeling and dysfunction and whether exercise before and after MI provides superior protection compared with either exercise intervention alone. After 2 wk of voluntary wheel running or sedentary housing, MI was induced in C57Bl/6 mice, after which exercise was stopped (EX-MI-SED and SED-MI-SED groups, where EX is exercise and SED is sedentary) or continued (EX-MI-EX and SED-MI-EX groups) for a period of 8 wk. Exercise after MI in SED-MI-EX mice had no effect on survival, the area of infarction, and global LV remodeling, but attenuated fibrosis and apoptosis in the remote myocardium and blunted LV dysfunction and pulmonary congestion compared with SED-MI-SED mice. Exercise before MI in both EX-MI-SED and EX-MI-EX mice decreased post-MI mortality compared with both SED-MI-SED and SED-MI-EX mice. Furthermore, in both pre-MI exercise groups, the infarct area was thicker, whereas interstitial fibrosis and apoptosis in the remote LV myocardium were blunted. In contrast, the ameliorating effects of either pre-MI or post-MI exercise alone on LV dysfunction were lost in EX-MI-EX mice, which may in part be related to the increased daily exercise distance in the first week post-MI in EX-MI-EX versus SED-MI-EX mice. In conclusion, exercise before or after MI blunted LV dysfunction, whereas only exercise before MI improved survival. These findings suggest that even when regular physical activity fails to prevent an acute MI, it can still act to improve cardiac function and survival after MI.

  4. Does postoperative radiation therapy impact survival in non-metastatic sarcomatoid renal cell carcinoma? A SEER-based study.

    Science.gov (United States)

    Eminaga, Okyaz; Akbarov, Ilgar; Wille, Sebastian; Engelmann, Udo

    2015-10-01

    The effect of adjuvant radiation therapy on survival in sarcomatoid renal cell carcinoma (sRCC) with no evidence of distant metastasis remains unclear. Subjects diagnosed with non-metastatic sRCC were identified using the Surveillance Epidemiology and End Results (SEER) (2004-2012) database and divided into groups based on their surgical treatment (ST): no surgery or radiation therapy (NSR); partial nephrectomy (PNE); radical nephrectomy with ureterectomy and bladder cuff resection (RNE + UE + BLAD); and radical nephrectomy (RNE). Certain radical nephrectomy cases also received adjuvant external-beam radiation therapy (RNE + RAD). The Kaplan-Meier method was used to estimate overall survival (OS). A multivariable competing risks regression analysis was used to calculate disease-specific survival (DSS) probability and to determine factors associated with cause-specific mortality (CSM). A total of 408 patients were included in this study. The 5-year OS and predicted DSS were significantly higher in the patients who underwent STs (i.e., PNE, RNE + UE + BLAD, RNE, and RNE + RAD) (20.1-54.0 and 20.1-59.9 %, respectively) than in the NSR group (9.0 and 11.6 %, respectively) (P therapy did not increase OS in non-metastatic sRCC patients.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ana-Maria Ticărat

    2011-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, B.E.; Buchsbaum, D.J. [Birmingham University of Alabama, Birmingham, AL (United States). Dept. of Radiation Oncology; Zinn, K.R. [Birmingham University of Alabama, Birmingham, AL (United States). Radiology

    2000-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-15

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

  9. Improved Survival in Patients with Recurrent Wilms Tumor: the Experience of the Seoul National University Children's Hospital

    OpenAIRE

    Park, Eun Sil; Kang, Hyoung Jin; Shin, Hee Young; Ahn, Hyo Seop

    2006-01-01

    The survival in cases with relapsed Wilms tumor is dismal. Recently, however the introduction of new therapeutic agents and experimental strategies has improved the survival. We analysed the survival of patients with relapsed Wilms tumor according to the treatment period. During the early period 1983-1993, patients who had received two drugs were treated with doxorubicin and the others were treated with cisplatin and etoposide, whereas during the late period 1994-2004, patients were treated w...

  10. Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis.

    Science.gov (United States)

    Fettiplace, Michael R; McCabe, Daniel J

    2017-08-01

    The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I2 to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies. Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

  11. Improving access to tuberculosis preventive therapy and treatment for children

    Directory of Open Access Journals (Sweden)

    Ben J. Marais

    2017-03-01

    Full Text Available Children suffer a huge burden of disease in tuberculosis (TB endemic countries. This disease burden was largely invisible when TB control programmes focused exclusively on adults with sputum smear-positive disease. High-level advocacy and better data have improved visibility, but the establishment of functional paediatric TB programmes remains challenging. The key issues that limit children's access to TB preventive therapy and treatment in endemic areas are briefly discussed. Barriers to preventive therapy include (1 the perceived inability to rule out active disease, (2 fear of creating drug resistance, (3 non-implementation of existing guidelines in the absence of adequate monitoring, and (4 poor adherence with long preventive therapy courses. Barriers to TB treatment include (1 perceived diagnostic difficulties, (2 non-availability of chest radiography, (3 young children presenting to unprepared maternal and child health (MCH services, and (4 the absence of child-friendly formulations. With drug-resistant disease there is currently no guidance on the use of preventive therapy and treatment is usually restricted to cases with bacteriologically confirmed disease, which excludes most young children from care, even if their likely source case has documented drug-resistant TB.

  12. Does "conversion chemotherapy" really improve survival in metastatic colorectal cancer patients with liver-limited disease?

    Science.gov (United States)

    Kataoka, K; Kanazawa, A; Iwamoto, S; Kato, T; Nakajima, A; Arimoto, A

    2014-04-01

    The clinical benefits of conversion chemotherapy followed by liver resection for initially unresectable colorectal liver metastases are still controversial. The criteria for unresectability vary from one team to another. To clarify this issue, we retrospectively assessed the survival and characteristics of metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) who underwent conversion therapy. Our criteria for resectability depended on the size of the remnant liver volume (>30 %) and expected function after removal of all metastases. Between December 2007 and September 2011, a total of 115 patients were diagnosed as having mCRC with LLD and received chemotherapy. Among them, 47 had tumors that were initially diagnosed as resectable. They underwent hepatic resection after chemotherapy (resected group). Of the 67 tumors were initially diagnosed as unresectable, 12 became resectable after chemotherapy (conversion group), leaving 55 tumors that remained unresectable after chemotherapy (unresected group). The median follow-up was 25.2 months. Hepatic resection was more invasive in the conversion group than in the resected group. Median disease-free survival was significantly higher in the resected group than in the conversion group (p = 0.013). Overall survival (OS) was also higher in the resected group, but the difference was not significant (p = 0.36). However, OS was significantly higher in the conversion group than in the unresected group (p = 0.034). Multivariate analysis of the resected and conversion groups showed that OS was significantly negatively influenced by abnormal carcinoembryonic antigen levels at surgery (p = 0.037) and a hospital stay >30 days (p = 0.009). Our results showed that conversion chemotherapy could contribute to longer OS in mCRC patients with LLD.

  13. Dance therapy improves self-body image among obese patients.

    Science.gov (United States)

    Muller-Pinget, Solange; Carrard, Isabelle; Ybarra, Juan; Golay, Alain

    2012-12-01

    Obesity and disturbed eating behaviors are both associated with low self-esteem and distorted body images. The aim of this study was to assess the influence of a dance therapy program on the evolution of mental representations linked to body image among obese patients. Changes in body image were evaluated in terms of four parameters: physical, psychological, cognitive, and social. In total, 18 obese patients were enrolled in a longitudinal dance therapy workshop (DTW) program lasting 36 weeks. Patients danced for 2h per week and were evaluated three times: at baseline, after 18 weeks, and at the end of the study (36 weeks). Evaluation was performed using questionnaires addressing health-related quality of life, sensorial-motor perception, and mental representations linked to body schema and self-body image. Obese patients enrolled in the DTW displayed a significant improvement in health-related quality of life (pconsciousness (pconsciousness of their body image. Patients are usually reluctant to practice physical activity. Dance therapy improves not only body image, but also psycho-social aspects of their personality. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis.

    Science.gov (United States)

    Unsinger, Jacqueline; McGlynn, Margaret; Kasten, Kevin R; Hoekzema, Andrew S; Watanabe, Eizo; Muenzer, Jared T; McDonough, Jacquelyn S; Tschoep, Johannes; Ferguson, Thomas A; McDunn, Jonathan E; Morre, Michel; Hildeman, David A; Caldwell, Charles C; Hotchkiss, Richard S

    2010-04-01

    Sepsis is a highly lethal disorder characterized by widespread apoptosis-induced depletion of immune cells and the development of a profound immunosuppressive state. IL-7 is a potent antiapoptotic cytokine that enhances immune effector cell function and is essential for lymphocyte survival. In this study, recombinant human IL-7 (rhIL-7) efficacy and potential mechanisms of action were tested in a murine peritonitis model. Studies at two independent laboratories showed that rhIL-7 markedly improved host survival, blocked apoptosis of CD4 and CD8 T cells, restored IFN-gamma production, and improved immune effector cell recruitment to the infected site. Importantly, rhIL-7 also prevented a hallmark of sepsis (i.e., the loss of delayed-type hypersensitivity), which is an IFN-gamma- and T cell-dependent response. Mechanistically, rhIL-7 significantly increased the expression of the leukocyte adhesion markers LFA-1 and VLA-4, consistent with its ability to improve leukocyte function and trafficking to the infectious focus. rhIL-7 also increased the expression of CD8. The potent antiapoptotic effect of rhIL-7 was due to increased Bcl-2, as well as to a dramatic decrease in sepsis-induced PUMA, a heretofore unreported effect of IL-7. If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis.

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

    Science.gov (United States)

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

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Roberta Fulthorpe

    2018-02-01

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

  17. The Hartford Consensus to improve survivability in mass casualty events: Process to policy.

    Science.gov (United States)

    Jacobs, Lenworth; Burns, Karyl J

    2014-01-01

    The Joint Committee to Create a National Policy to Enhance Survivability from Mass Casualty Shooting Events was formed to make recommendations to improve survival from intentional mass casualty incidents. This article describes the development of the Hartford Consensus and the process used to disseminate and implement its findings. Members of the Committee included individuals from select public safety organizations. The first meeting of the Committee was held on April 2, 2013, and a second meeting was held on July 11, 2013. Attendance at the second meeting was enlarged and included representatives from the Federal Emergency Management Agency and the National Security Staff of the Office of the President. The results of these meetings became known as the Hartford Consensus. The ideas generated at the meetings produced two documents, one from each meeting. These are referred to as Hartford Consensus I and II. Hartford Consensus I is a concept document and Hartford Consensus II is a call to action that no one should die from uncontrolled bleeding. The recommendations are being incorporated into training programs and have been endorsed by many organizations whose members are involved in the response to mass casualty incidents. The Joint Committee to Create a National Policy to Enhance Survivability from Mass Casualty Shooting Events was successful in stimulating policy to bring about change. Training and resources including tourniquets and hemostatic dressing are being directed to help ameliorate the unfortunate reality of intentional mass injury.

  18. Laparoscopic colectomy for cancer: Improved compliance with guidelines for chemotherapy and survival.

    Science.gov (United States)

    Kim, Roger H; Kavanaugh, Mindie M; Caldito, Gloria C

    2017-06-01

    Laparoscopic surgery for colon cancer has been demonstrated in clinical trials to have short-term benefits when compared to the open surgical approach. Guidelines of the National Comprehensive Cancer Network recommend that patients with stage III or high-risk stage II colon cancer undergo adjuvant chemotherapy. We hypothesized that laparoscopic colectomy is associated with increased compliance to recommendations for chemotherapy, a lesser time to start of chemotherapy, and increased overall survival. The National Cancer Data Base was queried to identify patients with stage III or high-risk stage II colon cancer (T4, positive margins, chemotherapy, time from diagnosis and date of operation to start of chemotherapy, and overall survival were compared. A total of 48,257 patients were included for analysis; 18,801 patients underwent laparoscopic colectomy and 29,456 underwent open colectomy. Laparoscopic colectomy patients received adjuvant chemotherapy at a somewhat greater rate than open colectomy (66.2% vs 59.4%, P chemotherapy, mean time to start of chemotherapy after definitive resection was somewhat less for laparoscopic colectomy than open colectomy (48.7 vs 52.7 days, P chemotherapy for stage III and high-risk stage II colon cancer, as well as a slightly lesser time to start of chemotherapy and improved overall survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Aortic root surgery improves long-term survival after acute type A aortic dissection.

    Science.gov (United States)

    Hysi, Ilir; Juthier, Francis; Fabre, Olivier; Fouquet, Olivier; Rousse, Natacha; Banfi, Carlo; Pinçon, Claire; Prat, Alain; Vincentelli, André

    2015-04-01

    Our objective was to analyze the long term survival of patient operated on for acute type A aortic dissection. Between 1990 and 2010, 226 patients underwent emergency surgical operation for acute type A aortic dissection. We have followed the long-term outcomes. 144 patients were operated on with a supracommissural replacement of the ascending aorta (SCR) and 82 with an aortic root surgery (ARS, including 77 Bentall procedures and 5 Tirone David operations). Aortic cross-clamp was longer in ARS group (150.8 vs. 103.6 min, p<0.0001). Overall in-hospital mortality was lower in ARS group (20% vs. 34%, p 0.03). Median follow-up was 11.6 years. 10-year survival was higher in ARS group (85.7% vs. 65.9%, p 0.03) and 10-year freedom from aortic root reoperation was significantly lower in ARS group (93.4% vs. 82.9%, p 0.02). In a multivariate analysis aortic root surgery was an independent protective factor for proximal reoperations OR 0.393, CI 95% [0.206-0.748], p=0.005. Our study suggests that complete aortic root replacement in type A aortic dissection does not burden short-term outcomes, improves long-term survivals and decreases the rate of late reoperation. Whether this approach has to be preferred in younger patient has to be demonstrated in further studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Xuebijing injection reduces organ injuries and improves survival by attenuating inflammatory responses and endothelial injury in heatstroke mice.

    Science.gov (United States)

    Xu, Qiulin; Liu, Jingxian; Guo, Xiaohua; Tang, Youqing; Zhou, Gengbiao; Liu, Yanan; Huang, Qiaobing; Geng, Yan; Liu, Zhifeng; Su, Lei

    2015-02-05

    The pathogenesis of heatstroke is a multi-factorial process involved with an interplay among subsequent inflammation, endothelial injury and coagulation disturbances, which makes pharmacological therapy of heatstroke a challenging problem. Xuebijing injection (XBJ), a traditional Chinese medicine used to sepsis, has been reported to suppress inflammatory responses and restore coagulation disturbances. However, little is known about the role of XBJ in heatstroke. Mice were treated with indicated dose of XBJ before and/or after the induction of heatstroke. Serum inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and endothelial markers, von Willebrand Factor (vWF) and E-selectin, were measured by ELISA. Liver, kidney and heart profiles including alanine aminotransferase, aspartic aminotransferase, creatinine, blood urea nitrogen, and lactate dehydrogenase, were evaluated by UniCel DxC 800 Synchron Clinical Systems, and troponin was measured by ELISA. Coagulation profiles, including thrombin time, prothrombin time, activated partial thromboplastin time, international normalized ratio, and fibrinogen were examined by STA Compact® Hemostasis System. Jejunum injury was evaluated with H&E staining. Changes in mitochondrial structure in cardiac tissue were assesed by electron microscopy. Pretreatment with XBJ decreased serum pro-inflammatory cytokines including TNF-α and IL-6, as well as endothelial injury markers, vWF and E-selectin, in a dose-dependent manner in heatstroke mice. Similar protective effects were observed when XBJ was administered after, or both before and after heat insult. These protective effects lasted for over 12 h in mice receiving XBJ before and after heat insult. XBJ also improved survival rates in heatstroke mice, ameliorated liver, heart, and kidney injuries, including mitochondrial damage to the heart, and reduced coagulation disturbances. XBJ prevents organ injuries and improves survival in heatstroke mice by

  1. Optimized surgical techniques and postoperative care improve survival rates and permit accurate telemetric recording in exercising mice

    Science.gov (United States)

    Schuler, Beat; Rettich, Andreas; Vogel, Johannes; Gassmann, Max; Arras, Margarete

    2009-01-01

    Background The laboratory mouse is commonly used as a sophisticated model in biomedical research. However, experiments requiring major surgery frequently lead to serious postoperative complications and death, particularly if genetically modified mice with anatomical and physiological abnormalities undergo extensive interventions such as transmitter implantation. Telemetric transmitters are used to study cardiovascular physiology and diseases. Telemetry yields reliable and accurate measurement of blood pressure in the free-roaming, unanaesthetized and unstressed mouse, but data recording is hampered substantially if measurements are made in an exercising mouse. Thus, we aimed to optimize transmitter implantation to improve telemetric signal recording in exercising mice as well as to establish a postoperative care regimen that promotes convalescence and survival of mice after major surgery in general. Results We report an optimized telemetric transmitter implantation technique (fixation of the transmitter body on the back of the mouse with stainless steel wires) for subsequent measurement of arterial blood pressure during maximal exercise on a treadmill. This technique was used on normal (wildtype) mice and on transgenic mice with anatomical and physiological abnormalities due to constitutive overexpression of recombinant human erythropoietin. To promote convalescence of the animals after surgery, we established a regimen for postoperative intensive care: pain treatment (flunixine 5 mg/kg bodyweight, subcutaneously, twice per day) and fluid therapy (600 μl, subcutaneously, twice per day) were administrated for 7 days. In addition, warmth and free access to high energy liquid in a drinking bottle were provided for 14 days following transmitter implantation. This regimen led to a substantial decrease in overall morbidity and mortality. The refined postoperative care and surgical technique were particularly successful in genetically modified mice with severely

  2. N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia.

    Science.gov (United States)

    Oldham, Justin M; Witt, Leah J; Adegunsoye, Ayodeji; Chung, Jonathan H; Lee, Cathryn; Hsu, Scully; Chen, Lena W; Husain, Aliya; Montner, Steven; Vij, Rekha; Strek, Mary E; Noth, Imre

    2018-02-08

    Mortality is similarly high among individuals with usual interstitial pneumonia (UIP) due to idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF). Circulating anti-nuclear antibodies (ANA) are commonly found in this patient population, suggesting possible aberrant immune activation. Because an environment of oxidative stress can result from immunologic activation, we hypothesized that ANA positive patients with UIP would have improved outcome when exposed to the antioxidant N-acetylcysteine (NAC) compared to ANA negative patients. A single center, retrospective cohort analysis was performed. Patients with UIP due to IPF and IPAF were stratified according to ANA status to and NAC exposure. Transplant-free survival (TFS) was assessed using the Kaplan-Meier estimator and multivariable Cox regression adjusted for diagnosis, gender/age/physiology score, immunosuppressant exposure and anti-fibrotic exposure. Of 293 individuals with UIP due to IPF (74%) or IPAF (26%), NAC exposure was documented in 58 (19.8%). Among NAC exposed individuals, 33 (56.9%) were ANA seropositive and 25 (43.1%) were seronegative. NAC exposure was associated with improved TFS survival among ANA seropositive individuals in unadjusted analysis (plogrank = 0.02) and after multi-variable adjustment (HR 0.51, 95% CI 0.30-0.87; p = 0.01). There was no association between NAC exposure and TFS in ANA seronegative individuals (HR 1.26, 95% CI 0.69-2.32; p = 0.45). Formal interaction testing confirmed NAC*ANA interaction (p = 0.04) and sensitivity analysis demonstrated an increasing effect size associated with NAC therapy as ANA titer increased. Among patients with available genetic data, a marginally higher proportion of ANA positive patients (p = 0.08) carried the rs3750920 (TOLLIP) genotype previously shown to predict favorable outcome in NAC exposed patients. NAC exposure is associated with improved transplant-free survival ANA positive

  3. Improving therapeutic activity of anti-CD20 antibody therapy through immunomodulation in lymphoid malignancies.

    Science.gov (United States)

    Lipowska-Bhalla, Grazyna; Fagnano, Ester; Illidge, Timothy M; Cheadle, Eleanor J

    2016-01-01

    Nearly two decades ago rituximab heralded a new era in management of B cell malignancies significantly increasing response rates and survival. However, despite clear therapeutic advantage, significant numbers of patients become refractory to anti-CD20 mAb therapy, suggesting urgent improvements are required. It is now well recognized that the suppressive tumor microenvironment plays an important role in the outcome of anti-CD20 mAb therapy and that manipulation of this environment may improve the efficacy and produce long-term tumor control. The past few years have seen a surge of interest in immunomodulatory agents capable of overwriting immune suppressive networks into favorable clinical outcome. Currently, a number of such combinations with anti-CD20 mAb is under evaluation and some have produced encouraging outcomes in rituximab refractory disease. In this review, we give an outline of anti-CD20 mAbs and explore the combinations with immunomodulatory agents that enhance antitumor immunity through targeting stimulatory or inhibitory pathways and have proven potential to synergize with anti-CD20 mAb therapy. These agents, primarily mAbs, target CTLA-4, PD-1/PD-L1, and CD40.

  4. Case Report: Improved Homonymous Hemianopia with Hyperbaric Oxygen Therapy

    Science.gov (United States)

    2017-06-29

    Oxygen Therapy presented at/published to Undersea and Hyperbaric Medicine (JournaUAbstract); Undersea and Hvperbaric Medical Society Annual Scientific...REY1EWER 9. REV1E\\\\’ER SIGNATURE 50. OATE PREY10US ECmONS ARE 06SO’_ETE 1’: e 3 of 3 FlIlles Improved Homonymous Hemianopia with Hyperbaric Oxygen Therapy ...01Do humlln5: 1S’oC~llrodby32 CFR211i1 tmd DODI321𔄀.02_Af’J .DC>r:oI’dJ.rIg to tfNl pn’DCipHicl :!lor fon~in tho IMllfll<r>Mms d rtxl.A Wofti ru Ace of1

  5. Crocetin Reduces Activation of Hepatic Apoptotic Pathways and Improves Survival in Experimental Hemorrhagic Shock

    Science.gov (United States)

    Yang, Rongjie; Vernon, Kathy; Thomas, Ann; Morrison, David; Qureshi, Nilofer; Van Way, Charles W

    2014-01-01

    Background Hemorrhagic shock results in cellular damage and cell death. A primary mechanism is cellular apoptosis from mitochondrial damage. This study demonstrated that administration of crocetin to experimental animals during resuscitation from shock significantly improved postshock survival and reduced apoptosis. Crocetin is a component of saffron and has long been used in traditional medicine in Asia. Methods Male Sprague-Dawley rats (350 ± 30g) were randomly assigned to 1 of 4 groups of 8 animals. Hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure was 35–40 mm Hg, and blood pressure was maintained at that level for 60 minutes with further withdrawals as needed. Resuscitation was carried out by administration of 21 mL/kg lactated Ringer’s solution and return of shed blood, with or without concurrent administration of crocetin (2 mg/kg). Control animals were sham-treated with surgical preparation, without shock or resuscitation, and with and without crocetin. Rats were sacrificed 24 hours after completion of resuscitation. The extent of activation of hepatic apoptosis was established by measuring levels of hepatic cytosolic cytochrome c, caspase-3, and bcl-2. A separate group of 53 animals treated identically was used to assess survival. Results Crocetin administration during resuscitation resulted in less extensive activation of hepatic apoptosis and significantly increased survival relative to controls. Conclusions Crocetin administration to experimental animals during resuscitation post hemorrhage increased survival, at least in part by protecting the liver from activation of apoptotic cell death. This agent continues to show promise as a potential treatment strategy for hemorrhagic shock. PMID:21224437

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-05-01

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

  7. Service delivery interventions to improve adolescents' linkage, retention and adherence to antiretroviral therapy and HIV care

    National Research Council Canada - National Science Library

    MacPherson, Peter; Munthali, Chigomezgo; Ferguson, Jane; Armstrong, Alice; Kranzer, Katharina; Ferrand, Rashida A; Ross, David A

    2015-01-01

    ... antiretroviral prevention of mother‐to‐child transmission was widely available are now surviving in adolescence due to increased availability of antiretroviral therapy (ART). Adolescents infected with HIV fac...

  8. Survival Comparisons for Breast Conserving Surgery and Mastectomy Revisited: Community Experience and the Role of Radiation Therapy

    Science.gov (United States)

    Onitilo, Adedayo A.; Engel, Jessica M.; Stankowski, Rachel V.; Doi, Suhail A.R.

    2015-01-01

    Objectives Evidence suggests superiority of breast conserving surgery (BCS) plus radiation over mastectomy alone for treatment of early stage breast cancer. Whether the superiority of BCS plus radiation is related to the surgical approach itself or to the addition of adjuvant radiation therapy following BCS remains unclear. Materials and Methods We conducted a retrospective cohort study of women with breast cancer diagnosed from 1994–2012. Data regarding patient and tumor characteristics and treatment specifics were captured electronically. Kaplan-Meier survival analyses were performed with inverse probability of treatment weighting to reduce selection bias effects in surgical assignment. Results Data from 5335 women were included, of which two-thirds had BCS and one-third had mastectomy. Surgical decision trends changed over time with more women undergoing mastectomy in recent years. Women who underwent BCS versus mastectomy differed significantly regarding age, cancer stage/grade, adjuvant radiation, chemotherapy, and endocrine treatment. Overall survival was similar for BCS and mastectomy. When BCS plus radiation was compared to mastectomy alone, 3-, 5-, and 10-year overall survival was 96.5% vs 93.4%, 92.9% vs 88.3% and 80.9% vs 67.2%, respectively. Conclusion These analyses suggest that survival benefit is not related only to the surgery itself, but that the prognostic advantage of BCS plus radiation over mastectomy may also be related to the addition of adjuvant radiation therapy. This conclusion requires prospective confirmation in randomized trials. PMID:25487237

  9. From palliative therapy to prolongation of survival: (223)RaCl2 in the treatment of bone metastases.

    Science.gov (United States)

    Liepe, Knut; Shinto, Ajit

    2016-07-01

    Patients with hormone-refractory prostate cancer often have multiple bone metastases. The resulting bone pain is associated with reduced life quality, increased cost of therapy and impairment of overall survival. Trials with bone-targeting β-emitters have mostly showed an effect on alleviation of bone pain along with prolongation in survival, documented in only a limited number of patients. A randomized phase III trial (ALSYMPCA) using the α-emitter (223)RaCl2 (Xofigo®) showed for the first time, a longer overall survival of 3.6 months in treated patients as a sign of an antitumor effect. The time to first skeletal-related events was also significantly longer in the therapy group compared with placebo. Because of the short range of α-emitter, the bone marrow toxicity of radium therapy is low, and so this radionuclide could also be a candidate for combination with chemotherapy. The elimination of (223)RaCl2 is mainly through the gastrointestinal tract and side effects are mainly in this area. The procedure is similar to treatment with other bone-seeking agents and consists of six administrations of 50 kBq/kg bodyweight Xofigo®, repeated every 4 weeks. At present Xofigo® is only approved for hormone-refractory prostate cancer.

  10. Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis.

    Science.gov (United States)

    Chang, Ronald; Holcomb, John B; Johansson, Par I; Pati, Shibani; Schreiber, Martin A; Wade, Charles E

    2017-06-06

    The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-hour survival in a rat sepsis model. Adult male Sprague-Dawley rats (375-425 g) were subjected to 35% cecal ligation and puncture (CLP) (t = 0 h). Twenty-two hours post-CLP and prior to resuscitation (t = 22 h), animals were randomized to resuscitation with normal saline (NS, 10 cc/kg/hr) or pooled rat fresh frozen plasma (FFP, 3.33 cc/kg/hr). Resuscitation under general anesthesia proceeded for the next six hours (t = 22 h to t = 28 h); lactate was checked every 2 hours, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t = 22 h) and after resuscitation (t = 28 h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisher's exact test was used to analyze the primary outcome of 48-hour survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of dry weight ratio (5.28 vs 5.94) (all p < 0.05). Compared to crystalloid, plasma resuscitation increased 48-hour survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.

  11. Amantadine improves cognitive outcome and increases neuronal survival after fluid percussion traumatic brain injury in rats.

    Science.gov (United States)

    Wang, Tao; Huang, Xian-Jian; Van, Ken C; Went, Gregory T; Nguyen, Jack T; Lyeth, Bruce G

    2014-02-15

    This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. Amantadine or saline control was administered intraperitoneally, starting at 1 h after TBI followed by dosing three times daily for 16 consecutive days at 15, 45, and 135 mg/kg/day. Terminal blood draws were obtained from TBI rats at the time of euthanasia at varying time points after the last amantadine dose. Pharmacokinetics analysis confirmed that the doses of AMT achieved serum concentrations similar to those observed in humans receiving therapeutic doses (100-400 mg/day). Acquisition of spatial learning and memory retention was assessed using the Morris water maze (MWM) on days 12-16 after TBI. Brain tissues were collected and stained with Cresyl-violet for long-term cell survival analysis. Treatment with 135mg/kg/day of AMT improved acquisition of learning and terminal cognitive performance on MWM. The 135-mg/kg/day dosing of AMT increased the numbers of surviving CA2-CA3 pyramidal neurons at day 16 post-TBI. Overall, the data showed that clinically relevant dosing schedules of AMT affords neuroprotection and significantly improves cognitive outcome after experimental TBI, suggesting that it has the potential to be developed as a novel treatment of human TBI.

  12. Does social feeding improve larval survival of the two-spotted lady beetle, Adalia bipunctata?

    Science.gov (United States)

    Moore, Michael P; Burt, Charles R; Whitney, Thomas D; Hastings, Steven A; Chang, Gary C

    2012-01-01

    Lady beetles typically lay eggs in clusters, and clutch-mates that emerge near to each other might benefit in multiple ways. For example, lady beetle larvae are attracted to the pheromone released by aphids under attack. Thus, one potential advantage to larvae emerging as a group is if one larva captures an aphid, others can share in consuming the same aphid. Sharing a meal likely reduces the per capita food intake of a hatchling, but it might also provide enough nutrition to prevent death by starvation during a particularly vulnerable stage. In an assay of the behavior of two-spotted lady beetles (Adalia bipunctata), larvae were attracted to chemical cues from damaged aphids, corroborating previous research. Densities of A. bipunctata hatchlings were then manipulated to test whether the presence of clutch-mates increasesed the probability of capturing prey, and the survivorship of hatchlings. In one experiment, a single aphid was placed with a number of lady beetle hatchlings ranging from 1 to 10 in a small arena for 72 hours to evaluate prey capture effectiveness and hatchling survival. As the initial density of lady beetle hatchlings increased, their prey capture rate increased. At the same time, survival of the hatchlings was not affected by their initial density. Five experiments were performed on individual fava bean plants by varying densities of aphids and lady beetle hatchlings to evaluate lady beetle survivorship measured after five days. In all five on-plant experiments, increasing the initial number of lady beetle larvae did not improve their survival. Lady beetle larvae shared meals during the small scale experiments, but that behavior did not improve their survivorship under any of the experimental conditions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1996-12-31

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

  14. Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis.

    Science.gov (United States)

    Antunes, Héliton S; Herchenhorn, Daniel; Small, Isabele A; Araújo, Carlos M M; Viégas, Celia Maria Pais; de Assis Ramos, Gabriela; Dias, Fernando L; Ferreira, Carlos G

    2017-08-01

    The impact of low-level laser therapy (LLLT) to prevent oral mucositis in patients treated with exclusive chemoradiation therapy remains unknown. This study evaluated the overall, disease-free and progression-free survival of these patients. Overall, disease-free and progression-free survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx cancer, who participated on a phase III study, was evaluated from 2007 to 2015. The patients were subjected to conventional radiotherapy plus cisplatin every 3weeks. LLLT was applied with an InGaAlP diode (660nm-100mW-1J-4J/cm2). With a median follow-up of 41.3months (range 0.7-101.9), patients receiving LLLT had a statistically significant better complete response to treatment than those in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT also displayed increase in progression-free survival than those in the placebo group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07-3.5) and had a tendency for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92-2.91). This is the first study to suggest that LLLT may improve survival of head and neck cancer patients treated with chemoradiotherapy. Further studies, with a larger sample, are necessary to confirm our findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Quantifying and Improving International Space Station Survivability Following Orbital Debris Penetration

    Science.gov (United States)

    Williamsen, Joel; Evans, Hilary; Bohl, Bill; Evans, Steven; Parker, Nelson (Technical Monitor)

    2001-01-01

    The increase of the orbital debris environment in low-earth orbit has prompted NASA to develop analytical tools for quantifying and lowering the likelihood of crew loss following orbital debris penetration of the International Space Station (ISS). NASA uses the Manned Spacecraft and Crew Survivability (MSCSurv) computer program to simulate the events that may cause crew loss following orbital debris penetration of ISS manned modules, including: (1) critical cracking (explosive decompression) of the module; (2) critical external equipment penetration (such as hydrazine and high pressure tanks); (3) critical internal system penetration (guidance, control, and other vital components); (4) hazardous payload penetration (furnaces, pressure bottles, and toxic substances); (5) crew injury (from fragments, overpressure, light flash, and temperature rise); (6) hypoxia from loss of cabin pressure; and (7) thrust from module hole causing high angular velocity (occurring only when key Guidance, Navigation, and Control (GN&C) equipment is damaged) and, thus, preventing safe escape vehicle (EV) departure. MSCSurv is also capable of quantifying the 'end effects' of orbital debris penetration, such as the likelihood of crew escape, the probability of each module depressurizing, and late loss of station control. By quantifying these effects (and their associated uncertainties), NASA is able to improve the likelihood of crew survivability following orbital debris penetration due to improved crew operations and internal designs.

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

    Directory of Open Access Journals (Sweden)

    Chunguang Chen

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

  17. Methods to Improve Adoptive T-Cell Therapy for Melanoma

    DEFF Research Database (Denmark)

    Donia, Marco; Hansen, Morten; Sendrup, Sarah L

    2013-01-01

    Further development of adoptive T-cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) has the potential to markedly change the long-term prognosis of patients with metastatic melanoma, and modifications of the original protocol that can improve its clinical efficacy are highly...... desirable. In this study, we demonstrated that a high in vitro tumor reactivity of infusion products was associated with clinical responses upon adoptive transfer. In addition, we systematically characterized the responses of a series of TIL products to relevant autologous short term-cultured melanoma cell...

  18. Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats.

    Science.gov (United States)

    Okponyia, Obiefuna C; McGraw, Matthew D; Dysart, Marilyn M; Garlick, Rhonda B; Rioux, Jacqueline S; Murphy, Angela L; Roe, Gates B; White, Carl W; Veress, Livia A

    2018-01-01

    Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD 58-67 ) in a whole-body exposure chamber, and given oxygen (0.8 Fi O 2 ) or air (0.21 Fi O 2 ) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

  19. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

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

  20. Molecular stratification of metastatic melanoma using gene expression profiling: Prediction of survival outcome and benefit from molecular targeted therapy.

    Science.gov (United States)

    Cirenajwis, Helena; Ekedahl, Henrik; Lauss, Martin; Harbst, Katja; Carneiro, Ana; Enoksson, Jens; Rosengren, Frida; Werner-Hartman, Linda; Törngren, Therese; Kvist, Anders; Fredlund, Erik; Bendahl, Pär-Ola; Jirström, Karin; Lundgren, Lotta; Howlin, Jillian; Borg, Åke; Gruvberger-Saal, Sofia K; Saal, Lao H; Nielsen, Kari; Ringnér, Markus; Tsao, Hensin; Olsson, Håkan; Ingvar, Christian; Staaf, Johan; Jönsson, Göran

    2015-05-20

    Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.

  1. Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy

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    Bowerman Melissa

    2012-03-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1 gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil. Methods Fasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at P t test for paired variables and one-way analysis of variance (ANOVA were used to test for differences between samples and data were considered significantly different at P Results Fasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific. Conclusions Our work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK inhibitors as a therapeutic strategy for SMA

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

    Science.gov (United States)

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

    2017-02-01

    Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

    2017-02-01

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

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

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

    2014-10-31

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

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

    Directory of Open Access Journals (Sweden)

    A Cupisti

    2012-06-01

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

  6. Survival outcome and treatment response of patients with late relapse from renal cell carcinoma in the era of targeted therapy.

    Science.gov (United States)

    Kroeger, Nils; Choueiri, Toni K; Lee, Jae-Lyn; Bjarnason, Georg A; Knox, Jennifer J; MacKenzie, Mary J; Wood, Lori; Srinivas, Sandy; Vaishamayan, Ulka N; Rha, Sun-Young; Pal, Sumanta K; Yuasa, Takeshi; Donskov, Frede; Agarwal, Neeraj; Tan, Min-Han; Bamias, Aristotelis; Kollmannsberger, Christian K; North, Scott A; Rini, Brian I; Heng, Daniel Y C

    2014-06-01

    A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence ≥5 yr after initial nephrectomy. To characterize the clinical outcome of patients with late recurrence beyond 5 yr. Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease >3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr. Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses. Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5-35 yr) after 5 yr. LRs presented with younger age (pcell histology (p=0.001), and lower Fuhrman grade (ptherapy were better in LRs versus ERs (31.8% vs 26.5%; p=0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5 mo; p=0.005) and overall survival (OS; 34.0 mo vs 27.4 mo; p=0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols. A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  7. Pyruvate oral rehydration solution improved visceral function and survival in shock rats.

    Science.gov (United States)

    Yu, Wen; Hu, Sen; Xie, Zhi-Yi; He, Zhi-Jie; Luo, Hong-Min; Lin, Hong-Yuan; Zhou, Fang-Qiang; Sheng, Zhi-Yong

    2015-01-01

    Recent findings showed advantages of a novel pyruvate-enriched oral rehydration solution (Pyr-ORS) in resuscitation of burns. This study focused on effects of Pyr-ORS on the visceral blood perfusion (VBP), gastrointestinal function, and survival rate, compared with the bicarbonate-based World Health Organization-guided oral rehydration solution (WHO-ORS), during intragastric rehydration of lethal hemorrhagic shock in rats. Sixty adult rats were subjected to 45% total blood volume loss and were randomly allocated to the following three groups (n = 20): group NR (no fluid resuscitation), group PORS (oral Pyr-ORS rehydration), and group BORS (oral WHO-ORS rehydration), respectively. Other 10 rats were served as group NH (the sham group). Enteral rehydration lasted for 4 h after hemorrhage. The mean arterial pressure (MAP), VBP, and plasma enzymes activities of heart, liver, and kidney, and intestinal fatty acid binding protein were measured. Liver, kidney, and ileum were harvested for the evaluation of activities of oxidative enzymes and intestinal barrier protein (ZO-1). Other 84 rats with identical procedures without sampling were observed for their 24-h survival rates. Pyr-ORS was more effective in enhancing the MAP and VBP, inhibiting tissue oxidative damage, and improving organ function, compared with WHO-ORS. Hypoxic lactic acidosis was fully corrected in group PORS in 4 h, whereas it worsened in group BORS, and the 24-h survival rate was twice higher in group PORS than in group BORS (45.8 versus 20.8%, P rehydration of lethal hemorrhagic shock. The Pyr-ORS may be an ideal oral fluid in resuscitation of hypovolemic shock, especially in prehospital and resource-poor settings. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia.

    Science.gov (United States)

    Hu, Xiaoxia; Fu, Weijun; Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2016-01-19

    Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients.

  9. Improvement Screening for Ultra-High Dimensional Data with Censored Survival Outcomes and Varying Coefficients.

    Science.gov (United States)

    Yue, Mu; Li, Jialiang

    2017-05-18

    Motivated by risk prediction studies with ultra-high dimensional bio markers, we propose a novel improvement screening methodology. Accurate risk prediction can be quite useful for patient treatment selection, prevention strategy or disease management in evidence-based medicine. The question of how to choose new markers in addition to the conventional ones is especially important. In the past decade, a number of new measures for quantifying the added value from the new markers were proposed, among which the integrated discrimination improvement (IDI) and net reclassification improvement (NRI) stand out. Meanwhile, C-statistics are routinely used to quantify the capacity of the estimated risk score in discriminating among subjects with different event times. In this paper, we will examine these improvement statistics as well as the norm-based approach for evaluating the incremental values of new markers and compare these four measures by analyzing ultra-high dimensional censored survival data. In particular, we consider Cox proportional hazards models with varying coefficients. All measures perform very well in simulations and we illustrate our methods in an application to a lung cancer study.

  10. Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study

    Directory of Open Access Journals (Sweden)

    Jaya Chakravarty

    2014-01-01

    Full Text Available Background & objectives: The National AIDS Control Organization (NACO of India has been providing free ARV (antiretroviral drugs since 2004. b0 y 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10% expired, 205 (12.13% were lost to follow up (LFU, 526 (31.14% were transferred out to other facilities and 686 (40.63% were alive at the end of two years. Majority (92% of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/μl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme.

  11. Increased neutrophil-to-lymphocyte ratio after neoadjuvant therapy is associated with worse survival after resection of borderline resectable pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Glazer, Evan S; Rashid, Omar M; Pimiento, Jose M; Hodul, Pamela J; Malafa, Mokenge P

    2016-11-01

    The neutrophil-to-lymphocyte ratio (neutrophil count divided by lymphocyte count) is a marker of inflammation associated with poor cancer outcomes. The role of neutrophil-to-lymphocyte ratio in borderline resectable pancreatic ductal adenocarcinoma is unknown. We hypothesized that increased neutrophil-to-lymphocyte ratio in patients with borderline resectable pancreatic ductal adenocarcinoma after neoadjuvant therapy is inversely associated with survival. We used our borderline resectable pancreatic ductal adenocarcinoma database to identify patients who had completed neoadjuvant therapy and underwent resection. The neutrophil-to-lymphocyte ratio difference was calculated as the neutrophil-to-lymphocyte ratio after neoadjuvant therapy minus the neutrophil-to-lymphocyte ratio before neoadjuvant therapy. Patients were assigned to the increased neutrophil-to-lymphocyte ratio cohort if the difference was ≥2.5 units; all others were assigned to the stable neutrophil-to-lymphocyte ratio cohort. Statistical analyses were performed with t test and regression. Of 62 patients identified, 43 were assigned to the stable neutrophil-to-lymphocyte ratio cohort, and 19 to the increased neutrophil-to-lymphocyte ratio cohort. There were no differences in stage, age, or sex. The preneoadjuvant neutrophil-to-lymphocyte ratio was 3.1 ± 2.4, whereas the postneoadjuvant neutrophil-to-lymphocyte ratio was 4.4 ± 3.5 (P = .002). Overall survival was worse in the increased neutrophil-to-lymphocyte ratio cohort compared with the stable neutrophil-to-lymphocyte ratio cohort (P = .009) with a Cox hazard ratio of 2.9 (P = .02). N0 disease conferred a survival advantage over N1 disease (Cox hazard ratio = 0.3, P = .01). On multivariate Cox hazard regression analysis, both increased neutrophil-to-lymphocyte ratio and N1 stage were associated with worse survival (P ratio in patients with borderline resectable pancreatic ductal adenocarcinoma. These findings support exploring

  12. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    Science.gov (United States)

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

  14. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival.

    Science.gov (United States)

    Hu, Chung-Yuan; Bailey, Christina E; You, Y Nancy; Skibber, John M; Rodriguez-Bigas, Miguel A; Feig, Barry W; Chang, George J

    2015-03-01

    With the advent of effective modern chemotherapeutic and biologic agents, primary tumor resection for patients with stage IV colorectal cancer (CRC) may not be routinely necessary. To evaluate the secular patterns of primary tumor resection use in stage IV CRC in the United States. A retrospective cohort study using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results CRC registry. Demographic and clinical factors were compared for 64,157 patients diagnosed with stage IV colon or rectal cancer from January 1, 1988, through December 31, 2010, who had undergone primary tumor resection and those who had not. Rates of primary tumor resection and median relative survival were calculated for each year. Joinpoint regression analysis was used to determine when a significant change in trend in the primary tumor resection rate had occurred. Logistic regression analysis was used to assess factors associated with primary tumor resection. Difference in primary tumor resection rates over time. Of the 64,157 patients with stage IV CRC, 43,273 (67.4%) had undergone primary tumor resection. The annual rate of primary tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 (Ptrend toward fewer primary tumor resections was seen. Despite the decreasing primary tumor resection rate, patient survival rates improved. However, primary tumor resection may still be overused, and current treatment practices lag behind evidence-based treatment guidelines.

  15. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis.

    Directory of Open Access Journals (Sweden)

    DongYu Liang

    Full Text Available Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3, a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP-induced sepsis in mice.C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation.Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05. Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis.Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.

  16. Going the Extra Mile: Improved Survival for Pancreatic Cancer Patients Traveling to High-volume Centers.

    Science.gov (United States)

    Lidsky, Michael E; Sun, Zhifei; Nussbaum, Daniel P; Adam, Mohamed A; Speicher, Paul J; Blazer, Dan G

    2017-08-01

    This study compares outcomes following pancreaticoduodenectomy (PD) for patients treated at local, low-volume centers and those traveling to high-volume centers. Although outcomes for PD are superior at high-volume institutions, not all patients live in proximity to major medical centers. Theoretical advantages for undergoing surgery locally exist. The 1998 to 2012 National Cancer Data Base was queried for T1-3N0-1M0 pancreatic adenocarcinoma patients who underwent PD. Travel distances to treatment centers were calculated. Overlaying the upper and lower quartiles of travel distance with institutional volume established short travel/low-volume (ST/LV) and long travel/high-volume (LT/HV) cohorts. Overall survival was evaluated. Of 7086 patients, 773 ST/LV patients traveled ≤6.3 (median 3.2) miles to centers performing ≤3.3 PDs yearly, and 758 LT/HV patients traveled ≥45 (median 97.3) miles to centers performing ≥16 PDs yearly. LT/HV patients had higher stage disease (P travel to a high-volume center remained associated with reduced long-term mortality (hazard ratio 0.75, P travel burden, patients treated at high-volume centers had improved perioperative outcomes, short-term mortality, and overall survival. These data support ongoing efforts to centralize care for patients undergoing PD.

  17. Short-term starvation of immune deficient Drosophila improves survival to gram-negative bacterial infections.

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    Anthony E Brown

    Full Text Available Primary immunodeficiencies are inborn errors of immunity that lead to life threatening conditions. These predispositions describe human immunity in natura and highlight the important function of components of the Toll-IL-1- receptor-nuclear factor kappa B (TIR-NF-kappaB pathway. Since the TIR-NF-kappaB circuit is a conserved component of the host defence in higher animals, genetically tractable models may contribute ideas for clinical interventions.We used immunodeficient fruit flies (Drosophila melanogaster to address questions pertaining to survival following bacterial infection. We describe here that flies lacking the NF-kappaB protein Relish, indispensable for countering Gram-negative bacteria, had a greatly improved survival to such infections when subject to dietary short-term starvation (STS prior to immune challenge. STS induced the release of Nitric Oxide (NO, a potent molecule against pathogens in flies, mice and humans. Administering the NO Synthase-inhibitory arginine analog N-Nitro-L-Arginine-Methyl-Ester (L-NAME but not its inactive enantiomer D-NAME increased once again sensitivity to infection to levels expected for relish mutants. Surprisingly, NO signalling required the NF-kappaB protein Dif, usually needed for responses against Gram-positive bacteria.Our results show that NO release through STS may reflect an evolutionary conserved process. Moreover, STS could be explored to address immune phenotypes related to infection and may offer ways to boost natural immunity.

  18. Myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats.

    Science.gov (United States)

    Silver, Stephen M; Schroeder, Barbara M; Sterns, Richard H; Rojiani, Amyn M

    2006-01-01

    When chronic hyponatremia is rapidly corrected, reaccumulation of brain organic osmolytes is delayed and brain cell shrinkage occurs, leading to the osmotic demyelination syndrome (ODS). We hypothesized that treatment with myoinositol, a major organic osmolyte, could prevent ODS. Severe hyponatremia was induced in adult male rats by administration of arginine vasopressin and intravenous infusion of dextrose and water. Sixty-four hours after induction of hyponatremia, all animals underwent rapid correction of hyponatremia with infusion of hypertonic saline over 4 hours, increasing the serum sodium from 105 to 135 mM; half of the animals were also given myoinositol intravenously beginning 20 minutes before correction and continuing for 28 hours. Serum sodium concentrations were equivalent in both groups at all time points. At 7 days, 7 of 8 animals that received myoinositol survived compared with one of the 9 control animals (p myoinositol. Animals were killed 96 hours after correction of hyponatremia was begun. Myoinositol-treated animals had significantly fewer demyelinating lesions than mannitol (2.25 +/- 1.1 versus 6.42 +/- 1.4 lesions/brain, p myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats.

  19. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice

    DEFF Research Database (Denmark)

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin

    2016-01-01

    /BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21......This study investigated the effect of post-stroke, direct AT2-receptor (AT2R) stimulation with the non-peptide AT2R-agonist compound 21 (C21) on infarct size, survival and neurological outcome after middle cerebral artery occlusion (MCAO) in mice and looked for potential underlying mechanisms. C57...... significantly improved survival after MCAO when compared to vehicle-treated mice. C21 treatment had no impact on infarct size, but significantly attenuated neurological deficits. Expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB) (receptor for BDNF) and growth...

  20. Filter Size Not the Anticoagulation Method is the Decisive Factor in Continuous Renal Replacement Therapy Circuit Survival

    Directory of Open Access Journals (Sweden)

    Monika Miklaszewska

    2017-06-01

    Full Text Available Background/Aim: As continuous renal replacement therapy (CRRT has emerged as a standard therapy in pediatric intensive care units (PICU, many related issues that may have an impact on circuit survival have gained in importance. Objective of the study was an evaluation of factors associated with circuit survival, including anticoagulation (ACG. Methods: Retrospective study that included 40 patients, who in total received 7636 hours of CRRT during 150 sessions (84 filters, 4260 hours with heparin anticoagulation (Hep-ACG; 66 filters, 3376 hours with regional citrate anticoagulation (RCA. Results: The Kaplan-Meier analysis of the total circuit survival time depending on the type of ACG did not demonstrate a significant difference between Hep-ACG and RCA. The percentage of clotted filters was significantly higher in case of smaller filters (HF20: 58.8%; ST60: 29.5%; ST100: 15.8%, and their lifetime was significantly lower regardless of ACG (the mean and median lifetime for HF20: 38.7/27.0 h; for ST60: 54.1/72.0 h., for ST100: 62.1/72.0 h, respectively. Conclusions: Irrespectively of filter size, filter clotting occurs within the first 24 hours after the initiation of CRRT. Most commonly, clotting affects small filters, and their lifetime is significantly shorter as compared to larger filters regardless of the type of the ACG.

  1. SLT-VEGF Reduces Lung Metastases, Decreases Tumor Recurrence, and Improves Survival in an Orthotopic Melanoma Model

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    Sini Skariah

    2010-08-01

    Full Text Available SLT-VEGF is a recombinant cytotoxin comprised of Shiga-like toxin (SLT subunit A fused to human vascular endothelial growth factor (VEGF. It is highly cytotoxic to tumor endothelial cells overexpressing VEGF receptor-2 (VEGFR-2/KDR/Flk1 and inhibits the growth of primary tumors in subcutaneous models of breast and prostate cancer and inhibits metastatic dissemination in orthotopic models of pancreatic cancer. We examined the efficacy of SLT-VEGF in limiting tumor growth and metastasis in an orthotopic melanoma model, using NCR athymic nude mice inoculated with highly metastatic Line IV Cl 1 cultured human melanoma cells. Twice weekly injections of SLT-VEGF were started when tumors became palpable at one week after intradermal injection of 1 × 106 cells/mouse. Despite selective depletion of VEGFR-2 overexpressing endothelial cells from the tumor vasculature, SLT-VEGF treatment did not affect tumor growth. However, after primary tumors were removed, continued SLT-VEGF treatment led to fewer tumor recurrences (p = 0.007, reduced the incidence of lung metastasis (p = 0.038, and improved survival (p = 0.002. These results suggest that SLT-VEGF is effective at the very early stages of tumor development, when selective killing of VEGFR-2 overexpressing endothelial cells can still prevent further progression. We hypothesize that SLT-VEGF could be a promising adjuvant therapy to inhibit or prevent outgrowth of metastatic foci after excision of aggressive primary melanoma lesions.

  2. Nutrition management for head and neck cancer patients improves clinical outcome and survival.

    Science.gov (United States)

    Müller-Richter, Urs; Betz, C; Hartmann, S; Brands, R C

    2017-12-01

    Up to 80% of patients with head and neck cancers are malnourished because of their lifestyle and the risk factors associated with this disease. Unfortunately, nutrition management systems are not implemented in most head and neck cancer clinics. Even worse, many head and neck surgeons as well as hospital management authorities disregard the importance of nutrition management in head and neck cancer patients. In addition, the often extensive resection and reconstruction required for tumors in the upper aerodigestive tract pose special challenges for swallowing and sufficient food intake, placing special demands on nutrition management. This article presents the basics of perioperative metabolism and nutrition management of head and neck cancer patients and makes recommendations for clinical practice. Implementing a nutrition management system in head and neck cancer clinics will improve the clinical outcome and the survival of the patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

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    Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd; Fischer-Valuck, Benjamin W. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Mutch, David G.; Powell, Matthew A. [Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri (United States); Schwarz, Julie K. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Grigsby, Perry W., E-mail: pgrigsby@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2015-11-01

    Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Cox proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.

  4. Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Yannick Nicolas Gerber

    2013-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder typified by a massive loss of motor neurons with few therapeutic options. The exact cause of neuronal degeneration is unknown but it is now admitted that ALS is a multifactorial disease with several mechanisms involved including glutamate excitotoxicity. More specifically, N-methyl-D-aspartate (NMDA-mediated cell death and impairment of the glutamate-transport has been suggested to play a key role in ALS pathophysiology. Thus, evaluating NMDAR antagonists is of high therapeutic interest. Gacyclidine, also named GK11, is a high affinity non-competitive NMDAR antagonist that may protect against motor neuron death in an ALS context. Moreover, GK11 presents a low intrinsic neurotoxicity and has already been used in two clinical trials for CNS lesions. In the present study, we investigated the influence of chronic administration of two doses of GK11 (0.1 and 1 mg/kg on the survival and the functional motor activity of hSOD1G93A mice, an animal model of ALS. Treatment started at early symptomatic age (60 days and was applied bi-weekly until the end stage of the disease. We first confirmed that functional alteration of locomotor activity was evident in the hSOD1G93A transgenic female mice by 60 days of age. A low dose of GK11 improved the survival of the mice by 4.3% and partially preserved body weight. Improved life span was associated with a delay in locomotor function impairment. Conversely, the high dose treatment worsened motor functions. These findings suggest that chronic administration of GK11beginning at early symptomatic stage may be beneficial for patients with ALS.

  5. Survival after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for advanced colorectal liver metastases: A case-matched comparison with palliative systemic therapy.

    Science.gov (United States)

    Olthof, Pim B; Huiskens, Joost; Wicherts, Dennis A; Huespe, Pablo E; Ardiles, Victoria; Robles-Campos, Ricardo; Adam, René; Linecker, Michael; Clavien, Pierre-Alain; Koopman, Miriam; Verhoef, Cornelis; Punt, Cornelis J A; van Gulik, Thomas M; de Santibanes, Eduardo

    2017-04-01

    Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows the resection of colorectal liver metastases with curative intent which would otherwise be unresectable and only eligible for palliative systemic therapy. This study aimed to compare outcomes of ALPPS in patients with otherwise unresectable colorectal liver metastases with matched historic controls treated with palliative systemic treatment. All patients with colorectal liver metastases from the international ALPPS registry were identified and analyzed. Survival data were compared according to the extent of disease. Otherwise unresectable ALPPS patients were defined by at least 2 of the following criteria: ≥6 metastasis, ≥2 future remnant liver metastasis, ≥6 involved segments excluding segment 1. These patients were matched with patients included in 2, phase 3, metastatic, colorectal cancer trials (CAIRO and CAIRO2) using propensity scoring in order to compare survival. Of 295 patients with colorectal liver metastases in the ALPPS registry, 70 patients had otherwise unresectable disease defined by the proposed criteria. Two-year overall survival was 49% and 72% for patients with ≥2 and palliative treatment (24.0 vs 17.6 months, P = .088). Early oncologic outcomes of patients with advanced liver metastases undergoing ALPPS were not superior to results of matched patients receiving systemic treatment with palliative intent. Careful patient selection is essential in order to improve outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Can survival prediction be improved by merging gene expression data sets?

    Directory of Open Access Journals (Sweden)

    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  7. Colon cancer survival with herbal medicine and vitamins combined with standard therapy in a whole-systems approach: ten-year follow-up data analyzed with marginal structural models and propensity score methods.

    Science.gov (United States)

    McCulloch, Michael; Broffman, Michael; van der Laan, Mark; Hubbard, Alan; Kushi, Lawrence; Abrams, Donald I; Gao, Jin; Colford, John M

    2011-09-01

    Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that of concurrent external controls from Kaiser Permanente Northern California and California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more modern methods were used for causal inference-namely, propensity score and marginal structural models (MSMs), which have not been used before in studies of cancer survival and Chinese herbal medicine. PAM+V combined with conventional therapy, compared with conventional therapy alone, reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was no significant difference between short-term and long-term PAM+V. Combining PAM+V with conventional therapy improved survival, compared with conventional therapy alone, suggesting that prospective trials combining PAM+V with conventional therapy are justified.

  8. Survival Benefit of Empirical Therapy for Staphylococcus aureus Bloodstream Infections in Infants.

    Science.gov (United States)

    Thaden, Joshua T; Ericson, Jessica E; Cross, Heather; Bergin, Stephen P; Messina, Julia A; Fowler, Vance G; Benjamin, Daniel K; Clark, Reese H; Hornik, Christoph P; Smith, P Brian

    2015-11-01

    The impact of early adequate empirical antibiotic therapy on outcomes of infants in the neonatal intensive care unit (NICU) who develop Staphylococcus aureus bloodstream infections (BSI) is unknown. Infants with S. aureus BSI discharged in 1997-2012 from 348 NICUs managed by the Pediatrix Medical Group were identified. Early adequate empirical antibiotic therapy was defined as exposure to ≥1 antibiotic with anti-staphylococcal activity on the day the first positive blood culture was obtained. All other cases were defined as inadequate empirical antibiotic therapy. We evaluated the association between inadequate empirical antibiotic therapy on outcomes controlling for gestational age, small for gestational age status, gender, discharge year, mechanical ventilation, inotropic support and use of supplemental oxygen. The primary outcome was 30-day mortality. Secondary outcomes were 7-day mortality, death before hospital discharge and length of bacteremia. Of the 3339 infants with S. aureus BSI, 2492 (75%) had methicillin-susceptible S. aureus (MSSA) BSI and 847 (25%) had methicillin-resistant S. aureus (MRSA) BSI. Inadequate empirical antibiotic therapy was administered in 725 (22%) cases. Inadequate empirical antibiotic therapy was associated with increased 30-day mortality (odds ratio: 2.03; 95% confidence interval: 1.08-3.82) among infants with MRSA BSI. Inadequate empirical antibiotic therapy was not associated with increases in mortality among infants with MSSA BSI. After controlling for confounders, inadequate empirical antibiotic therapy was associated with a modestly increased mortality at 30 days for infants with MRSA BSI.

  9. [Change in the survival of Cuban AIDS patients with tuberculosis in the Highly Active Antiretroviral Therapy (HAART) era].

    Science.gov (United States)

    Reyes-Corcho, Andrés; Capo de Paz, Virginia; Díaz-Jidy, Manuel; Pérez-Avila, Jorge; Bouza-Jiménez, Yadira

    2008-09-01

    HIV infection affected 0.06% of the Cuban population and AIDS associated tuberculosis (TB) represented 4.4% of cases in 2004. The objective of this study was to determine the survival of AIDS patients with TB. 167 individuals of both sexes and ages between 15 and 60 years old were studied; all of them were diagnosed in the Havana's Tropical Medicine Institute "Pedro Kourí", Cuba, between January 1st 1997 and May 31st 2005. The Kaplan-Meier's method and the Long-rank test were used for the survival, and the Cox's multivariate method to identify the variables associated with mortality by means of SPSS 9.0. 78 individuals of the total died at the end of study, 71.8% belonged to the pre highly active antiretroviral therapy (HAART) era and 28.2% to the later period. From all deceased cases due to TB, 82.1% were diagnosed in the pre HAART era. The median survival was 41 months (CI=20-62). TB diagnosis in the pre HAART period, TB not being the first disease indicator of AIDS, suffering from candidiasis of esophagus before TB and a LTCD4+ count < 200 at the diagnosis of TB, were all independently associated with mortality. This study demonstrated the positive impact of HAART in the survival of Cuban AIDS patients with TB and also identified advanced immunodepression and opportunistic infections as predictors of mortality.

  10. Growth and survival of blowfly Lucilia sericata larvae under simulated wound conditions: implications for maggot debridement therapy.

    Science.gov (United States)

    Čičková, H; Kozánek, M; Takáč, P

    2015-12-01

    Maggot debridement therapy has become a well-established method of wound debridement. Despite its success, little information is available about the optimum duration of the treatment cycle and larval growth in wounds. This study examines the development of Lucilia sericata (Diptera: Calliphoridae) larvae under two containment conditions (bagged and free range) under simulated wound conditions and assesses the impact of transport and further storage of larvae on their survival and growth. There was no significant difference in size between bagged and free-range larvae over the 72-h experimental period. Larvae grew fastest 8-24 h after inoculation and completed their growth at 40-48 h. Mortality rates were similar (0.12-0.23% per hour) in both containment conditions and did not differ significantly (P = 0.3212). Survival of free-range larvae was on average 16% lower than survival of bagged larvae. Refrigeration of larvae upon simulated delivery for > 1 day reduced their survival to < 50% and caused a reduction in growth of up to 30% at 12 h, but not at 48 h, of incubation. Therefore, it is recommended that free-range larvae are left in the wound for a maximum of 40-48 h, and bagged larvae for 48-72 h. Larvae should be used within 24 h of delivery to avoid high mortality caused by prolonged refrigeration. © 2015 The Royal Entomological Society.

  11. Strategies to Improve Cancer Photothermal Therapy Mediated by Nanomaterials.

    Science.gov (United States)

    de Melo-Diogo, Duarte; Pais-Silva, Cleide; Dias, Diana R; Moreira, André F; Correia, Ilídio J

    2017-05-01

    The deployment of hyperthermia-based treatments for cancer therapy has captured the attention of different researchers worldwide. In particular, the application of light-responsive nanomaterials to mediate hyperthermia has revealed promising results in several pre-clinical assays. Unlike conventional therapies, these nanostructures can display a preferential tumor accumulation and thus mediate, upon irradiation with near-infrared light, a selective hyperthermic effect with temporal resolution. Different types of nanomaterials such as those based on gold, carbon, copper, molybdenum, tungsten, iron, palladium and conjugated polymers have been used for this photothermal modality. This progress report summarizes the different strategies that have been applied so far for increasing the efficacy of the photothermal therapeutic effect mediated by nanomaterials, namely those that improve the accumulation of nanomaterials in tumors (e.g. by changing the corona composition or through the functionalization with targeting ligands), increase nanomaterials' intrinsic capacity to generate photoinduced heat (e.g. by synthesizing new nanomaterials or assembling nanostructures) or by optimizing the parameters related to the laser light used in the irradiation process (e.g. by modulating the radiation wavelength). Overall, the development of new strategies or the optimization and combination of the existing ones will surely give a major contribution for the application of nanomaterials in cancer PTT. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Modulation of the tumor vasculature and oxygenation to improve therapy

    DEFF Research Database (Denmark)

    Siemann, Dietmar W; Horsman, Michael R

    2015-01-01

    The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient......, and extracellular molecules which together are essential for the initiation, progression and spread of tumor cells. The physical conditions that arise are imposing and manifold, and include elevated interstitial pressure, localized extracellular acidity, and regions of oxygen and nutrient deprivation. No less...... that create a significant hindrance to the control of cancers by conventional anticancer therapies. However, the aberrant nature of the tumor microenvironments also offers unique therapeutic opportunities. Particularly interventions that seek to improve tumor physiology and alleviate tumor hypoxia...

  13. Nanosized ZSM-5 will improve photodynamic therapy using Methylene blue.

    Science.gov (United States)

    Kariminezhad, H; Habibi, M; Mirzababayi, N

    2015-07-01

    Nowadays, nanotechnology is growing to improve Photodynamic Therapy and reduce its side effects. In this research, the synthesized co-polymeric Zeolite Secony Mobile-5 (ZSM-5) was employed to modify Methylene Blue (MB) for these reasons. UV-Visible, FTIR, XRD analysis and SEM images were used to investigate obtained nanostructure. The crystal size for these nanostructures were determined 75 nm and maximum adsorption capacity of MB in the nanostructure was estimated 111 (mg g(-1)). Also, the role of Polyethylene Glycol (PEG) was studied as a capable non-toxic polymeric coating to overcome biological barriers. Moreover, potential of singlet oxygen production of the synthesized nanostructure was compared with MB and ZSM-5 nanoparticles control samples. Synthesized nanodrugs show impressive light induced singlet oxygen production efficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Continuous Veno-Venous Hemofiltration Improves Survival of Patients With Congestive Heart Failure and Cardiorenal Syndrome Compared to Slow Continuous Ultrafiltration.

    Science.gov (United States)

    Premuzic, Vedran; Basic-Jukic, Nikolina; Jelakovic, Bojan; Kes, Petar

    2017-06-01

    Continuous veno-venous hemofiltration (CVVH) could modulate the inflammatory response by removal of circulating cytokines and therefore improve cardiac function in patients with heart failure (HF). We hypothesized that patients with developed cardiorenal syndrome and treated with CVVH have lower risk for mortality than other patients treated with slow continuous ultrafiltration (SCUF). This was a prospective, longitudinal follow-up study for 24 months duration. In total, 120 patients were recruited from the intensive care units. Only patients with cardiorenal syndrome type 1 and 2 were enrolled. 54 CVVH and 23 SCUF patients survived. Mean survival time was longer in CVVH group with cardiomyopathy than in the SCUF group. When we compared patients with cardiomyopathy and hourly urine output cardiorenal syndrome. Better survival in patients treated with CVVH, which is mostly pronounced in patients with cardiomyopathy, is a consequence of a better preserved hourly urine output. Longer survival in patients with cardiomyopathy is most probably related to cytokine removal by CVVH with smaller UF rates and longer duration of each treatment. Slow continuous ultrafiltration remains the method of choice in patients with HF and preserved renal function but in cases of developed cardiorenal syndrome is much inferior to CVVH. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  15. HIF-1α- Targeting Acriflavine Provides Long Term Survival and Radiological Tumor Response in Brain Cancer Therapy.

    Science.gov (United States)

    Mangraviti, Antonella; Raghavan, Tula; Volpin, Francesco; Skuli, Nicolas; Gullotti, David; Zhou, Jinyuan; Asnaghi, Laura; Sankey, Eric; Liu, Ann; Wang, Yuan; Lee, Dong-Hoon; Gorelick, Noah; Serra, Riccardo; Peters, Michael; Schriefer, Destiny; Delaspre, Fabien; Rodriguez, Fausto J; Eberhart, Charles G; Brem, Henry; Olivi, Alessandro; Tyler, Betty

    2017-11-02

    Tumor progression, limited efficacy of current standard treatments, and the rise in patient mortality are associated with gene expression caused by the synergistic action of intratumoral hypoxia and HIF-1α activation. For this reason, recent investigations have focused on HIF-targeting therapeutic agents, with encouraging preclinical and clinical results in solid tumors. Here we describe the efficacy of a HIF-1α inhibitor, Acriflavine, and demonstrate its potency against brain cancer. This safe antibacterial dye induces cell death and apoptosis in several glioma cell lines, targets HIF-1α-mediated pathways, and decreases the level of PGK1, VEGF and HIF-1α in vitro and in vivo. Administered locally via biodegradable polymers, Acriflavine provides significant benefits in survival resulting in nearly 100% long term survival, confirmed by MRI and histological analyses. This study reports preclinical evidence that this safe, small molecule can contribute to brain tumor therapy and highlights the significance of HIF-1α-targeting molecules.

  16. Improving adherence to and persistence with oral therapy of osteoporosis.

    Science.gov (United States)

    Bianchi, M L; Duca, P; Vai, S; Guglielmi, G; Viti, R; Battista, C; Scillitani, A; Muscarella, S; Luisetto, G; Camozzi, V; Nuti, R; Caffarelli, C; Gonnelli, S; Albanese, C; De Tullio, V; Isaia, G; D'Amelio, P; Broggi, F; Croci, M

    2015-05-01

    Osteoporosis treatment has low adherence and persistence. This study evaluated if greater patient involvement could improve them. At 12 months, only 114 out of 344 participants were "fully adherent and persistent" (all drug doses taken throughout the study). Only frequency of drug administration had a significant influence on adherence. Osteoporosis affects millions of individuals worldwide. There are now several effective drugs, but adherence to and persistence with treatment are low. This 12-month multicenter, prospective, randomized study evaluated the efficacy of two different methods aimed at improving adherence and persistence through greater patient involvement, compared with standard clinical practice. Three hundred thirty-four post-menopausal women, receiving an oral prescription for osteoporosis for the first time, were recruited and randomized into three groups: group 1 (controls, managed according to standard clinical practice) and groups 2 and 3 (managed with greater patient and caregiver involvement and special reinforcements: group 2, instructed to use several different "reminders"; group 3, same "reminders" as group 2, plus regular phone calls from and meetings at the referring Center). All enrolled women had two visits (baseline and 12 months). Of 334 enrolled women, 247 (74%) started the prescribed therapy. Of those who started, 219 (88.7%) persisted in therapy for at least 10 months. At final evaluation, only 114 women were considered as "fully adherent and persistent" (all doses taken throughout the 12 months). There were no significant differences regarding "full adherence" among the three randomized groups. The frequency of drug administration had a significant influence: weekly administration had a >5-fold higher adherence and monthly administration an 8-fold higher adherence (p < 0.0001) than daily administration. The special effort of devising and providing additional reminders did not prove effective. Additional interventions during

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

    Science.gov (United States)

    May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.

    2016-01-01

    Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413

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

    Directory of Open Access Journals (Sweden)

    Adam Trickey

    Full Text Available To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years.We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA.During 50,593 person years 656/13,011 (5% patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years.Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes.

  19. Does hormonal therapy for fertility preservation affect the survival of young women with early-stage endometrial cancer?

    Science.gov (United States)

    Greenwald, Zoë R; Huang, Lina N; Wissing, Michel D; Franco, Eduardo L; Gotlieb, Walter H

    2017-05-01

    The incidence of endometrial cancer among young women is increasing. Some patients with low-grade endometrial cancer receive hormone therapy (HT) before surgery to preserve fertility. It is unclear whether this adversely affects survival. Patients with localized, low-grade endometrial cancer who were aged Cancer-specific and overall survival were measured using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (95% CIs) were estimated using Cox models adjusted for age, period of diagnosis, marital status, race, tumor grade, morphology, and previous radiotherapy. A total of 6339 women were included in the current study cohort, 161 of whom initially received HT and 6178 of whom received primary surgery. After 15 years of follow-up, all-cause mortality did not differ between the groups (HT group: 14.1% [95% CI, 6.7%-28.4%] and propensity score-matched primary surgery group: 9.3% [95% CI, 4.1%-20.5%]). Cancer-specific mortality appeared higher in patients treated with HT compared with those treated with primary surgery (9.2% [95% CI, 3.4%-24.0%] vs 2.1% [95% CI, 1.5%-2.8%]). However, this difference was driven by 3 late deaths in the HT group. Sensitivity analyses using a broader definition of cancer-specific mortality provided no statistical evidence of a survival difference between the treatment groups. The hazard ratio for the overall risk of death was 1.45 (95% CI, 0.44-4.74). Based on this population-based cohort, young patients with low-grade endometrial cancer appear to have excellent survival, regardless of the primary therapy chosen (HT vs primary surgery). The current selection of patients for HT to preserve fertility, which is managed carefully by experienced clinicians, does not appear to significantly worsen clinical outcomes. Cancer 2017;123:1545-1554. © 2017 American Cancer Society. © 2016 American Cancer Society.

  20. [Therapy resistant diabetes mellitus and lipodystrophy: leptin therapy leads to improvement].

    Science.gov (United States)

    Jazet, Ingrid M; Jonker, Jacqueline T; Wijngaarden, Marjolein A; Lamb, Hildo; Smelt, August H M

    2013-01-01

    Lipodystrophy is a congenital or acquired disorder characterized by complete or partial absence of subcutaneous fat tissue, often accompanied by insulin resistance, diabetes mellitus (DM), hypertriglyceridemia and hepatic steatosis. A decrease in both number and function of adipocytes leads to ectopic fat depositions and decreased production of adipokines such as leptin. We present 2 patients with inadequately regulated DM, hypertriglyceridemia and hepatic steatosis who were eventually diagnosed with lipodystrophy: 1 with congenital generalized lipodystrophy (Berardinelli-Seip syndrome) and 1 with congenital partial lipodystrophy (Dunnigan syndrome). Both received recombinant human leptin therapy (methionylleptin, available on a compassionate-use basis). This resulted in improved plasma levels of triglyceride, glucose and HbA1c and a decrease in liver size. In addition, hepatic triglyceride content decreased from 19.3% to 1.3% in the first patient and from 20.6% to 12.4% in the second. Leptin therapy is an effective and safe treatment for therapy-resistant diabetes and hypertriglyceridemia in patients with congenital lipodystrophy.

  1. A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival.

    Science.gov (United States)

    Lee, Karla C L; Palacios Jimenez, Carolina; Alibhai, Hatim; Chang, Yu-Mei; Leckie, Pamela J; Baker, Luisa A; Stanzani, Giacomo; L Priestnall, Simon; Mookerjee, Rajeshwar P; Jalan, Rajiv; Davies, Nathan A

    2013-04-01

    A clinically relevant, translational large animal model of acute liver failure (ALF) is required for testing of novel therapies to prolong survival in acute liver failure, to permit spontaneous liver recovery or to act as a bridge to transplantation. The aim was to establish a pig model of acetaminophen-induced ALF that mimics the human clinical syndrome, is managed as in a human intensive care unit and has a predictable survival time. Nine female pigs were anaesthetised and instrumented for continuous intensive care monitoring and management using: target-driven protocols for treatment of cardiovascular collapse, metabolic acidosis and electrolyte abnormalities; intermittent positive pressure ventilation; and continuous renal replacement therapy. Six animals were induced to ALF with acetaminophen (paracetamol). Three animals acted as controls. Irreversible acute liver failure, defined as rise in prothrombin time >3 times normal, occurred 19.3 ± 1.8 h after the onset of acetaminophen administration. Death occurred predictably 12.6 ± 2.7 h thereafter, with acute hepatocellular necrosis in all animals. Clinical progression of liver failure mimicked the human condition including development of coagulopathy, intracranial hypertension, hyperammonaemia, cardiovascular collapse, elevation in creatinine, metabolic acidosis and hyperlactataemia. In addition, cardiovascular monitoring clearly demonstrated progressive cardiac dysfunction in ALF. A reproducible, clinically relevant, intensively managed, large animal model of acute liver failure, with death as a result of multi-organ failure, has been successfully validated for translational studies of disease progression and therapies designed to prolong survival in man. © 2012 John Wiley & Sons A/S.

  2. Effect of low concentrations of benzalkonium chloride on acanthamoebal survival and its potential impact on empirical therapy of infectious keratitis.

    Science.gov (United States)

    Tu, Elmer Y; Shoff, Megan E; Gao, Weihua; Joslin, Charlotte E

    2013-05-01

    The significant antiacanthamoebal effect of benzalkonium chloride, at or below concentrations used for preservation of common ophthalmic preparations, should be understood both when choosing empiric antibiotic therapy for infectious keratitis and when assessing the persistent rise in Acanthamoeba cases in the United States since 2003. To characterize the antiacanthamoebal efficacy of low concentrations of benzalkonium chloride (BAK) for drug preservation and therapeutic effect against Acanthamoeba. Experimental study with a review of the literature. Laboratory. A concentration of 10(4) trophozoites of 3 well-characterized clinical strains of Acanthamoeba were exposed at 0.5, 2.0, 3.5, 5.0, and 6.5 hours to BAK (0.001%, 0.002%, and 0.003%), moxifloxacin hydrochloride (0.5%), and moxifloxacin (0.5%) + BAK (0.001% and 0.003%) with hydrogen peroxide (3%) and amoeba saline controls. Amoeba survival was calculated using the most probable number method recorded as log kill values. The relationship of BAK concentration and exposure time as well as the relative effect of BAK and moxifloxacin on acanthamoebal survival were analyzed. Amoebicidal activity of BAK is both time dependent and concentration dependent in pooled and strain-stratified analyses (P independent inhibitory effect or additive effect to BAK efficacy on acanthamoebal survival. The profound antiacanthamoebal effect of BAK, 0.003%, was similar to that of hydrogen peroxide for certain strains. Low concentrations of BAK, previously demonstrated to concentrate and persist in ocular surface epithelium, exhibit significant antiacanthamoebal activity in vitro at or below concentrations found in commercially available ophthalmic anti-infectives. The unexplained persistence of the Acanthamoeba keratitis outbreak in the United States, clusters abroad, and clinical studies reporting resolution or modification of Acanthamoeba keratitis without specific antiacanthamoebal therapy suggests that other contributing factors

  3. Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

    DEFF Research Database (Denmark)

    Maddika, S; Ande, SR; Panigrahi, S

    2007-01-01

    both for their apoptosis-regulating capacity and also for their effect on the cell cycle progression. The PI3-K/Akt cell survival pathway is shown as regulator of cell metabolism and cell survival, but examples are also provided where aberrant activity of the pathway may contribute to the induction......The partial cross-utilization of molecules and pathways involved in opposing processes like cell survival, proliferation and cell death, assures that mutations within one signaling cascade will also affect the other opposite process at least to some extent, thus contributing to homeostatic...... regulatory circuits. This review highlights some of the connections between opposite-acting pathways. Thus, we discuss the role of cyclins in the apoptotic process, and in the regulation of cell proliferation. CDKs and their inhibitors like the INK4-family (p16(Ink4a), p15(Ink4b), p18(Ink4c), p19(Ink4d...

  4. Association of clinical trial enrollment and survival using contemporary therapy for pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Moke, Diana J; Oberley, Matthew J; Bhojwani, Deepa; Parekh, Chintan; Orgel, Etan

    2018-02-01

    While early studies reported superior survival for cancer patients enrolled on clinical trials, recent findings are inconclusive. We investigated the association between enrollment on contemporary trials and event-free survival (EFS) in pediatric B-cell acute lymphoblastic leukemia (B-ALL). In a retrospective cohort of 274 children (1-21 years) treated for B-ALL from 2008 to 2015, 55.5% enrolled with no disparity in enrollment by age, sex, or ethnicity. Three-year EFS was similar for enrolled and not enrolled patients (90.1% [95% CI, 82.5-94.5] versus 86.5% [95% CI, 77.7-92.0]). Clinical trial enrollment did not affect pediatric B-ALL survival, albeit in a limited-size cohort treated at a single academic institution. © 2017 Wiley Periodicals, Inc.

  5. Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated Systemic Capillary-Leak Syndrome.

    Science.gov (United States)

    Pineton de Chambrun, Marc; Gousseff, Marie; Mauhin, Wladimir; Lega, Jean-Christophe; Lambert, Marc; Rivière, Sophie; Dossier, Antoine; Ruivard, Marc; Lhote, François; Blaison, Gilles; Alric, Laurent; Agard, Christian; Saadoun, David; Graveleau, Julie; Soubrier, Martin; Lucchini-Lecomte, Marie-Josée; Christides, Christine; Bosseray, Annick; Levesque, Hervé; Viallard, Jean-François; Tieulie, Nathalie; Lovey, Pierre-Yves; Le Moal, Sylvie; Bibes, Béatrice; Malizia, Giuseppe; Abgueguen, Pierre; Lifermann, François; Ninet, Jacques; Hatron, Pierre-Yves; Amoura, Zahir

    2017-10-01

    Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first

  6. Sequential unusual site metastases in renal cell cancer: Saga of repeated tumor implantation and prolonged survival without systemic therapy

    Directory of Open Access Journals (Sweden)

    Siddharth Yadav

    2016-01-01

    Full Text Available Renal cell cancer (RCC is known to produce metastasis to unusual sites both synchronously and metachronously several years after the primary treatment. We report a rare case of RCC with three different, sequential, and each time isolated rare site metastasis to ureteric stump, surgical site, and urinary bladder over a period of 6 years after radical nephrectomy. At each recurrence, metastasectomy was carried out and no systemic therapy was administered. Eleven years after radical nephrectomy and 5 years after last resection, the patient remains disease free. Multiple recurrences can occur in RCC and complete surgical resection results in disease free survival.

  7. Improvements in Renal Replacement Therapy Practice Patterns in Estonia

    Directory of Open Access Journals (Sweden)

    Külli Kõlvald

    2014-07-01

    Full Text Available Background: The clinical performance indicators (CPI are important tools to assess and improve the quality of renal replacement therapy (RRT. The aim of the current study was to compare the results of a longitudinal set of CPI in RRT patients and to determine the extent to which the guidelines for anaemia, calcium phosphate management and other CPI are met in Estonian renal centres. Methods: A long-term retrospective, observational, cross-sectional CPI analysis was undertaken in RRT patients from 2007 to 2011. The following CPI set of well-designed measures based on good evidence was analysed: anaemia management variables, laboratory analyses of mineral metabolism, nutritional status variables and dialysis adequacy variables. Results: Relatively small changes in the analysed mean CPI values were noticed during the study period. In the course of the study, we noticed an improvement in anaemia control, but not all centres achieved the standard of >80% of the dialysis patients with a haemoglobin (Hb level >100 g/l. There was a trend of decreasing Hb concentrations below 125 g/l in both haemodialysis (HD and peritoneal dialysis (PD patients. In 2011, hyperphosphataemia was present in 58% of the HD and 47% of the PD patients, whereas centre differences varied between 50 and 60% of both the HD and PD patients. HD adequacy was achieved in 77% of the HD patients. Conclusion: An improvement in the data collection was noticed, and the analysis of CPI allows renal centres to assess and compare their practices with others. The collection and evaluation of CPI of RRT patients is an important improvement and significantly increases the awareness of nephrologists.

  8. Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

    Science.gov (United States)

    Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

    2016-09-01

    The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lim Yiting [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Kastan, Michael B. [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Matsui, William, E-mail: matsuwi@jhmi.edu [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); DeWeese, Theodore L., E-mail: deweete@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  10. Pharmacologic cholinesterase inhibition improves survival in acetaminophen-induced acute liver failure in the mouse.

    Science.gov (United States)

    Steinebrunner, Niels; Mogler, Carolin; Vittas, Spiros; Hoyler, Birgit; Sandig, Catharina; Stremmel, Wolfgang; Eisenbach, Christoph

    2014-08-19

    Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic pharmaceutical substances in the world and accounts for most cases of drug induced liver injury resulting in acute liver failure. Acute liver failure initiates a sterile inflammatory response with release of cytokines and innate immune cell infiltration in the liver. This study investigates, whether pharmacologic acetylcholinesterase inhibition with neostigmine diminishes liver damage in acute liver failure via the cholinergic anti-inflammatory pathway. Acute liver failure was induced in BALB/c mice by a toxic dose of acetaminophen (APAP). Neostigmine and/or N-acetyl-cysteine (NAC) were applied therapeutically at set time points and the survival was investigated. Liver damage was assessed by serum parameters, histopathology and serum cytokine assays 12 h after initiation of acute liver failure. Serum parameters, histopathology and serum cytokine assays showed pronounced features of acute liver failure 12 h after application of acetaminophen (APAP). Neostigmine treatment led to significant reduction of serum liver enzymes (LDH (47,147 ± 12,726 IU/l vs. 15,822 ± 10,629 IU/l, p = 0.0014) and ALT (18,048 ± 4,287 IU/l vs. 7,585 ± 5,336 IU/l, p = 0.0013), APAP-alone-treated mice vs. APAP + neostigmine-treated mice), inflammatory cytokine levels (IL-1β (147 ± 19 vs. 110 ± 25, p = 0.0138) and TNF-α (184 ± 23 vs. 130 ± 33, p = 0.0086), APAP-alone-treated mice vs. APAP + neostigmine-treated mice) and histopathological signs of damage.Animals treated with NAC in combination with the peripheral cholinesterase inhibitor neostigmine showed prolonged survival and improved outcome. Neostigmine is an acetylcholinesterase inhibitor that ameliorates the effects of APAP-induced acute liver failure in the mouse and therefore may provide new treatment options for affected patients.

  11. Abandoning Peracetic Acid-Based Dialyzer Reuse Is Associated with Improved Survival

    Science.gov (United States)

    Wang, Weiling; Mooney, Ann; Ofsthun, Norma; Lazarus, J. Michael; Hakim, Raymond M.

    2011-01-01

    Summary Background and objectives Higher mortality risk reported with reuse versus single use of dialyzers is potentially related to reuse reagents that modify membrane surface characteristics and the blood-membrane interface. A key mechanism may involve stimulation of an inflammatory response. Design, setting, participants, & measurements In a prospective crossover design, laboratory markers and mortality from 23 hemodialysis facilities abandoning reuse with peracetic acid mixture were tracked. C-reactive protein (CRP), white blood cell (WBC) count, albumin, and prealbumin were measured for 2 consecutive months before abandoning reuse and subsequently within 3 and 6 months on single use. Survival models were utilized to compare the 6-month period before abandoning reuse (baseline) and the 6-month period on single use of dialyzers after a 3-month “washout period.” Results Patients from baseline and single-use periods had a mean age of approximately 63 years; 44% were female, 54% were diabetic, 60% were white, and the mean vintage was approximately 3.2 years. The unadjusted hazard ratio for death was 0.70 and after case-mix adjustment was 0.74 for single use compared with reuse. Patients with CRP ≥ 5 mg/L during reuse (mean CRP = 26.6 mg/ml in April) declined on single use to 20.2 mg/L by August and 20.4 mg/L by November. WBC count declined slightly during single use, but nutritional markers were unchanged. Conclusions Abandonment of peracetic-acid-based reuse was associated with improved survival and lower levels of inflammatory but not nutritional markers. Further study is needed to evaluate a potential link between dialyzer reuse, inflammation, and mortality. PMID:20947788

  12. Long-term regional chemotherapy for patients with epithelial malignant peritoneal mesothelioma results in improved survival.

    Science.gov (United States)

    Sugarbaker, P H; Chang, D

    2017-07-01

    Malignant peritoneal mesothelioma (MPM) is a rare disease with about 300 new cases per year in the USA. Its natural history is described as local progression within the peritoneal space in the absence of liver metastases or systemic disease. Cytoreductive surgery (CRS) is a series of peritonectomy procedures and visceral resections with a goal of complete removal of all visible disease from the abdomen and pelvis. Over 20 years, three protocols investigating increasing efficacy of additional chemotherapy treatments added to CRS have been initiated. Initially, hyperthermic perioperative chemotherapy (HIPEC) with doxorubicin and cisplatin was used in the operating room. Then, early postoperative intraperitoneal chemotherapy (EPIC) with paclitaxel was added for the first 5 days after CRS. The third protocol employed HIPEC, then EPIC, and then long-term intraperitoneal (IP) paclitaxel or IP pemetrexed plus intravenous (IV) cisplatin as a adjuvant normothermic intraperitoneal chemotherapy (NIPEC). The 5-year survival of 42 patients treated with CRS and HIPEC was 44%, for 58 patients treated with EPIC and HIPEC was 52% and 29 patients who received HIPEC, EPIC, and NIPEC was 75% (p = 0.0374). Prognostic variables of age, gender, treatment administered, peritoneal cancer index (PCI) and completeness of cytoreduction were significant by univariate analysis and treatments administered and completeness of cytoreduction significant by multivariate analysis. Long-term regional chemotherapy was associated with improved survival in patients with MPM. In this rare disease, additional phase 2 investigations are suggested. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  13. Salidroside, A Natural Antioxidant, Improves β-Cell Survival and Function via Activating AMPK Pathway

    Directory of Open Access Journals (Sweden)

    Linjie Ju

    2017-10-01

    Full Text Available Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM and induces β-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on β-cells against diabetes associated oxidative stress.Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased β-cell mass and β-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (ΔΨm via reducing NOX2 expression and inhibiting JNK–caspase 3 apoptotic cascade subsequently to protect β-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in β-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving β-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on β-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on β-cells were AMPK activation dependent.Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing β-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.

  14. Salidroside, A Natural Antioxidant, Improves β-Cell Survival and Function via Activating AMPK Pathway.

    Science.gov (United States)

    Ju, Linjie; Wen, Xiaohua; Wang, Chunjun; Wei, Yingjie; Peng, Yunru; Ding, Yongfang; Feng, Liang; Shu, Luan

    2017-01-01

    Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces β-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on β-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased β-cell mass and β-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (ΔΨm) via reducing NOX2 expression and inhibiting JNK-caspase 3 apoptotic cascade subsequently to protect β-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in β-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving β-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on β-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on β-cells were AMPK activation dependent. Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing β-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.

  15. Fluid overload and survival in critically ill patients with acute kidney injury receiving continuous renal replacement therapy

    Science.gov (United States)

    Kim, Il Young; Kim, Joo Hui; Lee, Dong Won; Lee, Soo Bong; Rhee, Harin; Seong, Eun Young; Kwak, Ihm Soo

    2017-01-01

    Background Fluid overload is known to be associated with increased mortality in patients with acute kidney injury (AKI) who are critically ill. In this study, we intended to uncover whether the adverse effect of fluid overload on survival could be applied to all of the patients with AKI who received continuous renal replacement therapy (CRRT). Methods We analyzed 341 patients with AKI who received CRRT in our intensive care units. The presence of fluid overload was defined as a minimum 10% increase in body weight from the baseline. Demographics, comorbid diseases, clinical data, severity of illness [the sequential organ failure assessment (SOFA) score, number of vasopressors, diagnosis of sepsis, use of ventilator] upon ICU admission, fluid overload status, and time elapsed from AKI diagnosis until CRRT initiation were reviewed from the medical charts. Results Patients with total fluid overload from 3 days before CRRT initiation to ICU discharge had a significantly lower survival rate after ICU admission, as compared to patients with no fluid overload (P < 0.001). Among patients with sepsis (P < 0.001) or with high SOFA scores (P < 0.001), there was a significant difference in survival of the patients with and without fluid overload. In patients without sepsis or with low SOFA score, there was no significant difference in survival of patients irrespective of fluid overload. Conclusion Our study demonstrates that the adverse effect of fluid overload on survival is more evident in patients with sepsis or with more severe illness, and that it might not apply to patients without sepsis or with less severe illness. PMID:28196107

  16. Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition.

    Science.gov (United States)

    Davis, Sally J; Sheppard, Karen E; Anglesio, Michael S; George, Joshy; Traficante, Nadia; Fereday, Sian; Intermaggio, Maria P; Menon, Usha; Gentry-Maharaj, Aleksandra; Lubinski, Jan; Gronwald, Jacek; Pearce, Celeste Leigh; Pike, Malcolm C; Wu, Anna; Kommoss, Stefan; Pfisterer, Jacobus; du Bois, Andreas; Hilpert, Felix; Ramus, Susan J; Bowtell, David D L; Huntsman, David G; Pearson, Richard B; Simpson, Kaylene J; Campbell, Ian G; Gorringe, Kylie L

    2015-06-01

    Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterized high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas datasets were also used to assess the correlation between gene expression, patient survival, and tumor classification. In a multivariate analysis, high GAB2 expression was associated with improved overall and progression-free survival (P = 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy number gain were enriched in the AOCS C4 subgroup. High GAB2 expression correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF-04691502 and could be used as a genomic marker for identifying patients who will respond to treatments inhibiting PI3K signaling. ©2015 American Association for Cancer Research.

  17. Survival Outcomes of Whole-Pelvic Versus Prostate-Only Radiation Therapy for High-Risk Prostate Cancer Patients With Use of the National Cancer Data Base

    Energy Technology Data Exchange (ETDEWEB)

    Amini, Arya; Jones, Bernard L.; Yeh, Norman; Rusthoven, Chad G.; Armstrong, Hirotatsu; Kavanagh, Brian D., E-mail: brian.kavanagh@ucdenver.edu

    2015-12-01

    Purpose/Objectives: The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB). Methods and Materials: Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) using Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted. Results: A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002). Conclusion: In the largest reported analysis of WPRT for patients with

  18. Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    M.C. Azevedo

    2015-02-01

    Full Text Available In adults with non-promyelocytic acute myeloid leukemia (AML, high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69 received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27 received an intermediate-high-dose (<27 g/m2, and group 3 (n=35 received a very-high-dose (≥27 g/m2. Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients. The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21 and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96 than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

  19. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    Science.gov (United States)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  20. Improving cultural diversity awareness of physical therapy educators.

    Science.gov (United States)

    Lazaro, Rolando T; Umphred, Darcy A

    2007-01-01

    In a climate of increasing diversity in the population of patients requiring physical therapy (PT) services, PT educators must prepare students and future clinicians to work competently in culturally diverse environments. To be able to achieve this goal, PT educators must be culturally competent as well. The purposes of the study were to develop a valid and reliable instrument to assess cultural diversity awareness and to develop an educational workshop to improve cultural diversity awareness of PT academic and clinical educators. Phase 1 of the study involved the development of an instrument to assess cultural diversity awareness. The Cultural Diversity Awareness Questionnaire (CDAQ) was developed, validated for content, analyzed for reliability, and field and pilot tested. Results indicated that the CDAQ has favorable psychometric properties. Phase 2 of the study involved the development and implementation of the Cultural Diversity Workshop (CDW). The seminar contents and class materials were developed, validated, and implemented as a one-day cultural diversity awareness seminar. A one-group, pretest-posttest experimental design was used, with participants who completed the CDAQ before and after the workshop. Results indicated that the workshop was effective in improving cultural diversity awareness of the participants. Results of the workshop evaluation affirmed the achievement of objectives and effectiveness of the facilitator. This study provided a solid initial foundation upon which a comprehensive cultural competence program can be developed.

  1. Local recurrence after breast-conserving therapy for invasive breast cancer: high incidence in young patients and association with poor survival

    NARCIS (Netherlands)

    Elkhuizen, P. H.; van de Vijver, M. J.; Hermans, J.; Zonderland, H. M.; van de Velde, C. J.; Leer, J. W.

    1998-01-01

    PURPOSE: To study risk factors for local recurrence (LR) after breast-conserving therapy (BCT) for invasive breast cancer and, for patients with an LR, the mode of detection, location, treatment, influence of radiation therapy, and impact on survival. METHODS AND MATERIALS: 1360 patients (median age

  2. Five year biochemical recurrence free survival for intermediate risk prostate cancer after radical prostatectomy, external beam radiation therapy or permanent seed implantation.

    Science.gov (United States)

    Vassil, Andrew D; Murphy, Erin S; Reddy, Chandana A; Angermeier, Kenneth W; Altman, Andrew; Chehade, Nabil; Ulchaker, James; Klein, Eric A; Ciezki, Jay P

    2010-11-01

    To compare biochemical recurrence-free survival (bRFS) for patients with intermediate-risk prostate cancer treated by retropubic radical prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), external beam radiation therapy (RT), or permanent seed implantation (PI). Patients treated for intermediate-risk prostate cancer per National Comprehensive Cancer Network guidelines from 1996 to 2005 were studied. Variables potentially affecting bRFS were examined using univariate and multivariate Cox regression analysis. Five-year bRFS rates were calculated by actuarial methods; bRFS was calculated using Kaplan-Meier analysis. Nadir +2 definition of biochemical failure was used for RT and PI patients; a PSA ≥ 0.4 ng/mL was used for radical prostatectomy (RP) patients. Time to initiation of salvage therapy was compared for each treatment group using the Kruskal-Wallis test. Nine-hundred seventy-nine patients were analyzed with a median follow-up of 65 months. Five years bRFS rate was 82.8% for all patients (89.5% PI, 85.7% RT, 79.9% RRP, and 60.2% LRP). Patients treated by LRP had significantly worse bRFS than RT (P PI (P PSA tests per year (P PI, 47.8 RT; P PI, RT, or RRP appear to have improved 5-year bRFS and delayed salvage therapy compared with LRP. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Case of buerger's disease Improve by Gi-Chim Treatment (Leech Therapy

    Directory of Open Access Journals (Sweden)

    Kwak Byung-min

    2009-06-01

    Full Text Available Objective : The purpose of this case is to show a case of buerger's disease improved by leech therapy. Methods : The patient received Leech Therapy and Oreintal medical therapy(acupunture and herb medicine. Result : We evaluate through visual analog scale(VAS, neurophatic total symptom score(TSS, fontaine grade and picture of patient's foot. Conclusion : Leech therapy and Oriental medical therapy had a good effect on buerger's disease.

  4. Case of buerger's disease Improve by Gi-Chim Treatment (Leech Therapy)

    OpenAIRE

    Kwak Byung-min; Hong Kwon-eui

    2009-01-01

    Objective : The purpose of this case is to show a case of buerger's disease improved by leech therapy. Methods : The patient received Leech Therapy and Oreintal medical therapy(acupunture and herb medicine). Result : We evaluate through visual analog scale(VAS), neurophatic total symptom score(TSS), fontaine grade and picture of patient's foot. Conclusion : Leech therapy and Oriental medical therapy had a good effect on buerger's disease.

  5. Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xiangpeng [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Schipper, Matthew [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Kidwell, Kelley [Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Lin, Jules; Reddy, Rishindra [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Ren, Yanping [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Chang, Andrew [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Lv, Fanzhen [Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai (China); Orringer, Mark [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Spring Kong, Feng-Ming, E-mail: Fkong@gru.edu [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States)

    2014-11-01

    Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

  6. Interventions for improving adherence to ocular hypotensive therapy.

    Science.gov (United States)

    Waterman, Heather; Evans, Jennifer R; Gray, Trish A; Henson, David; Harper, Robert

    2013-04-30

    Poor adherence to therapy is a significant healthcare issue, particularly in patients with chronic disease such as open-angle glaucoma. Treatment failure may necessitate unwarranted changes of medications, increased healthcare expenditure and risk to the patient if surgical intervention is required. Simplifying eye drop regimes, providing adequate information, teaching drop instillation technique and ongoing support according to the patient need may have a positive effect on improving adherence. To summarise the effects of interventions for improving adherence to ocular hypotensive therapy in people with ocular hypertension (OHT) or glaucoma. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (June 1946 to June 2012), EMBASE (June 1980 to June 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (June 1937 to June 2012), PsycINFO (1806 to June 2012), PsycEXTRA (1908 to June 2012), Web of Science (1970 to June 2012), ZETOC (1993 to June 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 June 2012. We did not search the National Research Register (NNR) as this resource has now been now archived. We contacted pharmaceutical manufacturers to request unpublished data and searched conference proceedings for the Association for Research in Vision and Ophthalmology (ARVO), and the Annual Congress for the Royal College of Ophthalmologists (RCO). We included randomised controlled trials (RCTs) and quasi-RCTs that compared interventions to improve adherence to ocular hypotensive therapy

  7. Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs.

    Science.gov (United States)

    Liu, Rui; Hu, Xiao-Hang; Wang, Shu-Ming; Guo, Si-Jia; Li, Zong-Yu; Bai, Xiao-Dong; Zhou, Fang-Qiang; Hu, Sen

    2016-06-01

    To investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. Forty dogs subjected to severe burn were randomly divided into four groups (n=10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. Hemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). Pyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  8. Induction chemotherapy for T3N0M0 non-small-cell lung cancer increases the rate of complete resection but does not confer improved survival.

    Science.gov (United States)

    Anderson, Kevin L; Mulvihill, Michael S; Yerokun, Babatunde A; Speicher, Paul J; D'Amico, Thomas A; Tong, Betty C; Berry, Mark F; Hartwig, Matthew G

    2017-08-01

    The objective of this study was to evaluate outcomes of induction therapy prior to an operation in patients with cT3 non-small-cell lung cancer (NSCLC). Patients diagnosed with cT3N0M0 NSCLC from 2006 to 2011 in the National Cancer Database who were treated with lobectomy or pneumonectomy were stratified by treatment strategy: an operation first versus induction chemotherapy. Propensity scores were developed and matched cohorts were generated. Short-term outcomes included margin status, 30- and 90-day mortality rates, readmission and length of stay. Survival analyses using Kaplan-Meier methods were performed on both the unadjusted and propensity matched cohorts. A total of 3791 cT3N0M0 patients were identified for inclusion, of which 580 (15%) were treated with induction chemotherapy. Prior to adjustment, patients treated with induction chemotherapy were younger, had a higher comorbidity burden and were more likely to have private insurance (all P  induction chemotherapy were more likely to subsequently undergo an open procedure (87.3 vs 77.8%, P  = 0.005). These patients were more likely to obtain R0 resection (93.1% vs 90.0%, P  = 0.04) and were thereby less likely to have positive margins at the time of resection (6.9% vs 10.0%, P  = 0.03). Patients who received induction therapy had higher rates of 90-day mortality (6.6% vs 3.4%) but there was no difference in long-term survival between the groups. Despite yielding increased rates of R0 resection, induction chemotherapy for cT3N0M0 NSCLC is not associated with improved survival and should not be considered routinely. Further studies are warranted to elucidate cohorts that may benefit from induction therapy.

  9. Clinical audit training improves undergraduates' performance in root canal therapy.

    Science.gov (United States)

    Fong, J Y M; Tan, V J H; Lee, J R; Tong, Z G M; Foong, Y K; Tan, J M E; Parolia, A; Pau, A

    2017-12-20

    To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates. Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test. Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001). Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008)

    DEFF Research Database (Denmark)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

    2017-01-01

    for intervention trials to identify clinically applicable strategies for individualised drug dosing to increase DNA-TGN concentration, and randomised studies to investigate whether such strategies improve cure rates compared with current dose adjustments based on white blood cell counts. FUNDING: Danish Cancer...... whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. METHODS: In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we...... of 1·5-3·0 × 10(9) cells per L). We measured DNA-TGN and erythrocyte concentrations of TGN nucleotides, methylated mercaptopurine metabolites, and methotrexate polyglutamates. The primary objective was the association of DNA-TGN concentrations and 6-mercaptopurine and methotrexate metabolites...

  11. Effects of a selective regimen of dry cow therapy on intramammary infection and on antibiotic sensitivity of surviving pathogens.

    Science.gov (United States)

    Schultze, W D

    1983-04-01

    Selective dry cow therapy with 1 million U of procaine penicillin G and 1 g of dihydrostreptomycin in a slow-release base was administered to all quarters of cows currently infected or treated for mastitis in the previous lactation. All other cows in the herd that were dried off during the experimental period were left untreated. Milk samples were cultured for detection of intramammary infection at drying off, 1 wk later (at time of treatment), and after next calving from 227 treated and 143 untreated cows. Isolants were tested for sensitivity to 12 antibiotics including penicillin and streptomycin. Although treatment resulted in clearance of Staphylococcus aureus, Staphylococcus epidermidis, streptococci other than agalactiae, and coliforms from 78, 82, 88, and 87% of infected glands, the net effect on udder health of the herd was a gain of 1.4% in infected quarters. Incidences of new infection in the early dry period (1 wk) were 18.1 and 12.3% among treated and untreated cows. Therapy failed to control new infection in the late dry and peripartum periods; incidence was about 18% of quarters among both long and short dry periods. Among 46 instances of apparent survival of an intramammary pathogen through a treated dry period, 7 of 10 strains previously sensitive to streptomycin became resistant and 8 of 10 strains previously sensitive to penicillin became resistant. The surviving pathogen population was not large enough to be considered a threat to herd udder health in the next lactation.

  12. The Evaluation of More Lymph Nodes in Colon Cancer Is Associated with Improved Survival in Patients of All Ages.

    Directory of Open Access Journals (Sweden)

    Wouter B Aan de Stegge

    Full Text Available Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of ≥ 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer.In a population-based cohort study, all patients (N = 41,074 diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival.Over an eight years time period there was a 41.2% increase in patients with ≥ 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%. After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which ≥ 12 lymph nodes were removed compared to patients with 75: HR: 0.734 (95% CI, 0.700-0.771 and relative survival ( 75: RER: 0.621 (95% CI, 0.567-0.681 in all three age groups.The removal of ≥ 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification.

  13. Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function

    Directory of Open Access Journals (Sweden)

    Pasque Michael K

    2007-01-01

    Full Text Available Abstract Objective Patients with severe left ventricular (LV dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF ≤25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+ in the post -operative period was compared to those without ICD (ICD-. Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5% patients received an ICD with a median of 2 (+/-2 years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT. There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.

  14. Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

    Science.gov (United States)

    Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

    2017-06-15

    The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (Pbrain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society. © 2017 American Cancer Society.

  15. Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor T cells.

    Science.gov (United States)

    Fraietta, Joseph A; Schwab, Robert D; Maus, Marcela V

    2016-04-01

    Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and redirecting the immune system against cancer. This review will briefly summarize T-cell therapies in development for CLL disease. We discuss the role of T-cell function and phenotype, T-cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Infused Therapy and Survival in Older Patients Diagnosed with Metastatic Breast Cancer who Received Trastuzumab

    OpenAIRE

    Griffiths, Robert I.; Lalla, Deepa; Robert J. Herbert; Doan, Justin F; Brammer, Melissa G; Danese, Mark D.

    2011-01-01

    We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [C...

  17. Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival.

    Science.gov (United States)

    Riaz, Ahsun; Ryu, Robert K; Kulik, Laura M; Mulcahy, Mary F; Lewandowski, Robert J; Minocha, Jeet; Ibrahim, Saad M; Sato, Kent T; Baker, Talia; Miller, Frank H; Newman, Steven; Omary, Reed; Abecassis, Michael; Benson, Al B; Salem, Riad

    2009-12-01

    Alpha-fetoprotein (AFP) is considered to be an indicator of tumor activity in hepatocellular carcinoma (HCC). We present a novel correlation of AFP response to radiologic response, time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) in patients treated with locoregional therapies. Four hundred sixty-three patients with HCC were treated with chemoembolization or radioembolization at our institution. One hundred twenty-five patients with baseline AFP higher than 200 ng/mL were studied for this analysis. AFP response was defined as more than 50% decrease from baseline. One hundred nineteen patients with follow-up imaging were studied for the AFP imaging correlation analysis. AFP response was correlated to radiologic response, TTP, PFS, and OS. Multivariate analyses were performed. Eighty-one patients (65%) showed AFP response. AFP response was seen in 26 (55%) of 47 and 55 (70%) of 78 of patients treated with chemoembolization and radioembolization, respectively (P = .12). WHO response was seen in 41 (53%) of 77 and 10 (24%) of 42 of AFP responders and nonresponders, respectively (P = .002). The hazard ratio (HR) for TTP in AFP nonresponders compared with responders was 2.8 (95% CI, 1.5 to 5.1). The HR for PFS was 4.2 (95% CI, 2.4 to 7.2) in AFP nonresponders compared with responders. The HR for OS in AFP nonresponders compared with responders was 5.5 (95% CI, 3.1 to 9.9) and 2.7 (95% CI, 1.6 to 4.6) on univariate and multivariate analyses, respectively. The data presented support the use of AFP response seen after locoregional therapy as an ancillary method of assessing tumor response and survival, as well as an early objective screening tool for progression by imaging.

  18. Survival Mediterranean Style: Lifestyle Changes to Improve the Health of the US Fire Service

    Directory of Open Access Journals (Sweden)

    Maria Korre

    2017-12-01

    Full Text Available Cardiovascular disease (CVD causes almost half of all on-duty deaths in US firefighters and is an important and costly cause of morbidity. In addition, cancer is a growing health concern in this population. Obesity and obesity-associated, cardiometabolic risk clustering are major, modifiable risk factors for fire service CVD and cancer risk. The Mediterranean diet (MedDiet is proven effective in primary and secondary CVD prevention. It is also associated with a decreased risk of cancer and other chronic diseases. Moreover, it can be adapted into successful workplace interventions. Emerging data from our group regarding the US Fire Service show that greater compliance with the MedDiet is associated with improved CVD risk profiles and less weight gain among career firefighters. Moreover, the fact that career firefighters take a considerable number of meals communally on the job also represents an excellent opportunity for a workplace Mediterranean Diet Nutritional Intervention (MDNI. The devastating effects of obesity, CVD, and cancer on the US fire service are recognized, but currently few effective preventive programs exist. The consistently positive health benefits from following a MedDiet and promising preliminary data in the fire service justify translational research to determine the most effective means of delivering MDNIs to US firefighters. Therefore, a high priority should be assigned to efforts, which can help further disseminate and implement our program of novel behavior change strategies, “Survival Mediterranean Style,” throughout the US fire service and eventually to other occupations.

  19. Glaucocalyxin A improves survival in bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Yang, Fei; Cao, Yiren; Zhang, Jian; You, Tao; Zhu, Li

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with unclear etiology and poor prognosis. Despite numerous studies on the pathogenesis of IPF, only scant treatment options are available for the management of IPF. Glaucocalyxin A (GLA), an ent-Kaurane diterpenoid, has been demonstrated to exert anti-inflammatory, anti-neoplastic and anti-platelet activities. In this study, we evaluated the role of GLA as an anti-fibrotic agent in bleomycin-induced pulmonary fibrosis in mice and investigated the underlying mechanisms by which GLA attenuates lung fibrosis. Intraperitoneal administration of GLA (10 mg/kg) significantly reduced collagen deposition and hydroxyproline content in mouse lungs treated with bleomycin. Importantly, GLA significantly improved survival in bleomycin treated mice. In addition, GLA reduced weight loss in mice that reflects cachexia due to pulmonary fibrosis. Mechanistically, GLA alleviated the infiltration of macrophages and neutrophils in lungs, attenuated the increases of proinflammatory cytokines in lung tissue and bronchoalveolar lavage fluid, and inhibited the activation of NF-κB in fibrotic lungs induced by bleomycin. These results provide evidence that GLA can effectively ameliorate pulmonary fibrosis through the antagonism of leukocyte infiltration and proinflammatory cytokine production, suggesting that it may become a potential anti-fibrotic agent in IPF management. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Lipid and other management to improve arterial disease and survival in end stage renal disease.

    Science.gov (United States)

    Dimmitt, Simon B; Martin, Jennifer H

    2017-03-01

    Arterial disease is common in advancing renal failure, culminating in myocardial infarction with cardiac failure, strokes and peripheral and renal artery disease. Attention to cardiac and arterial disease may slow deterioration of renal function. Management of risk factors can reduce these sequelae. Areas covered: Modifiable risk factors for arterial disease and relevant pharmacotherapies. Expert opinion: Cardiovascular disease is the biggest killer in renal failure. Statins are viewed as essential in symptomatic coronary disease and have been shown in non-renal patients to improve survival after myocardial infarction. Cochrane recommends statins in renal failure but not in end stage renal disease or transplant patients. Large well powered clinical trials focussed specifically on renal patients failed to demonstrate cardiovascular outcome or mortality benefits of statins when compared to placebo. Other lipid lowering pharmacotherapies are weaker and adverse effects may account for the absence of net clinical benefit in non-renal patients in published clinical trials. Patients should be started on a statin after myocardial infarction, regardless of lipid levels, but the risk of adverse effects in advanced renal failure with its comorbidities predicates employing only essential doses. Optimal antihypertensive and antithrombotic pharmacotherapy are also priorities.

  1. Supercritical carbon dioxide interpolymer complexes improve survival of B. longum Bb-46 in simulated gastrointestinal fluids.

    Science.gov (United States)

    Thantsha, Mapitsi S; Cloete, Thomas E; Moolman, Francis S; Labuschagne, Philip W

    2009-01-31

    Gastric acidity is the main factor affecting viability of probiotics in the gastrointestinal tract (GIT). This study investigated the survival in simulated gastrointestinal fluids of Bifidobacterium longum Bb-46 encapsulated in interpolymer complexes formed in supercritical carbon dioxide (scCO(2)). Bacteria were exposed sequentially to simulated gastric fluid (SGF, pH 2) for 2 h and simulated intestinal fluid (SIF, pH 6.8) for 6 or 24 h. Total encapsulated bacteria were determined by suspending 1 g of product in SIF for 6 h at 37 degrees C prior to plating out. Plates were incubated anaerobically at 37 degrees C for 72 h. The interpolymer complex displayed pH-responsive release properties, with little to no release in SGF and substantial release in SIF. There was a limited reduction in viable counts at the end of exposure period due to encapsulation. Protection efficiency of the interpolymer complex was improved by addition of glyceryl monostearate (GMS). Gelatine capsules delayed release of bacteria from the interpolymer complex thus minimizing time of exposure to the detrimental conditions. Use of poly(caprolactone) (PCL), ethylene oxide-propylene oxide triblock copolymer (PEO-PPO-PEO) decreased the protection efficiency of the matrix. Interpolymer complex encapsulation showed potential for protection of probiotics and therefore for application in food and pharmaceuticals.

  2. Deficiency of Bid protein reduces sepsis-induced apoptosis and inflammation, while improving septic survival.

    Science.gov (United States)

    Chung, Chun-Shiang; Venet, Fabienne; Chen, Yaping; Jones, Leslie N; Wilson, Douglas C; Ayala, Carol A; Ayala, Alfred

    2010-08-01

    Increased apoptotic cell death is believed to play a pathological role in patients with sepsis and experimental animals. Apoptosis can be induced by either a cell death receptor (extrinsic) or a mitochondrial (intrinsic) pathway. Bid, a proapoptotic member of the Bcl-2 family, is thought to mediate the cross talk between the extrinsic and intrinsic pathways of apoptosis; however, little is known about the action of Bid in the development of apoptosis and organ-specific tissue damage/cell death as seen in polymicrobial sepsis. Our results show that after the onset of sepsis, tBid (the active form of Bid) is significantly increased in mitochondrial fractions of the thymus, spleen, Peyer patches, and liver, and that Fas or FasL deficiency blocks Bid activation in various tissues after septic challenge. Increased Bid activation is correlated with increased active caspase-3, caspase-9, and apoptosis during sepsis. Bid-deficient mice exhibit significantly reduced apoptosis in the thymus, spleen, and Peyer patches compared with background mice after sepsis. Furthermore, Bid-deficient mice had significantly reduced systemic and local inflammatory cytokine levels and improved survival after sepsis. These data support not only the contribution of Bid to sepsis-induced apoptosis and the onset of septic morbidity/mortality, but also the existence of a bridge between extrinsic apoptotic signals, e.g., FasL:Fas, TNF:TNFR, and so on, and the intrinsic mitochondrial pathway via Bid-tBid activation during sepsis.

  3. Incorporating movement patterns to improve survival estimates for juvenile bull trout

    Science.gov (United States)

    Bowerman, Tracy; Budy, Phaedra

    2012-01-01

    Populations of many fish species are sensitive to changes in vital rates during early life stages, but our understanding of the factors affecting growth, survival, and movement patterns is often extremely limited for juvenile fish. These critical information gaps are particularly evident for bull trout Salvelinus confluentus, a threatened Pacific Northwest char. We combined several active and passive mark–recapture and resight techniques to assess migration rates and estimate survival for juvenile bull trout (70–170 mm total length). We evaluated the relative performance of multiple survival estimation techniques by comparing results from a common Cormack–Jolly–Seber (CJS) model, the less widely used Barker model, and a simple return rate (an index of survival). Juvenile bull trout of all sizes emigrated from their natal habitat throughout the year, and thereafter migrated up to 50 km downstream. With the CJS model, high emigration rates led to an extreme underestimate of apparent survival, a combined estimate of site fidelity and survival. In contrast, the Barker model, which allows survival and emigration to be modeled as separate parameters, produced estimates of survival that were much less biased than the return rate. Estimates of age-class-specific annual survival from the Barker model based on all available data were 0.218±0.028 (estimate±SE) for age-1 bull trout and 0.231±0.065 for age-2 bull trout. This research demonstrates the importance of incorporating movement patterns into survival analyses, and we provide one of the first field-based estimates of juvenile bull trout annual survival in relatively pristine rearing conditions. These estimates can provide a baseline for comparison with future studies in more impacted systems and will help managers develop reliable stage-structured population models to evaluate future recovery strategies.

  4. Age-dependent improvement in median and long-term survival in unselected population-based Nordic registries of patients with synchronous metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Sorbye, H; Cvancarova, M; Qvortrup, C

    2013-01-01

    In metastatic colorectal cancer (mCRC) trials, median survival has increased from 6 months to above 20 months during the previous decades. Uncertainty exists in how this survival improvement has translated to the general mCRC population.......In metastatic colorectal cancer (mCRC) trials, median survival has increased from 6 months to above 20 months during the previous decades. Uncertainty exists in how this survival improvement has translated to the general mCRC population....

  5. Extracorporeal life support with left ventricular decompression-improved survival in severe cardiogenic shock: results from a retrospective study.

    Science.gov (United States)

    Schmack, Bastian; Seppelt, Philipp; Weymann, Alexander; Alt, Christina; Farag, Mina; Arif, Rawa; Doesch, Andreas O; Raake, Philip W; Kallenbach, Klaus; Mansur, Ashham; Popov, Aron-Frederik; Karck, Matthias; Ruhparwar, Arjang

    2017-01-01

    Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression. Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with (n = 20, 41.7%) or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS) integrated left ventricular vent in our retrospective single centre trial. Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14), bridge to transplant in 10.4% (n = 5) and bridge to recovery in 8.3% (n = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent). Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival. ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.

  6. Cognitive behavioral therapy in combination with systemic family therapy improves mild to moderate postpartum depression

    Directory of Open Access Journals (Sweden)

    Yongmei Hou

    2014-03-01

    Full Text Available Objective: To explore the effect of cognitive behavioral therapy (CBT in combination with systemic family therapy (SFT on mild to moderate postpartum depression and sleep quality. Methods: 249 primiparous women with mild to moderate postpartum depression were recruited and randomly assigned to a control group (n=128, which received conventional postpartum care, or to a psychological intervention group (n=121, which received conventional postpartum care combined with psychological intervention. The Edinburgh Postnatal Depression Scale (EPDS and Pittsburgh Sleep Quality Index (PSQI were employed to evaluate depression and sleep quality, respectively. Results: 104 patients in the intervention group and 109 in the control group completed the study. After intervention, the EPDS score, PSQI score, sleep quality score, sleep latency score, sleep duration score, habitual sleep efficiency score, sleep disturbance score, and daytime dysfunction score were significantly lower in the intervention group than in the control group. The EPDS and PSQI scores of each group at different time points after intervention were markedly decreased compared with those before intervention, and the reduction in the intervention group was more evident than that in the control group. Conclusion: CBT in combination with SFT can improve depression and sleep quality in patients with mild to moderate postpartum depression.

  7. Clinical utility of far-infrared therapy for improvement of vascular access blood flow and pain control in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Soo Jeong Choi

    2016-03-01

    Conclusion: FIR therapy improved needling pain. Although FIR therapy improved Qa, the unassisted patency was not different compared with the control. A larger and multicenter study is needed to evaluate the effect of FIR therapy.