tbuckley/cabot-search huggingface dataset:
Abstract P164: Urban-rural Disparities Amongst Heart Failure Patients With Reduced Ejection Fraction
Authors: Sherrie Khadanga, Daniel N Silverman, Timothy B Plante, Charles Cubberly, Johannes Steiner
Journal: Circulation (2020)

Intro: Differences in health care delivery between urban and rural populations have been described, but the extent to which this impacts treatment and outcomes in patients with heart failure with reduced ejection fraction (HFrEF) within a large, rural HF referral network has not been evaluated to date. Objective: To describe differences in guideline directed medical therapy (GDMT) usage and cardiovascular (CV) mortality in urban vs rural dwelling individuals with HFrEF in Vermont. Methods: A retrospective analysis was performed on adult HFrEF patients residing in Vermont referred to University of Vermont Medical Center between January 1, 2015-2017. The study included all patients with a documented EF &lt; 35% on echo. Demographics, risk factors, use of GDMT, and all-cause CV mortality were obtained. Urban and rural designations were based on the ZIP code version of the Rural-Urban Commuting Area (RUCA) classification system. Poisson regression analysis was used to compare the relative risk for mortality and use of GDMT by rurality. Results: 838 patients were identified (mean age 71.4 + 12.9 years old; 66.5% male) and divided into 3 RUCA groups (urban, rural, isolated). Adjusting for age, sex, hypertension, diabetes mellitus, atrial fibrillation and smoking status, no difference was seen in GDMT (table 1) between urban and rural patients (relative risk [RR], 1.03; 95% CI, 0.64-1.67). Urban patients were less likely than isolated patients to use GDT (RR, 0.75; 95% CI 0.52-1.08). There was a CV mortality benefit for those in rural (RR, 0.50; 95% CI 0.34-0.73) or isolated areas (RR, 0.74; 95% CI 0.62-0.89) compared to those in urban areas. Conclusion: While GDMT reduces morbidity and mortality in HFrEF patients, it was underutilized throughout Vermont. Findings from this state-wide cohort of decreased CV mortality in rural and isolated areas are contrary to prior studies. This finding highlights the unique socioeconomic environment of Northern New England and has important implications for CHF management and resource allocation.
ACTR-20. EFFICACY OF INITIAL TEMOZOLOMIDE FOR HIGH-RISK LOW GRADE GLIOMAS IN A PHASE II AINO (ITALIAN ASSOCIATION FOR NEURO-ONCOLOGY) STUDY: A POST-HOC ANALYSIS WITHIN MOLECULAR SUBGROUPS OF WHO 2016
Authors: Roberta Rudà, Alessia Pellerino, Andrea Pace, Carmine Maria Carapella, Cristina Dealis, Manuela Caroli, Marina Faedi, Lorenzo Bello, Enrica Migliore, Giulia Marchese, Luca Bertero, Paola Cassoni, Riccardo Soffietti
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The optimal management of high risk WHO grade II gliomas after surgery is still debated. The efficacy of initial temozolomide to delay radiotherapy and risk of cognitive defects could vary across the molecular subgroups of WHO 2016, but information on this issue are lacking. PATIENTS AND METHODS A post-hoc analysis has been performed on a cohort of high risk WHO grade II gliomas, who received initial temozolomide alone in phase II multicenter study, with the objective of re-evaluating the long-term results across the different molecular subgroups of the WHO 2016 classification. The primary endpoint of the study, carried out between 2007 and 2010, was response rate according to RANO, being seizure response, PFS and OS secondary endpoints. RESULTS Response rate (partial and minor responses) among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency &gt;50% was observed in 87% patients and a seizure freedom in 72%. The probability of seizure reduction &gt;50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were all significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Of patients who did not recur or delay radiotherapy at recurrence for a median follow-up of 8.2 years, 67% and 59%, respectively, were oligodendrogliomas IDH-mutant and 1p/19q codeleted. CONCLUSIONS The post-hoc analysis of this phase II trial suggests that the beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery, especially when suffering from pharmacoresistant seizures, could receive temozolomide as initial treatment with radiotherapy and chemotherapy at recurrence. The trial was registered with EU Clinical Trials Register, EudraCT n. 2007/000386-38.
Are Pharmaceutical Companies Earning Too Much?
Authors: David M. Cutler
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020
Authors: John A. Thompson, Bryan J. Schneider, Julie Brahmer, Stephanie Andrews, Philippe Armand, Shailender Bhatia, Lihua E. Budde, Luciano Costa, Marianne Davies, David Dunnington, Marc S. Ernstoff, Matthew Frigault, Benjamin H. Kaffenberger, Matthew Lunning, Suzanne McGettigan, Jordan McPherson, Nisha A. Mohindra, Jarushka Naidoo, Anthony J. Olszanski, Olalekan Oluwole, Sandip P. Patel, Nathan Pennell, Sunil Reddy, Mabel Ryder, Bianca Santomasso, Scott Shofer, Jeffrey A. Sosman, Yinghong Wang, Ryan M. Weight, Alyse Johnson-Chilla, Griselda Zuccarino-Catania, Anita Engh
Journal: Journal of the National Comprehensive Cancer Network (2020)

The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor–related diarrhea/colitis and cardiovascular irAEs.
Coroner to ask GMC to check vulnerability of doctors it investigates
Authors: Clare Dyer
Journal: BMJ (2020)

A coroner is to write to the UK General Medical Council asking it to reform its procedures after a consultant anaesthetist killed himself within hours of receiving an email telling him he was being investigated.

Sridharan Suresh, 50, a consultant at North Tees and Hartlepool NHS Foundation Trust, drowned himself in the River Tees on 2 May 2018. That day he had received an emailed letter from the GMC telling him that his NHS and private employers would all be notified of allegations that he had inappropriately touched a teenage girl and would soon be called before an interim orders tribunal.

In April 2018 Suresh gave midazolam to a 15 year old girl to sedate her for a dental procedure. Among the occasional side effects of midazolam are confusion, hallucinations, and unusual thoughts or behaviour.

The girl accused him of touching her …
A New Therapeutic Era for Metastatic Renal Cell Carcinoma
Authors: Nirmish Singla
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Use of Disposable Perioperative Jackets and Surgical Site Infections
Authors: Cassandra L. Thiel, Jodi D. Sherman, Harriet W. Hopf
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Role of multivisceral cytoreductive surgery in patients (pts) with recurrent ovarian cancer (ROC): Who will not benefit from radical tumor debulking?
Authors: D. Koensgen, A. Mustea, H. Weidemann, U. Neumann, P. Neuhaus, C. Pirvulescu, D. Kozo, G. Oskay-Oezcelik, W. Lichtenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2007)

16036 Background: Despite improvement in surgery and adjuvant chemotherapy most pts with ovarian cancer (OC) experience a relapse within 2 years after first diagnosis. For primary OC a standard concensus on optimal staging and surgical guidelines is established. The role of radical tumor debulking surgery in ROC is not clearly defined. Aim of this study was to analyze clinical parameters for prediction of operability and impact on overall survival in ROC. Methods: Within the framework of the international project “Tumor bank Ovarian Cancer“ (TOC) a systematic prospective surgical and histomorphological tumor documentation for ROC was performed. Results: Between september 2000 and december 2006, 307 multivisceral operations on 254 pts with ROC were performed consecutively in our department. Median age was 55 years (19–83), median follow-up 15 months (1–75). 34.8% of pts experienced first relapse of OC. Overall, 96.3% of pts received a platinum-based first-line chemotherapy, whereas 73.4% were platinum sensitive. In 55% of pts first relapse surgery was performed. In 41.4% of pts complete macroscopic tumor resection was achieved, associated with a significantly better recurrence-free (median 20.6 vs 13.2, p=0.001) and overall survival (median 42 vs 12 months, p&lt;0.001) compared to pts with any postoperative residual tumor. In multivariate analysis, complete tumor resection was associated with the absence of tumor burden in the upper abdomen (p=0.001) and absence of ascites (p=0.05). Prognostic factors for postoperative survival were: tumor resection (0 cm vs &gt; 0 cm, p&lt;0.001), intraoperative volume of ascites (0 ml vs &gt; 0 ml, p=0.006) and response to platinum-based first-line therapy (platinum sensitive vs platinum-resistant, p=0.006). Conclusions: Radical tumor debulking in patients with ROC is associated with a low postoperative morbidity and mortality. Complete mascroscopic tumor resection is correlated with a significant better long-term prognosis and influenced by tumor spread and presence of ascites. Pts with ROC will not benefit from multivisceral cytoreductive surgery in case of platinum resistance to first-line chemotherapy, presence of intraoperative ascites and postoperative residual tumor. No significant financial relationships to disclose.
USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2
Authors: Zeng Cai, Meng-Xin Zhang, Zhen Tang, Qiang Zhang, Jing Ye, Tian-Chen Xiong, Zhi-Dong Zhang, Bo Zhong
Journal: The Journal of Experimental Medicine (2020)

USP22 is a cytoplasmic and nuclear deubiquitinating enzyme, and the functions of cytoplasmic USP22 are unclear. Here, we discovered that cytoplasmic USP22 promoted nuclear translocation of IRF3 by deubiquitianting and stabilizing KPNA2 after viral infection. Viral infection induced USP22-IRF3 association in the cytoplasm in a KPNA2-depedent manner, and knockdown or knockout of USP22 or KPNA2 impaired IRF3 nuclear translocation and expression of downstream genes after viral infection. Consistently, Cre-ER Usp22fl/fl or Lyz2-Cre Usp22fl/fl mice produced decreased levels of type I IFNs after viral infection and exhibited increased susceptibility to lethal viral infection compared with the respective control littermates. Mechanistically, USP22 deubiquitinated and stabilized KPNA2 after viral infection to facilitate efficient nuclear translocation of IRF3. Reconstitution of KPNA2 into USP22 knockout cells restored virus-triggered nuclear translocation of IRF3 and cellular antiviral responses. These findings define a previously unknown function of cytoplasmic USP22 and establish a mechanistic link between USP22 and IRF3 nuclear translocation that expands potential therapeutic strategies for infectious diseases.
The correlation of perfusion-weighted MRI with VEGF in resected pancreatic cancer
Authors: M. Ueno, S. Ohkawa, T. Niwa, T. Yoshida, S. Morinaga, Y. Sugimasa
Journal: Journal of Clinical Oncology (2007)

15092 Background: Perfusion-weighted magnetic resonance imaging (MRI) can detect angiogenesis in brain malignant tumors, and as angiogenesis increases in various carcinomas the prognosis becomes worse. We evaluated the usefulness of perfusion-weighted MRI as a prognostic predictor in pancreatic cancer patients in ASCO 2005. This time, we examined the correlation of perfusion-weighted MRI with vascular endothelial growth factor (VEGF) and microvessel density (MVD) immunohistochemically in resected pancreatic cancer patients. Methods: Perfusion-weighted MRI was performed on 14 consecutive resected pancreatic cancer cases. Imaging acquisition was continually repeated with echo-planar sequence every 2 sec for 2 min with bolus injection of gadolinium. We made the time intensity curve of perfusion-weighted images and calculated the signal ratio (SR). We investigated the expressions of VEGF and CD34 (for calculating MVD) immunohistochemically. MVD was assessed per 200x field. We compared SR with VEGF expression and MVD. The correlations were evaluated with t-test. Results: All cases showed transient decreases in tumor signal intensity (SR range: 18.2–66.0%) in perfusion-weighted MRI. The expressions of VEGF were divided into two groups (high and low expression). MVD ranged from 6 to 34 and was divided into two groups at the median value. The correlation of SR in perfusion-weighted MRI with VEGF expression was significant (p=0.002). High SR correlated with high VEGF expression. The correlation of SR in perfusion-weighted MRI with MVD was not significant. Conclusions: Perfusion- weighted MRI correlated with VEGF expression in pancreatic cancer. No significant financial relationships to disclose.
Abstract 26: Polygenic Risk Score for Obesity Modifies Associations of Proinflammatory Diets With Obesity, Long-term Weight Gain, and Cardiovascular Disease Risk: The Utilization of Polygenic Prediction in 3 US Prospective Cohorts
Authors: Jun Li, Jie Hu, Dong Hoon Lee, Wonil Chung, Baoshan Ma, Fred Tabung, Marta Guasch, Edward Giovannucci, Joann E Manson, Walter Willett, Frank B Hu, Liming Liang
Journal: Circulation (2020)

Background: Individuals predisposed to higher genetic risk of obesity may need early dietary interventions to prevent obesity and its comorbidities. Hypothesis: Proinflammatory diets may interact with genetic background to modify risks of obesity, long-term weight gain, and cardiovascular disease (CVD). Methods: We prospectively followed 16 281 and 11 832 women in the Nurses’ Health Study I and II, and 10 172 men in Health Professionals Follow-up Study, with available genetic data, for up to 28 years. Diet and weight were assessed every 4 years. Dietary inflammatory potential was assessed by an empirical dietary inflammatory pattern (EDIP) score pre-defined based on associations of foods with inflammatory markers. Polygenic risk scores (PRS) of body mass index (BMI), waist-hip ratio, and body fat mass, developed based on genome-wide association data of 9 million variants in 389 972 UK Biobank participants using LDpred, were applied to characterize genetic predispositions to obesity, central obesity, and adiposity. Results: All 3 PRS were highly predictive for BMI ( Fig. A ). In pooled multivariable analyses, higher EDIP scores were associated with a higher BMI, with the association 2-3 folds stronger comparing participants in the highest 10% to the lowest 10% of genetic risk of obesity/adiposity ( P interaction ≤0.001; Fig. B ). The positive association between EDIP and CVD incidence was 1.6-fold stronger in participants at a higher genetic risk of central obesity ( P interaction =0.04; Fig. C ). In addition, an increase in EDIP scores was associated with a greater long-term weight gain, while a reduction in EDIP was associated with a greater weight loss, comparing participants in the highest 10% of genetic risk to those at lower risks, among participants aged &lt;65 years but not above ( P interaction &lt;0.005; Fig. D ). Conclusions: Polygenic background modifies associations of proinflammatory diets with obesity, long-term weight change, and CVD risk. PRS may be useful tools to identify individuals in need for early dietary interventions.
A phase I safety and pharmacokinetic study of apomab, a human DR5 agonist antibody, in patients with advanced cancer
Authors: D. Camidge, R. S. Herbst, M. Gordon, S. Eckhardt, R. Kurzroc, B. Durbin, J. Ing, J. Ling, J. Sager, D. Mendelson
Journal: Journal of Clinical Oncology (2007)

3582 Background: Apomab, a fully human affinity-matured IgG1 monoclonal antibody, is a DR5 pro-apoptotic receptor agonist that triggers the extrinsic pathway of apoptosis. DR5 is expressed both on malignant and normal cells; however, pre-clinical data indicate that DR5 activation stimulates apoptosis predominantly in malignant cells. This first-in-human study assessed the safety, pharmacokinetics (PK) and any early evidence of anti-cancer efficacy of Apomab. Methods: Patients with advanced treatment-refractory solid tumors received Apomab IV on Day1 (cycle 1 = 28 days, cycles 2–8 = 14 days) at 1, 4, 10, 15, or 20 mg/kg (stage 1); with cohort expansion at 10 mg/kg or the MTD (if lower) every 14 days (stage 2). Tumor assessments were made after 2, 4 and 8 cycles. Therapy continued past 2 cycles as permitted by on-going evidence of benefit, until disease progression or unacceptable toxicity occurred. Results: 26 patients ECOG PS â‰¤1 have been enrolled and treated through 20 mg/kg. The 20 (8M, 12F) with confirmed data (up to 15mg/kg) received a median of 2 cycles (range 1–8). All dose levels have been tolerable (&lt;33% dose limiting (Grade 3 drug-related) toxicities in the first 2 doses + 24 hours). 2 disparate DLTs occurred among 11 patients treated at 10 mg/kg. 1 patient (ovarian cancer) had asymptomatic transaminitis (ALT and AST) at C1D5, reaching Grade 3 by D29, received no further Apomab with resolution by D53. 1 patient (colorectal cancer) had a pulmonary embolism C1D4. Six patients completed at least 4 cycles of Apomab, 4 completed 8 cycles. No objective responses have been seen but at 10 mg/kg 1 patient (appendiceal cancer) remains on study (stable disease) past 8 cycles and 1 patient (colorectal cancer) had 28% shrinkage of target lesions and symptomatic improvement after 4 cycles. PK of Apomab is dose-proportional at 1 and 4 mg/kg with a typical IgG1 half-life of ∼15–20 days. AUC/Css,min concentrations at &gt;4 mg/kg are greater than those displaying activity in preclinical models. No HAHA responses have been seen to date. Conclusions: Apomab is well tolerated with a minor response seen in a colorectal cancer patient. Enrollment is continuing at 10mg/kg. Further safety and efficacy data will be presented. No significant financial relationships to disclose.
A phase I multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer
Authors: S. Ohkawa, A. Amano, M. Ueno, K. Miyakawa, K. Sugimori, K. Tanaka, M. Kida
Journal: Journal of Clinical Oncology (2006)

14047 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 and report the results of the phase I trial. Methods: The subjects had unresectable pancreatic ductal cancer. The method of administration was single administration of GEM on the first day of the week from Level 1 to Level 4 at 400 to 1000 mg/m 2 , with concurrent administration of S-1 at 40 to 100 mg/day × 7 days, repeated every other week as a collaborative trial conducted at 3 facilities. The purpose was to determine the optimal dose with adverse events as an indicator. Results: Eighteen patients were enrolled (3 each at Levels 1, 2, 3 and 4’, 6 at Level 4). Average age was 60.9 years (38 - 71 years). There was no dose limiting toxicity (DLT) up to Level 3. Level 4 was the maximum tolerated dose since DLT was observed in 4/6 patients (mucositis 2, rash 1, anorexia 1), and no DLT was observed in 3 additional patients at Level 4’. The resulting recommended dose was Level 4 (GEM 1000 mg/m 2 , S-1 100 mg/day). For reference, partial response was observed in 5 patients, and median survival time at this stage is 336±39 days. Conclusions: The recommended dosage of GEM + S-1 combined chemotherapy for unresectable advanced pancreatic cancer was determined in a phase I trial. We intend to proceed to a phase II trial. No significant financial relationships to disclose.