tbuckley/cabot-search huggingface dataset:
Genomic alterations to refine prognostication of patients with metastatic renal cell carcinoma.
Authors: Dominick Bosse, Wanling Xie, Aly-Khan A. Lalani, Guillermo de Velasco, Martin Henner Voss, Nizar M. Tannir, Pheroze Tamboli, Leonard Joseph Appleman, Kimryn Rathmell, Daniel Yick Chin Heng, Guru Sonpavde, Sabina Signoretti, A. Ari Hakimi, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2018)

626 Background: The IMDC risk score is a valid and simple tool to prognosticate patients (pts) with metastatic renal cell carcinoma (mRCC). Some non-VHL common genomic alterations may be associated with outcomes. We therefore assessed the prognostic value of most commonly mutated genes in mRCC beside VHL overall, and within IMDC risk groups. Methods: We identified patients treated at Dana-Farber Cancer Institute (n = 65) or part of TCGA (n = 33) who had genomic data available and were treated with first line vascular endothelial growth factor tyrosine kinase inhibitors. Information on genomic alterations (GA) focused on PBRM1, BAP1, SETD2, KDM5C and TP53 was extracted. Cox regression was performed to assess the association of each GA with overall survival (OS), adjusting for IMDC risk groups and age. Results: Overall, 98 pts were identified. 96/98 pts had clear-cell histology. Pts distribution by IMDC risk groups was: 7% good, 58% intermediate, 27% poor and 8% unknown. Mutation rates were 27% PBRM1, 17% BAP1, 29% SETD2, 9% KDM5C and 8% TP53. In multivariable models, there was an association between GA and worse OS for BAP1 and BAP1 or TP53 combined (Table). When stratified by IMDC risk groups, GA in BAP1 or TP53 was associated with shorter median OS in poor risk pts [12.1 mo (95%CI 8.3- 24.0) v. 27.6 mo (95%CI 18.9- 53.4), aHR 4.64 (95%CI 1.32-16.4), p = 0.017] and a trend toward worse median OS in intermediate risk pts [20.5 mo (95%CI 7.4-54.6) v. 36.3 mo (95%CI 21.1, NR), aHR 2.11 (95%CI 0.94-4.74)] compared to pts without GA in BAP1 or TP53. Too few death events were observed in good risk pts to assess the prognostic value of GA in BAP1 or TP53. Conclusions: GA in BAP1 or TP53 are prognostic in mRCC and further discriminate pts with distinct outcomes within IMDC risk groups. Validation in larger dataset is ongoing. [Table: see text]
PROGNOSTIC IMPACT OF B-TYPE NATRIURETIC PEPTIDE ON LONG-TERM CLINICAL OUTCOMES IN PATIENTS WITH NON-ST-SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION WITHOUT CREATINE KINASE ELEVATION: JAPANESE REGISTRY OF ACUTE MYOCARDIAL INFARCTION DIAGNOSED BY UNIVERSAL DEFINITION (J-MINUET) SUBSTUDY
Authors: Norihito Takahashi, Ogita Manabu, Nakao Koichi, Yukio Ozaki, Kazuo Kimura, Junya Ako, Noguchi Teruo, Satoshi Yasuda, Satoru Suwa, Kazuteru Fujimoto, Nakama Yasuharu, Takashi Morita, Wataru Shimizu, Yoshihiko Saito, Atsushi Hirohata, Morita Yasuhiro, Teruo Inoue, Atsunori Okamura, Mano Toshiaki, Kazuhito Hirata, Kengo Tanabe, Kunihiro Nishimura, Yoshihiro Miyamoto, Hisao Ogawa, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2018)
Unique profiles of lesional T follicular helper cells in the pathogenesis of IgG4-related disease
Authors: Ryuta Kamekura, Hayato Yabe, Kenichi Takano, Motohisa Yamamoto, Ippei Ikegami, Fumie Ito, Hiroki Takahashi, Tetsuo Himi, Shingo Ichimiya
Journal: Journal of Allergy and Clinical Immunology (2018)
High-Intensity Exercise Safe in De Novo Parkinson Disease
Authors: Anita Slomski
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms
Authors: Maeve A Lowery, Winston Wong, Emmet J Jordan, Jonathan W Lee, Yelena Kemel, Joseph Vijai, Diana Mandelker, Ahmet Zehir, Marinela Capanu, Erin Salo-Mullen, Angela G Arnold, Kenneth H Yu, Anna M Varghese, David P Kelsen, Robin Brenner, Erica Kaufmann, Vignesh Ravichandran, Semanti Mukherjee, Michael F Berger, David M Hyman, David S Klimstra, Ghassan K Abou-Alfa, Catherine Tjan, Christina Covington, Hannah Maynard, Peter J Allen, Gokce Askan, Steven D Leach, Christine A Iacobuzio-Donahue, Mark E Robson, Kenneth Offit, Zsofia K Stadler, Eileen M O’Reilly
Journal: JNCI Journal of the National Cancer Institute (2018)

Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410–468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board–approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.
ELAMIPRETIDE RESTORES PROTEIN AND MRNA EXPRESSION LEVELS OF CARDIOLIPIN SYNTHASE-1 IN LEFT VENTRICULAR MYOCARDIUM OF DOGS WITH CHRONIC HEART FAILURE
Authors: Ramesh C. Gupta, Vinita Singh-Gupta, Kefei Zhang, Jiang Xu, Hani N. Sabbah
Journal: Journal of the American College of Cardiology (2018)
Precut fistulotomy – widening its limits
Authors: João Fernandes, Diogo Libânio, Sílvia Giestas, José Ramada, David Martinez-Ares, Jorge Canena, Luís Lopes
Journal: Endoscopy (2018)

Selective cannulation of the common bile duct (CBD) is the most important and challenging step in a biliary endoscopic retrograde cholangiopancreatography (ERCP) [1] [2]. However, in the first ERCP, even in experienced hands, biliary cannulation may fail in up to 15 % – 35 % of cases when using standard methods alone [3]. In this subset of patients, additional cannulation techniques are needed to access the CBD in order to continue with the ERCP. Precut is the most common strategy used by experienced endoscopists, when conventional methods have failed [2]. Needle-knife fistulotomy (NKF) and conventional precut are the two most common variants. Recently published guidelines recommend opting for NKF, as evidence suggests a lower risk of adverse events, especially pancreatitis, when used early in the biliary cannulation algorithm [2] [4].
Mechanism-based pharmacokinetic (MBPK) models describe the complex plasma kinetics of three antiretrovirals delivered by a long-acting anti-HIV drug combination nanoparticle formulation
Authors: John C. Kraft, Lisa A. McConnachie, Josefin Koehn, Loren Kinman, Jianguo Sun, Ann C. Collier, Carol Collins, Danny D. Shen, Rodney J.Y. Ho
Journal: Journal of Controlled Release (2018)
Palliative care intervention and aggressive care at end-of-life in patients with advanced pancreatic adenocarcinoma.
Authors: Caitlin Lees, Wilma M Hopman, Tallal Younis, Nathan William Dana Lamond, Ravi Ramjeesingh
Journal: Journal of Clinical Oncology (2018)

244 Background: Unresectable pancreatic cancer carries one of the worst prognoses amongst malignancies. For these patients, their treatment at end-of-life represents some of the most expensive care they will receive. Resource-intensive care at the end of life contrasts with the preferences of many patients and their family members. We have examined the intensity of end-of-life care in patients diagnosed with unresectable pancreatic adenocarcinoma using a previously published aggressiveness score. Methods: The surveillance and epidemiology unit of the program of care for cancer identified all patients diagnosed with unresectable pancreatic adenocarcinoma in Nova Scotia between January 1, 2011 and December 31, 2014. Charts were then reviewed for demographic data, Charlson Comorbidity Index, and consultation with Palliative Care. An aggressiveness of end-of-life care score, which has been previously described in the literature, was employed. Briefly, scores ranged from 0 to 6, with higher scores representing more aggressive care. One point was assigned for each of the following events in the last 30 days of life: two or more emergency department visits, two or more hospitalizations, 14 or more inpatient days, chemotherapy, intensive care unit admission, death in hospital. One-way ANOVA was then performed to determine factors associated with more aggressive end-of-life care. Results: In total, 264 patients met inclusion criteria. Mean aggressiveness of end-of-life care was 0.92 (95% CI 0.8 – 1.03). On average, patients seen by Palliative Care at any point in their illness had less aggressive treatment than those never seen by Palliative Care (0.83 vs 1.38, p = 0.001). Conclusions: In patients diagnosed with unresectable pancreatic cancer, less aggressive end-of-life care Further work, including prospective studies, is needed to identify a true association between palliative care intervention and less aggressive care at end-of-life. Such an association could lead to benefits for the patient and reduce costly resource-intensive care.
Multicomponent cyclodextrin system for improvement of solubility and dissolution rate of poorly water soluble drug
Authors: Mayank Patel, Rajashree Hirlekar
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The purpose of the present study was to investigate the interaction of Cinnarizine (CIN) with Hydroxypropyl-β-Cyclodextrin (HPβCD) in the presence of Hydroxy Acids (HA). Various binary and ternary systems of CIN with HPβCD and HA were prepared by kneading and coevaporation methods. For the ternary systems, HA were tried in three different concentrations. The interaction in solution phase was studied in detail by the phase solubility method, and the solid phase interactions were characterized by Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance (1H-NMR). Phase solubility revealed the positive effect of HA on the complexation of CIN with HPβCD. Solid phase characterization confirmed the formation of inclusion complex in the ternary systems. Solubility and dissolution studies illustrated that out of three different concentrations tried, HA were most effective at the 1 M concentration level. Ternary systems were very effective in improving the solubility as well as dissolution profile of CIN than the CIN–HPβCD binary systems. FTIR, 1H-NMR and Molecular docking studies gave some insight at molecular level that actually which part of CIN was interacting with the HPβCD. Molecular docking and free energy calculation even enlighten the role of tartaric acid in increasing solubility of CIN in the ternary system.
OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY WITH MILD PHENOTYPE: A NOVEL SUBGROUP OF PATIENTS AMENABLE TO SURGICAL MYECTOMY
Authors: Ethan Rowin, Barry J. Maron, Aalap Chokshi, Muhil Kannappan, Knarik Arkun, Hassan Rastegar, Martin Maron
Journal: Journal of the American College of Cardiology (2018)
Real-world (RW) evidence of vinflunine in metastatic urothelial cancer (mUC): A systematic review of seven European studies.
Authors: Rodolfo Passalacqua, Jacques Medioni, Daniel E. Castellano, Anders Ullén, Aristotelis Bamias, Syed Hussain, Axel Hegele
Journal: Journal of Clinical Oncology (2018)

463 Background: Vinflunine is the only chemotherapy agent for which there is a marketing authorisation in Europe for platinum-pretreated patients (pts) with mUC, based on a randomized phase III clinical trial. However, RW data regarding long-term efficacy and safety of vinflunine in unselected populations is needed. We conducted a systematic review gathering RW data from published observational European studies. Methods: Controlled studies and case series were excluded. We systematically explored the following endpoints: Overall Response Rate (ORR), Progression-Free Survival (PFS), Overall Survival (OS) and toxicity. Results: From 2014 to 2017, seven post-marketing studies including 750 pts were published: one was prospective and six were retrospective. Median ORR and median OS ranged from 13% to 29% and 6.3 to 11.9 months (mo) respectively (see Table below). In long-term survivors, OS reached 20.5 mo. Initial doses ranged from 250 to 320 mg/m2 adapted to patient’s conditions. In multivariate analysis, OS was found to be associated with the following risk-factors at baseline: ECOG PS &gt;0, hemoglobin &lt;10 g/dl, and presence of liver metastasis. The favorable safety profile demonstrated in randomized trials was confirmed. Main toxicity was hematological: neutropenia (G 3/4 in 1% to 23%) and anemia (G 3/4 in 4% to 33%). Constipation seemed to be less frequent than previously reported (G 3/4 in 5% to 22%). Conclusions: This is the largest experience of vinflunine use in platinum-pretreated pts with mUC. In our RW evidence, vinflunine shows both efficacy and a safe profile in an unselected patient population with similar criteria as in the pivotal trial. These findings reinforce the role of vinflunine in mUC, particularly if compared to evidence with taxanes or the increasing costs of immunotherapy.[Table: see text]
Randomised trials are not the only evidence, and for some questions they may not be the best
Authors: Jim Thornton
Journal: BMJ (2018)

Further to the debate on continuous electronic fetal heart rate monitoring,1 neither electronic fetal monitoring nor intermittent auscultation has ever saved a baby or harmed a mother directly. What saves (or harms) is intrauterine resuscitation or delivery. 

The trials of monitoring versus intermittent auscultation are difficult to interpret because none of them specified how obstetricians and midwives should respond to different heart rate patterns; it was just assumed that they knew what to …
Alterations of plasma glutamine and surgical stress in gastric cancer surgery.
Authors: Tsutomu Hayashi, Toru Aoyama, Hiroshi Yamamoto, Takanobu Yamada, Tsutomu Sato, Yasushi Rino, Munetaka Masuda, Haruhiko Cho, Akira Tsuburaya, Takashi Ogata, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2018)

176 Background: The plasma glutamine levels are known to decrease after major surgery, which is related to a negative clinical outcome. However, the influence of surgical stress on the decrease in the plasma glutamine concentration is unclear. The aim of this study was to evaluate the change in glutamine in relation to the types of gastrectomy and approaches as well as the amount of surgical stress evaluated by serum interleukin-6(IL-6) as an objective indicator. Methods: This was a prospective observational study. The eligibility criteria were (1) gastric adenocarcinoma of the stomach confirmed by pathology and (2) patients scheduled to receive gastrectomy with D1 or D2 lymphadenectomy for gastric cancer. Blood samples were taken at 7 AM on the day of surgery and at 12 h after surgery to measure the plasma glutamine and interleukin-6 (IL-6) levels. Results: Between May 2011 and December 2011, 81 consecutive patients were enrolled in this study. The plasma glutamine level was significantly decreased in all patients, regardless of distal or total gastrectomy and laparoscopic or open surgery. No significant differences were observed in the IL-6 level between total and distal gastrectomy patients or between patients treated via a laparoscopic or open approach. Decreases in the plasma glutamine level were positively correlated with the logarithmically transformed-plasma IL-6 (logIL6) (r = 0.471, p &lt; 0.001) overall. Conclusions: Decreases in the glutamine concentration depended on the amount of surgical stress. When conducting a clinical trial to evaluate glutamine administration, personalized adjustment may be key to avoiding glutamine depletion in response to surgical stress.
Doctors are awarded a 1% pay rise for 2013-14
Authors: Caroline White
Journal: BMJ (2013)

Doctors will receive a 1% increase in base pay across the board in 2013-14 in line with the recommendations of the Doctors’ and Dentists’ Review Body on Remuneration (DDRB), the Treasury has announced.

All salaried doctors and dentists will receive a pay uplift of 1%, whereas contractor GPs on the general medical services (GMS) contract will receive a gross uplift of 1.32% to cover a 1% increase in GP pay and increases in practice expenses.

Doctors’ leaders have said that the uplift will do little to boost flagging morale or adequately reward doctors’ efforts to make extensive efficiency savings while improving quality of services.

The pay increase, which …
High-Wattage E-Cigarettes Induce Tissue Hypoxia and Lower Airway Injury: A Randomized Clinical Trial
Authors: Martin Chaumont, Alfred Bernard, Stéphanie Pochet, Christian Mélot, Charaf El Khattabi, Florence Reye, Karim Zouaoui Boudjeltia, Pierre Van Antwerpen, Cédric Delporte, Philippe van de Borne
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
Authors: Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Sam Bhayani, William P. Bro, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Mayer Fishman, Thomas H. Gallagher, John L. Gore, Steven L. Hancock, Michael R. Harrison, Won Kim, Christos Kyriakopoulos, Chad LaGrange, Elaine T. Lam, Clayton Lau, M. Dror Michaelson, Thomas Olencki, Phillip M. Pierorazio, Elizabeth R. Plimack, Bruce G. Redman, Brian Shuch, Brad Somer, Guru Sonpavde, Jeffrey Sosman, Mary Dwyer, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2017)

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non–clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.
CYTO-CHIP: Cytoreductive surgery versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A propensity-score analysis from BIG RENAPE and FREGAT working groups.
Authors: Pierre Emmanuel Bonnot, Guillaume Piessen, Marc Pocard, Bernard Meunier, Jean Marc Bereder, Karine Abboud, Frederic Marchal, Francois Quenet, Diane Goere, Simon Msika, Catherine Arvieux, Nicolas Pirro, Romuald Wernert, Patrick RAT, Denis Pezet, Jérémie Lefevre, Thomas Courvoisier, Reza Kianmanesh, Pierre Meeus, Olivier Glehen
Journal: Journal of Clinical Oncology (2018)

8 Background: Gastric cancer with peritoneal carcinomatosis (PC) is considered by most as an end-stage disease. Poor outcomes are achieved with palliative chemotherapy. Aggressive combination of cytroreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are still debated in this indication. Purpose: to assess the impact of HIPEC on survival and postoperative outcomes after complete CRS compared with CRS alone (CRSa) Methods: Data from 277 consecutive patients treated for gastric cancer with PC in 19 French centers from 1989 to 2014 were collected. 180 patients who underwent CRS and HIPEC were compared to 97 treated by CRSa. Extension of PC was assessed by the Peritoneal Cancer Index (PCI). Only patients treated by complete CRS were included (CC-0 or CC-1). To assess the effect of HIPEC and to account for confounding factors, a Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used. Multivariate models and sensitivity analyses were also performed. Results: After propensity weighting, groups were similar except for the PCI that remained higher in the HIPEC group (median: 6 v 2, P = .003). However, there was no difference in the completeness of CRS (CC-0: 76.7% v 83.5 %, P = .904). HIPEC was associated with improved overall survival (OS) on both multivariate and IPTW models. On IPTW analysis, median OS was 18.8 v 12.1 months. 3- and 5-years OS were 26.21% and 19.87% v 10.82% and 6.43% (HR, 1.66; 95% CI, 1.17-2.37; P = .005). 3- and 5-years disease-free survival were 20.40% and 17.05% v 5.87% and 3.76% (P = .001). Mortality rate (7.4% v 10.1%, P = .820) and grade 3-4 morbidity (53.7% v 55.3%, P = .496) at 90 days were similar. Surgical morbidity was 37.1% v 38.8% in CRSa group. Conclusions: Compared to CRSa, HIPEC was associated with increased OS and potential disease eradication for gastric cancer with PC, without additional morbidity. This treatment, when optimal CRS can be achieved, should be considered as the gold standard since outcomes remain grim with chemotherapies. Clinical trail information: NCT03253939