tbuckley/cabot-search huggingface dataset:
Prevalence of <i>ESR1</i> Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer
Authors: Sarat Chandarlapaty, David Chen, Wei He, Patricia Sung, Aliaksandra Samoila, Daoqi You, Trusha Bhatt, Parul Patel, Maurizio Voi, Michael Gnant, Gabriel Hortobagyi, José Baselga, Mary Ellen Moynahan
Journal: JAMA Oncology (2016)

Estrogen receptor α (ESR1) mutations found in metastatic breast cancer (MBC) promote ligand-independent receptor activation and resistance to estrogen-deprivation therapy in laboratory models. The prevalence of these mutations and their potential impact on clinical outcomes has not been established.To determine the prevalence of ESR1 mutations (Y537S and D538G) in estrogen receptor (ER)-positive MBC and determine whether mutation is associated with inferior outcomes.From December 16, 2014, to August 26, 2015, we analyzed cell-free DNA (cfDNA) from baseline plasma samples from participants in the BOLERO-2 double-blind phase 3 study that randomized patients from 189 centers in 24 countries with MBC to exemestane plus placebo or exemestane plus everolimus. The study enrolled postmenopausal women with a diagnosis of MBC and prior exposure to an aromatase inhibitor. Baseline plasma samples were available from 541 of 724 patients (74.7%). We assessed the effect of mutation on overall survival of the population and the effect of mutation on progression-free survival (PFS) by treatment arm.Patients were randomized to treatment with exemestane (25 mg oral daily) together with everolimus (10 mg oral daily) or with placebo.The 2 most frequent mutations in ESR1 (Y537S and D538G) were analyzed from cfDNA using droplet digital polymerase chain reaction and samples scored as wild-type, D538G, Y537S, or double mutant. Cox-proportional hazards model was used to assess PFS in patient subgroups defined by mutations, and the effect of each mutation on overall survival.Of 541 evaluable patients, 156 (28.8%) had ESR1 mutation D538G (21.1%) and/or Y537S (13.3%), and 30 had both. These mutations were associated with shorter overall survival (wild-type, 32.1 months [95% CI, 28.09-36.40 months]; D538G, 25.99 months [95% CI, 19.19-32.36 months]; Y537S, 19.98 months [13.01-29.31 months]; both mutations, 15.15 months [95% CI, 10.87-27.43 months]). The D538G group (hazard ratio, 0.34 [95% CI, 0.02-0.57]) derived a similar PFS benefit as wild type from addition of everolimus to exemestane.ESR1 mutations are prevalent in ER-positive aromatase inhibitor-treated MBC. Both Y537S and D538G mutations are associated with more aggressive disease biology.clinicaltrials.gov Identifier: NCT00863655.
Wandering Pleural Mesothelial Fatty Cyst
Authors: Trevor T. Nicholson, Kirtee Raparia, Gökhan M. Mutlu, Peter H. S. Sporn, Ankit Bharat
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

A 50-year-old nonsmoking man with chronic cough underwent computed tomography of the chest, which revealed a lobulated mass abutting the pericardium overlying the right atrium (Figure 1A).Surprisingly, a subsequent positron emission tomogram showed that the mass was no longer present in the mediastinum; instead, a lobulated mass of similar soft tissue density was demonstrated in the right major fissure (Figure 1B).This mass was moderately fluorodeoxyglucose-avid, with a standard uptake value of 2.5 (Figure 1C), raising concern for malignancy.To reconcile the discrepancy between the prior imaging studies, a third computed tomography scan was obtained.Interestingly, this showed that the mass in the major fissure had disappeared and the lesion adjacent to the heart had reappeared, although its configuration was somewhat different (Figure 1D).The patient underwent video-assisted thoracoscopy, which revealed a mobile cystic lesion with a stalk, arising from the mediastinal fat pad at the diaphragmatic reflection (Figure 1E).The lesion was resected, using a stapling device (Figure 1F).Histopathology demonstrated a cystic mass containing large amounts of fat and lined by calretinin-positive mesothelial cells (Figure 1G).
Fertility Outcomes after Allogeneic Hematopoietic Stem Cell Transplants Conditioned with Busulfan 4 Mg/Kg and Cyclophosphamide 200 Mg/Kg to Treat Severe Aplastic Anemia
Authors: Mariana Nassif Kerbauy, Livia Caroline Barbosa Mariano, Erick Menezes, Evandro Dantas, Jayr Schmidt Sobrinho, Marina M Nascimento, Roberto Silva, Maria Cristina Macedo, Sandra Gualandro, Adriana Seber
Journal: Blood (2015)
P0317 : Down-regulation of Hao2 is associated with the onset and development of hepatocellular carcinoma in rodents
Authors: S. Mattu, A. Perra, S. Menegon, M.A. Kowalik, A. Petrelli, G.M. Ledda-Columbano, S. Giordano, A. Columbano
Journal: Journal of Hepatology (2015)
Visual Pigments, Ocular Filters and the Evolution of Snake Vision
Authors: Bruno F. Simões, Filipa L. Sampaio, Ronald H. Douglas, Ullasa Kodandaramaiah, Nicholas R. Casewell, Robert A. Harrison, Nathan S. Hart, Julian C. Partridge, David M. Hunt, David J. Gower
Journal: Molecular Biology and Evolution (2016)

Much of what is known about the molecular evolution of vertebrate vision comes from studies of mammals, birds and fish. Reptiles (especially snakes) have barely been sampled in previous studies despite their exceptional diversity of retinal photoreceptor complements. Here, we analyze opsin gene sequences and ocular media transmission for up to 69 species to investigate snake visual evolution. Most snakes express three visual opsin genes (rh1, sws1, and lws). These opsin genes (especially rh1 and sws1) have undergone much evolutionary change, including modifications of amino acid residues at sites of known importance for spectral tuning, with several tuning site combinations unknown elsewhere among vertebrates. These changes are particularly common among dipsadine and colubrine "higher" snakes. All three opsin genes are inferred to be under purifying selection, though dN/dS varies with respect to some lineages, ecologies, and retinal anatomy. Positive selection was inferred at multiple sites in all three opsins, these being concentrated in transmembrane domains and thus likely to have a substantial effect on spectral tuning and other aspects of opsin function. Snake lenses vary substantially in their spectral transmission. Snakes active at night and some of those active by day have very transmissive lenses, whereas some primarily diurnal species cut out shorter wavelengths (including UVA). In terms of retinal anatomy, lens transmission, visual pigment spectral tuning and opsin gene evolution the visual system of snakes is exceptionally diverse compared with all other extant tetrapod orders.
Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction
Authors: Marc P. Bonaca, Shinya Goto, Deepak L. Bhatt, P. Gabriel Steg, Robert F. Storey, Marc Cohen, Erica Goodrich, Laura Mauri, Ton Oude Ophuis, Mikhail Ruda, Jindřich Špinar, Ki-Bae Seung, Dayi Hu, Anthony J. Dalby, Eva Jensen, Peter Held, David A. Morrow, Eugene Braunwald, Marc S. Sabatine
Journal: Circulation (2016)

In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population.Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis.Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001).High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke.URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.
Cardiovascular Events in Obstructive Sleep Apnea — Can CPAP Therapy SAVE Lives?
Authors: Babak Mokhlesi, Najib T. Ayas
Journal: New England Journal of Medicine (2016)

Obstructive sleep apnea is a common disorder that has been associated with an increased risk of cardiovascular disease.1 Continuous positive airway pressure (CPAP) is frequently prescribed in patients with obstructive sleep apnea and is effective in reversing hypoxemia and upper airway obstruction. Meta-analyses of randomized trials have shown that CPAP therapy elicits significant reductions in systemic arterial pressure, and the effect is greater with higher adherence.2,3 Observational studies have shown significantly fewer cardiovascular events in patients adherent to CPAP therapy than in those who are not adherent,4,5 but the need for large trials has lingered.The Sleep Apnea . . .
Diabetes Is Associated With Decreased Limb Survival in Patients With Critical Limb Ischemia: Pooled Data From Two Randomized Controlled Trials
Authors: Marlon I. Spreen, Hendrik Gremmels, Martin Teraa, Ralf W. Sprengers, Marianne C. Verhaar, Randolph G. Statius van Eps, Jean-Paul P.M. de Vries, Willem P.Th.M. Mali, Hans van Overhagen
Journal: Diabetes Care (2016)

Although never assessed prospectively, diabetes mellitus (DM) is assumed to negatively affect the outcomes of critical limb ischemia (CLI). DM was highly prevalent in two recently conducted randomized controlled trials in CLI patients, the PADI (Percutaneous Transluminal Balloon Angioplasty [PTA] and Drug Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia) and JUVENTAS (Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-Arterial Supplementation) trials. To determine the implications of DM in a population of patients with infrapopliteal CLI, clinical outcomes were compared in patients with and without DM.Individual data from patients with CLI (Rutherford category ≥4) were pooled. Patients were considered to have DM when this diagnosis was reported in the hospital electronic medical records. Rates of major amputation (above ankle level) and major events (major amputation or death) were compared between CLI patients with and without DM. Hazard ratios (HRs) were calculated.Of a total of 281 patients, DM was present in 49.1%. The major amputation rate at 5 years of follow-up was higher in patients with DM than in patients without DM (34.1% vs. 20.4%, P = 0.015). The major event and death rate did not differ. The unadjusted HR of DM for the major amputation risk was 1.87 (95% CI 1.12-3.12). Model factors with significant HRs in the multivariate analysis were baseline Rutherford category (HR 1.95; 95% CI 1.24-3.06) and ankle-brachial index (ABI) >1.4 (HR 2.78; 95% CI 1.37-5.64).CLI patients with DM are at a significantly higher risk of major amputation than CLI patients without DM. This increased risk is associated with a higher prevalence of baseline ABI >1.4 and more severe ischemia at initial presentation in patients with DM.
Feasibility of LAA Closure for Left Atrial Thrombus in Patients With Aortic Stenosis and AF
Authors: Akhil Parashar, Karan Sud, Jasneet Devgun, Shikhar Agarwal, Mehak Bassi, E. Murat Tuzcu, Brian Griffin, Amar Krishnaswamy, Samir Kapadia
Journal: Journal of the American College of Cardiology (2016)
Fever of Unknown Origin
Authors: Jack Coulehan
Journal: JAMA (2013)

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
Phase II trial of carboplatin, abraxane, and bevacizumab in NSCLC.
Authors: R. S. Heist, G. D. Duda, D. Sahani, M. Ancukiewicz, P. Fidias, L. V. Sequist, A. T. Shaw, J. S. Temel, I. T. Lennes, J. W. Neal, N. A. Pennell, T. J. Lynch, J. A. Engelman, R. K. Jain
Journal: Journal of Clinical Oncology (2011)

e18016 Background: The addition of bevacizumab to carboplatin and paclitaxel has been shown to improve survival. Abraxane (nab-paclitaxel) may yield higher response rates than paclitaxel in NSCLC. This Phase II study was designed to investigate the combination of carboplatin (C), nab-paclitaxel (N-P), and bevacizumab (B) in first-line treatment of advanced NSCLC. Pharmacodynamic blood and imaging studies were performed to better understand the mechanism of action of bevacizumab both alone and in combination with chemotherapy and to assess biomarkers of response. Methods: Pts with previously untreated, non-squamous, advanced NSCLC were enrolled in an open-label Phase II trial. All patients were given a single induction dose of B 15 mg/kg on day -14. On day 1 combination therapy started with C AUC 6 d1, N-P 100 mg/m2 d 1, 8, 15, and B 15 mg/kg d1, on a 21 day cycle. Correlative imaging and biomarker studies were performed with FDG-PET, perfusion CT, and blood for circulating cellular and molecular biomarkers, on days -14 and -2 (prior to and 12 days after induction B), and every two cycles during treatment. Planned enrollment was 36. Changes in biomarkers from day -14 to day -2 were tested using the exact paired Wilcoxon test, and correlations with best percent difference in RECIST measurements of response were tested using the Kendall’s tau test. Results: Twenty-five pts have been enrolled thus far. Four pts came off study prior to first restaging; one for painful bony disease requiring radiation and three for toxicity (perforated diverticulitis, LFT abnormalities, and nausea/vomiting). One pt is currently in cycle 1; another pt dropped out before receiving any study drug. Of 19 pts evaluable for response to date, best response was 8 PR, 9 SD, and 2 PD. Induction B treatment was associated with statistically significant increases in levels of VEGF, PIGF, and SDF1a, and decrease in sVEGFR-1 levels. Blood flow and permeability decreased from baseline to day -2. Conclusions: Disease control rate (PR + SD) with combination therapy with C, N-P, and B was 74% (17/23). Pharmacodynamic blood and imaging biomarker studies in bevacizumab-treated NSCLC patients are feasible.
Academic Medicine and Concierge Practice
Authors: Robert Doherty
Journal: Annals of Internal Medicine (2016)

Letters6 September 2016Academic Medicine and Concierge PracticeRobert Doherty, BARobert Doherty, BAFrom American College of Physicians, Washington, DC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0104 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I appreciate Dr. Donohoe's observations about academic medical centers that sponsor “concierge” clinics. He is correct that our paper did not specifically address academic medical centers; rather, we looked at the broader movement to practices that charge retainer fees, do not accept insurance, and/or limit the number of patients they see. (We called such practices “direct patient contracting practices” [DPCPs] because descriptions of concierge practices commonly used in the literature lack consistency.) I agree that attention needs to be paid to the ethical, educational, and patient care implications of academic medical centers that operate such practices and on ... Author, Article, and Disclosure InformationAffiliations: From American College of Physicians, Washington, DC.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0366. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAssessing the Patient Care Implications of “Concierge” and Other Direct Patient Contracting Practices: A Policy Position Paper From the American College of Physicians Robert Doherty and Academic Medicine and Concierge Practice Martin Donohoe Metrics 6 September 2016Volume 165, Issue 5Page: 375-376KeywordsDisclosureHuman sexual behaviorMedical educationMotivationPatient advocacyPatientsPopulation statisticsRacial and ethnic issuesSexual identityStroke ePublished: 6 September 2016 Issue Published: 6 September 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Corrigendum to ‘Controlling chitosan-based encapsulation for protein and vaccine delivery’ [Biomaterials 35 (2014) 4382–4389]
Authors: Bhanu prasanth Koppolu, Sean G. Smith, Sruthi Ravindranathan, Srinivas Jayanthi, Thallapuranam K. Suresh Kumar, David A. Zaharoff
Journal: Biomaterials (2015)
Clinical Activity of Alectinib in Advanced RET -Rearranged Non–Small Cell Lung Cancer
Authors: Jessica J. Lin, Elizabeth Kennedy, Lecia V. Sequist, Priscilla K. Brastianos, Kelly E. Goodwin, Sara Stevens, Alexandra C. Wanat, Lisa L. Stober, Subba R. Digumarthy, Jeffrey A. Engelman, Alice T. Shaw, Justin F. Gainor
Journal: Journal of Thoracic Oncology (2016)
Counting Better — The Limits and Future of Quality-Based Compensation
Authors: Christopher R. Dale, Michael Myint, Amy L. Compton-Phillips
Journal: New England Journal of Medicine (2016)

Dr. Christopher Dale on better ways of deploying quality metrics to improve the value of health care. (07:42)Download A Seattle medical group found that although performance improved on the quality metrics it emphasized, those metrics didn't reflect the essence of patient care and the focus felt stifling to clinicians. So the group began charting a different path toward higher-value care.
Online Intervention for Prevention of Major Depression
Authors: Ion Anghelescu
Journal: JAMA (2016)

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
History of depression in grandparent and parent may raise risk of the condition
Authors: Ingrid Torjesen
Journal: BMJ (2016)

People have a higher risk of major depressive disorder if their parents and grandparents have a history of the disorder, a study published online by JAMA Psychiatry has found.1

Although it is well known that people have a greater risk of depression if their parents have experienced it, no previous published study had looked at whether the risk is also heightened if grandparents have a history …
Surgeon’s Responsibility for Patient Care
Authors: Richard B. Reiling
Journal: JAMA Surgery (2016)

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
Young female handball players and sport specialisation: how do they cope with the transition from primary school into a secondary sport school?
Authors: Elsa Kristiansen, Trine Stensrud
Journal: British Journal of Sports Medicine (2016)

The aim of the present study was to examine how six young female handball players (aged 13-14 years) perceived the transition from primary school to a sport-specialised secondary school.Physical and physiological data as well as data from questionnaires were collected at baseline and after the first year at the sport school, and qualitative interviews were performed retrospectively after the first year at school.Evidence of competition-related stressors, organisational stressors (sport and school balance) and personal stressors (social life and sport balance, lack of sleep and severe injuries) was found. Three girls developed long-lasting musculoskeletal injuries (>3 months out of ordinary training) and one experienced repeated short periods (≤2 weeks out of ordinary training) of injuries during the first year. Onset of menarche and a length growth between 6 and 8 cm during the first year were characteristic traits of the four injured girls.From our small study, it appears that young athletes attending a specialised secondary sport school experienced many stressors due to a significant increase in training volume, reduction in sleeping time and development of severe and long-lasting injuries. Hence, trainers at sport schools, club trainers and parents need to communicate and support them in order to prevent this.