tbuckley/cabot-search huggingface dataset:
Antitumor T-cell Reconditioning: Improving Metabolic Fitness for Optimal Cancer Immunotherapy
Authors: Dayana B. Rivadeneira, Greg M. Delgoffe
Journal: Clinical Cancer Research (2018)

With the rapid rise of immunotherapy for cancer treatment, attention has focused on gaining a better understanding of T-cell biology in the tumor microenvironment. Elucidating the factors underlying changes in their function will allow for the development of new therapeutic strategies that could expand the patient population benefiting from immunotherapy, as well as circumvent therapy resistance. Cancers go beyond avoiding immune recognition and inducing T-cell dysfunction through coinhibitory molecules. Recent work has demonstrated that the tumor microenvironment elicits metabolic changes in T cells that dampen their ability to respond and that manipulating these metabolic changes can strengthen an antitumor immune response. Here we review the metabolic status of various types of T cells, the energetic state of the tumor microenvironment, and proposed modalities for improvement of immunotherapy through metabolic remodeling. Clin Cancer Res; 24(11); 2473-81. ©2018 AACR.
How does inflammation contribute to pulmonary hypertension?
Authors: Rahul Kumar, Brian Graham
Journal: European Respiratory Journal (2018)

Pathogenic drivers of the pulmonary vascular disease that results in pulmonary arterial hypertension (PAH) are currently unclear, but there are many reasons to suspect that inflammation is a major contributor. Clinically, PAH is a complication of multiple autoimmune diseases including scleroderma and systemic lupus erythematosus, suggesting dysregulated immunity can trigger the vascular disease [1–3]. PAH can also complicate several infectious diseases, including HIV and schistosomiasis, suggesting there could be off-target effects of immune upregulation which inadvertently damage the pulmonary vasculature. Patients with these pro-inflammatory aetiologies often have systemic vascular diseases, including digital ischaemia in scleroderma and portal hypertension in schistosomiasis [4, 5], suggesting the same inflammatory stimuli can lead to diverse vascular pathologies. Blocking inflammation could be a curative approach in pulmonary vascular diseases <http://ow.ly/dW5M30hB6aj>
Abstract P107: Differences in Cardiovascular Mortality Risk Among African Americans in the Minnesota Heart Survey, 1985-2015, versus African Americans in the Atherosclerosis Risk in Communities Study (ARIC) Cohort: 1987-2015
Authors: Kristen M George, Aaron R Folsom, Lyn M Steffen, Lynne E Wagenknecht, Thomas H Mosley
Journal: Circulation (2018)

Geographic differences in CVD mortality across the U.S. are well-established, but frequently overlooked. ARIC enrolled African Americans (AA) from Jackson, MS and Forsyth County, NC, areas of the Southeast with some of the highest CVD mortality rates, especially among AAs. The Minnesota Heart Survey enrolled AAs from Minnesota where CVD rates are among the lowest. However, it is not known whether AAs in Minnesota also have low rates. Using these two cohorts, we assessed whether CVD-related mortality risk among AAs differs by region. Baseline measures of CVD risk factors for MHS were taken in 1985 from a population based sample of AAs, ages 45 to 65, living in the Minneapolis-St. Paul metropolitan area. These same measures were made at ARIC visit 1 (1987-89) in AA participants of the same age residing in Jackson, MS and Forsyth County, NC. CVD and total mortality were identified using ICD codes for underlying cause of death from State and National Death Index records in both cohorts. We compared MHS and ARIC on CVD death rates using Poisson regression, prevalence of risk factors, and risk factor hazard ratios using Cox regression. After risk factor adjustment, AA men in MHS had a rate of 5.2 (95% CI: 3.2, 7.2) CVD deaths per 1000 person-years compared to 15.1 (95% CI: 13.1, 17.1) for AA men in ARIC. For AA women, MHS had 4.1 (95% CI: 2.7, 5.5) CVD deaths per 1000 person-years versus 10.2 (95% CI: 9.0, 11.4) in ARIC. CVD mortality rates were higher in Jackson than Forsyth County within ARIC. CVD death rates paralleled risk factor prevalence at baseline. Compared to MHS, ARIC had significantly higher total cholesterol (215 vs. 202 mg/dL), albeit higher HDL cholesterol (55 vs. 53 mg/dL), as well as higher anti-hypertensive medication use (41 vs. 30%), diabetes (13 vs. 11%) and BMI (30 vs. 29 kg/m 2 ), while smoking did not differ. Despite risk factor differences, hazard ratios of CVD death associated with each risk factor did not differ between studies even after inclusion of a competing risk of non-CVD death. In conclusion, the CVD death rate was lower in AAs in MHS than in AAs residing in the Southeast in ARIC largely due to lower risk factor levels, since the hazard of CVD death for each risk factor did not differ. Study differences reflect incompletely identified geographic variation that need further exploration, especially in the context of health disparities, but support maintaining low risk as a key to CVD prevention.
Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: Results from the randomized phase III CELESTIAL trial.
Authors: Ghassan K. Abou-Alfa, Tim Meyer, Ann-Lii Cheng, Anthony B. El-Khoueiry, Lorenza Rimassa, Baek-Yeol Ryoo, Irfan Cicin, Philippe Merle, Joong-Won Park, Jean-Frédéric Blanc, Luigi Bolondi, Heinz Josef Klümpen, Stephen Lam Chan, Vincenzo Dadduzio, Colin Hessel, Anne E. Borgman-Hagey, Gisela Schwab, Robin Kate Kelley
Journal: Journal of Clinical Oncology (2018)

207 Background: C, an inhibitor of MET, VEGFR, and AXL, has previously shown clinical activity in pts with advanced HCC. This phase 3 trial (NCT01908426) evaluated C vs P in previously treated pts with advanced HCC. Methods: In this double-blind, global, phase 3 trial, pts were randomized 2:1 to receive C (60 mg qd) or matched P stratified by disease etiology (HBV, HCV, other), geographic region (Asia, other), and presence of extrahepatic spread and/or macrovascular invasion (EHS/MVI). Eligible pts had pathologic diagnosis of HCC, Child-Pugh score A, ECOG PS ≤1, and must have received prior sorafenib. Pts received up to two lines of prior systemic therapy for HCC and must have progressed following at least one. The primary endpoint was overall survival (OS). Secondary endpoints were investigator-assessed progression-free survival (PFS) and objective response rate (ORR) per RECIST 1.1. The study was designed to detect a hazard ratio (HR) for OS of 0.76 (90% power, 2-sided α = 0.05) at the final analysis with two prespecified interim analyses at 50% and 75% of the planned 621 events. Results: As of 1 Jun 2017, 707 pts were randomized, and 484 deaths had occurred (317 out of 470 for C; 167 out of 237 for P). Baseline characteristics were balanced between the two arms: median age was 64 years, 82% were male, 38% had HBV, 24% had HCV, 25% enrolled in Asia, 78% had EHS, 30% had MVI, 85% had EHS/MVI, and 27% had received two prior systemic therapy regimens for advanced HCC. The study met the primary endpoint at the second planned interim analysis with median OS 10.2 mo for C vs 8.0 mo for P (HR 0.76, 95% CI 0.63-0.92; p = 0.0049). Median PFS was 5.2 mo for C vs 1.9 mo for P (HR 0.44, 95% CI 0.36-0.52; p &lt; 0.001), and ORR was 4% vs 0.4% (p = 0.0086). The most common grade 3/4 adverse events (predominantly grade 3) with higher incidence in the C vs P arm included hand-foot skin reaction (17% vs 0%), hypertension (16% vs 2%), increased aspartate aminotransferase (12% vs 7%), fatigue (10% vs 4%), and diarrhea (10% vs 2%). Conclusion: C significantly improved OS and PFS vs P in previously treated pts with advanced HCC. Adverse events were consistent with the known safety profile of C. Clinical trial information: NCT01908426.
Children with facial morphoea managing everyday life: a qualitative study
Authors: E. Stasiulis, B. Gladstone, K. Boydell, C. O'Brien, E. Pope, R. M. Laxer
Journal: British Journal of Dermatology (2018)

Facial morphoea is a chronic inflammatory skin disorder, typically presenting in childhood and adolescence, which can be disfiguring, and which has been suggested to cause mild-to-moderate impairment in quality of life.To explore the everyday experiences of children with facial morphoea by examining the psychosocial impact of living with facial morphoea and how children and their families manage its impact.We used a qualitative, social constructionist approach involving focus groups, in-depth interviews and drawing activities with 10 children with facial morphoea aged 8-17 years and 13 parents. Interpretive thematic analysis was utilized to examine the data.Children and parents reported on the stress of living with facial morphoea, which was related to the lack of knowledge about facial morphoea and the extent to which they perceived themselves as different from others. Self-perceptions were based on the visibility of the lesion, different phases of life transitions and the reactions of others (e.g. intrusive questioning and bullying). Medication routines, and side-effects such as weight gain, added to the stress experienced by the participants. To manage the impact of facial morphoea, children and their parents used strategies to normalize the experience by hiding physical signs of the illness, constructing explanations about what 'it' is, and by connecting with their peers.Understanding what it is like to live with facial morphoea from the perspectives of children and parents is important for devising ways to help children with the disorder achieve a better quality of life. Healthcare providers can help families access resources to manage anxiety, deal with bullying and construct adequate explanations of facial morphoea, in addition to providing opportunities for peer support.
Communication in the Chinese doctor–patient–family relationship: a qualitative study of expectations and experiences in a breast surgery setting
Authors: Siyu C Xiao, Lixuan Wang, Xinchun Liu, Kaveh Khoshnood, E Jennifer Edelman
Journal: The Lancet Global Health (2018)

BackgroundProblems facing the doctor-patient-family relationship in China, including violence against doctors, have received international attention. Possible reasons for tension in the medical relationship include systems-level challenges such as imbalances between provider and patient populations and a biased media. Yet limited empirical work has been done to examine how interpersonal dynamics, particularly communication, between patients, their family members, and providers contribute to satisfaction or tension. The aim of this study was to identify actionable communication factors contributing to tension in the Chinese doctor–patient–family relationship among breast surgeons, surgical patients, and their family members in an urban, tertiary-level teaching hospital in Hunan Province, China.MethodsWe conducted a qualitative study between June and August, 2015. We recruited a convenience sample of 29 participants, including 11 breast lumpectomy inpatients, nine corresponding family members, and nine breast surgeons. In-depth, semi-structured interviews were conducted perioperatively in Mandarin and English, with patients and family members interviewed before and after surgery when possible. Interviews were transcribed and translated into English. Transcripts were coded and a thematic analysis was applied.FindingsWe identified three emergent themes. First, trust deteriorated before and during the health-care experience. Second, the health-care-seeking experience for patients and family members was marked by unmet expectations for achieving a basic understanding as well as powerlessness. Third, societal pressures on doctors contributed to a state of learned helplessness.InterpretationOur findings suggest that tension between doctors, patients, and family members is associated with both interpersonal and structural challenges, with communication having an important role. Reforms at all levels are needed to promote empowerment by providing a more patient-centred experience for patients and family members while ensuring the wellbeing and security of providers.FundingDowns International Health Student Travel Fellowship, Yale School of Public Health; Office of Student Research, Yale School of Medicine.
I am a staff grade doctor in accident and emergency, and a member of the Royal College of Physicians. How will the advent of MMC affect any future decisions to enter specialist training in accident and emergency, or do vocational training, or train in another specialty (from SHO level?)
Authors: Bill Irish
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer
Authors: Dana E. Rathkopf, Tomasz M. Beer, Yohann Loriot, Celestia S. Higano, Andrew J. Armstrong, Cora N. Sternberg, Johann S. de Bono, Bertrand Tombal, Teresa Parli, Suman Bhattacharya, De Phung, Andrew Krivoshik, Howard I. Scher, Michael J. Morris
Journal: JAMA Oncology (2018)

Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients.To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS.PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016.Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment.Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula.In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0.23 (SA5; 95% CI, 0.19-0.30), and 0.23 (SA6; 95% CI, 0.19-0.30) (P < .001 for all). Correlations of rPFS and OS in enzalutamide-treated patients were 0.89 (95% CI, 0.86-0.92) by Spearman ρ and 0.72 (95% CI, 0.68-0.77) by Kendall τ.Sensitivity analyses in PREVAIL demonstrated the robustness of the PCWG2 rPFS definition using additional measures of progression. There was concordance between central and investigator review and a positive correlation between rPFS and OS among enzalutamide-treated patients.clinicaltrials.gov Identifier: NCT01212991.
<i>JAMA Cardiology</i>—The Year in Review, 2017
Authors: Robert O. Bonow
Journal: JAMA Cardiology (2018)

After the run up to the launch of JAMA Cardiology in April 2016 and the 9 issues that followed in its first year, 2017 marked our first full year of publishing.Looking back, 2017 was a period of steady growth in original science manuscripts, opinions, reviews, and educational content and continued interest in the journal by the cardiovascular community.The 1328 manuscript submissions (Table ) represent an increase of 10.8% and the 1040 research submissions represent an increase of 10% compared with the comparable 12 months of submissions in 2016.As with other competitive journals in our specialty, our acceptance rate of original science manuscripts has fallen into single digits.Our weekly online content is now sent to nearly 25 000 readers, and there were more than 900 000 full-text/PDF downloads last year.We maintain an active presence on social media, and remarkably, our Twitter and Facebook followers have increased by 76% and 45%, respectively, during the past year.Feedback on our monthly podcasts has been very positive.As a member of the JAMA Network, our close connections with the dedicated JAMA editors and staff facilitate the many channels of delivery of our weekly and monthly content.Cardiovascular science continues to advance at a breathtaking pace, as does its opportunities for multimedia dissemination, and it is a privilege to serve as a conduit of fresh ideas, new scientific findings, and informative reviews.The Table also lists the articles that have received the highest Altmetric scores in 2017 and the most citations over the past 2 years.This brief listing provides a glimpse of the broad cardiovascular landscape that is covered in JAMA Cardiology.Two articles highlight the ongoing interest among professional and lay readers on topics related to nutrition.Brandt et al 1 identified an association between counties in New York that implemented bans in trans-fats and hospital admissions for myocardial infarction and stroke compared with counties with trans-fat bans, and Scragg et al 3 in New Zealand reported a clinical trial in which vitamin D supplements did not have a positive association on incident cardiovascular disease.The article by Wang et al 2 on the accuracy of wrist-worn heart monitors points to the growing awareness of the possibilities of digital health.Our highest-cited articles cover topics of valvular heart disease and atrial fibrillation from important national registries 4,5 and an analysis of the lack of association of dipeptidyl peptidase 4 inhibitors and incident heart failure in patients with diabetes enrolled in international clinical trials. 6he primary value of the journal rests on its standing as a home for exceptional authors, and on behalf of the editors, I sincerely thank our authors who have accepted JAMA Cardiology as the source for publishing some of their finest efforts.We greatly appreciate the constructive comments, suggestions, and criticisms we continue to receive from our
FAMILIAL COMBINED HYPERLIPIDEMIA IS CHARACTERIZED BY HIGHER HEPATIC FDG UPTAKE AND VISCERAL ADIPOSE TISSUE VOLUME COMPARED TO HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA
Authors: Georgios Benetos, Konstantinos Toutouzas, Iosif Koutagiar, Ioannis Skoumas, Nikoletta Pianou, Spyros Galanakos, Alexandros Georgakopoulos, Alexios Antonopoulos, Maria Drakopoulou, Evangelos Oikonomou, Pavlos Kafouris, Emmanouil Athanasiadis, Marinos Metaxas, George Spyrou, Zoi Pallantza, Constantina Aggeli, Charalambos Antoniades, Georgia Keramida, Adrien Peters, Constantinos Anagnostopoulos, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2018)
Transcatheter Aortic Valve Replacement in Patients With Low-Flow, Low-Gradient Aortic Stenosis
Authors: Henrique Barbosa Ribeiro, Stamatios Lerakis, Martine Gilard, João L. Cavalcante, Raj Makkar, Howard C. Herrmann, Stephan Windecker, Maurice Enriquez-Sarano, Asim N. Cheema, Luis Nombela-Franco, Ignacio Amat-Santos, Antonio J. Muñoz-García, Bruno Garcia del Blanco, Alan Zajarias, John C. Lisko, Salim Hayek, Vasilis Babaliaros, Florent Le Ven, Thomas G. Gleason, Tarun Chakravarty, Wilson Y. Szeto, Marie-Annick Clavel, Alberto de Agustin, Vicenç Serra, John T. Schindler, Abdellaziz Dahou, Rishi Puri, Emilie Pelletier-Beaumont, Melanie Côté, Philippe Pibarot, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2018)
Lessons From a Year With Breast Cancer: An Academic Physician's Perspective
Authors: Barbara W. Trautner
Journal: Annals of Internal Medicine (2018)

On Being a Patient20 March 2018Lessons From a Year With Breast Cancer: An Academic Physician's PerspectiveBarbara W. Trautner, MD, PhDBarbara W. Trautner, MD, PhDMichael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas (B.W.T.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-1750 Audio Reading - “Lessons From a Year With Breast Cancer: An Academic Physician's Perspective” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Lessons From a Year With Breast Cancer," by B.W. Trautner. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I recall the exact moment I knew that I had breast cancer. A 47-year-old white woman without any risk factors for breast cancer presented for annual screening mammography. That patient was me. Our breast center has integrated mammography and ultrasound services, and my “dense breast tissue” on mammography prompts an immediate follow-up ultrasound nearly every year. I was completely relaxed as the ultrasonographer collected the images. My usual practice when I am the patient is to engage the technician in conversation to show that I appreciate the care provided. Yet, in this case, I was unable to engage her. She ... Author, Article, and Disclosure InformationAffiliations: Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas (B.W.T.)Financial Support: Dr. Trautner is supported by the National Institutes of Health; U.S. Department of Veterans Affairs; and Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413) at the Michael E. DeBakey Veterans Affairs Medical Center.Corresponding Author: Barbara W. Trautner, MD, PhD, IQuEST (152), 2002 Holcombe Boulevard, Houston, TX 77030; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Lessons From a Year With Breast Cancer: An Academic Physician's Perspective” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Lessons From a Year With Breast Cancer," by B.W. Trautner. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 20 March 2018Volume 168, Issue 6Page: 448-449KeywordsBiopsyBreast cancerHealth careMammographyMortalityNauseaRadiologistsSafetyTechniciansUltrasound imaging ePublished: 20 March 2018 Issue Published: 20 March 2018 PDF downloadLoading ...
When working abroad what advantages does membership of a British college (for example, MRCP) offer?
Authors: Michael Dobson
Journal: BMJ (2006)

<b>www.bmjcareers.com/advicezone</b> Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.