tbuckley/cabot-search huggingface dataset:
Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin
Authors: Michael Lauseker, Katharina Bachl, Anna Turkina, Edgar Faber, Witold Prejzner, Ulla Olsson‐Strömberg, Michele Baccarani, Elza Lomaia, Daniela Zackova, Gert Ossenkoppele, Laimonas Griskevicius, Gabriele Schubert‐Fritschle, Tomasz Sacha, Sonja Heibl, Perttu Koskenvesa, Andrija Bogdanovic, Richard E. Clark, Joelle Guilhot, Verena S. Hoffmann, Joerg Hasford, Andreas Hochhaus, Markus Pfirrmann
Journal: American Journal of Hematology (2019)

Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population-based and out-study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20-29% blasts, the hazard ratio (HR) was 1.32 (95%-confidence interval (CI): [0.7-2.6]). Patients with 20-29% blasts had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%-CI: [1.2-4.0], P = .008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs non-high risk) with an HR of 3.01 (95%-CI: [1.81-5.00], P < .001). Regarding the contrasting definitions of blast crisis, our data clearly supported the 20% cut-off over the 30% cut-off in this cohort. Based on our results, we conclude that a one-phase rather than a two-phase categorization of de novo advanced phase CML patients is appropriate.
Which Is the Best Mobilizing Regimen in POEMS Syndrome? a Retrospective Italian Study of Two Haematological Centres
Authors: Francesco Autore, Nicola Piccirillo, Andrea Nozza, Idanna Innocenti, Rossana Putzulu, Patrizia Chiusolo, Federica Sora, Gina Zini, Andrea Bacigalupo, Luca Castagna, Simona Sica, Stefania Bramanti, Luca Laurenti
Journal: Blood (2018)
RNA Metabolism in Embryonic Development and Differentiation
Authors: Paul R. Gross
Journal: New England Journal of Medicine (1967)

To devote an entire paper in this series on nucleic acids and proteins to a discussion of the role of RNA synthesis in very early development might appear disproportionate. The bias of those who study the problem is, however, that to do so is no more disproportionate than was the role given by Juvenal to the debauchee, Crispinus, in the original fish story.1 The turbot's affairs were meant to have significance for Rome beyond those of an Egyptian parvenu, and what is emerging from contemporary study of RNA metabolism in animal embryos may be expected to have important applications to . . .
Simulated patient encounter to assess and improve fellows' ability to manage chemotherapy infusion reactions.
Authors: Danielle Elise Zimmerman
Journal: Journal of Clinical Oncology (2019)

TPS10541 Background: Medical educators have adopted simulation-based exercises (SBEs) because studies of their use in the aviation industry and other technical fields have shown that they reduce human error. While use of simulation has increased in undergraduate and graduate medical education, it hasn’t been used as frequently in educating subspecialty fellows. Fewer than 5% of participants in a survey of different subspecialists indicated that simulations were part of their fellowship curriculum (1) even though simulation-based training is an ACGME program requirement (2). Chemotherapy infusion reactions (CIRs) occur with about 5% of all cytotoxic chemotherapies and even more frequently with biologics (3). These CIRs present significant morbidity and cost. HFS improves knowledge and confidence in medical trainees (4). Therefore, I designed a high fidelity simulation (HFS)-based curriculum to measure fellows’ current medical knowledge and provide a mechanism for gaining increased understanding and confidence. Across subspecialty graduation medical education, only one SBE with IRs has been performed, and that project aimed only to measure existing knowledge (5). This project aims to measure oncology fellows’ knowledge of and confidence in CIR management, measure attitudes regarding SBEs, measure improvement in knowledge following the SBEs, and assess for changes in behavior (management of CIRS) that may occur following these interventions. Methods: The HFS takes place in the VA Hospital Interdisciplinary Simulation and Education Center, which consists of a programmable mannequin that can “talk” through a speaker and convey physical exam signs in an “outpatient clinic.” Participants will interact with the mannequin, who will be a patient experiencing a paclitaxel infusion reaction. An evaluator will be grading the participant’s actions with an OSCE style checklist. Immediate debriefing will be followed by a didactic. Participants will complete post-intervention surveys regarding their confidence in and knowledge of management of CIRS. Participants will later be evaluated on their attitudes regarding the simulation, their knowledge of CIR management, and will also provide critique of the same interaction done by another provider. These HFS-based activities will allow evaluation of fellows’ current knowledge of and comfort with CIRS, fellows’ attitudes regarding the intervention, improvement in knowledge occurred following the intervention, and anticipated change in management.
NHS pensions: law firm invites doctors forced to join 2015 scheme to join claim against government
Authors: Clare Dyer
Journal: BMJ (2019)

A law firm that successfully challenged the UK government over changes to younger judges’ pensions is inviting doctors who were forced to transfer to the 2015 NHS pension, while older colleagues were allowed to stay in the old scheme, to join a new discrimination claim.

Leigh Day has set up a website on which doctors who were obliged to transfer to the new scheme can register to take their cases to an employment tribunal (https://pensionschallenge.co.uk/doctors/).

In 2017 a tribunal ruled that the government unlawfully discriminated against younger judges by requiring them to leave the valuable judicial pensions scheme. The …
hnRNPU/TrkB Defines a Chromatin Accessibility Checkpoint for Liver Injury and Nonalcoholic Steatohepatitis Pathogenesis
Authors: Jing Xiong, Tongyu Liu, Lin Mi, Henry Kuang, Xuelian Xiong, Zhimin Chen, Siming Li, Jiandie D. Lin
Journal: Hepatology (2019)

Background and Aims Nonalcoholic steatohepatitis (NASH) is a progressive liver disease that is characterized by liver injury, inflammation, and fibrosis. NASH pathogenesis is linked to reprogramming of chromatin landscape in the liver that predisposes hepatocytes to stress‐induced tissue injury. However, the molecular nature of the putative checkpoint that maintains chromatin architecture and preserves hepatocyte health remains elusive. Approach and Results Here we show that heterogeneous nuclear ribonucleoprotein U (hnRNPU), a nuclear matrix protein that governs chromatin architecture and gene transcription, is a critical factor that couples chromatin disruption to NASH pathogenesis. RNA‐seq and chromatin immunoprecipitation‐seq studies revealed an extensive overlap between hnRNPU occupancy and altered gene expression during NASH. Hepatocyte‐specific inactivation of hnRNPU disrupted liver chromatin accessibility, activated molecular signature of NASH, and sensitized mice to diet‐induced NASH pathogenesis. Mechanistically, hnRNPU deficiency stimulated the expression of a truncated isoform of TrkB (TRKB‐T1) that promotes inflammatory signaling in hepatocytes and stress‐induced cell death. Brain‐derived neurotrophic factor treatment reduced membrane TRKB‐T1 protein and protected mice from diet‐induced NASH. Conclusions These findings illustrate a mechanism through which disruptions of chromatin architecture drive the emergence of disease‐specific signaling patterns that promote liver injury and exacerbate NASH pathogenesis.
Patient compliance to oral anticancer chemotherapy evaluated in breast and colorectal cancer patients receiving capecitabine: The OCTO study.
Authors: Emilie Henin, Aurelie Bourmaud, Olivier Colomban, Vérane Schwiertz, Veronique Regnier, Benoit You, Florence Ranchon, Jerome Guitton, Raymonde Maraval-Gaget, Pascal Girard, Franck Chauvin, Gilles Freyer, Michel Tod, Catherine Rioufol, Veronique N. Trillet-Lenoir
Journal: Journal of Clinical Oncology (2013)

e13594 Background: Given the expanding use of oral chemotherapies, optimal compliance to treatment is critical to achieve the best clinical outcome in terms of efficacy and safety. The aim of the OCTO clinical study was to measure patient compliance, either electronically or by self-assessment, to capecitabine-based treatment. Methods: A cohort of patients with either locally advanced or metastatic, breast or colorectal, cancer were monitored for 6 cycles, and ambulatory treated with monotherapy of capecitabine (Xeloda). Treatment was prescribed at 1250 mg/m² as a combination of 500 and 150 mg pills, taken twice daily for 14 days every 3-week cycle. Tumor response was evaluated after 3 and 6 cycles using the RECIST criteria. Toxicity was evaluated using the NCI CTC scale. Compliance was assessed in all patients by self-completed questionnaires on disease, treatment and ambulatory management of side effects; and in half of the cohort by electronic medication event monitoring systems (MEMS) recording the opening times of the pill bottle. Results: Forty patients were enrolled between November 2008 and September 2011 and treated by capecitabine for an average of 4.75 cycles (range: 1-6). 63% patients completed 6 cycles, 22% and 15% patients discontinued due to respectively disease progression and adverse events. Best tumor response was evaluable in 35 patients: 23% had partial response, 54% stable disease and 23% progressed. Hand-foot syndrome was the most reported toxicity (77% patients), and to a lesser extent diarrhea (45%), nausea (30%) and vomiting (30%). In the MEMS cohort, 20 patients were included. Patient compliance was excellent with very few missing occasions (23/2272 records). Timing of morning doses was less variable (p=0.03) than timing of evening ones. Thirty-eight questionnaires were returned. Autonomy of ambulatory oral treatment was appreciated by 54% patients, while resulting in anxiety in 6%. Only 39% patients were concerned by the potential impact of non-compliance while 45% declined answering the question. Conclusions: Compliance to oral anticancer chemotherapy was found excellent in this population, with few deviations from prescription.
Oncolytic Viruses Engineered to Enforce Leptin Expression Reprogram Tumor-Infiltrating T Cell Metabolism and Promote Tumor Clearance
Authors: Dayana B. Rivadeneira, Kristin DePeaux, Yiyang Wang, Aditi Kulkarni, Tracy Tabib, Ashley V. Menk, Padmavathi Sampath, Robert Lafyatis, Robert L. Ferris, Saumendra N. Sarkar, Stephen H. Thorne, Greg M. Delgoffe
Journal: Immunity (2019)
P011 The role of cellular metabolism in rheumatoid and psoriatic arthritis
Authors: CC Cunningham, S Ansboro, T McGarry, DJ Veale, U Fearon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) share common features such as synovial hyperplasia, cartilage degradation and subchondral bone remodelling, however, there are distinct pathologic differences, which aid their diagnosis, and may account for the differential responses to specific treatments. Increased proliferation and angiogenesis transforms the synovium into an aggressive, tumour-like 'pannus' which contributes to disease pathogenesis. Hypoxia, resulting from dysregulated angiogenesis, can cause cells to switch from mitochondrial respiration to anaerobic glycolysis in order to meet the cellular energy demand. The RA synovium is more hyperplastic and invasive than that of PsA, while a more abnormal vasculature is observed in the PsA synovium and correlates with a reduction in tissue pO2 levels. <h3>Objectives</h3> The aim of this study was to compare the metabolic profiles of RA and PsA synovial fibroblast cells (SFC) and to determine whether there is a correlation between dysregulated metabolism, cell function and disease pathogenesis. <h3>Methods</h3> The metabolic profiles of RA and PsA SFC were analysed using the XF96 Extracellular Flux Analyzer. Gene expression was determined by quantitative-PCR. SFC migration and invasion were observed by microscopy following wound-scratch and transwell invasion assays. <h3>Results</h3> RA SFC displayed increased migratory capacity and invasiveness compared to PsA SFC. Expression of IL-6, IL-8 and the glycolytic markers, GLUT1/3, HK2, PKM1/2, PDK2 and LDHA is higher in RA SFC compared to PsA SFC and is upregulated following TNF-α treatment. PsA SFC displayed higher baseline oxygen consumption rate (OCR), baseline extracellular acidification rate (ECAR) and ECAR:OCR ratio than RA SFC. Treatment with TNF-α increases the ECAR:OCR ratio in both RA and PsA SFC. <h3>Conclusions</h3> Consistent with clinical observations, RA SFC have a greater migratory and invasive capacity than PsA SFC. Despite the lower expression of glycolytic markers, PsA SFC display a more glycolytic phenotype than RA SFC, as indicated by a higher ECAR:OCR ratio. Interestingly, however, RA SFC display a higher glycolytic reserve, possibly due to the higher expression of glycolytic markers, which can be called upon in response to increases in cellular ATP demand. Preliminary data suggest a positive correlation between the ECAR:OCR ratio and DAS28 in RA but a negative correlation in PsA. Further investigation is required to determine the precise role of metabolism in specific pathogenic processes. <h3>Disclosure of Interest</h3> None declared.
In Memoriam—John Ross Jr, MD
Authors: Eugene Braunwald
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
The Role of Bariatric Surgery in Managing the Macrovascular Complications of Obesity-Related Type 2 Diabetes
Authors: Edward H. Livingston
Journal: JAMA (2019)

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
Effectiveness of Interventions Aimed at Increasing Statin-Prescribing Rates in Primary Cardiovascular Disease Prevention
Authors: Robert T. Sparrow, Anam M. Khan, Laura E. Ferreira-Legere, Dennis T. Ko, Cynthia A. Jackevicius, Shaun G. Goodman, Todd J. Anderson, Dawn Stacey, Ildiko Tiszovszky, Michael E. Farkouh, Jack V. Tu, Jacob A. Udell
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> Statins are a cornerstone medication in cardiovascular disease prevention, but their use in clinical practice remains suboptimal, with less than half of people who are indicated for statins actually taking the medication. <h3>Objective</h3> To perform a systematic review and synthesis of the literature on patient-oriented and physician-oriented interventions aimed at increasing statin-prescribing rates in adults without a history of cardiovascular disease. <h3>Evidence Review</h3> PubMed, Embase, and the Cochrane Library were searched for randomized clinical trials published between January 2000 and May 2019. Data abstraction was performed using the Cochrane Public Health Review Group's data collection template, and a narrative synthesis of study results was conducted. The risk of bias in each study was qualitatively assessed, and a funnel plot was created to further evaluate the risk of publication bias. <h3>Findings</h3> Among 7948 citations and 128 full-text articles reviewed, 20 studies (of 109 807 patients) were included in the review. Eight trials reported a statistically significant increases in statin-prescribing rates. Among the effective trials, absolute effect sizes ranged from 4.2% (95% CI, 2.2%-6.4%) to 23% (95% CI, 7.3%-38.9%) and odds ratios from 1.29 (95% CI, 1.01-1.66) to 11.8 (95% CI, 8.8-15.9). Patient-education initiatives were the most commonly effective intervention, with 4 of 7 trials indicating increases in statin-prescribing rates. Two trials combined electronic decision-support tools with audit-and-feedback systems, both of which were effective overall. Physician-education programs without dynamic input regarding patient risk or updated treatment recommendations were generally found to be less effective. <h3>Conclusions and Relevance</h3> While heterogeneous in their interventions and outcomes, a number of interventions have demonstrated increases in statin-prescribing rates, with patient-education initiatives demonstrating more promising results than those focused on physician education alone. As opposed to more education about generic recommendations, tailored patient-focused and physician-focused interventions were more effective when they provided personalized cardiovascular risk information, dynamic decision-support tools, or audit-and-feedback reports in a multicomponent program. There are a number of modestly successful approaches to implement increases in rates of statin prescribing, a proven yet underused cardiovascular disease prevention class of therapy.
Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades
Authors: Nariman Sepehrvand, Wendimagegn Alemayehu, Debraj Das, Arjun K. Gupta, Pishoy Gouda, Anukul Ghimire, Amy X. Du, Sanaz Hatami, Hazal E. Babadagli, Sanam Verma, Zakariya Kashour, Justin A. Ezekowitz
Journal: JAMA Cardiology (2019)

Pragmatic trials test interventions using designs that produce results that may be more applicable to the population in which the intervention will be eventually applied.To investigate how pragmatic or explanatory cardiovascular (CV) randomized clinical trials (RCT) are, and if this has changed over time.Six major medical and CV journals, including New England Journal of Medicine, Lancet, JAMA, Circulation, European Heart Journal, and Journal of the American College of Cardiology.All CV-related RCTs published during 2000, 2005, 2010, and 2015 were identified and included.Included RCTs were assessed by 2 independent adjudicators with expertise in RCT and CV medicine.The outcome measure was the level of pragmatism evaluated using the Pragmatic Explanatory Continuum Index Summary (PRECIS)-2 tool, which uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis.Of 616 RCTs, the mean (SD) PRECIS-2 score was 3.26 (0.70). The level of pragmatism increased over time from a mean (SD) score of 3.07 (0.74) in 2000 to 3.46 (0.67) in 2015 (P < .001 for trend; Cohen d relative effect size, 0.56). The increase occurred mainly in the domains of eligibility, setting, intervention delivery, and primary end point. PRECIS-2 score was higher for neutral trials than those with positive results (P < .001) and in phase III/IV trials compared with phase I/II trials (P < .001) but similar between different sources of funding (public, industry, or both; P = .38). More pragmatic trials had more sites, larger sample sizes, longer follow-ups, and mortality as the primary end point.The level of pragmatism increased moderately over 2 decades of CV trials. Understanding the domains of current and future clinical trials will aid in the design and delivery of CV trials with broader application.