tbuckley/cabot-search huggingface dataset:
The next step forward?
Authors: Ilona Kickbusch, Christian Franz, Maike Voss
Journal: BMJ (2018)

Clinical and laboratory studies in a patient whose rheumatoid arthritis appeared to be exacerbated by dairy produce showed that challenge with milk and cheese resulted in a produced increase in synovitis and changes in immune complexes, IgE antibodies, and heat-damaged red cell clearance rates. Exclusion of dairy products from the diet produced a considerable improvement in her previously aggressive disease.
CHARACTERISTICS OF CARDIOVASCULAR DISEASE IN CANCER PATIENTS: A CASE CONTROL STUDY
Authors: Nachiket Madhav Apte, Magdy Hanna, Parinita Dherange, Desiree Dawson, Jessica Atkins, Prakash Peddi, Pratap Reddy, Jerry McLarty, Richard Mansour
Journal: Journal of the American College of Cardiology (2018)
IgE‐expressing memory B cells and plasmablasts are increased in blood of children with asthma, food allergy, and atopic dermatitis
Authors: J. J. Heeringa, L. Rijvers, N. J. Arends, G. J. Driessen, S. G. Pasmans, J. J. M. van Dongen, J. C. de Jongste, M. C. van Zelm
Journal: Allergy (2018)

Despite the critical role of soluble IgE in the pathology of IgE-mediated allergic disease, little is known about abnormalities in the memory B cells and plasma cells that produce IgE in allergic patients. We here applied a flow cytometric approach to cross-sectionally study blood IgE+ memory B cells and plasmablasts in 149 children with atopic dermatitis, food allergy, and/or asthma and correlated these to helper T(h)2 cells and eosinophils. Children with allergic disease had increased numbers of IgE+CD27- and IgE+CD27+ memory B cells and IgE+ plasmablasts, as well as increased numbers of eosinophils and Th2 cells. IgE+ plasmablast numbers correlated positively with Th2 cell numbers. These findings open new possibilities for diagnosis and monitoring of treatment in patients with allergic diseases.
THE ROLE OF PLAQUE MORPHOLOGY IN DISCRIMINATING EARLY VERSUS LATE OCCURRING ACUTE CORONARY SYNDROME: THE ICONIC TRIAL
Authors: Wijnand J. Stuijfzand, Benjamin Chow, Fay Lin, Peña M. Jessica, Daniele Andreini, Filippo Cademartiri, Kavitha Chinnaiyan, Ricardo Cury, Gudrun Feuchtner, Martin Hadamitzky, Yong-Jin Kim, Jonathon Leipsic, Hugo Marques, Gianluca Pontone, Todd Villines, Daniel Berman, Matthew Budoff, Leslee Shaw, Jeroen J. Bax, James K. Min, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2018)
ASSESSMENT OF RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Mahesh Aher, Sandeep Bansal, Hermohander Isser, Rajat Jain, Praloy Chakraborty, Preeti Gupta, Mahendra Kumar, Ankit Jain
Journal: Journal of the American College of Cardiology (2018)
Review: Multilevel and patient-level implementation strategies reduce BP more than usual care in hypertension
Authors: Anne M. Holbrook
Journal: Annals of Internal Medicine (2018)

Source Citation Mills KT, Obst KM, Shen W, et al. Comparative effectiveness of implementation strategies for blood pressure control in hypertensive patients: a systematic review and meta-analysis. Ann Intern Med. 2018;168:110-20. 29277852
Use new screening test for early onset pre-eclampsia, say researchers
Authors: Jacqui Wise
Journal: BMJ (2018)

The current checklist method of screening for early onset pre-eclampsia is poor and should be replaced with a method combining maternal factors and various easily measured biomarkers, say researchers.

The authors of a prospective multicentre study published in Ultrasound in Obstetrics & Gynecology said that using this alternative method could double the detection rate of preterm pre-eclampsia.1 When pre-eclampsia leads to preterm birth before 37 weeks’ gestation the risk for complications is particularly high.

Pre-eclampsia complicates 2-3% of pregnancies and is a major cause of mortality and morbidity in mothers and of perinatal death and impairment in babies. Recent evidence suggests that giving low dose aspirin to women at high risk of the …
Early Changes in Health Insurance Coverage under the Trump Administration
Authors: Benjamin D Sommers, Kathryn L Clark, Arnold M Epstein
Journal: New England Journal of Medicine (2018)

Changes in Health Insurance Coverage in 2017 Survey data showed that the percentage of uninsured adults, 18 to 64 years of age, decreased by 6.3 percentage points between the fourth quarter of 2013 and the fourth quarter of 2016 and increased by 1.3 percentage points from January through December 2017.
P036 Neutrophil extracellular traps in systemic lupus: a proteomic analysis
Authors: F Pratesi, M Bruschi, A Bonanni, A Petretto, I Puxeddu, G Candiano, G Ghiggeri, P Migliorini
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> An altered formation and/or removal of neutrophil extracellular traps (NET) has been recently proposed as key event in systemic lupus (SLE): in fact, NETs have been detected in the skin and kidney of SLE patients, low density granulocytes from SLE patients form more frequently NETs and NET degradation is impaired. However, no data are yet available on NET composition in SLE patients. <h3>Objectives</h3> The aim of the study is to compare NETs from SLE patients and normals by means of proteomic analysis. <h3>Methods</h3> Neutrophils from 11 normals and 16 SLE patients (9/16 with active disease) were stimulated by PMA, NET proteins were released in supernatants by DNase treatment and characterised by Fusion Orbitrap Mass spectrometry. <h3>Results</h3> Overall, 802 proteins were detected (50% identified in all the samples); 236 are exclusively found in control NETs, 57 only in active SLE and 22 in inactive SLE. Multidimensional scaling (MDS) showed that NETs composition/amount allows the identification of 3 different clusters corresponding to active SLE, inactive SLE and controls in a bi-dimensional scatter plot. The heat map describing the proteome profiles shows two different clusters of proteins, one represented by 16 proteins that were more expressed in inactive disease, the other by 9 proteins more expressed in active SLE. A preliminary analysis of posttranslational modifications showed a differential expression of methyloxidized and phosphorylated proteins. <h3>Conclusions</h3> The data obtained suggest that NET composition and type/extent of posttranslational modifications are different in active SLE, in inactive disease and in controls. The different cytokine and autoantibody environment that distinguishes SLE flares from inactive may activate different pathways in NET induction and condition the quality and quantity of NET-associated proteins. <h3>Disclosure of interest</h3> None declared
Long Noncoding RNA LINC01234 Functions as a Competing Endogenous RNA to Regulate CBFB Expression by Sponging miR-204-5p in Gastric Cancer
Authors: Xin Chen, Zhenyao Chen, Shanxun Yu, Fengqi Nie, Shuai Yan, Pei Ma, Qinnan Chen, Chenchen Wei, Hangjiang Fu, Tianwei Xu, Shengnan Ren, Ming Sun, Zhaoxia Wang
Journal: Clinical Cancer Research (2018)

Purpose: Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the overall biological roles and clinical significance of most lncRNAs in gastric carcinogenesis are not fully understood. We investigated the clinical significance, biological function, and mechanism of LINC01234 in gastric cancer.Experimental Design: First, we analyzed LINC01234 alterations in gastric cancerous and noncancerous tissues through an analysis of sequencing data obtained from The Cancer Genome Atlas. Next, we evaluated the effect of LINC01234 on the gastric cancer cell proliferation and apoptosis, and its regulation of miR-204-5p by acting as a competing endogenous RNA (ceRNA). The animal model was used to support the in vitro experimental findings.Results: We found that LINC01234 expression was significantly upregulated in gastric cancer tissues and was associated with larger tumor size, advanced TNM stage, lymph node metastasis, and shorter survival time. Furthermore, knockdown of LINC01234-induced apoptosis and growth arrest in vitro and inhibited tumorigenesis in mouse xenografts. Mechanistic investigations indicated that LINC01234 functioned as a ceRNA for miR-204-5p, thereby leading to the derepression of its endogenous target core-binding factor β (CBFB).Conclusions: LINC01234 is significantly overexpressed in gastric cancer, and LINC01234-miR-204-5p-CBFB axis plays a critical role in gastric cancer tumorigenesis. Our findings may provide a potential new target for gastric cancer diagnosis and therapy. Clin Cancer Res; 24(8); 2002-14. ©2018 AACR.
Identifying locally invasive brain metastases to improve control and survival
Authors: Rasheed Zakaria, Philip Rudland, Nitika Rathi, Andrew Brodbelt, Angela Platt-higgins, Michael D Jenkinson
Journal: Neuro-Oncology (2018)

Imaging and pathological investigations of patients with brain metastases are identifying more local invasion than previously appreciated. Recurrence rates are 15–20% after focal treatment, and targeted treatment of the invasive areas may help improve local control. Prospective image guided study using matched MRI and biopsy samples at the brain-metastasis interface. Retrospective case note review of operative approach and survival. Samples were obtained during image guided neurosurgical resection of 26 metastases. Pathological analysis of 71/118 samples showed tumour cells present beyond the apparent brain-metastasis interface whereas 20/26 tumours were reported to show a clear macroscopic plane by the operating surgeon indicating significant discordance (kappa 0.02). There was no association of an invasive growth pattern with the type of primary cancer (Fisher’s exact test p=0.94) nor subsequent survival (HR 95% CI 0.42–1.28, p=0.28). It was not possible to identify a locally invasive phenotype using preoperative conventional, diffusion or perfusion MRI. In a retrospective review of 370 previously operated cases, gross total resection versus piecemeal resection was associated with an improved overall survival which was lost after 12 months, which may be due to the competing risk of progressive extracranial disease. There is a biological basis for extended local treatments such as supramarginal resection or cavity boost radiosurgery in patients with brain metastases. Identifying patients who will benefit from such treatments remains problematic.
TRANSCATHETER EDGE-TO-EDGE REPAIR OF SEVERE TRICUSPID REGURGITATION: MIDTERM OUTCOME IN 50 PATIENTS WITH RIGHT-SIDED HEART FAILURE
Authors: Mathias Orban, Christian Besler, Daniel Braun, Marion Zimmer, Martin Orban, Axel Linke, Joerg Seeburger, Thomas Stocker, Michael Nabauer, Michael Borger, Julinda Mehilli, Christian Hagl, Holger Thiele, Steffen Massberg, Joerg Ender, Philipp Lurz, Joerg Hausleiter
Journal: Journal of the American College of Cardiology (2018)
Genome-wide association study identifies three novel susceptibility loci for systemic lupus erythematosus in Han Chinese
Authors: L. Liu, X. Zuo, Z. Zhu, L. Wen, C. Yang, C. Zhu, L. Tang, Y. Cheng, M. Chen, F. Zhou, X. Zheng, W. Wang, X. Yin, H. Tang, L. Sun, S. Yang, Y. Sheng, Y. Cui, X. Zhang
Journal: British Journal of Dermatology (2018)
Abstract P4-04-04: Identification and development of oral estrogen receptor PROTAC degraders for breast cancer
Authors: JJ Flanagan, Y Qian, SM Gough, M Andreoli, M Bookbinder, J Bradley, E Rousseau, R Willard, CM Crews, AP Crew, I Taylor, J Houston
Journal: Cancer Research (2018)

Abstract ER-positive breast cancers comprise approximately 70-80% of all newly diagnosed cases. Downregulation or degradation of ER is a treatment approach currently used in the clinic to target estrogen receptor signaling. Faslodex, the only clinically-approved ER-downregulator, is administered as a monthly intramuscular injection with limiting pharmaceutical properties. Reasoning that an orally-available estrogen receptor degrader would be beneficial to patients, we have leveraged our experience in targeted protein degradation to generate and characterize novel proteolysis targeting chimeras (PROTACs) against estrogen receptor alpha. PROTACs are heterobifunctional molecules that facilitate the formation of a “trimer complex” comprised of the PROTAC, a pathogenic target protein of interest and an E3 ligase, which catalyzes the ubiquitylation and subsequent degradation of the target protein via the proteasome. To identify novel ER degraders (ER PROTACs), we have used several in vitro assays to characterize the extent of target engagement and receptor degradation. Potent ER PROTACs with good oral exposure and other pharmaceutical properties in multiple pre-clinical species were further evaluated in breast cancer xenograft models. Orally-administered ER PROTACs achieved &amp;gt;80% degradation of estrogen receptor alpha and demonstrated single agent tumor growth inhibition in these disease models. Further, combination with a CDK4/6 inhibitor resulted in the expected improvement in anti-proliferative activity. Citation Format: Flanagan JJ, Qian Y, Gough SM, Andreoli M, Bookbinder M, Bradley J, Rousseau E, Willard R, Crews CM, Crew AP, Taylor I, Houston J. Identification and development of oral estrogen receptor PROTAC degraders for breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-04.
Radiosurgery for malignant melanoma brain polymetastasis
Authors: Sara Meade, Charles Fong, Geoff Heyes, Rosemary Simmons, Ruth Stange, Timothy Jackson, Helen Benghiat, Garth Cruickshank, Neil Steven, Paul Sanghera, Andrew Hartley
Journal: Neuro-Oncology (2018)

To compare the outcomes following Cyberknife radiosurgery (SRS) to patients with malignant melanoma with solitary metastasis (SM), oligometastasis (2–4 metastases (OM)) and polymetastasis (>4 metastasis (PM)) within a departmental philosophy of whole brain radiotherapy avoidance for melanoma brain metastases. NHS England selection criteria were used. All target volumes were approved by a consultant neuro-radiologist and no planning target volume was used. Thirty-nine patients (SM=18, OM=14, PM=7) were treated June 2013-June 2016. In total 130 individual metastases were treated of which 15 were metachronous following initial SRS. Seven lesions were treated with 3 fractions (24-30Gy), 123 lesions received a single fraction (15-24Gy). The endpoints for this study were lesional control (LC), distant brain control (DBC) and overall survival (OS). For all lesions at 6 months: LC 88%, DBC 72%, OS 77% and at 12 months LC 74%, DBC 50%, OS 50%. DBC at 6months: SM 92%, OM 47%, PM 80% and at 12 months SM 71%, OM 23%, PM 45%. OS at 6 months: SM 86%, OM 67%, PM 85% and at 12 months SM 79%, OM 28%, PM 57%. Whilst outcomes for SM are as expected, treatment of PM appears feasible and there may be a self selecting subgroup of patients with small volume PM who benefit from SRS in the biological/immune therapy era. The apparent lower rate of DBC and OS with OM and the effect of both lesional volume and biological/immune therapy history will be discussed.
IMPACT OF POSITIVE AIRWAY PRESSURE THERAPY ON CARDIAC FUNCTION IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION AND OBSTRUCTIVE SLEEP APNEA: A RANDOMIZED, CONTROLLED TRIAL
Authors: Thomas Bitter, Kawa Mohemed, Henrik Fox, Birgit Wellmann, Dieter Horstkotte
Journal: Journal of the American College of Cardiology (2018)
American Diabetes Association’s Standards of Care: A Paradigm Shift in the Dissemination of Information
Authors: William T. Cefalu, Erika Gebel Berg, Matthew P. Petersen, Tamara Darsow
Journal: Diabetes Care (2018)

It is well understood that diabetes is a complex, chronic illness in which glycemic control reduces the development and progression of macrovascular and microvascular complications. Achieving risk reduction requires continuous medical care and self-management, with multifactorial risk-management strategies beyond just glycemic control, including lifestyle changes and cardiovascular risk reduction. Given the current knowledge of what is required to reduce complications, improve quality of life, and prevent progression to overt disease states, it is important that providers caring for people with diabetes have the latest and most updated clinical translation of the evidence as they consider the day-to-day management of their patients. In this regard, the American Diabetes Association (ADA) has been actively involved in the development and dissemination of diabetes care standards, guidelines, and related documents to support and improve patient care for over 25 years. Specifically, the ADA’s “Standards of Medical Care in Diabetes,” referred to as the Standards of Care, has always been intended to provide clinicians, patients, researchers, payers, and other interested individuals with evidence-based information on all aspects of diabetes care, general treatment goals, and tools to evaluate the quality of care (1).

The recent acceleration of the pace of new information being released regarding diabetes care and research has been startling. To put this in perspective, the first ADA Standards of Care, published in 1989, provided recommendations based on the available evidence at that time and filled only four pages in Diabetes Care (2). In the most recent update, 28 years later, the document is well over 170 pages! Over 40 new type 2 diabetes treatment options have been approved since 2005 (3), not even counting advances in technology, such as continuous glucose monitoring. In the last year alone, there have been many significant changes to the Standards of Care, and the 2018 version …
CQC may not be fit to register GP practices, MPs warn
Authors: Adrian O’Dowd
Journal: BMJ (2012)

MPs have raised fears that the Care Quality Commission (CQC) might be unfit to register the 10 000 general practices in England later this year.

In a review by the House of Commons Committee of Public Accounts of the commission’s operations, MPs heavily criticise the CQC for failing to be an effective regulator and raise serious questions over its governance, leadership, and culture.

“We are far from convinced that the CQC is up to the major challenge of registering and assessing 10 000 GP practices this year,” said Margaret Hodge, Labour MP for …
PYP IMAGING WITH CZT CAMERAS IS A SENSITIVE AND SPECIFIC IMAGING MODALITY TO DIAGNOSE TTR CARDIAC AMYLOIDOSIS
Authors: Rachelle Morgenstern, Ted Pozniakoff, Adam Castano, Zachary Bokhari, Corduta Chiuzan, Mathew Maurer, Sabahat Bokhari
Journal: Journal of the American College of Cardiology (2018)
I am an undergraduate medical student interested in pursuing a postgraduate degree in sports medicine. Can you advise me on the various options available in and out of the UK?
Authors: Dave Triffitt
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the 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>
TREND, ETIOLOGIES AND THE PREDICTORS OF 90-DAY RE-ADMISSIONS AFTER THE USE OF PERCUTANEOUS VENTRICULAR ASSIST DEVICE (PVAD): A NATIONAL POPULATION-BASED COHORT STUDY
Authors: Fnu Hafeez Hassan, Byomesh Tripathi, Sameer Ahmed, Saurav Chatterjee, Sandeep Dayanand, Chayakrit Krittanawong, Suchita Gupta, Shilpkumar Arora, Mohammad Nour Zabad, Parasuram Krishnamoorthi, Sanjog Karla, Gregg Pressman, Jon George, Aman Amanullah, Vincent Figueredo
Journal: Journal of the American College of Cardiology (2018)
Abiraterone acetate in metastatic castration-resistant prostate cancer post-docetaxel: A “real-life” retrospective analysis of outcomes in a Brazilian public health institution.
Authors: Thais Caroline Menegasso Flores, Carolina da Silva Miranda Emerich, Facundo Zaffaroni, Márcio Debiasi, Carolina Dutra
Journal: Journal of Clinical Oncology (2018)

287 Background: Abiraterone acetate (AA) is a selective inhibitor of CYP17 and showed to improve overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients progressing after docetaxel in the COU-AA-301 trial. AA is not widely available for patients treated at the public health system (SUS) and real-life data regarding this treatment in Brazil are lacking. This study aims to describe the epidemiological profile and outcomes of patients diagnosed with mCRPC who progressed after docetaxel treated with AA in a Brazilian public health institution. Methods: We retrospectively reviewed clinical data of patients with mCRPC who progressed after docetaxel and were treated with AA (1000mg/d PO) plus prednisone (5mg/BID PO) from January 2015 to December 2016 in our instituition. Patient demographic and clinical characteristics were described using summary statistics. Kaplan-Meyer method was used to estimate OS and time to prostate-specific antigen (PSA) progression for AA treatment. Results: 37 patients were included for analysis. Median age was 71 yo. Median PSA at AA start was 57 ng/mL (range 0.10-6,676.00), Gleason score was &gt; 7 in 59.5% and ≤7 in 32.4%. 75.7% of patients had symptomatic bone metastasis requiring opioids. At a median follow up of 68 months, the median duration of treatment was 5 months with a median OS of 13 months and a median time to PSA progression of 4 months. Gleason score did not correlate with outcomes (p = 0.56). Although patients who had a prior hormone therapy (PHT) &gt; 12mo had better OS (15mo) when compared to those with PHT &lt; 12 (10mo), this difference was not statistically significant (p = 0.26). AA was well tolerated and disease progression was the main reason for AA discontinuation (86.8%). Conclusions: This analysis shows that AA is an effective and safe treatment option for patients in public health system in a developing country, with comparable outcomes to COU 301 trial in OS, showing benefits regardless Gleason and PHT status. These patients did not receive later lines of treatment, and this could have impacted OS in this study. The incorporation of AA in the SUS should be considered.
Young and middle-aged adults with airflow limitation according to lower limit of normal but not fixed ratio have high morbidity and poor survival: a population-based prospective cohort study
Authors: Yunus Çolak, Shoaib Afzal, Børge G. Nordestgaard, Jørgen Vestbo, Peter Lange
Journal: European Respiratory Journal (2018)

A presumed consequence of using a fixed ratio for the definition of airflow limitation (AFL) has been overdiagnosis among older individuals and underdiagnosis among younger individuals. However, the prognosis of younger individuals with potentially underdiagnosed AFL is poorly described. We hypothesised that potential underdiagnosis of AFL at a younger age is associated with poor prognosis. We assigned 95 288 participants aged 20–100 years from the Copenhagen General Population Study into the following groups: individuals without AFL with forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ≥0.70 and ≥lower limit of normal (LLN) (n=78 779, 83%); individuals with potentially underdiagnosed AFL with FEV 1 /FVC ≥0.70 and &lt;LLN (n=1056, 1%); individuals with potentially overdiagnosed AFL with FEV 1 /FVC &lt;0.70 and ≥LLN (n=3088, 3%); and individuals with AFL with FEV 1 /FVC &lt;0.70 and &lt;LLN (n=12 365, 13%). We assessed risk of exacerbations, pneumonias, ischaemic heart disease, heart failure and all-cause mortality. Median follow-up was 6.0 years (range: 2 days–11 years). Compared to individuals without AFL, individuals with potentially underdiagnosed AFL had an increased risk of morbidity and mortality with age- and sex-adjusted hazard ratios (HR) of 2.7 (95% CI: 1.7–4.5) for pneumonias, 2.3 (95% CI: 1.2–4.5) for heart failure, and 3.1 (95% CI: 2.1–4.6) for all-cause mortality. Young and middle-aged adults with AFL according to LLN but not fixed ratio experience increased respiratory and cardiovascular morbidity and early death.