tbuckley/cabot-search huggingface dataset:
Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease
Authors: Emil ter Veer, L Bengt van Rijssen, Marc G Besselink, Rosa M A Mali, Jordan D Berlin, Stefan Boeck, Franck Bonnetain, Ian Chau, Thierry Conroy, Eric Van Cutsem, Gael Deplanque, Helmut Friess, Bengt Glimelius, David Goldstein, Richard Herrmann, Roberto Labianca, Jean-Luc Van Laethem, Teresa Macarulla, Jonathan H M van der Meer, John P Neoptolemos, Takuji Okusaka, Eileen M O'Reilly, Uwe Pelzer, Philip A Philip, Marcel J van der Poel, Michele Reni, Werner Scheithauer, Jens T Siveke, Chris Verslype, Olivier R Busch, Johanna W Wilmink, Martijn G H van Oijen, Hanneke W M van Laarhoven
Journal: The Lancet Oncology (2018)
The Edinburgh surgical sciences qualification (ESSQ)
Authors: Timothy M Brock
Journal: BMJ (2009)

The Edinburgh surgical sciences qualification (ESSQ) is an innovative programme developed by the University of Edinburgh and the Royal College of Surgeons of Edinburgh. It is a part time, modular course that is delivered entirely online. The course provides a strong grounding in basic sciences as applied to clinical surgery, and the level of learning is equivalent to the new intercollegiate membership of the Royal College of Surgeons syllabus (MRCS).

The course is delivered on a modular basis, with topics changing every two weeks. Students are given online case based scenarios, recommended reading, and multiple …
Early experience of general practice will keep junior doctors in medicine
Authors: Eleni Linos
Journal: BMJ (2005)

Doctors are deserting the NHS. The British Medical Association explains why—“they are not valued, not supported and have unacceptable work-life balance.”1 Perhaps they should have told us this in the induction pep talk on our first day. I started working as a junior doctor in August; by September I was ready to quit. Forms, exams, applications ready, I decided to cross the Atlantic to be trained in research methodology and never do clinical medicine again. Now, a year later, general practice has brought me back.

19 Beaumont Street General Practice in Oxford is different. It is efficient, modern. It features computerised records, online repeat prescriptions, futuristic locked doors that open with body movement, doctor-patient communication by email, and an intranet full of online evidence based resources for each consultation. Compared to the slow, technologically prehistoric, “teaching” hospital, this efficiency is stunning.

It is also pleasant—fresh flowers, poetry on the waiting room walls, …
Rhabdomyosarcoma Revealed by a Breast Metastasis
Authors: Marie Luporsi, Thibaut Cassou-Mounat, Henri-Marc Amiot, Valerie Laurence, Nina Jehanno
Journal: Clinical Nuclear Medicine (2018)

A 38-year-old woman was referred for staging of an alveolar rhabdomyosarcoma revealed by a breast metastasis with unknown primary. Whole-body F-FDG PET/CT localized the primary tumor as an asymptomatic soft tissue lesion of the right foot with a significant uptake. PET/CT detected hepatic and pancreatic metastases and also showed a multifocal bone marrow involvement, which was not detected by the contrast-enhanced CT. These results led to a significant change in treatment management as the patient received local radiotherapy of the primitive lesion and polychemotherapy.
67Ga Scintigraphy for Assessment of Disease Severity and Treatment Response in Patients With Paracoccidioidomycosis
Authors: Lilian Yuri Itaya Yamaga, Gil Benard, Tomoco Watanabe, Marcelo Buarque de Gusmão Funari, Fausto Haruki Hironaka, Carlos Alberto Buchpighel, Maria Aparecida Shikanai-Yasuda
Journal: Clinical Nuclear Medicine (2018)

The evaluation of therapy response of patients with deep mycosis is a major challenge. The aim of this study was to assess the severity of disease at admission and evaluate treatment response of patients with paracoccidioidomycosis using Ga scintigraphy.Seventy-three patients with fully active disease were enrolled. A scoring system based on clinicoradiological and serological evaluation and Ga scan was devised. Pretherapy Ga score of 73 patients was compared with clinicoradiological and serological scores. A subgroup of 23 patients was followed up during treatment, and the rates of improvement of their clinicoradiological, serological, and Ga scores during treatment were compared at 3 time points (fully active phase, after clinical improvement, and clinically inactive disease).The correlations between scores before therapy were statistically significant. Ga score correlated with clinical score (r = 0.47, P < 0.001). Serological score correlated with both Ga and clinical scores (r = 0.32, P = 0.006, and r = 0.25, P = 0.034, respectively). Concerning evaluation of therapy response, clinicoradiological, serological, and Ga scores decreased significantly after therapy (P < 0.001). Notably, Ga score was the single one to become negative in most patients at the end of treatment (20 of 23 patients compared with 7 on clinicoradiological evaluation and 10 on serology, P = 0.003).In patients with paracoccidioidomycosis, pretherapy Ga scintigraphy correlates with disease severity. Serial Ga scans seem to be helpful in evaluating the response to therapy.
Characterization of tumor mutation burden (TMB) and microsatellite instability (MSI) interplay for gastroesophageal adenocarcinoma (GA) and colorectal carcinoma (CRC).
Authors: Xiu Huang, Julie Y Tse, Alexei Protopopov, Meaghan Russell, Dilhan Weeraratne, Jennifer E. Ring, Andrew Bjonnes, Shermin Pei, Ruobai Sun, Maria Lvova, Yajuan Li, Stephen Lyle, Dana Vuzman
Journal: Journal of Clinical Oncology (2018)

22 Background: Tumor genomic instability is positively correlated with immunotherapy response. It confers different tumor phenotypes, including high TMB (TMB-H) and high MSI (MSI-H). Recently the US Food and Drug Administration approved MSI-H phenotype as a biomarker for immunotherapy, highlighting its importance, but also bringing up the question of how TMB as another promising biomarker is going to add value in the field. Here, we characterized TMB and MSI profiles to better understand the potential TMB contribution and identify genomic markers for it. Methods: 734 solid tumor were collected, with 462 CRC, and 272 GA samples. Large panel Next-Generation Sequencing assay with the ability to determine TMB and MSI, was performed on each sample. Based on the TMB and MSI status, patients were grouped into four categories: THMH (TMB-H and MSI-H), THMS (TMB-H and MSI-Stable), TLMH (TMB-Low and MSI-H), and TLMS (TMB-Low and MSI-Stable). To identify genes that are related to the interplay of TMB and MSI, Random Forest and Lasso Regression models were applied to identify genes most predictive of the four categories. Results: TMB and MSI are highly correlated in our cohort of CRC and GA tumors. However, 5.8% CRC and 12.9% GA samples are under THMS (Table 1). In these samples, alternate DNA repair pathways are potentially dysregulated, including the nucleotide excision pathway (ATRX, APC), DNA double strand break repair (FANCF, SETD2), and the previously described proofreading pathway (POLD1). We hypothesize that these patients may also derive clinical benefit from immunotherapy. Conclusions: Immunotherapy benefits could be extended to more patients by jointly measuring MSI and TMB. The corresponding marker genes could also be extended beyond the commonly known POLE/POLD1 genes. Orthogonal validation by Whole Exome Sequencing data of the in silico mined marker genes is currently underway. [Table: see text]
Private school students perform less well at medical school
Authors: Abi Rimmer
Journal: BMJ (2013)

Students from private and grammar schools perform less well at medical school than students from non-selective schools, a study has found.1

The study analysed the first year exam results of 4811 students at 12 UK medical schools, in light of their performance in the UK Clinical Aptitude Test (UKCAT). It found that students from grammar and private schools performed less well than those educated at non-selective schools. This was despite recent findings that private school pupils are still disproportionately represented in medical schools.2

Using data from secondary schools in England, the study also found that students who came …
OUTCOMES OF CATHETER ABLATION FOR SUPRAVENTRICULAR TACHYCARDIA IN ADULT PATIENTS WITH CONGENITAL HEART DISEASE
Authors: Lohit Garg, Sahil Agrawal, Manyoo Agarwal, Brijesh Patel, Mahek Shah, Aakash Garg, Sudip Nanda, Talha Nazir, Raman Dusaj
Journal: Journal of the American College of Cardiology (2018)
NATIONAL TRENDS IN THE EPIDEMIOLOGY OF HOSPITAL ADMISSIONS FOR ACUTE MYOCARDITIS: INSIGHTS FROM THE UK NATIONAL HEALTH SERVICE
Authors: Amrit Lota, Sadia Fazal, Rebecca Wassall, Pavithra Puvanasingam, Rameen Shakur, Brian Halliday, Upasana Tayal, James Ware, John Cleland, Piers Daubeney, Dudley Pennell, Nick Banner, Saidi Mohiddin, Stuart Cook, Sanjay Prasad
Journal: Journal of the American College of Cardiology (2018)
Gut microbiome composition and response to sunitinib in metastatic renal cell carcinoma (mRCC).
Authors: Jun Gong, Nazli Dizman, Valeriy Poroyko, Haejung Won, Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Manuel C. Maia, Joann Hsu, Paul Henry Frankel, Jeremy Jones, Ravi Salgia, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

657 Background: Recent evidence supports a link between stool microbiome composition and immunotherapy response. However, it is unclear how the microbiome may influence clinical outcome in mRCC where vascular endothelial growth factor-targeted therapies remains a standard of care. Methods: Five consecutive stool samples were collected at baseline and at weeks 2, 3, 4 and 12 of treatment with sunitinib in patients (pts) with mRCC. In responders (R: complete/partial response and stable disease) and non-responders (P: primary progression), gut microbiota composition was assessed through extraction of microbial DNA where 16s RNA gene tags (v4) were generated by PCR amplification and sequenced using MiSeq (Illumina). Sequence reads were processed by Mothur software, assembled in Operational Taxonomic Units (OTUs), taxonomically annotated to the genus level, and used to construct Bray-Curtis dissimilarity matrix. The similarity of samples was visualized by principle coordinate (PCo) analysis and further confirmed by k-means clustering and ANOSIM tests. Differentially abundant taxa were determined by METASTATS. Results: Stool bacteriomic profiling identified 25,304 OTUs attributable to 165 genera from 8 phyla in 4 of 6 pts evaluable for response. PCo analysis revealed clear separation of R and P (accounting for 28.9 % of dataset variation) where subsequent k-means clustering confirmed the difference of microbiota in 2 clusters that perfectly align with R and P groups. The significance of this separation was confirmed by ANOSIM analysis (p = 0.005). Analysis of microbiota composition in P and R groups revealed 14 differentially abundant taxonomic units at the genus level. Of those at ≥1% abundance, Bacteroides, Barnesiella and Phascolarctobacterium were elevated in R, while Bifidobacterium and Dorea were elevated in P (p &lt; 0.01 for all). Of those at &lt; 1% abundance, Lactococcus, Sporobacter, Acidaminococcus, Actinomyces, and Asaccharobacter were elevated in P (p &lt; 0.01 for all). Conclusions: Although limited by sample size, we report the first in-human study to suggest a link between microbiota and response to sunitinib as we identified a significant discrepancy in stool bacteriomic distribution between P and R.
FDG-Avid Focal Liver Reaction From Proton Therapy in a Patient With Primary Esophageal Adenocarcinoma
Authors: Hena S. Ahmed, Austin R. Pantel, James M. Metz, John P. Plastaras, Michael D. Farwell
Journal: Clinical Nuclear Medicine (2018)

A 25-year-old man with IgA deficiency was treated with 2 months of chemotherapy and proton therapy for gastroesophageal junction adenocarcinoma. Restaging PET/CT 18 days posttherapy demonstrated 2 new foci of increased FDG uptake in the left hepatic lobe, which were favored to represent radiation injury as opposed to new metastases. Follow-up MRI with contrast 2 weeks later demonstrated hypoenhancement and T1/T2 hypointensity in the liver, without restricted diffusion, which correlated with the dominant FDG-avid focus. The hepatic lesions resolved on subsequent FDG PET/CT and MRI studies, confirming the diagnosis of acute radiation injury.
Lack of standardisation of ANA and implications for drug development and precision medicine
Authors: Michael Mahler
Journal: Annals of the Rheumatic Diseases (2018)

The recent article by Pisetsky et al 1, showing data derived from a comparison between different antinuclear antibody (ANA) assays in a cohort of patients with established systemic lupus erythematosus (SLE), addresses several important and current aspects of ANA detection. In addition, the study touches on clinical trials for ANA-associated rheumatic diseases (AARDs) and raises several relevant points  that will be discussed in this letter.

One of the fundamental questions around ANA testing is: “What is an ANA and what are diagnostic tests actually measuring?”. In other words, there is no clear definition of what is and what should be included in ANA testing.2 For example, technically antibodies to cytoplasmic antigens do not belong to ANA, but can help in the diagnosis of certain AARDs and are in some countries reported as ANAs. This is important in the context of SLE as about 15%–30% of patients with SLE have anti-ribosomal antibodies that typically present with a cytoplasmic staining pattern. However, the cytoplasmic pattern need to be clearly defined as patients with other autoimmune diseases might also present with a cytoplasmic pattern (eg, myositis or autoimmune liver disease), although with different staining pattern.3

Although the ANA indirect immunofluorescence (IIF) test has been recommended as the method of choice,4 the method is not without limitations.5 In addition, novel solid phase assays (SPAs) have significantly improved6 and are increasingly being used as the screening test of choice in high-throughput laboratories for the detection of ANA.5 However, it remains a matter of debate whether or not SPA such …
Vitamin D inhibits TGF-β1-induced myofibroblast differentiation and extracellular matrix production via Smad2/3 signaling pathway in nasal polyp-derived fibroblasts
Authors: Jae-Min Shin, Hyun-Woo Yang, Seoung Ae Lee, Joo-Hoo Park, Hwee-Jin Kim, Heung Man Lee
Journal: Journal of Allergy and Clinical Immunology (2018)
Release of MicroRNAs into Body Fluids from Ten Organs of Mice Exposed to Cigarette Smoke
Authors: Alberto Izzotti, Mariagrazia Longobardi, Sebastiano La Maestra, Rosanna T. Micale, Alessandra Pulliero, Anna Camoirano, Marta Geretto, Francesco D'Agostini, Roumen Balansky, Mark Steven Miller, Vernon E. Steele, Silvio De Flora
Journal: Theranostics (2018)

Purpose: MicroRNAs are small non-coding RNAs that regulate gene expression, thereby playing a role in a variety of physiological and pathophysiological states. Exposure to cigarette smoke extensively downregulates microRNA expression in pulmonary cells of mice, rats, and humans. Cellular microRNAs are released into body fluids, but a poor parallelism was previously observed between lung microRNAs and circulating microRNAs. The purpose of the present study was to validate the application of this epigenetic biomarker by using less invasive collection procedures. Experimental design: Using microarray analyses, we measured 1135 microRNAs in 10 organs and 3 body fluids of mice that were either unexposed or exposed to mainstream cigarette smoke for up to 8 weeks. The results obtained with selected miRNAs were validated by qPCR. Results: The lung was the main target affected by smoke (190 dysregulated miRNAs), followed by skeletal muscle (180), liver (138), blood serum (109), kidney (96), spleen (89), stomach (36), heart (33), bronchoalveolar lavage fluid (32), urine (27), urinary bladder (12), colon (5), and brain (0). Skeletal muscle, kidney, and lung were the most important sources of smoke-altered microRNAs in blood serum, urine, and bronchoalveolar lavage fluid, respectively. Conclusions: microRNA expression analysis was able to identify target organs after just 8 weeks of exposure to smoke, well before the occurrence of any detectable histopathological alteration. The present translational study validates the use of body fluid microRNAs as biomarkers applicable to human biomonitoring for mechanistic studies, diagnostic purposes, preventive medicine, and therapeutic strategies.
Recent progress in the antiviral activity and mechanism study of pentacyclic triterpenoids and their derivatives
Authors: Sulong Xiao, Zhenyu Tian, Yufei Wang, Longlong Si, Lihe Zhang, Demin Zhou
Journal: Medicinal Research Reviews (2018)

Abstract Viral infections cause many serious human diseases with high mortality rates. New drug‐resistant strains are continually emerging due to the high viral mutation rate, which makes it necessary to develop new antiviral agents. Compounds of plant origin are particularly interesting. The pentacyclic triterpenoids (PTs) are a diverse class of natural products from plants composed of three terpene units. They exhibit antitumor, anti‐inflammatory, and antiviral activities. Oleanolic, betulinic, and ursolic acids are representative PTs widely present in nature with a broad antiviral spectrum. This review focuses on the recent literatures in the antiviral efficacy of this class of phytochemicals and their derivatives. In addition, their modes of action are also summarized.
Comprehensive analyses of the clinical benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer.
Authors: Qiyun Ou, Tuping Fu, Yunfang Yu, Dagui Lin, Quanlong Gao, Yuxin Zhang, Baoming Luo
Journal: Journal of Clinical Oncology (2018)

168 Background: Treatment with immune checkpoint inhibitors is becoming the standard of care for patients and it was approved for the treatment of non-small-cell lung cancer (NSCLC) growing at a rapid pace. However, selecting patients who are appropriate for therapy and which therapeutic strategies to use can be challenging. Methods: We searched for randomized clinical trials (RCTs) investigating immune checkpoint inhibitors versus observation in patients with advanced NSCLC until September 2017. Overall survival (OS) and progression-free survival (PFS) were pooled by meta-analysis. The GRADE system was used to describe the quality of evidence. Results: The analysis included 11 trials with 5,538 unique patients. High- to moderate-quality evidence indicated that immune checkpoint inhibitors extended NSCLC survival and PFS, expressed as hazard ratios (HRs) (OS: 0.79, P = 0.000; PFS: 0.78, P = 0.000). High- to moderate-quality evidence revealed prolonged OS and PFS were similar across preplanned subgroups in patients with squamous (0.77, P = 0.000 and 0.74, P = 0.001) or nonsquamous disease (0.76, P = 0.003 and 0.73, P = 0.041), EGFR wild-type positive status (0.67, P = 0.000 and 0.59, P = 0.010), current or former smokers (OS: 0.83, P = 0.009), and male (0.79, P = 0.000 and 0.67, P = 0.023). Increasing improvement in OS was associated with increasing PD-L1 expression (TC3 or IC3 HR 0.54, P = 0.000; TC2/3 or IC2/3 HR 0.62, P = 0.007; TC1/2/3 or IC1/2/3 HR 0.64, P = 0.000; TC0 and IC0 HR 0.72, P = 0.017; high- to moderate-quality evidence). In exploratory subgroup analysis suggest that there was advantageous of immune checkpoint inhibitors in previous definitive chemotherapy compared with chemoradiotherapy, with concurrent administration of chemotherapy (OS as HR: P = 0.001, P = 0.006, respectively). Conclusions: This large and comprehensive analysis produced firm evidence that immune checkpoint inhibitors extended advanced NSCLC survival and PFS, while in some patients with EGFR wild-type positive status, current or former smokers, male and higher PD-L1 expression had substantial benefit. The benefits from therapy appear to be influenced by preceding definitive therapy and concurrent chemotherapy.
Understanding Doctors' Performance
Authors: Mike Roddis
Journal: BMJ (2006)

Eds Jim Cox, Jennifer King, Allen Hutchinson, Pauline McAvoy

Radcliffe, £27.95, 184 pages

ISBN: 1 85775 766 1

Rating: ★★★★★/5



This is a much needed book, edited by experts in the field of medical performance analysis and management. It concentrates on issues of performance unrelated to clinical competence, the difficult doctor rather than the doctor in difficulty. It defines the reasons for poor performance with a clear presentation of the available evidence. It also puts a welcome emphasis on remediation, bucking the prevailing trend. There is plenty of advice on identifying the causes …
The “Moon Face” of Cushing Syndrome
Authors: Leonard J. Hoenig
Journal: JAMA Dermatology (2018)

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MOBILE PHONE DETECTION OF ATRIAL FIBRILLATION: THE MODE-AF STUDY
Authors: Jussi Jaakkola, Samuli Jaakkola, Olli Lahdenoja, Tero Hurnanen, Tero Koivisto, Mikko Pankaala, Timo Knuutila, Tuomas Kiviniemi, Tuija Vasankari, Juhani Airaksinen
Journal: Journal of the American College of Cardiology (2018)
I have dual nationality, one British, but I haven't lived in the United Kingdom for three years. How should I apply for an SHO position in the UK, and is there any difference compared with other overseas non-British doctors regarding the chances of being accepted, salary, or other aspects? Thank you.
Authors: Elitham B Turya
Journal: BMJ (2005)

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>
Stress levels of NHS staff are “astonishingly high” and need treating as a public health problem, says King’s Fund
Authors: Matthew Limb
Journal: BMJ (2015)

Levels of stress among NHS staff are “astonishingly high,” probably getting worse, and should be treated as a public health problem, the head of thought leadership at the King’s Fund has said.

Michael West said that widespread action was needed and that politicians should think carefully about the sort of health service they were creating. “At the national level the idea we can keep providing higher and higher quality care and more and more sophisticated treatments on a shrinking budget means that the pressures just increase on the staff, who are being asked to do more with less continually,” he said. “It’s such a huge problem across the NHS, and it’s as though we’ve come to accept it as being part of the territory—when it’s really unacceptable.”

West was speaking to BMJ Careers …