tbuckley/cabot-search huggingface dataset:
β-Catenin–mediated immune evasion pathway frequently operates in primary cutaneous melanomas
Authors: Jérémie Nsengimana, Jon Laye, Anastasia Filia, Sally O’Shea, Sathya Muralidhar, Joanna Poźniak, Alastair Droop, May Chan, Christy Walker, Louise Parkinson, Joanne Gascoyne, Tracey Mell, Minttu Polso, Rosalyn Jewell, Juliette Randerson-Moor, Graham P. Cook, D. Timothy Bishop, Julia Newton-Bishop
Journal: Journal of Clinical Investigation (2018)

Immunotherapy prolongs survival in only a subset of melanoma patients, highlighting the need to better understand the driver tumor microenvironment. We conducted bioinformatic analyses of 703 transcriptomes to probe the immune landscape of primary cutaneous melanomas in a population-ascertained cohort. We identified and validated 6 immunologically distinct subgroups, with the largest having the lowest immune scores and the poorest survival. This poor-prognosis subgroup exhibited expression profiles consistent with β-catenin–mediated failure to recruit CD141+ DCs. A second subgroup displayed an equally bad prognosis when histopathological factors were adjusted for, while 4 others maintained comparable survival profiles. The 6 subgroups were replicated in The Cancer Genome Atlas (TCGA) melanomas, where β-catenin signaling was also associated with low immune scores predominantly related to hypomethylation. The survival benefit of high immune scores was strongest in patients with double-WT tumors for BRAF and NRAS, less strong in BRAF-V600 mutants, and absent in NRAS (codons 12, 13, 61) mutants. In summary, we report evidence for a β-catenin–mediated immune evasion in 42% of melanoma primaries overall and in 73% of those with the worst outcome. We further report evidence for an interaction between oncogenic mutations and host response to melanoma, suggesting that patient stratification will improve immunotherapeutic outcomes.
P026 Baseline autoantibody profile in rheumatoid arthritis associates with early treatment response but not long-term outcomes
Authors: EC de Moel, VF Derksen, LA Trouw, H Bang, RJ Goekoop, I Speyer, TW Huizinga, CF Allaart, RE Toes, D van der Woude
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is clinically relevant and associates with treatment outcomes. <h3>Objectives</h3> To investigate whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. <h3>Methods</h3> In sera of 399 seropositive RA patients in the IMPROVED study<sup>1</sup> drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against 4 citrullinated and 2 acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on; change in disease activity score (DAS)–44 between 0 and 4 months, initial drug–free remission (DFR: drug–free DAS44&lt;1.6) achieved between 1 and 2 years of follow–up, and long–term sustained DFR until last follow–up. <h3>Results</h3> Corrected for age, gender, smoking, BMI, and baseline Health Assessment Questionnaire score, patients with a broad autoantibody profile at baseline had a significantly better early treatment response: ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 isotypes: −1.5 [p&lt;0.001], −1.7 [p=0.003], and −1.8 [p=0.001] vs −2.2. Similar results were observed for AMPA-number; ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 AMPAs, respectively: −1.7 [p=0.016], −1.5 [p&lt;0.001], and −1.9 [p=0.22] vs −2.1. However, patients with a broad baseline autoantibody profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar results were observed. <h3>Conclusions</h3> A broad baseline autoantibody profile is associated with a better early treatment response and a worse chance of achieving DFR at early stages, but not later in the treatment regimen, suggesting that the relevance of the autoantibody profile for treatment outcomes diminishes over time. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity which could make the underlying disease processes initially more suppressible by medication. <h3>Reference</h3> . Heimans. AR&amp;T2016;18:23. <h3>Disclosure of interest</h3> None declared
The effect of pregnancy on endometriosis—facts or fiction?
Authors: Brigitte Leeners, Fabia Damaso, Nicole Ochsenbein-Kölble, Cindy Farquhar
Journal: Human Reproduction Update (2018)

It is not uncommon for women with endometriosis to be advised that becoming pregnant might be a useful strategy to manage their symptoms and reduce disease progression. Consequently, many women diagnosed with endometriosis and motivated to become pregnant, may also have expectations regarding improvement of symptoms and the disease. However, study results on the effect of pregnancy on endometriosis are controversial and pregnancy in women with endometriosis is not always associated with improved symptoms. Moreover, there is increasing evidence that endometriosis may interfere with a successful pregnancy outcome.The objective was to evaluate the evidence on whether pregnancy and lactation has a beneficiary effect on growth characteristics and symptoms of endometriosis diagnosed prior to pregnancy.A search for articles containing keywords related to pregnancy and endometriosis was performed via PubMed. Manuscripts dealing with a potential effect of pregnancy on endometriosis were systematically reviewed. We included English, French and German language publications on human studies from 1966 to May 2017. Bibliographies of these manuscripts were searched for further relevant literature.Five small observational studies were identified concerning the longitudinal development of endometriotic lesions during and after pregnancy, four of medium and one of low quality. Eleven publications reported measurements of endometriomas during pregnancy and the postpartum period (the five studies just mentioned and six case reports). Another 22 case reports/small case series (maximum of five cases), six studies on histology of endometriotic lesions in pregnancy, plus eight studies on the role of pregnancy in initial development and recurrence of endometriosis were included. Few studies of very limited quality are available to evaluate the effect of pregnancy and the postnatal period on the development of endometriosis. The development of endometriosis is variable and there is no evidence that pregnancy can be expected to generally reduce the size and number of endometriotic lesions. Growth and structural changes of lesions during pregnancy may occur with decidualization. Results on the association between pregnancy and symptoms of endometriosis are controversial and strongly biased.Available data on the development of endometriosis during and after pregnancy show fewer beneficial effects than previously reported. Therefore, women aiming for pregnancy on the background of endometriosis should not be told that pregnancy may be a strategy for managing symptoms and reducing progression of the disease.
Universal screening for latent and active tuberculosis (TB) in asylum seeking children, Bochum and Hamburg, Germany, September 2015 to November 2016
Authors: Maya Mueller-Hermelink, Robin Kobbe, Benedikt Methling, Cornelius Rau, Ulf Schulze-Sturm, Isa Auer, Frank Ahrens, Folke Brinkmann
Journal: Eurosurveillance (2018)

BackgroundIn Germany, the incidence of tuberculosis (TB) in children has been on the rise since 2009. High numbers of foreign-born asylum seekers have contributed considerably to the disease burden. Therefore, effective screening strategies for latent TB infection (LTBI) and active TB in asylum seeking children are needed. Aim: Our aim was to investigate the prevalence of LTBI and active TB in asylum seeking children up to 15 years of age in two geographic regions in Germany. Methods: Screening for TB was performed in children in asylum seeker reception centres by tuberculin skin test (TST) or interferon gamma release assay (IGRA). Children with positive results were evaluated for active TB. Additionally, country of origin, sex, travel time, TB symptoms, TB contact and Bacille Calmette-Guérin (BCG) vaccination status were registered. Results: Of 968 screened children 66 (6.8%) had TB infection (58 LTBI, 8 active TB). LTBI prevalence was similar in children from high (Afghanistan) and low (Syria) incidence countries (8.7% vs 6.4%). There were no differences regarding sex, age or travel time between infected and non-infected children. Children under the age of 6 years were at higher risk of progression to active TB (19% vs 2% respectively, p=0,07). Most children (7/8) with active TB were asymptomatic at the time of diagnosis. None of the children had been knowingly exposed to TB. Conclusions: Asylum seeking children from high and low incidence countries are both at risk of developing LTBI or active TB. Universal TB screening for all asylum seeking children should be considered.
ASSOCIATION OF APPEARANCE OF L WAVE IN HEART FAILURE PATIENTS WITH PRESERVED VERSUS REDUCED EJECTION FRACTION
Authors: Kumiko Masai, Akiko Goda, Masataka Sugahara, Aika Matsumoto, Masanori Asakura, Masaharu Ishihara, Tohru Masuyama
Journal: Journal of the American College of Cardiology (2018)
Native T1 and ECV of Noninfarcted Myocardium and Outcome in Patients With Coronary Artery Disease
Authors: Valentina O. Puntmann, Gerry Carr-White, Andrew Jabbour, Chung-Yao Yu, Rolf Gebker, Sebastian Kelle, Andreas Rolf, Sabine Zitzmann, Elif Peker, Tommaso D’Angelo, Faraz Pathan, None Elen, Silvia Valbuena, Rocio Hinojar, Christophe Arendt, Jagat Narula, Eva Herrmann, Andreas M. Zeiher, Eike Nagel
Journal: Journal of the American College of Cardiology (2018)
Endoscopic treatment of esophageal intramural abscess caused by embedded metal clip: a rare delayed complication of endoscopic submucosal dissection
Authors: Peng Wang, Feng Liu
Journal: Endoscopy (2018)

Endoscopic submucosal dissection (ESD) is indicated for the treatment of superficial digestive tract cancers [1]. Bleeding and perforation are common complications of ESD. Metal clips have often been used for endoscopic closure of mucosal defects or exposed vessels, in order to reduce the risk of complications. After ESD, most metal clips fall off spontaneously.
Real-world Effectiveness of Pharmacologic Treatments for the Prevention of Rehospitalization in a Finnish Nationwide Cohort of Patients With Bipolar Disorder
Authors: Markku Lähteenvuo, Antti Tanskanen, Heidi Taipale, Fabian Hoti, Pia Vattulainen, Eduard Vieta, Jari Tiihonen
Journal: JAMA Psychiatry (2018)

Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations.To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder.This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N = 18 018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was used as his or her own control to eliminate selection bias. The study adjusted for the effect of concomitant psychotropic medications, duration of illness, and the temporal orders of exposure and nonexposure periods. Statistical analysis was conducted from January 1, 1996, to December 31, 2012.Adjusted hazard ratios (HRs) for rehospitalization were calculated.Among the cohort (9558 women and 8460 men; mean [SD] age, 46.6 [17.0] years), 9721 patients (54.0%) had at least 1 psychiatric rehospitalization. In comparison between use and no use among specific agents reaching nominal statistical significance, risperidone long-acting injection (HR, 0.58 [95% CI, 0.34-1.00]), gabapentin (HR, 0.58 [95% CI, 0.44-0.77]), perphenazine long-acting injection (HR, 0.60 [95% CI, 0.41-0.88]), and lithium carbonate (HR, 0.67 [95% CI, 0.60-0.73]) were associated with the lowest risk of psychiatric rehospitalization. Concerning all-cause hospitalization, lithium (HR, 0.71 [95% CI, 0.66-0.76]) was associated with the lowest risk. The most frequently used antipsychotic treatment, quetiapine fumarate, showed only modest effectiveness (risk of psychiatric rehospitalization: HR, 0.92 [95% CI, 0.85-0.98]; risk of all-cause hospitalization: HR, 0.93 [95% CI, 0.88-0.98]). Long-acting injections were associated with substantially better outcomes compared with identical oral antipsychotics (risk of psychiatric rehospitalization: HR, 0.70 [95% CI, 0.55-0.90]; risk of all-cause hospitalization: HR, 0.70 [95% CI, 0.57-0.86]). Results from sensitivity analyses showed consistent beneficial effects only for lithium and for long-acting injections compared with their oral counterparts.Lithium was the most effective mood stabilizer, and long-acting injections the most effective antipsychotics, in preventing hospitalization due to mental or physical illness.
Prophylactic Low-Dose Oxygen for Patients With Acute Stroke—Reply
Authors: Christine Roffe, Julius Sim, Richard Gray
Journal: JAMA (2018)

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Anaesthetist is investigated over deaths of several patients
Authors: Clare Dyer
Journal: BMJ (2018)

Police and the General Medical Council are investigating a consultant anaesthetist on suspicion of having inappropriately hastened the deaths of several patients.

Andrew Gregg, a consultant with North West Anglia NHS Foundation Trust, was originally investigated over the death of a 41 year old man with acute myeloid leukaemia, “Patient A,” who died in January 2016 two hours after his doses of sedative and analgesia were increased.

The trust excluded Gregg from work and notified police after a formal trust investigation concluded that there was a case to answer that the death had been inappropriately hastened. Police completed an investigation in November 2016 and decided to treat the death as homicide, …
GENDER DISPARITIES WITH THE USE OF PERCUTANEOUS LEFT VENTRICULAR ASSIST DEVICE IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION COMPLICATED BY CARDIOGENIC SHOCK: FROM PLVAD WORKING GROUP
Authors: Rajkumar Doshi, Krishin Shivdasani, Shani Varghese, Krunalkumar Patel, Devina Singh, Mohit Singh, Karanbir Singh, Daksh Vora, Varun Jauhar, Ayush Goel, Tejal Aurora, Sumaiyah Siddiqui, Perwaiz Meraj
Journal: Journal of the American College of Cardiology (2018)
A phase III trial to confirm the superiority of S-1 adjuvant chemotherapy for vulnerable elderly patients with pathological stage II/III gastric cancer after curative resection: JCOG1507 (BIRDIE).
Authors: Kazuya Yamaguchi, Kazuhiro Yoshida, Junki Mizusawa, Tomonori Mizutani, Seiji Ito, Yasunori Nishida, Hiroshi Yabusaki, Takeshi Sano, Mitsuru Sasako, Hiroshi Katayama, Haruhiko Fukuda, Narikazu Boku, Takaki Yoshikawa, Masanori Terashima
Journal: Journal of Clinical Oncology (2018)

TPS196 Background: Base on the ACTS-GC trial, adjuvant chemotherapy with S-1 at a dose of 80 mg/m 2 /day (4 weeks on and 2 weeks off, repeated for one year) is the standard care for stage II/III gastric cancer (GC) patients (pts) after D2 gastrectomy. As Japan has the most aged population in the world, the actual number of elderly GC pts is still increasing. While elderly pts population is heterogeneous and is conceptually composed of “fit”, “vulnerable” and “frail” pts, full-dose adjuvant chemotherapy tends to be given to fit elderly pts in clinical practice. However, it has not been determined yet whether S-1 should be administered to vulnerable pts over 80. Actually, according to the questionnaire survey conducted on 58 institutions of Stomach Cancer Study Group of Japan Clinical Oncology Group, S-1 was administered on only 15% to stage II/III pts &gt; = 80 years old suggesting that surgery alone is generally considered as community standard for vulnerable pts. It is an urgent need to establish the standard adjuvant treatment of the vulnerable elderly GC pts. Methods: The study is designed to confirm the superiority of S-1 treatment group over surgery alone group focusing on vulnerable &gt; = 80 years old pts in stage II / III GC after curative resection. The “vulnerable” is defined in this study based on the three factors [creatinine clearance (Ccr), weight loss, type of surgery] considered to have the most influence on compliance of S-1, that is Ccr &gt; = 30ml/min, weight loss &lt; 15% and total gastrectomy, or 80 &gt; Ccr &gt; = 30ml/min, weight loss &lt; 15% and other than total gastrectomy. Initial dose was reduced by 1 rank from the standard dose. The primary endpoint is overall survival (OS) and the secondary endpoints are relapse free survival, time to treatment failure, treatment continuity, relative dose intensity and adverse events. We assume expected 3-year OS in surgery alone arm will be 55% and S-1 treatment will improve the survival by more than 10%. 370 pts are required to provide 75% of power and 5% one-sided alpha error, with 4 years accrual and 3 years of follow up period. The trial has started from January 2017. Clinical trial information: UMIN000025742. Clinical trial information: 000025742.
RCP is to review training processes and exams in wake of Francis inquiry
Authors: Gareth Iacobucci
Journal: BMJ (2013)

The Royal College of Physicians is to review its training and assessment processes in light of the Francis inquiry, to ensure that trainee doctors are encouraged to focus on quality and that their competence in raising concerns and treating patients with dignity is assessed.

In a detailed response to Robert Francis’s public inquiry into failings at Mid Staffordshire NHS Foundation Trust, the college has pledged to strengthen doctors’ leadership skills and to publish new guidance on raising concerns, to help implement the inquiry’s recommendations. …
Communication for Doctors: how to improve patient care and minimize legal risks⇓
Authors: Domhnall MacAuley
Journal: BMJ (2004)

W rite clearly, speak clearly, think clearly, and be nice to people. This compendium of essays, articles, lessons, speeches, and random thoughts is about communication. But it also gives us an insight into what patients think of doctors and why they don't seem to like us any more. It seems that doctors are arrogant, cannot communicate, and make little attempt to explain to patients about their illness or show concern about their welfare as people. The personal reflections of Julia Schopick …
EDTA-related degranulation mimicking Storage Pool Disease
Authors: Marco Amoruso, Lorenzo Alberio, Monika Nagy
Journal: American Journal of Hematology (2018)

A platelet (PLT) count drop occurred in a 70-year-old man with pulmonary embolism 1 day after initiation of unfractioned heparin (48 × 109/L vs. 86 × 109/L at admission). Microscopic examination of the blood smear (Image 1A) confirmed thrombocytopenia with inconspicuous platelet aggregates and strikingly agranular, gray macro-thrombocytes (MPV 13.3 fL). The PLT histogram of the automated cell counter was compatible with the presence of an ethylene diamine tetra-acetic acid (EDTA)-induced pseudo-thrombocytopenia (Image 1B). Platelet imaging. Panel A, Peripheral blood smear (EDTA). Panel B, Platelet histogram, generated by Sysmex (EDTA). Panel C, Peripheral blood smear (Thromboexact). Panel D, Platelet histogram, generated by Sysmex (Thromboexact) Patient's PLT count had always been around 90–100 × 109/L in EDTA specimens since 2011. Once, in April 2016, because of a PLT count of 25 × 109/L, a citrate specimen was requested, showing a normal PLT value (231 × 109/L). A blood film examination had never been performed before. Because of abnormal PLT morphology and dimensions, pathologic PLT histogram and discordant PLT counts in April 2016, we requested a Thromboexact (magnesium-based anticoagulant) specimen. This showed a low normal PLT count by automated cell analyzer (145 × 109/L) and a normal PLT histogram (Image 1D). The blood smear revealed the absence of macro-thrombocytes, and, particularly, the appearance of normal platelet granules and coloration (Image 1C), allowing the diagnosis of EDTA-induced pseudo-thrombocytopenia and pseudo-storage pool disease. EDTA-related pseudo-thrombocytopenia is a well-known consequence of an in vitro EDTA-dependent conformational modification of glycoprotein IIb-IIIa, making available an epitope to agglutinating platelets antibodies. However, EDTA-induced degranulation has been rarely reported, to the best of our knowledge in five cases only.1 The present case illustrates that, besides classic pseudo-thrombocytopenia, EDTA can induce degranulation and the rare condition of pseudo-storage pool disease, mimicking the microscopic characteristics of gray platelet syndrome.1 Inspection of the PLT histogram and peripheral blood smear is the first, cheap and essential step for recognizing this condition. Nothing to report.
Locum doctor survival guide
Authors: Annabelle Banks
Journal: BMJ (2006)

Robbie Coull

locum 123.com, 2005, £24.99, 215 pages

ISBN 0 955 20720 7

Rating: ★★★★★/5



Working as a locum general practitioner since 1998 and for three years before that as a hospital locum, Robbie Coull described his progression from student to web based locum service provider as a “steep learning curve.” Having produced a number of more specialised advice pages on his locum123 website, Dr Coull published a “reasonably chunky” comprehensive locum guide online in 2004, which evolved into the Locum Doctor Survival Guide paperback. Although three times the size of the online version, its sharper text and easy layout much improve its …