tbuckley/cabot-search huggingface dataset:
Comprehensive genetic characterization of TFE3-positive renal cell carcinoma.
Authors: Chang Wook Jeong, Jae So Cho, Moses Lee, Murim Choi, Cheryn Song, Sangchul Lee, Ja Hyeon Ku, Cheol Kwak, Hyeon Hoe Kim
Journal: Journal of Clinical Oncology (2018)

635 Background: MiT family translocation renal cell carcinoma (RCC) is very rare variant which has translocation of Xp11.2/TFE3 gene or t(6;11)/TFEB gene. Xp11.2 translocation RCC is predominantly reported in younger age and has aggressive features. However, its pathophysiology or genetic characteristics are rarely understood. The aim of the study is to describe the comprehensive genetic characteristics of TFE3-positive RCC diagnosed by immunohistochemistry. Methods: We identified patients who were clinically diagnosed as Xp11.2 translocation RCC by immunostaining positive of TFE3 from two tertiary referral hospitals. Among them, a total of 19 patients whose fresh frozen tissue and normal DNA were achieved were included in the analysis. Whole exome sequencing (WES) was performed to evaluate somatic mutations and copy-number variation (CNV). We also performed RNAseq on the TFE3-positive RCC, 7 clear cell RCC, and 4 normal kidney tissue for comparison. Fusion partners were identified and clustering analysis was done by RNAseq. Results: Mutational landscape of TFE3-positive RCC is unique by low somatic mutation rate and very rare COSMIC variants. High prevalence of CNV with loss of 3p, 6q, 9, gain of 5, 7, and 12 were most frequent. We identified NONO, RBM10, SFPQ, ASPSCR1 and PRCC as fusion partner as previously described. We could not find TFE3 fusion in 6 out of 19 patients by RNAseq, and they were older and had more mutations than the others. They were also genetically clustered with clear cell RCC. Oxidative reducatase pathway was upregulated and immune response and cell adhesion were downregulated by gene ontology results from heatmap clusters. These may promote metastasis, resistant to immunity and cell survival in poorer condition which could be potential mechanism of Xp11.2 translocation RCC aggressiveness. Conclusions: TFE3-positive RCC showed distinctive mutation pattern with low somatic mutation and rare common driver gene. One-third clinically diagnosed Xp11.2 translocation RCC (6/19) did not have real gene fusion even in TFE3 overexpression. They were older and had more somatic mutations than the others. Furthermore, they were clustered with clear cell RCC.
Nutrition for doctors needs further study, researchers say
Authors: Tom Moberly
Journal: BMJ (2016)

Interventions to help doctors eat healthily at work need to be tested and studied to understand their impact, researchers in Canada have said.1

A team from University Health Network in Toronto, Canada, looked at the available evidence on how nutrition affects physicians’ wellbeing and performance at work. Maryam Hamidi and colleagues said that individual doctors, professional bodies, and employer organisations could all play a part in improving doctors’ nutrition.

The team said that it could be difficult for doctors to get the nutrition they needed while they were working because of a …
<i>Alternaria</i> sensitisation at age 6 years is associated with subsequent airway hyper-responsiveness in non-asthmatics
Authors: Anunya Hiranrattana, Debra A Stern, Stefano Guerra, Marilyn Halonen, Anne L Wright, Michael Daines, Fernando D Martinez, Wayne J Morgan
Journal: Thorax (2018)

In the non-selected birth cohort Tucson Children's Respiratory Study, early sensitisation to Alternaria was associated with increased airway hyper-responsiveness (AHR) into adult life among non-asthmatics. The increase in AHR was of a similar magnitude to that seen for Alternaria sensitised asthmatics and was primarily evident among those who were overweight or obese. In contrast, there was no significant association between early sensitisation to aeroallergens other than Alternaria and AHR among non-asthmatics. Why this group of Alternaria sensitised individuals without asthma demonstrated increased AHR of a magnitude similar to asthmatics is unknown and requires further investigation.
Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy
Authors: Jaap I. van Waning, Kadir Caliskan, Yvonne M. Hoedemaekers, Karin Y. van Spaendonck-Zwarts, Annette F. Baas, S. Matthijs Boekholdt, Joost P. van Melle, Arco J. Teske, Folkert W. Asselbergs, Ad P.C.M. Backx, Gideon J. du Marchie Sarvaas, Michiel Dalinghaus, Johannes M.P.J. Breur, Marijke P.M. Linschoten, Laura A. Verlooij, Isabella Kardys, Dennis Dooijes, Ronald H. Lekanne Deprez, Arne S. IJpma, Maarten P. van den Berg, Robert M.W. Hofstra, Marjon A. van Slegtenhorst, Jan D.H. Jongbloed, Danielle Majoor-Krakauer
Journal: Journal of the American College of Cardiology (2018)
BAUS introduction to urology course
Authors: Michael Fabricius
Journal: BMJ (2010)

Many people will need to see a urologist at some point during their lives, but urology is a subject that seems to attract little coverage at undergraduate level. Furthermore, it can be difficult to gain much experience of the specialty at foundation and core training levels, even if participating in a general surgical rota. The teaching on this British Association of Urological Surgeons course helps doctors to make the step to specialist training in urology.

The introduction to urology course is aimed at doctors recently appointed to year 3 specialty training (ST3) posts in urology, and also at doctors planning to apply for these posts. Most delegates at the course I attended were core trainees, clinical fellows, or in research posts, accompanied by …
BALLOON PULMONARY ANGIOPLASTY IMPROVES RIGHT VENTRICULAR (RV) ENERGETIC EFFICIENCY VIA THE IMPROVEMENT OF RV-PULMONARY ARTERY COUPLING IN PATIENTS WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Authors: Takafumi Sakamoto, Koshin Horimoto, Kazuya Hosokawa, Kohtaro Abe, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Journal of the American College of Cardiology (2018)
UK doctors in New Zealand stay for job satisfaction and lifestyle
Authors: Helen Jaques
Journal: BMJ (2012)

Doctors who trained in the United Kingdom but have chosen to work in New Zealand often stay in their adopted country because of higher levels of job satisfaction and a preference for the lifestyle, a study in the Journal of the Royal Society of Medicine has reported (2012;105:25-34, doi:10.1258/jrsm.2011.110146).

Almost nine in 10 (89%) of the 282 UK trained doctors living in New Zealand who responded to the authors’ survey said …
An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies
Authors: Matthew L Cooper, Jaebok Choi, Karl Staser, Julie K Ritchey, Jessica M Devenport, Kayla Eckardt, Michael P Rettig, Bing Wang, Linda G Eissenberg, Armin Ghobadi, Leah N Gehrs, Julie L Prior, Samuel Achilefu, Christopher A Miller, Catrina C Fronick, Julie O’Neal, Feng Gao, David M Weinstock, Alejandro Gutierrez, Robert S Fulton, John F DiPersio
Journal: Leukemia (2018)
Effect of number of computed tomography (CT) scans during follow-up (FUP) of patients with clinical stage I (CSI) seminoma: A trial-level meta-analysis.
Authors: Patrizia Giannatempo, Daniele Raggi, Elena Tagliabue, Mario Catanzaro, Davide Biasoni, Tullio Torelli, Silvia Stagni, Nicola Nicolai, Luigi Piva, Roberto Salvioni, Luigi Mariani, Andrea Necchi
Journal: Journal of Clinical Oncology (2018)

564 Background: Despite the overall high cure-rate for patients (pts) with CSI seminoma (sem) regardless of the intervention used, huge discrepancy exists in the number of CT scans that are proposed to pts during FUP period, mainly during active surveillance (AS). The impact of such discrepancy in diagnosing pts with a high-risk relapse was assessed in published literature with a meta-analysis (MA). Methods: We searched for arms of studies of AS or active treatment (AT, adjuvant chemotherapy and radiotherapy) in pts with CSI sem. Meta-analytic techniques were used to pool and compare study level data of AS and AT groups and to study the impact of the number of CT scans (as a continuous variable) during FUP upon the % of pts with CSIII or with IGCCCG intermediate (int) prognosis sem at relapse. Results: 22 studies were analyzed (33 arms, n = 11025 pts). 39.6% had a high-risk sem, 38.8% (n = 4274) underwent AS vs 61.2% (n = 6751) AT. The number of CT scans ≤2y ranged 4-8, and 0-7 for AS and AT groups. Overall, 922 pts experienced a relapse (651 in AS and 271 in AT arms), 73.9% &lt;2y and 22.3% at 2-5y FUP. Statistical modeling showed that the estimated rates of CSIII relapse (6% in AS, 32% in AT group, p = 0.0068) and int prognosis relapse (2% in AS, 11% in AT group, p = 0.0051), were divergent for the two groups. A higher number of CT scans in the first 2 years of FUP tended to reduce the occurrence rate of both endpoints, but failed to reach statistical significance in AS (p = 0.334 for CSIII, unidentifiable for int prognosis relapse), as well as in AT (p = 0.438, p = 0.103). The number of CT scans in 3-5y FUP had an even weaker prognostic effect. Similar trends were observed in AS cohort after adjusting for the CSI risk group. Conclusions: In this trial-level MA we did not find a statistically-significant association between the number of CT scans performed during FUP of CSI sem pts and the diagnosis of high-risk relapses. Huge discrepancy in the total number of CT scans was generally found between arms. In contrast, as expected, the pattern of relapse of CSI sem was different according to the treatment group. Based on these results, there is room for consistently reducing the number of CT scans during FUP of CSI sem pts undergoing AS.
FDA Approval: Ribociclib for the Treatment of Postmenopausal Women with Hormone Receptor–Positive, HER2-Negative Advanced or Metastatic Breast Cancer
Authors: Anand Shah, Erik Bloomquist, Shenghui Tang, Wentao Fu, Youwei Bi, Qi Liu, Jingyu Yu, Ping Zhao, Todd R. Palmby, Kirsten B. Goldberg, C.J. George Chang, Paresma Patel, Elleni Alebachew, Amy Tilley, William F. Pierce, Amna Ibrahim, Gideon M. Blumenthal, Rajeshwari Sridhara, Julia A. Beaver, Richard Pazdur
Journal: Clinical Cancer Research (2018)

Abstract On March 13, 2017, the FDA approved ribociclib (KISQALI; Novartis Pharmaceuticals Corp.), a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)–positive, HER2-negative advanced or metastatic breast cancer. The approval was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2). A total of 668 patients were randomized to receive either ribociclib plus letrozole (n = 334) or placebo plus letrozole (n = 334). An improvement in progression-free survival (PFS) was observed in patients receiving ribociclib plus letrozole compared with patients receiving placebo plus letrozole [HR = 0.556; 95% confidence interval (CI), 0.429–0.720]. Overall response rate (ORR) in patients with measurable disease was 52.7% (95% CI, 46.6–58.9) in the ribociclib plus letrozole arm and 37.1% (95% CI, 31.1–43.2) in the placebo plus letrozole arm. Overall survival data were immature. The most common adverse reactions observed in 20% or more of patients taking ribociclib were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. This article summarizes FDA decision-making and data supporting the approval of ribociclib. Clin Cancer Res; 24(13); 2999–3004. ©2018 AACR. See related commentary by Spring and Bardia, p. 2981
A NOVEL NUTRITIONAL INDEX BY SIMPLY MULTIPLYING SERUM LEVELS OF TRIGLYCERIDES AND TOTAL CHOLESTEROL, AND BODY WEIGHT SERVES AS A USEFUL INDICATOR FOR ALL-CAUSE, CARDIOVASCULAR AND CANCER MORTALITY IN PATIENTS UNDERWENT PERCUTANEOUS CORONARY INTERVENTION
Authors: Shinichiro Doi, Hiroshi Iwata, Hideki Wada, Jun Shitara, Hirohisa Endo, Ryo Naito, Hirokazu Konishi, Shuta Tsuboi, Manabu Ogita, Tomotaka Dohi, Takatoshi Kasai, Shinya Okazaki, Kikuo Isoda, Katsumi Miyauchi, Hiroyuki Daida
Journal: Journal of the American College of Cardiology (2018)
Genetic regulation of <i>IL1RL1</i> methylation and IL1RL1-a protein levels in asthma
Authors: F. Nicole Dijk, Chengjian Xu, Erik Melén, Anne-Elie Carsin, Asish Kumar, Ilja M. Nolte, Olena Gruzieva, Goran Pershagen, Neomi S. Grotenboer, Olga E.M. Savenije, Josep Maria Antó, Iris Lavi, Carlota Dobaño, Jean Bousquet, Pieter van der Vlies, Ralf J.P. van der Valk, Johan C. de Jongste, Martijn C. Nawijn, Stefano Guerra, Dirkje S. Postma, Gerard H. Koppelman
Journal: European Respiratory Journal (2018)

Interleukin-1 receptor–like 1 ( IL1RL1 ) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma. Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101). IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10 −16 ) and serum IL1RL1-a levels (p=2.8×10 −56 ). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma. In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1- methylation CpG sites nor IL1RL1-a levels are associated with asthma.
Most orthopaedic trainees undertake fellowships to land a consultant post
Authors: Matthew Billingsley
Journal: BMJ (2012)

Nearly all orthopaedic trainees have undertaken at least one fellowship to help them compete for the limited number of consultant posts, a survey of 176 senior members of the British Orthopaedic Trainees Association has found.1

The survey found that 42% of respondents had completed one fellowship, 41% had completed two, and 11% had completed three or more. Only 6% had not undertaken any fellowships.

When applying for consultant posts, applicants ranked their fellowship experience as the most important aspect of their CV, over operative experience, research, and subspecialty qualifications. A third of respondents saw their fellowship as an important stepping stone to becoming a consultant.

Orthopaedic and trauma surgery is one of the most competitive specialties. …
Expert urges doctors to report themselves to GMC
Authors: Deborah Cohen
Journal: BMJ (2018)

A prominent campaigner for transparency in medicine has asked the GMC to remove him from its register and for his clinical practice to be scrutinised, after admitting to clinical errors that are likely to have led to deaths of patients. He has called on other doctors who have made similar mistakes to also report themselves to the GMC.

Consultant cardiologist Peter Wilmshurst made the case for his clinical practice to be investigated after the erasure from the UK medical register of the trainee paediatrician Hadiza Bawa-Garba. 

Bawa-Garba was struck off after being convicted of gross negligence manslaughter over the death of a 6 year old boy. A medical practitioners tribunal had previously decided to suspend her for 12 months, after taking account of system failures that contributed to Jack Adcock’s death. But that decision was overturned in the High Court last week after the GMC …
Doctors invited to offer top tips to F1 colleagues on first day on job
Authors: Abi Rimmer
Journal: BMJ (2014)

With over 7000 UK medical graduates set to start their first day as doctors on 6 August, the BMA has asked doctors to support their new colleagues by giving advice through social media (http://bit.ly/1lLZE8E). Doctors are offering advice to those beginning foundation year one (F1) posts under the hashtag #tipsfornewdocs.

One such tip came from Latifa Patel, a member of the BMA’s Junior Doctors Committee, who said, “Write useful bleeps/numbers on a sticker and place on the back of your …
Low testosterone at first PSA failure and assessment of the risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.
Authors: Katelyn Mae Atkins, Ming-Hui Chen, Jing Wu, Andrew A. Renshaw, Marian Loffredo, Philip W. Kantoff, Eric Jay Small, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2018)

45 Background: Low testosterone at prostate cancer diagnosis has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at first PSA failure following definitive therapy and prior to the documentation of metastatic disease has not been elucidated and was studied. Methods: Between 1995 to 2001, 58 men with unfavorable-risk prostate cancer treated on clinical trials with radiation and androgen deprivation therapy (ADT) had testosterone levels at PSA failure available. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone at PSA failure was associated with the risk of prostate cancer-specific, other-cause and all-cause mortality (PCSM, OCM, ACM) adjusting for age, salvage ADT use and known prostate cancer prognostic factors. Results: After a median follow-up of 6.68 years following first PSA failure, 31 men (53.4%) died; 10 from prostate cancer (32.3%), of which 8/11 (72.7%) versus 2/47 (4.3%) occurred in men with low versus normal testosterone at PSA failure, respectively. A significant increase in the risk of ACM (adjusted hazard ratio, AHR [2.54, 95% CI 1.04-6.21]; P = 0.04) and PCSM (AHR [13.71, 95% CI 2.4-78.16]; P = 0.003), with a reciprocal trend toward decreased risk of OCM (AHR [0.18, 95% CI 0.02-1.55]; P = 0.12) was observed in men with low versus normal testosterone at first PSA failure. Conclusions: Low testosterone at first PSA failure confers a very poor prognosis. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic prostate cancer and possibly in men with localized high-risk prostate cancer provides rationale to support their use with ADT in men with low testosterone at PSA failure in the setting of a phase II trial.
Imaging modalities used for follow-up of localized renal cell carcinoma (RCC) and subsequent effect on overall survival after recurrence: RECUR-database analysis.
Authors: Christian Beisland, Saeed Dabestani, Grant Stewart, Karim Bensalah, Eirikur Guðmundsson, Thomas B Lam, William Gietzmann, Paimaun Zakikhani, Lorenzo Marconi, Sergio Fernandèz-Pello, Serenella Monagas, Samuel P Williams, Christian Torbrand, Thomas Powles, Erik van Werkhoven, Richard Paul Meijer, Alessandro Volpe, Michael D. Staehler, Borje Ljungberg, Axel Bex
Journal: Journal of Clinical Oncology (2018)

637 Background: Cross-sectional imaging (CSI) has emerged as preferred imaging modality for staging and follow-up (FU). Moreover, the 2017 EAU RCC guidelines discourage the use of Chest X-Ray (CXR). In an international database (RECUR) data were collected to compare imaging modalities in contemporary FU, and to explore if more frequent use of CSI translates into improved overall survival (OS) after recurrence. Methods: Consecutive non-metastatic RCC patients treated with curative intent at 12 institutes across 8 European countries between 2006 and 2011, with at least 4 years of FU were included. Leibovich or UICC risk group (RG) (low, intermediate, high), recurrence characteristics, type of FU imaging (CSI (CT or MRI) vs. Conventional (CXR or Ultrasound)) and survival data were recorded. Isolated local, solitary and oligometastatic recurrences were considered potentially curable (PC) while all others were considered probably incurable (PI). Patients were analysed according to type of imaging that resulted in detection of recurrence (CSI vs. conventional) and if &gt; or &lt; 50% of all FU imaging were CSI based. Landmark analysis of OS after recurrence was performed for CSI and conventional imaging. Results: In 1612 patients, 336 (21%) had a recurrence. Of these, 122 were PC and 213 PI. Of the 17333 FU imaging procedures performed, 7953 were CT (46%), 6540 (38%) were CXR, 183 (1%) were MRI and 2651 (15%) were Ultrasound (US) investigations. The overall CT thorax/CXR- ratio decreased significantly across the risk groups, being 1.0, 0.46 and 0.35 in the high, intermediate and low RG, respectively (p &lt; 0.001). Moreover, between the high RG and the other RG`s the overall CT Abd/US-ratio also decreased (3.2, 1.7 and 1.7, respectively)(p &lt; 0.001). There was no significant difference in OS between patients with PC or PI recurrences based on type of imaging with which the recurrence was detected, nor on the ratio of CSI ( &gt; / &lt; 50%) during FU. Conclusions: More than 50% of FU imaging was conventional, with CSI more often used in high risk groups. The present study suggests that the type of imaging (conventional vs. CSI) for detection of recurrence does not affect subsequent OS.
Patients urged to lobby MPs over emergency department crisis
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The Royal College of Emergency Medicine has urged patients to write to their MP asking for action to tackle the crisis facing emergency departments across England.1

The college said that it had made the intervention in light of the latest performance figures from NHS England,2 which show that in February just 76.9% of major emergency departments achieved the target to treat 95% of patients within four hours. This was the worst performance against the target since it was established. The …
Seven in eight doctors whose revalidation was deferred out of concerns were not previously known to GMC
Authors: Abi Rimmer
Journal: BMJ (2014)

Seven in every eight doctors who had their revalidation date deferred because of ongoing concerns, such as being involved in a disciplinary process, have not previously been the subject of concerns raised with the General Medical Council.

Earlier this year the GMC published revalidation operational data reports that gave figures on numbers of doctors who were revalidated or were due to be revalidated from December 2012 to September 2013.12

The figures show that …
RISK OF DIABETES MELLITUS ON INCIDENCE OF OUT-OF-HOSPITAL CARDIAC ARREST AND TRENDS OF OUTCOMES: A 22-YEAR OBSERVATIONAL STUDY FROM THE MIDDLE EAST
Authors: Ayobami Omosola, Abdulrahman Arabi, Jassim Al Suwaidi, Rajvir Singh, Nidal Asaad
Journal: Journal of the American College of Cardiology (2018)