tbuckley/cabot-search huggingface dataset:
Gender bias to be tackled by Medical Schools Council review
Authors: Matthew Limb
Journal: BMJ (2015)

The Medical Schools Council has launched a review to improve equality and diversity in the council. It follows concerns over the “small number” of women deans and “gender bias” in the profession. The Equality Challenge Unit, a registered charity funded through the UK higher education funding bodies and which supports equality and diversity in higher education institutions, has confirmed that it will work on a joint review with the Medical Schools Council and the …
BMA and NHS Employers agree basis for junior doctor contract discussions
Authors: Helen Jaques
Journal: BMJ (2013)

The BMA and NHS Employers have agreed to discuss pay, working hours, and how much time is spent on training versus service delivery in any potential negotiations over the junior doctor contract.

The two organisations have been holding exploratory talks on possible changes to the terms and conditions of employment of doctors and dentists in training since NHS Employers published a “scoping report” on improving the current contract at the end of 2012.1

NHS Employers and the association have now agreed the draft “heads of terms” of any talks on changing the junior doctor contract for postgraduate training programmes in the UK.

The discussions will …
Hepatitis B virus surface gene pre‐S2 mutant as a high‐risk serum marker for hepatoma recurrence after curative hepatic resection
Authors: Chia‐Jui Yen, Yu‐Lin Ai, Hung‐Wen Tsai, Shih‐Huang Chan, Chia‐Sheng Yen, Kuang‐Hsiung Cheng, Yun‐Ping Lee, Chia‐Wei Kao, Yu‐Chun Wang, Yi‐Lin Chen, Cheng‐Han Lin, Tsunglin Liu, Huey‐Pin Tsai, Jen‐Ren Wang, Ih‐Jen Su, Wenya Huang
Journal: Hepatology (2018)

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre‐S 2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre‐S 2 region as a high‐risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV‐related HCC who underwent curative hepatic resection was analyzed for pre‐S gene mutations using Pre‐S Gene Chip. Results of the multivariate regression analysis showed that the serum pre‐S 2 mutant level and the American Joint Committee on Cancer stage were the two main independent high‐risk factors for recurrence. A Cox proportional hazards analysis also revealed a prediction model, which indicated the recurrence‐free survival rate along with the time after surgery; this was developed and further validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (area under the curve values, 0.741 and 0.704, respectively). Conclusion : Unlike the major HBV surface antigen, LHBS is mostly expressed in the tumorous regions of HBV‐induced HCC, indicating that it plays a unique role in tumor progression; the relative level of pre‐S 2 mutant in serum is, independently of tumor stage, an important high‐risk marker for HCC recurrence after primary hepatic resection. (H epatology 2018).
Remote Respiratory Allergen Challenge Increases the Frequency of Small Intestinal Eosinophils in Allergen-Sensitized Mice
Authors: Courtney L. Olbrich, Maytal Bivas-Benita, Jason J. Xenakis, Samuel Maldonado, Evangeline W. Cornwell, Lisa A. Spencer
Journal: Journal of Allergy and Clinical Immunology (2018)
Genomic analysis of liver cancer unveils novel driver genes and distinct prognostic features
Authors: Xiangchun Li, Weiqi Xu, Wei Kang, Sunny H. Wong, Mengyao Wang, Yong Zhou, Xiaodong Fang, Xiuqing Zhang, Huanming Yang, Chi H. Wong, Ka F. To, Stephen L. Chan, Matthew T.V. Chan, Joseph J.Y. Sung, William K.K. Wu, Jun Yu
Journal: Theranostics (2018)

Objective: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with a dismal prognosis. However, driver genes and prognostic markers in HCC remain to be identified. It is hoped that in-depth analysis of HCC genomes in relation to available clinicopathological information will give rise to novel molecular prognostic markers. Methods: We collected genomic data of 1,061 HCC patients from previous studies, and performed integrative analysis to identify significantly mutated genes and molecular prognosticators. We employed three MutSig algorithms (MutSigCV, MutSigCL and MutSigFN) to identify significantly mutated genes. The GISTIC2 algorithm was used to delineate focally amplified and deleted genomic regions. Nonnegative matrix factorization (NMF) was utilized to decipher mutational signatures. Kaplan-Meier survival and Cox regression analyses were used to associate gene mutation and copy number alteration with survival outcome. Logistic regression model was applied to test association between gene mutation and mutational signatures. Results: We discovered 11 novel driver genes, including RNF213, VAV3 and TNRC6B, with mutational prevalence ranging from 1% to 3%. Seven mutational signatures were also identified in HCC, some of which were associated with mutations of classical driver genes (e.g., TP53, TERT) as well as alcohol consumption. Focal amplifications of TERT and other druggable targets, including AURKA, were also revealed. Targeting AURKA by a small-molecule inhibitor potently induced apoptosis in HCC cells. We further demonstrated that HCC patients with TERT amplification displayed shortened overall survival independent of other clinicopathological parameters. In conclusion, our study identified novel cancer driver genes and prognostic markers in HCC, reiterating the translational importance of omics data in the precision medicine era.
MECHANICAL CIRCULATORY SUPPORT BY VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION OR IMPELLA CP IN A PORCINE MODEL OF PROFOUND CARDIOGENIC SHOCK: IMPACT ON LEFT VENTRICULAR UNLOADING AND END ORGAN PERFUSION
Authors: Ole Kristian Møller-Helgestad, Janus Adler Hyldebrandt, Nanna Louise Junker Udesen, Ann Banke, Charlotte Svejstrup Rud, Louise Linde, Lisette Jensen, Henrik Schmidt, Hanne Berg Ravn, Jacob Møller
Journal: Journal of the American College of Cardiology (2018)
Assessment of Ki67 in relation to radiotherapy (RT) fractionation and prognosis in the CHHiP (CRUK/06/016) trial.
Authors: Anna Wilkins, Barry Gusterson, Zsolt Szijgyarto, Joanne Haviland, Clare Griffin, Christine Stuttle, Frances Daley, Catherine M Corbishley, David P. Dearnaley, Emma Hall, Navita Somaiah
Journal: Journal of Clinical Oncology (2018)

98 Background: A uniform fractionation schedule is used to deliver external beam RT for localised prostate tumours Individualising fractionation according to tumour biology may improve outcomes. In addition recurrence rates after RT vary considerably and better prognostic markers are needed to guide treatment choices. This study aims to identify if the cell proliferation marker Ki67 predicts response to RT fractionation in CHHiP, a randomised trial of 3 RT fractionation schedules. It also aims to identify if Ki67 predicts prognosis. Methods: A matched case:control study design was used, patients with biochemical or clinical failure &gt; 2 years after RT (BCR) were matched to patients without recurrence according to established prognostic factors (Gleason score, PSA, Tumour-stage) and fractionation schedule. Immunohistochemical (IHC) staining of diagnostic biopsy sections was carried out using the MIB1 Ki67 antibody. Two independent investigators scored Ki67 using the unweighted global method (1) to derive a mean and maximum percentage of cells staining positive (mean Ki67 and maximum Ki67 respectively). Conditional logistic regression models were fitted with interaction terms between the biomarker and the fractionation schedules to determine whether Ki67 predicted BCR according to fractionation. Secondly models were fitted using the entire case:control study sample to estimate the prognostic value of Ki67 on risk of BCR. Results: Ki67 results were available for 173 matched pairs. The interaction terms between Ki67 and the fractionation schedules were not significant. However mean and maximum Ki67 were significant prognostic markers for BCR in a model adjusted for established prognostic factors. Conditioning on matching variables and age, the odds of BCR is estimated to increase by 9% per 1 point increase in mean Ki67 (OR = 1.09, 95%CI:1.04–1.15, p = 0.001). Conclusions: Ki67 did not predict BCR according to fractionation schedule in CHHiP, however it did predict prognosis independently of established prognostic factors. Additional IHC biomarkers are under evaluation.
Pulmonary arteriovenous malformation presenting as spontaneous haemothorax on transthoracic ultrasound
Authors: Sze Shyang Kho, Mei Ching Yong, Swee Kim Chan, Martin Ngie Liong Wong, Siew Teck Tie
Journal: Thorax (2018)

A 45-year-old man with no known chronic medical illness presented with insidious onset of exertional dyspnoea and left pleuritic chest pain. He was pale on physical examination and left chest percussion note was dull. Otherwise, he had no telangiectasia, cyanosis or finger clubbing. No family history of telangiectasia or bleeding episodes were reported, he also denied any history of epistaxis or haemoptysis. Chest roentograph on admission demonstrated left pleural effusion. Transthoracic ultrasound showed a large thin-walled elongated hypoechoic nodule surrounded by collapsed lung and loculated hyperechoic pleural fluid (figure 1A, arrow). Colour Doppler ultrasound established turbulent flow within the nodule (figure 1B, arrow) which raised the suspicion of pulmonary arteriovenous malformation (PAVM). His haemoglobin level was 5.5 g/dL. Urgent CT thorax revealed multiple PAVMs with the largest at the left lower lobe, arising …
Cocaine and Marijuana Use Among Young Adults With Myocardial Infarction
Authors: Ersilia M. DeFilippis, Avinainder Singh, Sanjay Divakaran, Ankur Gupta, Bradley L. Collins, David Biery, Arman Qamar, Amber Fatima, Mattheus Ramsis, Daniel Pipilas, Roxanna Rajabi, Monica Eng, Jon Hainer, Josh Klein, James L. Januzzi, Khurram Nasir, Marcelo F. Di Carli, Deepak L. Bhatt, Ron Blankstein
Journal: Journal of the American College of Cardiology (2018)
The docetaxel-abiraterone acetate sequence compared to the abiraterone acetate-docetaxel sequence in metastatic castration-resistant prostate cancer patients with a response to previous castration superior to 12 months.
Authors: Maxime Desle, Alexandre Derminne, Sarah Lejeune, Emmanuel Seront
Journal: Journal of Clinical Oncology (2018)

353 Background: With the approval of the multiple new life-prolonging treatments for men with metastatic castration-resistant prostate cancer (mCRPC), the optimal sequencing of chemotherapy and androgen-receptor (AR) targeting agents remains unclear. Although response duration to castration could influence decision choice for second hormonal therapies, we do not know whether chemotherapy efficacy could be similar to AR targeting agents such as abiraterone acetate (AA). Methods: A retrospective analysis of mCRPC patients treated at Jolimont Hospital is reported. Patients included were castration-resistant PC with a response to castration superior to 12 months. They were treated with sequential docetaxel and AA, in either order. The combined progression-free survival (combined PFS: PFS1 + PFS2) of AA followed by docetaxel is compared to the reverse sequence (docetaxel followed by AA). Baseline characteristics are reported prior to the start of the first agent in the sequence. Results: Forty-two patients who started treatment for mCRPC between January 2013 and February 2017 were identified: 22 were in the docetaxel-AA sequence (Group A) and 20 were in the AA-docetaxel sequence (Group B). The median duration of response to castration was 16 months in Group A and 18 months in Group B. Proportion of Gleason &gt; 8 was higher in group A (60% vs 50%). Visceral or lymph node disease was more important in group A (35% vs 16%). Median pre-treatment PSA was similar in the two groups (27 and 30). In the group A, PFS1 was 9 months and PFS2 was 8 months, resulting in a combined PFS of 17 months (range 5 to 47months). In the group B, PFS1 was 8 months and PFS2 was 7 months, resulting in a combined PFS of 15 months (range 4 to 45 months). Conclusions: We do not observe differences in clinical outcomes based on alternative sequencing of AA and docetaxel in men with mCRPC with a previous response duration to castration longer than 12 months.
Just a painful swelling of the ankles?
Authors: Gisela Eugénio, João Tavares, Mary Marques, Cátia Duarte, J A P da Silva
Journal: BMJ (2018)

A 41 year old man presented with a three week history of acute painful swelling of both ankles accompanied by local erythema and heat, morning stiffness of short duration, and fever. During the fourth week, a tender nodular erythematous eruption developed in both legs, suggestive of erythema nodosum. The man had no personal, family, or epidemiological medical history. He reported no previous infections, trauma, or new medications. On physical examination, his temperature was 38.2°C. There was erythema, oedema, pain, and heat in both ankles, with a normal range of movement in the ankle joints, and lesions compatible with erythema nodosum on the anterior aspect of both legs. Laboratory results showed Fig 1 Radiograph of the chest showing bilateral hilar lymphadenopathies (arrows)
Cardioprotective Role of Myeloid-Derived Suppressor Cells in Heart Failure
Authors: Ling Zhou, Kun Miao, Bingjiao Yin, Huaping Li, Jiahui Fan, Yazhen Zhu, Hongping Ba, Zunyue Zhang, Fang Chen, Jing Wang, Chunxia Zhao, Zhuoya Li, Dao Wen Wang
Journal: Circulation (2018)

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand in cancer, inflammation, and infection and negatively regulate inflammation and the immune response. Heart failure (HF) is a complex clinical syndrome wherein inflammation induction and incomplete resolution can potentially contribute to HF development and progression. However, the role of MDSCs in HF remains unclear.The percentage of MDSCs in patients with HF and in mice with pressure overload-induced HF using isoproterenol infusion or transverse aortic constriction (TAC) was detected by flow cytometry. The effects of MDSCs on isoproterenol- or TAC-induced HF were observed on depleting MDSCs with 5-fluorouracil (50 mg/kg) or gemcitabine (120 mg/kg), transferring purified MDSCs, or enhancing endogenous MDSCs with rapamycin (2 mg·kg-1·d-1). Hypertrophic markers and inflammatory factors were detected by ELISA, real-time polymerase chain reaction, or Western blot. Cardiac functions were determined by echocardiography and hemodynamic analysis.The percentage of human leukocyte antigen-D-related (HLA-DR)-CD33+CD11b+ MDSCs in the blood of patients with HF was significantly increased and positively correlated with disease severity and increased plasma levels of cytokines, including interleukin-6, interleukin-10, and transforming growth factor-β. Furthermore, MDSCs derived from patients with HF inhibited T-cell proliferation and interferon-γ secretion. Similar results were observed in TAC- and isoproterenol-induced HF in mice. Pharmaceutical depletion of MDSCs significantly exacerbated isoproterenol- and TAC-induced pathological cardiac remodeling and inflammation, whereas adoptive transfer of MDSCs prominently rescued isoproterenol- and TAC-induced HF. Consistently, administration of rapamycin significantly increased endogenous MDSCs by suppressing their differentiation and improved isoproterenol- and TAC-induced HF, but MDSC depletion mostly blocked beneficial rapamycin-mediated effects. Mechanistically, MDSC-secreted molecules suppressed isoproterenol-induced hypertrophy and proinflammatory gene expression in cardiomyocytes in a coculture system. Neutralization of interleukin-10 blunted both monocytic MDSC- and granulocytic MDSC-mediated anti-inflammatory and antihypertrophic effects, but treatment with a nitric oxide inhibitor only partially blocked the antihypertrophic effect of monocytic MDSCs.Our findings revealed a cardioprotective role of MDSCs in HF by their antihypertrophic effects on cardiomyocytes and anti-inflammatory effects through interleukin-10 and nitric oxide. Pharmacological targeting of MDSCs by rapamycin constitutes a promising therapeutic strategy for HF.
PREDICTING CARDIOVASCULAR RISK USING COMMON UTILIZATION MANAGEMENT CRITERIA FOR PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 INHIBITORS IN COMMERCIALLY INSURED PATIENTS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
Authors: Machaon Bonafede, Stefan DiMario, Jeetvan Patel, Barbara Johnson, David J. Harrison
Journal: Journal of the American College of Cardiology (2018)
State Firearm Laws and Interstate Firearm Deaths From Homicide and Suicide in the United States
Authors: Elinore J. Kaufman, Christopher N. Morrison, Charles C. Branas, Douglas J. Wiebe
Journal: JAMA Internal Medicine (2018)

Firearm laws in one state may be associated with increased firearm death rates from homicide and suicide in neighboring states.To determine whether counties located closer to states with lenient firearm policies have higher firearm death rates.This cross-sectional study of firearm death rates by county for January 2010 to December 2014 examined data from the US Centers for Disease Control and Prevention for firearm suicide and homicide decedents for 3108 counties in the 48 contiguous states of the United States.Each county was assigned 2 scores, a state policy score (range, 0-12) based on the strength of its state firearm laws, and an interstate policy score (range, -1.33 to 8.31) based on the sum of population-weighted and distance-decayed policy scores for all other states. Counties were divided into those with low, medium, and high home state and interstate policy scores.County-level rates of firearm, nonfirearm, and total homicide and suicide. With multilevel Bayesian spatial Poisson models, we generated incidence rate ratios (IRR) comparing incidence rates between each group of counties and the reference group, counties with high home state and high interstate policy scores.Stronger firearm laws in a state were associated with lower firearm suicide rates and lower overall suicide rates regardless of the strength of the other states' laws. Counties with low state scores had the highest rates of firearm suicide. Rates were similar across levels of interstate policy score (low: IRR, 1.34; 95% credible interval [CI], 1.11-1.65; medium: IRR, 1.36, (95% CI, 1.15-1.65; and high: IRR, 1.43; 95% CI, 1.20-1.73). Counties with low state and low or medium interstate policy scores had the highest rates of firearm homicide. Counties with low home state and interstate scores had higher firearm homicide rates (IRR, 1.38; 95% CI, 1.02-1.88) and overall homicide rates (IRR, 1.32; 95% CI, 1.03-1.67). Counties in states with low firearm policy scores had lower rates of firearm homicide only if the interstate firearm policy score was high.Strong state firearm policies were associated with lower suicide rates regardless of other states' laws. Strong policies were associated with lower homicide rates, and strong interstate policies were also associated with lower homicide rates, where home state policies were permissive. Strengthening state firearm policies may prevent firearm suicide and homicide, with benefits that may extend beyond state lines.
Trainees removed from Kent hospital due to lack of consultant supervision
Authors: Abi Rimmer
Journal: BMJ (2017)

Health Education England (HEE) has recommended the removal of trainees from the Kent and Canterbury Hospital because of a lack of consultant supervision.

Trainees at the hospital, which is run by the East Kent Hospitals University NHS Foundation Trust, were receiving inadequate education and training, HEE said.

It said that 42 of the 76 trainees at the hospital should be moved to the trust’s other two acute hospitals—the William Harvey Hospital, Ashford and Queen Elizabeth The Queen Mother Hospital, Margate—to continue with their training.

In a statement HEE said that it had been working with the trust to improve the quality of education and training in the minor injuries …
Abstract P1-06-03: Breast cancer-specific survival (BCSS) in SEER patients with 21-gene Recurrence Score® (RS) results &amp;lt;11 classified as prognostic stage IA by new 8th edition AJCC staging manual
Authors: FL Baehner, VI Petkov, D McCullough, S Shak
Journal: Cancer Research (2018)

Abstract Introduction: The 8th edition of the AJCC Staging Manual added molecular features for the first time and now includes ER, PR, HER2, and the 21-gene assay for prognostic staging. We obtained real-world evidence of BCSS by age, tumor size, and grade in a population-based SEER analysis of N0, HR+, HER2-negative breast cancer and RS &amp;lt;11 (tumor size up to 5 cm) to obtain more detailed information on clinically “unfavorable” subgroups. Methods: RS results were provided to SEER registries as mandated by their methods for linkage (Petkov npj Breast Cancer 2016). Patients (pts) with RS &amp;lt;11 and size up to 5 cm were eligible if N0, HR+, HER2-negative, had no prior malignancy, and were diagnosed between Jan 2004 and Dec 2012 (SEER survival updated through 2013). 5-year BCSS was estimated using actuarial methods. Results: 9,304 pts had RS &amp;lt;11 (19% of those meeting all other eligibility), with median follow-up of 40 months. Median age was 59 y, with 22% &amp;lt;50 y and 16% ≥70 y. Tumor size was &amp;gt;2 cm in 21% of pts. Tumor grade was moderate in 54% and poor in 8% of pts. Overall, 5-year BCSS for pts with RS &amp;lt;11 was 99.6% (95% CI 99.4%, 99.7%), with reported chemotherapy (CT) use in 3.3% of pts. In contrast, BCSS for pts with RS &amp;gt;25 and RS ≥31 was 3.5% and 4.7%, respectively, with frequent CT use. 5-year BCSS for important clinicopathologic subgroups show high 5-year BCSS despite “unfavorable” age, tumor size, and grade (Table). 5-y BCSS for RS &amp;lt;11, by Clinicopathologic FactorsRS &amp;lt;11 and Age &amp;lt;50 yRS &amp;lt;11 and Tumor Size 2.1-5.0 cmRS &amp;lt;11 and Poor Tumor GradeN (% of N with CT ‘Yes’)5-y BCSS (95% CI)N (% of N with CT ‘Yes’)5-y BCSS (95% CI)N (% of N with CT ‘Yes’)5-y BCSS (95% CI)2009 (6.2%)100% (100%, 100%)1976 (5.5%)99.3% (98.5%, 99.7%)686 (5.8%)99.5% (97.9%, 99.9%) Conclusions: In this SEER population-based study, pts with RS &amp;lt;11 had a wide range of clinicopathologic features. 5-year BCSS was high (&amp;gt;99%), regardless of age, tumor size, or grade. These results support the new AJCC staging criteria that classify N0, HR+, HER2-negative pts with RS &amp;lt;11 and tumor size up to 5 cm as having Prognostic Stage IA disease. Citation Format: Baehner FL, Petkov VI, McCullough D, Shak S. Breast cancer-specific survival (BCSS) in SEER patients with 21-gene Recurrence Score® (RS) results &amp;lt;11 classified as prognostic stage IA by new 8th edition AJCC staging manual [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 P1-06-03.