tbuckley/cabot-search huggingface dataset:
IMPROVEMENT IN LARGE DENSITY HDL PARTICLE NUMBER BY NMR IS ASSOCIATED WITH IMPROVEMENT IN VASCULAR INFLAMMATION BY 18-FDG PET/CT AT ONE-YEAR IN PSORIASIS
Authors: Amit Dey, Martin Playford, Aditya Joshi, Agastya Belur, Aditya Goyal, Youssef Elnabawi, Jacob Groenendyk, Jonathan Chung, Joshua Rivers, Justin Rodante, Leonard Genovese, Aparna Sajja, Tushina Jain, Charlotte Harrington, Nevin Varghese, Parag Shukla, Heather Teague, Yvonne Baumer, Alan Remaley, Mark Ahlman, Joel Gelfand, Nehal Mehta
Journal: Journal of the American College of Cardiology (2018)
Women should not pretend to be Superwoman to be leaders, says King’s Fund
Authors: Matthew Limb
Journal: BMJ (2015)

Women need not pretend to have “Herculean” or superhero qualities to take up medical leadership roles, the King’s Fund has said.

Vijaya Nath, assistant director of leadership development at the King’s Fund, said she believed that women should be able to acknowledge potential failings. “It’s all right to say ‘sometimes we won’t get this right,’ just as we would expect that in men,” she said.

Nath co-chaired a discussion on inspiring and supporting women …
CIRCULATING MONOCYTE/MACROPHAGE-DERIVED EXTRACELLULAR VESICLES PREDICT POST-OPERATIVE MYOCARDIAL INFARCTION
Authors: Scott Damrauer, Maggie Schmierer, Annukka Atkins, Alex Fairman, Jinbo Chen, Luis Eraso, Jeffrey Carpenter, Ravi Dhanisetty, Jonni Moore, Wade Rogers, Emile Mohler
Journal: Journal of the American College of Cardiology (2018)
NanoVelcro rare-cell assays for detection and characterization of circulating tumor cells
Authors: Yu Jen Jan, Jie-Fu Chen, Yazhen Zhu, Yi-Tsung Lu, Szu Hao Chen, Howard Chung, Matthew Smalley, Yen-Wen Huang, Jiantong Dong, Li-Ching Chen, Hsiao-Hua Yu, James S. Tomlinson, Shuang Hou, Vatche G. Agopian, Edwin M. Posadas, Hsian-Rong Tseng
Journal: Advanced Drug Delivery Reviews (2018)
Tissue-Specific Immunoregulation: A Call for Better Understanding of the “Immunostat” in the Context of Cancer
Authors: William Pao, Chia-Huey Ooi, Fabian Birzele, Astrid Ruefli-Brasse, Michael A. Cannarile, Bernhard Reis, Sebastian H. Scharf, David A. Schubert, Klas Hatje, Nadege Pelletier, Olivia Spleiss, John C. Reed
Journal: Cancer Discovery (2018)

Abstract Checkpoint inhibitor therapy has been a breakthrough in cancer research, but only some patients with cancer derive substantial benefit. Although mechanisms underlying sensitivity and resistance to checkpoint inhibitors are being elucidated, the importance of organ-specific regulation of immunity is currently underappreciated. Here, we call for a greater understanding of tissue-specific immunoregulation, namely, “tissue-specific immunostats,” to make advances in treatments for cancer. A better understanding of how individual organs at baseline regulate the immune system could enable an improved precision medicine approach to cancer immunotherapy. Cancer Discov; 8(4); 395–402. ©2018 AACR.
Abstract 13135: The Clinical Significance of Intraoperative Iloprost Inhalation on Outcome of High Risk Cardiac Surgical Patients: A Multicenter Randomized Controlled Trial
Authors: Michael Winterhalter, Steffen Rex, Christian Stoppe, Peter Kienbaum, Hans-Helge Müller, Ines Kaufmann, Aristidis Dongas, Hermann Kuppe, Bernhard Zwissler
Journal: Circulation (2016)

Background: Perioperative right ventricular (RV) failure due to pressure overload resulting from pulmonary hypertension (PH) worsens postoperative outcomes in cardiac surgery. Inhaled iloprost is a potent pulmonary vasodilator improving biventricular performance, ameliorating myocardial and pulmonary ischemia-reperfusion injury and attenuating inflammation. We hypothesized that the prophylactic inhalation of iloprost improves postoperative outcome in patients undergoing elective open heart surgery being at an increased risk for perioperative RV failure. Methods and Results: In this phase 3, multicenter, randomized, double-blind, placebo-controlled trial, we randomly assigned 253 cardiac surgical patients at high risk for perioperative RV failure to the prophylactic inhalation of 20μg iloprost or placebo before and during weaning from extracorporeal circulation (ECC). The primary endpoint was the duration of postoperative ventilation. Secondary endpoints included perioperative hemodynamics, intensive care unit and hospital length of stay, and 90-days mortality. Safety was assessed by the incidences of adverse events. Iloprost had no significant effect on the time until extubation (iloprost: median: 720min [first quartile, third quartile][540min; 1218min]; placebo: 780min [468min; 1170min]; p=0.37). While the nebulization of iloprost decreased RV afterload and improved cardiac index, major secondary endpoints were not significantly affected. Treatment with iloprost was safe with the incidences of adverse events not differing between groups. Conclusions: The prophylactic inhalation of iloprost does not result in any meaningful improvement of perioperative morbidity and outcome in high-risk cardiac surgical patients. Clinical Trial Registration: URL: http://www.clinicaltrialsregister.eu . Unique identifier: EudraCT-number: 2008-002090-12; URL: http://www.clinicaltrials.gov . Unique identifier: NCT00927654
Junior doctor contract is to be renegotiated
Authors: Helen Jaques
Journal: BMJ (2012)

Junior doctors’ pay and conditions will be renegotiated after a report by NHS Employers branded the current contract “no longer fit for purpose.” 

NHS Employers proposes negotiating a new contract for junior doctors that would be based on the need to deliver more flexible working patterns and that recognised and rewarded trainees for clinical competences rather than simply hours worked. The recommendation comes in a scoping report that included input from employing organisations and the BMA.

Pay for trainees should be weighted more towards basic pay than banding, NHS Employers suggests, to reduce the financial risk …
Medical workforce is short of nearly 1000 GP trainees
Authors: Helen Jaques
Journal: BMJ (2012)

England has recruited almost 1000 fewer GP trainees over the past four years than planned, figures from the GP National Recruitment Office show.

This shortfall could threaten government plans to move more healthcare from secondary care to primary care and to have GPs lead the commissioning of health services, doctors’ leaders have said.

A 2008 report, A High Quality Workforce , set out government plans to increase the number of specialty training year 1 (ST1) places in general practice in England from 2500 to 3300 a year.1 The number of places was expected to rise by 200 in 2009, a further 300 in 2010, and 300 more in 2011.⇓

View this table:

Numbers of GP trainees recruited in comparison …
MYOCARDIAL CONTRACTILITY PREDICTS SYMPTOMATIC IMPROVEMENT ACROSS ALL FLOW-GRADIENT PATTERNS OF AORTIC STENOSIS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Vasvi Singh, Vijay Iyer, Asma Mursleen, Elizabeth Hansen, Stanley Fernandez, Saurabh Malhotra
Journal: Journal of the American College of Cardiology (2018)
Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas
Authors: Michelle A. Fanale, Steven M. Horwitz, Andres Forero-Torres, Nancy L. Bartlett, Ranjana H. Advani, Barbara Pro, Robert W. Chen, Andrew Davies, Tim Illidge, Mayur Uttarwar, Shih-Yuan Lee, Hong Ren, Dana A. Kennedy, Andrei R. Shustov
Journal: Blood (2018)
Doctors to be recruited on the basis of “values” as well as skills
Authors: Abi Rimmer
Journal: BMJ (2014)

NHS trusts will be able to allocate jobs to doctors on the basis of whether candidates have the “right values” as well as appropriate skills, Health Education England (HEE), the organisation responsible for medical education and training in England, has said.

HEE has launched a national values based recruitment framework to ensure that all students and staff …
Multi-parametric liquid biopsy analysis of circulating tumor cells (CTCs), cell-free DNA (cfDNA), and cell-free RNA (cfRNA) in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Emmanuelle Hodara, Daniel Zainfeld, Gareth Morrison, Alexander Cunha, Yucheng Xu, John D. Carpten, Peter V. Danenberg, Paul W. Dempsey, Joshua Usher, KATHLEEN DANENBERG, Farideh Z. Bischoff, Aditi Khurana, Philip D. Cotter, Mathew Moore, Shelly Gunn, Tanya B. Dorff, David I. Quinn, Amir Goldkorn
Journal: Journal of Clinical Oncology (2018)

274 Background: Molecular profiling of prostate cancer using liquid biopsies such as CTC capture and cell-free nucleic acid analysis yield informative yet distinct datasets. Additional insights may be gained by simultaneously interrogating multiple liquid biopsy components to construct a more comprehensive molecular disease profile. We have conducted an initial proof of principle study aimed at piloting this multi-parametric approach. Methods: Blood was drawn under an IRB-approved protocol from 20 mCRPC patients. Samples were analyzed simultaneously for the following: CTC enumeration and single CTC and matched white blood cell capture for whole genome amplification and low-pass copy number variation; CTC DNA and matched cfDNA for somatic single nucleotide variant analysis; plasma cfRNA extraction and qRT-PCR for AR, AR-V7, and PCA3. When available, liquid biopsies were compared with matched tumor profiles. Results: Fifteen of 20 patients (75%) had detectable CTCs by CellSearch (range: 1-692/7.5mL, median: 16.5/7.5mL). Thirteen of 20 patients (65%) had detectable SSNVs in CTC DNA and/or matched cfDNA, including mutations in TP53, PIK3CA, HRAS, and EGFR. Matched CTC DNA and cfDNA demonstrated both shared and distinct SSNVs. Copy number analysis of single CTCs was performed in 2 patients, and both had CNVs in multiple cancer relevant genes. A majority of CNVs were present in matched solid tumor profiles, but some were exclusive to the liquid biopsies. Plasma PCA3 and AR transcripts were detected in 18/20 (90%) and AR-V7 in 4/20 (20%) cfRNA samples. Unique SSNVs were detected at second time points at disease progression (more are being collected). Conclusions: In this pilot cohort, simultaneous multi-parametric profiling was feasible for CTC DNA mutations and CNVs, and matched plasma cfDNA mutations and cfRNA gene expression. These disease-specific molecular profiles were often concordant with tumor tissues but also contained new, potentially actionable alterations unique to CTC DNA or cfDNA. Expanded studies will build upon this approach to optimally leverage liquid biopsies for molecularly directed patient management.
Five-Year Follow-Up of Nivolumab in Previously Treated Advanced Non–Small-Cell Lung Cancer: Results From the CA209-003 Study
Authors: Scott Gettinger, Leora Horn, David Jackman, David Spigel, Scott Antonia, Matthew Hellmann, John Powderly, Rebecca Heist, Lecia V. Sequist, David C. Smith, Philip Leming, William J. Geese, Dennis Yoon, Ang Li, Julie Brahmer
Journal: Journal of Clinical Oncology (2018)

Purpose In two phase III studies, nivolumab, a programmed death-1 (PD-1) inhibitor antibody, improved overall survival (OS) versus docetaxel in pretreated advanced non–small-cell lung cancer (NSCLC). We report 5-year follow-up results from an early phase I study of nivolumab in this patient population and describe characteristics of 5-year survivors. Patients and Methods Patients with pretreated, advanced NSCLC received nivolumab 1, 3, or 10 mg/kg every 2 weeks in 8-week cycles for up to 96 weeks. OS from the time of first dose was estimated by the Kaplan-Meier method. Results The estimated 5-year OS rate was 16% for all treated patients (N = 129); 5-year OS rates were similar for squamous (16%) and nonsquamous (15%) NSCLC. Of 16 5-year survivors, most (88%) were known current or former smokers. Of 10 5-year survivors with quantifiable PD-1 ligand 1 expression, 70% had ≥ 1% PD-1 ligand 1 expression at baseline. Twelve 5-year survivors (75%) achieved a partial response to nivolumab per Response Evaluation Criteria in Solid Tumors, version 1.0, and two each (12%) had stable disease and progressive disease as best response. Nine 5-year survivors (56%) completed the maximum 96 weeks of nivolumab; four (25%) discontinued owing to adverse events and three (19%) owing to disease progression. As of a November 2016 database lock, 12 5-year survivors (75%) received no subsequent therapy and were without evidence of progressive disease at last follow-up. Conclusions Nivolumab treatment resulted in long-term OS and durable responses in a proportion of patients with pretreated advanced NSCLC. Long-term survivors had diverse baseline and on-treatment characteristics.
Abstract ES4-2: Adjuvant therapy for HER2-positive breast cancers: is less more?
Authors: RM O'Regan
Journal: Cancer Research (2018)

Abstract The use of trastuzumab-based chemotherapy has dramatically improved outcome for patients with early stage HER2-positive breast cancer. Given the excellent outcomes seen to date and the toxicities associated with therapy, it is critical to establish whether additional therapies can further improve outcome, and conversely if there are patients who would have a favorable outcome with less therapy. The addition of pertuzumab to trastuzumab-based chemotherapy results in improved survival for patients with metastatic HER2-positive breast cancer and higher response rates in the pre-operative setting. Although results of the AFFINITY trial demonstrated improved outcome for adding pertuzumab to trastuzumab-based chemotherapy, the benefit was largely restricted to patients with node-positive breast cancer. Additionally, it is unclear if patients treated pre-operatively require the continued addition of pertuzumab to trastuzumab. Neratinib, a pan-HER tyrosine kinase inhibitor, reduces recurrence rate when used following adjuvant trastuzumab, but the benefit appears restricted to hormone receptor-positive breast cancers and diarrhea is a significant issue with this agent. In contrast, de-escalating treatment for patients with stage 1 HER2-positive breast cancer with the use of paclitaxel and trastuzumab is associated with extremely favorable outcomes. To date, the treatment of HER2-positive early stage breast cancer has not taken hormone receptor status into account when selecting HER2-directed therapies. Breast cancers that express both hormone receptors and HER2 are heterogeneous and a significant proportion have a luminal A phenotype, suggesting the possibility that combined estrogen receptor and HER2 inhibition may be especially important, given the crosstalk between these pathways. Further evaluation of non-chemotherapeutic approaches in triple positive breast cancers is justified. Citation Format: O'Regan RM. Adjuvant therapy for HER2-positive breast cancers: is less more? [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 ES4-2.
Editor’s Choice: Mending a deteriorating relationship
Authors: Tom Moberly
Journal: BMJ (2015)

Government ministers, and particularly health secretary Jeremy Hunt, have not been endearing themselves to doctors in recent weeks and months. A quick perusal of mentions of Jeremy Hunt’s Twitter handle (@Jeremy_Hunt) or the hashtag #iminworkjeremy gives a flavour of the way in which many doctors view the man directing health policy in England.

It is not just …
Sex-Chromosome Recombination in Common Frogs Brings Water to the Fountain-of-Youth
Authors: Nicolas Rodrigues, Tania Studer, Christophe Dufresnes, Nicolas Perrin
Journal: Molecular Biology and Evolution (2018)

According to the canonical model of sex-chromosome evolution, the degeneration of Y or W chromosomes (as observed in mammals and birds, respectively) results from an arrest of recombination in the heterogametic sex, driven by the fixation of sexually antagonistic mutations. However, sex chromosomes have remained homomorphic in many lineages of fishes, amphibians, and nonavian reptiles. According to the "fountain-of-youth" model, this homomorphy results from occasional events of sex reversal. If recombination arrest in males is controlled by maleness per se (and not by genotype), then Y chromosomes are expected to recombine in XY females, preventing their long-term degeneration. Here, we provide field support for the fountain-of-youth, by showing that sex-chromosome recombination in Rana temporaria only depends on phenotypic sex: naturally occurring XX males show the same restriction of recombination as XY males (average map length ∼2 cM), while XY females recombine as much as XX females (average map length ∼150 cM). Our results challenge several common assumptions regarding the evolution of sex chromosomes, including the role of sexually antagonistic genes as drivers of recombination arrest, and that of chromosomal inversions as underlying mechanisms.
Abstract 2650: Safety and Efficacy of Crossover from Enoxaparin or Unfractionated Heparin to Bivalirudin: Results from ACUITY
Authors: Harvey D White, James Hoekstra, Charles V Pollack, E M Ohman, Gregg W Stone
Journal: Circulation (2006)

Objective: The ACUITY trial demonstrated that the use of bivalirudin monotherapy (Biv mono) resulted in superior net clinical outcomes compared to either unfractionated heparin (UFH) or enoxaparin (Enox) plus a glycoprotein IIb/IIIa inhibitor (GPI) in moderate and high risk ACS patients. Although previous ACS studies have shown that crossover from UFH to Enox and vice versa is associated with increased bleeding and ischemic events, the effect of crossover to Biv mono or remaining on consistent antithrombin (AT) therapy has not been studied.  Methods: We evaluated the incidence of net clinical outcome, composite ischemia and bleeding in patients on consistent therapy (single AT prior to angiography) and crossover therapy (single switch from UFH to Enox, Enox to UFH, or either heparin to Biv prior to angiography).  Results: Of the 13,819 patients enrolled in ACUITY, 6452 (46.7%) had consistent therapy and 4631 (33.5%) had crossover therapy. Patients receiving consistent therapy had less ischemic events and similar bleeding rates as those on crossover therapy. Within the consistent subgroup, patients receiving Biv mono had statistically significant improvements in net clinical outcome and bleeding. Outcomes were similar in the crossover subgroup except for decreased bleeding with Biv mono. See table.  Conclusion: Results from patients consistently treated with Bivalirudin monotherapy support the overall ACUITY findings with significant improvements in net clinical outcome and less bleeding. Patients can be crossed over from unfractionated heparin or enoxaparin to Bivalirudin monotherapy with improved net clinical outcome and similar ischemic events but with less bleeding. Bivalirudin monotherapy is a safe and effective alternative to consistent therapy.
International Cognition and Cancer Task Force Recommendations for Neuroimaging Methods in the Study of Cognitive Impairment in Non-CNS Cancer Patients
Authors: Sabine Deprez, Shelli R Kesler, Andrew J Saykin, Daniel H S Silverman, Michiel B de Ruiter, Brenna C McDonald
Journal: JNCI Journal of the National Cancer Institute (2017)

Cancer- and treatment-related cognitive changes have been a focus of increasing research since the early 1980s, with meta-analyses demonstrating poorer performance in cancer patients in cognitive domains including executive functions, processing speed, and memory. To facilitate collaborative efforts, in 2011 the International Cognition and Cancer Task Force (ICCTF) published consensus recommendations for core neuropsychological tests for studies of cancer populations. Over the past decade, studies have used neuroimaging techniques, including structural and functional magnetic resonance imaging (fMRI) and positron emission tomography, to examine the underlying brain basis for cancer- and treatment-related cognitive declines. As yet, however, there have been no consensus recommendations to guide researchers new to this field or to promote the ability to combine data sets. We first discuss important methodological issues with regard to neuroimaging study design, scanner considerations, and sequence selection, focusing on concerns relevant to cancer populations. We propose a minimum recommended set of sequences, including a high-resolution T1-weighted volume and a resting state fMRI scan. Additional advanced imaging sequences are discussed for consideration when feasible, including task-based fMRI and diffusion tensor imaging. Important image data processing and analytic considerations are also reviewed. These recommendations are offered to facilitate increased use of neuroimaging in studies of cancer- and treatment-related cognitive dysfunction. They are not intended to discourage investigator-initiated efforts to develop cutting-edge techniques, which will be helpful in advancing the state of the knowledge. Use of common imaging protocols will facilitate multicenter and data-pooling initiatives, which are needed to address critical mechanistic research questions.
Two thirds of emergency medicine training posts in Scotland are unfilled
Authors: Abi Rimmer
Journal: BMJ (2014)

Two thirds of emergency medicine training posts in Scotland have not been filled in the 2014 round of recruitment, and to fill these posts education officials have advertised in Europe, the United States, Canada, New Zealand, and Australia.

Figures from NHS Education for Scotland show that, as of June, just six of a total of 21 training posts in emergency medicine had been …
LONG-TERM SURVIVAL BETWEEN OFF VERSUS ON PUMP CORONARY ARTERY BYPASS GRAFTING: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Udit Thakur, Rahul Muthalaly, Nathan C. Wong, Francis J. Ha, James Cameron, Adam Brown, Julian Smith, Nitesh Nerlekar
Journal: Journal of the American College of Cardiology (2018)
Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth
Authors: Shayan Fakhraei Lahiji, Seol Hwa Seo, Suyong Kim, Manita Dangol, Jiyong Shim, Cheng Guo Li, Yonghao Ma, Chisong Lee, Geonwoo Kang, Huisuk Yang, Kang-Yell Choi, Hyungil Jung
Journal: Biomaterials (2018)
Practical palliative care for general practitioners
Authors: Sian Gilchrist
Journal: BMJ (2008)

This course has been designed principally for jobbing general practitioners and specialist nurses. Its aim is to provide evidence based or best practice knowledge and skills in the palliative care of patients. There is special emphasis on caring for patients at the end of their life. The focus of the course is on the practical care of patients and improving your current practice. A similar course with hospital based components is run for specialist registrars.

I have been a GP for 16 years and have had a career as a locum and as principal, but I am currently employed as a part time salaried GP for the …
Guselkumab 对使用优特克单抗疗效不佳的银屑病患者的有效性和安全性:随机、双盲 III 期 NAVIGATE 试验结果
Authors: R.G. Langley, T.‐F. Tsai, S. Flavin, M. Song, B. Randazzo, Y. Wasfi, J. Jiang, S. Li, L. Puig
Journal: British Journal of Dermatology (2018)

银屑病是一种慢性疾病,可导致发红以及鳞屑性皮损。当前治疗药物(尤其是生物制剂)经注射或静脉滴注 (IV) 给药,在治疗中度到重度的斑块状银屑病方面十分有效。但鉴于大部分患者希望痊愈,所以仍有改进的空间。优特克单抗是一种经批准的生物制剂,能够阻断人体的两种内蛋白质,即白介素 (IL)‐12 和 IL‐23。阻断这些蛋白质,人体就收不到引发银屑病炎症的信号。尽管优特克单抗对大部分患者有效,但患者大多无法痊愈。鉴于近期科学证据表明 IL‐23 在导致银屑病方面可能比 IL‐12 更重要,guselkumab 应时而生,这是一种专门针对 IL‐23 而非 IL‐12 研发的新型治疗方案,近期已经在美国获得批准,可用于治疗中度到重度的银屑病。在 NAVIGATE 试验中,871 位患有中度到重度斑块状银屑病的患者使用了优特克单抗。如果在 16 周后,患者未痊愈或几乎痊愈,则将被随机分配继续使用优特克单抗或开始使用 guselkumab 治疗,直到第 44 周为止。第 16 周至第 40 周,就患者实现痊愈或几乎痊愈的平均访视次数(最多 4 次)而言,使用 guselkumab 治疗的患者(1.5 次)显著高于使用优特克单抗治疗的患者(0.7 次)。此外第 28 周,使用 guselkumab 与使用优特克单抗治疗后痊愈或几乎痊愈的患者的比例相差一倍,分别是 31.1% 和 14.3%。在使用 guselkumab 或优特克单抗治疗的患者中,最常报告的不良反应是感染。作者得出结论,对于在使用优特克单抗治疗后未痊愈或几乎痊愈的患者,转用 guselkumab 可能是一种行之有效的治疗策略,并且不会引起安全问题。