tbuckley/cabot-search huggingface dataset:
Abstract OT3-03-03: PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients
Authors: J Abraham, A-L Vallier, W Qian, A Machin, L Grybowicz, S Thomas, M Weiss, C Harvey, K McAdam, L Hughes-Davies, A Roberts, R Roylance, E Copson, K Pinilla, A Armstrong, E Provenzano, M Tischkowitz, E McMurty, H Earl
Journal: Cancer Research (2019)

Abstract Background: No specific targeted therapies are available for Triple Negative Breast Cancers (TNBC), an aggressive and diverse subgroup. The basal TNBC sub-group share some phenotypic and molecular similarities with germline BRCA (gBRCA) tumours. In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow drugs called PARP inhibitors (Olaparib) to work more effectively. Aims: To establish if the addition of olaparib to neoadjuvant platinum based chemotherapy for basal TNBC and/or gBRCA breast cancer is safe and improves efficacy (pathological complete response (pCR)). Methods: Trial design: 3-stage open label randomised phase II/III trial of neoadjuvant paclitaxel and carboplatin +/- olaparib, followed by clinicians' choice of anthracycline regimen. Stage 1 and 2: Randomisation (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 for 4 cycles) or one of two research arms with the same chemotherapy regimen but with two different schedules of olaparib 150mg BD for 12 days. Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. End-points: Stage 1: Safety; Stage 2: Schedule selection using pCR rate and completion rate of olaparib using a “pick-the-winner” design. Stage 3: pCR rate. Enrichment design is applied with an overall significance level 0.05(α) and 80% power. A total of 527 patients will be included to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to platinum based chemotherapy. Trial Progress: PARTNER has been recruiting in UK since 27th May 2016. IDSMC recommended to continue the trial without change after reviewing the Stage 1 safety data. The recruitment of stage 2 was completed in April 2018 and results to be reviewed by the IDSMC in early 2019. The trial is open and enrolling patients to national and international sites. Citation Format: Abraham J, Vallier A-L, Qian W, Machin A, Grybowicz L, Thomas S, Weiss M, Harvey C, McAdam K, Hughes-Davies L, Roberts A, Roylance R, Copson E, Pinilla K, Armstrong A, Provenzano E, Tischkowitz M, McMurty E, Earl H. PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-03-03.
Evidence-Based and Patient-Centered Decisions Regarding Bariatric Surgery
Authors: Carolina Castillo-Castro, José Gerardo Gonzalez-Gonzalez, Rene Rodriguez-Gutierrez
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Influence of Renin-Angiotensin System Inhibitors on Lower–Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II
Authors: Timothy M.E. Davis, Wendy A. Davis
Journal: Diabetes Care (2020)

OBJECTIVE To determine whether ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) protect against lower–respiratory tract infections complicating type 2 diabetes. RESEARCH DESIGN AND METHODS Of 1,732 participants with diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II (FDS2) between 2008 and 2011, 1,482 had confirmed type 2 diabetes (mean age 65.8 years and median diabetes duration 9.0 years; 51.6% were male). All were followed for hospitalizations for or with, or deaths from, pneumonia/influenza, ascertained from validated administrative data linkage from study entry to end of 2016. Cox regression and competing risk regression were used to identify independent predictors of this outcome. RESULTS Two-thirds of participants (n = 982) were taking an ACEi and/or ARB at study entry (498 [33.6%] ACEi, 408 [27.5%] ARB, 76 [5.1%] both). During 9,511 person-years of follow-up (mean ± SD 6.4 ± 2.0 years), 174 participants had incident pneumonia/influenza (156 hospitalizations and 18 deaths without hospitalization). In Cox regression analysis, baseline ACEi/ARB use was independently associated with a reduced risk of incident pneumonia/influenza (cause-specific hazard ratio [HR] 0.64 [95% CI 0.45, 0.89], P = 0.008). Allowing for the competing risk of death did not change this finding (subdistribution HR 0.67 [0.48, 0.95], P = 0.024), and similar reductions were seen for ACEi, ARB alone, and ACEi/ARB combination therapy. There was no significant change in use of ACEi/ARB during follow-up [interaction with ln(time), P = 0.70]. Other significant predictors of incident pneumonia/influenza were previously reported, clinically plausible variables. CONCLUSIONS ACEi/ARB reduce the risk of pneumonia/influenza in people with type 2 diabetes.
Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer
Authors: Nicola Gaynor, John Crown, Denis M. Collins
Journal: Seminars in Cancer Biology (2020)

This review focuses on immune checkpoint inhibitors – immunomodulatory agents that aim to relieve tumour-mediated immune-cell suppression. Immune checkpoint proteins can be expressed on the tumour-cell or immune-cell populations. Immune checkpoint proteins dampen the immune response by inactivating immune cells capable of tumour destruction. Blockade of immune checkpoints has shown impressive results in a range of solid cancers, particularly melanoma and non-small cell lung cancer. The potential benefit of this class of drugs is widespread across most cancer types and an unprecedented number of clinical studies are underway to examine the benefit of these agents. The aims of this review are to: provide an overview of the key early immune checkpoint inhibitor trials involving drugs targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in multiple disease types; provide an overview of emerging therapies aimed at these targets; and provide a detailed exploration of the status of immune checkpoint inhibitors in breast cancer.
Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine
Authors: Nicolas Benech, Harry Sokol
Journal: Genome Medicine (2020)

Abstract Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.
Time for mental healthcare guidelines for recreational sports: a call to action
Authors: Stewart Anthony Vella, Christian Swann
Journal: British Journal of Sports Medicine (2020)

The mental health of professional athletes has become an important and visible global issue requiring strong and immediate action. Major organisations and governing bodies in sport psychology and sport science have published 10 position stands and statements on mental health in sport since 2016 (see table 1). These position stands and statements explicitly address, or emphasise, elite athletes (as defined by Swann et al ).1 None of the position stands, consensus statements, or guidelines directly address athletes that could be considered subelite participants–for example, standards below talent development programmes or university-level participation.1 These existing position stands exclude organised recreational sports where the vast majority of individuals participate.2 3 We call on sporting organisations and relevant professional bodies to urgently enact policy in regard to mental healthcare in recreational sport—which encompasses all sports participation outside of those who are investing or specialising in one or a few sports with the intended outcome of elite performance.4

View this table:

Table 1 
Existing statements on mental health in sport



At least 40% of children and adolescents in a majority of countries worldwide, and approximately 20% of all adults globally, participate in organised recreational sports.2 3 Fewer than …
Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma
Authors: Liang Lin, Shih-Feng Cho, Lijie Xing, Kenneth Wen, Yuyin Li, Tengteng Yu, Phillip A. Hsieh, Hailin Chen, Metin Kurtoglu, Yi Zhang, C. Andrew Stewart, Nikhil Munshi, Kenneth C. Anderson, Yu-Tzu Tai
Journal: Leukemia (2020)
Correction to: Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD
Authors: Xiaoqiang Tang, Arturo Toro, T. G. Sahana, Junli Gao, Jessica Chalk, Björn Oskarsson, Ke Zhang
Journal: Molecular Neurodegeneration (2020)

An amendment to this paper has been published and can be accessed via the original article.
Association of Sperm-Associated Antigen 5 and Treatment Response in Patients With Estrogen Receptor–Positive Breast Cancer
Authors: Tarek M. A. Abdel-Fatah, Graham R. Ball, Pulari U. Thangavelu, Lynne E. Reid, Amy E. McCart Reed, Jodi M. Saunus, Pascal H. G. Duijf, Peter T. Simpson, Sunil R. Lakhani, Lorinc Pongor, Balázs Gyorffy, Paul M. Moseley, Andrew R. Green, Alan G. Pockley, Carlos Caldas, Ian O. Ellis, Stephen Y. T. Chan
Journal: JAMA Network Open (2020)

There is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor-positive breast cancer.
Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease
Authors: Arno R. Bourgonje, Martin Feelisch, Klaas Nico Faber, Andreas Pasch, Gerard Dijkstra, Harry van Goor
Journal: Trends in Molecular Medicine (2020)

Inflammatory bowel disease (IBD) is associated with the production of reactive species that target cysteine redox switches in proteins, thereby affecting gene regulation, DNA damage, ion transport, intermediary metabolism, and mitochondrial function. Precursors of reactive species are derived from organic and inorganic compounds and their cofactors, including amino acids, vitamins, oxygen, nitrite, and sulfate. Nutrition and the gut microbiome fuel this process to a significant extent. The production of reactive species in IBD is reflected by a reduction in systemic free thiols, the major components of the antioxidant machinery. Systemic free thiols are amenable to nutritional or therapeutic intervention. This opens up future avenues for therapeutic modulation of redox status in IBD.
Role of regulatory T cells in psoriasis pathogenesis and treatment
Authors: L. Nussbaum, Y.L. Chen, G.S. Ogg
Journal: British Journal of Dermatology (2020)

Psoriasis is a chronic inflammatory disease with a strong genetic component that can be triggered by environmental factors. Disease pathogenesis is mainly driven by type 1 and type 17 cytokine-producing cells which, in healthy individuals, are modulated by regulatory T cells (Tregs). Tregs play a fundamental role in immune homeostasis and contribute to the prevention of autoimmune disease by suppressing immune responses. In psoriasis, Tregs are impaired in their suppressive function leading to an altered T-helper 17/Treg balance. Although Treg dysfunction in patients with psoriasis is associated with disease exacerbation, it is unknown how they are functionally regulated. In this review, we discuss recent insights into Tregs in the setting of psoriasis with an emphasis on the effect of current treatments on Tregs and how already available therapeutics that modulate Treg frequency or functionality could be exploited for treatment of psoriasis.
Academic Medicine and Black Lives Matter
Authors: Clyde W. Yancy
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Ambulatory management of primary spontaneous pneumothorax: an open-label, randomised controlled trial
Authors: Rob J Hallifax, Edward McKeown, Parthipan Sivakumar, Ian Fairbairn, Christy Peter, Andrew Leitch, Matthew Knight, Andrew Stanton, Asim Ijaz, Stefan Marciniak, James Cameron, Amrithraj Bhatta, Kevin G Blyth, Raja Reddy, Marie-Clare Harris, Nadeem Maddekar, Steven Walker, Alex West, Magda Laskawiec-Szkonter, John P Corcoran, Stephen Gerry, Corran Roberts, John E Harvey, Nick Maskell, Robert F Miller, Najib M Rahman
Journal: The Lancet (2020)

BackgroundPrimary spontaneous pneumothorax occurs in otherwise healthy young patients. Optimal management is not defined and often results in prolonged hospitalisation. Data on efficacy of ambulatory options are poor. We aimed to describe the duration of hospitalisation and safety of ambulatory management compared with standard care.MethodsIn this open-label, randomised controlled trial, adults (aged 16–55 years) with symptomatic primary spontaneous pneumothorax were recruited from 24 UK hospitals during a period of 3 years. Patients were randomly assigned (1:1) to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion, or both). The primary outcome was total length of hospital stay including re-admission up to 30 days after randomisation. Patients with available data were included in the primary analysis and all assigned patients were included in the safety analysis. The trial was prospectively registered with the International Standard Randomised Clinical Trials Number, ISRCTN79151659.FindingsOf 776 patients screened between July, 2015, and March, 2019, 236 (30%) were randomly assigned to ambulatory care (n=117) and standard care (n=119). At day 30, the median hospitalisation was significantly shorter in the 114 patients with available data who received ambulatory treatment (0 days [IQR 0–3]) than in the 113 with available data who received standard care (4 days [IQR 0–8]; p<0·0001; median difference 2 days [95% CI 1–3]). 110 (47%) of 236 patients had adverse events, including 64 (55%) of 117 patients in the ambulatory care arm and 46 (39%) of 119 in the standard care arm. All 14 serious adverse events occurred in patients who received ambulatory care, eight (57%) of which were related to the intervention, including an enlarging pneumothorax, asymptomatic pulmonary oedema, and the device malfunctioning, leaking, or dislodging.InterpretationAmbulatory management of primary spontaneous pneumothorax significantly reduced the duration of hospitalisation including re-admissions in the first 30 days, but at the expense of increased adverse events. This data suggests that primary spontaneous pneumothorax can be managed for outpatients, using ambulatory devices in those who require intervention.FundingUK National Institute for Health Research.
Remote assessment in sport and exercise medicine (SEM): a narrative review and teleSEM solutions for and beyond the COVID-19 pandemic
Authors: H Paul Dijkstra, Emin Ergen, Louis Holtzhausen, Ian Beasley, Juan Manuel Alonso, Liesel Geertsema, Celeste Geertsema, Sofie Nelis, Aston Seng Huey Ngai, Ivan Stankovic, Stephen Targett, Thor Einar Andersen
Journal: British Journal of Sports Medicine (2020)

Background The COVID-19 pandemic forces sport and exercise medicine (SEM) physicians to think differently about the clinical care of patients. Many rapidly implement eHealth and telemedicine solutions specific to SEM without guidance on how best to provide these services. Aim The aim of this paper is to present some guiding principles on how to plan for and perform an SEM consultation remotely (teleSEM) based on a narrative review of the literature. A secondary aim is to develop a generic teleSEM injury template. Results eHealth and telemedicine are essential solutions to effective remote patient care, also in SEM. This paper provides guidance for wise planning and delivery of teleSEM. It is crucial for SEM physicians, technology providers and organisations to codesign teleSEM services, ideally involving athletes, coaches and other clinicians involved in the clinical care of athletes, and to gradually implement these services with appropriate support and education. Conclusion teleSEM provides solutions for remote athlete clinical care during and after the COVID-19 pandemic. We define two new terms—eSEM and teleSEM and discuss guiding principles on how to plan for and perform SEM consultations remotely (teleSEM). We provide an example of a generic teleSEM injury assessment guide.
Microbial ingress and in vitro degradation enhanced by glucose on bioabsorbable Mg–Li–Ca alloy
Authors: Ling-Yu Li, Zhuang-Zhuang Han, Rong-Chang Zeng, Wei-Chen Qi, Xiao-Fan Zhai, Yi Yang, Yun-Tian Lou, Tingyue Gu, Dake Xu, Ji-Zhou Duan
Journal: Bioactive Materials (2020)

Biodegradable magnesium alloys are challenging to be implanted in patients with hyperglycemia and diabetes. A hypothesis is suggested that glucose accelerates microbial ingress and in vitro degradation of Mg-Li-Ca implants. Corrosion resistance and mechanical properties was demonstrated using electrochemical, hydrogen evolution and tensile tests. The bacteria from Hank's solution were isolated via 16S rRNA gene analysis. The results revealed that Mg-1Li-1Ca alloy exhibited different responses to Hank's solution with and without glucose. The solution acidity was ascribed to Microbacterium hominis and Enterobacter xiangfangensis, indicating that glucose promoted microbial activity and degradation and deterioration in mechanical property of Mg-1Li-1Ca alloy.
Coroners consider systemic failings in deaths of patients of convicted breast surgeon
Authors: Clare Dyer
Journal: BMJ (2020)

Coroners have opened an inquest into the deaths of four patients of the rogue breast surgeon Ian Paterson after concluding that some patients may have died of unnatural causes.

Opening the inquests into the deaths of four women from breast cancer, Birmingham and Solihull senior coroner Louise Hunt said she and area coroner Emma Brown would also consider the actions of other clinicians who worked alongside Paterson, and possible failings by management and regulators.

The move comes after West Midlands Police asked Hunt last January to review a random selection of Paterson’s cases. The …
The Contribution of Epigenetics to Cancer Immunotherapy
Authors: Lorea Villanueva, Damiana Álvarez-Errico, Manel Esteller
Journal: Trends in Immunology (2020)

Effective anticancer immunotherapy treatments constitute a qualitative leap in cancer management. Nonetheless, not all patients benefit from such therapies because they fail to achieve complete responses, suffer frequent relapses, or develop potentially life-threatening toxicities. Epigenomic signatures in immune and cancer cells appear to be accurate and promising predictors of patient outcomes with immunotherapy. In addition, combined treatments with epigenetic drugs can exploit the dynamic nature of epigenetic changes to potentially modulate responses to immunotherapy. Candidate epigenetic biomarkers may provide a rationale for patient stratification and precision medicine, thus maximizing the chances of treatment success while minimizing unwanted effects. We present a comprehensive up-to-date view of potential epigenetic biomarkers in immunotherapy and discuss their advantages over other indicators.
Specific targeting of PDGFRβ in the stroma inhibits growth and angiogenesis in tumors with high PDGF-BB expression: Erratum
Authors: Maria Tsioumpekou, Sara I. Cunha, Haisha Ma, Aive Åhgren, Jessica Cedervall, Anna-Karin Olsson, Carl-Henrik Heldin, Johan Lennartsson
Journal: Theranostics (2020)

[This corrects the article DOI: 10.7150/thno.37851.].
Occupation and cutaneous melanoma: a 45‐year historical cohort study of 14·9 million people in five Nordic countries*
Authors: J.H. Alfonso, J.I. Martinsen, E. Weiderpass, E. Pukkala, K. Kjærheim, L. Tryggvadottir, E Lynge
Journal: British Journal of Dermatology (2020)

The age‐adjusted incidence of cutaneous melanoma (CM) in the Nordic countries has increased during the last 60 years. Few prospective population‐based studies have estimated the occupational variation in CM risk over time. To determine occupational variation in CM risk. A historical prospective cohort study with a 45‐year follow‐up from 1961 to 2005 (Nordic Occupational Cancer Study, NOCCA) based on record linkages between census and cancer registry data for Nordic residents aged 30–64 years in Denmark, Finland, Iceland, Norway and Sweden. National occupational codes were converted to 53 occupational categories, and stratified into indoor, outdoor and mixed work, and into socioeconomic status. The standardized incidence ratios (SIRs) were estimated as observed number of CM cases divided by the expected number calculated from stratum‐specific person‐years and national CM incidence rates. During a follow‐up of 385 million person‐years, 83 898 incident cases of CM were identified. In all countries combined, men with outdoor work had a low SIR of 0·79 [95% confidence interval (CI) 0·77–0·81] and men with indoor work had a high SIR of 1·09 (95% CI 1·07–1·11). Differences in women pointed in the same direction. High socioeconomic status was associated with an excess risk: SIR 1·34 (95% CI 1·28–1·40) in men and SIR 1·31 (95% CI 1·26–1·36) in women. Technical, transport, military and public safety workers with potential skin exposure to carcinogens had excess risks. Occupational variation in CM risk may be partly explained by host, socioeconomic and skin exposure factors. Differences in CM risk across socioeconomic groups attenuated slightly over time.