tbuckley/cabot-search huggingface dataset:
ARASENS: A phase 3 trial of darolutamide in combination with docetaxel for men with metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Matthew Raymond Smith, Fred Saad, Maha Hussain, Cora N. Sternberg, Karim Fizazi, Karin Sayuri Yamada, Christian Kappeler, Iris Kuss, Bertrand F. Tombal
Journal: Journal of Clinical Oncology (2018)

TPS383 Background: The addition of either docetaxel or abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) improves overall survival (OS) compared with ADT alone in men with mHSPC. It is hypothesized that other androgen receptor (AR)-targeted therapies could be combined with docetaxel for mHSPC. Darolutamide (ODM-201) is an investigational oral AR antagonist with a unique chemical structure and negligible blood-brain barrier penetration that inhibits tumor growth by binding to AR and AR mutants (eg, W742L and F877L) with high affinity and specificity. In phase 1/2 ARADES and phase 1 ARAFOR trials, darolutamide demonstrated antitumor activity and was well tolerated in men with metastatic castration-resistant prostate cancer (mCRPC). ARASENS will evaluate the addition of darolutamide to standard ADT and docetaxel in men with mHSPC. Methods: This international, randomized, double-blind, placebo-controlled phase 3 trial (NCT02799602) is being conducted at &gt; 300 sites in 23 countries. ~1300 men with newly diagnosed mHSPC will be randomized 1:1 to darolutamide (600 mg orally twice daily) or matching placebo. All patients will receive standard ADT + docetaxel (6 cycles). Patients will be stratified by disease extent and alkaline phosphatase level. Key inclusion criteria: histologically or cytologically confirmed PC with documented metastases, started ADT ± first-generation antiandrogen therapy ≤12 weeks before randomization, and ECOG performance status 0-1. The primary end point is OS. Secondary end points include time to mCRPC, initiation of subsequent anticancer therapy, symptomatic skeletal event (SSE)-free survival, time to first SSE, first opioid use, pain progression, and worsening of physical symptoms. Safety will be assessed. ARASENS is actively enrolling at &gt; 280 sites across 23 countries. Clinical trial information: NCT02799602.
False Information About Breast Cancer Screening
Authors: Burcu Zeynep Ozdemir, Paula M. Podrazik
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Helen McShane and colleagues reply to Deborah Cohen
Authors: Helen McShane, Adrian Hill, Mark Hatherill, Michele Tameris, Jacqui Shea, Ann Ginsberg
Journal: BMJ (2018)

Cohen questions the justification for a large efficacy trial of the novel tuberculosis (TB) vaccine MVA85A in South African infants.12 This trial confirmed that MVA85A was safe and provided valuable understanding of the TB vaccine.3 These trial results were published within 10 working days of our first seeing the data.24 We strongly agree with calls for rigor in conducting, and openness in reporting, preclinical studies, but we are confident that moving forward with this efficacy trial was justified.

Cohen’s article fails to distinguish between a lengthy academic disagreement and scientific misconduct. Buried within the article are three key points.

Firstly, none of the 14 trials of MVA85A in over 400 humans (the target species) before the infant efficacy trial showed a safety signal. When the University of Cape Town human research ethics committee reviewed the patient information …
Does signet-ring cell carcinoma of the stomach (SRCC) need stimulation of neoangiogenesis?
Authors: Ekaterina Igorevna Surikova, Elena Frantsiyants, Irina A. Goroshinskaya, Yulia A. Pogorelova, Valeria A. Bandovkina, Irina Valerevna Neskubina, Andrey A. Maslov, Dar'ja E. Medvedeva, Gennadiy V. Kaminskiy, Irina Tishchenko, Sergey A. Malinin, Lusegen Chilhahyan, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2018)

33 Background: Tumor neoangiogenesis is a complex coordinated process involving various regulatory molecules. Vascular endothelial growth factors, in particular VEGF-A, are important effectors. A multipotent TGF-β1 cytokine can modulate stromal angiogenesis reactions promoting the tumor growth. Our purpose was to study the function of the system of pro-angiogenic cytokines in tissues of stomach tumors of various histological types - adenocarcinoma (AC) and signet-ring cell carcinoma (SRCC). Methods: The concentrations of VEGF-A, VEGF-R1 and TGF-β1 were studied by ELISA in tumors, peritumoral zone and resection line tissues of gastric cancer patients without preoperative therapy: 15 patients with AC (T2-4N0-2M0, G2-G3, 50-84 years) and 10 patients with SRCC, comparable by sex, age and prevalence of cancer process. Results: Levels of VEGF-A, VEGF-R1 and TGF-β1 in the resection line tissues of AC and SRCC did not differ significantly. VEGF-A in AC tumor tissues exceeded significantly the levels in the resection line (by 2.3 times) and in the peritumoral zone (by 1.8 times). VEGF-A in SRCC tumor tissue did not differ significantly from the levels in the corresponding tissues of the resection line and peritumoral zone, but it was 2.6 times lower than in AC tumor tissues. VEGF-R1 levels in AC and SRCC were similar. TGF-β1 in AC tumor tissues was 3.2 and 2.6 times higher than in the resection line and peritumoral zone, respectively. TGF-β1 in SRCC tumor tissues did not differ from the levels in the peritumoral zone and in healthy tissues; TGF-β1 in tumor tissues was 3.2 times lower in SRCC than in AC. Conclusions: SRCC tumor tissues have significantly lower levels of pro-angiogenic VEGF-А and TGF-β1 cytokines, compared to AC tissues, which can indicate that SRCC has no need to form its own vasculature. It is probably associated with the biological characteristic of this histotype of gastric cancer - diffuse growth pattern, in contrast to the solid structure of AC.
治疗银屑病的青黛软膏中的靛玉红含量对比:一项随机、双盲、剂量对照试验
Authors: Y.‐K. Lin, L.‐C. See, Y.‐H. Huang, C.‐C. Chi, R.C.‐Y. Hui
Journal: British Journal of Dermatology (2018)

皮质类固醇是治疗银屑病中的常用外用药(皮肤外用),尽管确有疗效,但研究人员对长期使用表示担忧并且需要探索行之有效的替代方案。许多草本药也在局部使用,但疗效证据通常有限。青黛在中药中已经使用多年,但遗憾的是,经口服用可能导致胃肠道不良反应或肝损伤。以往研究表明,青黛作为天然软膏或改良制剂(含活性成分靛玉红)可能具有疗效,它有助于减少皮肤染色,效果好于天然制剂。靛玉红具有抗炎特性,并且能够减少银屑病中皮肤最外层(即表皮)角化细胞的过度更新。位于台湾地区的作者想要探索局部用制剂中靛玉红的最适含量。他们招募了 109 位成年银屑病患者,这些患者的皮损面积不到体表面积的 20%。受试者在 8 周治疗期内使用了不同含量的靛玉红(10 lg/g 至 200 lg/g),随后进入为期 12 周的监测期。研究人员在治疗前后测量了银屑病皮损面积和严重度指数 (PASI),作为衡量患者银屑病严重度的指标。200 lg/g 是最有效的含量:该组中,56.5% 患者的 PASI 分数提高 75%,且 30.4% 患者的 PASI 分数提高 90%,且瘙痒减轻。在停止治疗后,这种情况一直保持。未观察到严重不良反应,不过部分患者(甚至在使用最低剂量时)出现皮肤过敏。当然,该研究尚待确认,但作者提出局部使用靛玉红对治疗银屑病有效,其疗效介于单用钙泊三醇外用药与联用钙泊三醇和强效皮质类固醇之间,但毒性低于后者。
Individual and joint effect of postdiagnostic metformin and statin use on prostate cancer mortality among patients with high-risk prostate cancer.
Authors: Grace L. Lu-Yao, Jian-Yu E, Yong Lin, Timothy Rebbeck, Shou-En Lu, William Kevin Kelly, Anthony Victor D'Amico, Mark N. Stein, Lanjing Zhang, Isaac Kim, Kitaw Demissie, Anna C. Ferrari, Xiang-Lin Tan
Journal: Journal of Clinical Oncology (2018)

202 Background: Metformin and statin together may delay prostate cancer (CaP) metastasis. However, the joint effects on CaP mortality remain unknown. This study is to quantify individual and joint effects of post diagnostic statin and metformin use on CaP mortality in survivors with high-risk CaP. Methods: This population-based study includes patients identified from the SEER database linked with Medicare files diagnosed with high-risk CaP (T category ≥T2c or prostate specific antigen level ≥20 or Gleason score ≥8) in 2008-2011. Comparators did not have documented use of statin or metformin. Hazard ratios (HR) and 95% were calculated using a time-varying Cox proportional hazard model with competing causes of death. Results: Based on 12,700 patients, post-diagnostic use of statin and metformin was associated with a substantial reduction in CaP mortality (Table), with more pronounced effects in patients with obesity (HR=0.32) or M1 disease (HR=0.54). Effects of statins vary widely by brand, with atorvastatin being associated with the largest reduction in CaP mortality (HR=0.18, 95% 0.07-0.50). Conclusions: CaP mortality was substantially lower in post-diagnostic users of statin with high-risk CaP within 6 years of follow-up. Synergistic effect of statin and metformin was observed in M1 disease only. Randomized trials are warrant to confirm the findings.[Table: see text]
Transitioning patients with immune thrombocytopenia to second‐line therapy: Challenges and best practices
Authors: Adam Cuker
Journal: American Journal of Hematology (2018)

In patients with immune thrombocytopenia who do not adequately respond to first-line therapy, there is no clear consensus on which second-line therapy to initiate and when. This situation leads to suboptimal approaches, including prolonged exposure to treatments that are not intended for long-term use (eg, corticosteroids) and overuse of off-label therapies (eg, rituximab) while approved, more efficacious options exist. These approaches may not only fail to address symptoms and burden of disease, but may also worsen health-related quality of life. A better understanding of available second-line treatments may ensure best use of therapeutic options and thereby optimize patient outcomes.
Response to: ’M-CSF and GM-CSF monocyte-derived macrophages in systemic sclerosis: the two sides of the same coin?' by Lescoat <i>et al</i>
Authors: Jacques Behmoaras, Enrico Petretto
Journal: Annals of the Rheumatic Diseases (2018)

In the quest for identification of genes for complex disorders, the functional annotation of disease-risk variants in the relevant cell type remains a challenge. Lescoat and colleagues1 pose the question ‘ what is a scleroderma macrophage? ’ and in view of current literature (including the study by Moreno-Moral et al 2), argued how the heterogeneous range of activated macrophages can vary between target organs of interest and possibly across different fibrotic diseases.

While we share Lescoat’s point of view on the underlying complexity of functional cells in disease, it remains open to debate whether GM-CSF or M-CSF-mediated differentiation conditions of peripheral blood monocytes are sufficient to fully capture the characteristics of these cells in their disease context. As stated by Lescoat et …
BIOFLOW V: COMPARISON OF ULTRATHIN SIROLIMUS-ELUTING BIORESORBABLE POLYMER STENTS WITH THIN EVEROLIMUS-ELUTING DURABLE POLYMER STENTS - TARGET VESSEL MYOCARDIAL INFARCTION ANALYSIS
Authors: David E. Kandzari, Laura Mauri, Jacques Koolen, Joseph Massaro, Gheorghe Doros, Hector Garcia Garcia, Donald Cutlip, Ron Waksman
Journal: Journal of the American College of Cardiology (2018)
Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions
Authors: James E. Cassat, Jessica L. Moore, Kevin J. Wilson, Zach Stark, Boone M. Prentice, Raf Van de Plas, William J. Perry, Yaofang Zhang, John Virostko, Daniel C. Colvin, Kristie L. Rose, Audra M. Judd, Michelle L. Reyzer, Jeffrey M. Spraggins, Caroline M. Grunenwald, John C. Gore, Richard M. Caprioli, Eric P. Skaar
Journal: Science Translational Medicine (2018)

Multimodal mass spectrometric imaging identifies bacterial and host analytes in intact tissues during invasive infection in mice.
Understanding the Possible Nonmedical Risks of Preexposure Prophylaxis Prescription in Adolescents—Reply
Authors: Sybil G. Hosek, Craig M. Wilson
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
SEVERE MYOCARDITIS AS A COMPLICATION OF A NOVEL DUAL IMMUNOTHERAPY TREATMENT IN A PATIENT WITH ESOPHAGEAL CANCER
Authors: Giselle Suero-Abreu, Miguel Gonzalez Velez, Luke Chong, Arturo Perez, Shalini Krishnasamy, Tracy A. Proverbs-Singh, Martin Gutierrez
Journal: Journal of the American College of Cardiology (2018)
Metformin increases urinary sodium excretion by reducing phosphorylation of the sodium-chloride cotransporter
Authors: Hiroko Hashimoto, Naohiro Nomura, Wakana Shoda, Kiyoshi Isobe, Hiroaki Kikuchi, Kouhei Yamamoto, Takuya Fujimaru, Fumiaki Ando, Takayasu Mori, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Journal: Metabolism (2018)
Doctors must understand personal health budgets before roll out, says BMA
Authors: Caroline White
Journal: BMJ (2012)

The roll out of personal health budgets should be deferred until doctors fully understand their potential role and the benefits of allowing certain groups of patients with long term conditions to use NHS funds to “buy” care packages, the BMA has said.

Its stance follows a survey of doctors’ views of the budgets, carried out in September 2012, which showed that most respondents knew little or nothing about the scheme.

A national pilot of personal health budgets has been under way in England since 2009, and the final evaluation is due to be published later this month.

The government said that it would only go ahead with the scheme subject to the results of the final evaluation, but it has already indicated that it intends to implement …
Saline may raise risk of death and kidney complications more than balanced crystalloids
Authors: Susan Mayor
Journal: BMJ (2018)

Using saline as intravenous fluid treatment is associated with a higher risk of death and kidney complications than balanced crystalloid solutions in critically and non-critically ill adults admitted to hospital, two pragmatic randomised studies have shown.12 But a commentator warned that more research is needed before changing practice.

Intravenous resuscitation fluids are among the most common medical treatments in hospitals and are used routinely in emergency departments, hospital wards, intensive care units, and operating theatres.

Commonly used crystalloid solutions are saline (0.9% saline), which has a higher chloride concentration than plasma, and balanced crystalloids that contain additional anions, such as lactate or acetate, to act as physiological buffers to achieve near …
Impaired Tumor-Infiltrating T Cells in Patients with Chronic Obstructive Pulmonary Disease Impact Lung Cancer Response to PD-1 Blockade
Authors: Jérôme Biton, Hanane Ouakrim, Agnès Dechartres, Marco Alifano, Audrey Mansuet-Lupo, Han Si, Rebecca Halpin, Todd Creasy, Claudie Bantsimba-Malanda, Jennifer Arrondeau, François Goldwasser, Pascaline Boudou-Rouquette, Ludovic Fournel, Nicolas Roche, Pierre-Régis Burgel, Jeremy Goc, Priyanka Devi-Marulkar, Claire Germain, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Diane Damotte
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Patients with chronic obstructive pulmonary disease (COPD) have a higher prevalence of lung cancer. The chronic inflammation associated with COPD probably promotes the earliest stages of carcinogenesis. However, once tumors have progressed to malignancy, the impact of COPD on the tumor immune microenvironment remains poorly defined, and its effects on immune-checkpoint blockers' efficacy are still unknown.To study the impact of COPD on the immune contexture of non-small cell lung cancer.We performed in-depth immune profiling of lung tumors by immunohistochemistry and we determined its impact on patient survival (n = 435). Tumor-infiltrating T lymphocyte (TIL) exhaustion by flow cytometry (n = 50) was also investigated. The effectiveness of an anti-PD-1 (programmed cell death-1) treatment (nivolumab) was evaluated in 39 patients with advanced-stage non-small cell lung cancer. All data were analyzed according to patient COPD status.Remarkably, COPD severity is positively correlated with the coexpression of PD-1/TIM-3 (T-cell immunoglobulin and mucin domain-containing molecule-3) by CD8 T cells. In agreement, we observed a loss of CD8 T cell-associated favorable clinical outcome in COPD+ patients. Interestingly, a negative prognostic value of PD-L1 (programmed cell death ligand 1) expression by tumor cells was observed only in highly CD8 T cell-infiltrated tumors of COPD+ patients. Finally, data obtained on 39 patients with advanced-stage non-small cell lung cancer treated by an anti-PD-1 antibody showed longer progression-free survival in COPD+ patients, and also that the association between the severity of smoking and the response to nivolumab was preferentially observed in COPD+ patients.COPD is associated with an increased sensitivity of CD8 tumor-infiltrating T lymphocytes to immune escape mechanisms developed by tumors, thus suggesting a higher sensitivity to PD-1 blockade in patients with COPD.
Association between Emphysema and Chronic Obstructive Pulmonary Disease Outcomes in the COPDGene and SPIROMICS Cohorts: A <i>Post Hoc</i> Analysis of Two Clinical Trials
Authors: MeiLan K. Han, Nabihah Tayob, Susan Murray, Prescott G. Woodruff, Jeffrey L. Curtis, Victor Kim, Gerard Criner, Craig J. Galban, Brian D. Ross, Eric A. Hoffman, David A. Lynch, Ella Kazerooni, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The use of thoracic computed tomographic (CT) imaging in current and former smokers is becoming increasingly more common because of its widespread availability and utility in lung cancer screening.Prior studies have demonstrated associations between CT measures of emphysema and respiratory symptoms, exacerbations, and mortality (1-5).However, thus far, practical guidance on how to incorporate increasingly available quantitative imaging data into clinical practice is lacking.In this analysis, we use data from two large NIH-sponsored cohort studies, SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) and COPDGene (COPD Genetic Epidemiology), to examine the relationship between a readily available metric, CT-based emphysema, and risk for important patient outcomes including symptoms, exacerbations, and mortality.The goal of our analysis is not to advocate for routine CT imaging in chronic obstructive pulmonary disease (COPD) but, rather, to provide clinicians with guidance on how to translate increasingly available quantitative imaging data into information that can guide patient decision-making.We used data from COPDGene and SPIROMICS, both NIH-funded multicenter cohort studies of smokers with and without airflow obstruction.All subjects were age 40-80 years with 10 pack-years or more of exposure (6, 7).Exacerbations were defined by use of an antibiotic and/or steroid, emergency room visit, or hospital admission for a respiratory "flare-up" on the American Thoracic Society Respiratory Disease questionnaire.Exacerbation data for both cohorts were captured via longitudinal follow-up protocols.For both studies, all participants underwent spirometry before and after the administration of a short-acting bronchodilator; postbronchodilator values were used in this
Please can you inform me of the various routes into counselling? What are the different types of counselling?
Authors: Philip Crockett
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1β/NLRP3 Inflammasome
Authors: Soichi Sano, Kosei Oshima, Ying Wang, Susan MacLauchlan, Yasufumi Katanasaka, Miho Sano, María A. Zuriaga, Minoru Yoshiyama, David Goukassian, Matthew A. Cooper, José J. Fuster, Kenneth Walsh
Journal: Journal of the American College of Cardiology (2018)
Abstracts accepted for publication only
Authors: V Vankerckhoven, N Hens, A Thijssen, C Lammens, S Chapelle, A Vanderstraeten, D Jonkers, C Clemens, A Masclee, H Goossens, J Parra, J Gonzalez, M Gutierrez-Cuadra, J Rodríguez-Cabello, P De Lucio, C Fariñas-Alvarez, G Blanco, M Sanjuan, M Fariñas, I Fidalgo, T Gosiewski, M Strus, K Fyderek, K Kowalska-Duplaga, A Wedrychowicz, A Pietrzyk, P Heczko, R Humphries, P Wollenberg, M Lewinski, J Dien Bard, C Chiang-Ni, P Zheng, P Tsai, W Chuang, Y Lin, C Liu, J Wu
Journal: Clinical Microbiology and Infection (2011)
Executives are “not in tune” with how doctors feel about NHS
Authors: Matthew Limb
Journal: BMJ (2014)

NHS boards are “not in tune” with how doctors and other clinical staff feel about their organisations and how they view key components of compassionate care, analysis by the King’s Fund has found.1

The think tank said that it was particularly worried by the “lack of consensus” found on facets such as openness, honesty, and the ability of staff to raise concerns effectively.

“The disconnect between the views of executive directors and other staff, especially nurses and doctors, is cause for concern,” said Nicola Hartley, director of leadership development at the King’s Fund. “Creating truly compassionate patient services requires collective leadership, where all staff take responsibility for the success of the organisation and this is actively promoted by leaders in the organisation.”

The fund has published a survey of NHS staff alongside two reports on collective leadership,23 and it argued that NHS boards should make developing collective leadership a priority. Some 2000 NHS managers and clinicians were questioned in February and March 2014 about leadership, care, and culture. Just over half worked in acute organisations, the rest in mental health, community, commissioning, and primary care settings. The most notable finding, …