tbuckley/cabot-search huggingface dataset:
Assisted dying: Doctors could organise locally for law change while BMA refuses national poll, says US activist
Authors: Richard Hurley
Journal: BMJ (2018)

Even where national representative bodies remain opposed to assisted dying, doctors could influence legal change through their local organisations, such as GPs’ local medical committees in the UK, a US campaigner has said.

“In Colorado individual county medical societies—for example, Boulder—began passing resolutions for neutrality or even support,” Barbara Coombs-Lee, president of the US campaign group Compassion and Choices, told The BMJ .

A position of considered neutrality among doctors’ representatives is key to enabling legislative change, she said, and to her knowledge properly conducted polls of doctors by medical societies have never found a majority opposing assisted dying.

The BMA has not polled its members to justify its continuing opposition to assisted suicide, despite recent calls for it to do so, including from The BMJ .1 The BMA’s policy2 was set in 2006 by a vote at its annual representatives meeting, which is attended by only a small proportion of its membership. A debate on the issue was held at the annual meeting in 2016 and the policy of opposition upheld.3 Commenting on the issue this …
Abstract 13861: Overexpression of Plasminogen Activator Inhibitor-1 Ameliorates Cardiac Rupture after Experimental Myocardial Infarction in PAI-1 Transgenic Mice via Inhibiting Inflammatory Cell Accumulation and MMPs Activity
Authors: Takeaki Kaneko, Naoki Ishimori, Hiroyuki Tsutsui
Journal: Circulation (2012)

Background:  Left ventricular (LV) remodeling after myocardial infarction (MI) leads to congestive heart failure and sudden cardiac death. Ischemic injury and the inflammatory response involved in this maladaptive process may also contribute to cardiac rupture. Plasminogen activator inhibitor-1(PAI-1) plays a critical role in cardiac fibrosis. However little is known about the role of the plasminogen-plasmin system in cardiac rupture. We assessed the hypothesis that PAI-1 overexpression in the heart inhibits MMPs activity and reduces cardiac rupture after MI by using PAI-1 transgenic (TG) mice.    Methods:  We have developed TG mice which overexpress PAI-1 in vascular endothelial cells virtually exclusively. The TG mice were generated with expression of human PAI-1 driven by murine endothelin promoter. MI was induced by coronary artery occlusion in 12 to 16 weeks old PAI-1 TG mice and wild-type (WT) mice. Hearts were harvested at 0, 2, 4, 7 and 28 days after MI. LV function was assessed with echocardiography and infarct area was determined histologically and inflammatory cell accumulation in infarct area was characterized by immunocytochemistry. Gelatin zymography was performed to analyze activated MMP-2 and MMP-9 at each day.    Results:  As compared with WT mice, the rate of cardiac rupture during 28 days of follow-up was significantly lower in PAI-1 TG mice (WT 24.2% vs. TG 11.7%, n=34, P   Conclusions:  PAI-1 overexpression in the heart ameliorates cardiac rupture after MI in PAI-1 TG mice via inhibiting inflammatory cell accumulation and MMPs activity.
Turning the Tables — The New European General Data Protection Regulation
Authors: Charlotte J Haug
Journal: New England Journal of Medicine (2018)

Interview with Dr. Charlotte Haug on a new European privacy law that gives consumers, including patients, more explicit control of their own data. (06:33)Download Europe's General Data Protection Regulation shifts data ownership and control from organizations to consumers. The health care sector and the health research community have been surprisingly quiet, though they collect exactly the type of data the GDPR aims to protect.
What Is the BET on Solid Tumors?
Authors: Panagis Filippakopoulos
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors. May 07, 2018 ARTICLE CITATION DOI: 10.1200/JCO.2018.78.8695 Journal of Clinical Oncology - published online before print May 30, 2018 PMID: 29847297 What Is the BET on Solid Tumors? Panagis FilippakopoulosxPanagis FilippakopoulosSearch for articles by this author Show More Panagis Filippakopoulos, University of Oxford, Oxford, United Kingdom https://doi.org/10.1200/JCO.2018.78.8695 First Page Full Text PDF Figures and Tables © 2018 by American Society of Clinical Oncology Companion Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors
HALO 110-101: A phase Ib, randomized, open-label study of PEGPH20 (pegvorhyaluronidase alfa) in combination with cisplatin (CIS) + gemcitabine (GEM) (PEGCISGEM) or atezolizumab and CIS + GEM (PEGCISGEMATEZO) in hyaluronan-high subjects with locally advanced or metastatic cholangiocarcinoma and gallbladder cancer.
Authors: Mitesh J. Borad, Rachna T. Shroff, Ghassan K. Abou-Alfa, J. Randolph Hecht, Andrea J. Bullock, Paul S. Ritch, Dimitrios Chondros, Mann Muhsin, Do-Youn Oh
Journal: Journal of Clinical Oncology (2018)

TPS543 Background: Cholangiocarcinoma (CCA) is treated with CIS and GEM (CISGEM), but prognosis is poor. Hyaluronan (HA) accumulation in solid tumors may impede drug and immune cell access. PEGPH20 targets tumors that accumulate HA (HA-high). This study (NCT03267940) plans to enroll 70 subjects to evaluate the safety and activity of PEGPH20 + programmed cell death-ligand 1 (PD-L1) agent atezolizumab, (PEGCISGEMATEZO), &amp; PEGPH20 + CISGEM (PEGCISGEM) in HA-high subjects with CCA and gallbladder cancer. Study will comprise initial run-in and expansion portions. Primary endpoints include incidence of AEs and other laboratory/safety parameters and ORR (RECIST v1.1). Secondary endpoints include PK parameters; DOR, DCR, PFS, and ORR (RECIST v1.1 and immune-modified RECIST); and OS and OS by PD-L1 expression. Methods: ~6 HA-high subjects will be enrolled in PEGCISGEM arm run-in portion and undergo at ≥1 cycle; subsequently, 6 HA-high subjects will enter the PEGCISGEMATEZO arm. Treatment period will be 21-day cycles. In the expansion portion, ~50 HA-high subjects will be enrolled and randomized in a 2:2:1 ratio into PEGCISGEMATEZO, PEGCISGEM, and CISGEM arms. PEGPH20 is planned to be administered at 3.0 μg/kg on Days 1, 8 and 15 of all cycles in both portions. ATEZO will be administered at 1200 mg 1–3 hours after PEGPH20 on Day 1 of each 21-day cycle in the PEGCISGEMATEZO arm in both portions. In the PEGCISGEM &amp; PEGCISGEMATEZO arms, dosing schedule for CISGEM is the same during both portions, with administration of 25 mg/m 2 CIS and 1000 mg/m 2 GEM on Days 2 and 9 of each cycle. In CISGEM control arm (expansion only), dosing schedule will be on Days 1 and 8 of each cycle. Treatment will continue until death, withdrawal of consent, disease progression, or unacceptable toxicity. Tumor response will be evaluated using RECIST v1.1. AEs will be graded per NCI CTCAE v4.03. Tumor samples will be tested retrospectively for PD-L1 expression. Safety data will be periodically monitored by an independent data monitoring committee. Clinical trial information: NCT03267940.
Injury rate and prevention in elite football: let us first search within our own hearts
Authors: Martin Buchheit, Cristiano Eirale, Ben Michael Simpson, Mathieu Lacome
Journal: British Journal of Sports Medicine (2018)

Research and discussions about injury rates and their prevention in elite football is one of the hottest topics in the medical and sport science literature. Over the past years, there has been an explosion of the number of publications, including surveys,1 observational, retrospective or prospective2 studies, training interventions and various types of expert opinions and commentaries.3 This array of information are likely useful to improve our understanding of what the best practices may be and, in turn, increase our ability to better prepare, manage and treat players. However, a recent survey has shown that 83% of UEFA clubs do not follow evidenced-based prevention programmes.1 It was also shown that hamstring injuries kept increasing over the last 13 years.2 Taken together, those two papers may suggest that the majority of elite club practitioners likely disregard research findings1 and may therefore be the one to be blamed for those increased injury rates.2 

Making supporting staff and coaches responsible for those injuries is easy, especially when considering their perceived typical personality traits (ie, so-called type 2,4 high egos and little open-mindedness and willingness to learn—‘why could they be bothered applying the new study findings?’). While this may be true sometimes, the reality is that …
Shape-, size- and structure-controlled synthesis and biocompatibility of iron oxide nanoparticles for magnetic theranostics
Authors: Wensheng Xie, Zhenhu Guo, Fei Gao, Qin Gao, Dan Wang, Bor-Shuang Liaw, Qiang Cai, Xiaodan Sun, Xiumei Wang, Lingyun Zhao
Journal: Theranostics (2018)

In the past decade, iron oxide nanoparticles (IONPs) have attracted more and more attention for their excellent physicochemical properties and promising biomedical applications. In this review, we summarize and highlight recent progress in the design, synthesis, biocompatibility evaluation and magnetic theranostic applications of IONPs, with a special focus on cancer treatment. Firstly, we provide an overview of the controlling synthesis strategies for fabricating zero-, one- and three-dimensional IONPs with different shapes, sizes and structures. Then, the
Spillover of a hepatitis A outbreak among men who have sex with men (MSM) to the general population, the Netherlands, 2017
Authors: Ingrid HM Friesema, Gerard JB Sonder, Mariska WF Petrignani, Annemarie E Meiberg, Gini GC van Rijckevorsel, Wilhelmina LM Ruijs, Harry Vennema
Journal: Eurosurveillance (2018)

Since 2015, outbreaks of hepatitis A among men who have sex with men (MSM) have been reported worldwide. To examine the impact of these MSM outbreaks in the Netherlands, we combined notification and epidemiological data with sequence analysis. Our results show the hazards of outbreaks within risk-groups spilling over into the largely susceptible general population. One third of the outbreak-related hepatitis A virus genotypes were detected in non-MSM cases.
Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial
Authors: Andrew X Zhu, Richard S Finn, Julien Edeline, Stephane Cattan, Sadahisa Ogasawara, Daniel Palmer, Chris Verslype, Vittorina Zagonel, Laetitia Fartoux, Arndt Vogel, Debashis Sarker, Gontran Verset, Stephen L Chan, Jennifer Knox, Bruno Daniele, Andrea L Webber, Scot W Ebbinghaus, Junshui Ma, Abby B Siegel, Ann-Lii Cheng, Masatoshi Kudo, Angela Alistar, Jamil Asselah, Jean-Frederic Blanc, Ivan Borbath, Timothy Cannon, Ki Chung, Allen Cohn, David P Cosgrove, Nevena Damjanov, Mukul Gupta, Yoshivasu Karino, Mark Karwal, Andreas Kaubisch, Robin Kelley, Jena-Luc Van Laethem, Timothy Larson, James Lee, Daneng Li, Atisha Manhas, Gulam Abbas Manji, Kazushi Numata, Benjamin Parsons, Andrew S. Paulson, Carmine Pinto, Robert Ramirez, Suresh Ratnam, Magnus Rizell, Olivier Rosmorduc, Yvonne Sada, Yutaka Sasaki, Per I Stal, Simone Strasser, Joerg Trojan, Gina Vaccaro, Hans Van Vlierberghe, Alan Weiss, Karl-Heinz Weiss, Tatsuya Yamashita
Journal: The Lancet Oncology (2018)
The Sheath Hold
Authors: Geoffrey Rubin
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Adjuvant NY-ESO-1 vaccine immunotherapy in high-risk resected melanoma: a retrospective cohort analysis
Authors: Michael Lattanzi, Joseph Han, Una Moran, Kierstin Utter, Jeremy Tchack, Rachel Lubong Sabado, Russell Berman, Richard Shapiro, Hsin-Hui Huang, Iman Osman, Nina Bhardwaj, Anna C. Pavlick
Journal: Journal for ImmunoTherapy of Cancer (2018)

Cancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls.All melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort. All such patients with stage III melanoma were subsequently compared to historical control patients identified via a prospective institutional database with protocol-driven follow-up. Survival times were calculated using the Kaplan-Meier method, and Cox proportional hazard models were employed to identify significant prognostic factors and control for confounding variables.A total of 91 patients were treated with an NY-ESO-1 vaccine for the treatment of high-risk resected melanoma. Of this group, 67 patients were stage III and were selected for comparative analysis with 123 historical control patients with resected stage III melanoma who received no adjuvant therapy. Among the pooled vaccine cohort (median follow-up 61 months), the estimated median recurrence-free survival was 45 months, while the median overall survival was not yet reached. In the control cohort of 123 patients (median follow-up 30 months), the estimated median recurrence-free and overall survival were 22 and 58 months, respectively. Within the retrospective stage III cohort, NY-ESO-1 vaccine was associated with decreased risk of recurrence (HR = 0.56, p < 0.01) and death (HR = 0.51, p = 0.01). Upon controlling for sub-stage, the adjuvant NY-ESO-1 clinical trial cohort continued to exhibit decreased risk of recurrence (HR = 0.45, p < 0.01) and death (HR = 0.40, p < 0.01).In this small retrospective cohort of resected stage III melanoma patients, adjuvant NY-ESO-1 vaccine immunotherapy was associated with longer recurrence-free and overall survival relative to historical controls. These data support the continued investigation of adjuvant NY-ESO-1 based immunotherapy regimens in melanoma.
Beyond <i>Oxalobacter</i>: the gut microbiota and kidney stone formation
Authors: Gwen Falony
Journal: Gut (2018)

In the last decade, disease-association studies have dominated gut microbiome research. In many cases, the set-up of these studies has been explorative, screening faecal microbiomes for diagnostic signals with potential predictive or therapeutic perspectives. While such data-driven approaches contributed substantially to tool development and the establishment of metagenome research as a stand-alone field within microbial sciences, they also demonstrated that the untargeted characterisation of microbiome variation in the function of disease pathology is far from trivial.1 Researchers able to successfully establish microbiota–disease associations beyond microbiome background variation awaited the long and painful task to discriminate between causes and consequences, taking into account the continuously expanding list of microbiome covariates. Top-ranked among those covariates is the use of medication,2 emphasising a need for careful study design and cautious statistics when attempting to differentiate between drug and disease associations.3

Aside from data-driven gut microbiome research, far fewer studies have applied metagenome analyses to investigate predefined hypotheses. For some pathologies, a (co-)causative role of the gut microbial community in disease development had been hypothesised long before advance in sequencing technology revolutionised gut microbiota research. One such long-standing hypothesis concerns the potential implication of gut bacteria in idiopathic kidney stone …
Effect of immunotherapy and stereotactic radiosurgery on cognitive function and quality of life in long term survivors of metastatic brain malignancies.
Authors: Naveen Kumar Reddy, Franklin Brown, Judith Hess, Miklos C. Fogarasi, Veronica Chiang
Journal: Journal of Clinical Oncology (2018)

125 Background: Use of whole brain radiation, radiosurgery, targeted therapies, and more recently, immunotherapies have resulted in improved survival for patients with brain metastases. As patients live longer, it is becoming increasingly important to understand the long-term cognitive function (CF) and quality of life (QOL) changes associated with these therapies. Methods: The Yale Gamma Knife Database was searched for patients surviving greater than 2 years after brain metastasis diagnosis. Of 79 patients identified, 19 were willing to participate in study. All participants underwent a single assessment session of cognitive tests that evaluated executive function (TMTa and TMTb), processing speed (COWA), memory (HVLT), and quality of life (FACT-Br). Results: Within the whole group, mean age was 65.5 years (range 50-88), median time from brain metastasis diagnosis to testing was 60 months (range 25.6-120.6). Mean number of lesions treated was 3.8 (range 1-10). Mean total lesion volume treated was 14.1 mm 3 (range 0.6 - 39). Only 2 patients were treated with whole brain radiation therapy. Patient scores were compared to validated normative data for their age group. Patients performed worse than normal for their age on TMTb (p &lt; 0.0001), total word recall (p &lt; 0.0001) and discriminative ability (p = 0.0004). Patients performed as expected for age on TMTa, animal naming, FAS, and % retention. A negative correlation was seen between executive function results and QOL (TMTa: r = -0.569, p ≤ 0.05, TMTb: r = -0.484, p ≤ 0.05) and a positive correlation was seen between processing speed results and QOL (r = 0.672, p ≤ 0.001). Conclusions: In patients surviving more than 2 years after diagnosis and successful treatment of brain metastases, this study shows that portions of executive function and memory are worse than expected for their age, while cognitive processing speed is similar to norms. Cognitive function was correlated with QOL; patients with lowered cognitive function reported a lower quality of life. Given this preliminary data, a further study in a larger population is needed to determine if certain treatments preferentially predispose patients to declines in CF and QOL.
Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study
Authors: Charles Kyung Min Lee, Shufeng Li, Duy Cong Tran, Gefei Alex Zhu, Jinah Kim, Bernice Y. Kwong, Anne Lynn S. Chang
Journal: Journal of the American Academy of Dermatology (2018)
Enhancing the Potency and Specificity of Engineered T Cells for Cancer Treatment
Authors: Sujita Sukumaran, Norihiro Watanabe, Pradip Bajgain, Kanchana Raja, Somala Mohammed, William E. Fisher, Malcolm K. Brenner, Ann M. Leen, Juan F. Vera
Journal: Cancer Discovery (2018)

The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells has produced tumor responses even in patients with refractory diseases. However, the paucity of antigens that are tumor selective has resulted, on occasion, in "on-target, off-tumor" toxicities. To address this issue, we developed an approach to render T cells responsive to an expression pattern present exclusively at the tumor by using a trio of novel chimeric receptors. Using pancreatic cancer as a model, we demonstrate how T cells engineered with receptors that recognize prostate stem cell antigen, TGFβ, and IL4, and whose endodomains recapitulate physiologic T-cell signaling by providing signals for activation, costimulation, and cytokine support, produce potent antitumor effects selectively at the tumor site. In addition, this strategy has the benefit of rendering our cells resistant to otherwise immunosuppressive cytokines (TGFβ and IL4) and can be readily extended to other inhibitory molecules present at the tumor site (e.g., PD-L1, IL10, and IL13).Significance: This proof-of-concept study demonstrates how sophisticated engineering approaches can be utilized to both enhance the antitumor efficacy and increase the safety profile of transgenic T cells by incorporating a combination of receptors that ensure that cells are active exclusively at the tumor site. Cancer Discov; 8(8); 972-87. ©2018 AACR.See related commentary by Achkova and Pule, p. 918This article is highlighted in the In This Issue feature, p. 899.
A prospective long term follow up of pulmonary diffusion capacity reduction caused by dose dense chemotherapy in breast cancer patients.
Authors: Yosef Landman, Salomon M. Stemmer, Mordechai R. Kramer, Aaron Sulkes, Victoria Neiman, Tal Granot, Daniel Hendler, Karen A. Gelmon, Rinat Yerushalmi
Journal: Journal of Clinical Oncology (2018)

e12537 Background: We investigated pulmonary function in breast cancer patients receiving adjuvant dose dense chemotherapy (DDC). A total of 34 patients with no preexisting lung disease underwent repeated pulmonary function tests (PFT) before, during and after DDC, revealing a significant absolute mean reduction in Carbon Monoxide Diffusing Capacity (DLCO) of 16.4%, with 21 (61.8%) patients showing a relative decrease from baseline DLCO of over 20%. This update presents the long term follow up of these patients’ oncological and pulmonary outcomes. Methods: The DDC protocol used consisted of 4 bi-weekly cycles of Doxorubicin and Cyclophosphamide with growth factor support followed by 12 doses of weekly Paclitaxel. 25 patients without disease recurrence underwent a later PFT, performed after a median of 24 months from administration of DDC (ranging from 8 to 97 months). DLCO values were corrected for hemoglobin levels and displayed as percentage from expected value according to sex, age and height. Clinical data regarding additional therapies and disease recurrence and mortality were obtained from medical records. Statistical analysis was performed using t-test, Pearson correlation and Cox proportional Hazard regression. Results: The mean DLCO in the later PFT (81.9%) was significantly lower than the baseline mean DLCO (92.0%, P < 0.001) and significantly higher than the post DDC mean DLCO (75.6%, P = 0.003). 5 (20%) patients still showed a relative decrease from baseline of over 20%. DLCO recovery was found to be inversely correlated with age (R = -0.39, P = 0.05), and no correlation was found with the time passed until the later PFT or with any additional therapies. DDC related DLCO reduction was not found to be related to disease recurrence or survival. Conclusions: The significant reduction in DLCO seen after administration of DDC to breast cancer patients is evident even years afterwards. While some patients recover and return to their baseline pulmonary function, others will endure lasting diminished diffusion capacity. Practitioners and patients should be aware of these long term effects of treatment, especially regarding older women or those with preexisting lung disease.