tbuckley/cabot-search huggingface dataset:
Randomized Comparison of Percutaneous Transluminal Coronary Angioplasty and Medical Therapy in Stable Survivors of Acute Myocardial Infarction With Single Vessel Disease
Authors: UweZeymer, RainerUebis, AlbrechtVogt, Hans-GeorgGlunz, Hans-FriedrichVöhringer, DietrichHarmjanz, Karl-LudwigNeuhaus
Journal: Circulation (2003)

Background— Percutaneous transluminal coronary angioplasty of the infarct-related artery in stable survivors of acute myocardial infarction is often performed, even in patients without any symptoms or residual ischemia. Despite the lack of randomized studies, it is widely believed that this intervention will improve the clinical outcome of these patients. Methods and Results— Three hundred patients with single vessel disease of the infarct vessel and no or minor angina pectoris in the subacute phase (1 to 6 weeks) after an acute myocardial infarction were randomized to angioplasty (n=149) or medical therapy (n=151). Primary end point was the survival free of reinfarction, (re)intervention, coronary artery bypass surgery, or readmission for severe angina pectoris at 1 year. The event-free survival at 1 year was 82% in the medical group and 90% in the angioplasty group (P=0.06). This difference was mainly driven by the difference in the need for (re)interventions (20 versus 8, P=0.03). At long-term follow-u...
Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial
Authors: Carolyn S Calfee, Kevin L Delucchi, Pratik Sinha, Michael A Matthay, Jonathan Hackett, Manu Shankar-Hari, Cliona McDowell, John G Laffey, Cecilia M O'Kane, Daniel F McAuley, Andrew J Johnston, Archana Paikray, Cat Yates, Petra Polgarova, Esther Price, Amy McInerney, Katarzyna Zamoscik, Ged Dempsey, Colette Seasman, Lynn Gilfeather, Noel Hemmings, Sinead O'Kane, Paul Johnston, Lukas Pokorny, Chris Nutt, Orla O'Neill, Prashast Prashast, Chris Smalley, Reni Jacob, James O'Rourke, Syed Farjad Sultan, Carole Schilling, Gavin D Perkins, Teresa Melody, Keith Couper, Ron Daniels, Fang Gao, Julian Hull, Timothy Gould, Matthew Thomas, Katie Sweet, Dorothy Breen, Emer Neau, Willis J Peel, Catherine Jardine, Paul Jefferson, Stephen E Wright, Kayla Harris, Matthew Thomas, Sarah Hierons, John Laffey, Veronica McInerney, Luigi Camporota, Katie Lei, Sundeep Kaul, Molly Chibvuri, Andrew Gratrix, Rachael Bennett, Victoria Martinson, Lisa Sleight, Neil Smith, Philip A Hopkins, Daniel Hadfield, Sarah Casboult, Fiona Wade-Smith, Julie Dawson, Clare Mellis, Clair Harris, Georgina Parsons, Sinead Helyar, Andrew R Bodenham, Stuart Elliot, Zoe Beardow, Sian Birch, Brian Marsh, Teresa Martin, Akesh Dhrampal, Melissa Rosbergen, Stephen Webb, Fiona Bottrill, Henrik Reschreiter, Helena Barcraft-Barnes, Julie Camsooksai, Andrew Johnston, Aisling Clarkson, Conor Bentley, Lauren Cooper, Yongyan Qui, Natalie Mitchell, Ronald Carrera, Arlo Whitehouse, Christopher M Danbury, Nicola Jacques, Abby Brown, David Rogerson, Craig Morris, Timothy Walsh, Mike Gillies, Grant Price, Kallirroi Kefala, Neil Young, David Hope, Corrienne McCulloch, Jean Antonelli, Pam Ramsay, Kirsty Everingham, Louise Boardman, Heidi Dawson, Fiona Pollock, Joanne Thompson, Ingeborg D Welters, Lee Poole, Peter Hampshire, Alison Hall, Karen Williams, Anna Walker, Laura Youds, Samantha Hendry, Victoria Waugh, Julie Patrick-Heselton, David Shaw, Irfan Chaudry, Jacqueline Baldwin, Stephen Drage, Laura Ortiz-Ruiz de Gordoa, Daniel McAuley, Leona Bannon, Vanessa Quinn, Lia McNamee, Griania White, Maurizio Cecconi, Johannes Mellinghoff, Donal Ryan, Alistair Nichol, Banwari Agarwal, Paula Meale, Sarah James, Kulwant Dhadwal, Daniel Martin, Agnieszka Walecka, Stephen Ward, John Trinder, Samantha Hagan, Janice Montgomery, Catherine Leonard, Elizabeth Lemon, Tom Trinick, Murthy Buddhavarapu, Geraldine Ward, Christopher Bassford, Alan Davidson, Kate McGuigan, Anissa Benchiheub, Naomi Hickey, Alexander Binning, Steven Henderson, J A Wood, Andrew J Burtenshaw, Dawn Kelly, Terry Martin, Jessica Thrush, Julie Wollaston, Stephen Graystone, Gavin Nicol, Gareth Sellors
Journal: The Lancet Respiratory Medicine (2018)
Accuracy of Digital Pathologic Analysis vs Traditional Microscopy in the Interpretation of Melanocytic Lesions
Authors: Tracy Onega, Raymond L. Barnhill, Michael W. Piepkorn, Gary M. Longton, David E. Elder, Martin A. Weinstock, Stevan R. Knezevich, Lisa M. Reisch, Patricia A. Carney, Heidi D. Nelson, Andrea C. Radick, Joann G. Elmore
Journal: JAMA Dermatology (2018)

Use of digital whole-slide imaging (WSI) for dermatopathology in general has been noted to be similar to traditional microscopy (TM); however, concern has been noted that WSI is inferior for interpretation of melanocytic lesions. Since approximately 1 of every 4 skin biopsies is of a melanocytic lesion, the use of WSI requires verification before use in clinical practice. To compare pathologists' accuracy and reproducibility in diagnosing melanocytic lesions using Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) categories when analyzing by TM vs WSI. A total of 87 pathologists in community-based and academic settings from 10 US states were randomized with stratification based on clinical experience to interpret in TM format 180 skin biopsy cases of melanocytic lesions, including 90 invasive melanoma, divided into 5 sets of 36 cases (phase 1). The pathologists were then randomized via stratified permuted block randomization with block size 2 to interpret cases in either TM (n = 46) or WSI format (n = 41), with each pathologist interpreting the same 36 cases on 2 separate occasions (phase 2). Diagnoses were categorized as MPATH-Dx categories I through V, with I indicating the least severe and V the most severe. Accuracy with respect to a consensus reference diagnosis and the reproducibility of repeated interpretations of the same cases. Of the 87 pathologists in the study, 46% (40) were women and the mean (SD) age was 50.7 (10.2) years. Except for class III melanocytic lesions, the diagnostic categories showed no significant differences in diagnostic accuracy between TM and WSI interpretation. Discordance was lower among class III lesions for the TM interpretation arm (51%; 95% CI, 46%-57%) than for the WSI arm (61%; 95% CI, 53%-69%) (P = .05). This difference is likely to have clinical significance, because 6% of TM vs 11% of WSI class III lesions were interpreted as invasive melanoma. Reproducibility was similar between the traditional and digital formats overall (66.4%; 95% CI, 63.3%-69.3%; and 62.7%; 95% CI, 59.5%-65.7%, respectively), and for all classes, although class III showed a nonsignificant lower intraobserver agreement for digital. Significantly more mitotic figures were detected with TM compared with WSI: mean (SD) TM, 6.72 (2.89); WSI, 5.84 (2.56); P = .002. Interpretive accuracy for melanocytic lesions was similar for WSI and TM slides except for class III lesions. We found no clinically meaningful differences in reproducibility for any of the diagnostic classes.
Abstract 13368: Acetylation of VGLL4 Tdu Domain Modulates Its Activity to Regulate Postnatal Cardiac Growth <i>(Best of Basic Science Abstract)</i>
Authors: Zhiqiang Lin, Haidong Guo, Pingzhu Zhou, Qing Ma, Jin Zhang, Sean Stevens, Feng Liang, Qimin Quan, David Clapham, William T Pu
Journal: Circulation (2015)

Mammalian cardiomyocytes (CM) largely exit the cell cycle shortly after birth, limiting the heart’s capacity to recover from injury. The mechanisms that enforce neonatal CM cell cycle withdrawal are largely unknown. CM proliferation is stimulated by interaction of the co-activator YAP, the terminal effector of Hippo signaling, with the transcription factor TEAD1, but YAP’s mitogenic potency declines in the adult compared to fetal or newborn heart. Here we show that VGLL4, a CM-enriched TEAD1 binding protein, inhibits CM proliferation by competing with YAP for TEAD1 binding. Moreover, VGLL4 activity is regulated by acetylation of the lysine 225 (K225) residing in its first Tondu (Tdu) domain. Acetylation at K225 antagonized its interaction with TEAD1 in the neonatal heart. Overexpression of VGLL4 with a point mutation that blocks its acetylation enhanced VGLL4-TEAD1 interaction and limited CM proliferation, resulting in lethal cardiac hypoplasia. Our study defines a novel acetylation-mediated, VGLL4-dependent switch that regulates Hippo-YAP signaling and that restrains CM proliferation. These insights may enable more effective approaches to cardiac regeneration.
Abstract 1083A: An ex vivo 3D bone metastasis model for prostate cancer
Authors: Jenny Zilberberg, Saba Choudhary, Eugenia Dziopa, Cirian Mannion, Yair Kissin, Erika Parasido, Christopher Albanese, Woo Lee
Journal: Cancer Research (2018)

Abstract Introduction: Bone is the preferred site for prostate cancer (PCa) metastases and there is virtually no cure once the tumor is established within this niche. The development of therapeutic strategies against metastatic PCa has been limited by the lack of an all-human preclinical model to: (1) study PCa-bone interactions under physiologically relevant three dimensional (3D) microenvironments, (2) understand how these interactions result in the development of drug resistance, and (3) explore paradigm-changing precision medicine concepts. Methods: Conditionally reprogrammed primary PCa cells (CR-PCa, derived from a lymph node metastatic site) were integrated with our ex vivo human 3D bone tissue platform, as a transformative approach for modeling tumor behavior at the bone niche. The 3D bone tissue was engineered using primary osteoblastic (OSB) cells from human bone samples. These cells were biomimetically assembly with biphasic calcium phosphate microbeads (BCPm) in perfusion microfluidic culture devices. BCPm were used to replicate the 3D cellular network of OSTs in human bone. This 3D tissue model was successfully used to support the osteocytic differentiation of primary human OSB cells within the BCPm structure, while maintaining a single cell layer of osteoblasts on the surface of the 3D tissue resembling the bone endosteum. Results: Integration of the 3D bone tissue with CR-PCa cells resulted in a compromised endosteal layer after only 4 days of coculture, with more apoptotic OSTs in the tissues with CR-PCa vs. no PCa cells controls (P&amp;lt;0.01). For functional analysis, we stained 5 μm sections of the 3D tissues for alkaline phosphatase (ALP, an OSB marker) and sclerostin, an osteocytic marker and major signaling molecule released by embedded OSTs that suppresses osteoblastogenesis. Quantification of immunofluorescence staining revealed that ALP was significantly increased (P&amp;lt;0.05), whereas sclerostin significantly decreased (P&amp;lt;0.01) with the introduction of CR-PCa cells. This OSB phenotype, induced by PCa-bone interactions ex vivo, is entirely consistent with the OSB prostate cancer-bone metastasis niche seen in patients with advanced disease. Conclusions: Our model recapitulates: (1) an OSB monolayer closely resembling the endosteum at the bone/ bone marrow interface, (2) the complex microphysiological features and functions of 3D-networked OSTs, and (3) the interactions of primary PCa cells with osteoblasts and OSTs. Citation Format: Jenny Zilberberg, Saba Choudhary, Eugenia Dziopa, Cirian Mannion, Yair Kissin, Erika Parasido, Christopher Albanese, Woo Lee. An ex vivo 3D bone metastasis model for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1083A.
Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest
Authors: Nicolas Deye, Alain Cariou, Patrick Girardie, Nicolas Pichon, Bruno Megarbane, Philippe Midez, Jean-Marie Tonnelier, Thierry Boulain, Hervé Outin, Arnaud Delahaye, Aurélie Cravoisy, Alain Mercat, Pascal Blanc, Charles Santré, Hervé Quintard, François Brivet, Julien Charpentier, Delphine Garrigue, Bruno Francois, Jean-Pierre Quenot, François Vincent, Pierre-Yves Gueugniaud, Jean-Paul Mira, Pierre Carli, Eric Vicaut, Frédéric J. Baud
Journal: Circulation (2015)

Targeted temperature management is recommended after out-of-hospital cardiac arrest. Whether advanced internal cooling is superior to basic external cooling remains unknown. The aim of this multicenter, controlled trial was to evaluate the benefit of endovascular versus basic surface cooling.Inclusion criteria were the following: age of 18 to 79 years, out-of-hospital cardiac arrest related to a presumed cardiac cause, time to return of spontaneous circulation <60 minutes, delay between return of spontaneous circulation and inclusion <240 minutes, and unconscious patient after return of spontaneous circulation and before the start of cooling. Exclusion criteria were terminal disease, pregnancy, known coagulopathy, uncontrolled bleeding, temperature on admission <30°C, in-hospital cardiac arrest, immediate need for extracorporeal life support or hemodialysis. Patients were randomized between 2 cooling strategies: endovascular femoral devices (Icy catheter, Coolgard, Zoll, formerly Alsius; n=203) or basic external cooling using fans, a homemade tent, and ice packs (n=197). The primary end point, that is, favorable outcome evaluated by survival without major neurological damage (Cerebral Performance Categories 1-2) at day 28, was not significantly different between groups (odds ratio, 1.41; 95% confidence interval, 0.93-2.16; P=0.107). Improvement in favorable outcome at day 90 in favor of the endovascular group did not reach significance (odds ratio, 1.51; 95% confidence interval, 0.96-2.35; P=0.07). Time to target temperature (33°C) was significantly shorter and target hypothermia was more strictly maintained in the endovascular than in the surface group (P<0.001). Minor side effects directly related to the cooling method were observed more frequently in the endovascular group (P=0.009).Despite better hypothermia induction and maintenance, endovascular cooling was not significantly superior to basic external cooling in terms of favorable outcome.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00392639.
Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non–Small Cell Lung Cancer
Authors: Baohui Han, Kai Li, Qiming Wang, Li Zhang, Jianhua Shi, Zhehai Wang, Ying Cheng, Jianxing He, Yuankai Shi, Yizhuo Zhao, Hao Yu, Yang Zhao, Weiqiang Chen, Yi Luo, Lin Wu, Xiuwen Wang, Robert Pirker, Kejun Nan, Faguang Jin, Jian Dong, Baolan Li, Yan Sun
Journal: JAMA Oncology (2018)

Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A phase 2 trial showed anlotinib to improve progression-free survival with a potential benefit of overall survival, leading to the phase 3 trial to confirm the drug's efficacy in advanced non-small cell lung cancer (NSCLC).To investigate the efficacy of anlotinib on overall survival of patients with advanced NSCLC progressing after second-line or further treatment.The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical trial designed to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC. Patients from 31 grade-A tertiary hospitals in China were enrolled between March 1, 2015, and August 31, 2016. Those aged 18 to 75 years who had histologically or cytologically confirmed NSCLC were eligible (n = 606), and those who had centrally located squamous cell carcinoma with cavitary features or brain metastases that were uncontrolled or controlled for less than 2 months were excluded. Patients (n = 440) were randomly assigned in a 2-to-1 ratio to receive either 12 mg/d of anlotinib or a matched placebo. All cases were treated with study drugs at least once in accordance with the intention-to-treat principle.The primary end point was overall survival. The secondary end points were progression-free survival, objective response rate, disease control rate, quality of life, and safety.In total, 439 patients were randomized, 296 to the anlotinib group (106 [36.1%] were female and 188 [64.0%] were male, with a mean [SD] age of 57.9 [9.1] years) and 143 to the placebo group (46 [32.2%] were female and 97 [67.8%] were male, with a mean [SD] age of 56.8 [9.1] years). Overall survival was significantly longer in the anlotinib group (median, 9.6 months; 95% CI, 8.2-10.6) than the placebo group (median, 6.3 months; 95% CI, 5.0-8.1), with a hazard ratio (HR) of 0.68 (95% CI, 0.54-0.87; P = .002). A substantial increase in progression-free survival was noted in the anlotinib group compared with the placebo group (median, 5.4 months [95% CI, 4.4-5.6] vs 1.4 months [95% CI, 1.1-1.5]; HR, 0.25 [95% CI, 0.19-0.31]; P < .001). Considerable improvement in objective response rate and disease control rate was observed in the anlotinib group over the placebo group. The most common grade 3 or higher adverse events in the anlotinib arm were hypertension and hyponatremia.Among the Chinese patients in this trial, anlotinib appears to lead to prolonged overall survival and progression-free survival. This finding suggests that anlotinib is well tolerated and is a potential third-line or further therapy for patients with advanced NSCLC.ClinicalTrials.gov identifier: NCT02388919.
Abstract 18189: Direct Binding of LOX-1 With AT1 Receptors Mediates Ox-LDL-Induced Cardiomyocyte Hypertrophy
Authors: Hui Gong, Li Lin, Ning Zhou, Jian Wu, Yong Ye, Chunjie Yang, Guoping Zhang, Junbo Ge, Yunzeng Zou
Journal: Circulation (2016)

Introduction: Lectin-like oxidized low-density lipoprotein (ox-LDL) and its receptor LOX-1 as well as angiotensin II (AngII) and its type 1 receptor (AT1-R) have been implicated in the development ...
THU0287 The prevalence of remission in a real-life cohort of psoriatic arthritis patients treated with synthetic or biologic disease modifying drugs
Authors: E.G. Favalli, A. Fassio, S. Bugatti, A. Batticciotto, L. Quartuccio, M. Filippini, S. Parisi, M. Biggioggero, G. Zanframundo, I. Giovannini, M.C. Ditto, L. Idolazzi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The treat-to-target (T2T) strategy for the management of psoriatic arthritis (PsA) recently proposed by EULAR recommendations suggests to ideally achieve remission/Low Disease Activity (LDA) in all treated patients, but nowadays data on remission/LDA rate in a real-world setting are still lacking. <h3>Objectives</h3> To evaluate the disease activity state in a real-life cohort of PsA patients treated with synthetic and/or biologic disease modifying drugs (DMARDs). <h3>Methods</h3> We undertook a cross-sectional analysis of all PsA consecutive patients enrolled in a large Italian multicentric registry including 7 Italian tertiary rheumatology centres. Disease activity defined as number of swollen (SJ) and tender (TJ) joints, Leeds Enthesitis Index (LEI), number of dactylitis, Body Surface Area (BSA), patient global assessment (PGA), patient pain (PP), Health Assessment Questionnaire Disability Index (HAQ-DI), and C-reactive protein (CRP, mg/L) were computed and the rates of patients achieving Disease Activity in PSoriatic Arthritis (DAPSA) remission/LDA and Minimal Disease Activity (MDA) were calculated. Subanalysis after stratification according to ongoing treatment (sDMARDs or bDMARDs) were also performed. <h3>Results</h3> The study population included 362 PsA patients (56.6% men; mean [±standard deviation, SD] age 53.3±12.4 years; mean [±SD] disease duration 9.4±8.2 years), treated with sDMARDs (15.8%, mainly methotrexate [66.6%]) or bDMARDs (79.6%, mainly anti-TNF agents [72.9%], as monotherapy [78.1%] or in combination with sDMARDs [21.9%]). Oligoarthritis (32%), polyarthritis (42%), axial involvement (11.9%), enthesitis (10.5%), and dactilytis (3.6%) were the reported predominant subsets of PsA. In the overall population the mean values [±SD] of disease activity measures were: SJ count 1.4±2.6, TJ count 1.9±3, LEI 0.5±1.1, number of dactylitis 0.1±0.3, BSA 2.6±6.9, PGA 1.4±2.6, PP 3±2.6, HAQ-DI 0.4±0.5, CRP level 3.4±8, and DAPSA 9.3±9.2. The rates of DAPSA LDA and remission were 46.9% and 31.7%, respectively. We found 51.6% of patients achieving MDA, without significant difference according to ongoing treatment (53.4% and 51% in bDMARD versus sDMARD treated patients, respectively; p=0.87). <h3>Conclusions</h3> In our real-life cross-sectional analysis, an acceptable comprehensive disease control was reported only in half of patients, irrespectively of ongoing therapy. These findings suggest the need to further improve the real-world application of T2T strategy for the management of PsA. <h3>Disclosure of Interest</h3> None declared
Abstract 15214: Commuting by Public Transportation is Associated With Lower Prevalence of Excess Body Weight, Hypertension, and Diabetes
Authors: HisakoTsuji, IchiroShiojima
Journal: Circulation (2015)

Background: Physical activity reduces body weight and incidence of diabetes mellitus (DM). We examined associations of commuting mode with prevalence of excess body weight, hypertension and DM. Methods: We studied 16,397 subjects who had the annual health checkup offered to adult citizens of Moriguchi city, Osaka, Japan in 2012. The subjects were asked about their work (Is your work physically active, sedentary or cannot say?) and commuting mode (walking or cycling / bus or train / car driving). Odds ratios (OR) of prevalence of excess body weight (body mass index >25.0 kg/m2), hypertension, and DM with 95% confidence intervals (CI) relative to the car driving group were calculated using logistic regression analyses adjusted for clinical variables. Results: There were 5,908 eligible workers. Characteristics of the subjects according to commuting mode are presented in the table. Compared to the car driving group, logistic regression analyses showed that the public transportation group had a significantly...