tbuckley/cabot-search huggingface dataset:
Cellular Mechanisms Underlying the Development of Catecholaminergic Ventricular Tachycardia
Authors: Gi-ByoungNam, AlexanderBurashnikov, CharlesAntzelevitch
Journal: Circulation (2005)

Background— Mutations in the ryanodine 2 receptor (RyR2) gene have been identified in patients with catecholaminergic polymorphic ventricular tachycardia. We examined the cellular basis for the ECG features and arrhythmia mechanisms using low-dose caffeine to mimic the defective calcium homeostasis encountered under these conditions. Methods and Results— A transmural ECG and action potentials were recorded simultaneously from epicardial, M, and endocardial cells in arterially perfused canine ventricular wedge preparations. Caffeine alone produced no change (10 to 100 μmol/L) or a slight abbreviation (300 μmol/L) of the QT interval and no change in transmural dispersion of repolarization. Isoproterenol (100 nmol/L) alone induced sustained monomorphic ventricular tachycardia (VT) that originated in the epicardium in 3 of 14 wedge preparations. Isoproterenol in the presence of caffeine (100 to 300 μmol/L) induced epicardial VT in 9 of 16 wedge preparations. Delayed afterdepolarization–induced triggered beats...
Abstract 3597: Failure of Suppression of Circulating Free Fatty Acids is Associated with Increased Low-Density Lipoprotein Cholesterol in Response to Weight Loss
Authors: Marybeth Allian-Sauer, Warren H Capell, Julie P Sutherland, Pamela Wolfe, Natalie D Talley, Teri L Hernandez, Holly R Wyatt, Gary Foster, James O Hill, Robert H Eckel
Journal: Circulation (2007)

Introduction: Low carbohydrate (LCARB) diets are a popular method for weight loss. It is unclear how these diets affect metabolic and lipid profiles during active weight loss. Methods: 35 patients ...
Long‐term prognosis, subsequent pregnancy, contraception and overall management of peripartum cardiomyopathy: practical guidance paper from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy
Authors: Karen Sliwa, Mark C. Petrie, Denise Hilfiker‐Kleiner, Alexandre Mebazaa, Alice Jackson, Mark R. Johnson, Peter van der Meer, Amam Mbakwem, Johann Bauersachs
Journal: European Journal of Heart Failure (2018)
Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study
Authors: Neil Murphy, Heather A. Ward, Mazda Jenab, Joseph A. Rothwell, Marie-Christine Boutron-Ruault, Franck Carbonnel, Marina Kvaskoff, Rudolf Kaaks, Tilman Kühn, Heiner Boeing, Krasimira Aleksandrova, Elisabete Weiderpass, Guri Skeie, Kristin Benjaminsen Borch, Anne Tjønneland, Cecilie Kyrø, Kim Overvad, Christina C. Dahm, Paula Jakszyn, Maria-Jose Sánchez, Leire Gil, José M. Huerta, Aurelio Barricarte, J. Ramón Quirós, Kay-Tee Khaw, Nick Wareham, Kathryn E. Bradbury, Antonia Trichopoulou, Carlo La Vecchia, Anna Karakatsani, Domenico Palli, Sara Grioni, Rosario Tumino, Francesca Fasanelli, Salvatore Panico, Bas Bueno-de-Mesquita, Petra H. Peeters, Björn Gylling, Robin Myte, Karin Jirström, Jonna Berntsson, Xiaonan Xue, Elio Riboli, Amanda J. Cross, Marc J. Gunter
Journal: Clinical Gastroenterology and Hepatology (2018)

Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.
Making Measurement Matter
Authors: Stephan D. Fihn
Journal: JAMA Network Open (2018)

Mitesh S. Patel, MD, MBA, MS; Gregory W. Kurtzman, BA; Sneha Kannan, MD; Dylan S. Small, PhD; Alexander Morris, BS; Steve Honeywell Jr, BS; Damien Leri, MSEd, MPH; Charles A. L. Rareshide, MS; Susan C. Day, MD, MPH; Kevin B. Mahoney, MBA; Kevin G. Volpp, MD, PhD; David A. Asch, MD, MBA
Monthly High-Dose Vitamin D Supplementation and Cancer Risk
Authors: Robert Scragg, Kay-Tee Khaw, Les Toop, John Sluyter, Carlene M. M. Lawes, Debbie Waayer, Edward Giovannucci, Carlos A. Camargo
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Previous randomized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence. <h3>Objective</h3> To examine whether high-dose vitamin D supplementation received monthly, without calcium, is associated with a reduction in cancer incidence and cancer mortality in the general population. <h3>Design, Setting, and Participants</h3> This is a post hoc analysis of data from the Vitamin D Assessment (ViDA) study, a randomized, double-blind, placebo-controlled trial that recruited participants from family practices and community groups in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up completed December 31, 2015. Participants were adult community residents aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D<sub>3</sub>(n = 2558) or placebo (n = 2552). Two participants withdrew consent, and all others (n = 5108) were included in the primary analysis. Data analysis was by intention to treat. <h3>Interventions</h3> Oral vitamin D<sub>3</sub>, in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). <h3>Main Outcomes and Measures</h3> Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms (excluding nonmelanoma skin cancers) diagnosed from randomization until the study medication was discontinued on July 31, 2015. <h3>Results</h3> Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 58.1% were male, and 4253 (83.3%) were of European or another race/ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 (9.0) ng/mL. In a random sample of 438 participants, the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of cancer comprised 328 total cases of cancer (259 invasive and 69 in situ malignant neoplasms) and occurred in 165 of 2558 participants (6.5%) in the vitamin D group and 163 of 2550 (6.4%) in the placebo group, yielding an adjusted hazard ratio of 1.01 (95% CI, 0.81-1.25;<i>P</i> = .95). <h3>Conclusions and Relevance</h3> High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer. This study suggests that daily or weekly dosing for a longer period may require further study. <h3>Trial Registration</h3> anzctr.org.au Identifier:ACTRN12611000402943
Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction
Authors: Caroline Haig, David Carrick, Jaclyn Carberry, Kenneth Mangion, Annette Maznyczka, Kirsty Wetherall, Margaret McEntegart, Mark C. Petrie, Hany Eteiba, Mitchell Lindsay, Stuart Hood, Stuart Watkins, Andrew Davie, Ahmed Mahrous, Ify Mordi, Nadeem Ahmed, Vannesa Teng Yue May, Ian Ford, Aleksandra Radjenovic, Paul Welsh, Naveed Sattar, Keith G. Oldroyd, Colin Berry
Journal: JACC. Cardiovascular imaging (2018)

The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI). The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood. Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used. In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post–percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99). Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850)
Abstract 308: CTRP9 Regulates the Fate of Implanted Mesenchymal Stem Cells and Mobilizes Their Protective Effects Against Ischemic Heart Injury via Multiple Novel Signaling Pathways
Authors: Wenjun Yan, Wayne Lau, Theodore Christopher, Bernard Lopez, Erhe Gao, Walter Koch, Yajing Wang, Xinliang (Xin) Ma
Journal: Circulation Research (2017)

Cell therapy remains the most promising approach against ischemic heart failure. However, the poor survival of engrafted stem cells in the ischemic environment limits their therapeutic efficacy for cardiac repair post-MI. CTRP9 is a novel pro-survival cardiokine with significantly downregulated expression after MI. Here, we tested a hypothesis that CTRP9 might be a cardiokine required for a healthy microenvironment promoting stem cell survival and cardioprotection. Mice were subjected to MI and treated with adipose-derived mesenchymal stem cells (ADSCs, intramyocardial transplantation), CTRP9, or their combination. Administration of ADSCs alone failed to exert significant cardioprotection. However, administration of ADSCs in addition to CTRP9 further enhanced the cardioprotective effect of CTRP9 (P&lt;0.05 vs. CTRP9 alone), suggesting a synergistic effect. CTRP9 significantly increased ADSCs survival and migration after implantation. Conversely, the number of engrafted ADSCs was significantly reduced in the CTRP9KO heart. CTRP9 promoted ADSCs proliferation and migration in vitro, and protected ADSCs against hydrogen peroxide-induced cellular death. Discovery-drive approaches followed by cause-effect analysis identified that CTRP9 enhances ADSCs proliferation/migration by ERK1/2-MMP-9 signaling. CTRP9 promotes anti-apoptotic/cell survival via ERK-Nrf2/anti-oxidative protein expression. Mass spectrometry, immunocytochemistry, and immunoprecipitation identified N-cadherin as the novel CTRP9 binding partner on ADSC. N-cadherin knockdown completely abolished the above noted CTRP9 biological effects. Finally, CTRP9 promotes Sod-3 expression and secretion from ADSCs, protecting cardiomyocytes against oxidative stress-induced cell death. We provide the first evidence that CTRP9 promotes ADSCs proliferation/survival, stimulates ADSCs migration, and attenuates cardiomyocyte cell death by previously unrecognized signaling mechanisms (N-cadherin-ERK/MMP-9 and N-cadherin-ERK/Nrf2-SOD). These results suggest that CTRP9 is a cardiokine critical in maintaining a healthy microenvironment facilitating stem cell engraftment in infarcted myocardial tissue, thereby enhancing stem cell therapeutic efficacy.
Abstract 14903: Impact of Triple Antithrombotic Therapy on Amount of Unfractionated Heparin During Percutaneous Coronary Intervention
Authors: Naotaka Okamoto, Ryu Shutta, Motoki Yasunaga, Kyosuke Yanagawa, Yutaka Matsuhiro, Hitoshi Nakamura, Koji Yasumoto, Keisuke Yasumura, Akihiro Tanaka, Naoki Mori, Daisuke Nakamura, Masamichi Yano, Nobuhiko Makino, Yasuyuki Egami, Masami Nishino, Jun Tanouchi
Journal: Circulation (2016)

Introduction:  Monitoring of activated clotting time (ACT) is most frequently used to assess the degree of anticoagulation with unfractionated heparin (UFH) during percutaneous coronary intervention (PCI). Patients receiving oral anticoagulation including warfarin and direct oral anticoagulant (DOAC) who underwent PCI usually require dual antiplatelet therapy (DAPT). Such triple antithrombotic therapy (TATT) may be correlated with elevated bleeding risk, but it is unclear whether we should reduce UFH using ACT monitoring for the patients with TATT during PCI or not.   Purpose:  We investigated the effect of oral anticoagulants on ACT.   Methods:  We enrolled consecutive patients with DAPT who underwent elective PCI in our hospital from January 2014 to December 2015. We excluded the dialysis patients. We divided our patients into three groups: the patients with only DAPT, with DAPT + warfarin, and with DAPT + DOAC. We compared ACT values which were measured at 30 minutes after initial UFH, whose amount was determined by body weight, administration during the procedure among three groups.   Results:  The results among three groups were shown in a table. ACT and age was significantly different among three groups, but the other parameters including gender, body surface area (BSA), body mass index (BMI), serum-creatinine, amount of UFH per a kilogram were similar among three groups. In comparison between each two groups in terms of ACT, ACT was higher in DAPT + Warfarin group (n=26), and DAPT + DOAC group (n=16) than only DAPT group (n=295) (Only DAPT vs. DAPT + Warfarin; p   Conclusions:  ACT values during PCI were prolonged in the patients with TATT as compared to those with DAPT while initial dose of UFH was similar. The degree of effect on ACT is similar between warfarin and DOAC. We should reduce the amount of UFH during PCI in patients with triple antithrombotic therapy.
Abstract 18385: The Impact of Chronic Kidney Disease on Survival in Patients With Cardiac Resynchronization Therapy
Authors: David D Daly, Arasi Maran, Ashley Waring, Frank Cuoco, Lacy Sturdivant, Robert B Leman, Michael R Gold
Journal: Circulation (2015)

Introduction: The prevalence of chronic kidney disease (CKD) is increasing worldwide and it is associated with increased risk of cardiac death. Cardiac resynchronization therapy (CRT) has been shown to increase survival in heart failure patients with left ventricular systolic dysfunction and interventricular conduction delay, but patients with moderate to severe CKD were excluded from the large pivotal randomized trials. Little is known regarding the impact of CKD on survival with CRT long-term. Hypothesis: CKD reduced long-term survival among patients with CRT. Methods: The follow up of a prospective cohort of 431 consecutive patients undergoing de novo CRT-D implantation from 2002-2010 was performed. The primary endpoint was all cause mortality and was determined using hospital records and the US Social Security Death Index. Glomerular filtration rate was calculated from pre-implant serum creatinine, weight, height, age and race using the Modified Diet in Renal Dysfunction equation. A Kaplan Meier survival analysis was performed grouping patients by CKD stage. Results: Patients were followed for up to 12 years with a mean follow up duration of 4.7 ± 3.0 years. The cohort was 72% male with a mean age of 67 ± 11 years, ejection fraction of 25 ± 10 percent and QRS duration of 156 ± 24 msec. The patients with normal renal function and mild CKD (Stages 1 and 2) had improved survival compared with patients with moderate, severe or end stage kidney disease (Stages 3-5). The estimated five year survival was 68.9% for stage 1, 73.5% for stage 2, 55.5% for stage 3 and 45.4% for stage 4/5 CKD with a p&lt;0.001 by log rank test . Multivariate analysis showed that CKD Stage, QRS duration and age were independent predictors of survival with CRT. Conclusions: Renal disease is a strong predictor of long term survival with CRT. Moderate to severe CKD is associated with a near 2-fold increased mortality and this should be considered when making decision about the suitability for implantation.
Abstract 16361: Outcomes, and Cost in Patients With End-Stage Renal Disease Treated With Either Transcatheter or Surgical Aortic Valve Replacement
Authors: Viraj Bhise, Pushkar Kanade, Prakash Balan, Tuyen Nguyen, Anthony L Estrera, Richard Smalling, Abhijeet Dhoble
Journal: Circulation (2016)

Introduction: Transcatheter aortic valve replacement (TAVR) has emerged as a viable alternative to surgical replacement (SAVR) for treating patients with severe aortic stenosis (AS). The data on ao...
Enforcing Conscientious Objection to Abortion in Medical Emergency Circumstances: Criminal and Unethical
Authors: Udo Schuklenk, Benjamin Zolf
Journal: The American Journal of Bioethics (2018)

"Enforcing Conscientious Objection to Abortion in Medical Emergency Circumstances: Criminal and Unethical." The American Journal of Bioethics, 18(7), pp. 60–61
Cellular and Ionic Basis for T-Wave Alternans Under Long-QT Conditions
Authors: WataruShimizu, CharlesAntzelevitch
Journal: Circulation (1999)

Background—T-wave alternans (TWA), an ECG phenomenon characterized by beat-to-beat alternation of the morphology, amplitude, and/or polarity of the T wave, is commonly observed in the acquired and congenital long-QT syndromes (LQTS). This study examines the cellular and ionic basis for TWA induced by rapid pacing under conditions mimicking the LQT3 form of the congenital LQTS in an arterially perfused canine left ventricular wedge preparation. Methods and Results—Transmembrane action potentials from epicardial, M, and endocardial cells and 6 to 8 intramural unipolar electrograms were simultaneously recorded together with a transmural ECG and isometric tension development. In the presence of sea anemone toxin (ATX-II; 20 nmol/L), an increase in pacing rate (from a cycle length [CL] of 500 to 400 to 250 ms) produced a wide spectrum of T-wave and mechanical alternans. Acceleration to CLs of 400 to 300 ms produced mild to moderate TWA principally due to beat-to-beat alternation of repolarization of cells in t...
Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal miRNA to Promote Brain Metastasis
Authors: Fei Xing, Yin Liu, Shih-Ying Wu, Kerui Wu, Sambad Sharma, Yin-Yuan Mo, Jiamei Feng, Stephanie Sanders, Guangxu Jin, Ravi Singh, Pierre-Alexandre Vidi, Abhishek Tyagi, Michael D. Chan, Jimmy Ruiz, Waldemar Debinski, Boris C. Pasche, Hui-Wen Lo, Linda J. Metheny-Barlow, Ralph B D'Agostino, Kounosuke Watabe
Journal: Cancer Research (2018)

Up to 30% of patients with metastatic breast cancer eventually develop brain metastasis, yet the pathologic mechanism behind this development remains poorly understood. Here, we profiled long noncoding RNAs in brain metastatic tumors from patients with breast cancer and found that the X-inactive-specific transcript (XIST) was significantly downregulated in these tissues. XIST expression levels inversely correlated with brain metastasis, but not with bone metastasis in patients. Silencing of XIST preferentially promoted brain metastatic growth of XIST
Association of Apathy With Risk of Incident Dementia
Authors: Jan Willem van Dalen, Lennard L. van Wanrooij, Eric P. Moll van Charante, Carol Brayne, Willem A. van Gool, Edo Richard
Journal: JAMA Psychiatry (2018)

Fear of dementia is pervasive in older people with cognitive concerns. Much research is devoted to finding prognostic markers for dementia risk. Studies suggest apathy in older people may be prodromal to dementia and could be a relevant, easily measurable predictor of increased dementia risk. However, evidence is fragmented and methods vary greatly between studies.To systematically review and quantitatively synthesize the evidence for an association between apathy in dementia-free older individuals and incident dementia.Two reviewers conducted a systematic search of Medline, Embase, and PsychINFO databases.Inclusion criteria were (1) prospective cohort studies, (2) in general populations or memory clinic patients without dementia, (3) with clear definitions of apathy and dementia, and (4) reporting on the association between apathy and incident dementia.PRISMA and MOOSE guidelines were followed. Data were extracted by 1 reviewer and checked by a second.Main outcomes were pooled crude risk ratios, maximally adjusted reported hazard ratios (HR), and odds ratios (OR) using DerSimonian-Laird random effects models.The mean age of the study populations ranged from 69.2 to 81.9 years (median, 71.6 years) and the percentage of women ranged from 35% to 70% (median, 53%). After screening 2031 titles and abstracts, 16 studies comprising 7365 participants were included. Apathy status was available for 7299 participants. Studies included populations with subjective cognitive concerns (n = 2), mild cognitive impairment (n = 11), cognitive impairment no dementia (n = 1), or mixed cognitive and no cognitive impairment (n = 2). Apathy was present in 1470 of 7299 participants (20.1%). Follow-up ranged from 1.2 to 5.4 years. In studies using validated apathy definitions (n = 12), the combined risk ratio of dementia for patients with apathy was 1.81 (95% CI, 1.32-2.50; I2 = 76%; n = 12), the hazard ratio was 2.39 (95% CI, 1.27-4.51; I2 = 90%; n = 7), and the odds ratio was 17.14 (95% CI, 1.91-154.0; I2 = 60%; n = 2). Subgroup analyses, meta-regression, and individual study results suggested the association between apathy and dementia weakened with increasing follow-up time, age, and cognitive impairment. Meta-regression adjusting for apathy definition and follow-up time explained 95% of heterogeneity in mild cognitive impairment.Apathy was associated with an approximately 2-fold increased risk of dementia in memory clinic patients. Moderate publication bias may have inflated some of these estimates. Apathy deserves more attention as a relevant, cheap, noninvasive, and easily measureable marker of increased risk of incident dementia with high clinical relevance, particularly because these vulnerable patients may forgo health care.