tbuckley/cabot-search huggingface dataset:
Abstract 142: Combined Therapy with Polyethylene Glycol-20k and MCC950 Preserves Post-resuscitation Myocardial Mitochondrial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Lian Liang, Guozhen Zhang, Hui Li, Cheng Cheng, Tao Jin, Chengli Su, yan xiao, Jennifer Bradley, Ria Fyffe-Freil, Mary Ann A Peberdy, Joseph P Ornato, Martin Mangino, Wanchun Tang
Journal: Circulation (2020)

Introduction: Mitochondrial dysfunction from global ischemic-reperfusion (I/R) injury is a major contributor to post-resuscitation myocardial dysfunction. Polyethylene Glycol-20k (PEG-20k) shortens the no-flow phenomenon and improves microcirculation while MCC950 selectively inhibits activation of the NLRP3-inflammasome ensuing pyroptosis. We evaluated the effect of combined therapy with PEG-20k and MCC950 on myocardial mitochondrial function as measured by electron transport chain complex respiration in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Methods: 30 Sprague-Dawley rats weighing between 450-550 g were randomized into five groups (n=6): (1) sham (S); (2) control (C); (3) PEG-20k (P); (4) MCC950 (M); (5) combined (P&amp;M). Ventricular fibrillation (VF) was electrically induced and untreated for 6min, followed by 8min CPR. Resuscitation was attempted with a 4J defibrillation. 2mL P was infused over 2 min at the beginning of CPR, while M (10mg/kg) was administered intraperitoneal (IP) immediately after return of spontaneous circulation (ROSC). At ROSC 6hr, 100mg of heart was harvested, transferred directly into ice-cold K medium (1mL), and homogenized to obtain a 10% homogenate. Homogenates (50μL) were transferred to calibrated Oxygraph-2 chambers. Mitochondrial function was measured using high resolution respirometry. Oxygen flux was corrected and expressed by tissue wet weight, pmol/(min*mg). Data were analyzed by one-way analysis of variance (one-way ANOVA) followed by Tukey’s post hoc test for comparisons between multiple groups. Results: Complex I respiration in C was compromised at ROSC 6hr compared to S (564.0±160.0 vs 2729.5±339.5, p&lt;0.001). As expected, P and M restored complex I respiration (1224.4±328.6, p&lt;0.001) and (1804.4±293.1, p&lt;0.01) compared to C. P&amp;M further consolidated Complex I respiration function recovery (2527.6±145.5). Conclusion: Combined Therapy with PEG-20k and MCC950 preserves post-resuscitation myocardial mitochondrial function in a rat model of CA and CPR.
Abstract 14293: Echocardiographic Predictors of Symptomatic Cardiotoxicity Among Patients Undergoing Chemotherapy: Systematic Review and Meta-analysis
Authors: Muhammad U Siddiqui, Mohammad S Khan, Youssef Yaacoub, Heidi-Anne Hanson, Muhammad Danial Siddiqui, Omar Yacob
Journal: Circulation (2020)

Introduction: Chemotherapeutic agents have been associated with cardiotoxicity and thus require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity (SC) in patients undergoing chemotherapy. Hypothesis: We hypothesized that global longitudinal strain (GLS) is a better predictor of SC compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy. Methods: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from through March 2019. Adults who developed SC (symptomatic congestive heart failure, decline in LVEF &lt;50%, cardiac death) after undergoing chemotherapy with pre- and post-chemotherapy echocardiographic measures of cardiac function were included. Primary focus was on the prediction of SC. Estimates were reported as random effects hazard ratios (HR) with 95% confidence intervals (CI). Results: Eight studies met inclusion criteria. Six studies analyzed LVEF and demonstrated a significant association between LVEF and the prediction of SC (HR 1.27; 95% CI, 1.02-1.57; P=0.03) (Figure 1) . Two studies that analyzed GLS found it to be a strong predictor of SC in patients undergoing chemotherapy (HR 1.46; 95% CI, 1.34-1.58; P=&lt;.001) (Figure 2) . Conclusions: Both LVEF and GLS can predict SC, and therefore can be utilized for monitoring patients on chemotherapy for cardiac dysfunction. The data for GLS is more homogenous but definite evidence that GLS may be superior to LVEF is lacking. More randomized blinded trials are required to identify if one echocardiographic parameter may be superior to the other.
Association of Subclinical Heart Maladaptation With the Pooled Cohort Equations to Prevent Heart Failure Risk Score for Incident Heart Failure
Authors: Nicholas Cauwenberghs, Francois Haddad, Tatiana Kuznetsova
Journal: JAMA Cardiology (2020)

The Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) estimate the 10-year risk for symptomatic heart failure (HF) from routine clinical data. The PCP-HF score should detect asymptomatic individuals with cardiac maladaptation preceding HF symptoms for it to be a useful HF prediction tool in primary prevention.To assess the concordance between PCP-HF risk scoring and the presence of subclinical cardiac maladaptation in the community.This cross-sectional analysis included participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes who underwent a clinical examination including echocardiography between May 2005 and January 2015. Participants younger than 30 years, older than 79 years, had prevalent cardiovascular disease, and/or had suboptimal echocardiographic imaging quality were excluded. Analysis began February 2020 and ended April 2020.Ten-year HF risk as calculated from routine clinical data using the PCP-HF. Based on tertile limits, participants were categorized as having low (≤0.4%), intermediate (0.4%-2.4%), and high (≥2.4%) 10-year HF risk score.Echocardiographic profiles of subclinical heart remodeling and dysfunction.A total of 1020 individuals were analyzed (mean [SD] age, 52.8 [11.4] years; 541 female [53.0%]). The prevalence of left ventricular (LV) remodeling and dysfunction was significantly higher from low to intermediate and high 10-year HF risk score. A doubling in 10-year HF risk score was associated with higher odds for LV concentric remodeling (odds ratio [OR], 1.48; 95% CI, 1.36-1.61; P < .001), LV hypertrophy (OR, 1.66; 95% CI, 1.51-1.83; P < .001), abnormal LV longitudinal strain (OR, 1.12; 95% CI, 1.05-1.19; P < .001), and LV diastolic dysfunction (OR, 2.28; 95% CI, 1.94-2.69; P < .001). Moreover, the PCP-HF score detected echocardiographic abnormalities with an accuracy of 74% (LV concentric remodeling), 78% (LV hypertrophy), 59% (abnormal LV longitudinal strain), and 87% (LV diastolic dysfunction). The likelihood of LV concentric remodeling, hypertrophy, and diastolic dysfunction were 3.1, 3.8, and 9.4 times higher in participants with high 10-year HF risk score than the average population risk, respectively (P < .001). Of all PCP-HF score components, age, body mass index, and systolic blood pressure were key correlates of echocardiographic abnormalities in multivariable-adjusted analysis.PCP-HF risk scoring adequately detected individuals with subclinical heart maladaptation that precedes HF symptoms by years. Thus, it may be a valuable HF prediction tool in primary prevention.
Hospital-Acquired SARS-CoV-2 Infection
Authors: Aaron Richterman, Eric A. Meyerowitz, Muge Cevik
Journal: JAMA (2020)

This Viewpoint reviews the rare incidence of nosocomial SARS-CoV-2 infection and discusses ways it can be minimized, including use of surgical masks, proper ventilation, physical distancing, eye protection, regular testing, and the availability of sick leave for health care workers.
Abstract 14574: Assessing Cardiovascular, Thrombotic and Bleeding Outcomes in Patients With Chronic Liver Disease Undergoing Left Ventricular Assist Device Implantation: Analysis of the National Inpatient Sample Database
Authors: Jelani Grant, Louis Vincent, Bertrand Ebner, Jennifer Maning, neal olarte, Odunayo P Olorunfemi, Nidah Khakoo, Gabriella Aitcheson, Rosario A Colombo, Sandra V Chaparro
Journal: Circulation (2020)

Introduction: Coagulopathy and hematologic abnormalities are major concerns in patients with chronic liver disease (CLD) and refractory heart failure which combined with the use of anticoagulation or anti-platelet therapy, may affect perioperative outcomes in patients undergoing left ventricular assist device (LVAD) implantation. Methods: The National Inpatient Sample Database was queried from 2012 to 2017 for relevant International Classification of Diseases (ICD)-9 and ICD-10 procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes were compared in patients with chronic liver disease and those without, who underwent LVAD implantation. Results: A total of 23,435 patients underwent LVAD implantation, 2,200 patients with CLD and 20,755 patients without CLD. See Table 1 for baseline characteristics. All-cause inpatient mortality (14.8% vs. 11.1%, p&lt;0.001), major bleeding (34.3% vs. 30.2%, p&lt;0.001), transfusion of platelets (18.0% vs. 14.0%, p&lt;0.001), and the occurrence of a subarachnoid hemorrhage (1.6% vs. 0.7%, p&lt;0.001) were greater in patients with CLD. LVAD thrombosis (6.6% vs. 9.4%, p&lt;0.001) and post-operative ischemic stroke (3.4% vs. 6.1%, p&lt;0.001) occurred less in patients with CLD. Using a multivariate logistic regression model to adjust for confounding factors, revealed that CLD was predictive of increased mortality in patients undergoing LVAD implantation (odds ratio: 1.29, 95% confidence interval [CI]; 1.06 to 1.56, p=0.010). Conclusions: We demonstrated between 2012 to 2017, given the clinical paradox of pro- and anticoagulant risks in patients with CLD and advanced HF, LVAD implantation was associated with increased mortality, major bleeding with increased utilization of platelet products and yet increased thrombotic complications. Further studies are needed to evaluate both thrombotic and bleeding risks in this population, along with mitigating factors without compromising either outcome.
Hepatitis A Vaccines
Authors: David S. Krause
Journal: JAMA (1996)

<h3>To the Editor.</h3> —A Medical News &amp; Perspectives article entitled "Changes Ahead in Childhood Immunization"<sup>1</sup>mentioned an investigational hepatitis A vaccine manufactured by Merck and Co (Vaqta). In the article, a Merck spokesperson stated that he hopes this vaccine will "translate into a safety advantage" compared with the currently licensed inactivated hepatitis A vaccine (Havrix, SmithKline Beecham Biologicals, Rixensart, Belgium). Havrix appears to be an extraordinarily safe vaccine. In the efficacy trial by Innis et al,<sup>2</sup>more than 104 000 doses of Havrix were administered to children and adolescents without the occurrence of a single serious adverse event related to the vaccine.<sup>2</sup>This safety record has been confirmed in clinical trials elsewhere.<sup>3</sup> To date, Havrix is the only licensed vaccine in the United States for the prevention of hepatitis A. No trials have been published comparing the safety of Havrix with that of Vaqta. Given the
Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity
Authors: María José Torres, Axel Trautmann, Ingrid Böhm, Kathrin Scherer, Annick Barbaud, Sevim Bavbek, Patrizia Bonadonna, Josefina Rodrigues Cernadas, Anca Mirela Chiriac, Francesco Gaeta, Ana M. Gimenez‐Arnau, Hye‐Ryun Kang, Esther Moreno, Knut Brockow
Journal: Allergy (2020)

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.
Abstract 17134: Biomarker-Based Risk Prediction of Incident Heart Failure Over 5 Years in Prediabetes and Diabetes: Pooled Analysis Across 3 US Community Cohorts
Authors: Muthiah Vaduganathan, Ambarish Pandey, Kershaw Patel, Colby Ayers, Christie M Ballantyne, Mikhail N Kosiborod, Mercedes R Carnethon, Christopher DEFILIPPI, Darren K McGuire, Sadiya Khan, Melissa Caughey, James A De Lemos, Brendan M Everett
Journal: Circulation (2020)

Introduction: While patients with dysglycemia and known CV disease face high risks of transition to HF and benefit from risk reduction strategies (such as SGLT-2 inhibitors), identification of at-risk patients without CV disease for allocation of primary prevention interventions is less clear. Biomarkers may improve risk stratification and inform targeted application of preventive strategies. Methods: Participants free of CV disease from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were included. A biomarker score was developed incorporating hs-cTnT ≥ 6 ng/L, NT-proBNP ≥ 100 pg/mL, hs-CRP ≥ 3 mg/L, and LVH by electrocardiogram. Among participants with dysglycemia, 5-year risks of incident HF and the number of HF events potentially prevented per 1,000 participants treated with an SGLT-2 inhibitor for 5-years were estimated. Results: Among 6,799 participants with prediabetes (66.8%) and diabetes (33.3%), there were 891 incident HF events over median follow-up of 17 years. The biomarker score alone demonstrated good discrimination and calibration for predicting 5-year HF risk [C-statistic 0.76 (0.71 to 0.81), calibration p value = 0.62]. Among those with dysglycemia, 5-year risk of HF in the very low (score = 0) and low biomarker score groups (score = 1) were similar to that observed among individuals with euglycemia (0.74%). The 5-year risk of HF increased in a graded fashion across increasing biomarker score groups. For every 1,000 participants with diabetes treated with an SGLT-2 inhibitor for 5-years, the estimated number of HF events prevented was estimated to be 4, 5, 14, and 41, respectively for individuals with scores of 0, 1, 2, and 3-4. Conclusions: Among adults with prediabetes and diabetes, a biomarker score can inform HF risk stratification. Individuals with diabetes and high biomarker scores face the highest risk of HF and are expected to benefit the most from SGLT-2 inhibitors.
Abstract 17215: Differences in Anatomy, Physiology and Outcomes Between Blacks and Whites With Hypertrophic Cardiomyopathy
Authors: Milla E Arabadjian, Gary Yu, Mark Sherrid, Victoria V Dickson
Journal: Circulation (2020)

Introduction: Hypertrophic cardiomyopathy (HCM) in Black populations remains underexplored even though this inherited disorder can affect more than 220,000 Blacks in the US alone. Existing data suggest that Blacks with HCM are less likely to have obstructive physiology, but uncommon phenotypes, such as mid-ventricular obstruction have not been reported. Mortality outcomes have been reported as similar between groups. Objective: To evaluate structural HCM features and outcomes in Blacks and Whites with HCM Methods: The study design was a retrospective analysis of a prospective longitudinal observational study of a referred patient population with confirmed HCM and self-identifying as Black/African American and White/Caucasian. Results: We studied 434 individuals, 57 (13.1%) were Black. Males were 52.6% of the Black cohort and 59% of the White cohort. Blacks were younger, mean (SD) 54.6 (13.4) vs 62.6 (14.8) years, p&lt;0.001. Ejection fraction and left ventricular hypertrophy (LVH) magnitude were similar between groups but LVH distribution differed with Blacks having more sub-basal LVH, which includes apical, apical-mid and mid LVH, 22 (38.6%) vs 56 (14.9%), p&lt;0.001, and diffuse LVH, 6 (10.5%) vs 15 (4.0%), p=0.017, than Whites. Blacks also had more mid-ventricular obstruction, 7 (12.3%) vs 21 (5.5%), p=0.025. Of those who had a cardiac MRI, Blacks had more significant fibrosis (≥15% of LV mass), 10 (30.3%) vs 20 (9.5%), p&lt;0.001. Mortality was low overall and both groups had similar proportion of ICD insertion for primary prevention of sudden death. However, Blacks had more appropriate ICD interventions, 5 (38.5%) vs 5 (6.8%), p=0.001. Conclusions: Blacks with HCM have more sub-basal LVH and mid-ventricular obstruction than Whites with HCM, phenotypes associated with worse disease progression. They are more likely to have significant myocardial fibrosis which has a pro-arrhythmic effect. They also had more aborted sudden death events. Precise evaluation of HCM structural and physiologic characteristics can improve targeted treatment and outcomes in this population.
Abstract 13200: Relationship Between Baseline Low-Density Lipoprotein Cholesterol and Percent Low-Density Lipoprotein Cholesterol Reduction With Evolocumab in the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) Trial
Authors: Dan P Marcusa, Robert P Giugliano, Jeong-Gun Park, Peter Sever, Huei Wang, Andrew Hamer, Terje R Pedersen, Anthony C Keech, Marc S Sabatine
Journal: Circulation (2020)

Introduction: The FOURIER trial demonstrated that the PCSK9 inhibitor evolocumab robustly reduced LDL-C amongst patients on moderate or high intensity statins. We investigated whether the magnitude of the percentage LDL-C reduction is consistent across baseline LDL-C levels. Methods: FOURIER enrolled 27,564 patients with ASCVD and an LDL-C ≥70 mg/dl or a non-HDL-C ≥100 mg/dl on optimized statin therapy at the time of enrollment. The % LDL-C reduction from baseline to 12 wks was examined in patients on study drug through 12 wks (N=25,847) using a quadratic regression model including terms for treatment (evolocumab vs. placebo), baseline LDL-C and [LDL-C] 2 , and interaction terms. Stratified analyses were done for patients on high vs. moderate intensity statin. Results: Overall, compared with placebo, evolocumab reduced LDL-C by 61% (95% CI 61-62%). Patients with lower baseline LDL-C had significantly greater % LDL-C reductions (Figure top; P&lt;0.001 for interaction between baseline LDL-C and % LDL-C reduction with evolocumab). Among patients with a baseline LDL-C of 70 mg/dL, LDL-C reduction was 68% (95% CI 67-69%) vs. 54% (95% CI 53-55%) in patients with a baseline LDL-C of 130 mg/dl. When stratified by concomitant statin intensity, similar relationships were observed (Figure middle &amp; bottom). Conclusions: The magnitude of % LDL-C reduction with evolocumab is greater in patients with lower baseline LDL-C levels. These data are encouraging for the use of PCSK9 inhibition even for patients at the lower end of LDL-C.
Five Things to Know When a Psychiatric Patient Is Prescribed Opioids for Pain
Authors: Roger Chou
Journal: JAMA Psychiatry (2020)

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In Vivo Validation of a Reversible Small Molecule-Based Switch for Synthetic Self-Amplifying mRNA Regulation
Authors: Sean Mc Cafferty, Joyca De Temmerman, Tasuku Kitada, Jacob R. Becraft, Ron Weiss, Darrell J. Irvine, Mathias Devreese, Siegrid De Baere, Francis Combes, Niek N. Sanders
Journal: Molecular Therapy (2020)

Synthetic mRNA therapeutics have the potential to revolutionize healthcare, as they enable patients to produce therapeutic proteins inside their own bodies. However, convenient methods that allow external control over the timing and magnitude of protein production after in vivo delivery of synthetic mRNA are lacking. In this study, we validate the in vivo utility of a synthetic self-amplifying mRNA (RNA replicon) whose expression can be turned off using a genetic switch that responds to oral administration of trimethoprim (TMP), a US Food and Drug Administration (FDA)-approved small-molecule drug. After intramuscular electroporation, the engineered RNA replicon exhibited dose-dependent and reversible expression of its encoded protein upon TMP administration. The TMP serum level needed for maximal downregulation of protein translation was approximately 45-fold below that used in humans for therapeutic purposes. To demonstrate the therapeutic potential of the technology, we injected mice with a TMP-responsive RNA replicon encoding erythropoietin (EPO) and successfully controlled the timing and magnitude of EPO production as well as changes in hematocrit. This work demonstrates the feasibility of controlling mRNA kinetics in vivo, thereby broadly expanding the clinical versatility of mRNA therapeutics.