tbuckley/cabot-search huggingface dataset:
Abstract 13055: Endotrophin is Significantly Associated With Risk of Mortality in HFpEF Patients Irrespective of Underlying Atrial Fibrillation
Authors: Alexander L Reese-petersen, Arantxa Gonzalez, BEGONA LOPEZ, Susana Ravassa, Morten Karsdal, Federica Genovese, Javier Díez
Journal: Circulation (2021)

Introduction: The global burden of heart failure with preserved ejection fraction (HFpEF) is increasing. HFpEF is projected to become the dominant type of HF, and atrial fibrillation (AF) is known to contribute to pathogenesis by aggravating fibrosis. Endotrophin is a bioactive molecule released from collagen type VI during its maturation, and it is a marker of fibroblast activity. The aim of this post-hoc analysis was to confirm the previously observed prognostic potential of endotrophin (measured by PRO-C6) for adverse outcome in HFpEF and to investigate the potential influence in risk stratification by AF. Methods: 166 patients with hypertensive HFpEF were included for analysis. 48.2% were NYHA Class II, 49.4% NYHA Class III and 1.2% NYHA Class IV. 50.6% of patients had a previous history of AF. Cardiac function was assessed by echocardiography and standard clinical measures. Circulating endotrophin was quantified at baseline in serum by means of an enzyme-linked immunosorbent assay, PRO-C6. Results: PRO-C6 levels increased significantly with disease severity in HFpEF patients (NYHA Class III vs II, p=0.0003), and in HFpEF patients with AF (p=0.023). PRO-C6 was able to discriminate between patients at risk of all-cause mortality (AUC=0.73, p&lt;0.001), but no improvement in this association was observed when factoring in AF (AUC=0.72, p=0.001). When looking at patients stratified in PRO-C6 tertiles, patients in the upper tertile had a significantly higher risk of mortality (p&lt;0.0001, hazard ratios 3 vs 1=4.1, 3 vs 2=3.5, respectively) and HF hospitalization (p&lt;0.0001, hazard ratio 3 vs 1=4.4, 3 vs 2=1.6, respectively) compared to tertiles 1 and 2. Conclusions: In this population of hypertensive HFpEF patients, circulating endotrophin, measured by PRO-C6, was increased with increasing disease severity, and associated with a higher risk of adverse outcome in HFpEF, regardless of underlying AF. The data presented here suggest a potential role of endotrophin in HFpEF pathophysiology, associated to disease progression in HFpEF patients with or without AF. These data confirm previous observations, and strengthen the usefulness of endotrophin, measured by the PRO-C6 biomarker, as a prognostic tool aiding in assessment of HFpEF patients.
<scp>SARS</scp>–<scp>CoV</scp>‐2 Infection and <scp>COVID</scp>‐19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta‐Analysis
Authors: Richard Conway, Alyssa A. Grimshaw, Maximilian F. Konig, Michael Putman, Alí Duarte‐García, Leslie Yingzhijie Tseng, Diego M. Cabrera, Yu Pei Eugenia Chock, Huseyin Berk Degirmenci, Eimear Duff, Bugra Han Egeli, Elizabeth R. Graef, Akash Gupta, Patricia Harkins, Bimba F. Hoyer, Arundathi Jayatilleke, Shangyi Jin, Christopher Kasia, Aneka Khilnani, Adam Kilian, Alfred H. J. Kim, Chung Mun Alice Lin, Candice Low, Laurie Proulx, Sebastian E. Sattui, Namrata Singh, Jeffrey A. Sparks, Herman Tam, Manuel F. Ugarte‐Gil, Natasha Ung, Kaicheng Wang, Leanna M. Wise, Ziyi Yang, Kristen J. Young, Jean W. Liew, Rebecca Grainger, Zachary S. Wallace, Evelyn Hsieh
Journal: Arthritis & Rheumatology (2021)

The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients.
Abstract 14038: Deficiency of Arachidonate 5-Lipoxygenase Intensifies Sepsis-Induced Cardiac Dysfunction in Aging
Authors: Ganesh V Halade, Gabriel A Grilo, Bochra Tourki, Vasundhara Kain
Journal: Circulation (2021)

Introduction: Age-related cardiac dysfunction is a prime component of sepsis-induced multi-organ failure in the clinical setting. Arachidonate 5-lipoxygenase (5LOX) pathway and 5LOX-derived lipid mediators are critical in early inflammation and immune response signaling. In addition, 5LOX derived mediators activate macrophages and other cells to counter infection via surface receptors. However, the role of 5LOX in sepsis-induced cardiac dysfunction superimposed on aging is still under-investigated. Hypothesis: Given that the inflammatory role of 5LOX, we tested the hypothesis that deletion of 5LOX in aging would be deleterious to cardiac function in sepsis. Methods: To induce sepsis, lipopolysaccharide (LPS; E. coli O55:B5) was injected into aging male C57BL/6J (WT) and 5LOX -/- mice (18-20 months). To study heart function, molecular, and cellular mechanisms, mice were challenged with a single subcutaneous dose of LPS (20mg/kg) for 4 hours. Survival was monitored for 7 days post-LPS challenge to testify therapeutic application of outcome. Results: Lack of 5LOX increased mortality (~70%) in aging mice with severe depression in cardiac function post-LPS compared with age-matched WT controls. LPS challenge in 5LOX -/- aging mice decreased resolution mediators (RvD1) and inflammation mediators (LTB 4 ) in the spleen with robust recruitment of leukocytes in a spleno-cardiac manner indicative of non-resolving inflammation. The spleen monocytes (CD11b + ), macrophages (F4/80 + ), and neutrophils (Ly6G + ) were significantly decreased in 5LOX -/- mice post-LPS with the consistent increase in the heart. The absence of 5LOX blunted physiological inflammatory response in aging by attenuating TLR4 and CD169 in both the heart and spleen as a sign of immunosuppression. Conclusion: Our results suggest that 5LOX -/- aging mice fail to initiate physiological inflammation-resolution signaling in response to LPS-induced septic shock, leading to cardiac dysfunction and immunosuppression. Our study highlights the role of 5LOX and 5LOX-derived mediators as targets for the inflammation-resolution response and therapeutics potential in aging-related sepsis.
A Randomized Phase 3 Trial of Blinatumomab Vs. Chemotherapy As Post-Reinduction Therapy in Low Risk (LR) First Relapse of B-Acute Lymphoblastic Leukemia (B-ALL) in Children and Adolescents/Young Adults (AYAs): A Report from Children's Oncology Group Study AALL1331
Authors: Patrick A. Brown, Lingyun Ji, Xinxin Xu, Meenakshi Devidas, Laura Hogan, Teena Bhatla, Michael Borowitz, Elizabeth A. Raetz, Lia Gore, James A. Whitlock, Stephen P. Hunger, Mignon L. Loh
Journal: Blood (2021)
The long non-coding RNA NRON promotes the development of cardiac hypertrophy in the murine heart
Authors: Jeannine Hoepfner, Julia Leonardy, Dongchao Lu, Kevin Schmidt, Hannah J. Hunkler, Sinje Biß, Ariana Foinquinos, Ke Xiao, Kumarswamy Regalla, Deepak Ramanujam, Stefan Engelhardt, Christian Bär, Thomas Thum
Journal: Molecular Therapy (2021)

Physiological and pathological cardiovascular processes are tightly regulated by several cellular mechanisms. Non-coding RNAs, including long non-coding RNAs (lncRNAs), represent one important class of molecules involved in regulatory processes within the cell. The lncRNA non-coding repressor of NFAT (NRON) was described as a repressor of the nuclear factor of activated T cells (NFAT) in different in vitro studies. Although the calcineurin/NFAT-signaling pathway is one of the most important pathways in pathological cardiac hypertrophy, a potential regulation of hypertrophy by NRON in vivo has remained unclear. Applying subcellular fractionation and RNA fluorescence in situ hybridization (RNA-FISH), we found that, unlike what is known from T cells, in cardiomyocytes, NRON predominantly localizes to the nucleus. Hypertrophic stimulation in neonatal mouse cardiomyocytes led to a downregulation of NRON, while NRON overexpression led to an increase in expression of hypertrophic markers. To functionally investigate NRON in vivo, we used a mouse model of transverse aortic constriction (TAC)-induced hypertrophy and performed NRON gain- and loss-of-function experiments. Cardiomyocyte-specific NRON overexpression in vivo exacerbated TAC-induced hypertrophy, whereas cardiomyocyte-specific NRON deletion attenuated cardiac hypertrophy in mice. Heart weight, cardiomyocyte cell size, hypertrophic marker gene expression, and left ventricular mass showed a NRON-dependent regulation upon TAC-induced hypertrophy. In line with this, transcriptome profiling revealed an enrichment of anti-hypertrophic signaling pathways upon NRON-knockout during TAC-induced hypertrophy. This set of data refutes the hypothesized anti-hypertrophic role of NRON derived from in vitro studies in non-cardiac cells and suggests a novel regulatory function of NRON in the heart in vivo.
Abstract 14274: Machine Learning-Enhanced Determinants of Oral Anticoagulation in Atrial Fibrillation: Findings From the PINNACLE Registry
Authors: Fatima Rodriguez, Andrew Ward, Donghyun Lee, Sanchit Gad, Robert Beetel, Robert A Harrington, Salim S Virani, John Rumsfeld, Rajesh Dash
Journal: Circulation (2021)

Introduction: Current atrial fibrillation (AF) guidelines recommend use of oral anticoagulation (OAC) to reduce the risk of stroke and systemic embolism. Machine learning (ML) techniques may enhance our understanding of factors associated with gaps in real-world prescription of OAC. Hypothesis: There will be large variation in county-level OAC prescription rates among ambulatory patients with AF, and geographic and medication factors will be stronger predictors than clinical comorbidities of lack of OAC prescriptions. Methods: Between January 2017 and June 2018, we identified patients with AF from the American College of Cardiology’s (ACC) Practice Innovation and Clinical Excellence (PINNACLE) Registry. We examined associations between patient and site-of-care factors and prescription of OAC across U.S. counties. Several ML methods were used to identify factors associated with lack of OAC prescription. Results: Among 864,339 patients with AF, 586,560 (68%) were prescribed OAC. County OAC prescription rates ranged from 26.8% (15/56) to 93% (41/44), with higher OAC use in the Western US. Supervised ML analysis (extreme gradient boosting: area under the receiver operating characteristic curve [AUC]: 0.811, 95% confidence interval [CI]: 0.809-0.813) outperformed the CHA2DS2-VASc score (AUC: 0.571, 95% CI: 0.569-0.574) in predicting likelihood of OAC prescriptions and identified a rank order of patient features associated with OAC prescription. In the ML models, use of aspirin, antihypertensives, lipid modifying agents, antiarrhythmic agents, age, inter-normalized ratio, median household income, and clinic size were the most important predictors of OAC prescription. Conclusions: In a national cohort of patients with AF underuse of OAC remains high, with notable geographic variation. ML algorithms can identify factors associated with use of OAC.
EPID-09. VARIATION IN GLIOMA INCIDENCE AMONG US HISPANICS BY GEOGRAPHIC REGION OF ORIGIN
Authors: Kyle Walsh, Melissa Bondy, Carol Kruchko, Jason Huse, Christopher Amos, Jill Barnholtz-Sloan, Quinn Ostrom
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioma incidence is 25% lower in U.S. Hispanics than in White non-Hispanics. The US Hispanic population is diverse and registry-based analyses may mask incidence differences associated with geographic/ancestral origins. METHODS County-level glioma incidence data in U.S. Hispanics were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS), which includes data from the Centers for Disease Control’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and covers ~100% of the U.S. population. American Community Survey (ACS) data were used to determine county-level proportion of the Hispanic population of Mexican/Central American origin, Caribbean origin (Puerto Rican, Cuban, Dominican), or other origin. Incidence rate ratios (IRRs) were generated to assess the association of glioma incidence in Hispanics with predominant origin group. RESULTS Compared to Hispanics living in predominantly Caribbean-origin counties, Hispanics in predominantly Mexican/Central American-origin counties were at lower age-adjusted risk of glioma (IRR=0.83; P&amp;lt; 0.0001), glioblastoma (IRR=0.86; P&amp;lt; 0.0001), diffuse and anaplastic astrocytoma (IRR=0.78; P&amp;lt; 0.0001), oligodendroglioma (IRR=0.82; P&amp;lt; 0.0001), ependymoma (IRR=0.88; P=0.0121), and pilocytic astrocytoma (IRR=0.76; P&amp;lt; 0.0001). Associations were consistent in children and adults, and when using more granular regions of origin. However, Central American origin was associated with modestly increased incidence of several lower-grade glioma histologies. Associations were only partially attenuated after adjusting for state-level estimated of European admixture in Hispanics using 23andMe data. CONCLUSIONS Glioma incidence in U.S. Hispanics differs significantly in association with the geographic origins of the Hispanic community, with those of Mexican/Central American origin at significantly reduced risk relative to those of Caribbean origin. U.S. Hispanics are culturally, socioeconomically, and genetically diverse. Although classified as a single ethnic group in most registry data, more granular analytic approaches could advance cancer epidemiology and disparities research.
Abstract 14484: Spatial Electrical Synchronization in Patients With Atrial Fibrillation and Atrial Tachycardia
Authors: Prasanth Ganesan, Brototo Deb, Miguel Rodrigo, Ruibin Feng, neal bhatia, Albert J Rogers, David Krummen, Paul J Wang, Paul L Clopton, Wouter-Jan Rappel, Sanjiv M Narayan
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) shows regional organization in multiple studies, but it is undefined how such regions are similar to or differ from, organization characteristic of atrial tachycardia (AT, spontaneous or paced). Hypothesis: Spatiotemporal analysis of AF will show spatial islands in which electrograms (EGMs) show 1:1 synchronization and other characteristics, similar to but smaller in size than in AT. Methods: We recruited N=70 patients (age 64±10yrs, 72%male) in group (I) N=10 patients with AT, (II) N=30 patients with AF that terminated by ablation, and (III) N=30 AF patients without termination. All patients had 64-pole unipolar recordings (basket catheter) during AF. We quantified spatial organization by correlating electrogram shape and timing in simultaneous overlapping electrode grids throughout the atria, indicating 1:1 synchronization over time (Fig A-D, red boxes). We related results to acute success of ablation (at organized sites, then pulmonary vein isolation). Results: Organized electrogram islands were seen in all patient groups. REACT values globally showed a spectrum from groups (I) to (III) (0.82±0.02, 0.60±0.10, 0.44±0.22 p=0.034, ANOVA). Fig B-D illustrate organized islands (B) in entire atrium in AT; (C) near site of AF termination by ablation; (D) near a site that did not terminate AF. There was no difference in organization value for AT globally (group I) and near the site of termination in AF patients (group II) (0.82±0.02 vs 0.78±0.04, p=NS). Conclusions: Spatial atrial synchronization is present across a spectrum of atrial arrhythmias, and is higher for AF patients with acutely successful ablation versus those without. Mechanistically, organization was similar at AF termination sites and to patients with atrial tachycardia.
Abstract 12634: Impact of New-Onset Atrial Fibrillation (NOAF) versus Pre-Existing Atrial Fibrillation on Outcomes After Transcatheter Aortic Valve Replacement/Implantation (TAVR/TAVI)
Authors: Nso Nso, KELECHI EMMANUEL, Adedapo Iluyomade, Hakeem Ayinde
Journal: Circulation (2021)

Background: Aortic stenosis patients who undergo Transcatheter Aortic Valve Replacement/Transcatheter Aortic Valve Implantation (TAVR/TAVI) experience a high incidence of pre-existing atrial fibrillation and new-onset atrial fibrillation (NOAF) post-operatively. We aim to update current evidence concerning the incidence of 30-day mortality, stroke, acute kidney injury, length of stay, and early/late bleeding in TAVR/TAVI with NOAF or pre-existing atrial fibrillation (preAF). Methods: We searched Pubmed, Google Scholar, JSTOR, Cochrane Library and Web of Science for studies published between January 2012 and December 2020 that reported the association between NOAF/preAF and clinical complications after TAVR/TAVI. Relevant studies were included in our systematic review and meta-analysis. Our primary clinical outcomes included 30-day mortality, stroke, early bleeding, and late bleeding. The secondary clinical outcomes included acute kidney injury and extended length of stay. Results: We included 15 studies based on 158,220 TAVI/TAVR adult patients (&gt;18 years of age) with NOAF or preAF. Compared to patients in sinus rhythm, TAVR/TAVI patients who developed NOAF had higher risk of 30-day mortality, acute kidney injury, early bleeding events, extended length of stay and stroke (OR: 3.18 [95% CI 1.58, 6.40]) (OR: 3.83 [95% CI 1.18, 12.42]) (OR: 1.70 [95% CI 1.05, 2.74]) (OR: 13.96 [95% CI, 6.41, 30.40]) (OR: 2.51 [95% CI 1.59, 3.97], respectively). Compared to patients in sinus rhythm, TAVR/TAVI patients with pre-AF had higher risk of acute kidney injury and early bleeding episodes (OR: 2.43 [95% CI 1.10, 5.35]) (OR: 17.41 [95% CI 6.49, 46.68], respectively). Pre-AF was not associated with an increase in 30-day mortality, late bleeding, stroke, and length of stay after TAVR/TAVI. Conclusions: The findings of our meta-analysis showed that atrial fibrillation (AF) was associated with higher risk of all primary and secondary outcomes. Specifically, NOAF but not pre-AF was associated with higher risk of 30-day mortality, stroke, and extended length of stay in TAVR/TAVI patients.
Abstract 118: Interleukin 4 And 13 Signaling In Macrophages Regulates Neonatal Cardiac Regeneration
Authors: Santiago Alvarez, Caitlin Omeara
Journal: Circulation Research (2021)

Introduction: Heart failure (HF) is a prevalent disease, projected to affect over 8 million Americans by 2030. Current therapy partially decreases progression; however, mortality and disease burden continue to be high. Therefore, there is an unmet need to develop new strategies that target HF progression. Our lab employs the neonatal mouse model of cardiac regeneration to identify pro-reparative pathways that can be applied to treating HF in humans. Previously we demonstrated that the anti-inflammatory cytokine, Interleukin 13 (IL13), promotes cardiac regeneration, however, the cell types mediating this response remain unknown. IL13 and the related cytokine, IL4, share a common receptor (IL4Rα) and both cytokines polarize macrophages into a reparative phenotype. Here, we hypothesize that IL4/13 signaling to macrophages promotes heart regeneration after cardiac injury and we explore the cell source of these cytokines during neonatal development and cardiac regeneration. Methods and Results: We generated a genetic model whereby IL4Rα is depleted in macrophages by crossing IL4Rα floxed (IL4Rα fl/fl ) mice with transgenic mice CX3Cr1 driven-Cre recombinase (CX3CR1 Cre ). Flow cytometry analysis confirmed depletion of IL4Rα in cardiac macrophages. We performed myocardial infarction (MI) on postnatal day 1 (P1) mice and assessed cardiac regeneration by ultrasonography 21 days post-injury (dpi). We found that IL4Rα fl/fl CX3CR1 Cre mice had lower ejection fraction compared to IL4Rα fl/fl littermate controls. Preliminary results suggest there is a reduced capillary density in peri-ischemic myocardium. In addition, we used fluorescent reporter mouse lines; IL4-enhanced green fluorescent protein (IL4-GFP) and IL13-yellow fluorescent protein (IL13-YFP), to assess the cellular source of IL4 and IL13 expression in the hearts of neonatal mice. In unoperated mice, we found no detectable expression of IL13 by any cell type in the heart, whereas IL4 was expressed in innate lymphoid cells (ILCs) and T cells. 4 days after MI in P1 mice IL13 was upregulated in ILCs and T cells and IL4 was expressed by ILCs and T cells and upregulated in myeloid cells. Conclusions and Discussion: We found that IL13 and IL4 are primarily expressed in ILCs and T cells following neonatal injury, suggesting a novel role for ILCs and T cells in the production of IL4 and 13 during the neonatal regeneration process. In addition, we found that lack of IL4/13 signaling in macrophages via depletion IL4Rα impairs cardiac regeneration after MI in neonatal mice, and results in reduced capillary density in peri-ischemic myocardium. We hypothesize that IL4Rα depletion in macrophages impairs reparative macrophage polarization after MI and promotes an inflammatory polarization. Future studies will be aimed to assess macrophage phenotypes in response to IL13/IL4 signaling by transcriptional profiling and flow cytometry.
Abstract 12934: The Association of Health Literacy With Health Status Outcomes in Heart Failure Patients
Authors: R. Angel Garcia, Scott D Rothenberger, Bea H Belnap, Philip Jones, Bruce L Rollman, John Spertus
Journal: Circulation (2021)

Background: Low health literacy (HL) is a known barrier to care and is associated with worse overall health status. The association of HL with disease-specific health status in heart failure (HF) patients is unknown. To address this gap we used data from Hopeful Heart , a randomized trial examining the impact of two 12-month treatment strategies in patients with HF and depression vs usual care. Methods: Health literacy was assessed at baseline via a brief screening tool previously validated in patients with HFrEF, classifying patients into adequate vs. low literacy. HF-specific health status was quantified with the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at baseline, 3, 6, and 12 months. Using linear regression, we estimated the association of low HL with 12-month KCCQ-12 Summary Score, adjusting for treatment group, age, gender and LVEF. We also assessed the association of low HL with 12-month change in KCCQ-12, additionally adjusting for baseline score. Finally, we analyzed depression severity as a moderator in the interaction between HL and PROMIS-D depression score. Results: Among 756 patients, those with low HL (N=235, 31%) were similar in demographics (65±13 vs 64±13 years; 43% vs. 44% female; 24% vs. 28% non-White), but had less education (36% vs. 61% high school) and employment (10% vs. 19%) compared to those with adequate HL. Mean KCCQ-12 scores were consistently lower in participants with low HL at all time points (Figure). After adjusting for treatment group, age, sex, and LVEF, low HL was strongly associated with lower 12-month KCCQ-12 score (-9.5 points, CI [-13.7,-5.3]). After adjustment for baseline score, low HL remained associated with less improvement in KCCQ-12 (-5.9 points, CI [-9.7, -2.2]). Depressive symptoms did not moderate this association (interaction p=0.72). Conclusion: In patients with HF, low HL is associated with worse disease-specific health status and with poorer recovery in health status at 12-month follow up.