tbuckley/cabot-search huggingface dataset:
Abstract 12518: Susceptibility of Mature Human Myocardial Cell Types to SARS-CoV-2
Authors: Alex Sotolongo, Jon Klein, Mario Pena-Hernandez, Justin Johnson, Arnar Geirsson, Jordan S Pober, Akiko Iwasaki, Peter J Gruber
Journal: Circulation (2021)

Background: SARS-CoV-2 is a highly transmissible and virulent respiratory pathogen responsible for the global coronavirus disease 2019 (COVID-19) pandemic. A significant number of patients infected with SARS-CoV-2 show signs of myocardial injury ranging from asymptomatic troponemia to acute congestive heart failure and cardiogenic shock. The precise mechanisms underlying myocardial injury in this cohort are unclear, and it is difficult to distinguish weather new onset cardiac dysfunction is representative of active myocardial infection or a consequence of systemic illness. To address this gap in knowledge we constructed a model to assess replicative potential of SARS-CoV-2 in primary cell lines derived from adult and pediatric myocardium including cardiomyocytes, fibroblasts, and endothelial cells and corroborated our in vitro findings with a pathologic analysis of myocardial tissue obtained from patients infected with SARS-CoV-2. Methods: Samples of atrial myocardium obtained from patients undergoing cardiac surgery were enzymatically digested and purified into cardiomyocyte, fibroblast, and endothelial cell populations. Susceptibility to infection with SARS-CoV-2 was then assessed in primary human myocardial cell types and compared against induced cardiomyocytes derived from human pluripotential stem cells. Infectivity was quantitatively assessed using qPCR against genomic and subgenomic viral RNA and normalized to GAPDH. Postmortem heart and lung FFPE tissue from de-identified patients who died from SARS CoV-2 infection were obtained and analyze by immunofluorescence for viral spike and nucleocapsid protein or stained with hematoxylin and eosin for histological evaluation. Results: Primary cardiomyocytes obtained from adult (n=7) and pediatric (n=7) atrial myocardium could not support active replication SARS-CoV-2 virus and there was no evidence of viral replication in pathologic myocardial specimens obtained from COVID infected patients (n=7). Collectively our data indicate that primary cardiac cell types are unable to support the level of viral replication observed in iPSCM (p=0.0007) suggesting that induced pluripotential stem cells may not adequately model the response of mature myocardium to SARS-CoV-2.
Abstract 9843: Sex-Related Differences in Premature Cardiovascular Disease in Individuals with Familial Hypercholesterolemia
Authors: Anandita P Agarwala, Elena Deych, Laney Jones, Amy C Sturm, Karen E Aspry, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg
Journal: Circulation (2021)

Background: Familial hypercholesterolemia (FH) is associated with elevated risk for premature atherosclerotic cardiovascular disease (ASCVD) (&lt;55 years in men and &lt;65 years in women). Little is known about sex-specific differences in risk factors and treatment outcomes in individuals with FH and premature ASCVD. Objective: To characterize sex-specific risk factor burdens and treatment outcomes in individuals with FH and premature ASCVD. Methods: The prevalence of premature ASCVD in 782 adults with FH (diagnosed by clinical scores and/or genetic testing) from 7 US-based lipid clinic practices was assessed retrospectively. A multivariate logistic mixed effects model with random study site effect and sex-specific analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension (HTN), and current smoking. Results: 98/280 men and 89/502 women had premature ASCVD. Women with premature ASCVD were older by an average of 3 years (mean age 58 vs. 55 years, p= 0.04) and had higher on treatment total cholesterol (216 vs. 178 mg/dl, p&lt;0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005) (Table 1). In men, the strongest predictors of premature ASCVD were HTN (OR 5.39, 95% CI 2.85, 10.93, p&lt;0.001) and DM (OR 2.25 95% CI 1.17, 4.37, p=0.016). In women, the strongest predictors of premature ASCVD were HTN (OR 5.48, 95% CI 3.22, 9.71, p&lt;0.001) and smoking (OR 2.85, 95% CI 1.35, 5.94, p=0.005). Treated LDL-C was not a significant predictor of ASCVD in either men or women. Conclusion: The normal delay in age of onset of ASCVD in women vs. men may be shortened in individuals with FH. Both women and men with FH have an increased risk of premature ASCVD in the setting of HTN, but risks from smoking and DM differ by sex. Women with FH and premature ASCVD had higher on-treatment LDL-C. Aggressive treatment strategies are needed to reduce risk factor burdens and residual hyperlipidemia in these patients.
Abstract 14118: Racial Disparities In The Incidence And Outcomes Of Peripartum Cardiomyopathy Complicated By Cardiogenic Shock
Authors: Titilope Olanipekun, Temidayo Abe, Valery S Effoe, Micheal Fatuyi, Obiora Egbuche
Journal: Circulation (2021)

Introduction: There is limited data on racial disparities in the outcomes of PPCM complicated by cardiogenic shock Methods: We identified 5,838 patients hospitalized with the PPCM and CS from the 2007 to 2018 National Inpatient Sample, of which 2214 (38%) were White, 3006 (51.4%) Black, and 618 (11%) Hispanic. Cochrane Armitage test and multivariable logistic regression were used to assess the temporal trends in the incidence of CS among patients with PPCM stratified by the racial group stated above. In addition, we compared in-hospital mortality, systemic thromboembolism, mechanical circulatory support (MCS) use (intra-aortic balloon pump, temporal ventricular assist device, extracorporeal membrane oxygenation), heart transplant referral in Blacks and Hispanics compared to Whites using multivariable logistic regression. Results: The mean age of the study sample was 34 +/- 8. An increase was noted in the incidence of CS in PPCM among all racial groups from 2007 to 2018 (Whites; 0.8% to 4.1%, Blacks; 0.3% to 8.5%, Hispanics; 2.4% to 2.9%, P &lt; 0.0001 for all). After adjusting for confound variables at baseline, the adjusted odds ratio for in-hospitality remained significantly higher in Hispanics and Blacks than whites. MCS and heart transplant referral were lower in Blacks than Whites (Table 1). Most significant factors associated in-hospital mortality among patients with PPCM and CS included baseline chronic kidney disease, chronic hemodialysis, and mechanical circulatory support use Conclusions: We found an incidence rate of 2.1% for CS in PPCM. Though there was an upward trend in the incidence across all ethnicities during the study period, the increase was most striking among African Americans. Hispanics and African Americans were more likely to die and less likely to be referred for heart transplant compared to Whites. African Americans were more likely to be treated with MCS compared to Whites.
춘계학술대회 : 포스터발표 ; HBeAg 음성 만성B형간염 환자에서 라미부딘의 최적 치료 기간에 관한 연구: 24개월 치료와 24개월 이상 치료 비교
Authors: 김영균, 이관식, 백용한, 김지현, 김도영, 안상훈, 문병수, 한광협, 전재윤, 문영명
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: HBeAg음성 만성B형간염 환자에서 라미부딘의 최적 치료기간은 아직까지 정립되어 있지 않다. 라미부딘 12개월 치료는 투여 종료후 재발이 매우 흔하며, 장기적인 투여는 YMDD 변이로 인한 내성균주 발현으로 viral breakthrough와 간염 악화가 나타나는 문제가 있다. 이에 연자등은 HBeAg음성 만성B형간염 환자에서 라미부딘의 최적 치료 기간에 대해 알아보고자 하였다. 대상 및 방법: 48명의 HBeAg 음성, HBV DNA 양성
Abstract 13979: Meta-Analysis of Efficacy and Safety of Colchicine Therapy in Patients With Acute Coronary Syndrome
Authors: Muhammad U Khan, Ahmad Naeem Lone, Safi U Khan, Muhammmad Zia Khan, Christopher Bianco, Sudarshan balla
Journal: Circulation (2021)

Introduction: Colchicine is known to be effective in treatment of inflammatory disorders, however, the effects of colchicine in patients with acute coronary syndrome (ACS) on top of background standard medical therapy remains uncertain. Hypothesis: There is paucity of data about colchicine therapy in patients presenting with acute coronary syndrome which may be associated with significant reduction in cardiovascular events. Methods: Six randomized controlled trials reporting CV outcomes in patients with acute coronary syndrome were included in MEDELINE, EMBASE and CENTRAL database (Inception to May 2021). The outcome measures were the summary random effects risk ratio (RR) with 95% confidence intervals. Results: In 6282 patients presenting with ACS, colchicine therapy did not significantly reduce the risk of all-cause mortality (RR, 1.62 [0.45, 5.88], P=0.87) or CV mortality (RR, 0.98 [0.43, 2.25], P=0.97) or myocardial infarction (MI) (RR, 0.88 [0.69, 1.11], P=0.28). Colchicine therapy had a significant effect on Major adverse cardiovascular events (MACE) (RR, 0.79 [0.64, 0.97], P=0.02), Stroke (RR, 0.33 [0.15, 0.72], P=0.01), and revascularization (RR, 0.46 [0.29, 0.73], P&lt;0.01). In comparison to control, colchicine had significantly higher rate of GI side effects (RR, 1.53 [1.05, 2.23], P=0.03) Conclusions: Colchicine therapy in patients presenting with acute coronary syndrome was associated with significant reduction in MACE, stroke and revascularization at the cost of higher rate of GI side effects.
PHASE II TRIAL OF CONTINUOUS LOW-DOSE TEMOZOLOMIDE (TMZ) FOR PATIENTS WITH RECURRENT MALIGNANT GLIOMA (MG) WITH AND WITHOUT PRIOR EXPOSURE TO BEVACIZUMAB (REV)
Authors: Mustafa Khasraw, LE Abrey, AB Lassman, A Hormigo, C Nolan, IT Gavrilovic, IK Mellinghoff, AS Reiner, L DeAngelis, AM Omuro
Journal: Neuro-Oncology (2010)
Abstract 10360: Trends in Surgical Aortic Valve Replacement Outcomes in the Post Transcatheter Aortic Valve Replacement
Authors: Johnny Chahine, Jacob Fiocchi, Ranjit John, Andrew Shaffer, Ryan C Knoper, Demetris Yannopoulos, Ganesh Raveendran, Sergey Gurevich
Journal: Circulation (2021)

Introduction: Transcatheter aortic valve replacement (TAVR) is currently the mainstay of treatment of severe aortic stenosis (AS). We aim to investigate the evolution of transaortic mean gradients in surgical aortic valve replacement (SAVR) patients before and after the Food and Drug Administration (FDA) approval of TAVR. Hypothesis: We assessed the hypothesis that mean gradients across the aortic valve were higher in 2011-2012 before FDA approval of TAVR. Methods: Patients who underwent SAVR in 2011-2012 (n=138) and 2019-2020 (n=134) at the University of Minnesota Medical Center were included. Those with implanted mechanical valves (n=602) were excluded. Valve size and mean aortic gradients were compared between the 2 study groups. Results: Out of 272 patients included in this study, 65.8% were males. Patients underwent SAVR at an older age in 2011-2012 (median 74, IQR 65-82) compared to 2019-2020 (median 67, IQR 60-73). The mean aortic valve gradient post-SAVR was higher in 2011-2012 (median 12, IQR 8-18 vs. median 10, IQR 7-13 in 2019-2020, p=0.016). The median valve size was smaller in 2011-2012 (21 mm vs. 23 mm, p&lt;0.001) (table) . Conclusion: Patients who underwent SAVR in 2011-2012 were older, more likely to receive smaller valve sizes, and had higher mean aortic valve gradients after SAVR.
Wheat in vivo RNA structure landscape reveals a prevalent role of RNA structure in modulating translational subgenome expression asymmetry
Authors: Xiaofei Yang, Haopeng Yu, Wenqing Sun, Ling Ding, Ji Li, Jitender Cheema, Ricardo Ramirez-Gonzalez, Xuebo Zhao, Azahara C. Martín, Fei Lu, Bao Liu, Cristobal Uauy, Yiliang Ding, Huakun Zhang
Journal: Genome biology (2021)

Abstract Background Polyploidy, especially allopolyploidy, which entails merging divergent genomes via hybridization and whole-genome duplication (WGD), is a major route to speciation in plants. The duplication among the parental genomes (subgenomes) often leads to one subgenome becoming dominant over the other(s), resulting in subgenome asymmetry in gene content and expression. Polyploid wheats are allopolyploids with most genes present in two (tetraploid) or three (hexaploid) functional copies, which commonly show subgenome expression asymmetry. It is unknown whether a similar subgenome asymmetry exists during translation. We aim to address this key biological question and explore the major contributing factors to subgenome translation asymmetry. Results Here, we obtain the first tetraploid wheat translatome and reveal that subgenome expression asymmetry exists at the translational level. We further perform in vivo RNA structure profiling to obtain the wheat RNA structure landscape and find that mRNA structure has a strong impact on translation, independent of GC content. We discover a previously uncharacterized contribution of RNA structure in subgenome translation asymmetry. We identify 3564 single-nucleotide variations (SNVs) across the transcriptomes between the two tetraploid wheat subgenomes, which induce large RNA structure disparities. These SNVs are highly conserved within durum wheat cultivars but are divergent in both domesticated and wild emmer wheat. Conclusions We successfully determine both the translatome and in vivo RNA structurome in tetraploid wheat. We reveal that RNA structure serves as an important modulator of translational subgenome expression asymmetry in polyploids. Our work provides a new perspective for molecular breeding of major polyploid crops.
Abstract 10411: Recurrent Spontaneous Coronary Artery Dissection
Authors: Tatiana Echeverry, Shivalika Mehan, Karlene Williams
Journal: Circulation (2021)

Spontaneous coronary dissection (SCAD) accounts for 25% of ACS in females &lt;50 years of age. The recurrence rate of SCAD within one to two years is 11%. Currently, there are no universal guidelines for the treatment of SCAD. However, the literature reports higher rates of complications associated with stenting than with medical treatment. Beta-blockers are believed to be protective against SCAD recurrence due to its direct mechanism of action on the vasculature and heart. The following case describes a patient on recommended medical therapy, including a beta-blocker who presented with a dissection of the second diagonal branch. A 51-year-old female with a history of SCAD in 2007 and right MCA aneurysm on metoprolol, presented with sudden onset of mid-sternal chest pain radiating to the back. The initial EKG showed T wave inversions in lead V2-V3 and elevated troponin of 2.58 which peaked at 9.9. The patient immediately underwent cardiac catheterization which revealed spontaneous dissection in the circumflex marginal. An ECHO revealed EF of 60-65% without wall motion abnormalities. The patient was treated medically with DAPT, and continuation of her home medication metoprolol. SCAD is a rare etiology of ACS with a predilection for young to middle-aged females. In the United States, SCAD has an approximate yearly incidence of 3.4% in females. The coronary vessels affected more frequently are the LAD and the RAC with 57% and 29% rate of dissection respectively. SCAD was noted to have a recurrence rate of 11% within 2-3 years with an increased recurrence rate of 29% at the 10-year follow-up. While the reasons for recurrence are unclear, there is a clear association between vessel tortuosity and HTN with higher rates of recurrence. A previous study reported that beta-blockers can reduce the risk of recurrence by almost two-thirds. The decreased risk was attributed to the mechanism of action of beta-blockers: decreasing intracoronary shear stress, decreasing heart contractility, and reducing aneurysm degeneration. Our patient suffered a recurrent case of SCAD despite recommended treatment with a beta-blocker. Further research is needed to risk-stratify patients and to clarify if a specific dose or type of beta-blocker will protect against SCAD recurrence.
Abstract 12085: Impact of Pre-Fontan Hemodynamics on Long-Term Outcomes of Patients With Fontan Palliation
Authors: Divya Suthar, Asaad Beshish, Amanda S Thomas, J'Neka Claxton, Jessica Knight, Fawwaz Shaw, William T Mahle, Matthew Oster, Lazaros Kochilas
Journal: Circulation (2021)

Introduction: Fontan procedure for single ventricle (SV) is frequently preceded by cardiac catheterization. The impact of pre-Fontan hemodynamics on long-term outcomes is not completely understood. Methods: This is a cohort study of patients undergoing Fontan in the Pediatric Cardiac Care Consortium (PCCC), a US-based registry of congenital heart surgeries. Deaths and transplants were captured through 2019 in the PCCC and by linkage with the National Death Index and the Organ Procurement Transplant Network. The relationship between pre-Fontan hemodynamics and post-Fontan transplant-free survival were evaluated with Kaplan Meier (KM) and Cox regression with adjustment for age at Fontan, sex, era of surgery, Fontan type, and type of systemic ventricle. Results: Between 1986 and 2003, 1498 patients were enrolled in the PCCC and underwent pre-Fontan cardiac catheterization. Table 1 demonstrates the relationship of patient characteristics on the risk of death or transplant after Fontan discharge. After adjustment for other risk factors PVRi (aHR 1.28; 95% CI 1.09 - 1.49) and mPAP (aHR 1.07; 95% CI 1.02- 1.12) were the main factors associated with risk of death or transplant. KM survival curves stratified by PVRi and mPAP tertile depict the loss of transplant-free survival years for the top tertile of mean PAP (&gt;13 mmHg) or PVRi (&gt;2.3 WU m 2 ) (Figures A and B). Conclusions: This study of a large cohort of single ventricle patients demonstrates that abnormal pre-Fontan hemodynamics are associated with increased risk of death or transplant even many years after Fontan procedure. Such data may help to guide therapeutic considerations and monitoring intensity after Fontan completion.
Abstract P348: Pathophysiological Basis Of A Compound Variant In Calcium And Sarcomere Regulation Causing Cardiac Arrhythmias And Hypertrophic Cardiomyopathy
Authors: Mohit Kumar, Sholeh Bazrafshan, Perundurai Dhandapany, Kobra Haghighi, Rohit Singh, Ralph Knoell, Evangelia Kranias, Sakthivel Sadayappan
Journal: Circulation Research (2021)

Rationale: Hypertrophic cardiomyopathy (HCM) is common inheritable heart disease. HCM is highly associated with arrhythmias and/or sudden death. Studies show that molecular defects in calcium handling impairing the cardiomyocyte contractility is a predominant cause. However, the pathophysiology underlying HCM with arrhythmias is not well understood, hindering the identification of novel therapies. Objective: To investigate the pathophysiological consequences of compound variants, consisting of Histidine Rich Calcium Binding Protein gene ( HRC S96A ) and an intronic 25bp deletion in cardiac myosin binding protein-C ( MYBPC3 Δ25bp ). Methods and Results: Clinical data revealed that co-segregation of HRC S96A and MYBPC3 ΔInt32 results in cardiac arrhythmia, heart failure, and sudden cardiac death in South Asians. To determine the cellular/molecular trigger underlying the pathophysiology of this dual variant, we used humanized, knock-in, heterozygous mouse models, including HRC S81A (equivalent to HRC S96A ) MYBPC3 Δ25bp , HRC S81A / MYBPC3 Δ25bp (double variant, DV), and wild-type controls. Echocardiography revealed a significant decrease in the percentage of ejection fraction and fractional shortening in DV mice, as well as the presence of diastolic dysfunction, at 12 weeks of age, compared to single-variant and wild-type mice. Electrocardiogram tracing of DV mice showed the presence of stress-induced arrhythmias, such as ventricular tachycardia after caffeine and epinephrine administration. Using isolated cardiomyocytes in vitro , Calcium transient experiments indicated a significant decrease in fractional shortening, Ca 2+ transient amplitude, and a higher number of after-contractions in cardiomyocytes from DV mice. DV mouse hearts showed increased phosphorylation of CaMKII and SR Ca 2+ leak by cardiomyocytes. Inclusion of the CaMKII inhibitor KN-93 rescued the increases in SR Ca 2+ leak and in aftercontractions. Conclusion: Impaired Ca 2+ -handling, owing to the HRC S96A variant, aggravates SR Ca 2+ leak and aftercontractions in MYBPC3 Δ25bp cardiomyocytes, subsequently triggering cardiac arrhythmias and sudden death in vivo .
Abstract 11434: Emergency Department Disposition for Patients with Low-Risk Acute Pulmonary Embolism: A Nationwide Analysis
Authors: Ahmed Elkaryoni, Sovik De Sirkar, Matthew Collins, Nicolas Krepostman, David Sutherland, Kevin Walsh, Sorcha Allen, Joshua Newman, Matthew C Bunte, Amir Darki
Journal: Circulation (2021)

Background: Outpatient management has been shown to be safe and effective for patients presenting to the emergency department (ED) with low-risk acute pulmonary embolism (PE). The degree to which outpatient management for PE has evolved in contemporary clinical practice is uncertain, as is an understanding of whether certain patient or hospital factors are associated with outpatient PE management. Methods: Using the Nationwide Emergency Department Sample, we identified hospitalizations with primary or secondary PE between 2006-2018. We excluded patients who were &lt;18 years old, died during ED visit, received systemic or catheter-directed thrombolysis, or had any of the following: acute coronary syndrome, heart failure, atrial fibrillation, chronic kidney/lung disease, gastrointestinal bleeding, or respiratory failure. Multivariable regression models were utilized to identify patient and hospital factors that predicted discharge to home from the ED. Results: Among 516,670 ED visits with acute PE, 92,108 (17.8%) patients were discharged to home. As compared to those admitted, patients who were managed as an outpatient were younger (median 52, interquartile range (IQR) 26-78 vs 61 IQR (35-87) years, P&lt;0.001), and more female (57.9% vs 53.1%, P&lt;0.001). In more recent years there was a significant increase in discharge from ED to home (9.2% in 2016 to 29.7% in 2018 (relative increase 69.0%, P&lt;0.001)) Panel A. In a sensitivity analysis, when PE was only a primary diagnosis, the rate of home disposition increased from 4.8% to 27.7%, P&lt;0.001. Patient and hospital factors associated with an increased likelihood of home discharge are listed Panel B . Conclusion: Outpatient management of patients with low-risk PE has become increasingly common, with more than one-quarter of patients evaluated in the ED now discharged to home. Patient demographics, seasonal variation, and hospital characteristics were associated with a differential effect on the home disposition.