tbuckley/cabot-search huggingface dataset:
Abstract 15603: Discovery of Plasminogen Activator Inhibitor-1 Platelet-derived Extracellular Vesicles to Predict Major Adverse Cardiac Events
Authors: Richard Jung, Trevor Simard, Pietro Di Santo, Anne-Claire Duchez, Alisha Labinaz, Simon Parlow, Jiayue Yang, Shan Dhaliwal, F Daniel Ramirez, Fengxia Xiao, Marie Lordkipanidze, Dylan E Burger, Benjamin M Hibbert
Journal: Circulation (2020)

Objective: To evaluate the utility of plasminogen activator inhibitor-1 positive platelet-derived extracellular vesicles (PAI-1 + PEV) as a biomarker for major adverse cardiac events (MACE) following angiography. Background: The stented coronary artery is at high-risk for complications, predominantly in the form of stent thrombosis and in-stent restenosis. Clinical risk scores have been attempted but no current models nor biomarkers yet accurately identifies the high-risk cohort following revascularization. Methods: PAI-1 + PEV was measured by flow cytometry in 172 patients undergoing coronary angiography. Biological characteristics and utility of PAI-1 + PEV as a biomarker were evaluated. The primary outcome was the incidence of MACE (composite of death, myocardial infarction, cerebrovascular accident, and unplanned revascularization) at 12 months. Results: During a median follow-up period of 377 days (IQR, 269.5 to 442.5 days), 38 patients (20.9%) experienced MACE. In this study, the existence of PAI-1 + PEV complex was validated by flow cytometry (Figure 1A). Furthermore, low log-transformed PAI-1 + PEV levels were associated with MACE (4.17 0.40 vs. 4.33 0.59 logPAI-1 + PEV, p=0.02). After adjustment for known clinical risk factors, low PAI-1 + PEV levels were independently associated with MACE with a hazard ratio of 7.79 (95% CI, 1.87 to 32.4, p=0.005). Finally, low plasma PAI-1 + PEV levels was predictive of MACE in both the discovery and validation cohort (Figure 1B-C). Conclusion: Our results demonstrate the existence of a PAI-1 + PEV and its potential utility as a biomarker to predict MACE. Low plasma PAI-1 + PEV levels was predictive of MACE in both the discovery and validation cohort.
Abstract 14312: Hexokinase 1 Cellular Localization Regulates the Metabolic Fate of Glucose
Authors: Adam DEJESUS
Journal: Circulation (2020)

Introduction: The product of hexokinase (HK) enzymes, glucose-6-phosphate (G6P), can be metabolized through glycolysis or directed to alternative pathways, such as the pentose-phosphate-pathway (PPP) for anabolism. However, it is not known what determines the fate of G6P. HK1 contains an N-terminal mitochondrial-binding domain, but its physiologic significance remains unclear. Inflammation is a tightly controlled process sensitive to dynamic changes in the tissue environment and the intrinsic state of immune cells, both contributing to the initiation and resolution of inflammation. The loss of HK1 attenuates glycolytic reprogramming and inflammatory cytokine production in LPS stimulated macrophages. Given the importance of HK1 in the innate immune response, we used myeloid cells as a model system to study the effect of HK1 subcellular localization on cellular metabolism and inflammation. Results: We overexpressed full-length and truncated HK1 in tissue culture and generated mice lacking the HK1 mitochondrial-binding domain (ΔE1HK1). Although ΔE1HK1 mice displayed no overt phenotype, HK1 dislocation from the mitochondria increased glucose flux through the PPP, decreased flux below the level of GAPDH, and induced a hyper-inflammatory response to lipopolysaccharide. The mechanism for the increased PPP flux is through a glycolytic block at GAPDH, which is mediated by binding of cytosolic HK1 with S100A8/A9 and increased GAPDH nitrosylation through iNOS. Human and mouse macrophages from conditions of low-grade inflammation, such as aging and diabetes, displayed an increase in cytosolic HK1 and cytokine production, along with reduced GAPDH activity. Conclusions: Our data indicate that HK1 subcellular localization is a critical regulator of glucose metabolism and determines whether glucose is shuttled into PPP at the expense of glycolysis, and regulates the inflammatory response in macrophages (Figure).
Abstract 14170: Reduction in Venous Thromboembolism With Rivaroxaban versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD
Authors: Connie N Hess, Sonia Anand, Rupert Bauersachs, Manesh R Patel, E. Sebastian Debus, Mark R Nehler, Warren H Capell, Lihong Diao, Eva Muehlhofer, Scott berkowitz, Lloyd P Haskell, William R Hiatt, Marc P Bonaca
Journal: Circulation (2020)

Background: Prior studies suggest that atherosclerotic vascular disease may be associated with risk of venous thromboembolism (VTE), though the relationship remains uncertain and has not been well-studied in peripheral artery disease (PAD) after lower extremity revascularization (LER). Hypothesis: We hypothesized that patients with PAD undergoing LER are at risk for VTE and that this risk may be reduced by low-dose rivaroxaban plus aspirin versus aspirin alone. Methods: VOYAGER PAD randomized 6,564 PAD patients undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. Clopidogrel was allowed for up to 6 months. Patients could not be enrolled if they had an indication for therapeutic anticoagulation, including secondary prevention of VTE. Symptomatic VTE was a prespecified secondary endpoint. Results: Over a median of 28 months, there were 66 patients with VTE. In patients randomized to placebo, risk for VTE accrued steadily after randomization at a rate of ~0.5% per year resulting in a 3-year rate of 1.66%. Compared with placebo, rivaroxaban reduced the risk of VTE by 39% (HR 0.61, 95% CI 0.37-1.00, p=0.047), with benefit apparent early and sustained over time (Figure). The efficacy of rivaroxaban was not modified by use of clopidogrel at randomization (without clopidogrel HR 0.55, 95% CI 0.29, 1.07; with clopidogrel HR 0.69, 95% CI 0.32, 1.48; p-interaction = 0.67). Conclusions: PAD is associated with continuous and linearly increasing risk for VTE after LER. A strategy of low-dose rivaroxaban plus aspirin versus aspirin alone reduced this risk by 39% with benefits apparent early and continued over time. The addition of clopidogrel does not modify this benefit. VTE, along with arterial thrombotic events, is part of the adverse thrombotic risk profile in PAD patients, and low-dose rivaroxaban plus aspirin provides protection against venous and arterial thrombosis.
Abstract 15423: Hope is Not a Plan: Re-engaging Transition-aged Young Adults With Congenital Heart Disease Actively Missing From Cardiac Care
Authors: Judson A Moore, Shreya Sheth, Wilson W Lam, Andre Espaillat, Alexander Alexander, John Shabosky, DONNA LOVICK, Nicole Broussard, Karla J Dyer, Keila N Lopez
Journal: Circulation (2020)

Introduction: Many studies describe gaps in care for youth with congenital heart disease (CHD), but few reach out to patients actively missing from care. Our study goal was to identify young adults with CHD actively missing from cardiac care to: 1) administer a needs assessment and 2) re-engage patients in cardiac care. Methods: We performed a retrospective review of outpatient medical records (2012-2019) for patients 15-21 yrs with CHD at Texas Children’s Hospital. ICD 9/10 codes identified CHD patients; those ≥1 year beyond requested clinic follow-up were defined as ‘actively missing’. Sociodemographic data was collected, and a telephone needs assessment conducted to determine CHD knowledge, barriers to care, and health status. Either a patient or parent completed the survey and was offered to re-engage in cardiac care. Descriptive statistics were performed on available data. Results: Of 1057 CHD patients, 33% (n=353) were actively missing. Of those missing, 58% were male and median age was 17 yrs (IQR 16-19). Patients were 46% Non-Hispanic White, 9% Non-Hispanic Black, and 33% Hispanic. Moderately complex CHD was noted in 71%. Insurance status was 63% private and 31% public. Ninety-eight patients/parents (28%) participated in our survey. Fifty-two percent reported having no cardiac care, often citing lack of or incompatible hospital insurance (33%; n = 32). Active cardiac symptoms were reported in 25%. Half of patients felt they could explain their cardiac condition well, and 82% could name their medications. Scheduling barriers (26%; n = 25) and being unaware adults could be cared for at our heart center (15%; n = 15) were the most common obstacles to re-engaging in care. Participants felt text messaging and scheduling visits during cardiology clinic would improve care access. More than half of patients/parents (55%) accepted our help to re-engage in cardiac care (scheduling assistance). Conclusions: This data suggests patients require assistance beyond CHD knowledge to stay in care. Problems with insurance, scheduling, and perceptions of adult CHD care were key barriers to maintaining cardiac care despite moderate CHD complexity and active symptoms. Future quality initiatives should include scheduling, insurance coverage, and adult CHD services.
Characteristics of Hospitalized COVID-19 Patients Discharged and Experiencing Same-Hospital Readmission — United States, March–August 2020
Authors: Amy M. Lavery, Leigh Ellyn Preston, Jean Y. Ko, Jennifer R. Chevinsky, Carla L. DeSisto, Audrey F. Pennington, Lyudmyla Kompaniyets, S. Deblina Datta, Eleanor S. Click, Thomas Golden, Alyson B. Goodman, William R. Mac Kenzie, Tegan K. Boehmer, Adi V. Gundlapalli
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

The Premier Healthcare Database includes discharge records for adult and pediatric patients from >1
CHARACTERISTICS OF SARS-Cov2 AND LIVER CIRRHOSIS- A SINGLE-CENTRE EXPERIENCE IN THE UNITED KINGDOM
Authors: M. O. Mandour, K. K. Rafique, J. M. Koh, K. Iliadou, D. Forton, A. Singanayagam
Journal: Hepatology (2020)

Background: Cirrhosis is a state of immune dysfunction and is associated with a higher susceptibility to infection Cytopaenias in this group of patients is not uncommon As such, given the current coronavirus pandemic, we sought to determine the impact of SARS-Cov2 on mortality in patients with cirrhosis and whether popular risk assessment tools such as the CALL (Co-morbidities, older age, higher lactate dehydrogenase and lower lymphocyte count) model, could be applied to this cohort Methods: A retrospective study was conducted between 1st January 2020 and June 2020 at St George's University Hospital NHS foundation trust Demographic and clinical information was retrieved from the electronic patient record Laboratory parameters (including lymphocyte count), and MELD-Na were assessed on admission and day 3 for the non-Covid group and the day of positive nasopharyngeal swab and day 3 for the Covid group The primary outcome was all-cause mortality, defined by the death recorded at data-lock (11th June 2020) The secondary outcomes were to compare the length of hospital stay and to assess whether baseline predictors were reliable diagnostic and prognostic markers for patients with SARS-Cov2 Results: 85 patients included were dichotomised to Covid negative (n=75) and Covid positive (n=10) groups according to polymerase chain reaction results Characteristics were similar between the two groups with males representing 69% (n=52) in the Covid negative and 60% (n=6) in the Covid positive groups Mean age was 60 8 and 61 05 respectively SARS-Cov-2 in the context of cirrhosis was found to be associated with longer hospital stay with a median of 11 5 days (Q1-Q3: 8 25 -15 8, p=0 047, Mann Whitney) 30% (n=3) of patients in the Covid positive group died within 30 days compared to 9 3% (n=7) in the Covid negative group Primary cause of death for the Covid positive patients was respiratory failure MELD-Na score ≥15 was found to be a statistically significant predictor for mortality in the Covid negative group alone [RR 8 37 (95%CI 1 10-63 15, p=0 015]  There was no statistically significant difference between the lymphocyte counts of the two groups at the time of diagnosis (p=0 561) Conclusion: In patients with underlying cirrhosis, SARS-Cov-2 infection is associated with a longer hospital stay As lymphopenia is not uncommon in patients with underlying cirrhosis, the lymphocyte count should not be used as an early assessment tool in this group to triage patients to suspected COVID wards and all patients should be tested for SARS-Cov-2 Risk assessment models such as CALL should be currently avoided in patients with cirrhosis
Abstract 13617: Newborn Critical Congenital Heart Disease Screening Fails to Detect Target Lesions or Reduce Mortality
Authors: Robin Miller, Timothy Martens, Upinder Jodhka, Jade Tran, Richard Lion, Rambod Amirnovin, Anees Razzouk, Matthew J Bock
Journal: Circulation (2020)

Introduction: Congenital heart disease (CHD) affects over one million children in the United States. Studies show mixed outcomes regarding a survival benefit from newborn cardiac screening (NCS). California began a NCS program on 7/1/13. We evaluated the effect of mandatory NCS on surgical outcomes of our program. Hypothesis: Neonates with critical CHD (CCHD), requiring surgery as infants, who are not diagnosed prior to or at the NCS have lower survival than those diagnosed prior to or at the NCS. Methods: We evaluated all infants with CCDH undergoing cardiac surgery at our center between 07/01/13 - 12/31/18. Subjects were stratified by timing of diagnosis (pre-screen, screen positive, screen negative). Sensitivity to detect specific lesions was calculated. Primary end-points were operative mortality, absolute mortality, and actuarial survival. Results: Two-hundred-seventy-four infants with CCHD were included. Seventy-nine percent were diagnosed prior to screening, while 8% were diagnosed by NCS, and 13% were screen negative. Total anomalous pulmonary venous return (TAPVR) (47%) and aortic coarctation (CoA) (40%) were the most likely to be undiagnosed at time of NCS (p&lt;0.001). Sensitivity to detect target lesions was 38% overall [TAPVR 73%, CoA 12%, hypoplastic left heart syndrome (HLHS) 25%, Tetralogy of Fallot (TOF) 29%]. Primary end-points were not different based on timing of diagnosis (p&gt;0.05) (Figure). Conclusions: We found only a 38% sensitivity of mandatory newborn CCHD screening to detect target cardiac lesions requiring surgery in the first year of life. A high proportion of newborns with HLHS, TOF, and CoA remained undiagnosed after screening, though TAPVR was readily detected. There were no differences in survival between the screening groups. Mandatory newborn CCHD pulse oximetry screening can detect some newborns with critical heart disease, but should not replace traditional methods of monitoring in the fetal, newborn, and infant periods.
Abstract 14914: Advanced 4D-flow Measurements of Aortic Forward Flow, Reverse Flow, and Stasis in Bicuspid Aortic Valve Patients Without Aortic Stenosis or Regurgitation
Authors: Patrick Geeraert, Fatemehsadat jamalidinan, Ali Fatehi Hassanabad, James White, Julio Garcia Flores
Journal: Circulation (2020)

Introduction: Precise analysis of aortic hemodynamics is crucial in the study of bicuspid aortic valve (BAV) disease. This study provides a comprehensive evaluation of aortic forward flow (FF), reverse flow (RF) and stasis in BAV patients using novel 3D-based techniques previously shown to be more accurate than traditional 2D analysis methods. Hypothesis: BAV patients without valve dysfunction show abnormal aortic FF, RF, and stasis compared to healthy controls. Methods: We recruited 44 BAV patients (48±15 yrs, 27% female) and 23 healthy controls (37±14 yrs, 35% female). Cardiac MRI at 3T was performed inclusive of 4D-flow imaging. Patients with any aortic stenosis (AS) or ≥mild regurgitation (AR) were excluded. Flow analysis was performed by segmented volumetric regions: left ventricular outflow tract (LVOT), ascending aorta (AAo), arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region, forward flow (FF), reverse flow (RF) and stasis were averaged over the cardiac cycle on a voxel-by-voxel basis. Left ventricular (LV) end-diastolic volume, end-systolic volume and ejection fraction were also measured. T-tests (or non-parametric equivalent) compared differences in parameters between cohorts. Results: BAV patients were significantly older than controls (48±15 vs. 37±14 yrs; p=0.01) but exhibited no significant differences in LV measures. Patients showed reduced FF in the AAo (0.09±0.03 vs. 0.11±0.04 mL/cycle; p&lt;0.01), but greater FF in all downstream regions (eg. PDA: 0.02±0.03 vs. 0.01±0.02 mL/cycle; p=0.01). RF was significantly elevated in patients in the AAo (0.06±0.02 vs. 0.02±0.02 mL/cycle; p&lt;0.01). BAV patients exhibited significantly less stasis in every region except the DDAo (eg. AAo: 23±11 vs. 50±10 % of cardiac cycle). Conclusions: 3D-derived measurements of FF, RF, and stasis are significantly altered in the thoracic aorta of BAV patients in the absence of AS or AR.
New insights into the role of lipids in plant hypoxia responses
Authors: Li-Juan Xie, Ying Zhou, Qin-Fang Chen, Shi Xiao
Journal: Progress in Lipid Research (2020)

In plants, hypoxia (low-oxygen stress) is induced by soil waterlogging or submergence and this major abiotic stress has detrimental effects on plant growth, development, distribution, and productivity. To survive low-oxygen stress, plants have evolved a set of morphological, physiological, and biochemical adaptations. These adaptations integrate metabolic acclimation and signaling networks allowing plants to endure or escape from low-oxygen environments by altering their metabolism and growth. Lipids are ubiquitously involved in regulating plant responses to hypoxia and post-hypoxic reoxygenation. In particular, the polyunsaturation of long-chain acyl-CoAs regulates hypoxia sensing in plants by modulating acyl-CoA-binding protein–Group VII ethylene response factor dynamics. Moreover, unsaturated very-long-chain ceramide species protect plants from hypoxia-induced cellular damage by regulating the kinase activity of CONSTITUTIVE TRIPLE RESPONSE1 in the ethylene signaling pathway. Finally, the oxylipin jasmonate specifically regulates plant responses to reoxygenation stress by transcriptionally modulating antioxidant biosynthesis. Here we provide an overview of the roles of lipid remodeling and signaling in plant responses to hypoxia/reoxygenation and their effects on the downstream events affecting plant survival. In addition, we highlight the key remaining challenges in this important field.
Abstract 16278: Discordant Lipid Phenotype and Other Determinants of Statin Response in the Pravastatin Inflammation/crp Evaluation (PRINCE) Trial
Authors: Oluremi N Ajala, Olga Demler, Yanyan Liu, Paul M Ridker, Robert J Glynn, Daniel Chasman, Samia Mora
Journal: Circulation (2020)

Introduction: Wide variability in LDL-C change is observed with statins, yet determinants of statin response are uncertain. Methods: Participants were selected from the primary prevention cohort of the Pravastatin Inflammation/CRP Evaluation double-blind trial that randomized participants to pravastatin 40 mg/d or placebo over 24 weeks. Baseline and 24-week levels of LDL-C and 15 other biomarkers were measured in 495 participants. We defined optimal statin response as &gt;=30% LDL-C reduction and suboptimal response as &lt;30% reduction. Sub-optimal hs-CRP response was defined as &gt;=median (14%) decline in hs-CRP from baseline to 24 weeks and non-response as no decrease or an increase in hs-CRP. χ 2 , t-tests and ANOVA were used to compare variables across optimal statin response (N=166) and suboptimal response (N=287). Multivariable logistic regression models evaluated associations of determinants of statin response. Forward selection identified variables that associated with response. Xgboost was used to train and validate the models using 2/3 and 1/3 of the data respectively. Results: Significant determinants of optimal statin response included older age, and higher baseline levels of LDL-C and triglyceride-rich lipoproteins. By contrast, female sex, alcohol intake &gt;=1 drink/day, diabetes, higher baseline levels of apo B and lipoprotein(a) were associated with decreased response, as was hs-CRP non-response (Table). Race, baseline hs-CRP and sub-optimal hs-CRP response, smoking, HDL-C and BMI had no significant effect on statin LDL-C response. Training and validation of models predicted suboptimal LDL-C response with an AUC of 0.71. Similarly, training and validation of models using Xgboost yielded an AUC of 0.85. Conclusion: This study identified discordant lipid phenotype and other determinants of moderate-intensity statin response and suggests other pathways of CVD risk beyond those addressed by statin treatment that require further investigation.
Abstract 13474: Rivaroxaban Reduces Major Cardiovascular and Limb Events in Patients With the High-risk Triad of Chronic Kidney Disease, Peripheral Artery Disease and Recent Lower Extremity Revascularization: Insights From VOYAGER PAD
Authors: Judith A Hsia, Sonia Anand, Mark R Nehler, Rupert Bauersachs, Manesh R Patel, Sebastian Debus, Connie N Hess, Warren Capell, Lihong Diao, Scott D Berkowitz, Eva Muehlhofer, Lloyd P Haskell, William R Hiatt, Marc P Bonaca
Journal: Circulation (2020)

Introduction: Chronic kidney disease (CKD) is common among patients undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD) and identifies a population at high risk for adverse outcomes. The VOYAGER PAD trial demonstrated the efficacy of rivaroxaban in PAD patients after LER on a composite of cardiovascular (CV) and limb ischemic events (HR 0.85 vs placebo, 95% CI 0.76-0.96; p=0.009); this analysis examines the prespecified subgroup of patients with CKD. Methods: VOYAGER PAD (NCT02504216) was a double-blind, placebo-controlled trial which randomized PAD patients with recent LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. The primary endpoint was a composite of acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke or CV death. The primary safety endpoint was TIMI major bleeding. Analysis of the intention-to-treat population utilized Kaplan Meier estimates and Cox proportional-hazards models. Results: Among 6319 VOYAGER patients with baseline estimated glomerular filtration rate (eGFR), 21% were &lt;60 (mostly CKD stage 3) and 79% were ≥60 ml/min/1.73m 2 . During 28-month (median) follow up, patients with CKD had a higher rate of major CV and limb events: placebo group 10.0 events/100 patient-years (95% CI 8.5, 11.8) for eGFR &lt;60 vs 7.4 (95% CI 6.7, 8.2) for eGFR ≥60. Rivaroxaban reduced primary outcome events with no heterogeneity by eGFR category (Figure, p for interaction 0.62). Acute limb ischemia and major amputation were significantly reduced among patients with eGFR&lt;60 (HR 0.55, 95% CI 0.36, 0.86) as well as ≥60 (HR 0.77, 95% CI 0.63, 0.94). TIMI major bleeding was numerically more frequent among patients with CKD with no heterogeneity by treatment group (Figure, p for interaction 0.37). Conclusions: Rivaroxaban reduced major CV and limb events in patients with PAD undergoing LER, including those with CKD, a particularly high-risk population.