tbuckley/cabot-search huggingface dataset:
Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients With Hepatitis C in the Era of Direct-Acting Antiviral Agents
Authors: Qiushi Chen, Turgay Ayer, Madeline G. Adee, Xiaojie Wang, Fasiha Kanwal, Jagpreet Chhatwal
Journal: JAMA Network Open (2020)

In the US, hepatocellular carcinoma (HCC), primarily associated with hepatitis C virus (HCV) infection, is the fastest rising cause of cancer-related death. Wider use of highly effective direct-acting antiviral agents (DAAs) substantially reduces the burden of chronic HCV infection, but the subsequent impacts with HCV-associated HCC remain unknown.To assess projected changes in the incidence rate of and surveillance burden for HCC in the era of DAA treatment for HCV.This decision analytical model study was performed from January 2019 to February 2020, using an individual-level state-transition simulation model to simulate disease progression, screening, and different waves of antiviral treatments for HCV in the US from 2012 to 2040.Current clinical management for chronic HCV infection.Model outcomes were projected temporal trends and age distribution of incident HCC cases and candidates for HCC surveillance among patients with viremia and patients with virologically cured HCV.The simulation model projected that the annual incidence of HCC among patients with viremia and patients with virologically cured HCV will continue increasing to 24 000 (95% uncertainty interval [UI], 18 000-31 000) cases until 2021. In patients with virologically cured HCV, incident HCC cases are projected to increase from 1000 (95% UI, 500-2100) in 2012 to the peak of 7000 (95% UI, 5000-9600) in 2031 with a subsequent decrease to 6000 (95% UI, 4300-8300) by 2040. The proportion of incident HCC cases that occur in individuals with virologically cured HCV is estimated to increase from 5.3% in 2012 to 45.8% in 2040. The number of candidates for HCC surveillance in the population with virologically cured HCV is projected to increase from 106 000 (95% UI, 70 000-178 000) in 2012 to the peak of 649 000 (95% UI, 512 000-824 000) in 2030 and decrease to 539 000 (95% UI, 421 000-687 000) by 2040, while the proportion of all candidates for surveillance who are virologically cured is estimated to increase from 8.5% to 64.6% during the same period. The average age of HCC incidence and surveillance candidates is estimated to increase from 55 in 2012 to 72 and 71, respectively, by 2040.The results of this study suggest that the burden of HCC will shift from patients with viremia to patients with virologically cured HCV, and to older populations. Appropriate management may be warranted for early detection of HCC in patients who may no longer be receiving specialty care for liver conditions.
Abstract 19242: Allele-Specific Silencing of MYH7 in Human iPSC-Derived Cardiomyocytes Using Antisense Oligonucleotides
Authors: Alexandra Dainis, Matthew Wheeler, Euan Ashley
Journal: Circulation (2016)

Introduction: Hypertrophic cardiomyopathy (HCM) is an autosomal genetic disease which results in hypertrophy of the left ventricular wall and remains a leading cause of sudden death in young adults...
Abstract 15862: Abnormal Exercise-induced Aortic Stiffness in Heart Failure
Authors: Connie W Tsao, Lana Myerson, Inbar Raber, Ulf Neisius, Warren J Manning
Journal: Circulation (2020)

Introduction: Afterload conferred by aortic stiffness contributes to heart failure (HF) pathogenesis. Hypothesis: Patients with HF have a greater rise in aortic stiffness with physical exertion compared to individuals without HF. Methods: Outpatients with HF (n=21) and without HF (n=26) underwent cardiovascular magnetic resonance (1.5T CMR) at rest and following submaximal supine bicycle ergometry. Short axis cine steady-state free precession (SSFP) images were obtained to quantify left ventricular volumes and ejection fraction. Cross-sectional aortic SSFP imaging at the level of the pulmonary artery bifurcation was obtained to measure descending aorta (DA) distensibility at rest and immediately after exercise. We compared least squares (LS) means of DA distensibility between HF and control groups, adjusting for age, sex, and metabolic equivalents (METs) achieved. Results: Characteristics of controls and HF patients are presented in the TABLE . There was no difference of DA distensibility between control and HF groups either at rest or after exercise (p=0.77 and p=0.13, respectively). However, compared to controls with no significant change in aortic stiffness with exercise, individuals with HF had a reduction in DA distensibility post-exercise in analyses adjusted for age, sex, and METs achieved ( TABLE ). In subgroup analyses, patients with HF with reduced ejection fraction (n=14) had lower post-exercise DA distensibility vs. rest (adjusted-LS means 3.06 x10 -3 mm Hg -1 , 95% CI 2.35x10 -3 —3.76x10 -3 mm Hg -1 , vs. 4.55 x10 -3 mm Hg -1 , 95% CI 3.84 x10 -3 —5.26 x10 -3 mm Hg - 1, respectively, p=0.020). DA distensibility at rest vs. exercise in patients with HF with preserved ejection fraction was similar (p=0.38). Conclusions: Patients with HF have exercise-induced aortic stiffness not seen in individuals without HF. This may result in less favorable ventricular-vascular coupling with exertion in HF patients. Character count: 1653 (limit=1700)
Abstract PO-016: STAT3 in cancer-associated fibroblasts promotes an immunosuppressive tumor microenvironment in PDAC
Authors: Julia E. Lefler, Katie MarElia, Blake E. Hildreth, Katie A. Thies, Maria C. Cuitino, Michael C. Ostrowski
Journal: Cancer Research (2020)

Abstract One of the defining characteristics of pancreatic ductal adenocarcinoma (PDAC) is the formation of a dense stroma comprised of cancer associated fibroblasts (CAFs) and immune cell populations. This stroma is immunosuppressive and can act as a physical barrier against common therapeutic treatments. Attempts to therapeutically target the PDAC stroma have yielded contradictory results, suggesting both tumor promoting and tumor limiting roles for CAFs. These studies emphasize the need to understand important transsignaling pathways between CAFs, tumor cells, and the immune microenvironment. IL-6 is a pleiotropic cytokine involved in several physiological functions and its increased expression is strongly associated with poor survival rates in PDAC patients. STAT3 is a major downstream target of IL-6, and its aberrant activation has been implicated in PDAC tumor progression and immune evasion. IL-6 expression and the IL-6/STAT3 signaling axis in PDAC has been characterized in epithelial tumor cells, however its stromal-specific function on PDAC has yet to be elucidated. We hypothesized that the STAT3 signaling axis in pancreatic CAFs contributes to the immunosuppressive and fibrotic phenotype seen with disease progression. Employing CreLoxP technology, the fibroblast specific protein-1 (Fsp-Cre) transgene was used to conditionally delete STAT3 in fibroblasts in the PdxFlp; KrasG12D; p53 frt/frt (KPF) PDAC mouse model developed by our lab. Deletion of STAT3 in fibroblasts significantly increased the survival in a cohort of KPF mice compared to those with intact STAT3. Loss of fibroblast STAT3 also resulted in a significant decrease in ECM deposition in the pancreas. In preliminary investigations into the immune microenvironment, we found an increase in overall T cell infiltration and decrease in regulatory T cell populations in the STAT3 deleted cohort. Further, STAT3 deletion resulted in an increase in the ratio of M1 to M2 macrophages within the PDAC stroma, suggesting CAF STAT3 signaling is important to maintaining an immune microenvironment conducive to tumor progression. Ultimately, these preliminary results suggest STAT3 signaling in PDAC CAFs contributes to an overall survival disadvantage, an immunosuppressive tumor microenvironment, and an increase in ECM deposition. Citation Format: Julia E. Lefler, Katie MarElia, Blake E. Hildreth, Katie A. Thies, Maria C. Cuitino, Michael C. Ostrowski. STAT3 in cancer-associated fibroblasts promotes an immunosuppressive tumor microenvironment in PDAC [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-016.
Abstract 323: Three-dimensional Transesophageal Echocardiography and Speckle Tracking Echocardiography in Infective Aortic Endocarditis: Analysis of Parameters Predictors of Outcome
Authors: Lidia Capotosto, Maria Ciardi, Gaetano Tanzilli, Mangieri Enrico, Fabio Miraldi, Claudio Mastroianni, Vincenzo Vullo, Antonio Vitarelli
Journal: Circulation (2020)

Purpose: Due to the high mortality and morbidity of patients with aortic endocarditis, careful monitoring is necessary to recognize an early failure of antibiotic and cardiokinetic therapy and avoid a possible cardiogenic or septic shock. The timing of surgery is crucial for patients in whom medical therapy fails. The aim of our study is to identify potential echocardiographic "markers" of adverse events in patients with aortic regurgitation from infective endocarditis. Methods: Seventeen patients with aortic regurgitation (AR) from infective endocarditis were studied by 3-dimensional transesophageal echocardiography (3D-TEE) and transthoracic speckle tracking echocardiography (STE). Fifteen healthy subjects were selected as controls. Vegetation size was assessed by 3D-TEE. Standard transthoracic echocardiographic parameters were determined. Global left ventricular (LV) longitudinal strain (LS), radial and circumferential strain were measured by STE. Averaged LV rotation and rotational velocities from the base and apex were obtained and used for calculation of LV torsion (LVtor). Results: Severe AR had decreased LS compared with control subjects. LVtor decreased significantly in severe AR compared to normals (p&lt;.005) as a result of a predominant decrease in apical rotation. By multivariate analysis, LV-LS (p=0.005), LV-tor (p=0.006) and vegetation size (p=0.009) were predictive of adverse events. ROC curves suggested that thresholds offering an adequate compromise between sensitivity and specificity for adverse events detection were -18.2% for mean global LV-LS (AUC .79), 13mm for vegetation size (AUC .86), and 19.4degrees for LVtor (AUC .81). The combination of vegetation size and LV strain had the highest diagnostic accuracy for identifying adverse outcome, superior to vegetation size (p=.006) or LV strain alone (p=.002). Conclusions: The combined assessment of the characteristics of vegetating masses and LV function strain parameters improves the sensitivity of the echocardiographic indices in predicting cardiac morbidity and mortality of aortic regurgitation from infective endocarditis.
Abstract 15866: The Utility of Extended Electrocardiographic Monitoring for Detecting Atrial Fibrillation in Cryptogenic Stroke in the African-american Population
Authors: Romy Rodriguez Ortega, Mohammed AlSadawi, Violeta Capric, Baho Sidiqi, Jonathan Francois, Adam Budzikowski
Journal: Circulation (2020)

Introduction: Cryptogenic stroke comprises about 25% of all ischemic strokes. Depending on modality and duration of ECG monitoring, subclinical atrial fibrillation (AF) is detectable in 2.7-30% of cryptogenic stroke patients. Hypothesis: Extended ECG monitoring has not been studied in the African American (AA) population. This retrospective study aims to study the incidence and risk factors of subclinical AF in African-Americans. Methods: We retrospectively reviewed 96 patients who received implantable loop recorders (ILR) for detecting subclinical atrial fibrillation after cryptogenic stroke. In the vast majority of patients, the ILR was implanted during the index hospitalization. Binary univariate and multivariate analyses were performed to determine predictors for AF detection. Results: AF was detected in 29% of patients (28/96) at 1000 days. All AF that was detected was exquisitely paroxysmal and ranged in duration between 0.05-103 minutes (mean 8.4 minutes with SD= 22.1 minutes). Baseline characteristics of patients are presented (Table 1A). Binary univariate analysis revealed the use of non-dihydropyridine calcium-channel blockers to be associated with decreased odds of AF detection. (Table 1B, C). Multivariate analysis found coronary artery disease diagnosis to be associated with increased odds of AF detection. Fifty-percent of the events in the AF group were detected within the first 36 days of loop recorder implantation (Fig 1). Conclusions: AF detection in our population occurs very early after index stroke and at significantly higher rates than reported in the CRYSTAL AF trial. Baseline characteristics have a poor predictive ability for the detection of AF. These findings emphasize the need for pre-discharge ILR implantation to improve AF detection in all patients with cryptogenic stroke.
Abstract 13654: Air Pollution, Environmental Greenness, and Total Cardiovascular Disease Mortality
Authors: William W Aitken, Kefeng Wang, Abraham Parrish, Diego Celli, Joanna Lombard, Jose Szapocznik, Scott C BROWN
Journal: Circulation (2020)

Introduction: Air quality is a major environmental determinant of health. Environmental greenness – a measure of vegetative presence – has been associated with reduced risk of cardiovascular disease. However, the impact of greenness on the relationship between air pollution and cardiovascular disease (CVD) has been less studied. Hypothesis: Environmental greenness is associated with reduced total CVD mortality and mediates some of the relationship between air pollution and CVD mortality. Methods: The Centers for Disease Control and Prevention Interactive Atlas of Heart Disease provided national CVD death rates, Environmental Protection Agency air quality measurements (particulate matter PM2.5), and Census sociodemographic information (age, race, education, and income) by county across the United States. These data were matched to mean county normalized difference vegetation index (NDVI) derived from National Aeronautics and Space Administration (NASA) Moderate Resolution Imaging Spectroradiometer (MODIS) 250 m spatial resolution data. Linear regression modeling estimated the relationship between air pollution and greenness on CVD mortality using SAS version 9.4 software. Mediation analysis of greenness on the relationship between air pollution and CVD mortality was then conducted. Results: Ambient concentration of PM2.5 ranged from 3 to 19.7 μg/m3 with a mean of 9 μg/m3 ± 1.9 μg/m3 and NDVI ranged from 0.00 to 0.80 with mean of 0.41 ± 0.13. For every 0.1-unit increase in NDVI, CVD mortality decreased by 13.2 deaths per 100,000 adults (p = 0.0001). For every 1 μg/m3 increase in PM2.5, CVD mortality increased by 38.8 deaths per 100,000 adults (p &lt; 0.0001). Mediation analysis suggests that NDVI is a statistically significant mediator of the PM2.5 to CVD mortality relationship, with NDVI explaining 4.3% of this relationship (p=0.0009). Conclusions: Our analysis of air quality, environmental greenness, and CVD death rates demonstrates that greenness is independently associated with reduced CVD morality and also mediates the relationship between air pollution and CVD mortality. The evidence suggests that environmental interventions to increase greenness and reduce air pollution may reduce excess cardiovascular mortality.
Abstract 14090: Multiparity is Associated With Aortic Pathology in Women From the Dallas Heart Study
Authors: Kavisha Singh, Rina Mauricio, Wanpen Vongpatanasin, Katy Lonergan, Monika Sanghavi, Amit Khera, James A De Lemos, Colby Ayers, Parag H Joshi
Journal: Circulation (2020)

Introduction: The proximal aorta has been shown to enlarge with aging in humans, but the long-term impact of hormonal and hemodynamic changes associated with pregnancy on aortic size and function are unknown. We examined if number of live births was independently associated with aortic dimensions and stiffness in a healthy multi-ethnic population-based cohort, the Dallas Heart Study (DHS). We hypothesized that multiparity (&gt;/=4 live births) is independently associated with aortic dilation and aortic stiffness after adjustment for CV risk factors. Methods: Women with available thoracic aortic MRI measurements (n=1468, mean 44.5 years old) from DHS were stratified based on self-reported number of live births (0,1,2,3,&gt;/=4). Sequential multivariable logistic regression models were used to assess independent associations of the number of live births with ascending aortic cross-sectional area/height, aortic pulse wave velocity (PWV) and aortic compliance. Models were adjusted for major CV risk factors. Results: Women with &gt;/=4 live births were older, more likely to be Black, and had higher blood pressure, triglycerides and body mass index. Compared with nulliparous women, women with &gt;/=4 had larger ascending aortic areas indexed to height [5.19 vs 4.74 cm2/m; p&lt;0.0001; Table 1]. After adjustment for risk factors, multiparity remained a significant predictor of aortic size. Compared to nulliparous women, women with &gt;/=4 live births also had higher aortic PWV (5.54 vs 4.54 m/s; p&lt;0.0001) and lower aortic compliance (21.9 vs 27.2 mL/mmHg; p 0.0002), but these relationships were no longer significant after multivariable adjustment (Table 1). Analyzing live births as a continuous variable did not change these results. Conclusions: Multiparity was associated with thoracic aortic enlargement, independent of age and relevant risk factors. Parity is an emerging sex-specific risk factor in cardiovascular disease that may have an impact on aortic remodeling in women.
Abstract 15928: Relative Sparing of Apical Longitudinal Strain for Detection of Cardiac Amyloidosis: Intervendor Variation
Authors: Julia M Simkowski, Michael Jiang, NADIA El HANGOUCHE, Jeesoo Lee, Milica Marion, Inga Vaitenas, James D Thomas
Journal: Circulation (2020)

Introduction: Relative apical longitudinal strain (RALS) is defined as (average apical LS/(average basal &amp; mid-ventricular LS)). A threshold of 2 has been found to have high sensitivity and specificity for differentiating cardiac amyloidosis (CA) from other causes of left ventricular hypertrophy (LVH). This threshold was developed using General Electric (GE) software, and its reproducibility among different software vendors is unknown. Hypothesis: In patients with CA, regional segmental LS patterns and relative apical longitudinal strain will vary among software vendors. Methods: Speckle-tracking echocardiography was retroactively performed by an experienced technician on two patient cohorts, CA (n=52) and LVH (n=52), using software from two independent vendors: EchoPAC (GE Medical Systems) and TomTEC (TOMTEC Imaging Systems GMBH). For each vendor and patient, strain values for the basal, mid, and apical segments were averaged to obtain three regional LS values which were then used to calculate global longitudinal strain (GLS) and RALS. Results: EchoPAC demonstrated greater average apical LS (-16.5±5.7 vs -13.1±6.6, p&lt;0.001) and RALS (2.1±0.9 vs 1.7±0.7, p&lt;0.001) compared to TomTEC. Bland-Altman analysis yielded a mean bias of -0.4 with limit of agreement 2.2 (p&lt;0.001) in RALS between the two vendors. ROC curve analysis using a RALS cutoff of 2 to differentiate CA from the overall control group showed similarly high specificity (EchoPAC 85%, TomTEC 83%) between vendors but lower sensitivity for TomTEC (23% vs 45%) (Figure 1). LVH subgroup analysis showed similar comparisons. Overall difference in area-under-curve (AUC) was significant (AUC = 0.78 EchoPAC vs AUC = 0.52 TomTEC, p &lt; 0.001). Conclusions: Software measurements of regional LS and thus RALS vary between vendors. Further efforts are needed for intervendor regional strain fidelity. For now, different RALS thresholds to diagnose CA may be needed for various vendors.
Abstract 14634: Hospital Teaching Status and Variation in Outcomes: Evidence From Patients Undergoing Multi-vessel Percutaneous Coronary Interventions
Authors: Temitope Ajibawo
Journal: Circulation (2020)

Background and Objectives: Evidence suggests variations in medical services provided by hospital teaching status. However, there is limited data on how it affects hospital outcomes. The aim of this study is to examine differences in outcomes among patients who underwent multi-vessel percutaneous coronary intervention (MVPCI) stratified by hospital teaching status. Methods: We queried the 2016 Nationwide Inpatient Sample database and identified patients who underwent MVPCI using ICD-10 procedure codes. Hospital teaching status was classified as urban teaching vs. non- teaching. Chi-square and Wilcoxon rank-sum tests were used to compare the following outcomes between hospitals: patient demographics, clinical outcomes, in-hospital mortality, length of stay (LOS), and total charges. Results: Among the 15,611 MVPCI procedures performed, 73.5% were done in teaching hospitals. 68.4% of the MVPCI in teaching hospitals were in males and 54.1% in patients aged ≥65 years. Teaching hospitals had a lower proportion of whites (74.1% vs 79.5%, p&lt;0.001). Teaching and non-teaching hospitals did not differ significantly in impella use (1.7% vs 1.7%, p=0.9928), IABP use (2.2% vs. 2.3%, p=0.7156) and in-hospital mortality (2.0% vs 2.2% p=0.3399). The incidence of acute renal failure (14.0% vs 13.5%, p=0.3858), cardiogenic shock (4.5% vs 4.7%, p=0.5969), cardiac tamponade (0.2% vs 0.2% p=0.5769), and ventricular fibrillation (2.6% vs 2.9%, p=0.2570) did not differ significantly. However, the median length of stay (LOS) (3 vs 2 days, p=0.0075) and hemorrhage requiring transfusion (HRT) (5.6% vs 4.7%, p=0.0414) were significantly greater in teaching centers. In contrast, total hospital charges ($96,465 vs. $106,711, p&lt;0.0001) was lower in teaching centers. Conclusion: Our analysis did not show any differences with regards to in-hospital deaths, IABP use, impella use and many of the hospital outcomes in MVPCI. In teaching centers, the occurrence of HRT and the mean LOS was increased, but there was no increased financial costs.
Abstract 14285: Scoring Tool to Accurately Predict 10 Year Major Adverse Cardiac Events Following Drug-eluding Stent Placement
Authors: Stephen G Ellis, Chetan Huded, A Michael Lincoff, ravi nair, Samir R Kapadia
Journal: Circulation (2020)

Background: Although most drug-eluding stent (DES) patients live longer than 10 years, there is no generally accepted clinical tool to predict risk of major adverse cardiac events (MACE) after DES over that period of time. Methods: Local consecutive patients receiving their first limus-eluting DES from 6/04-6/12 were characterized at baseline and prospectively followed. Patients were randomly allocated to a training or validation cohort, and a predictive Cox model using pre-procedural variables was developed in the training set. This model was then retested in a validation cohort. The primary endpoint was the c-index in the validation cohort. CIF and Fine-Gray were used for sensitivity analysis. Results: Patients (n=1321) had mean follow up of 10±3 years (3% were lost to follow up). Baseline characteristics included age=63±11 years, 65% male, SYNTAX Score=10±7, 1st/2nd Gen DES (%)=42.8/57.2, DES length (mm)=33±22. In the training set, MACE was independently correlated with renal insufficiency (p&lt;0.001), prior CABG (p=0.003), LVEF (p=0.004), restenotic lesion (p=0.013), insulin use (p=0.023), peripheral vascular disease (PVD) (p=0.030), age (p=0.037) and SYNTAX score (p=0.047). Assigning 1 point each to these 8 parameters (and dichotomizing continuous variables at age≥75, LVEF≤35 and SYNTAX score ≥23) resulted in 10 year Kaplan-Meier MACE in the validation set of 0=35.2%, 1=53.0%, 2=79.0%, ≥3=100.0% (figure), c-index= 0.81. Within the low risk group, if complete revascularization could be achieved the risk dropped to 28.2%. Conclusions: Ten year risk of MACE can be accurately modeled using this simple model, with risk ranging from about 30% to nearly 100%.