tbuckley/cabot-search huggingface dataset:
Assessment of Patient Preferences for Telehealth in Post–COVID-19 Pandemic Health Care
Authors: Zachary S. Predmore, Elizabeth Roth, Joshua Breslau, Shira H. Fischer, Lori Uscher-Pines
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Telehealth use greatly increased in 2020 during the first year of the COVID-19 pandemic. Patient preferences for telehealth or in-person care are an important factor in defining the role of telehealth in the postpandemic world. <h3>Objective</h3> To ascertain patient preferences for video visits after the ongoing COVID-19 public health emergency and to identify patient perceptions of the value of video visits and the role of out-of-pocket cost in changing patient preference for each visit modality. <h3>Design, Setting, and Participants</h3> This survey study was conducted using a nationally representative sample of adult members of the RAND American Life Panel. The data were obtained from the American Life Panel Omnibus Survey, which was fielded between March 8 and 19, 2021. <h3>Main Outcomes and Measures</h3> Preferences for video visits vs in-person care were analyzed in the survey. The first question was about participants' baseline preference for an in-person or a video visit for a nonemergency health issue. The second question entailed choosing between the preferred visit modality with a cost of $30 and another modality with a cost of $10. Questions also involved demographic characteristics, experience with video visits, willingness to use video visits, and preferences for the amount of telehealth use after the COVID-19 pandemic. <h3>Results</h3> A total of 2080 of 3391 sampled panel members completed the survey (participation rate, 61.3%). Participants in the weighted sample had a mean (SE) age of 51.1 (0.67) years and were primarily women (1079 [51.9%]). Most participants (66.5%) preferred at least some video visits in the future, but when faced with a choice between an in-person or a video visit for a health care encounter that could be conducted either way, more than half of respondents (53.0%) preferred an in-person visit. Among those who initially preferred an in-person visit when out-of-pocket costs were not a factor, 49.8% still preferred in-person care and 23.5% switched to a video visit when confronted with higher relative costs for in-person care. In contrast, among those who initially preferred a video visit, only 18.9% still preferred a video visit and 61.7% switched to in-person visit when confronted with higher relative costs for video visits. <h3>Conclusions and Relevance</h3> This survey study found that participants were generally willing to use video visits but preferred in-person care, and those who preferred video visits were more sensitive to paying out-of-pocket cost. These results suggest that understanding patient preferences will help identify telehealth's role in future health care delivery.
Abstract 13271: Combined Assessments of Monogenic and Polygenic Risk for Dilated Cardiomyopathy
Authors: Krishna G Aragam, Kiran Biddinger, Sean J Jurgens, Minxian Wang, James Pirruccello, Dimitri Maamari, Mark Chaffin, Seung H Choi, Valerie Morrill, Christopher Newton-cheh, Amit V Khera, Steven A Lubitz, Patrick T Ellinor
Journal: Circulation (2021)

Introduction: Genetic testing for non-ischemic dilated cardiomyopathy (DCM) currently comprises assessment of rare (monogenic) mutations in DCM-relevant genes. The role of a common-variant (polygenic) predictor for DCM has yet to be evaluated. Methods: Leveraging genotyping array and exome-sequencing data from UK Biobank, we curated monogenic, predicted loss-of-function (LOF) mutations in 91 genes on clinical genetic testing panels for DCM, and tested their prevalence and penetrance. Next, we constructed and evaluated a polygenic score for DCM from measures of left ventricular structure and function by cardiac magnetic resonance imaging. Finally, we combined monogenic carrier status with the polygenic score to estimate aggregate genetic risk for DCM. Results: Among study participants (N= 166,690), mean age was 57 (SD, 8.1) years, 75,154 (41%) were male, and 336 (0.21%) had DCM. 14.4% of DCM cases harbored a disease-relevant LOF mutation, including 8.8% within cardiac exons of the sarcomeric gene TTN . LOF mutations in TTN (OR, 25.36), DSP (OR, 17.55), and RBM20 (OR, 12.85) were the most strongly associated with dilated cardiomyopathy (all P &lt; 0.001). 0.7% of all LOF carriers - and 4.0% of LOF carriers in TTN - developed DCM. A polygenic score comprising 2.3 million common genetic variants was strongly associated with DCM in all participants (OR per SD=1.62, p=8.61E-39), and in non-carriers (OR per SD=1.60, p=6.28E-15; N=159,811) and carriers (OR per SD=1.79, p=4.76E-05; N=6,879) of LOF mutations. Comparing the top and bottom 20% of the polygenic score, a &gt;3-fold risk difference was observed among non-carriers of TTN LOF, and a &gt;10-fold risk difference among TTN LOF carriers. TTN LOF carriers with high polygenic risk were at 46-fold odds of developing DCM as compared to non-carriers with intermediate polygenic risk (p=4.16E-29). Conclusions: Combining monogenic and polygenic risk expands the scope and improves the precision of clinical genetic testing for DCM.
Abstract P331: Upregulated TBX1 by genetic variants are associated with human congenital heart disease
Authors: Liwei Yu, Binbin Li, Hongyan Wang
Journal: Circulation Research (2021)

Congenital heart disease (CHD) is the most common human birth defect worldwide. The cause of CHD is so far not well understood. Uncovering genetic factors leading to CHD is still a pressing task to be solved. TBX1 is one of the transcription factors early expressed in embryonic cardiac progenitors. In animal models, imbalanced TBX1 activity leads to cardiac defects. Given the dosage effect of TBX1, it is possible that genetic variant altering TBX1 function or expression level would affect heart development and contribute to CHD. In order to study the association of genetic variants of TBX1 and CHD susceptibility, we performed genetic screening in 409 CHD patients and 213 healthy controls. Bioinformatic and in vitro functional studies were performed to evaluate the impact of genetic variants. One single nucleotide polymorphism (SNP), rs41260844, in TBX1 promoter region was identified to be associated with CHD. The minor allele of rs41260844 is associated with higher CHD risk and shows increased TBX1 promoter activity (Fig A). Further study showed the minor allele attenuates TBX1 promoter binding affinity with nuclear protein(s) (Fig B). In addition, a novel case-specific missense rare mutation, p.P164L, in T-box domain was identified and predicted as a deleterious mutation. Functional analysis showed a trend of increased TBX1 function with the rare mutation. In summary, we concluded that a higher TBX1 expression level or activity is associated with CHD susceptibility, which could affect TBX1 downstream targets and thus disrupt the balance of the complex regulation network during cardiogenesis.
Abstract 10659: Blood DNA Methylation at TXNIP and Glycemic Changes in Response to Weight-Loss Diet Interventions: The POUNDS Lost Trial
Authors: Xiang Li, Xiaojian SHAO, Qiaochu Xue, Elin Grundberg, George Bray, Frank Sacks, Lu Qi
Journal: Circulation (2021)

Introduction: Thioredoxin Interacting Protein ( TXNIP ) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5'-cytosine-phosphate-guanine-3' (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes; however, little is known about whether the DNAm level at TXNIP in blood is associated with glycemic changes in response to weight-loss diet interventions. Hypothesis: We hypothesized that participants with varying DNAm level of TXNIP responded differentially to weight-loss diet interventions on glycemic changes. Method: We included 639 overweight and obese participants from Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, who were randomly assigned to 1 of 4 weight-loss diets varying in macronutrient contents. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. We defined regional methylation level of TXNIP as average methylation level over CpGs within 500 bp of cg19693031. Results: Higher regional methylation level at TXNIP was correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (p&lt;0.05 for all). Participants with distinct regional methylation level of TXNIP showed significantly different changes in fasting insulin (p-interaction=0.007) and HOMA-IR (p-interaction=0.009) in response to average- vs. high-protein diet intervention at 6 months, independent of weight loss. Among participants with an average-protein diet, higher regional methylation level at TXNIP was associated with a greater reduction of fasting insulin and HOMA-IR at 6 months, while an opposite association was found among those with a high-protein diet. Such difference was attenuated to be nonsignificant at 2 years. Conclusions: DNAm level at TXNIP in blood may modify the effects of diet interventions on changes in glycemic traits, independent of weight loss. Overweight and obese individuals with higher methylation level at TXNIP may benefit more in improving insulin and HOMA-IR by consuming an average-protein diet than a high-protein diet.
Preeclampsia Predicts Risk of Hospitalization for Heart Failure With Preserved Ejection Fraction
Authors: Dominique Williams, Molly J. Stout, Joshua I. Rosenbloom, Margaret A. Olsen, Karen E. Joynt Maddox, Elena Deych, Victor G. Davila-Roman, Kathryn J. Lindley
Journal: Journal of the American College of Cardiology (2021)
Abstract 13165: Increasing Incidence Rates and High Case Fatality Rates for Acute Myocardial Infarction in the Caribbean Island of Barbados
Authors: Natasha Sobers, Shelly-ann Forde, Ian Hambleton, Ashley Henry, Nicolette Roachford, Abigail Robinson, Martinette Forde, rudolph Delice, Angela M Rose
Journal: Circulation (2021)

Introduction: The Caribbean sub-region has the highest rates of cardiovascular disease in the Region of the Americas. We present data from one of the few population-based registries in the region - the Barbados National Registry for NCDs (BNR). We describe trends in incidence and case fatality rates for acute myocardial infarction(MI) in the high income small island developing state of Barbados. Hypothesis: Myocardial infarction age-standardized incidence rates (ASIRs) are increasing. Methods: Data from the BNR were collected prospectively from charts of patients diagnosed with acute myocardial infarction from all private and public hospitals for the period 2010-2019. Out-of-hospital deaths and in-hospital deaths within 24 hours, were identified through the national vital registration department. Cases are defined in accordance with the Universal Definition of Myocardial Infarctions published by the American Heart Association. Population estimates were obtained from the United Nation World Population Prospects. We calculated incidence rates by sex, age-standardized to the World Health Organization 2000 population and assessed trends in case fatality rates for those admitted to hospital. Results: For the period 2010-2019, 4065 cases of as myocardial infarction (MI) were registered by BNR. Numbers of cases ranged from 294 in 2011 to 547 in 2019. The 3-year average for 2014 - 2016 is 391 cases versus 499 cases for 2017 - 2019 - a 28% increase in new cases. ASIRs increased from 67 per 100,000 (95%UI 59 to 75) in 2011 to 123 per 100,000 (95%UI 113 to 135) in 2019. ASIRs were consistently higher in men ranging from 83 per 100,00 (95% UI 71 - 98) to 120 (95% UI 106 to 136) while rates in women ranged from 43 per 100,000 95% CI (35 - 53) to 83 per 100,000 (73 - 95). The in-hospital case fatality rate (CFR) was 25% in 2019, ranging from 15% in 2011 to 31% in 2014. Overall, CFR was higher in women (24%) versus men (19%) and this was true in 9/10 years. Conclusions: Despite its status as a high income country, ASIRs for MIs in Barbados are increasing while case fatality rates are more than twice as high as rates found in developed countries.
STEM-11. HYDROGEN SULFIDE FUNCTIONS AS A TUMOR SUPPRESSION IN GLIOBLASTOMA
Authors: Daniel J Silver, Gustavo Roversi, Nazmin Bithi, Sabrina Wang, Katie M Troike, Chase K Neumann, Grace Ahuja, Ofer Reizes, J Mark Brown, Christopher Hine, Justin Lathia
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) cancer stem cells (CSCs) respond to a variety of stimuli within their immediate surroundings. However, little is known about the lifestyle factors that alter CSC enrichment and function within the tumor microenvironment (TME). To examine the consequences of diet-induced obesity on the progression of GBM, we interrogated tumor growth using patient-derived and syngeneic GBM models implanted into the brains of mice fed either an obesogenic high-fat diet (HFD) or a low-fat, control diet. HFD consumption resulted in an accelerated disease trajectory, presenting significantly shortened overall survival. HFD reshaped the TME altering the lipid landscape, enhancing the CSC phenotype, stimulating tumor cell proliferation, and protecting from necrotic cell death. Similar results were not observed in metabolically obese, leptin-deficient (ob/ob) mice. We simultaneously identified a potent suppression of the gasotransmitter, hydrogen sulfide (H2S). H2S functions principally through protein S-sulfhydration and regulates multiple programs including bioenergetics, metabolism, and immune response. Inhibition of H2S increased tumor cell proliferation and chemotherapy resistance, whereas treatment with H2S donors reduced tumor cell fitness in vitro and attenuated GBM growth in vivo. Exogenous treatment with H2S donors also rescued the lipid-mediated increase in tumor cell proliferation. As H2S exerts its action though protein S-sulfhydration, we confirmed that HFD-fed mice, which experienced decreased H2S synthesis, presented a severely depleted S-sulfhydrated protein landscape. Loss of this post-translational modification was confirmed in GBM patient tissues compared to age- and sex-matched controls. Taken together, our findings provide evidence that H2S functions as a tumor suppressor in GBM. Our observations highlight a new mechanism for tumor growth dynamics that can be leveraged for new therapeutic strategies focused on boosting H2S. Finally, our findings indicate that lifestyle factors can have pleiotropic effects on GBM progression through concomitant mechanisms involving tumor metabolism, modifications to the TME, and regulation over the CSC phenotype.
Abstract 12160: Predicting Atrial Fibrillation Recurrence After Thoracoscopic Ablation by Left Atrium Appendage Emptying Velocity
Authors: Minjung Bak, Jihoon KIM, Sung-ji Park, Eun Kyoung Kim, Dong Seop Jeong
Journal: Circulation (2021)

Introduction: Totally thoracoscopic ablation (TTA) is the latest tool for in patient with persistent or long-standing atrial fibrillation (AF). Left atrium appendage (LAA) emptying velocity is known related with maintenance sinus rhythm after successful cardioversion and catheter ablation. There were no studies about the value of LAA emptying velocity in thoracoscopic ablation since now. Hypothesis: We assessed the hypothesis that LAA emptying velocity could predict AF recurrence also in patient who underwent TTA. Methods: Between February 2012 and March 2015, 150 patients underwent TTA in a tertiary center in South Korea. The primary outcome was AF recurrence detection in either 12-lead electrocardiogram or holter during 3 years after TTA, excluding initial 3 months of blanking period. After baseline characteristics comparison between no AF recurrence group and AF recurrence group, main contributing factor for AF recurrence was analyzed with multivariable cox regression. Additionally, time-dependent ROC (receiver operating characteristic) analysis was done to estimate predictive power of LAA emptying velocity for AF recurrence. Results: Proportion of paroxysmal AF and LAA emptying velocity were higher in no AF recurrence group. LA volume size was larger in AF recurrence group. Except these values, other clinical characteristics like age, sex, underlying disease, CHA 2 DS 2 -VASc score, history of RFCA, use of antiarrhythmic drug or surgical method were not significantly different. In multivariable cox regression, female sex (HR 2.474, 95% CI [1.036-5.905], p value=0.041) and LAA emptying velocity (HR 0.941, 95% CI [0.915-0.967], p value&lt;0.001) were meaningful contributing factor for AF recurrence. Also, LAA emptying velocity showed modest degree predictive performances for predicting AF recurrence (AUC 0.754, 95% CI [0.675 - 0.834])(figure 1). Conclusions: In conclusion, LAA emptying velocity could predict AF recurrence after TTA.
Timing of Tocilizumab and Corticosteroids Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia
Authors: Yinqiang Zhang, Heng Mei, Chenggong Li, Yingnan Li, Mengyi Du, Wenjing Luo, Lu Tang, Jianghua Wu, Linghui Xia, Yu Hu
Journal: Blood (2021)
Abstract 13262: Improved Rabbit Model of Calcific Aortic Valve Disease Induces Severe Medial Calcification and Stenosis Equivalent to Human Disease
Authors: Nikolaos Anousakis-Vlachochristou, Manolis Mavroidis, Dimitra Athanasiadou, Aimilia Varela, Manousos Makridakis, Maria Katsa, Antigoni Miliou, Dimitra Lali, Karina Carneiro, Antonia Vlahou, Nikolaos Thomaidis, Constantinos D Anagnostopoulos, Dennis V Cokkinos, Costas Tsioufis, Konstantinos Toutouzas
Journal: Circulation (2021)

Introduction: Accurate animal models of calcific aortic valve stenosis (CAVS) are needed to get insights into the early stages. We had previously modified a rabbit model to achieve CAVS. Here, we sought to assess its ability to produce similar lesion to humans. Methods: New Zealand rabbits were randomized to normal diet or +1% cholesterol + 3500 I.U.s/kg Vitamin D2 daily. Aortic valve area was assessed with echocardiography. At 7 weeks, blood serum and valve cusps were retrieved from sacrificed animals. Valve cusps were ex-vivo imaged with 18F-NaF microPET/CT, snap-frozen or formalin-fixed. Cusps were homogenized with an optimized protocol. Pyrophosphate (PPi) was measured in serum and cusps, metabolites analyzed with LC-MS/MS. Phosphatase activity was detected with BCIP/NBT assay. Protein content was analyzed with immunohistochemistry, quantitative ELISA and proteomics analysis (LC-MS/MS), and compared to human databases. Fixed cusps were analyzed using FT-IR and imaged with atomic force, scanning and transmission electron microscope. EDX chemical maps were obtained from the regions of interest Results: Vitamin D and metabolites were validated in serum and tissue. Echocardiography confirmed significant valve stenosis. Sodium fluoride activity was quadrupled in experimental valves. Histology revealed severe medial calcification, positive for osteopontin, negative for TNAP, BSPII and osteocalcin. Endogenous phosphatase activity colocalized with calcification in the medium. Serum PPi levels were increased, and tissue PPi levels were decreased. Proteomics analysis revealed 96 differentially expressed proteins validating important proteins, including apolipoproteins, complement, osteonectin, matrix Gl(a), galectin-3, fetuin-A, sortiltin, and TGF-b axis proteins. Ultrastructural analysis revealed the pathognomonic calcified spherical particles composed predominantly of phosphorus in the experimental valves. Conclusions: The improved high-fat - vitamin D toxicity rabbit model produced severe phosphate-induced CAVS, with similar protein and ultrastructural content to human disease, related to TGF-b pathway. Further investigations are needed in the underlying molecular networks driving the lesion.
Abstract 14346: High Intensity Exercise Increases Cardiorespiratory Capacity in a Preclinical Hypertrophic Cardiomyopathy Mouse Model
Authors: Jonathan J Herrera, Danielle Szczesniak, Kate Szczesniak, Pranjal Gaur, Miranda Manzo, Rose-Carmel Goddard, Jaime Yob, Jil C Tardiff, Sharlene Day
Journal: Circulation (2021)

Introduction: Patients with Hypertrophic Cardiomyopathy (HCM) who possess greater cardiorespiratory capacity (pVO 2 ) are at lower risk for heart transplant and mortality. High intensity exercise (HIE) training used in cardiac rehabilitation for heart failure and cardiovascular disease results in superior increases in pVO 2. The purpose of this investigation was to evaluate the effects of high intensity interval training (HIIT) on pVO 2 , as well as cardiac structural and functional parameters known to be altered by exercise in a transgenic cardiac troponin T (TG) HCM mouse model. Methods: Female and male C57BL/6J non-transgenic nTG (n=27) and TG (n=32) mice underwent a translationally parallel cardiac rehabilitation HIIT protocol. One treadmill training bout included 4-4 minute high intensity intervals (~80% preVO2 max speed) interspersed by 5-3 minute recovery intervals (~50% preVO2 max speed) for 31 total minutes. Bouts were repeated 3 times/wk for 6 wks. Pre and post HIIT pVO 2 and murine echocardiography were measured and analyzed by a blinded technician. Results: Following 6 weeks of the HIIT, nTG female (+13.5 mL/kg/min ± 3.6, p&lt;0.01), nTG male (+13.5 mL/kg/min ± 3.6, p&lt;0.01) and TG female (+7.06 ± 3.3 mL/kg/min, p&lt;0.05) mice demonstrated an average increase in pVO 2 . TG male mice did not reach statistical significance (+4.34 ± p=0.12). Sedentary female (-15.9 mL/kg/min ± 3.3,p&lt;0.001) and male (-13.1 mL/kg/min ± 3.9, p&lt;0.01) TG control mice experienced a significant decrease in pVO 2 following the same period, while no change was observed in nTG sedentary controls. Independent of sex, nTG and TG HIIT mice had a significantly greater change in pVO 2 compared to sedentary counterparts. HIIT training did not result in changes to the following echocardiography measures in either nTG or TG mice: LV mass, LA volume, cardiac output, or stroke volume. Conclusions: Our results indicate that a translationally derived HIIT protocol improves cardiorespiratory capacity in HCM mice, absent of any adverse events or worsening of organ level disease pathology.
Abstract 14371: Incidence of Cardiogenic Shock in In-Hospital vs Out of Hospital ST-elevation Myocardial Infarction
Authors: Raunak Nair, Nicholas Kassis, Anirudh Kumar, Chetan P Huded, Michael J Johnson, Kathleen A Kravitz, Grant W Reed, Amar Krishnaswamy, Venu Menon, A M Lincoff, Stephen Meldon, Damon M Kralovic, Samir R Kapadia, Umesh N Khot
Journal: Circulation (2021)

Background: Cardiogenic shock (CS) remains the most common cause of death in patients with acute myocardial infarction. We aimed to study if the incidence of CS is different in patients who develop in-hospital STEMI compared to patients admitted with out-of-hospital STEMI (Direct STEMI). Methods: All STEMI patients who underwent Percutaneous Coronary Intervention (PCI) at the Cleveland Clinic main campus between January 1, 2011, to July 15, 2019, were included in our study. Patients were classified depending on the location of STEMI into in-hospital or out of hospital (direct STEMI) and the incidence of cardiogenic shock was compared between both the groups. Results: There were a total of 1715 patients who were admitted to our hospital with STEMI from outside (direct STEMI) compared to 132 patients who developed in-hospital STEMI. Baseline characteristics were quite similar except for a higher prevalence of smoking in the direct STEMI group and a higher prevalence of prior PCI and prior heart failure in the in-hospital STEMI group. We found that 25.8% of patients with In-hospital STEMI developed cardiogenic shock whereas only 7.9% of patients with direct STEMI developed cardiogenic shock. Conclusion: Patients with in-hospital STEMI are three times more likely than direct STEMI patients to develop cardiogenic shock. Integration of therapeutic strategies around cardiogenic shock may be important in improving outcomes of this high-risk group of patients with STEMI.