tbuckley/cabot-search huggingface dataset:
Abstract 11738: Outcomes and Readmissions of ST-Elevation Myocardial Infarction With Cardiogenic Shock Patients Supported by Temporary Mechanical Circulatory Support
Authors: Ernesto A Ruiz, Ilias P Doulamis, Polydoros Kampaktsis, Toshiki Kuno, Aaqib Malik, Alexandros Briasoulis
Journal: Circulation (2021)

Introduction: Despite advances in the field of temporary mechanical circulatory support (TMCS), in-hospital mortality and morbidity related to cardiogenic shock due to ST elevation myocardial infarction (CS-STEMI) remain high. Hypothesis: We sought to investigate readmissions and respective outcomes among patients with CS-STEMI supported by TMCS. Methods: The National Readmission Database (NRD) was queried to identify adults who were admitted with CS-STEMI between 2016 and 2018 using the International Classification of Diseases, Tenth Revision (ICD-10) codes. Patients with sepsis, pulmonary embolism, cardiac tamponade, aortic dissection, or missing data were excluded. Results: A total of 7,501 patients did not undergo TMCS implantation, while the rest received various types of TMCS (ECMO alone: n=3,659; IABP alone: n=1,268; Impella alone: n=293; ECMO with IABP or Impella: n=525). Readmissions occurred in 16.7% and 25.1% by 30 and 90 days, respectively, with most readmissions occurring in patients requiring ECMO and IABP or Impella ( Table 1 ). Multivariable logistic regression revealed age, female gender, diabetes, prior CABG, previous stroke, liver disease and Elixhauser score as risk factors for in-hospital mortality ( Table 2 ). Conclusions: Our study has unveiled several important factors associated with readmission and mortality. Approaches to identify and prevent readmissions early after TCMS by addressing these factors may lead to lower morbidity, healthcare cost related to readmission, and improved quality of life.
A Descriptive Analysis of Immune Thrombotic Thrombocytopenic Purpura (iTTP) Patients with Fatal Outcomes in the U.S. Thrombotic Microangiopathy (USTMA) TTP Registry
Authors: Mouhamed Yazan Abou-Ismail, Chong Zhang, Angela Presson, Marshall Mazepa, Ming Yeong Lim, United States Thrombotic Microangiopathies Consortium Investigators
Journal: Blood (2021)
Abstract 11023: Assessment of Cognitive Dysfunction Using the Montreal Cognitive Assessment Test: Rate, Severity and Comparison with the Clock Test Alone in a Population of Patients Referred for TAVI
Authors: Charles Monnin, Matthieu Besutti, Fiona Ecarnot, Benoit Guillon, Marion Chatot, Romain Chopard, Mohamed Chouaib Yahia, Nicolas Meneveau, Francois Schiele
Journal: Circulation (2021)

Introduction: Although not recommended in routine practice, the detection and quantification of Cognitive Dysfunction (CD) in older patients might have an impact on clinical decisions. Hypothesis: We assessed the rate and severity of CD in an unselected population of patients referred for Transcatheter Aortic Valve Implantation (TAVI) using the Montreal Cognitive Assessment (MoCA) and using the Clock Drawing Test (ClockT) alone. Methods: The MoCA was performed before TAVI by an experienced operator. The ClockT was scored out of 10 points according to the Rouleau rating scale. CD was defined according to the MoCA score: No CD if score ≥26, mild CD if score 18-25, moderate if 10-17 and severe if &lt;10. Inter-observer reliability of scoring on the ClockT was estimated with the Bland-Altman method. Agreement between MoCA scores and the ClockT for ruling out and for detecting CD were measured with the Kappa coefficient. Results: MoCA was performed in 83 consecutive patients referred for TAVI, median age 85 years. The mean time required for assessment was 11±2 min for the MoCA and 3±2 min for the ClockT. The mean MoCA score was 21± 4.5: CD was excluded in 17(20%) pts, mild CD was found in 50(60%), moderate in 15(18%) and severe in one (1%). The median ClockT score was 8 (interquartile 6; 9), with excellent inter-observer concordance (Kappa= 0.84). Overall, 51% of the variance of the MoCA score was explained by the ClockT alone according to multiple regression. A ClockT &lt;7 detected a group with significantly lower MoCA score, compared to pts with higher ClockT scores (figure). Conclusions: Among patients referred for TAVI, CD can be excluded using the MoCA test in 20%, while moderate or severe CD is observed in 18%. The ClockT alone is faster to implement, reliable to interpret and enabled detection of patients with moderate CD when Rouleau scoring was &lt;7.
Abstract 13035: A Potent Protective Vascular Endothelium Property of Garcinia mangostana L. Extract in High-Risk Framingham Score Patients With Type 2 Diabetes: A Prospective Randomized Control Trial
Authors: Olivia Handayani
Journal: Circulation (2021)

Background: Endothelial dysfunction is the hallmark of vascular complications in cardiovascular disease with type 2 diabetes as the comorbid. Garcinia mangostana L., or mangosteen, has been known a...
Abstract 12465: Clinical Results of a Novel Chest-Based Wearable During Transcatheter Aortic Valve Replacement Surgery for Real-Time Remote Monitoring
Authors: Alexi Charalambides, Rohith Krishnan Pillai, Maahin Beri, Jesse Carpenter, Brian Stancil, Carmel Majidi, Philip Leduc, Louis Rauso, Dustin Kliner, Derek Serna-Gallegos, Catalin Toma, Saurabh Sanon, Ibrahim Sultan
Journal: Circulation (2021)

Objective: Transcatheter Aortic Valve Replacement (TAVR) is the most common strategy for treating stenotic aortic valves in older adults. However, up to 18% of patients in the US are readmitted within 30 days, with about a third of these patients readmitted due to cardiac issues [1]. It would therefore be desirable to monitor discharged patients remotely to catch early signs of deterioration before more serious complications occur, and thereby reduce hospital readmission rates. The current gold standard for arrhythmia monitoring involves a single-lead Holter monitor in the form of a wearable chest-based patch. However, these devices usually do not track cardiac rhythms in real-time, and are typically mailed in after the wear period is over resulting in further delays. Methods: A novel chest patch capable of single-lead ECG that achieves real-time monitoring via Bluetooth and smartphone communications was used. To validate, the patch was placed on the chest of patients undergoing a TAVR; ECG was recorded and compared to gold-standard equipment. Results: ECG rhythms were collected from four patients using the patch and compared to an institutional hemodynamic monitoring system (GE MACLAB). The ECGs from each system were time aligned using a Fourier Transform method [2], R-peaks were identified using the Pan-Tompkins algorithm, heart rates were calculated over the course of the procedure by averaging R-R intervals over a 10 sec sliding window, and lastly Pearson correlation coefficients were calculated between the patch and gold-standard equipment. Pearson coefficients ranged from 0.995 to 0.999 with a Mean Absolute Error of 0.55 BPM and Root Mean Square Error of 2 BPM (see fig). Conclusion: These early results suggest an excellent agreement and accuracy between the wearable device and gold-standard ECG equipment, and may pave the way for monitoring discharged patients remotely. [1] Kolte, Dhaval et al 2017 [2] Fridman, Lex et al 2016
Abstract 12100: Exploration of Proteomic Risk Markers for Incident Heart Failure and Cardiac Remodeling in Three European Population-Based Cohorts
Authors: Anna Dieden, Amra Jujic, Filip Ottosson, John Molvin, Manan Pareek, Olle MELANDER, Lennart Råstam, Ulf Lindblad, Bledar Daka, Margret Leosdottir, Hannes Holmes, Peter Nilsson, Michael Hecht Olsen, Kevin Duarte, Faiez ZANNAD, Nicolas Girerd, Martin Magnusson
Journal: Circulation (2021)

Introduction: Several biomarkers have been linked with incident heart failure (HF), but the pathophysiology of HF is complex and multifactorial. Hypothesis: We explored 92 biomarkers’ associations with left ventricular hypertrophy (LVH), prevalent LV diastolic dysfunction (LVDD), and incident HF in three European population-based cohorts. Methods: Profiling of 92 biomarkers was carried out in 1737 participants from the echocardiography subsample of the population-based cohort study, the Malmö Preventive Project (mean age 67 years, 29% women). The final study sample consisted of 1681 subjects for analyses of incident HF (n=130), and 1530 subjects for analyses of LVDD (n=109) and LVH (n=498). Multivariable Cox regression analyses excluding subjects with prevalent HF were carried out for incident HF. Multivariable logistic regression analyses excluding subjects with reduced or mid-range LV ejection fraction (&lt;50%) were carried out for LVDD and LVH. Replication analyses of significant findings were carried out in the HOMAGE (562 cases of incident HF, 871 controls) and STANISLAS cohorts (304 cases of LVDD and 1668 controls; and 245 cases of LVH and 1681 controls). Results: In the multivariable model adjusted for clinical risk factors, six proteins were associated with incident HF (median follow-up time 12.6, interquartile range 10.9-13.6 years): ST2 (hazard ratio (HR) 1.40; 95% confidence interval (1.03-1.91); p=0.031), GDF-15 (HR 1.33 (1.00-1.77); p=0.048), AZU1 (HR 1.42 (1.10-1.82); p=0.006), MPO (HR 1.48 (1.02-2.15); p=0.041), Gal-4 (HR 1.37 (1.02-1.85); p=0.038) and NT-proBNP (HR 1.98 (1.66-2.36); p=2.1x10 -14 ) in the discovery cohort. In the replication cohort, ST2, GDF15, NT-proBNP and Gal-4 also displayed significant associations with incident HF. In analyses of DD, none of the associated proteins in the discovery cohort (AZU1; TR; PCSK9 and NT-proBNP) were replicated in the STANISLAS cohort. Among AZU1, PGLYRP1, and NT-proBNP, NT-proBNP was the only protein that was significantly associated with LVH in both cohorts. Conclusions: We replicated the association of ST2, GDF-15, NT-proBNP and Gal-4 with incident HF, whereas NT-proBNP was the only biomarker that was associated with LVH as well as incident HF in discovery and replication cohorts.
Abstract 11049: Rare Genetic Variants in Individuals with Low ASCVD Risk and Hard Chd or High Coronary Artery Disease: Multi-Ethnic Study of Atherosclerosis
Authors: Mahsima Shabani, Diptavo Dutta, Wendy Post, Charles J Lowenstein, Bharath Ambale Venkatesh, Nilanjan Chatterjee, Matthew Budoff, Stephen S Rich, Jerome I Rotter, Dan E Arking, Joao Lima
Journal: Circulation (2021)

Introduction: Even though various risk estimators are widely used to predict atherosclerosis from subclinical levels to hard CHD, there is a remarkable proportion of low-risk individuals with inordinately high coronary artery calcification (CAC) or with hard CHD events. Rare pathogenic variants (&lt;0.1%) in the atherosclerosis gene panel with larger effect sizes may predispose low-risk individuals to develop atherosclerosis. Hypothesis: There are rare pathogenic variants in the atherosclerosis gene panel in low-ASCVD-risk individuals with high CAC scores or hard CHD events than low-risk individuals with a CAC score of zero or no events. Methods: The MESA whole-genome sequencing data (2000-02) was evaluated to capture variants in 224 atherosclerosis-related genes. Coding variants with a frequency of &lt;0.1% in each racial/ethnic group and damaging effects were assessed by the ClinVar and ACMG-AMP guidelines for pathogenicity. Participants with an ASCVD score of &lt;7.5% were defined as low risk. Two different case groups were defined based on (1) hard CHD events and (2) CAC scores higher than the 90 th percentile of age, sex, and race-adjusted reference scores. Associated control groups were age-, sex-, and race-matched participants with no CHD events or zero CAC score. Results: A total of 159 cases with high CAC and 1256 matched controls were evaluated within the low-risk group. In the case group, there were three rare, likely pathogenic variants ( LDLR c.681C&gt;G, p.D227E and c.2026G&gt;A, p.G676S; and AHI1 c.2168G&gt;A, p.R723Q ) . None of these variants were observed in the control group. A total of 86 cases had a hard CHD event, among whom two had rare, likely pathogenic variants ( KCNQ1 c.517G&gt;A, p.A173T and LDLR c.1201C&gt;G, p.L401V). None of the 1546 controls had these variants. The LDLR c.1201C&gt;G variant is currently a variant of uncertain significance that would be likely pathogenic with the assumption of genotype-phenotype specificity [pathogenicity supporting criterion 4]. Conclusions: We observed five likely pathogenic variants in atherosclerosis-related genes in low-risk individuals for ASCVD who had high CAC scores or hard CHD events. Rare variants with large effect sizes may unravel the missed risk prediction of a common trait like atherosclerosis.
Abstract 11284: Relationship of Inflammatory Cytokines and Six-Month Hospital Readmission in Heart Failure
Authors: Teresita Corvera-Tindel, Lynn V Doering
Journal: Circulation (2021)

Hospital readmission rates (HRR) in heart failure (HF) remains high. Psychosocial and clinical factors are linked with HF hospital readmission. Brain natriuretic peptide (BNP) is strongly associated with acute decompensated HF. However, the relationships of inflammatory cytokines (i.e. tumor necrosis factor-alpha [TNFα], interleukin-6 [IL6], interleukin-10 [IL10]) and HRR in HF are rarely evaluated. Objective: Evaluate the relationship of BNP, TNF-α, IL6 and IL10 with all-cause HRR within 6 months post-HF hospital discharge. Methods: A cross-sectional study was conducted in 104 HF patients: age 68.4 ± 11.7 years, left ventricular ejection fraction 37.9% ± 17%, Specific Activity Scale (SAS) I/II- 40 (39%), and III/IV- 64 (61%) , Charlson Comorbidity Index (CCI) score: 0-1= 24%, 2-3= 26%, and =/&gt;4= 50%. Hospital readmission rate is the number of hospital readmissions of all causes occurring 2 weeks to 6 months after HF hospital discharge. Initially, we analyzed bivariate correlations of HRR with sociodemographic, depression (via Hamilton depression rating scale [HDRS] score), functional status, comorbidities, BNP, and inflammatory cytokines (i.e. TNF-α, IL-6 and IL10). A multiple linear regression was performed, with important and significant psychosocial and clinical variables entered first as a block, followed by BNP and inflammatory cytokines. Results: Incidence of 6-month HRR: 0= 49 (47%); 1-2= 43 (41%); 3-6= 12 (12%). Bivariate correlation of HRR with: 1) sociodemographic: age- ( r = .21, p= .02), non-white- 37% ( r = .04, p= .36), living alone- 42% ( r = .17, p= .04); 2) functional status: SAS ( r = .28, p= .002); 3) CCI score ( r = .21, p= .02); 3) HDRS score ( r = .14, p= .07); 4) BNP: ( r = .14, p= .08); and 5) inflammatory cytokines: IL6 ( r = .41, p= &lt;.001, and IL10 ( r = .16, p= .06). Together, age, living alone, being non-white, HDRS score, SAS, CCI score, and IL6 accounted for 24% of the variance in HRR (p= .001). Specific variables contributing significant variance to HRR were: higher IL6- 34% (p= .001), and living alone= 14% (p= .10). Conclusion: Six-month HRR in HF remains high. Higher IL6 is associated with high HRR. After HF hospital discharge, patients with high inflammatory cytokines may require more frequent monitoring and intervention.
EXTH-39. DUAL CHLOROTOXIN CAR AND MGMT ΓΔ T CELLS FOR DRUG RESISTANT IMMUNOTHERAPY OF GLIOBLASTOMA MULTIFORME
Authors: Lei Ding, Lawrence Lamb
Journal: Neuro-Oncology (2021)

Abstract While recent advances in immunotherapies have shown promise in extracranial tumors, Glioblastoma Multiforme (GBM) has remained challenging. We have previously developed a novel approach to the treatment of primary GBM by combining simultaneous intracranial administration of gene-modified γδ T cells expressing O-6-Methylguanine-DNA Methyltransferase (MGMT) and standard temozolomide (TMZ) chemotherapy. To further improve tumor targeting and the efficacy of the γδ T cell against GBM, we modified γδ T cells with a CAR using chlorotoxin (CLTX), a small peptide derived from scorpion venom that specifically binds the glioma-specific chloride channel, as binding domains (CLTX-CARs). MGMTp140k was co-expressed within the same CLTX-CAR vectors to confer TMZ resistance to the CAR-T cells. We optimized the CAR constructs as CLTX-CD8a-CD28TM-CD28co-CD3z-P2A-MGMT and the activation of CD69 was verified in CLTX-CAR transduced Jurkat T cells with GBM cell co-culture. We further tested dual-CLTX-CAR constructs with 2x CLTX peptide as binding domains (dCLTX-CAR) and demonstrated dCLTX-CAR-Jurkat T cells can activate T cells efficiently with improved persistence compared to the mono-CLTX-CAR-Jurkat T cells 3 weeks after transduction (84% vs 37%). In order to preserve the powerful innate-recognition properties of γδ T cells, we developed CLTX-CARs without CD3z activation domain (NoZ-CLTX-CAR) to mitigate activation induced cell death (AICD) and tonic signaling issues. NoZ-CLTX-CAR-Jurkat T cells showed no CD69 activation with GBM cells co-culture and superior CAR-T persistence compared to CLTX-CARs with a CD3z signaling domain. Furthermore, we were able to efficiently transduce (up to 70% transduction efficiency) γδ T cells with NoZ-dCLTX-CAR lentiviral which demonstrated enhanced cytotoxicity against GBM cells compare to non-transduced control γδ T cells. Our approach of combining the dCLTX-CAR and TMZ resistance will be further validated in animal model experiments and could be a potential candidate for clinical development for GBM.
A microRNA-21–mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis
Authors: Richard Y. Kim, Krishna P. Sunkara, Ken R. Bracke, Andrew G. Jarnicki, Chantal Donovan, Alan C. Hsu, Antonio Ieni, Emma L. Beckett, Izabela Galvão, Sara Wijnant, Fabio LM. Ricciardolo, Antonino Di Stefano, Tatt Jhong Haw, Gang Liu, Angela L. Ferguson, Umamainthan Palendira, Peter A. Wark, Griet Conickx, Pieter Mestdagh, Guy G. Brusselle, Gaetano Caramori, Paul S. Foster, Jay C. Horvat, Philip M. Hansbro
Journal: Science Translational Medicine (2021)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause in developed countries. Current therapies have limited efficacy in controlling disease or halting its progression. Aberrant expression of microRNAs (miRNAs) is associated with lung disease, including COPD. We performed miRNA microarray analyses of the lungs of mice with CS-induced experimental COPD. miR-21 was the second highest up-regulated miRNA, particularly in airway epithelium and lung macrophages. Its expression in human lung tissue correlated with reduced lung function in COPD. Prophylactic and therapeutic treatment with a specific miR-21 inhibitor (Ant-21) inhibited CS-induced lung miR-21 expression in mice; suppressed airway macrophages, neutrophils, and lymphocytes; and improved lung function, as evidenced by decreased lung hysteresis, transpulmonary resistance, and tissue damping in mouse models of COPD. In silico analyses identified a potential miR-21/special AT-rich sequence–binding protein 1 (SATB1)/S100 calcium binding protein A9 (S100A9)/nuclear factor κB (NF-κB) axis, which was further investigated. CS exposure reduced lung SATB1 in a mouse model of COPD, whereas Ant-21 treatment restored SATB1 and reduced S100A9 expression and NF-κB activity. The beneficial effects of Ant-21 in mice were reversed by treatment with SATB1-targeting small interfering RNA. We have identified a pathogenic role for a miR-21/SATB1/S100A9/NF-κB axis in COPD and defined miR-21 as a therapeutic target for this disease.
Demographics and Outcomes of Multiple Myeloma Patients Undergoing Modern Modality Treatments Proceeding to ASCT: A Retrospective Study
Authors: Shubham Adroja, Arslan Babar, Muhammad Ali, Gauranga Mahalwar, Taeyeong Ko, Ashish Kumar, Tapas Ranjan Behera, Doaa Attia, Fatima Babar, Faiz Anwer
Journal: Blood (2021)
INNV-26. NCI-CONNECT PROGRAM PROVIDES RESOURCES TO IMPROVE CARE FOR PEOPLE WITH RARE CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Kristin Odom, Brittany Cordeiro, Kathleen Wall, Claudia Chambers, Kelly Mentges, Marta Penas-Prado, Jing Wu, Jill Barnholtz-Sloan, Carol Kruchko, Lorna Patrick, Linda Saucedo, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2021)

Abstract The National Cancer Institute Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) program focuses on improving approaches to care and treatment for 12 rare CNS tumors, each with &amp;lt; 2,000 diagnoses per year. To reach this rare population, the primary objective was to develop a website to share educational resources that provide patients direct access to clinical care and trials. METHODS: The NCI-CONNECT website uses the Drupal platform within NCI’s framework and the content is free to syndicate. A multidisciplinary team developed tumor-specific content in English and Spanish, clinical trial information, and survivorship resources using evidence-based sources. The Central Brain Tumor Registry of the United States provided statistics on incidence and prevalence of rare tumors. Population reach was calculated using Adobe Experience Cloud website analytics. NCI-CONNECT referrals and study participation data were collected prospectively. RESULTS: The English website launched in September 2018 and visits have increased 2,384%. The Spanish website launched in March 2020 and visits have increased 1,137%. From April 2020 to March 2021, top website page views by English page views / Spanish page views / people living with this disease include oligodendroglioma (43,859 / 8,241 / 11,757), ependymoma (31,579 / 12,684 / 13,294), meningioma (30,261 / 19,507 / 2,692), medulloblastoma (28,487 / 9,999 / 3,840), diffuse midline gliomas (23,064 / 3,851 / 6,033), and pineal region tumors (19,939 / 9,973 / 1,297). Referral rates and participation have accelerated – 45% of patients visiting the Neuro-Oncology Clinic at NIH have a rare CNS tumor and 409 patients enrolled in an NCI-CONNECT study. CONCLUSION: Patient-focused websites can provide guidance to those affected by rare cancers outside of in-person health care visits. The NCI-CONNECT website is an educational and clinical resource for patients and families affected by rare CNS tumors and was created to raise awareness and improve patient outcomes.
Abstract 11429: Post-Mortem Study of the Cause of Excess Mortality in Patients with Atrial Fibrillation and Heart Failure
Authors: Otilia Tica, Ovidiu Tica, Karina V Bunting, Joseph de Bono, Georgios Gkoutos, Mircea I Popescu, Dipak Kotecha
Journal: Circulation (2021)

Aims: To provide robust data on mortality in patients with atrial fibrillation (AF) and heart failure (HF), accounting for differences in mode of death using post-mortem information. Methods and Results: Retrospective cohort of 1009 patients admitted to a Romanian hospital between 2014-2017, with mean age 73±11 years, 47% women, NYHA class 3.0±0.9, left ventricular ejection fraction (LVEF) 40.1±11.0% and 100% anticoagulated. The primary outcome was mortality during 1.5±0.9 years follow-up, of which 291 (29%) died. Post-mortems were performed in 186 (64%) of patients. Baseline factors associated with mortality were dependent on the cause of death. HF-related death in 136 (47%) was associated with higher NYHA class (hazard ratio [HR] 2.45 per one class increase, 95% CI 1.73-3.46; p&lt;0.001) and lower LVEF (0.95 per 1% increase, 0.93-0.97; p&lt;0.001). Vascular death occurred in 75 (26%) and was associated with hypertension (HR 2.83, 1.36-5.90; p=0.005) and higher LVEF (1.08 per 1% increase, 1.05-1.11; p&lt;0.001). Non-cardiovascular death in 80 (28%) was associated with clinical obesity (HR 2.20, 1.21-4.00; p=0.010), and higher LVEF (1.10 per 1% increase, 1.06-1.13; p&lt;0.001). Across all causes, there was no relationship between mortality and AF type (p=0.77), HF type (p=0.85) or LVEF (p=0.58). Conclusions: Supported by post-mortem data, the cause of death in AF and HF patients is heterogeneous, and the relationships with typical markers of mortality are critically dependent on mode of death. The poor prognosis in this group demands further attention to improve management beyond anticoagulation.