tbuckley/cabot-search huggingface dataset:
Abstract 12882: Risk Prediction in Adolescent Males With Congenital Long QT Syndrome
Authors: Ilan Goldenberg, Arwa Younis, Anita Chen, David T Huang, Ayhan Yoruk, Mehmet Aktas, Spencer Z ROSERO, Valentina Kutyifa, Scott McNitt, Nona Sotoodehnia, Peter Kudenchuk, Thomas Rea, Dan E Arking, Wojciech Zareba
Journal: Circulation (2021)

Introduction: Men and women with either type 1 (LQT1) or type 2 (LQT2) congenital long QT syndrome (LQTS) exhibit differential risk of cardiac events (CEs) after the onset of adolescence. Hypothesis: We have recently reported a novel prediction model for LQTS women after the onset of adolescence. We now report a risk prediction model for adolescents LQT1 or LQT2 males that integrates genotype-phenotype data. Methods: The prognostic model was derived from the Rochester LQTS Registry through March 2021, comprising 611 males with LQT1 (N=304) and LQT2 (N=307) from age 10 through 20 years. Anderson-Gill modeling was employed to develop risk groups for the endpoint of non-terminal CEs (total number of syncope, aborted cardiac arrest [ACA], and appropriate ICD shocks). The covariates in the CE model were then applied to the endpoint of a first life-threatening event (LTE: ACA, LQTS-related SCD, or appropriate ICD shocks). The prediction model included the following prespecified variables: genotype/mutation-locations, QTc-specific thresholds, history of syncope prior to 10 years of age, and time-dependent beta-blocker therapy. Results: During a total follow-up duration of 6048 patient-years, there were a total of 270 non-terminal CEs. The risk-prediction model identified three risk-groups based on genotype-phenotype variables (Figure). Compared with the Low-Risk group, High-Risk patients experienced a pronounced 5.2-fold (p&lt;0.001) increased risk of CEs; Intermediate-Risk patients had a 2.1-fold (p=0.004) risk-increase. The 10-year rates of a first LTE for the Low- Intermediate- and High-Risk groups were 2%, 6%, and 8%, respectively. C-statistic for the CE prediction model was 0.61 (0.56-0.67). Conclusions: This is the first risk-prediction model that provides risk-estimates for CE and LTE in adolescent males with either LQT1 or LQT2 based on personalized genotype-phenotype data. The projected risk estimates can be used to guide sex-specific management in LQTS.
Abstract 14394: Cardiovascular Toxicities After Chimeric Antigen Receptor T-cell (CAR-T) Therapy: A Single Center Experience
Authors: Prarthana Dalal, Nikita Patel, Gregory Cascino, Arjun Sinha, Ashwin Sunderraj, Matthew J Feinstein, Nausheen Akhter
Journal: Circulation (2021)

Introduction: Chimeric Antigen Receptor (CAR)-T cell therapy has shown improved response rates in relapsed and refractory B-cell malignancies, but has been associated with adverse cardiac events. We investigated the correlation between pre-existing clinical factors and CAR-T cell therapy-related adverse cardiovascular (CV) events. Methods: Adult patients undergoing CAR-T cell therapy at Northwestern Memorial Hospital between 2016 and 2020 were identified. A comprehensive retrospective chart review was performed. CV events including CV death, new/worsening cardiomyopathy, and new/worsening arrhythmia were identified. Grade 2 cytokine release syndrome (CRS) with associated hypotension was a secondary outcome. Results: 75 patients (mean age 64 years) were identified. CV events occurred in ten patients (13%; mean age 71 years). One patient had CV death, 3 patients had new/worsening cardiomyopathy, and 6 patients had new/worsening arrhythmias. Eighteen patients with grade 2 CRS and hypotension were identified. Baseline characteristics differed between patients with vs. without post-therapy CV events (Table 1). Of the 11 patients with elevated post-infusion BNP, 6 experienced a CV event after CAR T-cell therapy (55%), whereas only 2 of the 16 patients without an elevated BNP had therapy-related cardiac events (13%; p-value = 0.03). Of 9 patients with pre-existing CAD, 3 experienced a CV event after CAR T-cell therapy (33%), whereas only 7 of the 66 patients without pre-existing CAD had CV events (11%; p-value=0.09). Conclusions: Patients with post-infusion elevation in BNP may have increased risk for CV adverse events following CAR-T cell therapy. Increased age and pre-existing CAD may also increase risk of CAR-T cell cardiotoxicity. Clinical factors predisposing to CAR-T cell therapy-related CV toxicity merit further investigation with larger sample sizes and prospective studies.
Abstract 13349: Circulating Factors Promote Metabolic Remodeling and Mitochondrial Dysfunction in Single Ventricle Congenital Heart Disease
Authors: Anastacia M Garcia, Julie Pires Da Silva, Angela Baybayon-Grandgeorge, Carissa A A Miyano, Genevieve C Sparagna, Carmen C Sucharov, Shelley Miyamoto
Journal: Circulation (2021)

Introduction: While heart failure (HF) remains a leading cause of death and indication for transplant in single ventricle heart disease (SV) patients, the molecular mechanisms associated with the progression to HF are poorly understood. The purpose of this study is to investigate if serum circulating factors from failing SV patients remodel cardiomyocyte metabolism, as is seen in the failing SV heart. Additionally, we investigated the effect of sildenafil on cardiomyocyte metabolism in vitro. Methods: We used a novel in vitro model that consists of primary cardiomyocytes (NRVMs) treated with serum from failing SV patients (SVHF) or bi-ventricular non-failing (BVNF) controls, +/- sildenafil. Mass spectroscopy was used to quantitate mitochondrial cardiolipin and investigate the metabolite composition of serum-treated NRVMs. Mitochondrial respiration was assessed using the Seahorse Bioanalyzer (Agilent), and reactive oxygen species (ROS) were quantified using the Amplex Red (Thermo Fisher). Enzyme and gene expression were analyzed using RT-qPCR and western blot, and relative mtDNA copy numbers were determined by qPCR. Results: While relative mitochondrial copy number was not significantly altered, failing SV serum decreases NRVM mitochondrial function (Fig. 1A-C), which is associated with decreased mitochondrial cardiolipin, increased reactive oxygen species (Fig. 1D), and altered expression of enzymes implicated in lipid and metabolic remodeling. Importantly, many of these changes are abrogated by sildenafil (Fig 1A-D). Conclusions: Together these data suggest that SV serum circulating factors promote lipid and metabolic remodeling in cardiomyocytes and that mitochondria represent a novel therapeutic target of sildenafil in the failing SV heart. Elucidation of the molecular mechanisms involved in modulation of cardiac energy metabolism in SV will be important to improve cardiac function and enhance transplant-free SV survival.
BIOM-26. SURVIVAL OUTCOMES AND PROGNOSTIC FACTORS IN PRIMARY GLIOBLASTOMA FROM A REAL-WORLD RETROSPECTIVE STUDY
Authors: Nicholas Brown, Diego Ottaviani, John Tazare, John Gregson, Neil Kitchen, Sebastian Brandner, Naomi Fersht, Paul Mulholland
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Glioblastoma has limited therapeutic options and is associated with a poor prognosis. Treatment, clinical outcomes, and prognostic factors remain poorly characterised outside of the selected population enrolled in clinical trials. METHODS Demographic, tumour molecular profiles, treatment, and survival data was collated for patients who underwent a biopsy or resection diagnostic of de novo glioblastoma at our centre between July 2011 and December 2015. We used multivariate proportional hazards models to examine the association of potential prognostic markers with survival. RESULTS 490 patients were identified: 60% were male with a median age of 59 years. 60% of patients had surgical debulking, and 40% biopsy only. Subsequently, 56% had standard chemoradiotherapy, 25% non-standard chemo/radio-therapy, and 19% no further treatment; 22% of patients who had adjuvant therapy had surgery at relapse, 37% second-line chemotherapy, and 11% third-line chemotherapy. Median survival was 9.2 months (IQR 7.9-10.3 months), with survival at 12- and 24-months 41% and 13% respectively. In multivariate analysis, longer survival was associated with debulking surgery vs biopsy alone (14.9 vs 8 months) (HR 0.54 [95%CI 0.41-0.70]); subsequent treatment after diagnosis (HR 0.12 [0.08-0.16]) (standard chemoradiotherapy [16.9 months] vs non-standard regimens [9.2 months] vs none [2.0 months]); tumour MGMT promotor methylation (HR 0.71 [0.58-0.87]); and younger age (hazard ratio vs age&amp;lt; 50: 1.70 [1.26-2.30] for ages 50-59; 3.53 [2.65-4.70] for ages 60-69; 4.82 [3.54-6.56] for ages 70+). IDH mutation was associated with longer survival (HR 0.64 [0.66-0.97] in univariate but not multivariate analysis. CONCLUSION Median survival for patients with glioblastoma is less than a year. Younger age, debulking surgery, treatment with chemoradiotherapy, and MGMT promotor methylation are independently associated with longer survival.
R-CHOP Chemotherapy Including Biosimilar Rituximab (Redditux ®) for De-Novo Diffuse Large B-Cell Lymphoma Patients: Real-Life Single Center Experience
Authors: Murat Ozbalak, Metban Mastanzade, Ozden Ozluk, Tarik Onur Tiryaki, Simge Erdem, Ezgi Pınar Özbalak, Tuğrul Elverdi, Ipek Yonal Hindilerden, Mustafa Nuri Yenerel, Teoman Soysal, Meliha Nalcaci, Burhan Ferhanoglu, Sevgi Kalayoglu Besisik
Journal: Blood (2021)
Digital Cardiovascular Epidemiology—Ushering in a New Era Through Computational Phenotyping of Cardiovascular Disease
Authors: Rohan Khera
Journal: JAMA Network Open (2021)

Andrew P. Ambrosy, MD; Rishi V. Parikh, MPH; Sue Hee Sung, MPH; Anand Narayanan, MD; Rajeev Masson, MD; Phuong-Quang Lam, MD; Kevin Kheder, MD; Alan Iwahashi, MD; Alexander B. Hardwick, MD; Jesse K. Fitzpatrick, MD; Harshith R. Avula, MD, MPH; Van N. Selby, MD; Xian Shen, PhD; Navneet Sanghera, MPharm; Joaquim Cristino, MSc; Alan S. Go, MD
Abstract 13143: Sushi Containing Domain 2 in Cultured Human Cardiac Myofibroblasts Predicts the Assembly of Intact Fibronectin-Rich Sheets
Authors: Tianhua Zhou, Sushmita Roy, Eric G Schmuck, James Conklin, Nisha Wattanayuth, Deane F Mosher, Jean E Schwarzbauer, Amish N Raval
Journal: Circulation (2021)

Introduction: Fibronectin (FN) has key roles in cell adhesion, differentiation, migration, alignment and immune modulation in the developing heart, but is of low abundance in the postnatal heart. Replenishing injured myocardium with insoluble FN could be a novel therapeutic approach; however, methods to produce ECM enriched with insoluble FN have remained elusive. Our team recently developed a method to produce decellularized fibronectin-rich (dFN) sheets assembled by dense human cardiac myofibroblast (CMF) cultures. We discovered that the transmembrane protein, Sushi Containing Domain 2 (SUSD2), is broadly expressed on cultured CMFs. Hypothesis: We hypothesized that SUSD2 abundance predicts whether CMFs produce intact dFN sheets. Methods: Primary CMFs were isolated from healthy left ventricles of human cadaveric donors. CMFs were sorted by median fluorescence intensity (MFI) into SUSD2-Bright and SUSD2-Dim populations using flow cytometry. Our previously reported methods to produce dFN sheets were applied to both populations, and the resulting ECM was graded: 0=no ECM, 1=fragmented, 2=friable, and 3=intact sheet (Figure). Results: SUSD2 was detected on 98±1% of CMFs among 7 strains with each evaluated in triplicate. The average MFI across all samples was 167,000 ± 51,000. CMFs that produced Grade 0-2 (n=4) and Grade 3 (n=3) dFN sheets had an average MFI of 62,000 and 270,000, respectively (P=&lt;0.0001). SUSD2-Bright cells sorted from natural SUSD2-Dimmer strains produced intact sheets. Conversely, SUSD2-Dim cells sorted from natural SUSD2-Brighter strains failed to produce intact sheets. Conclusions: SUSD2 abundance on CMFs predicts intact dFN sheet production. Ongoing protein analyses of CMFs and their matrices across varying ages, gender and health status will clarify SUSD2’s previously unidentified role in CMFs and ECM assembly, which has important implications for tissue-engineering and cardio-therapeutic applications.
Abstract 13728: Gender and Socioeconomic Bias in Patients With Atrial Fibrillation
Authors: Pooja Mishra, Maham Malik, ahmad jabri, Hani Hamade, Muhammad Umer Butt
Journal: Circulation (2021)

Background: Atrial fibrillation (AF) is one of the most common arrhythmias. We aimed to study both, the gender and socioeconomic bias in AF patients and outcomes in terms of ablations and all-cause mortality. Methods: This was a cross-sectional study using a large population-based database, Explorys. Data were collected from electronic health records of approximately 63 million patients until October 2019 using the search terms - AF, persistent AF, ablation operation for arrhythmia. Among all AF patients, we used insurance status (Medicare, private, and Medicaid) as a surrogate for socioeconomic status. For each gender and insurance type, we investigated all-cause mortality. Result: Out of 1.7 million patients, 712,700 patients had atrial ablation procedures. The distribution of insurance was as: Medicare 46.5%, private 50.2%, and Medicaid 3.3%. 45 % of total ablated patients were female. Females had overall Higher mortality as compared to males in general (10.64 % versus 7.82%; p&lt;0.0001). Using binary logistic regression there was heterogeneity in the mortality with the highest mortality in the females in the Medicaid insurance group as compared to the private insurance group (Adjusted OR=1.5; 95% CI: 1.4-1.6). Conclusion: The prevalence of AF is almost similar in males and females. However, ablations in men are thrice as common when compared to females, and &lt;5% of the Medicaid population end up getting ablations suggesting that there is a treatment bias in our society. Clinical Implications: Our findings suggest that there is a healthcare disparity in females, especially with low socioeconomic status. We will conduct a retrospective study of patients in our hospital to further investigate the above findings and implement measures to overcome these barriers such as close follow-up, early referral to electrophysiologists.
Abstract 11543: Assessing Reporting of Low-Gradient Severe Aortic Stenosis Based on Race and Ethnicity: Observations from a Large Academic Health System
Authors: Nimish N Shah, Lissa Sugeng, Kangxin Wang, Robert L McNamara, Vratika Agarwal, David Hur, Bernardo Lombo, Lavanya Bellumkonda, John K Forrest, Harlan M Krumholz, Eric J Velazquez, Kamil Faridi
Journal: Circulation (2021)

Introduction: Though low-gradient (LG) aortic stenosis (AS) is common and frequently reported as non-severe on transthoracic echocardiogram (TTE) in real world practice, the association of race and ethnicity with LG AS type and reported severity is not well understood. Methods: We identified all adults ≥ 18 years old from 9/2015-11/2019 with AS, aortic valve area &lt; 1.0cm 2 , and mean gradient &lt;40mmHg on TTE within a large academic health system. We determined frequency of LG AS type (classical low-flow LG [CLFLG], paradoxical low-flow LG [PLFLG], and normal-flow LG [NFLG]) by race and ethnicity. We assessed whether race and ethnicity were associated with reporting severe-range AS on TTE using multivariable logistic regression accounting for age, sex, body mass index, mean gradient, aortic valve area, AS type, and quaternary vs. non-quaternary TTE site. Results: Among 2740 adults with LG AS, 92.4% were white, 4.3% were black, and 3.7% were Hispanic. PLFLG AS was the most common LG AS type among white and black patients and the least common among Hispanic patients (Figure). Among those with PLFLG AS, black patients had the highest proportion of TTEs reported as severe-range AS, while Hispanic patients had the lowest; there were no differences in reporting for CLFLG or NFLG AS (Figure). After multivariable adjustment, there were no significant differences in reporting severe-range AS based on black race (adjusted OR 1.63, 95% CI 0.95-2.82) or Hispanic ethnicity (adjusted OR 1.05, 95% 0.39-2.75) compared to white patients. Quaternary site was a strong independent predictor of reporting severe-range AS (adjusted OR 4.97, 95% CI 3.81-6.54). Conclusions: There are race- and ethnicity-based differences in frequency of LG AS type, and in reporting severe AS on TTE for PLFLG AS in particular. Differences in reporting for PLFLG AS are attenuated after accounting for factors such as TTE site. Additional factors influencing reporting of LG AS in real-world practice should be investigated.
Treatment outcomes of triple class refractory multiple myeloma: a benchmark for new therapies
Authors: Susan Bal, Ehsan Malek, Ankit Kansagra, Saad Z. Usmani, Ravi Vij, Kelly N. Godby, Robert F. Cornell, Yubin Kang, Elvira Umyarova, Smith Giri, Saurabh Chhabra, Michaela Liedtke, Natalie S. Callander, Parameswaran Hari, Shaji Kumar, Luciano J. Costa
Journal: Leukemia (2021)
CTNI-53. RADIATION TREATMENT VOLUMES BEFORE AND AFTER BRAF/MEK THERAPY IN NEWLY DIAGNOSED PAPILLARY CRANIOPHARYNGIOMAS: A CORRELATIVE ANALYSIS OF THE ALLIANCE A071601 PHASE II TRIAL
Authors: Helen Shih, Shervin Tabrizi, Brian Kabat, Erin Twohy, Susan Geyer, Shivangi Vora, Elizabeth Gerstner, Timothy Kaufmann, Michael Ruff, David Reardon, Adam Cohen, Daniela Bota, Pankaj Agarwalla, Macarena De la Fuente, Glen Lesser, Jian Campian, Priya Kumthekar, Michael Knopp, Daniel Cahill, Sandro Santagata, Fred Barker, Evanthia Galanis, Priscilla Brastianos, Paul Brown
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Standard of care for craniopharyngiomas is surgery with or without radiotherapy (RT). Cohort A of Alliance A071601 evaluated the efficacy of BRAF/MEK inhibition with vemurafenib/cobimetinib in patients with previously untreated papillary craniopharyngiomas (PCP), which carry the BRAF V600E mutation. Cohort B is currently enrolling patients with recurrence after RT. In a correlative analysis, we examined changes in RT volumes after BRAF/MEK therapy in Cohort A. METHODS Previously unirradiated patients with BRAF-mutated PCP were treated with vemurafenib/cobimetinib. Sixteen patients had scans available before starting vemurafenib/cobimetinib (“pre-therapy”) and after completing therapy (“post-therapy”). Two patients went off study treatment after 8 and 9 days due to side-effects and were excluded for this analysis. Gross target volumes (GTV) were contoured on pre-therapy and post-therapy scans. On post-therapy scans, an additional target comprising gross disease and at-risk regions for microscopic residual disease (GTV-micro) was defined and considered the treatment volume. Clinical target volume (CTV) was a 5-mm uniform expansion on pre-therapy GTV and post-therapy GTV-micro. Volumes were independently reviewed by two radiation oncologists. Changes in volumes from pre- versus post-therapy were compared using the Wilcoxon signed rank test. RESULTS In 14 patients evaluated, 57% were female and median age at enrollment was 49.5 years (range 33-83). Median time on treatment was 8.9 months (range 4.0-18.0). Median GTV pre-therapy was 3.8 mL (range 0.2-23.4) versus 0.3 mL (range 0.0-3.2) post-therapy (p=0.0001) and 1.7 mL (range 0.1-8.0) post-therapy GTV-micro (p=0.0001). Median CTV pre-therapy was 13.7 mL (range 2.8-51.8) versus 9.1 mL (range 2.2-27.5) post-therapy (p=0.0001). All tumors abutted the optic chiasm pre-therapy, only 6 did post-therapy. CONCLUSIONS Vemurafenib/cobimetinib resulted in smaller RT volumes. BRAF/MEK inhibitors could reduce RT volumes and spare dose to surrounding normal structures. Enrollment to Cohort B of Alliance A071601 should be considered for patients with recurrent tumors after RT. SUPPORT https://acknowledgments.alliancefound.org
Polatuzumab Vedotin As a Salvage Treatment in Relapsed or Refractory DLBCL: Single Center Experience
Authors: Marwa Bin Morya, Mohammed A. Marei, Imran K. Tailor, Abdullah M Alrajhi, Adel Alnakhli, Foud Alnajjar, Mohammed S. Alnoamani, Hassan Alshehri, Ibraheem H. Motabi, Nawal AlShehry, Mansour Alfayez
Journal: Blood (2021)
Abstract 13632: The Relationship Between Health Information Technology Use and Pneumococcal Vaccine Uptake in Adults With Heart Disease
Authors: onoriode kesiena, Shreyas Singireddy, Joseph Atarere, Oluwaseun Famojuro
Journal: Circulation (2021)

Introduction: Health information technology (HIT) has been shown to influence medication adherence and healthy behaviors. This influence may increase the uptake of vaccines especially in high risk groups. Hypothesis: HIT use may be associated with increase pneumococcal vaccine uptake in adults ≥ 40 years with heart disease. Methods: Using the National Health Interview Survey data, 2,134 united states adults ≥ 40 years with heart disease were analyzed in this cross-sectional study. The independent variables were: Use of the internet to (1) to look up health information (2) to fill a prescription and (3) to schedule a medical appointment and use of an email (4) to communicate with a healthcare provider, which were dichotomous. The dependent variable was pneumococcal vaccine uptake which was also dichotomous. Chi-square analysis was used to identify group differences. Multiple logistic regression was used to analyze the association between HIT utilization and pneumococcal vaccine uptake. Results: Those who use the internet to fill up prescription and to communicate with their healthcare provider were more likely to take up the PCV [AOR 1.56; 95% CI 1.03, 2.37, p =.035] and [AOR 1.95; 95% CI 1.23, 3.10, p =.005] respectively. Compared to those who did not use HIT in any form, those who used HIT in at least three or four forms had a higher PCV uptake [AORs 1.93; 95% CI 1.19, 3.13, p-value .008] and [AOR 2.33 95% CI 1.22, 4.47, p-value .011] respectively. Conclusions: Our analysis shows a positive association of HIT utilization and pneumococcal vaccine uptake. It further stresses the importance of electronic health in preventive medicine. Larger studies should evaluate the relationship between different uses of health information technology and different vaccines uptake.