tbuckley/cabot-search huggingface dataset:
Abstract 6929: Acute Echocardiographic Effects of Exogenous Ketone Administration and Relationship to Myocardial Glucose Uptake on Fdg-pet
Authors: Senthil Selvaraj, Ray Hu, Mahesh K Vidula, Supritha Dugyala, Ann Tierney, Kenneth B Margulies, Bonnie Ky, Svati H Shah, Daniel P Kelly, Paco E Bravo
Journal: Circulation (2021)

Background: Interest in therapeutic applications of exogenous ketones has grown significantly, spanning endurance athletes to heart failure (HF) patients. Exogenous ketones engender significant effects on cardiac function in HF and provide an ergogenic benefit in athletes. We sought to assess the effects of exogenous ketones on cardiac function and metabolism in healthy participants. Methods: Twenty healthy participants completed echocardiograms before and 30 minutes after administration of ketone ester (KE), followed by FDG-PET imaging. We used mixed effects linear regression to assess the association between regional left ventricular (LV) strain on the post-KE drink echocardiogram with regional myocardial glucose uptake (SUV myocardium/blood pool) on FDG-PET (N=176 myocardial segments). Results: Mean age was 307 years, 50% were female, 45% were non-white, and average BMI was 24.33.1 kg/m 2 . Ketone ingestion acutely elevated beta-hydroxybutyrate levels (median, 25 th -75 th percentile) from 0.12 (0.10-0.32) to 3.23 (2.40-4.97) mmol/L (p&lt;0.001). After KE consumption, LV/RV/LA function strain all augmented, while systemic vascular resistance decreased ( Figure ). Specifically, LV ejection fraction (3.5±2.1%, p&lt;0.001), global longitudinal strain (2.0±1.5, p&lt;0.001), cardiac output (1.1±0.8 L/min, p&lt;0 . 001), right ventricular S’ velocity (1.1±1.4, p=0.004), LA reservoir strain (7±11%, p=0.005) and LA contractile strain (4±5%, p=0.001) increased. After multivariable regression, each halving of regional glucose uptake was independently associated with a 2.2% increase in regional strain (p=0.016). Conclusions: KE ingestion acutely augments even in healthy participants, mirroring many hemodynamic effects seen in HF. The ability of KE to augment myocardial function was directly associated with reducing myocardial glucose uptake, supporting myocardial metabolic modulation as a mechanism of benefit.
Abstract 11209: KER-012, a Novel Modified ActrII Ligand Trap, Attenuated Cardiac Pathology in a Pulmonary Arterial Banding Model of Right Ventricle Overload
Authors: Keith Babbs, Chris Materna, ffolliott Fisher, Jasbir Seehra, Jennifer Lachey
Journal: Circulation (2021)

Pulmonary arterial hypertension (PAH) is a debilitating disorder, characterized by right ventricle (RV) pressure overload, cardiac hypertrophy, and progressive RV dysfunction. PAH is associated with unbalanced TGFß signaling, favoring signaling of SMAD2/3 and opposing SMAD1/5/9. The result is an increase in vascular proliferation and disruption of vascular homeostasis. KER-012 is a modified ActRII ligand trap designed to inhibit ligands that signal through SMAD2/3 to promote restoration of vascular homeostasis. To investigate the cardio-protective effects of RKER-012, a research version of KER-012, we evaluated the effect of treatment in a pulmonary arterial banding (PAB) model. In this study, 8-week-old, male C57BL/6 mice underwent sham or PAB surgery to increase RV pressure and induce cardiac remodeling. The sham cohort received vehicle (VEH) treatment and PAB mice received either vehicle (VEH) or 10 mg/kg RKER-012 twice weekly for 3 weeks. Relative to sham mice, all PAB mice had elevated pulmonary arterial pressures on day 1 (all ps&lt;0.0001) that persisted until day 21 (all ps&lt;0.01), indicating that the PAB procedure was effective. VEH PAB mice also exhibited diminished cardiac function, including increased end systolic pressure volume relationship (ESPVR; +79.3%; p&lt;0.001) and increased myocardial performance index (MPI; +45.6%; p&lt;0.0001) compared to Sham VEH. Additionally, VEH PAB mice had markers of cardiac remodeling, including increased Fulton Indices (+54.8%; p&lt;0.0001), increased RV free wall thickness (RVFWT; +95.8%; p&lt;0.0001) and increased cardiac fibrotic tissue (+529.9%; p&lt;0.0001). In contrast, RKER-012 treatment was cardioprotective and prevented changes in cardiac function and tissue remodeling. In treated mice, there was a trend for decreased ESPVR (-14.2%), decreased MPI (-13.2%, p&lt;0.01), decreased Fulton Index (-13.5%; p&lt;0.01), and decreased RVFWT (-22.9%; p&lt;0.0001) compared to VEH PAB. Treated mice also had reduced cardiac fibrotic tissue (-38.9%, p&lt;0.01). Taken together, these data provide evidence that KER-012 has the potential to reduce cardiac remodeling and improve cardiac performance in pathologies involving constricted pulmonary arterial blood flow and could provide benefit in diseases such as PAH.
Abstract 13424: Lack of Improvement in Prevalence of Overtly Uncontrolled Blood Pressure Over the Past Decade and Its Association With Social Determinants
Authors: Aayush Visaria, Soko Setoguchi
Journal: Circulation (2021)

Introduction: Despite improvements in treatment strategies, BP control continues to be a public health challenge. We determined the 20-year national trends for overtly uncontrolled BP (OUBP). Methods: In this serial cross-sectional study, we included adults with 3 consecutive BP measurements from the 1999-2018 National Health and Nutrition Examination Surveys. OUBP was defined as mean SBP≥160 or DBP≥100. We calculated crude, age-adjusted, and covariate-adjusted prevalence estimates using multivariable logistic regression, and determined the effect of covariates on OUBP trends. Results: Among 44,622 participants (mean age 47 years, 51% female, 69% White), 2,613 (4%) had OUBP. OUBP individuals in 2015-18 were more likely to be male, non-Hispanic Black, diabetic, and lack insurance compared to those from earlier cycles (Table). There was a decreasing trend in multivariable-adjusted OUBP prevalence from 6.0% in 1999-2002 to 3.0% in 2007-10 (p&lt;0.001), followed by an insignificant increase to 3.4% in 2015-18 (Figure). Although the downward trend in OUBP persisted after multivariable adjustment, family income, education, and insurance coverage modestly attenuated the trend (change in slope [95% CI] from 1.3% [0.9-1.7] to 1.0% [0.7-1.4] decrease/year). Lack of insurance was increasingly associated with OUBP (OR [95% CI]; 1999-2002=1.19 [0.61, 2.30], 2007-2010=1.83 [1.19, 2.82], 2015-2018=2.70 [1.64, 4.45]). Conclusions: Although OUBP prevalence has overall significantly decreased, it has remained stagnant since 2011. Social determinants, including insurance, income, education, and race may be playing increasingly important roles in OUBP prevalence.
Evaluation of Efficacy and Immune Modulation Associated with the Addition of IMiDs to Daratumumab Backbone in Patients Refractory to Both Drug Classes
Authors: Despina Fotiou, Ioannis V Kostopoulos, Maria Krevvata, Maria Gavriatopoulou, Ioannis Ntanasis-Stathopoulos, Pantelis Roussakis, Chrysanthi Panteli, Panagiotis Malandrakis, Magdalini Migkou, Nikolaos Kanellias, Evangelos Eleutherakis Papaiakovou, Foteini Theodorakakou, Evangelos Terpos, Ourania E. Tsitsilonis, Meletios-Athanasios Dimopoulos, Efstathios Kastritis
Journal: Blood (2021)
BIOM-27. INTEGRATED PREDICTION OF VENOUS THROMBOEMBOLISM IN GLIOMA PATIENTS
Authors: Dusten Unruh, Michael Drumm, Jonathan Lamano, Margaret Schwartz, Anh Tran, Rodrigo Javier, Kathleen McCortney, Christina Amidei, Kirsten Burdett, Denise Scholtens, Craig Horbinski
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Venous thromboembolism (VTE) is a debilitating and life-threating condition that is common in patients with cancer, especially glioma. There are no widely-accepted guidelines for antithrombotic prophylaxis in glioma patients, in part because of the risk of iatrogenic intracerebral hemorrhage. Effective VTE prediction models exist for patients with other cancers, but not glioma. Our prior publications suggested a protective role of IDH mutation (IDHmut) against VTE, as well as a positive association between elevated circulating Tissue Factor (TF), a procoagulant secreted by cancers, and VTE in glioma patients. Others have recently found a correlation between podoplanin, a platelet activator, and cancer-associated VTE, but this has not yet been proven in gliomas. Our objective was to develop a multidimensional VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers. METHODS The Northwestern University Nervous System Tumor Bank provided preoperative arterial blood, tumor tissue, and clinical-pathologic data from 254 grade II-IV glioma patients over a 4-year interval. Molecular profiling was done by GlioSeq NGS. RESULTS Forty-six out of 254 grade II-IV glioma patients (18%) experienced VTE during their disease course. VTE was associated with worse median overall survival (18 vs. 54 months, P&amp;lt; 0.001). Positive risk factors for VTE included advanced patient age, high body mass index, high glioma grade, prior history of VTE, coronary artery disease, hyperlipidemia, hypertension, and elevated circulating TF activity, among other variables. While tumor expression of podoplanin positively correlated with VTE, circulating podoplanin did not. Among molecular markers, the strongest was IDHmut, being associated with greatly reduced VTE risk (OR=0.28; 95% CI=0.12-0.64, P=0.001). CONCLUSIONS This study identified multiple risk factors for glioma-associated VTE. Using these data, we have developed a web-based multivariable integrated prediction calculator to identify glioma patients who would benefit the most from prophylactic anticoagulation.
NIMG-23. MACHINE LEARNING METHODS IN GLIOMA GRADE PREDICTION: A SYSTEMATIC REVIEW
Authors: Ryan Bahar, Sara Merkaj, W R Brim, Harry Subramanian, Tal Zeevi, Eve Kazarian, Ming Lin, Khaled Bousabarah, Sam Payabvash, Jana Ivanidze, Jin Cui, Irena Tocino, Ajay Malhotra, Mariam Aboian
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Machine learning (ML) technologies have demonstrated highly accurate prediction of glioma grade, though it is unclear which methods and algorithms are superior. We have conducted a systematic review of the literature in order to identify the ML applications most promising for future research and clinical implementation. MATERIALS AND METHODS A literature review, in agreement with PRISMA, was conducted by a university librarian in October 2020 and verified by a second librarian in February 2021 using four databases: Cochrane trials (CENTRAL), Ovid Embase, Ovid MEDLINE, and Web of Science core-collection. Keywords and controlled vocabulary included artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, and glioblastoma. Screening of publications was done in Covidence, and TRIPOD was used for bias assessment. RESULTS The search identified 11,727 candidate articles with 1,135 articles undergoing full text review. 86 articles published since 1995 met the criteria for our study. 79% of the articles were published between 2018 and 2020. The average glioma prediction accuracy of the highest performing model in each study was 90% (range: 53% to 100%). The most common algorithm used for cML studies was Support Vector Machine (SVM) and for DL studies was Convolutional Neural Network (CNN). BRATS and TCIA datasets were used in 47% of the studies, with the average patient number of study datasets being 186 (range: 23 to 662). The average number of features used in machine learning prediction was 55 (range: 2 to 580). Classical machine learning (cML) was the primary machine learning model in 68% of studies, with deep learning (DL) used in 32%. CONCLUSIONS Using multimodal sequences in ML methods delivers significantly higher grading accuracies than single sequences. Potential areas of improvement for ML glioma grade prediction studies include increasing sample size, incorporating molecular subtypes, and validating on external datasets.
Abstract P393: Fabrication Of Immunomodulatory Hydrogels For Cardiac Repair After Acute Myocardial Infaction
Authors: Weiang Yan, Alireza Rafieerad, Abhay D Srivastava, Keshav Narayan Alagarsamy, Rakesh C Arora, Sanjiv Dhingra
Journal: Circulation Research (2021)

Introduction: The balance of pro- and anti-inflammatory processes is tightly linked to left ventricular remodeling after myocardial infarction. Immune activation also plays a key role in rejection of transplanted allogeneic stem cells. In this study, we present the design, fabrication and characterization of immunomodulatory chitosan-based hydrogels for cardiac repair after myocardial infarction. Methods: Chitosan hydrogels conjugated with small immunomodulatory molecules were synthesized through a thermogelation process. Resultant hydrogels were characterized using scanning electron microscopy and Fourier-transformed infrared spectroscopy. Human mesenchymal stem cells were encapsulated into the hydrogels and biocompatibility was assessed after one week using fluorescence microscopy and a colorimetric assay. Immunomodulatory activity was assessed after co-culture with human T-lymphocytes using flow cytometry for CD4+IFN-γ+ pro-inflammatory and CD4+CD25+FoxP3+ regulatory T-lymphocytes. Results: Small immunomodulatory molecules were successfully integrated into chitosan hydrogels. Physico-chemical characterization revealed no significant changes to the 3D structure and porosity of hydrogels. The addition of 10μM atorvastatin or 10μM rosuvastatin did not result in significant cytotoxicity to encapsulated mesenchymal stem cells at 3 or 7 days. Addition of statins resulted in marked suppression of CD4+ T-lymphocyte proliferation (Control 25.1 Fold, Atorvastatin 1.0 Fold, Rosuvastatin 2.3 Fold, p&lt;0.001) and activation (CD4+IFN-γ+ Population: Control 87.1%, Rosuvastatin 23.7%, p&lt;0.001) after stimulation. No differences were seen in percentages of CD4+CD25+FoxP3+ regulatory T-lymphocytes (Control 5.5%, Rosuvastatin 5.7%, ns). Conclusion: A biocompatible immunomodulatory hydrogel was created through integration of atorvastatin and rosuvastatin into a chitosan hydrogel. Experiments are currently underway in vivo to examine its usefulness for stem cell delivery and reducing adverse left ventricular remodeling after myocardial infarction.
Abstract 11836: Higher Burden of Supraventricular Ectopy is Independently Associated With Greater Risk of Dementia in Older Adults Without Atrial Fibrillation: The Atherosclerosis Risk in Communities Study
Authors: Romil R Parikh, Wendy Wang, Mary R Rooney, Michael J Zhang, Jeremy R Vant Hof, Kuni Matsushita, Elsayed Z Soliman, B Gwen Windham, Thomas Mosley, James R Pike, Bruce A Wasserman, Michelle C Johansen, Rebecca F Gottesman, Alvaro Alonso, Lin Y Chen
Journal: Circulation (2021)

Introduction: In older adults without atrial fibrillation (AF), it is unclear if higher burden of supraventricular ectopy (SVE) is associated with dementia risk independent of cardiovascular risk factors and clinically documented stroke. Hypothesis: In older adults without AF, higher burden of SVE including premature atrial contractions (PAC) and atrial tachycardias (AT) are associated with a higher risk of dementia. Methods: Among 2167 participants (mean age, 79 years, 60% female, 26% Black) without adjudicated dementia, stroke or AF, at baseline (2016-17), AT and PAC were measured over 2 weeks by an ambulatory, continuous electrocardiogram recorder (Zio XT patch, iRhythm Technologies, Inc.). We quantified burden of PACs and ATs as: 1) natural log of frequency (episodes/day) due to skewed distributions, and 2) a dichotomous frequency measure, split at the median. Additionally, we dichotomized duration of the longest AT episode at the median. Dementia was adjudicated based on cognitive assessments through 2019 using the Clinical Dementia Rating scale at study visits or by telephone cognitive interviews, informant interviews, and ongoing linkage to medical records. We calculated relative risk of incident dementia using Poisson regression with robust error variance. Results: At baseline, median Zio XT patch wear time was 13.8 days (interquartile interval 13-14 days). Over 2 years of follow-up, 66 (3.0%) participants developed dementia. Higher frequency of AT and PAC (continuous or dichotomous) were associated with a higher risk of dementia independent of incident AF, stroke, and cardiovascular risk factors (Table). Conclusions: In older adults without AF, higher burden of SVE is associated with a greater risk of dementia independent of incident AF, stroke, and cardiovascular risk factors. Future research should define underlying mechanisms and evaluate the effect of lowering SVE burden on the risk of dementia in older adults with a higher SVE burden.
Shared Genetic Pathways Contribute to Risk of Hypertrophic and Dilated Cardiomyopathies With Opposite Directions of Effect
Authors: Rafik Tadros, Catherine Francis, Xiao Xu, Alexa M. Vermeer, Andrew R. Harper, Roy Huurman, Ken Kelu Bisabu, Roddy Walsh, Benjamin Meder, Philippe Charron, Rudolf A. De Boer, Imke Christiaans, Michelle Michels, Arthur A. Wilde, Hugh Watkins, Paul Matthews, James S. Ware, Connie R. Bezzina
Journal: Circulation (2020)
Abstract 10251: Intracranial Aneurysms in Sickle Cell Adults Screened by Mra
Authors: Igor Gomes Padilha, Stéphanie Forté, Laurent Letourneau-guillon, Denis Soulieres, KRISTOFF NELSON, Manon Belair, Jean Raymond, François Guilbert
Journal: Circulation (2021)

Introduction: Sickle cell disease(SCD) is the most common genetic disease globally. It is an autosomal recessive disease that affects the β-globin chain which most often presents with anemia and vaso-occlusive symptoms. This condition includes multiples genotypes/phenotypes, the most common of which is HbSS (homozygosity for Hemoglobin S); others are compound heterozygosity with HbC variant (HbSC) and HbS-β-thalassemia (HbSβ+/HbSβ0). Stroke occurs in up to 25% of SCD patients and MRI screening is already recommended by the American Society of Hematology. Small case series have shown a higher prevalence of intracranial aneurysms (ICAN) in SCD, and MR angiography (MRA) may therefore be of benefit for the detection of arterial pathology. Hypothesis: There is an increased prevalence of ICAN in adults with SCD; Frequency of anevrysms is associated with SCD genotype and age. Methods: Adult patients from the SCD clinic of our institution were screened with 3T brain MR complemented with MRA in order to accurately determine the prevalence of ICAN. Results: Our study included 245 asymptomatic SCD adults (369 MRIs). Median age was 32; 52% were women. The overall prevalence of ICAN was 0.11 (0.95 CI 0.07-0.15). All aneurysms were saccular ≤ 10 mm. Forty-four aneurysms were detected in 27 patients with a third presenting with multiple aneurysms. Genotype subgroup analysis revealed a higher prevalence of ICAN in SS/Sb0 (0.17; 0.95 CI 0.11-0.25) compared to the SC/Sb+ (0.06; 0.95 CI 0.02-0.11) (p = 0.007). An association between age and ICAN was also statistically significant (p = 0.03) with stratification revealing a higher prevalence of ICAN for &gt;30 years old, 0.15 (0.95 CI 0.09-0.21). In addition, in patients aged 18-30, the prevalence was 0.06 (0.95 CI 0.26-0.12). Conclusions: This is the largest cohort of SCD adults screened specifically with MRA. We confirm with higher confidence the increased prevalence of ICAN in this population which is in the range of other established indications for aneurysm screening such as Familial Intracranial Aneurysm and Autosomal Dominant Polycystic Kidney Disease. This knowledge could therefore impact the existing screening guidelines for SCD patients via systematic inclusion of an MRA sequence in the recommended imaging protocol.
Abstract 12657: Overexpression of Small-Cajal Body Associated RNA20 (scaRNA20) Reduces Inflammatory Response and Improve Cardiomyogenesis
Authors: VINOTH SIGAMANI, Narasimman Gurusamy, SHEEJA RAJASINGH, Rajasingh Johnson
Journal: Circulation (2021)

Introduction: The non-coding RNAs, particularly small cajal-body associated RNAs (scaRNAs) play a critical role in alternative splicing and maturation of mRNAs. Although scaRNAs have been implicated in autoimmune diseases, their roles in the immune responses are largely unknown. Recently, we have identified that scaRNA20 play a major role during the differentiation of cardiomyocytes. In this study, we elucidated the role of scaRNA20 and its immune response towards the ischemic myocardium, using in vitro induced pluripotent stem cell (iPSC)-derived normal cardiomyocytes (iCMC). Hypothesis: We hypothesize that overexpression of scaRNA20 reduces the inflammatory response in cardiomyocytes leading to enhanced cardiomyogenesis. Methods &amp; Results: scaRNA20 gene was cloned into mammalian expression vector CAG-GFP, and transfected into iPSCs for its overexpression and further differentiated into cardiomyocytes (scaRNA20-OE-iCMC). The results were compared with the iCMCs and transfected with empty vector (TC-iCMC). Our qRT-PCR results showed that the scaRNA20-OE-iCMCs led to a significant reduction in the fold change expression of pro-inflamatory genes such as TNFa and IL11 when compared to the TC-iCMCs and normal iCMCs normalized with normal skin fibroblast (SF) (Fig. A). In addition, the scaRNA20-OE iCMCs showed an increased expression of cardiac specific genes such as GATA4 and cardiac troponin T, compared with the TC-iCMCs and iCMCs. The functional cardiomyocytes can be assessed by the number of beating colonies. Our data showed a significantly increased number of beating colonies in scaRNA20-OE iCMCs when compared to the TC-iCMCs and iCMCs (Fig. B). Conclusions: Taken together, our results show for the first time that the overexpression of scaRNA20 reduced the inflammatory response, and at the same time improved the cardiomyogenesis. These results suggest that treatment with scaRNA20 can improve the regeneration of the ischemic myocardium.
Abstract 11003: Racial Disparities in Induction Immunosuppression Use Among Heart Transplant Recipients in the United States
Authors: Soziema J Salia, Elizabeth Mostofsky, Suruchi Gupta, Laura L Lehman, Shweta R Motiwala, Murray A Murray Mittleman
Journal: Circulation (2021)

Introduction: Black heart transplant recipients have higher rates of acute rejection, graft failure, and mortality compared to other races. Induction immunosuppression in the immediate peri-transplant period may lower the risk of acute rejection among high-risk patients, including Black transplant recipients. However, it is not known whether the odds of receiving this treatment are different across races. Therefore, we evaluated whether there are disparities in the use of induction immunosuppression following heart transplants among Black patients compared to other races. Methods: We conducted a cross-sectional study of U.S. adults in the Scientific Registry of Transplant Recipients who received their first heart transplant between 2008 - 2018. We used mixed-effects logistic regression to compare the odds of receiving induction immunosuppression agents (IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, and CD52 monoclonal antibodies) across different races. Results: Among 23,935 adult heart transplant recipients, 5,160 (21.6%) were Black, including 2,797 (54.2%) who received induction immunosuppression, and 18,775 (78.4%) were non-Black, including 9,499 (50.6%) who received induction immunosuppression. After accounting for demographic and clinical characteristics and treatment center, Black race was associated with 28% higher odds (Odds Ratio=1.28, 95% CI 1.17-1.40) of induction immunosuppression use compared to other races. Similar results were observed when race was further stratified (Table 1). Conclusions: In our study, Black heart transplant recipients were more likely to receive induction immunosuppression than transplant recipients of other races. However, further research on post-transplant clinical outcomes including survival following induction immunosuppression among Black patients is needed to formulate treatment guidelines.