tbuckley/cabot-search huggingface dataset:
Abstract 13250: Factors Associated With Improvement of Left Ventricular Function After Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure
Authors: Marcos Roberto Q França, Bruno R Nascimento, Reynaldo C Miranda, Gustavo A Silva, Anna Terra França, Henrique B Moreira, Vitor F Fontes, Antonio L Ribeiro, Andre A Carmo
Journal: Circulation (2021)

Introduction: Catheter ablation is a well-established therapy for atrial fibrillation (AF), and studies have shown positive outcomes in patients with heart failure (HF). We aimed to evaluate the impact of AF ablation on echocardiographic and clinical parameters in patients with HF in Brazil, and to assess factors associated with improvement of the left ventricular ejection fraction (LVEF). Methods: Consecutive patients diagnosed with HF and LVEF &lt;50%, who underwent successful radiofrequency AF ablation in 5 high-volume institutions, were prospectively included. All patients underwent standard transthoracic echocardiography before the procedure and during clinical follow-up, and the analysis by the examiner was considered. The primary outcome was LVEF normalization (LVEF ≥50%) at follow-up. Clinical, echocardiographic, and procedure-related variables associated with the primary outcome were assessed by univariate logistic regression. P-value &lt;0.05 was considered significant. Results: From 2018 to 2020, 44 patients were included, being 28 (64%) males, mean age 66±11 years. Of these, 12 were in NYHA functional class 3/4, 35 had persistent AF, and only 3 had previous ablations. Mean pre-procedural LVEF was 38±7%, with 13 (30%) having LVEF&lt;35%. Complications occurred in only 2 patients, with 1 case of arterial pseudoaneurysm. In the 8.0±7.6 month follow-up, there was a substantial improvement of the LVEF to 53±14% (p&lt;0.001), and 27 (61%) achieved the primary outcome of LVEF normalization. Thirty patients (68%) had LVEF improvement of ≥10%, only 5 remained in NYHA class 3/4, and recurrent AF occurred in 11 (25%). Predictors of LVEF normalization were: pre-ablation LVEF (OR: 1.32, 95%CI 1.13-1.54, p=0.001), baseline left atrial diameter (OR: 0.87, 95%CI 0.77-0.98, p=0.02), baseline NYHA functional class 1/2 (OR: 5.11, 95%CI 1.29-21.28, p=0.025) and the absence of indication of spironolactone (OR: 5.60, 95%CI 1.20-26.14). There were 3 deaths, and none of them had LVEF improvement in follow-up echo. Conclusion: AF ablation in patients with HF resulted in remarkable echocardiographic and functional improvement, with low complication rates. Less clinical severity and less morpho-functional impairment were associated with LVEF normalization.
Phase II Study of Cladribine, Idarubicin, Cytarabine (CLIA) Plus Gilteritinib in Patients with FLT3 Mutated Acute Myeloid Leukemia (AML)
Authors: Tareq Abuasab, Hagop Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo, Yesid Alvarado, Musa Yilmaz, Naveen Pemmaraju, Kelly S. Chien, Shehab Fareed Mohamed, Naval Daver, Steven M. Kornblau, Jan A. Burger, Nitin Jain, Rubiul Islam, Courtney D. DiNardo, Gautam Borthakur, Farhad Ravandi, Tapan M. Kadia
Journal: Blood (2021)
Safety and Pharmacokinetics of Calaspargase Pegol in Adults with Newly Diagnosed Philadelphia-Negative ALL: A Phase 2/3 Study
Authors: Wendy Stock, Jae H Park, Ashkan Emadi, Maher Abdul-Hay, Ryan D. Cassaday, Vinod A. Pullarkat, Jonathan Webster, Shuchi S. Pandya, Mark J Mogul, Yelena Shvenke, Jian J Zhu, Adrien Tessier, Daniel J. DeAngelo
Journal: Blood (2021)
BIOM-44. PRE-SURGICAL ADVANCED MRI IS USEFUL FOR FORECASTING DRUG DISTRIBUTION IN BRAIN TUMORS
Authors: Pamela Jackson, Minjee Kim, Andrea Hawkins-Daarud, Kyle Singleton, Afroz Mohammad, Terence Burns, Ian Parney, Leland Hu, Timothy Kaufmann, William Elmquist, Jann Sarkaria, Kristin Swanson
Journal: Neuro-Oncology (2021)

Abstract Choosing effective chemotherapies for intravenous delivery to brain tumors is challenging, especially given the protective nature of the blood brain barrier (BBB). Connecting drug distribution to non-invasive, pre-surgical magnetic resonance imaging (MRI) could allow for predictive insight into drug distribution. In a previous study, we found that T2Gd images were predictive of a low BBB penetrant drug (Cefazolin), and FLAIR images were predictive of a high BBB penetrant drug (Levetiracetam). While these results are promising, we further seek to explore how advanced MRI sequences might inform image-based models of drug distribution. Prior to surgery, we acquired advanced dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) MRI sequences for eight brain tumor patients (7 gliomas and 1 metastatic adenocarcinoma) in addition to the anatomic MRIs. All resulting quantitative maps and acquired images were co-registered. Prior to incision, patients received injections of cefazolin and levetiracetam. Next, multiple blood samples and biopsies were collected during surgery. Biopsies and plasma samples were analyzed for drug concentration using liquid chromatography mass spectrometry (LCMS), and biopsy drug levels were reported as Brain-Plasma Ratio (BPR). Mean image intensity was extracted from a 15x15 voxel window surrounding the biopsy location. We performed linear regression analyses to determine which combination of images were predictive of BPR. We found that considering quantitative imaging improved our initial ability to predict BPR for both drugs. For cefazolin, the third diffusion tensor eigenvalue (L3) map was significantly correlated with BPR (p&amp;lt; 0.001, R2= 0.36). For levetiracetam, the best model consisted of a combination of images and maps with the L3 map and the isotropic diffusion map (P) being the most influential (p= 0.001, R2= 0.63). Advanced MRI-based modeling is a promising tool for forecasting drug distribution in brain tumors and could be of great importance for understanding efficacy and selecting therapeutic strategies.
Abstract P488: FAK Inhibition Reduces Hemangioma Proliferation By Blocking YAP Mediated HBEGF Expression
Authors: Yelitza Rodriguez Rodirguez, James Murphy, Kyuho Jeong, Thuy Phung, Erin Ahn, Steve Lim
Journal: Circulation Research (2021)

Hemangiomas are vascular tumors that develop from proliferative endothelial cells (EC). While primarily occurring on the skin of the head, neck, back and chest, hemangiomas can occur within any vascular beds including brain, liver and heart, which can lead to life-threatening complications. Non-surgical treatments are limited, and there are few phases I and II trials underway. Therefore, better understanding of what drives hemangioma proliferation and new therapeutic targets are needed. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that acts as a primary nexus of extracellular signals from integrins and growth factor receptors that sustain EC migration, proliferation, and survival. We observed that genetic and pharmacological inhibition of FAK significantly blocked vascular endothelial growth factor (VEGF)/ fibroblast growth factor (FGF)-induced Matrigel plug angiogenesis in vivo. To identify angiogenic factors regulated by FAK catalytic activity, we used an angiogenesis array in human umbilical vein ECs (HUVECs) and found that FAK inhibition reduced major regulators of angiogenesis including heparin-binding epidermal growth factor (HB-EGF). Further, using immunoblotting and RT-qPCR, we confirmed that FAK inhibition significantly reduced HB-EGF protein and mRNA expression in various mouse, human EC lines and human infantile hemangioma cell line, resulting in reduced EC proliferation. Importantly, HB-EGF mRNA expression was also reduced within in vivo Matrigel plugs of FAK inhibitor treated mice. Mechanistically, FAK binds to and phosphorylates YAP, which enhances HB-EGF expression. Loss of YAP tyrosine phosphorylation following FAK inhibition decreased YAP nuclear localization and protein stability. Since FAK inhibitors are undergoing clinical trials to treat cancer, these results suggest that FAK inhibitors could also prove beneficial in blocking EC proliferation associated with hemangioma.
Abstract 14044: Virtual Teaching Kitchen: A Feasibility Study of a Nutrition Intervention for Patients With Food Insecurity and Metabolic Disease
Authors: Iniya Rajendran, Olivia Weinstein, Preya Patel, Paige Lambert, Lisa M Quintiliani, Naomi Hamburg
Journal: Circulation (2021)

Introduction: Food insecurity is a well-established risk factor for cardiometabolic conditions. The objective of this study is to examine the feasibility and acceptability of a virtual teaching kitchen-based intervention to promote healthful food intake, cooking skills, and motivation to make dietary changes. Method: We conducted a single-group study among patients with metabolic syndrome and food insecurity. The intervention consisted of four classes delivering dietary education promoting healthy food intake, diet strategies, and practical cooking skills, facilitated by a physician and a registered dietician chef. An internet-capable tablet was provided for remote participation via the zoom platform. Interviewer-administered surveys measured food intake and internal motivation via Likert scale screeners at baseline and at immediate post-intervention time points. Interviews were conducted to explore acceptability. Results: Of 100 participants invited, 22 were recruited and 10 attended the intervention. Mean age was 61.2 years, nine were female, nine self-identified as Black, and two were Hispanic. Mean BMI was 32.7, all ten participants had hypertension, eight had both diabetes and obesity and seven had hyperlipidemia. Mean attendance per class was seven and five attended all four sessions. From baseline to post-intervention, there was a significant increase in consumption of low-fat milk (0.14 to 0.50, p=0.02), whole grains (0.28 to 0.99, p=0.01), breakfast (0.37 to 1.60, p=0.002) and home cooking (1.09 to 1.88, p=0.04). Internal motivation score was high at baseline and unchanged at follow-up (5.6 to 5.9, p=0.9). Qualitative analysis revealed the following themes: Increase in knowledge of healthy recipes; Barriers to healthy eating including competing household and childcare responsibilities; and Convenience of a virtual group while interacting with group members. Conclusions: Our virtual nutrition education intervention addressing cardiometabolic disease in a safety net hospital was deemed feasible and acceptable. Participants made modest changes to their diet. Future directions include measuring health outcomes and primary and secondary prevention of cardiovascular disease.
Abstract 12499: Risk of Venous Thromboembolism in Autoimmune Connective Tissue Diseases: A Population-Based Retrospective Study
Authors: Parth V Desai, Tauseef Akhtar, Axi Patel, Sovik De Sirkar, Kevin Walsh, Nicolas Krepostman, Matthew Collins, augustine manadan, Jawed Fareed, Amir Darki
Journal: Circulation (2021)

Introduction: Autoimmune Connective tissue diseases (CTD) are known to induce systemic and intravascular inflammation, endothelial damage, and the resulting surge in the prothrombotic milieu. However, the literature describing the correlation between various CTD and risk of Venous thromboembolism (VTE) is limited. Objective: We sought to assess the association of VTE and CTD in a nationwide larger population-based database. Methods: We conducted a retrospective analysis on all adults (aged &gt;=18 years) admitted with an index diagnosis of either acute Pulmonary Embolism (PE) or deep venous thrombosis (DVT) from the National Inpatient Sample (NIS) database (2017) using ICD 10 codes. Logistic regression models were used to adjust for the potential confounders of VTE including factors related to admission, hospital, and patients’ comorbidities. Results: Out of more than 30 million hospital admissions, a total of 285,650 patients (mean age 63±17 vs 57±20 yrs, p&lt;0.01; Females 51% vs 57%, p&lt;0.01) were identified with a primary diagnosis of VTE. Advancing age and black race (OR 1.38, 95% CI 1.35-1.42, p&lt;0.001) had a higher risk of VTE, whereas females had a lower risk of VTE compared to men (OR 0.82, 95% CI 0.8-0.83, p&lt;0.001). Out of twenty-one, autoimmune CTD evaluated in this study, eight diseases [antiphospholipid antibody syndrome (APS), ANCA vasculitis, dermatopolymyositis, giant cell arteritis (GCA), Polymyalgia rheumatica (PMR), Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and sarcoidosis] were independently associated with risk of VTE. APS (OR 4.4, 95% CI 3.8-5.1, p&lt;0.001), GCA (OR 1.8, 95% CI 1.4-2.3, p&lt;0.001), and SLE (OR 1.6, 95% 1.4-1.7, p&lt;0.001) had the highest risk of VTE based on their odds ratio. Conclusions: In our study, various autoimmune connective tissue diseases were significantly associated with the risk of VTE. Further studies are warranted to identify the underlying mechanism and preventive strategies in this population.
Abstract 13218: CITED4 is Required for Exercise-Induced Cardiac Growth and Cardiomyogenesis in Mice
Authors: Lena E Trager, Alexandra Kuznetsov, Margaret Lyons, Yoshiko Iwamoto, Robert Kitchen, Carolin Lerchenmueller, Colin Platt, James S Guseh, Nicholas Houstis, Haobo Li, Anthony Rosenzweig
Journal: Circulation (2021)

Introduction: CITED4 (CBP/p300-interacting transactivators with E [glutamic acid]/D [aspartic acid]-rich-carboxylterminal domain 4) is a transcriptional regulator which limits pathologic remodeling after ischemic and pressure overload models of cardiac stress. It is also upregulated in the heart with exercise, an effective intervention which induces physiological hypertrophy and cardiomyogenesis in adult mice. We hypothesized that CITED4 is required for exercise-induced cardiac growth and cardiomyogenesis. Methods and Results: Eight- to ten-week-old mice with cardiomyocyte-specific CITED4 knockout (C4KO) and littermate controls underwent 8 weeks of voluntary wheel running in comparison to sedentary controls. 5-Ethynyl-2′-deoxyuridine (EdU) was injected subcutaneously every two days for the first two weeks. There were no significant differences in cardiac size and function at baseline between C4KO and control mice. In control mice, running increased heart weight to tibial length ratio (HW/TL, 6.26±0.25 vs 7.37±0.75, p=0.01, n=5-9 per group), heart weight to body weight ratio (HW/BW, 4.08±0.40 vs 4.93±0.48, p=0.01), and cardiomyocyte (CM) size without affecting fractional shortening (FS), consistent with physiologic remodeling. There was also a nonsignificant trend to increased EdU+ CMs in the control exercised mice (2.96±2.34% vs 5.23±6.28%, p=0.44), suggestive of previously documented exercise-induced cardiomyogenesis. In contrast, running did not change HW/TL and CM size in C4KO mice (HW/TL, 6.44±0.48 vs 6.66±0.29, p=0.22, n= 0-13 per group) but reduced %FS (58.78±3.27 vs 53.67±4.59, p=0.03) and increased chamber size (LVIDs, 1.32±0.13 vs 1.50±0.17, p=0.032), suggesting maladaptive cardiac remodeling with exercise, confirming prior findings observed in a more extreme swim-exercise model. Rather than the expected increase, hearts from exercised C4KO mice had fewer EdU+ CMs compared to sedentary C4KO mice (3.76±2.60% vs 2.11±0.76%, p=0.05) and reduced expression of cell cycle genes Cdkn1b, Cyclin B1, Cdkn2a, and Ki-67. Conclusions: CITED4 is required for exercise-induced cardiomyogenesis, CM hypertrophy, and adaptive remodeling. CITED4 deficiency leads to maladaptive cardiac remodeling with physiologic stress.
COVID-19 Infection Among Women in Iran Exposed vs Unexposed to Children Who Received Attenuated Poliovirus Used in Oral Polio Vaccine
Authors: Farrokh Habibzadeh, Mohammad M. Sajadi, Konstantin Chumakov, Mahboobeh Yadollahie, Shyamasundaran Kottilil, Ashraf Simi, Kristen Stafford, Saeid Saeidimehr, Mohammad Rafiei, Robert C. Gallo
Journal: JAMA Network Open (2021)

Live attenuated vaccines may provide short-term protection against infectious diseases through stimulation of the innate immune system.To evaluate whether passive exposure to live attenuated poliovirus is associated with diminished symptomatic infection with SARS-CoV-2.In a longitudinal cohort study involving 87 923 people conducted between March 20 and December 20, 2020, the incidence of COVID-19 was compared between 2 groups of aged-matched women with and without exposure to live attenuated poliovirus in the oral polio vaccine (OPV). Participants were people receiving health care services from the Petroleum Industry Health Organization and residing in 2 cities in Iran (ie, Ahwaz and Shiraz). Participants were women aged 18 to 48 years whose children were aged 18 months or younger and a group of age-matched women from the same residence who had had no potential exposure to OPV.Indirect exposure to live attenuated poliovirus in OPV.Symptomatic COVID-19, diagnosed by reverse transcription-polymerase chain reaction.After applying the inclusion and exclusion criteria, 419 mothers (mean [SD] age, 35.5 [4.9] years) indirectly exposed to the OPV and 3771 age-matched women (mean [SD] age, 35.7 [5.3] years) who had no exposure to OPV were available for analysis. COVID-19 was diagnosed in 1319 of the 87 923 individuals in the study population (151 per 10 000 population) during the study period. None of the mothers whose children received OPV developed COVID-19 after a median follow-up of 141 days (IQR, 92-188 days; range, 1-270 days); 28 women (0.74%; 95% CI, 0.47%-1.02%) in the unexposed group were diagnosed with COVID-19 during the 9 months of the study. Point-by-point comparison of the survival curves of the exposed and unexposed groups found that indirect exposure to OPV was significantly associated with decreased COVID-19 acquisition; probability of remaining without infection was 1.000 (95% CI, 1.000-1.000) in the exposed group vs 0.993 (95% CI, 0.990-0.995) in the unexposed group after 9 months (P < .001).In this cohort study, indirect exposure to live attenuated poliovirus was associated with decreased symptomatic infection with COVID-19. Further study of the potential protective effect of OPV should be conducted, especially in nations where OPV is already in use for polio prevention and specific COVID-19 vaccines are delayed, less affordable, or fail to meet demand.
SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy
Authors: Xingyu Li, Peili Hou, Wenqing Ma, Xuefeng Wang, Hongmei Wang, Zhangping Yu, Huasong Chang, Tiecheng Wang, Song Jin, Xue Wang, Wenqi Wang, Yudong Zhao, Yong Zhao, Chunqing Xu, Xiaomei Ma, Yuwei Gao, Hongbin He
Journal: Cellular and Molecular Immunology (2021)

The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused severe morbidity and mortality in humans. It is urgent to understand the function of viral genes. However, the function of open reading frame 10 (ORF10), which is uniquely expressed by SARS-CoV-2, remains unclear. In this study, we showed that overexpression of ORF10 markedly suppressed the expression of type I interferon (IFN-I) genes and IFN-stimulated genes. Then, mitochondrial antiviral signaling protein (MAVS) was identified as the target via which ORF10 suppresses the IFN-I signaling pathway, and MAVS was found to be degraded through the ORF10-induced autophagy pathway. Furthermore, overexpression of ORF10 promoted the accumulation of LC3 in mitochondria and induced mitophagy. Mechanistically, ORF10 was translocated to mitochondria by interacting with the mitophagy receptor Nip3-like protein X (NIX) and induced mitophagy through its interaction with both NIX and LC3B. Moreover, knockdown of NIX expression blocked mitophagy activation, MAVS degradation, and IFN-I signaling pathway inhibition by ORF10. Consistent with our observations, in the context of SARS-CoV-2 infection, ORF10 inhibited MAVS expression and facilitated viral replication. In brief, our results reveal a novel mechanism by which SARS-CoV-2 inhibits the innate immune response; that is, ORF10 induces mitophagy-mediated MAVS degradation by binding to NIX.
Retinal Nerve Fiber Layer Thickness and Rim Area Profiles in Asians
Authors: Shivani Majithia, Yih-Chung Tham, Crystal Chun Yuen Chong, Marco Yu, Carol Y. Cheung, Mukharram M. Bikbov, Gyulli M. Kazakbaeva, Ningli Wang, Jie Hao, Kai Cao, Ya Xing Wang, Mariko Sasaki, Yoshikazu Ito, Ian Y. Wong, Jonathan Cheuk-Hung Chan, Rohit C. Khanna, Srinivas Marmamula, Eri Nakano, Yuki Mori, Tin Aung, Tien Yin Wong, Jost B. Jonas, Masahiro Miyake, Ching-Yu Cheng, Seema Banerjee, Miao Li Chee, Timur R. Gilmanshin, Ellina M. Iakupova, Fumihiko Matsuda, Asha Latha Mettla, Chi Pui Pang, Tyler Rim, Zhi-Da Soh, Clement C. Tham, Kazuo Tsubota, Akitaka Tsujikawa, Wen Bin Wei, Jian Wu, Jie Xu, Kenya Yuki
Journal: Ophthalmology (2021)
Abstract 13750: In-Hospital Outcomes of Mechanical Circulatory Support in Transcatheter Aortic Valve Implantation
Authors: Qasim Jehangir, Yi Lee, Nikolaos Kakouros, Osama Abdel-Hafez, Justin Field, Yessar Takruri, Mohammed Salih, Abdul R Halabi, Kirit Patel, Waqas Qureshi
Journal: Circulation (2021)

Introduction: Transcatheter aortic valve implantation (TAVI) is rarely complicated by acute circulatory collapse. Mechanical circulatory support (MCS) acts as a bridge to definitive intervention in these patients, however, the outcomes of MCS devices in TAVI patients are not well studied. Methods: Using the Nationwide Inpatient Sample Database from 2016 to 2018, we identified patients who underwent TAVI and required MCS using ICD-10 codes. The MCS devices included intra-aortic balloon pump (IABP) (group 1), Impella (group 2), and extracorporeal membrane oxygenation (ECMO) (group 3). Patients &lt;18 years and those requiring more than one device use were excluded. The primary outcome was in-hospital mortality and secondary outcomes were cardiac arrest, cerebrovascular accident, myocardial infarction, and renal failure. Results: Our analysis included 148,210 TAVI patients (based on weighted sample) with 1250 requiring MCS devices (IABP N=655, Impella N=360, ECMO N=235). Patients who required Impella were older than those who required ECMO and IABP (mean age group 1 75.8 ± 11.3, group 78.3 ± 10.1, group 3). The utilization of MCS devices was not different among the gender (females 46.2%; p = 0.2376) and races (Whites 86.8%, African Americans 4.26%, Hispanics 4.96%; p = 0.5038). Incidence of in-hospital mortality was highest in ECMO (group 1 27.5%, group 2 38.9%, group 3 42.6%, p &lt; 0.001) (Figure). The multivariate logistic regression model adjusted for MCS devices, age, race, sex, hypertension, diabetes, cardiopulmonary disease, kidney disease (CKD), liver disease, peripheral arterial disease (PAD), and arrhythmias indicated that use of any MCS device, age, female sex, congestive heart failure, CKD, liver disease, PAD, and arrhythmias were independent predictors of in-hospital mortality. Conclusions: In TAVI, the use of ECMO was associated with higher in-hospital mortality, cardiac arrest, major bleeding, and renal failure when compared to Impella and IABP.