tbuckley/cabot-search huggingface dataset:
Abstract 12409: Two-Dimensional Speckle Tracking of the Ascending Aorta: A Novel Approach to Evaluate Arterial Stiffness in Pediatric Patients With Repaired Conotruncal Abnormalities
Authors: Anmol Goyal, Anitha Parthiban, David A White, Daniel E Forsha, Doaa Aly
Journal: Circulation (2021)

Introduction: Children with repaired conotruncal abnormalities (rCTA) are at risk for progressive aortic dilation and arterial stiffness even after surgical correction. Pediatric data regarding use of 2D speckle tracking echocardiography (STE) for assessment of arterial stiffness is lacking. Our aim was to assess the feasibility and utility of 2D-STE derived ascending aorta (AAo) stiffness in children with rCTA. Methods: This was a prospective study, where pediatric patients with rCTA were included and compared to age and sex matched healthy controls. AAo strain, stiffness index and distensibility were measured using M-mode echo across the short axis of the AAo at the level of the right pulmonary artery. Peak AAo global circumferential strain (GCS) was measured using the left ventricle dedicated GCS algorithm by TomTec software version 4.6 SP3, CPA. Results: Total of 19 cases [13 (68%) with Tetralogy of Fallot, 4 (21%) with transposition of great arteries and 2 (10.5%) with truncus arteriosus], with mean age of 10.6 ± 4.2 yr and 17 matched controls have been enrolled to date. No subjects were excluded due to poor strain tracking. Patients with rCTA showed statistically significantly lower AAo GCS (8.2 ± 1.4 vs 15.2 ± 1.3), M-mode AAo strain (12.2 ± 5.3 vs 19.6 ± 3.8), AAo distensibility (3.6 ± 1.1 vs 6.1 ± 1.2), and higher AAo stiffness index (5.5 ± 2.1 vs 3.1 ± 0.6) than controls; fig 1. AAo GCS had strong correlation with age since surgical repair (r -0.8, p&lt;0.001); fig1. AAO distensibility and AAo stiffness index had moderate correlation (r -0.5; P&lt;0.05, r 0.4; P&lt;0.05 respectively) while M-mode AAO strain had weak correlation (-0.3 p=0.2) with age. Conclusions: 2D-STE measured AAo arterial stiffness is technically feasible in pediatric patients post rCTA and controls with significant between-group difference and a stronger correlation with age than the traditional measures of aortic stiffness. This may represent a new index in evaluating vascular biomechanics in pediatrics.
Abstract 9903: CT Number Predicts Calcium Thickness in Optical Coherence Tomography Guided Percutaneous Coronary Intervention
Authors: Kazumasa Kurogi, Masanobu Ishii, sou ikebe, Ryota Kaichi, Takayuki Mori, Soichi Komaki, Nobuyasu Yamamoto, Yuichiro Arima, Eiichiro Yamamoto, Koichi Kaikita, Kenichi Matsushita, Kenichi Tsujita
Journal: Circulation (2021)

Introduction: Optical coherence tomography (OCT) can assess calcium thickness, which is the key factor for predicting good stent expansion in calcified lesions. However, OCT can underestimate coronary calcium severity due to its penetration limitation and lipid accumulation while multi-slice computed tomography (CT) allows for a noninvasive assessment of coronary calcification. This study aimed to compare cross-sectional CT and OCT images for the assessment of calcification. Methods and Results: We investigated 33 lesions using coronary CT and OCT for the assessment of calcification. Of the 33 lesions, 211 regions of interest were set every 30 degrees in both the CT and OCT cross-sectional images. In 88 (41.7%) regions of interest with CT-detected calcium, the thickness of calcium was not detectable in the corresponding OCT image due to limited penetration, lipid attenuation, and guidewire artifact. There was an excellent correlation between CT number and thickness of calcium in the corresponding OCT image (R=0.797, P&lt;0.001). Receiver-operator curve analysis also showed fair discrimination between calcium thickness less than 500 μm and 500 μm or higher at a CT number of 1021 HU. Conclusions: Cross-sectional CT imaging could complement the underestimation of calcium severity in OCT-guided PCI, predicting the calcium thickness by CT number.
Abstract 11261: Impact of Baseline Heart Failure on RV:LV Diameter Ratio in Patients with Acute Pulmonary Embolism
Authors: Ayla Cash, Vanessa Pasadyn, Konrad Katterle, Matthew Niedoba, Pamela Brewster, Alexandria Mann, Rajesh Gupta
Journal: Circulation (2021)

Introduction: Among patients with acute pulmonary embolism (PE), an elevated right ventricular to left ventricular diameter (RV:LV) ratio is associated with increased morbidity and mortality. RV:LV cut-offs used to identify PE patients at elevated risk for adverse events range from 0.9-1.0. It is unclear whether this cut-off should be used for PE risk stratification among patients with heart failure (HF), who may have abnormal cardiac chamber dimensions. Methods: Patients diagnosed with acute PE between 2010 and 2015 at the University of Toledo Medical Center were identified. Patients were categorized as: no HF, heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF). No HF was defined as having no prior history of HF and an ejection fraction (EF) ≥ 50%. HFrEF was defined as history of HF and an EF &lt; 50%. HFpEF was defined as history of HF and an EF ≥ 50%. Results: One hundred and eighty-three patients were identified for this study. Twelve patients were excluded due to missing EF records. Among the remaining 171 patients, 142 were categorized as no HF, 13 were categorized as HFrEF, and 16 were categorized as HFpEF. There were no significant differences in mean RV diameter between HFrEF [39.1 mm, standard deviation (SD) ± 5.9], no HF [36.9 mm, SD ± 7.5], or HFpEF [38.5 mm, SD ± 6.6] (p=0.575). However, mean LV diameter among patients with HFrEF was significantly higher [52.2 mm, SD ± 7.2] compared to no HF [38.1 mm, SD ± 8.3] and HFpEF [42.1 mm, SD ± 6.6] (p&lt;0.001). Median RV:LV ratio was 0.77 [interquartile range (IQR) 0.65-0.89] for HFrEF, 0.91 [IQR 0.79-1.17] for no HF, and 0.89 [IQR 0.80-1.04] for HFpEF (p=0.024). Conclusions: Patients with HFrEF who presented to the hospital with acute PE had significantly higher mean LV diameter and lower RV:LV ratio compared to patients with HFpEF or no HF. These results suggest that risk stratification using current RV:LV ratio guidelines may underestimate PE risk among patients with HFrEF.
Abstract 11279: Coronary Microvascular Dysfunction in Patients with Elevated Filling Pressures During Exercise
Authors: Tess Allan, Frazer Tessema, Camron Shirkhodaie, Cynthia M Arévalo, John Blair
Journal: Circulation (2021)

Introduction: Ischemia due to coronary microvascular dysfunction (CMD) may cause a loss of lusitropy and resultant elevated filling pressures which can worsen with exercise. CMD is prevalent in patients with heart failure with preserved ejection fraction (HFpEF) and exercise studies are useful in diagnosing early HFpEF. The relationship between CMD and early HFpEF is not well characterized. Hypothesis: CMD is prevalent in patients with elevated pulmonary capillary wedge pressure (PCWP) at rest and those with normal resting PCWP but elevated post-exercise PCWP. Methods: All patients without obstructive CAD who underwent cardiac catheterization with coronary physiology and exercise bicycle studies at the University of Chicago Medical Center between 2015-2021 were included. Elevated resting PCWP was defined as &gt; 15 and elevated post-exercise PCWP was defined as &gt; 25. Patients were separated into three groups: elevated resting PCWP (group 1), normal resting &amp; elevated exercise PCWP (group 2), and normal resting and exercise PCWP (group 3). Results: A total of 22 patients (mean age 56 + 10 years, 77% female) were studied. There were 9 patients in group 1, 8 patients in group 2, and 5 patients in group 3. A diagnosis of HFpEF was present in all patients in groups 1 and 2 and no patients in group 3. There was a nonsignificant trend towards lower median CFR in groups 1 (2.1 IQR 1.6-2.8) and 2 (2.3 IQR 1.75-3.65) compared to group 3 (3.8 IQR 1.8-5.5; Figure 1). Similarly, there was a nonsignificant trend towards higher median IMR in groups 1 (23.2 IQR 16.9-41.3) and 2 (25.9 IQR 19.0-35.2) compared to group 3 (14.4 IQR 11-25; Figure 1). Conclusion: Like patients with elevated resting PCWP, patients with normal resting and elevated post-exercise PCWP tend to have lower CFR and higher IMR than those patients with normal pre and post-exercise PCWP. This may indicate that CMD plays a role in the development of early HFpEF though more patients are needed to further characterize this relationship.
IMMU-09. HUMAN MICROBIOTA INFLUENCE THE EFFICACY OF IMMUNOTHERAPY IN A MOUSE MODEL OF GLIOBLASTOMA
Authors: Kory Dees, Hyunmin Koo, James Humphreys, Joseph Hakim, David Crossman, Michael Crowley, L Burt Nabors, Etty Benveniste, Casey Morrow, Braden McFarland
Journal: Neuro-Oncology (2021)

Abstract Although immunotherapy works well in glioblastoma (GBM) pre-clinical mouse models, the therapy has unfortunately not demonstrated efficacy in humans. In melanoma and other cancers, the composition of the gut microbiome has been shown to determine responsiveness or resistance to immune checkpoint inhibitors (anti-PD-1). Most pre-clinical cancer studies have been done in mouse models using mouse gut microbiomes, but there are significant differences between mouse and human microbial gut compositions. To address this inconsistency, we developed a novel humanized microbiome (HuM) model to study the response to immunotherapy in a pre-clinical mouse model of GBM. We used five healthy human donors for fecal transplantation of gnotobiotic mice. After the transplanted microbiomes stabilized, the mice were bred to generate five independent humanized mouse lines (HuM1-HuM5). Analysis of shotgun metagenomic sequencing data from fecal samples revealed a unique microbiome with significant differences in diversity and microbial composition among HuM1-HuM5 lines. Interestingly, we found that the HuM lines responded differently to anti-PD-1. Specifically, we demonstrate that HuM2 and HuM3 mice are responsive to anti-PD-1 and displayed significantly increased survival compared to isotype controls, while HuM1, HuM4, and HuM5 mice are resistant to anti-PD-1. These mice are genetically identical, and only differ in the composition of the gut microbiome. In a correlative experiment, we found that disrupting the responder HuM2 microbiome with antibiotics abrogated the positive response to anti-PD-1, indicating that HuM2 microbiota must be present in the mice to elicit the positive response to anti-PD-1 in the GBM model. The question remains of whether the “responsive” microbial communities in HuM2 and HuM3 can be therapeutically exploited and applicable in other tumor models, or if the “resistant” microbial communities in HuM1, HuM4, and HuM5 can be depleted and/or replaced. Future studies will assess responder microbial transplants as a method of enhancing immunotherapy.
Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics
Authors: Xiaomin Yuan, Biqing Chen, Zhenglan Duan, Ziqian Xia, Yang Ding, Tuo Chen, Huize Liu, Baosheng Wang, Bolin Yang, Xiaoyong Wang, Shijia Liu, Jin-Yong Zhou, Yajun Liu, Qiong Wang, Zhaofeng Shen, Jun Xiao, Hongtao Shang, Weiwei Liu, Guoping Shi, Lei Zhu, Yugen Chen
Journal: Gut Microbes (2021)

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2ʹ-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2ʹ-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.
QOLP-12. ILLNESS UNDERSTANDING AND PERCEPTIONS ABOUT PROGNOSIS IN PATIENTS WITH MALIGNANT GLIOMAS AND THEIR CAREGIVERS
Authors: John Rhee, Michelle Mesa, Emilia Kaslow-Zieve, Lara Traeger, Areej El-Jawahri, Jennifer Temel, Deborah Forst
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Malignant gliomas (MG) are incurable tumors with limited survival. Prognostic awareness is essential for informed decision making, but patients’ and caregivers’ perceptions about their illness and prognosis are not well understood. METHODS We conducted a prospective, single-institution study in patients with newly diagnosed MG and their caregivers, following the outpatient visit in which their neuro-oncologist disclosed pathology results and discussed treatment options. Participants (patients and caregivers) completed the Prognosis and Treatment Perceptions Questionnaire to assess information preferences, treatment goals and prognostic understanding. RESULTS Of patients approached, 82% (14/17) were eligible and enrolled in the study. The majority of patients were male (9/14, 64%), median age 60 years (range 26-76) and had a glioblastoma (11/14, 79%). Most caregivers were female (8/11, 73%) and married to the patient (7/11, 64%). The majority of patients said their cancer was curable (10/13, 77%, one patient did not answer), while only 3/11 caregivers (27%) said the patient’s cancer was curable. Furthermore, 7/13 patients (54%) and 8/11 caregivers (73%) reported that their oncologist said their cancer was not curable, and the remainder (6/13 patients, 46% and 3/11 caregivers, 27%) said the oncologist “did not say” whether it was curable. Most patients (10/14, 71%) and caregivers (8/11, 73%) expressed a tendency to focus on the best-case scenario in response to information from their oncology team about their cancer. CONCLUSION Although most patients with MG and their caregivers acknowledged being told that their cancer was incurable, the majority of patients reported that their cancer was curable. Patients and caregivers often reported focusing on the best-case scenario regarding their cancer. Further investigation is warranted to explore strategies to support patients and caregivers learning about their incurable cancer.
Hepatology Highlights
Authors: Nabeel Wahid, Arun Jesudian, Adam Buckholz, Robert S. Brown, Danielle Kovac, Amani Lee, Enis Kostallari, Robert E. Schwartz, Petra Hirsova, Nidhi Jalan‐Sakrikar, Amneet Hans, Giorgio Roccaro, Alyson Kaplan, Hirsh Trivedi, Mina Choudhry, Daryl T.Y. Lau, Anthony J. Choi
Journal: Hepatology (2021)
Abstract 13669: Secondary Prevention Aspirin Trends in the Upper Midwest, 2015-2019
Authors: Jeremy R Vant Hof, Sue Duval, Milton Eder, Niki C Oldenburg, John Finnegan, Russell Luepker
Journal: Circulation (2021)

Introduction: Secondary prevention (SP) aspirin use after a cardiovascular disease (CVD) event is strongly recommended and supported by consistent guidelines. Aspirin recommendations for primary prevention have varied over time, recently becoming more restrictive after clinical trials published in 2018. Hypothesis: Negative scientific and media attention regarding primary prevention aspirin would result in unintentional decline in SP aspirin use. Methods: We conducted random telephone surveys of adults aged 45-79 years in the upper Midwest in 2015, 2017, and 2019. We queried participant demographics, CVD history and risk factors and aspirin use. Using logistic regression, we evaluated i) the trend in SP aspirin use over the 3 surveys and ii) characteristics associated with SP aspirin non-use, adjusting for other antithrombotic use. Results: A total of 1907 adults with history of CVD provided data for analysis, median age 70 years, 38% female. There was no significant change in SP aspirin use in the total sample, nor by age, sex, or CVD risk factors. SP aspirin use was significantly lower among participants with 0-1 CVD risk factors compared with those diagnosed with ≥2 (Figure). Younger participants also used aspirin less frequently (67% for &lt;60 years vs 76% for 60+ years). Respondents who talked with their healthcare provider about aspirin had much higher aspirin use than those who did not (87% vs 60%). In the 2019 survey, 11% of participants stopped aspirin. Stoppers were more likely to be on another antithrombotic medication (61% vs 43%) and less likely to have the diagnosis of hypertension (78% vs 81%) or hyperlipidemia (68% vs 72%) compared with those on aspirin. Stoppers also had fewer aspirin discussions with their provider (45% vs 69%). Conclusions: It is reassuring that SP aspirin use did not drop during a time of negative messaging for primary prevention aspirin. Unfortunately, underuse remains evident in younger adults and those with fewer CVD risk factors.
Abstract 10506: Cardiac Rehabilitation Visits Have Not Recovered to Pre-Pandemic Levels
Authors: Mike P Thompson, Hechuan Hou, Jessica Yaser, Steven J KETEYIAN, Francis D Pagani, Donald S Likosky, Hari Nathan, Devraj Sukul
Journal: Circulation (2021)

Introduction: The COVID-19 pandemic led to temporary restrictions on in-person cardiac rehabilitation (CR) services to mitigate high-risk exposure. Hypothesis: In order to better understand the impact of COVID-19 restrictions on CR services, we evaluated changes in the frequency and characteristics of CR visits in 2020 compared with 2019 in a commercially-insured population. Methods: We queried the Michigan Value Collaborative statewide claims data registry for outpatient CR visits between 01/01/2019 and 12/31/2020 using CPT codes (93797, 93798) among patients with diagnoses of ischemic heart disease, heart failure, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or heart valve procedure. We described monthly trends in CR visits, and used bivariate analyses to compare changes in the demographics and medical diagnoses for CR visits in 2020 compared with 2019. Results: We identified a total of 45,553 CR visits in 2019 and 30,236 visits in 2020, representing a 33.6% relative decline. Monthly CR visits reached a nadir of 138 visits in April 2020 (96.5% reduction compared with April 2019), recovered to 3072 visits in September (-17.9%), and fell again to 2434 visits in December (-34.7%) (Figure). Relative changes in CR visits from 2019 to 2020 varied by diagnosis (p&lt;0.001): -50.3% for heart failure (2931 to 1456, -37.5% for CABG (10121 to 6329), -35.3% for PCI (19669 to 12729), -28.9% for valve surgery (5621 to 3994), and -20.6% for ischemic heart disease (7211 to 5728). There were no significant differences in patient mean age (68.0 vs. 68.1 years, p=0.62) or gender (39.8% vs. 39.9% female, p=0.839) in 2019 compared with 2020. Conclusions: Total cardiac rehabilitation visits in 2020 were 33.6% lower compared with 2019, with heterogeneity in declines by underlying eligible diagnosis. Continued monitoring is needed to understand the public health impact of reduced CR use due to the COVID-19 pandemic.
Abstract 117: Ponatinib Mediated Cardiotoxicity Is Driven By Pro-inflammatory S100A8/A9-NLRP3-IL-1β Signaling Circuit
Authors: Anand P Singh, Sultan Tousif, Prachi Umbarkar, Cristi L Galindo, Nicholas Wheeler, Qinkun Zhang, Sumanth Prabhu, Hind Lal
Journal: Circulation Research (2021)

Background: Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) for chronic myelogenous leukemia (CML) treatment. Of note, ponatinib is the only treatment option for CML patients with T315I (gatekeeper) mutation. Unexpected clinical cardiotoxicity, including fatal myocardial infarction and congestive heart failure, has hampered its clinical use. Herein, we aimed to investigate the cardiotoxic mechanism of ponatinib and strategies to prevent the cardiotoxic manifestations. Methods: We employed wild-type C57BL/6, cardiovascular (CV) comorbidity models e.g., transverse aortic constriction (TAC)-pressure overload (cardiac comorbidity) and high-fat diet fed ApoE -/- (vascular comorbidity), to investigate the cardiotoxic mechanism of ponatinib. Echocardiography was performed to assess cardiac function. Comprehensive immune profiling was performed to identify ponatinib-induced immune dynamics using flow cytometry analysis. Results: Echocardiographic assessment of ponatinib treated high-fat diet fed ApoE -/- and pressure overload (PO) murine model showed significant decline in cardiac function, suggesting the key role of CV-comorbidities in ponatinib-induced cardiomyopathy. An unbiased RNA-Seq analysis identified the enrichment of dysregulated inflammatory genes, including a multi-fold upregulation of alarmins S100A8/A9 as a top hit in ponatinib-treated hearts. A combination of in vitro and in vivo mechanistic analysis, identified that ponatinib activates the S100A8/9-TLR4-NLRP3-IL-1β signaling pathway in cardiac and systemic myeloid cells (monocytes and neutrophils), thereby leading to excessive myocardial and systemic inflammation. Finally, we demonstrate that ponatinib-induced excessive inflammation is central to the cardiac pathology because a broad immunosuppressive agent dexamethasone abolished the adverse cardiac remodeling and dysfunction of ponatinib treated hearts. Conclusions: These findings uncover a novel mechanism of ponatinib-induced cardiac inflammation leading to cardiac dysfunction. Our results provide critical preclinical data and rationale for clinical investigation into immunosuppressive interventions to mitigate ponatinib-induced cardiotoxicity.