tbuckley/cabot-search huggingface dataset:
Abstract 15772: Cardiovascular Hospitalizations and Procedures Plummet Nationwide During Covid-19 - an Analysis of US Medical Claims
Authors: Monica R Shah, Tanya F Partridge, Xiaoqing Xue, Justin L Gregg
Journal: Circulation (2020)

Introduction: Regional studies have reported a decline in cardiovascular (CV) hospitalizations and procedures with the onset of the coronavirus disease-2019 (COVID-19) pandemic. Factors may include patient reluctance to seek care and de-prioritization of approvals for CV admissions by hospitals. We wanted to assess these observations at a national level. Hypothesis: To examine national trends in CV hospitalizations for acute myocardial infarction (AMI), unstable angina (USA), and heart failure (HF), as well as left heart catheterizations (LHC), using US medical claims data. Methods: We interrogated IQVIA US Claims data, a verified source, from Jan 2019 to May 2020 (214 million patients; 76% private insurance claims, 19% Medicare claims, 5% Medicaid claims). Since confirmed COVID-19 cases in the US began rising in Mar 2020, this was used as reference point to identify cohorts for comparison. Trends in volumes of hospitalizations for key CV events (AMI, USA, and HF) and LHC were compared from Mar 1 to May 8, 2020 to the equivalent time period in 2019. We used a Bayesian hierarchical model to assess trends. Results: From Mar to May 2020, compared to 2019, there were significantly fewer hospitalizations for: key CV events (1,110,492 vs. 1,487,558; p=0.0016); AMI (277,615 vs. 412,235; p=0.0002); USA (1,007 vs. 1,688, p=0.1245); and, HF (831,870 vs. 1,073,635; p=0.0036). There were significantly fewer LHC (118,393 vs. 221,701; p=0.0002). As shown in the Figure, there was a significant decline in CV hospitalizations in 2020 compared to 2019. Conclusions: During the COVID-19 pandemic, CV hospitalizations have declined significantly in the US. We observed an ~25% drop in CV hospitalizations and an ~50% drop in LHC. To the best of our knowledge, this is the first national evaluation of trends in CV care during COVID-19 and validate concerns that acute CV care in the US has been delayed or deferred, potentially foreshadowing a surge of CV complications in the future.
The National Cancer Institute’s Role in Advancing Health-Care Delivery Research
Authors: Paul B Jacobsen, Janet de Moor, V Paul Doria-Rose, Ann M Geiger, Sarah C Kobrin, Annie Sampson, Ashley Wilder Smith
Journal: JNCI Journal of the National Cancer Institute (2021)

Improvements in cancer care delivery have the potential to reduce morbidity and mortality from cancer, however, challenges to delivery of recommended care limit progress. These challenges include growing demands for care, increasing treatment complexity, inadequate care coordination, dramatic increases in costs, persistent disparities in care, and insufficient use of evidence-based guidelines. Recognizing the important role of research in understanding and addressing these challenges, the National Cancer Institute created the Healthcare Delivery Research Program (HDRP) in 2015 as a catalyst for expanding work in this area. Health-care delivery research is a multidisciplinary effort which recognizes that care delivery occurs in a multilevel system encompassing individuals, health-care systems, and communities. HDRP staff use a range of activities to fulfill the program's mission of advancing innovative research to improve delivery of care across the cancer control continuum. In addition to developing funding opportunities, HDRP staff; support and facilitate the use of research infrastructure for conducting health-care delivery research; oversee publicly available data that can be used to evaluate patterns, costs, and patient experiences of care; contribute to development and dissemination of standardized health measurement tools for public use; and support professional development and training to build capacity within the field and grow the workforce. As HDRP enters its sixth year, we appreciate the opportunity to reflect on the program's progress in advancing the science of health-care delivery. At the same time, we recognize the need for the program to evolve and develop additional resources and opportunities to address new and emerging challenges.
175P Tumour biology in young breast cancer patients (YBCP): A different disease?
Authors: B. Cantos Sanchez De Ibarguen, M. Mendez Garcia, M. Blanco Clemente, B. Nunez Garcia, C. Corbacho, C. Gonzalez Lois, R. Aguado, Y. Garitaonaindia, M. Provencio Pulla, J.C. Sánchez
Journal: Annals of Oncology (2021)
Correspondence on ‘Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry’
Authors: James Todd Rosenbaum, Michael H Weisman, Cassie Shafer, Elin Aslanyan, Richard A Howard, Kimberly Ogle, Hedley Hamilton, John D Reveille, Kevin L Winthrop, Dongseok Choi
Journal: Annals of the Rheumatic Diseases (2021)

Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecine] is a water-soluble analogue of camptothecine used in the second-line treatment of advanced colon cancer. Recently, we identified, in the plasma of patients and in human liver microsomal incubations, the presence of a new metabolite of irinotecan, 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecine (NPC), which is produced by cleavage of the distal piperidine ring of irinotecan. The kinetics of biotransformation of the lactone and carboxylate forms of irinotecan into NPC were studied using human liver microsomes. The formation of NPC was characterized by the following parameters:<i>K<sub>M</sub></i> = 48.2 ± 6.8 and 273 ± 122 μM and <i>V</i><sub>max</sub> = 74.1 ± 4.9 and 78.6 ± 27.7 pmol/min/mg of protein for the lactone and carboxylate forms of irinotecan, respectively. Interestingly, there was no formation of NPC from 7-ethyl-10-[4-<i>N</i>-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecine, a major metabolite of irinotecan that has an open distal piperidine ring and could be considered a possible metabolic precursor of NPC. The transformation of irinotecan into NPC was found to be catalyzed principally by cytochrome P450 (CYP) 3A, based on three key results, as follows: 1) the CYP3A-selective inhibitors ketoconazole (1 μM) and troleandomycin (100 μM) inhibited NPC formation by 99 and 100%, respectively; 2) of a series of microsomal preparations from transfected lymphoblastoid cells expressing specific CYPs, only those from CYP3A4 cDNA-transfected cells transformed irinotecan into NPC; and 3) incubations with 15 individual preparations of human liver microsomes yielded highly significant correlations between the formation of NPC and both immunoreactivity with anti-CYP3A antibodies and testosterone 6β-hydroxylation (an activity specifically mediated by CYP3A). The effects of 11 drugs (used at 100 μM) on this metabolism were studied with irinotecan lactone (25 μM). Although ondansetron, loperamide, and racecadotril inhibited this pathway by 75, 95, and 95%, respectively, the concentrations used may not be clinically achievable. However, significant inhibition by ketoconazole and troleandomycin indicates that NPC formation in patients may be influenced by coadministration of drugs with known anti-CYP3A activities.
Abstract MP10: A Novel Genetic Locus Influences Microvascular Reactivity To Acute Psychological Stress
Authors: Zakaria Almuwaqqat, Chang Liu, Jeong Hwan Kim, Bruno B Lima, Muhammad Hammadah, Ayman Alkhoder, Amit J Shah, James Douglas Bremner, Viola Vaccarino, Yan Sun, Arshed A Quyyumi
Journal: Circulation (2021)

Background: Excessive peripheral microvascular constriction during acute psychological stress, measured using peripheral arterial tonometry reflects similar changes in coronary blood flow.The ratio of digital pulse wave amplitude during stress compared to rest (sPAT) is used to estimate the degree of microvascular response to stress. Hypothesis: We hypothesized that genetic factors contribute to the degree of microvascular constriction during mental stress and that excessive vasoconstriction is associated with adverse cardiovascular outcomes. Methods: A total of 580 stable CAD subjects of European and African ancestries from two prospective cohort studies underwent mental stress testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured using PAT and the stress/rest PAT ratio (sPAT) of pulse wave amplitude during mental stress/baseline was calculated. Genotyping was performed using Illumina’s Multi-Ethnic Genotyping Array platform and imputed to the 1000 Genome reference panel. Ethnicity-specific genome-wide association studies (GWAS) of sPAT were conducted using linear regression of additive genetic mode adjusted for age, sex and population stratification in both cohorts. A trans-ethnic meta-analysis integrated the GWAS results from four sub-cohorts. Upon 5-year follow-up, Fine and Gray’s sub-distribution hazard ratios (sHR) were used to examine the association between sPAT ratio (&gt; vs=&lt; median) and the composite endpoint of cardiovascular death, myocardial infarction, revascularization, and hospitalization for heart failure. Results: Mean age was 63±9; 65% male, 35% African American. We identified three SNPs in linkage disequilibrium on chr7:111,666,943 T&gt;C (rs6466396); chr7: 111,668,622 T&gt;G (rs876170); chr7: 111,668,623 T&gt;G (rs876169) that were associated with greater sPAT ratio by means of 0.13, 0.12 and 0.10, ( P = 1.42E-08). The sPAT-associated locus was within DOCK4 gene which encodes Dedicator of Cytokinesis 4, an essential protein for angiogenesis and brain development, and a known locus for obesity. After adjusting for demographic and cardiovascular risk factors, medications, and rate-pressure product change during mental stress, those with low sPAT ratio were at significantly higher risk of adverse outcomes (sHR 1.8 [95% CI 1.1 - 2.8]). Conclusion: We have identified a genetic basis for stress-induced vasomotion. Presence of allele C (rs6466396) is associated with increased vasoconstriction during mental stress, and thus may predispose CAD patients to a higher risk for adverse cardiovascular outcomes with stressful exposure.
How machine learning is impacting research in atrial fibrillation: implications for risk prediction and future management
Authors: Ivan Olier, Sandra Ortega-Martorell, Mark Pieroni, Gregory Y H Lip
Journal: Cardiovascular Research (2021)

There has been an exponential growth of artificial intelligence (AI) and machine learning (ML) publications aimed at advancing our understanding of atrial fibrillation (AF), which has been mainly driven by the confluence of two factors: the advances in deep neural networks (DeepNNs) and the availability of large, open access databases. It is observed that most of the attention has centred on applying ML for dvsetecting AF, particularly using electrocardiograms (ECGs) as the main data modality. Nearly a third of them used DeepNNs to minimize or eliminate the need for transforming the ECGs to extract features prior to ML modelling; however, we did not observe a significant advantage in following this approach. We also found a fraction of studies using other data modalities, and others centred in aims, such as risk prediction, AF management, and others. From the clinical perspective, AI/ML can help expand the utility of AF detection and risk prediction, especially for patients with additional comorbidities. The use of AI/ML for detection and risk prediction into applications and smart mobile health (mHealth) technology would enable 'real time' dynamic assessments. AI/ML could also adapt to treatment changes over time, as well as incident risk factors. Incorporation of a dynamic AI/ML model into mHealth technology would facilitate 'real time' assessment of stroke risk, facilitating mitigation of modifiable risk factors (e.g. blood pressure control). Overall, this would lead to an improvement in clinical care for patients with AF.
Abstract 13131: Cardiovascular Manifestations and Outcomes in Systemic Lupus Erythematosus: The Cleveland Clinic Contemporary Experience
Authors: Tom Kai Ming Wang, Nicholas Chan, Mohamed Khayata, Patrick Flanagan, Richard A Grimm, Brian P Griffin, Elaine M Husni, Emily Littlejohn, Bo Xu
Journal: Circulation (2020)

Background: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting multiple organs including the heart, which when affected portends poor prognosis. Given the advances in therapies and vigilance for cardiovascular screening for SLE patients, we evaluated the contemporary cardiovascular characteristics, manifestations and outcomes in SLE patients at our tertiary referral center. Methods: Consecutive patients from the prospective SLE bio-repository at our center between October 2012 and March 2020 were included. Cardiovascular data pertaining to manifestations, investigations, management and outcomes were collected. Results: 258 SLE patients were studied, with mean age 42.2 ± 14.7 years and 233 (90.3%) females. Cardio-respiratory symptoms were present in 92 (35.7%), most commonly dyspnea in 62 (24.0%) and chest pain in 53 (20.5%). Cardiac manifestations occurred in 97 (37.6%) patients, with pericardial disease in 38 (14.7%), valvular disease in 20 (7.8%), stroke/transient ischemic attack in 20 (7.8%), coronary heart disease in 17 (6.6%) and heart failure hospitalizations in 13 (5.0%) (Table 1). During a mean follow-up of 3.0 ± 2.2 years, there were 5 (1.9%) deaths, 19 (7.4%) developed cardiac events (table 1), 6 (2.3%) had cardiovascular procedures (3 cardiac surgeries, 2 percutaneous interventions and 1 device), and 44 (17.1%) had SLE-related hospitalizations. Conclusion: Cardiac manifestations remain prevalent in SLE, especially for pericardial, valvular and atherosclerotic diseases. With appropriate contemporary SLE and cardiovascular management, subsequent medium term adverse cardiovascular outcomes are low.
Glucose-lowering treatments and COVID-19 mortality in T2DM
Authors: Samy Hadjadj, Matthieu Wargny
Journal: Nature Reviews Endocrinology (2021)

The poor prognosis in patients with diabetes mellitus who contract COVID-19 urged physicians to question routine drug treatment for people with type 2 diabetes mellitus. What treatment should we prioritize? So far only observational studies are available, although complementary interventional studies are needed to address this issue.
Abstract 10946: Innovate Therapeutic Strategy Using Prostaglandin I2 Agonist (Ono1301) Combined With Nano Drug Delivery System for Pulmonary Hypertension Through the Mechanism of Suppression of Smooth Muscle Cell Proliferation in Rat
Authors: Tomomitsu Kanaya, Shigeru Miyagawa, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2018)

Introduction: Pulmonary arterial hypertension (PAH) is a life-threatening disease and administration of drugs having new concept with efficient delivery system may be crucial for improvement of cli...
Neutralization of PD-L2 is Essential for Overcoming Immune Checkpoint Blockade Resistance in Ovarian Cancer
Authors: Yu Rebecca Miao, Kaushik N. Thakkar, Jin Qian, Mihalis S. Kariolis, Wei Huang, Saravanan Nandagopal, Teddy Tat Chi Yang, Anh N. Diep, Gerald Maxwell Cherf, Yu Xu, Eui Jung Moon, Yiren Xiao, Haizea Alemany, Tiane Li, Wenhua Yu, Bo Wei, Erinn B. Rankin, Amato J. Giaccia
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Ovarian cancer represents a major clinical hurdle for immune checkpoint blockade (ICB), with reported low patient response rates. We found that the immune checkpoint ligand PD-L2 is robustly expressed in patient samples of ovarian cancers and other malignancies exhibiting suboptimal response to ICB but not in cancers that are ICB sensitive. Therefore, we hypothesize that PD-L2 can facilitate immune escape from ICB through incomplete blockade of the PD-1 signaling pathway. Experimental Design: We engineered a soluble form of the PD-1 receptor (sPD-1) capable of binding and neutralizing both PD-L2 and PD-L1 with ×200 and ×10,000 folds improvement in binding affinity over wild-type PD-1 leading to superior inhibition of ligand-mediated PD-1 activities. Results: Both in vitro and in vivo analyses performed in this study demonstrated that the high-affinity sPD-1 molecule is superior at blocking both PD-L1– and PD-L2–mediated immune evasion and reducing tumor growth in immune-competent murine models of ovarian cancer. Conclusions: The data presented in this study provide justification for using a dual targeting, high-affinity sPD-1 receptor as an alternative to PD-1 or PD-L1 therapeutic antibodies for achieving superior therapeutic efficacy in cancers expressing both PD-L2 and PD-L1.
Abstract 17024: Clinical and Echocardiographic Predictors of Death and Hospital Readmission in Patients With Recent Onset Severe Secondary Tricuspid Regurgitation
Authors: Katherine M Nichols, Andrew Milbridge, Bruce W Andrus
Journal: Circulation (2020)

Introduction: Tricuspid regurgitation (TR) is often asymptomatic leading to delayed diagnosis. Predictors of decompensation and indications and timing for intervention are not well delineated. We studied the clinical and echocardiographic outcomes of patients with recent onset severe, secondary TR to identify risk factors for death, hospital readmission and hepatobiliary disease. Methods: We queried our institutional echo database to identify all patients with severe secondary TR in 2010 and a TTE within the previous two years prior showing less than moderate disease. Baseline and follow up clinical and echocardiographic variables over the subsequent 10 years were collected retrospectively. We analyzed our data for predictors of death, hospital readmission, and hepatobiliary disease. Results: We identified 34 patients. Over 10 years of follow up, 27/34 (79%) of the patients died. Elevated pulmonary artery systolic pressure (PASP) was a significant predictor of death. PASP was 48 mm Hg in those who died compared to 33 mm Hg in those who survived (p=0.02) (Figure 1). Pulmonary hypertension (PH) and pulmonary embolism (PE) were predictors of readmission. A history of PH was present in 7/10 (70%) of patients requiring readmission compared to 7/24 (29%) in those who did not require readmission (p=0.03). A history of PE was present in 2/10 (20%) of those requiring readmission compared to 0/24 (0%) of those who did not require readmission (p=0.02). No patients were diagnosed with hepatobiliary disease. Conclusions: New onset severe, secondary TR is associated with a high ten year mortality rate. Elevated PASP is a predictor of death and history of PE and pulmonary HTN are predictors for hospital readmission.
Increased Plasma von Willebrand Factor (vWF) Level Predicts Left Atrial Appendage Thrombus Formation in Patients with Acute Ischemic Stroke
Authors: Wanezaki Masahiro, Watanabe Tetsu, Tamura Harutoshi, Nishiyama Satoshi, Sasaki Shintaro, Arimoto Takanori, Takahashi Hiroki, Shishido Tetsuro, Miyamoto Takuya, Nitobe Joji, Kubota Isao
Journal: Circulation (2011)
Abstract 13062: Epicardial Fat Associates With Endothelial Dysfunction, but Not With Coronary Calcium Score: From the Elsa-brasil Cohort Study
Authors: Karina P Martins, Sandhi Barreto, Daniel Bos, JESIANA PEDROSA, Douglas Mesquita, Murilo Foppa, Bruce Duncan, Antonio Ribeiro, Luisa C Brant
Journal: Circulation (2020)

Introduction: Epicardial fat has been related to coronary artery disease (CAD) independent of visceral or subcutaneous fat. The mechanism responsible for this association has not yet been elucidated. Our objective was to evaluate the association between automatically measured epicardial fat volume (EFV), cardiovascular risk factors, coronary artery calcium (CAC) and endothelial function in participants of ELSA-Brasil. Methods and Results: The sample comprised 470 (mean age 55± 8y, 52.3% men) participants from ELSA-MG, one of the Investigation Centers of the cohort, who had valid computed tomography scans and endothelial function evaluated by peripheral arterial tonometry (PAT). The mean EFV was 111 (IQ 86-144) mL. CAC=0 was detected in 55% of participants. In the multivariable analyses between cardiovascular risk factors and EFV, the following associations were observed with higher EFV: female sex; and increased age, waist circumference and triglycerides (p &lt;0.001 for all). In multivariable analyses, higher EFV remained associated with worse endothelial function - basal pulse amplitude (q2=1.22, CI95% 1.07-1.40, p=0.004; q3=1.50, CI95% 1.30-1.74, p&lt;0.001; q4=1.50, CI95% 1.28-1.79, p&lt;0.001) and PAT ratio (q2=0.87, CI95% 0.81-0.95, p&lt;0.001; q3=0.86, CI95% 0.79-0.94, p&lt;0.001; q4=0.80, CI95% 0.73-0.89, p&lt;0.001), but not with CAC. Conclusions: Higher EFV was associated with impaired endothelial function, but not with higher CAC. Our results suggest that the mechanism by which epicardial fat deposits relates to CAD may be different from the pathway of CAC, which relates to calcified plaques. A possible mechanism may be through the enhancement of endothelial dysfunction, microvascular disease and predominantly lipidic non-calcified plaques.
Abstract 17048: The Association of Neighborhood Deprivation With Racial Disparities in 30-day Heart Failure Readmissions in Middle Aged Adults
Authors: Shivani A Patel, Aditi Nayak, Theresa Shirey, Kaitlyn Long, Neal W Dickert, Alanna A Morris
Journal: Circulation (2020)

Introduction: Neighborhood socioeconomic status (N-SES) is associated with incident heart failure (HF) and HF readmissions. N-SES may have a greater impact on young and middle-aged adults with heart failure (HF) due to fewer resources. Hypothesis: N-SES modifies the disparity in 30-d HF readmissions between Blacks and Whites in the Southeastern US. Methods: We created a geo-coded retrospective cohort of patients aged &lt;65 years (N=11,469, mean age 52.1 yrs, 48% female, 46.5% Black) with at least one HF hospitalization at any Emory Healthcare facility from 2010-2018. Quartiles of the Social Deprivation Index (SDI), derived from US Census data, characterized neighborhood deprivation at the census tract level. Linear probability models estimated the “excess 30-d HF readmissions” between Blacks and Whites (referent) within each quartile of neighborhood deprivation. A base model accounted for geographical clustering, age, gender, and insurance type; a fully adjusted multivariable model further adjusted for clinical variables (composite Charlson Comorbidity Index, HbA1c, BP, SaO2, and HR). Results: Compared with Whites, Blacks were more likely to reside in deprived census tracts, be female, have public insurance, and higher comorbidity scores (Table 1). Between 2010-2018, 20.5% of Black and 12.5% of White patients experienced a 30-d HF readmission (p&lt;.001). Black excess in HF readmissions ranged from 6.7% (95%CI: 3.6%-9.7%) to 8.4% (95%CI: 4.9%-12.0%) within the 2 nd and 4 th deprivation quartiles, respectively (Figure 1), with no excess readmissions in the least deprived quartile. Accounting for comorbidities and clinical presentation eliminated the Black excess in 30-d HF readmissions in the 2 nd quartile but not within higher levels of area deprivation. Conclusions: Excess 30-d HF readmissions in middle aged Blacks increases with neighborhood deprivation and was not explained by patient sociodemographics or comorbidities in the most deprived Census tracts.
Erratum: Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy (Circulation (1997) 95 (1494-1470))
Authors: G. Mancia, A. Zanchetti, E. Agabiti-Rosei, G. Benemio, R. De Cesaris, R. Fogari, A. Pessina, C. Porcellati, A. Rappelli, A. Salvetti, B. Trimarco
Journal: Circulation (1997)