tbuckley/cabot-search huggingface dataset:
Abstract 16061: Antihypertensive Therapy Prescribing Pattern Among Patients With Markedly Elevated Blood Pressure in a Real-world Setting
Authors: Yuan Lu, Chenxi Huang, Shiwani Mahajan, Cesar Caraballo, Erica S Spatz, Wade Schulz, Harlan M Krumholz
Journal: Circulation (2020)

Introduction: Combination therapy with two or more antihypertensive agents is recommended for management of patients with markedly elevated blood pressure (systolic blood pressure [SBP] ≥160 mmHg or diastolic blood pressure [DBP] ≥100 mmHg) by the 2017 AHA/ACC hypertension guideline. Using electronic health records (EHR) data from a large health system, we characterized real-world antihypertensive drug prescribing patterns and assessed guideline adherence among ambulatory patients with markedly elevated BP. Methods: Our cohort included patients aged 18-85 years with at least 2 outpatient visits in the Yale New Haven Hospital System between January 1 st , 2013 and December 31 st , 2018, resulting in a total of 665,691 patients. We defined the phenotype of markedly elevated BP as two consecutive outpatient visits with SBP ≥160 mmHg or DBP ≥100 mmHg. We described the number and class of antihypertensive drugs (previously taken and newly prescribed) at the second visit with BP ≥160/100 mmHg. Results: We identified 38,098 patients with markedly elevated BP with a mean age of 62.4 (SD: 13.7) years; 47.9% were male; and 67.8%, 20.9%, and 9.3% were White, Black and Hispanic. Among them, 49.3% were not on any antihypertensive drugs at the end of the second visit, 26.2% had one active antihypertensive drug prescription, and 24.5% had two or more agents prescribed (Figure). Among patients with two or more antihypertensive drug prescriptions, the most common drug class combination prescribed was diuretic/ACE inhibitor (10.2%), followed by diuretic/ARB (9.3%), and ACE inhibitor/calcium channel blocker (6.5%). The low prescription of combination therapy was consistent across age, gender, and race subgroups. Conclusions: Prescribing of guideline-recommended combination antihypertensive drugs for patients with markedly elevated BP is suboptimal. Major opportunities exist for improving the guideline adherence of antihypertensive drug prescription in this population.
Abstract 15550: Fully Automated "Hands-off" Validation of Left Ventricular Ejection Fraction in Children
Authors: Hunter Kauffman, Kevin K Whitehead, Matthew J O’Connor, Michael D Quartermain, Michael Convery, Anirban N Banerjee
Journal: Circulation (2020)

Introduction: Three-dimensional echocardiography (3DE) has been shown to be superior to 2DE when quantifying chamber dimensions. However, the clinical utility of 3DE has been limited by time-consuming analysis and need for 3D-specific training. This study aims to assess the clinical utility of a “hands-off,” artificial intelligence-driven software program, Philips Dynamic HeartModelA.I. (DHM), in a pediatric population. Hypothesis: We hypothesize that this program will be able to accurately calculate LVEF in children when compared to Cardiac MRI (CMRI) used as a gold standard. Methods: To date, 10 patients (Average Age 14.8±1.9) have undergone CMRI immediately followed by echocardiography at the Children’s Hospital of Philadelphia. Echocardiographic images were analyzed via DHM without manual editing and from full-volume 3D border tracing (3DEF). We excluded 3D imaging of 2 patients due to poor image quality. 2D LVEF was also evaluated visually in all patients by three experts, and by 2D Simpson’s Biplane method. All analyses were timed with a stopwatch. Each technique was correlated with CMRI. Results: Our results showed that LVEF measured via DHM was rapid and correlated very well with CMRI (R=0.85). DHM had a stronger correlation with CMRI than Biplane, 3DEF, and visual EF (R=0.56; R=0.68; R=0.57). Moreover, DHM analysis was faster than both Biplane and 3DEF (32±8 seconds vs 100±19 seconds, p&lt;0.005; 32±8 seconds vs 98±16 seconds, p&lt;0.005) (Figure 1). Notably, 3DEF correlated very well with visual estimation by expert observers (R=0.83). Conclusions: Based on our pilot data, DHM analysis in children was faster than both 3DEF and biplane method likely due to its hands-off nature. Furthermore, its correlation with CMRI was superior to both 3DEF and Biplane. Based on further patient enrollment by us and others, this completely automated method will likely be clinically useful as it has potential to become a standard application in large volume, busy echo labs.
Abstract P174: First Trimester Blood Pressure Elevation May Have A Greater Impact On The Risk Of Spontaneous Abortion Than Preconception Blood Pressure
Authors: Fouzia Farooq, Kalpana Basany, Guru Rajesh Jammy, Gong Tang, Emma Barinas-Mitchell, Akira M Sekikawa, Janet M Catov, Maisa Feghali, Sudhakar Reddy, Catherine Haggerty
Journal: Circulation (2021)

Background: Spontaneous abortion (SAB) is a common early pregnancy complication globally, impacting 15% of clinically recognized pregnancies. The biological pathways leading to SAB are not clearly understood, although early SAB is often attributed to chromosomal abnormalities. Elevated blood pressure (BP) in women of reproductive age predicts cardiovascular disease later in life, but less clear is whether elevated BP during preconception and/or early pregnancy BP elevations can affect prenatal outcomes. Hypothesis: Elevated BP during preconception and the first trimester will be positively associated with SAB. Methods: We conducted a secondary analysis of data collected from 577 primiparous women (15-35 years) who participated in the Longitudinal Indian Family hEalth (LIFE) prospective pregnancy cohort study in Telangana State, India. Resting blood pressure was measured by trained technicians using a standardized study protocol at a preconception registration visit and in the first trimester. Odds ratio (OR) and 95% confidence intervals (CI) of any SAB (&lt;22 weeks of gestation, n=108), early SAB (&lt;8 weeks of gestation, n=25), and late SAB (8 to &lt;22 weeks of gestation n=83) were assessed with a log link binomial distribution. Results: Preconception measurements were assessed at the first study visit, conducted at registration and within a mean±SD of 11±12 months prior to pregnancy. Higher than optimal preconception BP (120/80 mmHg) was not associated with SAB (OR adj 0.82 (95% CI 0.51, 1.32)). In contrast, first trimester elevated BP was associated with a two-fold increased likelihood of SAB, although results were of borderline significance (OR adj 2.12 (95%CI 0.87, 5.14). In addition, we observed an association between elevated first trimester BP and late SAB (OR adj 2.32 (95%CI 0.95, 5.68)); there were no associations between elevated preconception or first trimester BP and early SAB. Conclusions: We found that elevated first trimester but not preconception BP was associated with an increased risk of pregnancy loss, suggesting that dysregulated adaption to pregnancy may impact pregnancy loss more than preconception BP status, especially SABs that occur after 8 weeks gestation. Our findings support the notion that clinical and environmental factors may have a greater impact on later SABs as opposed to earlier losses. The null relationship with early pregnancy loss in our study may be due to an expected genetic mutation etiology for those losses. Studies exploring the trajectory of preconception and prenatal blood pressure changes and impact on pregnancy outcomes are warranted.
Abstract 15110: Atherospectrum Identified Novel Foaming Programs and Monocyte Predictor Genes for Residual Cardiovascular Risk
Authors: Chuan Li, Lili Qu, Yongmei Liu, Anthony Vella, Patrick Murphy, Annabelle Rodriguez, Beiyan Zhou
Journal: Circulation (2020)

Despite lipid-control therapies, substantial risk of major cardiovascular event remains. New approaches are needed to define and mitigate residual risks in a patient specific manner. Monocytes, critical player in CVD, transcriptionally respond to metabolic and inflammatory cues in the circulation and contribute to atherogenesis. However, previous studies of monocytes only found moderate associations to CVD events and with limited predictive power. Here we developed a novel computational approach, named AtheroSpectrum, which effectively depicted heterogeneity of foam cells. Our analysis revealed two distinct programs of plaque macrophages: the homeostatic-foaming and the inflammatory pathogenic-foaming, which we found to be associated with severity of atherosclerosis in multiple studies. Next, we screened the genes enriched in the pathogenic-foaming program using our original self-optimizing progressive machine learning algorithms, and identified 29 signature genes (including SOD2, SLC39A8, etc) that were strongly associated with cardiovascular events in 936 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) whose LDL levels were below 129 mg/dl, and were further validated in additional human data (gtexportal.org, GSE43292), while traditional risk factors (BMI, lipid profiles, smoking, etc) showed no significant association. We further developed a novel residual CVD risk score system that incorporated the newly identified 29 pathogenic foaming signature genes, gender, age, and the inflammation index (MPI) of AtheroSpectrum. Our scores presented strong prediction power for depicting residual cardiovascular risks (AUC 0.805) compared with the JAMA 2001 (AUC 0.620) and Framingham risk scores (AUC 0.650).In summary, we successfully identified pathogenic foam cell subpopulations with active inflammatory and lipid metabolic programs. Characterization of these subsets revealed novel feature-based key genes directly contributing to CVD residual risks and endowed creation of a CVD prediction score with high accuracy. Further optimizing this score system will facilitate both mechanistic investigations and development of therapeutic and prognosis strategies of CVD residual risk.
4-Aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay, structure-activity relationships of the 7, 8-positions
Authors: Sui Xiong Cai, William Kemnitzer, Shailaja Kasibhatla, Songchun Jiang, Jianghong Zhao, Ben Tseng, John Drewe, Denis Labrecque, Serge Lamothe, Henriette Gourdeau
Journal: Cancer Research (2006)

1129  We have recently reported the discovery of 2-amino-3-cyano-7-dimethylamino-4- (3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) as potent apoptosis inducers using a novel cell- and caspase-based HTS assay and the SAR of the 4-position with a dimethylamino group in the 7-position (Kemnitzer, W. et al. J. Med. Chem. 2004, 47, 6299). These chromenes were found to be active in the HUVEC tube formation assay, suggesting that this series of compounds may have antivascular activity, and several compounds were also found to be highly active in anti-cancer in vivo tumor models. (Kasibhatla, S. et al. Mol. Cancer Ther. 2004, 3, 1365, and Gourdeau, H. et al. Mol. Cancer Ther. 2004, 3, 1375). In this presentation, we will describe the SAR of the 7-and 8-positions of 4-aryl-4H-chromenes as inducers of apoptosis, including 7,8-disubstituted analogs (Kemnitzer, W. et al. Bioorg. Med. Chem. Lett. 2005, 15, 4745), as well as analogs with a fused ring at the 7, 8-positions. We will report in detail the chemistry, in vitro and in vivo characterization of these compounds.
99P Analysis of ctDNA in advanced breast cancer reveals polyclonal disease associated with adverse outcome
Authors: B. Kingston, R. Cutts, M. Beaney, G. Walsh-Crestani, S. Hrebien, L. Kilburn, S. Kernaghan, L. Moretti, K. Wilkinson, I. MacPherson, R.D. Baird, R. Roylance, J.S. Reis-Filho, M. Hubank, I. Faull, K. Banks, I. Garcia-Murillas, J. Bliss, A. Ring, N. Turner
Journal: Annals of Oncology (2021)
Abstract 15791: Evaluation of Medicare Claims for Heart Failure Diagnostic Development: A Multisense-linkage Feasibility Analysis
Authors: Ramesh Wariar, Gezheng Wen, Caroline Jacobsen, Stephen B Ruble, John Boehmer
Journal: Circulation (2020)

Introduction: The validity of utilizing claims data for the development of worsening heart failure (HF) diagnostics has not been previously reported. Therefore, we linked data from the MultiSENSE study, in which the HeartLogic diagnostic was first reported, with claims data in order to validate claims HF events and compare diagnostic performance. Methods: Identifiers from 791 United States study patients were directly linked with Medicare claims to produce 320 patients with continuous Medicare Part A/B fee-for-service (FFS) coverage during study participation. Claims HF events were defined using primary HF diagnosis codes (DRG and ICD-9-CM) and included inpatient events as well as outpatient events with intravenous decongestive therapy. We matched events by patient and date, calculated agreement between events (Cohen’s kappa coefficient κ), and evaluated HeartLogic diagnostic performance using sensitivity and false positive rate (FPR). Results: The linked cohort was older than the remaining patients and had greater disease burden. Study deaths (N=14) matched exactly with claims. In contrast, matching of 207 study hospitalizations with 197 acute inpatient events resulted in a total of 239 events of which 193 matched with claims (81%), 32 (13%) were claims-unique, and 14 (6%) were study-unique. Claims HF events had substantial agreement with study adjudicated hospitalizations (observed = 93.3%, κ = 0.823). The HeartLogic algorithm detected claims-derived events with a sensitivity of 75.6% and an FPR of 1.539 alerts/pt-year, which was not different from performance derived using study events (sensitivity = 77.6% and FPR = 1.528, P = 0.82 and 0.92). HeartLogic detected events contributed to 91% of HF event costs used for performance evaluation ($605,000 out of $663,000). Conclusions: The agreement between claims and study events, and equivalence of HeartLogic diagnostic performance suggest that claims data may have utility for future diagnostic development/enhancement. Additional data are needed to demonstrate safety, efficacy, and cost-effectiveness of HeartLogic-directed interventions.
Abstract 12575: Feasibility of Management in General Ward Settings for Hemodynamic Stable Patients With Acute Myocardial Infarction
Authors: Kazuya Tateishi, Hideki Kitahara, Yuichi Saito, Atsushi Nakagomi, Hiroyo Kuwabara, Takahiro Inoue, Yoshio Kobayashi
Journal: Circulation (2020)

Background: Although admission to the coronary care unit (CCU) is strongly recommended for ST-segment elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PPCI) by current guidelines, it remains unclear whether it is suitable for hemodynamically stable patients with acute myocardial infarction (AMI). The aim of this study was to evaluate the safety of management in the general ward (GW) in hemodynamically stable AMI patients after PPCI compared to the CCU. Methods: Using a large nationwide administrative database, a cohort of 19,426 patients who were diagnosed as AMI in 52 hospitals, which were capable of admission to CCU, between Jan 2015 and Dec 2019, was retrospectively analyzed. Patients with mechanical circulatory support and Killip classification 4, and without PPCI, on the day of admission were excluded. Consequently, 5,736 patients were divided into the CCU group (n=3,488) and the GW group (n=2,248) based on the type of hospitalization room on admission after PPCI. A propensity score-matched (PSM) analysis was performed between the 2 groups, and 1,690 pairs of patients were matched. Results: The CCU group showed a higher prevalence of Killip classification 3 and ambulance use compared to the GW group. In the PSM model, Kaplan-Meier curve analysis showed there was no significant difference in the incidence of 30 days in-hospital mortality (Log rank p=0.48). On the other hand, total cost of hospitalization was lower in the GW group. Multivariable analysis did not show the association of GW admission with 30 days in-hospital mortality (HR: 1.07, 95% CI: 0.63-1.82, p=0.795). Conclusions: Management in the GW was not associated with 30 days in-hospital mortality for hemodynamically stable AMI patients after PPCI compared to the CCU, whereas it reduced the total cost of hospitalization. It may be feasible for hemodynamically stable AMI patients to be admitted directly to the GW after PPCI.
106P Palbociclib (PAL) in male patients (pts) with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC): Pt characteristics and treatment (Tx) patterns from the POLARIS study
Authors: J.L. Blum, C. Dicristo, D. Gordon, M. Karuturi, D. Oubre, E. Jepsen, J. Cuevas, S. Lakhanpal, Z. Zhang, M. Drucker, Y. Wang, D. Tripathy
Journal: Annals of Oncology (2021)
Bronchial gene expression signature associated with rate of subsequent FEV<sub>1</sub> decline in individuals with and at risk of COPD
Authors: Elizabeth J Becker, Alen Faiz, Maarten van den Berge, Wim Timens, Pieter S Hiemstra, Kristopher Clark, Gang Liu, Xiaohui Xiao, Yuriy O Alekseyev, George O'Connor, Stephen Lam, Avrum Spira, Marc E Lenburg, Katrina Steiling
Journal: Thorax (2021)

Background COPD is characterised by progressive lung function decline. Leveraging prior work demonstrating bronchial airway COPD-associated gene expression alterations, we sought to determine if there are alterations associated with differences in the rate of FEV 1 decline. Methods We examined gene expression among ever smokers with and without COPD who at baseline had bronchial brushings profiled by Affymetrix microarrays and had longitudinal lung function measurements (n=134; mean follow-up=6.38±2.48 years). Gene expression profiles associated with the rate of FEV 1 decline were identified by linear modelling. Results Expression differences in 171 genes were associated with rate of FEV 1 decline (false discovery rate &lt;0.05). The FEV 1 decline signature was replicated in an independent dataset of bronchial biopsies from patients with COPD (n=46; p=0.018; mean follow-up=6.76±1.32 years). Genes elevated in individuals with more rapid FEV 1 decline are significantly enriched among the genes altered by modulation of XBP1 in two independent datasets (Gene Set Enrichment Analysis (GSEA) p&lt;0.05) and are enriched in mucin-related genes (GSEA p&lt;0.05). Conclusion We have identified and replicated an airway gene expression signature associated with the rate of FEV 1 decline. Aspects of this signature are related to increased expression of XBP1-regulated genes, a transcription factor involved in the unfolded protein response, and genes related to mucin production. Collectively, these data suggest that molecular processes related to the rate of FEV 1 decline can be detected in airway epithelium, identify a possible indicator of FEV 1 decline and make it possible to detect, in an early phase, ever smokers with and without COPD most at risk of rapid FEV 1 decline.
Tumor-on-chip modeling of organ-specific cancer and metastasis
Authors: Nuala Del Piccolo, Venktesh S. Shirure, Ye Bi, S. Peter Goedegebuure, Sepideh Gholami, Christopher C.W. Hughes, Ryan C. Fields, Steven C. George
Journal: Advanced Drug Delivery Reviews (2021)

Every year, cancer claims millions of lives around the globe. Unfortunately, model systems that accurately mimic human oncology – a requirement for the development of more effective therapies for these patients – remain elusive. Tumor development is an organ-specific process that involves modification of existing tissue features, recruitment of other cell types, and eventual metastasis to distant organs. Recently, tissue engineered microfluidic devices have emerged as a powerful in vitro tool to model human physiology and pathology with organ-specificity. These organ-on-chip platforms consist of cells cultured in 3D hydrogels and offer precise control over geometry, biological components, and physiochemical properties. Here, we review progress towards organ-specific microfluidic models of the primary and metastatic tumor microenvironments. Despite the field's infancy, these tumor-on-chip models have enabled discoveries about cancer immunobiology and response to therapy. Future work should focus on the development of autologous or multi-organ systems and inclusion of the immune system.
Abstract 15182: Acute Complications of Type B Aortic Intramural Hematoma Compared With Classic Aortic Dissection
Authors: Yutaro Miyoshi, Shuichirou Kaji, Akiko Masumoto, Toshiaki Toyota, Taiji Okada, Kitae Kim, Takeshi Kitai, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Yutaka Furukawa
Journal: Circulation (2020)

Introduction: Although acute type B aortic intramural hematoma (B-IMH) is a variant of acute aortic syndrome having similar clinical demographics to type B classic aortic dissection (B-AD), early clinical course including acute complications are not well investigated. The purpose of this study was to investigate early clinical course and acute complications of B-IMH in comparison with that of B-AD. Methods: Clinical features and early clinical course including acute complications were retrospectively analyzed in 270 B-IMH and 177 B-AD consecutive patients who were admitted to our hospital between 1991 and 2020. Acute complications were defined as rupture, impending rupture, re-dissection, and visceral and leg ischemia. Results: As compared with B-AD, B-IMH presented at older age (72±11 vs 62±15 years; p&amp;lt;0.001), predominantly in females (37% vs 25%). During in-hospital courses, limb ischemia and mesenteric ischemia were less common in patients with B-IMH than those with B-AD (0.4% versus 5.1%, p=0.003, 0.4% versus 2.8%, p=0.03; respectively). In contrast, spinal ischemia was more common in B-IMH patients (2.4% versus 0.6%, p=0.05). Aortic rupture and impending rupture were comparable between B-IMH and B-AD patients (5.9% versus 7.3%. p=0.28). Besides, re-dissection was also comparable between two groups (2.2% versus 5.1%, p=0.06). As a result, prevalence of acute complications was significantly lower in patients with B-IMH (8.8% versus 17%, p=0.008). In-hospital mortality rate in B-IMH was significantly lower than that in B-AD (0.4% versus 9.0%, p&amp;lt;0.001). Conclusions: Although patients with B-IMH had lower in-hospital mortality rates than patients with B-AD, significant portion of B-IMH patients had fatal complications including spinal ischemia or aortic rupture. Patients with B-IMH should be carefully observed as well as patients with B-AD patients.