tbuckley/cabot-search huggingface dataset:
Abstract 14981: Altered Gene Expression in Diabetic Heart Failure Patients
Authors: Kajari Dhar, Fang Qiu, Daniel Zolty, Hesham Basma, John Um, Daniel R Anderson, Brian D Lowes
Journal: Circulation (2020)

Introduction: Diabetes and heart failure are very closely associated. Diabetes patients have an increased risk of developing heart failure and heart failure patients are at higher risk of developing diabetes. Changes occur in myocardial glucose metabolism in end stage heart failure patients and newer therapies for diabetes such as SGLTi improve heart failure outcomes. Our objective was to identify transcriptional changes associated with diabetes in heart failure patients. Methods: Transcriptional profiles were compared in heart tissues obtained at the time of LVAD implant among diabetic heart failure (HF) (n=16), non-diabetic (n=10) HF patients and control (n=3) non failing hearts. RNASeq analysis utilized a custom-targeted panel for 140 genes on the Ion Torrent Personal Genome Machine. Coverage analysis as well as mapping the reads and alignment was done using the Ion Torrent Browser SuiteTM. The Bejamini-Hochberg method was used to control the false discovery rate to be no more than 0.05. Ingenuity Pathway Analysis (IPA) was also performed to understand the biological pathways involved. Results: Our sample population was 82% male with an average age of 51 and 84% Caucasian, 14% African American and 2% Asian. Average ejection fraction was quite low &lt;25% and average NYHA was 3.5 in the HF populations. Expressions of contractile muscle and ion channels proteins decreased significantly between HF patients and control. Increased expression of chemokine ligand 4 (CCL4), chemokine ligand 2 (CCL2) and collagen type 1 alpha1 (COL1A1) were observed in diabetic HF compared to non-diabetic HF patients. IPA analysis with log fold change between HF and control revealed activation of both methylation genes DNMT3A and B, necrosis of cardiac muscle and death of cardiomyocytes with 2.0 Z score. Conclusions: Diabetic heart failure patients have increased expression of chemokines and extracellular matrix genes, which may contribute to disease progression. Up regulation of CCL4 and CCL2 in diabetic HF patients may cause additional risk of heart diseases through inflammatory pathways and increased expression of collagen may contribute to myocardial fibrosis. Down regulation of contractile proteins, and ion channels were similar in diabetic and non-diabetic HF patients.
Nonpharmacological Interventions for Managing Breathlessness in Patients With Advanced Cancer
Authors: Arjun Gupta, Ramy Sedhom, Ritu Sharma, Allen Zhang, Julie M. Waldfogel, Josephine L. Feliciano, Jeff Day, Rebecca A. Gersten, Patricia M. Davidson, Eric B. Bass, Sydney M. Dy
Journal: JAMA Oncology (2020)

Breathlessness is a frequent and debilitating symptom in patients with advanced cancer. Often, in the context of breathlessness, aggressive cancer treatment is not beneficial, feasible, or aligned with goals of care. Targeted symptom-focused interventions may be helpful in this scenario.To evaluate the advantages and harms of nonpharmacological interventions for managing breathlessness in adults with advanced cancer.PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception through May 2020 for published randomized clinical trials (RCTs), nonrandomized controlled trials, and observational studies of the advantages and/or harms of nonpharmacological interventions on alleviating breathlessness in adults with advanced cancer. Only English-language studies were screened for eligibility, titles, abstracts, and full text. Risk of bias and strength of evidence (SOE) were independently assessed. The key outcomes reported in studies were breathlessness, anxiety, exercise capacity, health-related quality of life, and harms. Data were analyzed from October 1, 2019, to June 30, 2020.A total of 29 RCTs (2423 participants) were included. These RCTs evaluated various types of interventions, such as respiratory (9 RCTs), activity and rehabilitation (7 RCTs), behavioral and psychoeducational (3 RCTs), integrative medicine (4 RCTs), and multicomponent (6 RCTs). Several nonpharmacological interventions were associated with improved breathlessness, including fan therapy (standardized mean difference [SMD], -2.09; 95% CI, -3.81 to -0.37; I2 = 94.3%; P for heterogeneity = .02; moderate SOE) and bilevel ventilation (estimated slope difference, -0.58; 95% CI, -0.92 to -0.23; low SOE), lasting for a few minutes to hours, in the inpatient setting. In the outpatient setting, nonpharmacological interventions associated with improved breathlessness were acupressure and reflexology (integrative medicine) (low SOE) and multicomponent interventions (combined activity and rehabilitation, behavioral and psychoeducational, and integrative medicine) (low SOE) lasting for a few weeks to months. Five of the 29 RCTs (17%) reported adverse events, although adverse events and study dropouts were uncommon.Findings of this review include the safety and association with improved breathlessness of several nonpharmacological interventions for adults with advanced cancer. Guidelines and clinical practice should evolve to incorporate nonpharmacological interventions as first-line treatment for adults with advanced cancer and breathlessness.
CHOLESTEROL-LOWERING AGENTS
Authors: D L Warkentin
Journal: JAMA (1961)

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Abstract 13607: Seasonal Variation in the Attenuation of Epicardial Adipose Tissue on Cardiac Computed Tomography
Authors: John M Archer, Paolo Raggi, Amin B Sagar, Chao Zhang, Varuna Gadiyaram, Arthur E STILLMAN
Journal: Circulation (2020)

Introduction: The role of epicardial adipose tissue (EAT) in the development and vulnerability of coronary artery atherosclerosis has been the focus of extensive research for the past several years. EAT is visceral fat that surrounds the coronary arteries and it consists of beige adipose tissue that is functionally similar to brown adipose tissue and has a higher computed tomography (CT) attenuation than subcutaneous white adipose tissue. Given the brown-like composition of EAT, its attenuation may be affected by several factors including seasonal temperature variations and clinical factors. Hypothesis: We investigated the effect of season on EAT attenuation and additional clinical factors that may influence attenuation measurements. Methods: Single center, retrospective study of 597 cardiac CT exams performed for coronary artery calcium (CAC) scoring obtained on a single CT scanner during winter and summer months. Summer was defined as June, July, and August. Winter was defined as December, January, and February. EAT attenuation in Hounsfield units (HU) was measured in a region of interest near the right coronary artery ostium. Subcutaneous adipose tissue (SCAD) attenuation was measured in the thoracic subcutaneous tissue. Patients’ demographic and clinical characteristics were obtained by questionnaire and chart review. Results: The clinical and demographic characteristics of patients scanned during the summer (N=253) and the winter (N=344) months were similar. One third of patients were women, one quarter used statins and anti-hypertensive drugs each and 30% had a BMI&gt;30. There was a significantly lower EAT attenuation measured during the summer than the winter months (-98.17±6.94 HUs vs -95.64±7.99 HUs; P&lt;0.001). Additionally, gender, obesity, treatment with statins and anti-hypertensive agents significantly modulated the seasonal variation in EAT attenuation. SCAD attenuation was not affected by season or any other factor. Conclusions: Our study shows that the measurement of EAT attenuation is complex and is likely affected by season, demographics and clinical factors. Attempts to use EAT attenuation as a biomarker for risk of cardiovascular events should take these potential confounders into consideration.
Response to: ‘Correspondence on ‘Increased risk of systemic lupus erythematosus in patients with autoimmune haemolytic anaemia: a nationwide population-based cohort study’’ by Goulielmos and Zervou
Authors: Han-You Mo, Xiao-Huan Chen, James Cheng Chung Wei, Hsin-Hua Chen
Journal: Annals of the Rheumatic Diseases (2020)

We thank Goulielmos and Zervou1 for their interest on our article entitled ‘Increased risk of systemic lupus erythematosus in patients with autoimmune haemolytic anaemia: a nationwide population-based cohort study.2

Goulielmos and Zervou1 commented that the occurrence of systemic lupus erythematosus (SLE) and autoimmune haemolytic anaemia (AIHA) may be related to genetic and environmental factors, in addition to the abnormal immune system function. In the recently presented data, Goulielmos and Zervou1 showed that various shared genetic polymorphisms were associated with the increased susceptibility of ITP and SLE. According to existing research, it has been reported that AIHA and SLE share common genetic susceptibility as well, including human leucocyte antigen (HLA)-B8 and HLA-DQ6 regions,3 4 and single-nucleotide polymorphisms of the CTLA-4 ,5 NFATC1 ,6 LT-a ,7 FcgRIIa ,8 FOXP3 9 and CARD11 10 genes. We strongly agree with the point put forward by …
Abstract 14539: Incidence, Risk Factors, Natural History, and Outcomes of Atrial Fibrillation in Patients With Graves’ Disease
Authors: Jwan A Naser, Sorin Pislaru, Marius N Stan, Grace Lin
Journal: Circulation (2020)

Background: Hyperthyroidism is associated with atrial fibrillation (AF) with a reported prevalence of 16-60%. However, risk factors for onset of AF with hyperthyroidism are not well defined. We sought to identify patients with hyperthyroidism most likely to develop AF. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. GD-related AF was defined as AF diagnosed up to 30 days before or at any time after Grave’s disease (GD). Spontaneous recovery was defined as sinus rhythm after attainment of euthyroidism without the need for pharmacologic or electrical cardioversion. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were compared between cases and controls (GD without AF) matched 1:1 for age, gender, and history of coronary artery disease. Results: AF occurred in 140 patients with an incidence of 10.2%. Older age (RR 1.63 per 10 years, p &lt;0.001), male gender (RR 2.06, p &lt; 0.001), overt hyperthyroidism (RR 2.48, p = 0.002), COPD (RR 2.14, p =0.006), and higher BMI (RR 1.03 per unit, p=0.023) were independent risk factors for AF. Spontaneous AF recovery occurred in 44 of 128 (34.6%) patients with adequate follow up. The multivariate risk factor for failed recovery was the presence of heart failure (HF) (OR =3.52, p= 0.004). GD patients with AF had higher rates of cardiac hospitalizations (Figure) that persisted even after adjusting to HF presence (27.9% vs 2.9%, p &lt; 0.001). Conclusion: Risk factors for AF in GD are similar to those in the general population, although overt hyperthyroidism conferred the highest risk. These data argue for careful monitoring of GD patients with multimorbidity who may be at high risk of developing AF.
Abstract 16770: The Epigenetic Modifier EP300: A New Corner Stone in the Regulation of Both Vascular Remodeling and Right Ventricle Failure in Pulmonary Arterial Hypertension
Authors: Alice Bourgeois, Sarah-Eve Lemay, Yann Grobs, Charlotte romanet, Junichi Omura, Victoria Toro, Valerie Nadeau, Eve Tremblay, Sandra Breuils-Bonnet, Steeve Provencher, Olivier BOUCHERAT, Sebastien Bonnet
Journal: Circulation (2020)

Introduction: Pulmonary Arterial Hypertension (PAH) is characterized by excessive proliferation and resistance to apoptosis of pulmonary artery (PA) smooth muscle cells (PASMCs), leading to progressive increases in pulmonary vascular resistance, and ultimately right ventricular (RV) failure and death. Thanks to omics technologies, we made tremendous progress in understanding gene misregulation during disease processes and identified the epigenetic factor EP300 as a critical player in pathological processes like proliferation/apoptosis and hypertrophy/fibrosis all of which are critical features of both PA remodeling and RV failure in PAH. We hypothesized that EP300 is upregulated in PAH and contributes to both PA remodeling and RV failure. Methods and Results: By Western blot (WB) and immunofluorescence (IF), we found that EP300 is up-regulated in isolated PASMCs and distal PAs from PAH patients (n=11-14) compared to controls (n=8-10) (p&lt;0.01). Similar results were observed in 3 PAH animal models, namely the monocrotaline (MCT), the Sugen/Hypoxia (Su/Hx) and the Fawn-Hooded rat (FHR) (p&lt;0.05). In vitro, pharmacological inhibition of EP300 using CCS-1477 reduces PAH-PASMC proliferation (Ki67 labeling &amp; WB PCNA; p&lt;0.05) and resistance to apoptosis (Annexin V assay &amp; WB Survivin; p&lt;0.05). These effects were confirmed at the molecular level by RNA-Seq analysis. In addition, increased EP300 expression was observed in hypertrophied and failed RV from PAH patients, as well as in rats injected with MCT or subjected to pulmonary artery banding (WB, p&lt;0.05). In animal models, EP300 negatively correlates with CO and positively correlates with RVEDP, cardiomyocyte surface area and fibrosis. Finally, we demonstrated that inhibition of EP300 using CCS-1477 or SGC-CBP30 significantly improved established PAH (right heart catheterization) in two animal models (MCT and FHR). Conclusion: EP300 upregulation contributes to both pulmonary vascular remodeling and RV dysfunction seen in PAH and its inhibition represents a promising therapeutic avenue.
The in silico macrophage: toward a better understanding of inflammatory disease
Authors: Peter Ghazal, Steven Watterson, Kevin Robertson, David C Kluth
Journal: Genome Medicine (2011)

Macrophages function as sentinel, cell-regulatory hubs capable of initiating, perpetuating and contributing to the resolution of an inflammatory response, following their activation from a resting state. Highly complex and varied gene expression programs within the macrophage enable such functional diversity. To investigate how programs of gene expression relate to the phenotypic attributes of the macrophage, the development of in silico modeling methods is needed. Such models need to cover multiple scales, from molecular pathways in cell-autonomous immunity and intercellular communication pathways in tissue inflammation to whole organism response pathways in systemic disease. Here, we highlight the potential of in silico macrophage modeling as an amenable and important yet under-exploited tool in aiding in our understanding of the immune inflammatory response. We also discuss how in silico macrophage modeling can help in future therapeutic strategies for modulating both the acute protective effects of inflammation (such as host defense and tissue repair) and the harmful chronic effects (such as autoimmune diseases).
Abstract 17277: Holistic Health-Related Quality of Life in Older Adults Undergoing Transcatheter Aortic Valve Replacement
Authors: Menal Huroy, Julia Rodighiero, Jonathan Afilalo
Journal: Circulation (2020)

Introduction: Health-related quality of life (HRQoL) is a prioritized outcome for older adults undergoing transcatheter aortic valve replacement (TAVR). Previous studies have used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to evaluate HRQoL, which is heavily weighted on heart failure symptoms with only one question on mental wellbeing. We sought to determine the incidence and determinants of poor HRQoL using a novel holistic scale. Methods: The FRAILTY-AVR prospective multi-centre cohort study of older adults undergoing TAVR was used to develop a holistic HRQoL scale. Construct validity was evaluated using the Spearman’s rank correlation with the 12-item KCCQ, and clinically meaningful change was evaluated using the anchor-based method. The primary endpoint was “poor outcome” defined as all-cause mortality or clinically meaningful decrease in HRQoL at 1 year. Results: The cohort consisted of 693 patients with a mean age of 82.9 years and 47% females. A 23-item HRQoL scale was developed, with the total score ranging from 0 (worst) to 40 (best) across 5 domains: disease burden (3 items), general health (1 item), physical (6 items), mental (5 items), and social (8 items) functioning. This scale was correlated with the KCCQ (Spearman’s rho 0.56, P&lt;0.0001) and a 3-unit change was found to be clinically meaningful in longitudinal follow-up. A total of 269 (39%) patients experienced a poor outcome at 1 year post-TAVR, including 144 (21%) deaths. The predictors of poor outcome were Essential Frailty Toolset score &gt;=3 [OR 1.88; 95% CI 1.28, 2.76], mean aortic gradient &lt;40 mmHg [OR 1.83; 95% CI 1.27, 2.63] and Charlson comorbidity index [OR 1.09; 95% CI 1.01, 1.18]. Conclusions: Two of five patients had a poor outcome 1 year post-TAVR, despite a procedure success rate of 95%. The incidence and determinants of poor outcome using our holistic HRQoL scale, notably the impact of frailty, are highly consistent with previous studies using the KCCQ. These determinants should be integrated in patient-centered decision making and optimized to improve HRQoL post-procedure.
Low-Density Lipoprotein Reduction and Cancer: Not Definitive But Provocative⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Anthony N. DeMaria, Ori Ben-Yehuda
Journal: Journal of the American College of Cardiology (2007)
Adrenergic Excess, hNET1 Down-Regulation, and Compromised mIBG Uptake in Heart Failure: Poverty in the Presence of Plenty⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Nezam Haider, Ragavendra R. Baliga, Y. Chandrashekhar, Jagat Narula
Journal: JACC. Cardiovascular imaging (2010)
Abstract 14936: Prevention of Contrast-induced Nephropathy by Inferior Vena Cava Ultrasonography-guided Hydration in Chronic Heart Failure Patients
Authors: Yuanming Yan, Mingfang Ye, qin chen, yukun luo
Journal: Circulation (2020)

Introduction: Contrast-induced nephropathy (CIN) is a common complication resulting from the administration of contrast media. This study was designed to determine whether inferior vena cava ultrasonography (IVCU)-guided hydration can reduce the risk of CIN in chronic heart failure patients undergoing coronary angiography or coronary angiography with percutaneous coronary intervention (PCI) than standard hydration. Methods: This prospective clinical trial enrolled 207 chronic heart failure patients from February 2016 to November 2017, who were randomly assigned to either IVCU-guided hydration group (n = 104) or the routine hydration group (n = 103). In the IVCU-guided group, the hydration infusion rate was set according to inferior vena cava diameter (IVC-D) determined by IVCU; while the control group received intravenous infusion of 0.9% saline at 0.5 ml/((kg·h)). Serum creatinine (SCr) was measured before and 48-72 hours after procedure. All patients were followed up for 18 months. The incidence of nephropathy and major adverse cardiovascular or cerebrovascular events (MACCE) were also compared between two groups. Results: Statistically significant difference between two groups regarding the occurrence of CIN were observed (12.5% vs. 29.1%, p = 0.003); The hydration volume of the IVCU-guided group is significantly higher than routine group (p&lt;0.001). In addition, patients receiving IVCU-guided hydration had significantly lower risk of developing MACCE compared with patients in control group during 18 months follow-up (14.4% vs. 27.2%, p = 0.027). Conclusions: IVCU-guided hydration is superior to standard hydration in prevention of CIN and substantially reduce longtime composite major adverse events.
Abstract 15414: Diagnostic Performance of Deep Learning on 12-lead Electrocardiography to Distinguish Takotsubo Syndrome and Acute Anterior Myocardial Infarction
Authors: Masato Shimizu, shummo cho, Yoshiki Misu, Mari Ohmori, Ryo Tateishi, Toshio Kaneda, Yosuke Yamakami, Hiroshi Shimada, Tomoko Manno, Ami Isshiki, Shigeki Kimura, Fujii Hiroyuki, Makoto Suzuki, Mitsuhiro Nishizaki, Tetsuo Sasano
Journal: Circulation (2020)

Introduction: Takotsubo syndrome (TTS) and acute anterior myocardial infarction (ant-AMI) show very similar 12-lead electrocardiography (ECG) featured at onset, and it is often difficult to distinguish them without cardiac catheterization. The difference of ECG between them was studied, but the diagnostic performance of machine learning (deep learning) for them had not been investigated. Hypothesis: Deep learning on 12-leads ECG has high diagnostic performance to diagnose TTS and ant-AMI at onset. Methods: Consecutive 50 patients of TTS were one-to-one matched to ant-AMI randomly by their age and gender, and total 100 patients were enrolled. No sinus rhythm patients were excluded. All ECGs were divided into each 12-lead, and 5 heart beats from one lead were extracted. For each lead, 250 ECG waves of TTS/AMI were sampled as 24bit bitmap image, and prediction model construction by convolutional neural network (CNN: transfer learning, using VGG16 architecture) underwent to distinguish the two diseases in each lead. Next, gradient weighted class activation color mapping (GradCam) was performed to detect the degree and position of convolutional importance in the leads. Results: Lead aVR (mean accuracy 0.748), I (0.733), and V1 (0.678) were the top 3 leads with high accuracy. In aVR lead, GradCam showed strong convolution of negative T wave in TTS, and sharp R wave in ant-AMI. In I lead, it spotlighted several parts of ECG wave in ant-AMI. However in TTS, whole shape of the wave, P wave onset, and negative T were invertedly convoluted in TTS. Conclusions: Deep learning was a powerful tool to distinguish TTS and ant-AMI at onset, and GradCam method gave us new insight of the difference on ECG between the two diseases.