tbuckley/cabot-search huggingface dataset:
Abstract 15719: Levosimendan Improves Liver Function in Patients With Advanced Chronic Heart Failure
Authors: Gregor Zemljic, Ajda Anzic Drofenik, Andraz Cerar, Sabina Frljak, Gregor Poglajen, Miran Sebestjen, Renata Okrajsek, Ivan Knezevic, Bojan VRTOVEC
Journal: Circulation (2020)

Introduction: Although there is evidence of beneficial effects of levosimendan on heart and renal function in patients with advanced chronic heart failure, the impact of levosimendan on liver function remains undefined. Hypothesis: We investigated the effects of levosimendan on liver function in patients with advanced chronic heart failure. Methods: We enrolled 299 patients with chronic heart failure (NYHA class 3) and left ventricular ejection fraction &lt;30%, aged between 18 and 80 years. 150 patients were randomized to receive levosimendan (0.1 mcg/kg/min infusion for 24 hours; LS Group), and 149 received no levosimendan (Controls). Liver function was evaluated at baseline and again at 3 months by measuring total bilirubin, direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gGT) and lactate dehydrogenase (LDH). Results: At baseline, the groups did not differ in age (59±11 years in LS Group vs. 60±10 years in Controls; P=0.74), sex (male: 77% vs. 75%; P=0.36), heart failure etiology (ischemic: 45% vs. 47%; P=0.64), left ventricular ejection fraction (27±2% vs. 26±3%; P=0.97), and plasma NT-proBNP levels (4758±3912 pg/mL vs. 5111±4271 pg/mL; P=0.71). Liver function tests of both groups at the time of enrollment were comparable. At 3 months we found a significant improvement in liver function in LS Group, but not in Controls, with a decrease in total bilirubin (21.9±16.4 μmol/L to 18.5±13.1 μmol/L in LS Group vs. 22.1±17.1 μmol/L to 22.0±17.3 μmol/L in Controls; P&lt;0.001), direct bilirubin (8.6±6.4 μmol/L to 7.1±5.2 μmol/L vs. 8.7±6.6 μmol/L to 8.8±6.7 μmol/L; P&lt;0.001), AST (1.18±0.98 μkat/L to 0.42±0.40 μkat/L vs. 1.16±0.92 μkat/L to 1.15±0.87 μkat/L; P=0.03), ALT (0.73±0.71 μkat/L to 0.50±0.49 μkat/L vs. 0.75±0.77 μkat/L to 0.74±0.70 μkat/L; P=0.006), gGT (2.25±2.30 μkat/L to 1.87±1.94 μkat/L vs. 2.23±2.18 μkat/L to 2.22±2.16 μkat/L; P=0.003) and LDH (3.66±2.46 μkat/L to 3.36±1.96 μkat/L vs. 3.58±2.77 μkat/L to 3.62±2.82 μkat/L; P=0.006). Conclusions: Levosimendan appears to improve long-term liver function in advanced chronic heart failure patients. Thus, repetitive levosimendan infusions may potentially slow the progression of cardio-hepatic syndrome to cardiac cirrhosis.
Final Report of a Trial of Intensive versus Standard Blood-Pressure Control
Authors: Cora E Lewis, Lawrence J Fine, Srinivasan Beddhu, Alfred K Cheung, William C Cushman, Jeffrey A Cutler, Gregory W Evans, Karen C Johnson, Dalane W Kitzman, Suzanne Oparil, Mahboob Rahman, David M Reboussin, Michael V Rocco, Kaycee M Sink, Joni K Snyder, Paul K Whelton, Jeff D Williamson, Jackson T Wright, Walter T Ambrosius
Journal: New England Journal of Medicine (2021)

In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.
4.2タンパクの翻訳後修飾:72・74kDsを有する4.2タンパクdoublet Nagano
Authors: Yawata Y, Kanzaki A, Inoue T, Kaku M, Yawata A, Takezono M, Shimohira Y, Ishida F, Kobayashi H
Journal: Blood (1996)
Abstract 16465: Mode of Death and Outcomes of Implantable Cardioverter Defibrillators in Transthyretin Cardiac Amyloidosis
Authors: Zack Dale, Lana Rashdan, Pranav Chandrashekar, Stephen B Heitner, Babak Nazer, Ahmad Masri
Journal: Circulation (2020)

Introduction: Patients with transthyretin cardiac amyloidosis (ATTR-CM) may have higher risk of sudden cardiac death yet the role of implantable cardioverter defibrillators (ICD) remains poorly defined. We report our experience with ICDs in a cohort with ATTR-CM. Methods: A single center observational cohort study of patients who had been seen at our Amyloidosis Center with either wild-type or hereditary ATTR-CM diagnosed between 2005-2019. ICD implant was at discretion of treating cardiologists. Device data was obtained from record review. Results: Ninety-seven patients with ATTR-CM (mean age 71.4±11 years, 89.7% male) had mean follow-up 2.2±1.9 years. Twenty-one patients (21.6%) got ICD - 19 for primary prevention and 2 for secondary prevention - with cumulative 137 interrogations over mean 2.0±2.7 years of device follow-up. In patients with primary prevention ICD, 1 patient got 2 inappropriate shocks - both for 1 episode of atrial flutter in the VT therapy zone; 1 patient got appropriate ATP on 3 occasions. In those with secondary prevention ICD, 1 patient got 15 appropriate shocks for 3 discrete episodes of VT storm; the other got ATP for 1 episode of monomorphic VT. In patients without ICD, 101 ambulatory monitors were reviewed (cumulative 12,313 hours) without sustained ventricular arrhythmia. In this group, 13/76 met at least a class IIB criterion for ICD per current guidelines. EF was higher in those without ICD versus with primary prevention ICD (45.0±13.9 vs 33.4±15.1 %, p=&lt;0.01). Death was seen with similar frequency in those with primary prevention ICD and those without ICD (p=0.60) and mode of death did not vary between them (Table 1). Conclusions: Patients with ATTR-CM and primary prevention ICD have low rates of appropriate device therapy without differing in mode of death compared to those with no ICD. Use of ICD for secondary prevention was uncommon but all patients got appropriate device therapy. Further study on ICDs in ATTR-CM is needed to inform best care.
Abstract P006: Multimorbidity In Patients With Atrial Fibrillation: A Community Study
Authors: Alanna M Chamberlain, Alvaro Alonso, Peter A Noseworthy, Jill Killian, Susan Weston, Veronique L Roger, Euijung Ryu
Journal: Circulation (2021)

Background: Multimorbidity is common in patients with atrial fibrillation (AF), yet comorbidity patterns are not well documented. Methods: The prevalence of 18 chronic conditions was obtained in patients with AF from 2013-2017 from a 27-county region in the Midwest. All patients had AF documented on an electrocardiogram or Holter monitor. To compare comorbidity patterns between patients with and without AF, controls were matched 1:1 on age (± 5 years) and sex. For AF patients and controls separately, the Somers’ D statistic was used to quantify the non-random concordance of each pair of chronic conditions beyond chance (ranging from -1 [perfect disagreement] to 1 [perfect agreement]; 0 indicating coincidental agreement by chance alone). Significance of the Somers’ D statistic was evaluated using a permutation approach with the Benjamini-Hochberg procedure for controlling the false discovery rate at 0.1%. Results: Among the 16,543 patients with AF (median age 76 years, 57% men), the most common conditions were hypertension (70%), hyperlipidemia (61%), arthritis (41%), and diabetes (40%). Many pairs of chronic conditions co-occurred more frequently than expected. However, no material differences were observed in the co-occurrence of conditions in patients with AF compared to controls (data not shown). Among patients with AF, the co-occurrence of conditions differed by age (Figure). In those ≤65 years, the strongest co-occurrence of conditions was depression/anxiety, although several condition pairs had Somers’ D statistics of &gt;0.4. In those aged 65-74 years, hypertension/hyperlipidemia and depression/anxiety had the strongest co-occurrence, whereas hypertension/hyperlipidemia was strongest for those aged ≥75 years. Conclusion: Although differences in the co-occurrence of conditions did not exist between AF and community controls, among the patients with AF, the patterns of co-existing conditions differed by age. A better understanding of the clinical consequences of multimorbidity in AF patients is needed.
Intratumoral CD39+CD8+ T Cells Predict Response to Programmed Cell Death Protein-1 or Programmed Death Ligand-1 Blockade in Patients With NSCLC
Authors: Joe Yeong, Lisda Suteja, Yannick Simoni, Kah Weng Lau, Aaron C. Tan, Hui Hua Li, Sherlly Lim, Jie Hua Loh, Felicia Y.T. Wee, Sanjna Nilesh Nerurkar, Angela Takano, Eng Huat Tan, Tony K.H. Lim, Evan W. Newell, Daniel S.W. Tan
Journal: Journal of Thoracic Oncology (2021)
Abstract P009: Growth Differentiation Factor 15 And The Subsequent Risk Of Atrial Fibrillation: The Atherosclerosis Risk In Communities Study
Authors: Mengkun Chen, Ning Ding, Lena Mathews, Ron C Hoogeveen, Christie M Ballantyne, Lin Yee Y Chen, Kunihiro Matsushita
Journal: Circulation (2021)

Introduction: Growth differentiation factor 15 (GDF-15) is a marker of oxidative stress and inflammation and has been associated with several cardiovascular disease (CVD) phenotypes. However, conflicting results have been reported regarding the association of GDF-15 with incident atrial fibrillation (AF) in the general population. Hypotheses: Higher GDF-15 level is associated with increased risk of incident AF independent of potential confounders. Methods: In 10,101 White and Black ARIC participants (mean age 60 years and 20.9% Blacks) free of AF at baseline (1993-95), we quantified the association of GDF-15 and incident AF using three Cox proportional hazards models. GDF-15 was measured by SOMA scan assay. AF was defined by hospitalizations with AF diagnosis or death certificates (ICD-9 codes: 427.31-427.32; ICD-10 codes: I48.x) or AF diagnosis by ECG at subsequent ARIC visits. Results: There were 2165 cases of incident AF over a median follow-up of 20.7 years (incidence rate 12.1 cases/1,000 person-years). After adjusting for demographic characteristics and cardiovascular risk factors, log GDF-15 was significantly associated with incident AF (hazard ratio 1.42 (1.25-1.63) for top vs. bottom quartile) (Model 1 in Table ). The result was robust even further adjusting for history of other CVD phenotypes and cardiac markers (Models 2 and 3 in Table ). In Model 3, quartiles of high-sensitive cardiac troponin T (hs-cTnT) did not demonstrate significant associations with incident AF. Conclusions: In community-based population, elevated GDF-15 level was independently and robustly associated with incident AF (even more strongly than troponin). These results suggest the involvement of GDF-15 in the development of AF and the potential of GDF-15 as a risk marker to identify individuals at high risk of AF.
Abstract MP16: A Behavioral Weight-loss Intervention, But Not Metformin, Decreases A Marker Of Gut Barrier Permeability In Adult Cancer Survivors With Overweight Or Obesity
Authors: Curtis Tilves, Hsin-Chieh Yeh, Nisa Maruthur, Stephen Juraschek, Edgar R Miller, Lawrence J Appel, Noel T Mueller
Journal: Circulation (2021)

Background: Serum lipopolysaccharide-binding protein (LBP), a surrogate biomarker for gut barrier permeability, is higher in adults with obesity and type 2 diabetes and may trigger inflammation. It is unknown whether a behavioral weight loss intervention or metformin — current first-line treatments for obesity or diabetes — can reduce gut permeability. Objective: To determine the effects of behavioral weight loss intervention or metformin, compared to self-directed weight loss, on serum LBP. Methods: SPIRIT was a parallel-arm, randomized trial of adult cancer survivors with overweight or obesity. Participants were randomized to a self-directed weight loss (control), metformin, or coach-directed (healthy diet/physical activity) weight loss arm. Of 121 randomized participants, a random subset (n=88) had LBP measured at baseline, 6-months, and 12-months post intervention. The effects of interventions on LBP over time were assessed using generalized estimating equations (GEE). Models were further adjusted for absolute change in fiber intake to investigate potential mediation. Results: Arms were balanced by sex (83% female), race (48% black), and age (mean 60 years). There were no between-group differences in LBP at baseline (median 42.3 μg/dL). Over the 12-month period, only the coach-directed and metformin arms showed weight loss (both mean -3% from baseline). Similar increases in LBP were seen in the self-directed and metformin arms, while a decrease in LBP was seen in the coach-directed arm ( figure ). In GEE models, the difference in slopes between the coach vs. self-directed arms was statistically significant (β=-1.67, p=0.037), but not between the metformin and self-directed arms (β=0.003, p=0.997). The effect of coach-directed weight loss on LBP was similar by sex and race and was not mediated by changes in fiber intake. Conclusion: The manner of weight loss can differentially impact gut permeability and thus subsequent exposure to proinflammatory microbial products.
Functional Assessment (FA) in Multiple Myeloma (MM) Patients Predicts Survival: Use of Most Valuable Comorbidity Scores and Functional Tests in a German Study Group (Deutsche Studiengruppe Multiples Myelom [DSMM]) Incentive
Authors: Sophia Scheubeck, Gabriele Ihorst, Sandra M. Dold, Katja Schoeller, Martin Boeker, Stefan J. Müller, Johannes M. Waldschmidt, Rebeka Javorniczky, Alessandra Larocca, Margrit Ott, Hermann Einsele, Justus Duyster, Ralph Wäsch, Monika Engelhardt
Journal: Blood (2017)
Incorporating Present-on-Admission Indicators in Medicare Claims to Inform Hospital Quality Measure Risk Adjustment Models
Authors: Elizabeth W. Triche, Xin Xin, Sydnie Stackland, Danielle Purvis, Alexandra Harris, Huihui Yu, Jacqueline N. Grady, Shu-Xia Li, Susannah M. Bernheim, Harlan M. Krumholz, James Poyer, Karen Dorsey
Journal: JAMA Network Open (2021)

Present-on-admission (POA) indicators in administrative claims data allow researchers to distinguish between preexisting conditions and those acquired during a hospital stay. The impact of adding POA information to claims-based measures of hospital quality has not yet been investigated to better understand patient underlying risk factors in the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision setting.
Abstract 16855: NOX4 NADPH Oxidase Mediates Diastolic Dysfunction in Stress Cardiomyopathy via Regulation of Inflammation and Fibrosis
Authors: Aleksandr E Vendrov, Han Xiao, Andrey Lozhkin, Nageswara R Madamanchi, Youyi Zhang, Marschall Runge
Journal: Circulation (2020)

Acute sympathetic stress in adults results in catecholamine overload and often leads to development of stress cardiomyopathy complicated by long-lasting diastolic dysfunction. We previously reported that activation of β-adrenergic signaling in the heart increases reactive oxygen species-mediated inflammasome activation and IL-18 release, inducing myocardial inflammation, fibrosis, and dysfunction. Here we tested the hypothesis that NOX4 NADPH oxidase is a primary mediator of myocardial inflammation and diastolic dysfunction in the setting of acute stress. Acute stress in wild-type and mice with cardiomyocyte (CM)-specific Nox4 deletion ( Nox4 CM-/- ) was induced with a single dose of β-adrenergic receptor agonist isoproterenol (ISO; 5 mg/kg) injection. After 3 days, ISO-treated wild-type mice had higher myocardial H 2 O 2 , inflammasome activation and IL-1β, IL-18, IL-6, CCL2, and TNF-α levels and enhanced myocardial interstitial macrophage infiltration compared with vehicle-treated or Nox4 CM-/- mice (p&lt;0.001). Wild-type mice left ventricles had increased presence of activated fibroblasts (periostin + ) and myofibroblasts (α-actin-2 + ) and significantly higher interstitial collagen deposition compared with Nox4 CM-/- mice 7 days post-ISO. Assessment of left ventricular function showed significantly increased mitral valve E, decreased deceleration time, decreased tissue Doppler E’ and increased E/E’ without changes in ejection fraction and end systolic or diastolic volumes, suggesting restrictive pattern of diastolic dysfunction with increased filling pressure in wild-type compared with control or Nox4 CM-/- mice. ISO treatment of ventricular CMs isolated from wild-type mice significantly increased levels of H 2 O 2 and expression of NLRP3 and cleaved caspase-1 and IL-18 as compared with Nox4 -deficient or wild-type CMs pretreated with NOX4/NOX1 inhibitor GKT137831. These data suggest that NOX4 NADPH oxidase is a critical mediator of CM sympathetic overstimulation inducing inflammasome activation and cytokine release, myocardial inflammation, and fibrosis, resulting in impaired diastolic function. Inhibiting myocardial NOX4 during acute sympathetic stress may be beneficial to preserve cardiac function.
Abstract 15547: Sfrp2 Mediates Ipsc to Cardiomyocyte Differentiation via Competing Actions on Wnts
Authors: Ying-chang Hsueh, Conrad Hodgkinson, Richard E Pratt, Victor J Dzau
Journal: Circulation (2020)

Induced pluripotent stem (iPS) cells provide a novel avenue to investigate how precursors differentiate into cardiomyocytes. In this study we examined our hypothesis that iPS differentiation is regulated by a balance between cardiogenic and inhibitory Wnt proteins. Recently, we have discovered that iPS cells differentiate into cardiomyocytes in response to Sfrp2 (control: 0% cardiomyocytes; Sfrp2 treated: 25% cardiomyocytes. N=3. P&lt;0.01). Since Sfrp2 mediates its effects by binding to Wnt proteins, we hypothesized that Sfrp2 promotes cardiomyocyte differentiation by binding to a Wnt that prevents iPS cells from differentiating into cardiomyocytes. To identify the inhibitory Wnt protein, we studied the effects of Wnt blocking antibodies on iPS and differentiation into cardiomyocytes. We observed that in control iPS cells or iPS cells incubated with a Wnt5 blocking antibody no cardiomyocytes appeared. In contrast, iPS cells incubated with a Wnt3a blocking antibody spontaneously and robustly differentiated into cardiomyocytes (40%, N=5, P&lt;0.001). Co-immunoprecipitation experiments demonstrated that Sfrp2 binds to Wnt3a (N=3, P&lt;0.001). Furthermore, Sfrp2 binding to Wnt3a inhibited b-catenin activation in iPS cells (80% active b-catenin in control cells; 10% active b-catenin in Sfrp2 and Wnt3a blocking antibody treated cells. N=3. P&lt;0.05). To identify the cardiogenic Wnt, we again screened iPS differentiation following incubation with various Wnt blocking antibodies. Through this process, we found that the positive effects of Sfrp2 or Wnt3a blocking antibodies were completely lost when the iPS were co-cultured with Wnt11 blocking antibodies (Wnt3a blocking antibody alone: 40% cardiomyocytes; Wnt3a plus Wnt11 blocking antibody: 0% cardiomyocytes). Interestingly, in iPS cells incubated with Wnt11 blocking antibody, b-catenin was re-activated (control cells: 10% active b-catenin; cells incubated with Wnt11 blocking antibody: 60% active b-catenin. N=3. P&lt;0.05). In summary, iPS cells do not spontaneously differentiate into cardiomyocytes because of opposing effects of Wnt3a and Wnt11. Sfrp2 promotes cardiomyocyte differentiation by binding to Wnt3a, allowing Wnt11 to induce iPS cells to differentiate into cardiomyocytes.
Abstract 17058: Phenotypically Sex Differences in Transthyretin Amyloidosis V122I Mutation Patients
Authors: Victoria Kalinoski-Dubose, Samantha LoRusso, Yvonne Efebera, Samir Parikh, Salem almaani, Nidhi Sharma, Elyse Redder, Miriam Freimer, naresh bumma, Rami Kahwash, Ajay Vallakati, Courtney Campbell
Journal: Circulation (2020)

Introduction: Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease, in which destabilized transthyretin protein misfolds and deposits in tissue leading to organ dysfunction. The most common mutation in the United States, transthyretin valine 122 isoleucine (V122I), primarily affects African Americans and is historically associated with cardiomyopathy phenotype in men. Recent studies have described a mixed V122I phenotype with both cardiomyopathy and polyneuropathy. Sex differences in V122I presentations have yet to be examined. Methods: We identified 38 ATTR patients treated at The Ohio State University with genetic testing demonstrating V122I mutation (31.6% female). Clinical data was analyzed for cardiac and nerve involvement including cardiac biopsy or nuclear pyrophosphate scan, echocardiography - interventricular septal thickness (IVSd), posterior wall thickness (PWd), ejection fraction (EF), and electromyography (EMG). Cohorts were divided by sex. Unpaired t-tests were used to calculate statistics. Asymptomatic patients (n=2) were not included. Results: In women with V122I ATTR, the clinical phenotypes were polyneuropathy (75%) and cardiomyopathy (25%) with symptom onset most often in the fourth or fifth decade of life. In men with V122I ATTR, the most common phenotypes were cardiomyopathy (52%) and mixed cardiomyopathy/polyneuropathy (48%) with symptom onset in the seventh and eighth decades of life. In affected individuals, EMG data revealed generalized neuropathy with reduced or absent sural nerve sensory response. Carpal tunnel syndrome, often due to thickening of the transverse ligament, was more common in men than women (84% versus 36%). Men had significant cardiac differences compared to women with thickened ventricles (IVSd 19.9 mm vs 12.5 mm, p&lt;0.001 and PWd 17.3 mm vs 12.1 mm, p&lt;0.001) and decreased ejection fraction (40% versus 55%, p=0.008). Conclusion: Based on our cohort, female ATTR V122I patients present predominantly with polyneuropathy phenotype at a younger age, and males present with predominantly cardiovascular or mixed phenotype. Recognizing these different sex phenotypes in ATTR V122I will improve diagnosis and treatment of patients.
Abstract 13676: No Difference in Timing and Risk for Sudden Death in Women and Men With Hypertrophic Cardiomyopathy
Authors: William Gionfriddo, Barry J Maron, Christopher Madias, Sophie Wells, Martin S Maron, Ethan J Rowin
Journal: Circulation (2019)

Background: Women with hypertrophic cardiomyopathy (HCM) have been described as having worse long-term survival, with adverse events occurring later in life as compared to men. Sudden death (SD) is...
Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells <i>in vitro</i>
Authors: Dušan Radojević, Sergej Tomić, Dušan Mihajlović, Maja Tolinački, Bojan Pavlović, Dragana Vučević, Svetlana Bojić, Nataša Golić, Miodrag Čolić, Jelena Đokić
Journal: Gut Microbes (2021)

Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher α-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-α, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFNγ, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower α-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-α, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.