tbuckley/cabot-search huggingface dataset:
L‐ornithine L‐aspartate in acute treatment of severe hepatic encephalopathy: A double‐blind randomized controlled trial
Authors: Arpan Jain, Barjesh Chander Sharma, Bhawna Mahajan, Siddharth Srivastava, Ajay Kumar, Sanjeev Sachdeva, Ujjwal Sonika, Ashok Dalal
Journal: Hepatology (2021)

Abstract Background and Aims Data on the use of intravenous L‐ornithine L‐aspartate (LOLA) in the treatment of overt HE (OHE) is limited. We evaluated the role of intravenous LOLA in patients of cirrhosis with OHE grade III–IV. Approach and Results In a double‐blind randomized placebo‐controlled trial, 140 patients were randomized to a combination of LOLA, lactulose, and rifaximin ( n = 70) or placebo, lactulose, and rifaximin ( n = 70). LOLA was given as continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF‐α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the grade of HE at day 5. Higher rates of improvement in grade of HE (92.5% vs. 66%, p &lt; 0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p = 0.03), and lower 28‐day mortality (16.4% vs. 41.8%, p = 0.001) were seen in the LOLA group as compared with placebo. Levels of inflammatory markers were reduced in both groups. Significantly higher reductions in levels of blood ammonia, IL‐6, and TNF‐α were seen in the LOLA group. Conclusions Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28‐day mortality.
Abstract 12488: Serum Cystatin C is an Early Predictor of Acute Renal Injury in Infants After Cardiac Surgery With Cardiopulmonary Bypass
Authors: Maher Abadeer, Alison L Kent, George J SCHWARTZ, Susan Martin, Michael F Swartz, patrick brophy, George Alfieris, Jill M Cholette
Journal: Circulation (2021)

Introduction: Acute kidney injury (AKI) following infant cardiac surgery is common, with increased morbidity and mortality. Changes in urine output and/or serum creatinine (SCr) are unreliable in the detection of AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, and lag behind onset of renal injury. Serum Cystatin C (SCC) has been used as a biomarker of AKI in adults and older children. If SCC predicts AKI in infants following cardiopulmonary bypass (CPB) is unknown. Hypothesis: SCC is an early biomarker of AKI following infant cardiac surgery requiring CPB. Methods: 42 infants (&lt; 1 year of age) were prospectively enrolled when presenting for cardiac surgery requiring CPB. SCC and SCr were measured at baseline (pre-operatively), and at 12, 24, and 48 hours following CPB initiation, and changes in SCC and SCr compared to baseline (ΔSCC and ΔSCr, respectively) were calculated. AKI was defined using KDIGO guidelines, as an increase in SCr ≥ 50% and/or a urine output &lt; 0.5mL/kg/hr for ≥ 6-12 consecutive hours in the first 3 post-operative days. Subjects were divided in 2 groups: AKI and non-AKI. Receiver Operating Characteristic (ROC) curves were utilized to predict AKI based on ΔSCC and ΔSCr, and the area under the curve (AUC) was quantified. Results: AKI occurred in 17 (40.4%) subjects. Baseline SCC and SCr measurements were similar between groups, as were age, gender, weight, and CPB time. Post-operative SCC values decreased from baseline, suggesting volume overload. While SCC concentrations did not differ significantly between the 2 groups, ΔSCC measurements were significantly different in those with AKI at 12 hours (0.2 ± 0.3 vs 0.4 ± 0.2; p &lt; 0.01) and remained different at 24 hours (0.1 ± 0.3 vs 0.3 ± 0.2; p = 0.02). ΔSCr measurements were significantly greater in the AKI group at 24 hours (0.1 ± 0.1 vs 0.0 ± 0.1; p &lt; 0.01) and 48 hours (0.1 ± 0.1 vs. 0.0 ± 0.1; p &lt; 0.01) but not at 12 hours. ROC curves demonstrated that both the ΔSCC at 12 hours (AUC = 0.72; p = 0.02) and the ΔSCr at 24 hours (AUC= 0.78; p &lt; 0.01) predicted AKI. Conclusions: The 12 hour ΔSCC predicts AKI in infants after cardiac surgery, and correlated with a rise in ΔSCr the following day. Earlier detection of AKI would allow earlier post-operative intervention to mitigate renal injury in infants.
Abstract P493: Histone Reader PHF7 Cooperates With The SWI/SNF Complex At Cardiac Super Enhancers To Promote Direct Reprogramming
Authors: Glynnis A Garry, Svetlana Bezprozvannaya, Huanyu Zhou, Hisayuki Hashimoto, Kenian Chen, Ning Liu, Rhonda S Bassel-duby, Eric N Olson
Journal: Circulation Research (2021)

Ischemic heart disease is the leading cause of death worldwide. Direct reprogramming of resident cardiac fibroblasts (CFs) to induced cardiomyocytes (iCLMs) has emerged as a potential therapeutic approach to treat heart failure and ischemic disease. Cardiac reprogramming was first achieved through forced expression of the transcription factors Gata4, Mef2c, and Tbx5 (GMT); our laboratory found that Hand2 (GHMT) and Akt1 (AGHMT) markedly enhanced reprogramming efficiency in embryonic and postnatal cell types. However, adult mouse and human fibroblasts are resistant to reprogramming due to staunch epigenetic barriers. We undertook a screen of mammalian gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified the epigenetic reader PHF7 as the most potent activating factor. We validated the findings of this screen and found that PHF7 augmented reprogramming of adult fibroblasts ten-fold. Mechanistically, PHF7 localized to cardiac super enhancers in fibroblasts by reading H3K4me2 marks, and through cooperation with the SWI/SNF complex, increased chromatin accessibility and transcription factor binding at these multivalent enhancers. Further, PHF7 recruited cardiac transcription factors to activate a positive transcriptional autoregulatory circuit in reprogramming. Importantly, PHF7 achieved efficient reprogramming through these mechanisms in the absence of Gata4. Collectively, these studies highlight the underexplored necessity of cardiac epigenetic readers, such as PHF7, in harnessing chromatin remodeling and transcriptional complexes to overcome critical barriers to direct cardiac reprogramming.
Abstract 13781: Megakaryocytes Participating in Thrombosis Under Inflammatory Stress and Sepsis: Direct Pathological Evidence in Two Cases
Authors: Hua Zhang, kuan zeng, Liang Li, Lu Zhang, Jianfen Li, Mo Yang, Yanqi Yang
Journal: Circulation (2021)

Introduction: Megakarycytes (MKs) produce platelets (PLTs) which enter the circulation and play its roles in hemostasis and thrombosis. However, direct pathological evidence that MKs participate in thrombosis has not been reported in clinical practice. We describe here direct observations in two cases where MKs were found in thrombosis in coronary artery and in the right atrium under open-heart surgery. Hypothesis: MKs might be mobilized into circulation and directly participate in and magnify thrombosis under sepsis, inflammatory stress and full heparinization. Methods: Case one was a 51-year-old male with ischemic cardiomyopathy, coronary stenoses and severe mitral insufficiency who underwent coronary artery bypass grafting (CABG) and mitral annuloplasty under cardiopulmonary bypass (CPB). A thrombus was pulled out from the right atrium when an atrial cannula was removed under full heparinization. Case two was a 53-year-old male with known mitral endocarditis and acute anterior myocardial infarction. Acute coronary angiogram after admission showed thrombosis in the left anterior descending (LAD) branch. The patient underwent emergency thrombectomy, CABG and mitral valve replacement with CPB. The thrombus was completely removed from the LAD through a small incision. Both thrombi, valve tissue and vegetation were sent for pathological examination with HE and CD41-IHC staining on paraffin sections. Results: Large number of giant polyploidy MKs surrounded by PLTs were seen in different areas in the thrombi of MKs-PLTs-fibrin networks from the right atrium and LAD. The coronary thrombus was consisted of MKs, PLTs and red cells in fibrin networks while the infected vegetation was consisted dominantly of inflammatory cells, bacterial legions and fibrin. Conclusions: MKs may enter both venous and arterial circulation, actively participate in thrombosis under inflammatory stress and sepsis, and be capable of escaping from inhibition of full heparinization.
Abstract 11852: Prognostic Value of B-type Natriuretic Peptide Reduction and Uric Acid Levels as Predictors of 30-day Re-Admission in Patients With Acute Decompensated Heart Failure With Preserved Ejection Fraction
Authors: Muhammad Madkour, Javad Savoj, Mimi S Biswas
Journal: Circulation (2021)

Introduction: There is limited data comparing re-admission outcomes in patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to determine the prognostic value of B-natriuretic peptide (BNP) level reduction and uric acid levels in hospitalized HFpEF patients. Hypothesis: Higher BNP level reduction and uric acid levels are associated with higher 30-day re-admission rates. Methods: This was a multi-center retrospective analysis of 3,398 patients admitted with acute decompensated HFpEF from January 2017 to December 2019. HFpEF was defined as a left ventricular function ≥ 50% and at least stage I diastolic dysfunction. Outcomes were defined by 30-day re-hospitalization rates for the two groups in the inpatient setting. Baseline characteristics, cardiovascular risk factors, admission laboratory data (troponin, sodium, hemoglobin A1c, uric acid), vital signs, length of stay and time to readmission due to heart failure exacerbation were gathered and compared. Results: The median age was 75.5 years and the mean length of stay was 11.1 days. The mean BNP at admission was 910 and the second BNP following standard therapy was 786. The median percent change in BNP was found to be 16.95%. Of the hypothesized clinical predictors of re-admission, we found that none of them; including change in BNP reduction and uric acid, were predictive of re-admission. Those who were re-admitted had lower sodium levels (136.6±5.86 vs 137.0±6.07, p=0.06), while improved creatinine levels (1.94±1.31 vs 2.06±1.66, p=0.02) was associated with re-admission for unclear reasons. For those patients who are white, the odds of experiencing re-admission is 1.54 times more likely compares to those who are of other race. Conclusions: Lower sodium levels and lower creatinine levels were found to be important risk factors for readmission. None of the hypothesized clinical variables including BNP reduction and uric acid predicted re-admission except for white race, which we feel is a surrogate for socioeconomic status. These findings underline the need for further studies and complexity in planning re-admission prevention algorithms in HFpEF patients.
Abstract 10416: Rising Trends in the Burden of Cardiovascular Comorbidities and Major Adverse Cardiovascular Events in Young Female Smokers Across Two Nationwide Cohorts Studied a Decade Apart (2017 vs. 2007)
Authors: Rupak Desai, Harsh Sura, Khizran Agha, Nayana Sasidharan, Umarani Badarabandi, Prerna Bansal, NFN Hiba Ambreen, Sonali Sachdeva, Akhil Jain
Journal: Circulation (2021)

Background: Ample evidence has suggested that female smokers are at a higher risk of smoking-related health problems compared to men. With the increasing number of young smokers in the US, there is limited data on the impact of smoking in young female smokers in the last decade. Methods: The National Inpatient Sample datasets (2007 and 2017) were utilized to identify hospitalizations among young (18-44 years) female tobacco smokers. We compared differences in frequency of admissions, comorbidity burden, and in-hospital outcomes (all-cause mortality and MACE) and resource utilization across two young cohorts 10-years apart. Results: A total of 1,224,479 (median age 32) admissions among young female smokers were identified in 2017 vs. 665,901 (median age 35) in 2007. Both cohorts showed the majority of admissions among white female smokers, followed by African Americans (Table 1) . Compared to the 2007 cohort, the rate of alcohol abuse, hyperlipidemia, uncomplicated diabetes and chronic pulmonary disease decreased inn 2017, whereas a rising trend was observed for deficiency and chronic blood loss anemias, diabetes with complications, drug abuse, hypertension, congestive heart failure, depression, liver disease, and obesity (p&lt;0.001). On adjusted multivariable analysis, the 2017 cohort showed significantly higher odds of all-cause mortality [aOR 1.25 (95%CI: 1.16-1.35)] with a higher risk of MACE [aOR 1.17 (95%CI:1.14-1.20)] (p&lt;0.001). There were fewer routine discharges and higher requirements of home health care in the 2017 cohort vs. 2007. Conclusion: The study reveals escalating trends in the burden of comorbidities, MACE and healthcare resource utilization in admissions (irrespective of primary cause) among young female smokers in this decade apart analysis. It is essential to raise awareness among young female smokers about the adverse impact of tobacco and associated polysubstance abuse on cardiovascular outcomes.
Abstract 12976: Insulin Resistance and Cardiometabolic Risk Profile Among Non-Diabetic American Young Adults: Insights From NHANES
Authors: Vibhu Parcha, Brittain F Heindl, Rajat Kalra, Peng Li, Barbara Gower, Garima Arora, Pankaj Arora
Journal: Circulation (2021)

Introduction: The burden of insulin resistance (IR) among young American adults has not been previously assessed. We evaluated the 1) trends and prevalence of IR and cardiometabolic risk factors and, 2) assessed the association between measures of adiposity and IR among adults aged 18-44 years without diabetes and preexisting cardiovascular diseases. Methods: Young adult participants aged 18-44 years from the National Health and Nutrition Examination Survey 2007-2018 cycles were analyzed. IR was defined as homeostatic model assessment for IR (HOMA-IR) of ≥2.5. The temporal trends of IR, prevalence of cardiometabolic risk factors (hypertension [HTN], hypercholesterolemia, obesity, poor physical activity, smoking, and poor diet), and the relationship between IR and measures of adiposity were assessed using multivariable-adjusted regression models. Results: Among 6,247 young adults, the prevalence of IR was 44.8% (42.0%-47.6%) in 2007-2010 and 40.3% (36.4%-44.2%) in 2015-2018 (P=0.07). There was a modest association of HOMA-IR with higher body mass index (BMI), waist circumference, total lean fat mass, and total and localized fat mass (all p&lt;0.001)( Fig 1 ). Participants with IR had a higher prevalence of HTN (31.3% [29.2%-33.5%] vs. 14.7% [13.2-16.2%]), hypercholesterolemia (16.0% [12.4%-19.5%] vs. 7.0% [5.8%-8.5%]), obesity (56.6% [53.9-59.3%] vs. 14.7% [13.0%-16.5%]) and poor physical activity levels (18.3% [16.4%-20.2%] vs. 11.7% [10.3%-13.1%]) compared to participants without IR (all p&lt;0.05). The prevalence of current smoking status (21.2% [19.1%-23.3%] vs. 21.6% [19.4%-23.9%]) and poor diet (79.1% [77.2%-81.0%] vs. 77.4% [75.2%-79.6%]) was similar between those with and without IR. Conclusions: Four-in-ten young American adults have IR which occurs in a cluster with cardiometabolic risk factors. Nearly half of young adults with IR are non-obese. Implementation of IR screening irrespective of BMI may be required.
Abstract 11459: Mitochondrial Metabolites Predict Cardiovascular Outcomes and Heart Failure in Individuals with Type 2 Diabetes Mellitus: An Exscel Biomarker Substudy
Authors: Jessica A Regan, Robert J Mentz, Maggie Nguyen, Jennifer Green, Lauren Truby, Olga Ilkayeva, John Buse, Harald Sourij, David Sjostrom, Naveed Sattar, Adrian F Hernandez, Rury Holman, Svati H Shah
Journal: Circulation (2021)

Introduction: Metabolic substrate utilization is central to metabolic disease. Metabolic pathways linking type 2 diabetes (T2D) to major adverse cardiac events (MACE) and heart failure (HF) remain poorly understood and T2D drug effects on metabolite biomarkers could improve biological understanding and support precision medicine approaches. Hypothesis: Circulating metabolites characterizing mitochondrial dysfunction are predictors for MACE and hospitalization for HF (hHF), and are improved with exenatide. Methods: We performed targeted mass-spectrometry profiling of 60 metabolites on baseline and 12-month plasma samples from 978 participants from EXSCEL, a randomized trial of the GLP-1 receptor agonist, exenatide. Principal components analysis (PCA) was used; resultant metabolite factors were analyzed with univariate and multivariable logistic regression (adjusted for history of HF, coronary artery disease, BMI, HbA 1c , eGFR, blood pressure) for association with MACE (CV death, non-fatal MI or stroke) and hHF. Results were validated in participants from TECOS, a randomized trial of the DPP-4 inhibitor sitagliptin. Metabolite changes by treatment arm were tested. Results: Of 12 PCA metabolite factors, two nominally associated with MACE in both univariate and multivariable models and two associated with hHF in univariate, but not multivariable models ( Table ). Individual metabolites remained associated with MACE in multivariable models and with hHF in univariate models. Similar results were seen in the TECOS validation cohort. Individual metabolites decreased to a greater extent in exenatide randomized individuals compared with placebo. Conclusions: Metabolites reporting on dysregulated mitochondrial fatty acid oxidation are increased in individuals with T2D who experience MACE. These biomarkers may improve CV risk prediction models, appear to be beneficially modified by exenatide, and highlight emerging risk mechanisms.
Effect of BCR-ABL1 Transcript Type and Body Weight on Outcome in Chronic Myeloid Leukemia
Authors: Mohammad Abdul-Jaber Abdulla, Prem Chandra, Susana El akiki, Mahmood B Aldapt, Sundus Sardar, Ammar Chapra, Abdulqadir Jeprel Nashwan, Claudio Sorio, Luisa Tomasello, Christian Boni, Mohamed A Yassin
Journal: Blood (2021)
Systematic Construction of an Autophagic Risk Model in Bone Marrow for Prognostic Prediction in Multiple Myeloma
Authors: Lingling Shu, Han-Ying Huang, Yang Liu, Yang Li, Weida Wang, Jinyuan Li, Shuzhao Chen, Xiaoping Wu, Yun Wang, Huan-xin Lin, Yang Liang
Journal: Blood (2021)
Abstract 6919: Comparative Effectiveness of Long-Acting Insulin Analogs and Neutral Protamine Hagedorn (nph) Insulin for the Reduction of Major Adverse Cardiovascular Events Among Patients With Type 2 Diabetes
Authors: Vanessa C C Brunetti, Oriana H Yu, Robert W Platt, Kristian B Filion
Journal: Circulation (2021)

Introduction: Although long-acting insulin analogs (glargine, detemir, and degludec) and neutral protamine Hagedorn (NPH) insulin show similar efficacy for glycemic control among patients with type 2 diabetes, their comparative effectiveness in reducing cardiovascular events is unclear. Objective: To compare the risk of major adverse cardiovascular events (MACE) with the use of long-acting insulin analogs versus NPH among patients with type 2 diabetes. Methods: We conducted a retrospective cohort study using the Clinical Practice Research Datalink, a primary care database from the United Kingdom, linked with hospitalization and vital statistics data. The cohort included adults with type 2 diabetes initiating basal insulin therapy between 2002 and 2018. Exposure was defined as time-varying where each person-month of follow-up was classified as either current use of long-acting insulin analogs or NPH; patients who discontinued insulin treatment or were exposed to both insulin analogs and NPH in the same month were censored. The primary endpoint was MACE, a composite endpoint of myocardial infarction, ischemic stroke, and cardiovascular death. We used inverse probability of treatment and censoring weighting to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for MACE associated with current use of long-acting insulin analogs versus NPH. We also conducted secondary analyses stratified by age, sex, history of cardiovascular disease . Results: A total of 57,334 patients entered our cohort (31,136 using a long-acting analog and 26,198 using NPH. Mean age was 63.8 years, and 44.3% of patients were female. A total of 3,494 MACE events occurred over a mean follow-up of 1.62 years. Long-acting insulin analogs were not associated with a decreased risk of MACE compared to NPH (Table). Conclusions: Current use of long-acting insulin analogs is not associated with a reduced risk of MACE compared to use of NPH insulin among patients with type 2 diabetes.
Abstract 9869: Adverse Effects of Smoking/Vaping of Several Types of Tobacco Products and Marijuana on Cardiac Function and Platelet Aggregation
Authors: Xiaoyin Wang, Huiliang Qiu, Daniel D Han, Kelly Tan, Ronak Derakhshandeh, Matthew L Springer
Journal: Circulation (2021)

Tobacco and marijuana smoke contains ~7,000 chemicals that cause disorders in cardiac autonomic function, vascular biology, and platelet function. Along with marijuana, e-cigarettes (e-cigs) and heat-not-burn tobacco products (e.g., IQOS) are often viewed as being less harmful than smoking tobacco. However, there are many unknowns about how marijuana, e-cigs, and IQOS impact cardiovascular physiology and platelet function over the long term. To explore cardiovascular effects of smoking/vaping, we exposed conscious rats to single (one time) and multiple (one time daily for 10 days) pulsatile mainstream smoking/vaping of e-cigs (JUUL), IQOS (American and Russian HeatSticks), marijuana (~10% THC), and cannabinoid-depleted (“placebo”) marijuana, relative to regular tobacco (Marlboro Red) smoking and air controls. Cardiac function was assessed by echocardiography pre- and post- single exposure. Platelet aggregation was measured to determine changes in platelet response immediately post-single exposure and one day after the last of multiple exposures. Single exposure induced acute effects on echocardiographic function with reduced ventricular end-diastolic volume (EDV) in IQOS and marijuana groups of both genders (Fig. A), potentially indicating incomplete ventricular relaxation between heart beats after exposure. However, marijuana caused adjustments of end-systolic volume (ESV) and EDV without changes in ejection fraction (EF) in females, with smaller ESV and reduced EDV. Tobacco, marijuana, and placebo marijuana smoking immediately increased collagen-induced platelet aggregation post-single exposure in female rats. Tobacco smoking, JUUL, IQOS, and both kinds of marijuana significantly increased platelet aggregation post-multiple exposure as compared to air controls in mixed genders (Fig. B). P values ≤ 0.1 are shown. Conclusion: smoking/vaping causes clinically relevant adverse effects on cardiac function and platelet aggregation.