tbuckley/cabot-search huggingface dataset:
Abstract 12808: Nobel Murine Model of Atherosclerosis Progression Induced by a Modified-Paigen Diet
Authors: Mary Alvarez, Adolfo Virgen-Ortiz, ALEJANDRINA RODRIGUEZ-HERNANDEZ, Adriana Ceballos-Gutierrez, Alejandro Figueroa, Felipa Andrade, SANCHEZ PASTOR ENRIQUE ALEJANDRO
Journal: Circulation (2021)

To better understand the mechanisms involved in the atherosclerosis progression, different models have been used. Currently there is no ideal model, each one has its advantages and disadvantages, especially when you want to study the disease progress. In this context we tested the hypothesis: the atherogenic “Paigen type” diet with modifications (APTDM), generates a stable model for the study of each phase of atherogenic process. Atherosclerosis was induced in 80 Wistar rats using APTDM consisting of 2 phases: 1) Hypervitamin, administered orally at a dose of 1.5 ml / kg / day for 12 days and 2) Hyperlipidic, administered for 48 days ad libitum . Experiments were carried out in 4 groups (n=16) with different doses (G1 = 75%, G2 = 50%, G3 = 33% and G4 = 25%) to obtain a dose-response curve, a healthy group (n=8; C) and a positive control (100% of the diet for 15 days; n=8; C+). Analysis was performed at day 15 for C+ and at day 30 (D30) and day 60 (D60) for the other groups. Aorta artery descending portion was extracted and histological analysis was performed to evaluate the atherosclerosis degree. Rats from C+ had severe grades (V-VII) at D15. All rats from G1 were sacrificed due to a poisoning for vitamin D2 excess. G2 rats were sacrificed at the end of D30 showing atherosclerotic lesions classified severe grades (V-VII). G3 showed mild degrees (I-III) at D30 and showed severe degrees (IV-VII) at D60. G4 showed mild degrees (I-III) at D30 and D60. Glucose, lipid profile, systolic (SBP) and diastolic (DBP) blood pressure was determined for G3. SBP decreased on D30 and D60 (123 ± 1 vs 109 ± 2 (p &lt;0.01) and 124 ± 1 vs 99 ± 2 mmHg (p &lt;0.01) respectively). Similar results in DBP were observed (83 ± 2 vs 69 ± 1 mmHg (p &lt;0.01) at D60). Glucose increased on D30 and D60 (C = 98 ± 5 vs 159 ± 17 (p = 0.02) and 134 ± 4 mg/dL (p &lt;0.01) respectively). Similar behavior for cholesterol (C = 56 ± 1 vs 114 ± 5 (p &lt;0.01) and 128 ± 8 mg/dL (p &lt;0.01) respectively), LDL (C = 39 ± 3 vs 103 ± 3 (p &lt;0.01) and 123 ± 13 mg/dL (p &lt;0.01) respectively) and triglycerides (C = 39 ± 2 vs 40 ± 1 (p = 0.01) and 74 ± 11 mg/dL (p = 0.01) respectively) was observed. HDL only increased on D60 (C = 22 ± 1 mg/dL vs 34 ± 3 (p &lt;0.01)). In conclusion, APTDM to 33% (G3), generates a stable model for the study of the progress of each of the atherosclerosis phases in rats.
Phase 2 Suzhou MM02 Study: Chidamide with VRD Versus VRD in Newly Diagnosed High Risk Transplant Eligible Multiple Myeloma Patients
Authors: Weiqin Yao, Lingzhi Yan, Jingjing Shang, Song Jin, Xiaolan Shi, Shuang Yan, Depei Wu, Chengcheng Fu
Journal: Blood (2021)
Abstract 17200: Plasma BNP Declines in the First Two Years After Transplant and is Elevated at the Time of Treated Rejection
Authors: Tom J Valikodath, Neal Jorgensen, Erin Albers, Borah Hong, Joshua Friedland-Little, Mariska Kemna, Yuk Law
Journal: Circulation (2018)

Introduction: Plasma B-type natriuretic peptide (BNP) is a biomarker used to diagnose and monitor ventricular dysfunction and heart failure. However, the response of the allograft to produce BNP from ventricular wall stress and inflammation may be different, particularly in an understudied population such as pediatric recipients. Hypothesis: BNP levels decrease over time after transplant as the allograft recovers; but BNP will be higher during rejection. Methods: Enrolled all heart recipients from January 2007 to December 2016. Rejection surveillance included serial echocardiography, annual biopsy, and BNP q 1-3 months. Rejection is defined as requiring augmentation of immunosuppression from biopsy grade ≥ 2R or ≥ pAMR2 or from clinical diagnosis. Results: Among 114 patients studied, 60% were male with age at transplant 5.8 ± SD 6.5 yrs. Follow-up was 3.7 ± 2.7 yrs and 37 patients (32%) experienced 75 episodes of rejection. A total of 8358 BNP samples were obtained. BNP decreased linearly after transplant leveling off after 2 years (Fig 1). BNP was 671 ± 1115 (n=75) at rejection vs. 187 ± 423 pg/mL (n=501) without rejection confirmed by biopsy. By multivariable analysis, Ln BNP was associated with rejection (RR 1.56; 95% CI 1.35-1.80). Figure 2 shows the relationship between change in BNP and risk of rejection. Multivariable longitudinal Cox proportional model incorporating BNPs leading to 1 st rejection showed Ln BNP to be associated with rejection (HR 2.22; 95% CI 1.53-3.23, p&lt;0.001). Conclusion: BNP continues to decrease in the 1 st 2 years after transplant. At rejection, BNP is elevated, and this test can be further developed to screen for rejection.
Abstract 10223: Tissue-Entrapped Extracellular Vesicles Modulate Divergent Mechanisms of Cardiovascular Calcification
Authors: Mark C Blaser, Fabrizio Buffolo, Arda Halu, Florian Schlotter, Hideyuki Higashi, Lorena Pantano Rubino, Louis A Saddic, Samantha Atkins, Maximillian Rogers, Tan Pham, Amelie Vromman, Eugenia Shvartz, Galina K Sukhova, Silvia MONTICONE, giovanni. camussi, Simon C Body, Tsuyoshi Kaneko, J Daniel D Muehlschlegel, Sasha A Singh, Masanori Aikawa, Elena Aikawa
Journal: Circulation (2021)

Introduction: Fewer than 50% of patients develop vascular and valvular calcification, implying differential pathogenesis. Tissue-entrapped extracellular vesicles (EVs) are implicated in mineralization but their contents and functions are unstudied. We investigated entrapped EV cargoes in human cardiovascular disease. Methods: Human carotid endarterectomy specimens and stenotic aortic valves were obtained from 53 patients. Disease stage-specific proteomics was performed on whole tissue (non-diseased/fibrotic/calcified areas). Tissue EVs were enriched by gradient fractionation then underwent proteomics and miRNA-seq. miR targets were predicted by TargetScan, pathway analyses utilized BioCarta/KEGG/Reactome, and protein-protein interaction networks employed STRING. Results: Disease progression drove significant convergence (p&lt;0.0001) of atherosclerotic plaque and valve proteomes (2,318 proteins). 548 and 158 proteins were exclusively altered (q&lt;0.05) by disease in plaques or valves, respectively. Vesicular GO terms increased 2.2x (p&lt;0.01) amongst proteins altered by disease in both tissues (202). Proteomics found 24 EV markers in the low-density fractions of plaques and valves, confirmed by electron microscopy and nanoparticle tracking. EV omics quantified 1,104 proteins and 123 miR cargoes. Networks of proteins and miR targets shared by plaque and valve EVs revealed common regulation of Rho GTPase and MAPK signaling. 179 proteins and 5 miRs were altered between plaque and valve EVs (q&lt;0.05); multi-omics integration found that EVs modulated cellular contraction and p53-mediated transcriptional regulation in plaques and valves, respectively. Conclusions: This first comparative proteomics study of human valves and arteries finds shared EV functionality in both diseases. Using novel means to examine tissue EV molecular cargoes, we also reveal critical divergent tissue-specific roles for EVs in mediating cardiovascular disease.
Abstract 11920: Early Changes in Echocardiographic Variables of Patients With Pulmonary Hypertension Undergoing Bilateral Pulmonary Thrombo-Endarterectomy: Experience of a Tertiary Care Center in Latin-America at 8660 Feet Above Sea Level
Authors: Diego Eduardo Garnica Sepulveda, Gabriel Salazar, RAFAEL CONDE, Frida T Manrique, Albert F Guerrero, Hector Medina, Juan P Umaña
Journal: Circulation (2021)

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a reversible cause of pulmonary hypertension when patients undergo bilateral pulmonary thrombo-endarterectomy (BPT). We aim to compare TTE findings before and after BPT in a tertiary care center with an unusual altitude above sea level in Bogota, Colombia. Methods: Retrospective cohort, including CTEPH patients undergoing BPT between 2016 and 2021. We compared TTE done pre and post-operatively. We evaluated TTE volumetric and functional data including inter-ventricular dependence using the ratio of end-systolic diameter of right and the left ventricle (RV/LV). Results: We included CTEPH 17 who underwent BPT in our institution and compared studies done before and within the first 6 months after the procedure. Compared to the pre-op studies, the post-op TTE′s showed lower basal and middle diameters of the RV, lower TAPSE and higher CAF values with no changes in tricuspid S’ wave. The LVEF and right atrium area were similar to pre-operative TTE′s. Of notice, diastolic parameters such as E/A and E/e’ ratios improved to a normal diastolic filling pattern. Higher left atrium volume was also noticed. Finally, we observed lower PASP, a longer pulmonary valve acceleration time and lower RV/LV end-systolic diameter ratio in the early post-operative state (Table 1). Conclusions: In a tertiary care center with an altitude of 8660 feet above sea level, early TTE post BPT in CTEPH patients demonstrated decrease in the size of the right-sided chambers, higher volumes in left-sided chambers, normalization of diastolic parameters, decrease in PSAP, increase in the pulmonary valve acceleration time, and decrease of inter-ventricular dependance. Our findings suggest early remodeling phenomena after BPT despite the high altitude of where the surgery was performed.
Abstract 9926: A Controlled Study of Frailty and Clinical Outcomes in Acute Care Patients with Atrial Fibrillation
Authors: Su Su Htwe, Natalie Sae-Rian, Sumitha Bhaskaran, Paw Min Thein
Journal: Circulation (2021)

Background: Frailty has multidimensional aetiology. AF may predict frailty and is associated with hospital mortality in epidemiological studies. In geriatric patients receiving acute hospital care, interrelationship between AF, frailty, a predisposition to subacute care and overall mortality is unclear. Aim: To investigate an association between frailty and in-hospital mortality in acute care patients with AF Methods: A retrospective study was conducted to investigate acute geriatric inpatients (&gt;65 years, n=1518) with AF admitted under General Medicine units at three Monash Health affiliated hospitals between July and November 2020. Exclusion criteria were: non-English speaking background, MMSE&lt;25, high-level care requiring residents. Frailty was measured by Rockwood clinical frailty scale. Primary endpoint was all-cause mortality. Results: Prevalence of AF was 19%. Of 294 with AF, 6% were new-onset. Mean age was 82±7 years and 43% were female. Mean left ventricular ejection fraction was 56±13 % and 30% had regional hypokinesis on transthoracic echocardiogram. Median Rockwood score was 5(IQR 3,6), acute hospital length of stay was 11±15days and 9% died during hospital stay. In comparison, Rockwood score was lower 4 (IQR 3,5) and only 2% died in a control group without AF (P=0.017). On univariate logistic regression, higher Rockwood score was associated with subacute admissions (OR=1.4,P=0.001) whereas, regional hypokinesis (OR=2.5,P=0.048), chronic kidney disease (OR=2.7,P=0.015) and higher Rockwood score (OR=2.9,P&lt;0.0001) were associated with all-cause in-hospital mortality. After adjusting for age, premorbid status, and comorbidities, higher Rockwood score remained predictive of all-cause in-hospital mortality (OR=3.0,P&lt;0.0001) in AF group. Conclusion: Frailty measured by Rockwood scale in acute care patients with AF is associated with in-hospital mortality. All-cause in-hospital mortality is significantly lower in a control group without AF. Prospective controlled studies are warranted to further strengthen the evidence.
Aberrant <i>Dntt</i> Expression, TdT-Aided Gene Length Mutations, and Prognosis Relevance in ATG/Alg Based Regimen Allo-HSCT in Acute Myeloid Leukemias
Authors: Xiaosu Zhou, Daijing Nie, Yang Zhang, Zhixiu Liu, Jianping Zhang, Yanli Zhao, Fang Wang, Jiancheng Fang, Panxiang Cao, Xue Chen, Xiaoli Ma, Jiaqi Chen, Qisheng Wu, Peihua Lu, Hongxing Liu
Journal: Blood (2021)
Abstract P436: Modeling Genetic Dilated Cardiomyopathy Using Induced Pluripotent Stem Cell-derived Engineered Heart Tissues For Precision Medicine
Authors: Renee E Butler, Stephanie S Steltzer, Bernardo Zepeda, Jonathan H Tsui, Mo A Mandegar, Tim Hoey, Jaclyn J Ho
Journal: Circulation Research (2021)

Recent advancement of human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) technologies has opened the door to next-generation modeling of human cardiac biology and disease. Not only does this alleviate the need for human primary tissue and compensate for the well documented deficiencies of rodent models for cardiovascular disease, but these technologies may lead to the identification of better candidates for clinical development. Unfortunately, most current 2D hiPSC-CM models lack the biochemical, mechanical, and electrical feedback that cardiomyocytes endure in a multi-cellular aligned tissue, which limits their translatability into clinical settings. To address this, we incorporated hiPSC-CMs modeling various genetic dilated cardiomyopathies (DCM) into 3D engineered heart tissues (EHTs). Here, we show these models develop distinguishable contractile defects recapitulating hallmarks of DCM when compared to biologically relevant controls. Moreover, this distinct phenotype is quantitative, reproducible, and demonstrates utility for drug discovery. As this innovative technology continues to develop, EHTs are on the forefront of emerging biomimetic assays that can be used to prevent drug attrition in the late stages of drug development.
Abstract 10177: Optimal Reperfusion Strategy in Acute High-Risk Pulmonary Embolism Requiring Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-Analysis
Authors: Romain Chopard, Peter B Nielsen, Fabio Ius, Fiona Ecarnot, Hugo Pilichowski, Gregory Piazza, Nicolas Meneveau
Journal: Circulation (2021)

Introduction: The optimal pulmonary revascularization strategy in acute high-risk pulmonary embolism (PE) requiring the implantation of extra corporeal membrane oxygenation (ECMO) remains controversial. Methods: We conducted a systematic review and meta-analysis of available evidence comparing mechanical reperfusion and other strategies, including systemic or catheter-directed thrombolysis and ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes. Results: The literature search identified 835 studies, 17 of which were included, totaling 321 PE patients with ECMO. Overall, 31.1% were treated with mechanical pulmonary reperfusion, while 78.9% received other strategies. The mortality rate was 23.0% in the mechanical reperfusion group and 43.1% in the other strategy group. The pooled OR for mortality with mechanical reperfusion was 0.46 (95%CI, 0.213-0.997; I 2 = 28.3%) versus other reperfusion strategies (Figure). The rate of bleeding in PE patients under ECMO was 29.1% in the mechanical reperfusion group and 26.0% in the other reperfusion group (OR, 1.09; 95% CI, 0.46-2.54; I 2 , 0.0%) among 10 eligible studies with available bleeding data. The meta-regression model did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy” and “ECMO implantation before pulmonary reperfusion therapy”, and outcomes. Conclusions: The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, yields the best results, regardless of the timing of ECMO implantation in the reperfusion timeline, and regardless of whether thrombolysis has been administered or not.
Abstract 14079: Targeted Deletion of Cardiac miR-17-92 Cluster Exacerbates Ischemic Myocardial Injury in Diabetic Mice Through Induction of Sphingolipid Biosynthesis and Cardiomyocyte Inflammation
Authors: Arun Samidurai, Sean Roh, Shruti Yerramothu, Lauren Cowart, Fadi N Salloum, Anindita Das
Journal: Circulation (2021)

Background: The miR-17-92 cluster is indispensable for normal cardiac development and its deletion leads to cardiovascular disease. Aberrancies in bioactive sphingolipid metabolism, specifically ceramide (CER), contribute to diabetic cardiomyopathy, where induction of ceramide synthases (CerS) predicts elevated risk of cardiovascular complications. We investigated the role of miR-17-92 in suppression of ceramide synthesis to attenuate cardiac inflammation following myocardial ischemia/reperfusion (I/R) injury in diabetic mice. Methods and Results: Hearts from adult high-fat-diet fed diabetic tamoxifen-inducible cardiac-specific miR-17-92-deficient (miR-17-92-def) and wild type (WT) mice were subjected to 30 min of myocardial ischemia (I) and 60 min of reperfusion (R) in Langendorff mode. Myocardial infarct size was exacerbated with severe ventricular dysfunction in diabetic miR-17-92-def mice as compared to diabetic WT mice ( Fig. A ). Cardiomyocytes isolated from diabetic miR-17-92-def and WT mice were subjected to 40 min simulated ischemia and 2-hr reoxygenation (SI/RO). Immunofluorescence staining demonstrated an enhanced inflammasome formation with ASC (apoptosis speck-like protein with a caspase recruitment domain) aggregation ( Fig. B ) and caspase-1 activation ( Fig. C ) following SI/RO in cardiomyocytes isolated from diabetic miR-17-92-def mice. Lipidomics analysis revealed that C16:0 ceramide, a product of Ceramide Synthase 6 (CerS6), was induced after I/R injury and was more prominent in the hearts of diabetic miR-17-92-def mice (Fig. D). Western blot analysis revealed that CerS6 expression was nearly undetectable in the hearts of diabetic WT mice, but was dramatically induced by I/R in diabetic miR-17-92-def mice ( Fig. E ). Conclusion: The deletion of cardiac miR-17-92 exacerbates myocardial I/R injury under diabetic condition through accumulation of CER by inducing CerS6 and stimulating inflammation in cardiomyocytes.
Evaluating optimal treatment durations for bloodstream infections: methodological perspectives on the choice of outcomes and sample sizes for non-inferiority design and margins
Authors: Divyajot Sadana, Robert A. Fowler
Journal: Clinical Microbiology and Infection (2021)

There are an increasing number of trials evaluating the efficacy of shorter versus longer treatment durations for a variety of infections, including ventilator-associated pneumonia [ [1] Chastre J. Wolff M. Fagon J. Chevret S. Thomas F. Wermert D. et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003; 290: 2588-2598 Google Scholar ], intra-abdominal infection [ [2] Sawyer R.G. Claridge J.A. Nathens A.B. Rotstein O.D. Duane T.M. Evans H.L. et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015; 372: 1996-2005 Google Scholar ], and community-acquired pneumonia [ [3] Dunbar L.M. Wunderink R.G. Habib M.P. Smith L.G. Tennenberg A.M. Khashab M.M. et al. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis. 2003; 37: 752-760 Google Scholar ]. In the SHORTEN trial, Molina and colleagues tackle an important question about the optimal duration of antibiotics for Enterobacterales bacteraemia, enrolling both hospitalized patients and outpatients in a comparison of 7 versus 14 days of antibiotics, with 28 days of follow-up [ [4] Molina J. Montero-Mateos E. Praena-Segovia J. León-Jiménez E. Natera C. López-Cortés L.E. et al. SHORTEN trial teamSeven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial. Clin Microbiol Infect. 2022; 28: 550-557 Google Scholar ]. Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trialClinical Microbiology and InfectionVol. 28Issue 4PreviewTo prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes. Full-Text PDF Re: 'Seven versus 14-days course of antibiotics for the treatment of bloodstream infections by Enterobacterales' by Molina et al.Clinical Microbiology and InfectionVol. 28Issue 5PreviewWe read the article by Molina et al. [1] with interest. Generally, the current standard therapy for Enterobacteriaceae bacteraemia is considered to be antibiotic administration for 14 days; the authors suggest the possibility that the duration of the antibiotic administration can be successfully reduced to 7 days [1]. A shorter period of antibiotics could reduce medical costs as well as reducing side effects and the development of drug-resistant bacteria. However, the results should be interpreted with caution. Full-Text PDF
Abstract 12192: Arterial Tortuosity Syndrome: A Longitudinal Assessment Of Cardiovascular Features
Authors: Bita Salamat, Andrea Taylor, Sara Stephens, Taylor Beecroft, Justin Weigand, Ben Jacob, Shaine A Morris
Journal: Circulation (2021)

Introduction: Arterial tortuosity syndrome (ATS) is an ultra-rare arteriopathy caused by pathogenic biallelic variants in SLC2A10 leading to tortuosity, elongation, and dilation of vessels, and pulmonary artery (PA) stenosis (Fig 1). No studies to date have evaluated the progression of cardiovascular (CV) features, including aortic root (AR) and ascending aorta (AA) dilation. Hypothesis: We hypothesize AR and AA dilation progress similar to other aortopathies with increase dimensions but stable z-scores in childhood. Methods: A retrospective cohort study of patients at our institution with ATS, defined by homozygous or compound heterozygous SLC2A10 mutations with consistent phenotypes, from 2000-2021 was conducted. CV imaging, medications, and interventions were reviewed. AR and AA measurements were collected from echocardiographic reports and z-scores were calculated. Dilation was defined as z-score &gt; +2. Slopes were calculated using mixed linear regression. Results: Six subjects (5 males) aged 1 month-16 years at diagnosis were included. All had AR dilation, 50% had AA dilation, and 50% had main or branch PA stenosis at a given point. CV intervention was only performed in 1 patient who underwent multiple bilateral PA angioplasties and stenting for severe distal branch PA hypoplasia. Three patients were prescribed beta-blockers, of whom one was also prescribed losartan. Figure 2 shows mean slopes for AR and AA changes. No patients had aortic dissection or CV surgery. Conclusions: In conclusion, AR and AA dilation persist in ATS but with stable z-scores similar to other aortopathies. Larger sample size investigations may further elucidate the role of medications in ATS.