tbuckley/cabot-search huggingface dataset:
Eutos long-term survival score discriminates different Sokal score categories in chronic myeloid leukemia patients, showing better survival prediction. Analysis of the GIMEMA CML observational study
Authors: Massimo Breccia, Patrizia Pregno, Fausto Castagnetti, Massimiliano Bonifacio, Mario Tiribelli, Antonella Gozzini, Anna Rita Scortechini, Luigiana Luciano, Bruno Martino, Fabio Stagno, Giovanni Caocci, Gaetano La Barba, Michele Pizzuti, Giovannino Ciccone, Giuseppe Saglio, Giorgina Specchia
Journal: Leukemia (2021)
The Closing Argument for Surgical Left Atrial Appendage Occlusion
Authors: Richard L. Page
Journal: New England Journal of Medicine (2021)

It is widely accepted that the increased risk of stroke among patients with atrial fibrillation is substantially due to embolization of thrombi that develop in the left atrial appendage. On the basis of multiple randomized trials showing that the risk of stroke is reduced with oral anticoagulation therapy among high-risk patients with nonvalvular atrial fibrillation, clinical practice guidelines provide the strongest level of recommendation for oral anticoagulation in these patients, as guided by CHA2DS2-VASc1,2 or CHADS-653 risk scores. In comparison with the robust data that underlie the recommendation for oral anticoagulation, the strategy of percutaneous occlusion of the left atrial . . .
Abstract 16552: Chromosomal Microarray Abnormalities in More Than 1300 Patients With Congenital Heart Disease Provide Novel Clinical and Etiological Insights
Authors: Benjamin J Landis, Lindsey R Elmore, Gabrielle C Geddes, Jiuann-huey I Lin, Svetlana A Yatsenko, Cecilia W Lo, Steven B Bleyl, William L Border, Stephanie B Wechsler, Chaya N Murali, Seema R Lalani, Robert B Hinton, Vidu Garg, Kim L McBride, Jennelle C Hodge, Stephanie M Ware
Journal: Circulation (2020)

Introduction: The genetic basis of congenital heart disease (CHD) is incompletely understood. Approximately 10-20% of infants with CHD have abnormal chromosome microarray (CMA) results, however, the spectrum of genomic and phenotypic abnormalities remains incompletely characterized. Methods: All study patients had abnormal CMA on clinical testing and abnormal cardiac findings on echocardiogram, as identified at 9 pediatric cardiac centers. Clinical genetic testing results, diagnoses, and echocardiogram reports for detailed cardiac phenotyping were collected. CMA results were denoted as abnormal for any reported findings that included copy number variants (CNVs) and/or regions of homozygosity. Cardiac classification was performed with minor modification to National Birth Defect Prevention Study methods. Recurrent CNVs were identified algorithmically. Functional enrichment analysis of genes predicted to be intolerant of loss-of-function (LOF) in CNVs and genes located in monogenic CNVs was performed using ToppGene. Results: The study included 1369 patients. Genetic syndromes highly associated with CHD such as Trisomy 21, Turner syndrome, and 22q11.2 deletion syndrome among others were identified in 401 patients and elucidated less recognized cardiac phenotypes in these groups. Analyzing genes known to be causative of CHD in the remaining patients (N=968) showed enrichment in CNVs &lt; 5 megabases (N=51; 7%). Common recurrent loci included duplications in 15q13.2-13.3 (N=16 patients) and 16p11.13 (N=12; 8 with left-sided cardiac lesion), and deletions in 15q11.2 (N=14; 6 with total anomalous pulmonary venous return) and 2q13 (N=10; 8 with conotruncal defect). Genes predicted to be intolerant of LOF (495 genes) or located in monogenic CNVs (137 genes) were enriched for neuronal processes. Conclusions: The consortium provides the largest data set of abnormal clinical CMA results in patients with detailed CHD phenotyping to our knowledge. The findings provide novel understanding of CHD phenotypes, a roadmap of recurrent loci, and pathways and candidate genes in CNV-associated CHD. The consortium’s data will lead to improved genetic understanding and clinical care of patients with CHD.
Abstract P099: Pulse Pressure And Long-term Post-kidney Transplant Systolic Hypertension Among Different Age
Authors: Ekamol Tantisattamo, Natnicha Leelaviwat, Natchaya Polpichai, Busara Songtanin, Sakditad Saowapa, Chawit Lopimpisuth, Possawat Vutthikraivit
Journal: Circulation (2021)

Introduction: Wide pulse pressure (PP) is common in elderly and associated with poor cardiovascular outcomes. Association between PP and long-term hypertension (HTN) in kidney transplant recipients (KTR) among different age groups is unclear. Hypothesis: We hypothesize that PP at early post-kidney transplant (KT) predicts different long-term post-KT HTN among different age groups. Methods: This is a retrospective cohort study of consecutive KT recipient in a single center. With age categorized into &lt; and ≥ 50 years old, association between PP at 4 and 12 weeks post-KT (when a baseline kidney allograft function is generally established) and post-KT systolic and diastolic HTN (SHTN and DHTN) at a 48-week post-KT defined by SBP and DBP ≥ 130 and 80 mmHg, respectively were examined by using multiple logistic regression. Results: Of all 105 KTR, 40 and 65 patients were &lt;50 and 65 years old, respectively. Mean age±SD was 54±12 years with a median follow-up of 47.71 weeks. At a 4-week post-KT, mean PP was 54±13 mmHg with a mean difference young - old ±SE of -7±3 (p 0.011; 95%CI -11.55, -1.53). Mean PP at a 12-week post-KT was 56±16 mmHg and a mean difference±SE of -8±3 mmHg (p 0.018; 95%CI -13.95, -1.35). At 48-week post-KT, 50% of the young had SHTN 66% of the old had SHTN; whereas, 58% and 38% of the corresponding groups had DHTN. Mean SBP of the young and old groups were 129±16 and 135±16 mmHg, respectively (mean difference -6±3; p 0.076; 95%CI -12.66, 0.63). Mean DBP of the corresponding groups were 80±12 and 75± 10 with a mean difference 5±2; p 0.036; 95%CI 0.332, 9.394). After adjusted for pre-KT BMI, type of KT, and induction immunosuppression, every 1 mmHg increase in PP at the 4-week post-KT was associated with 6% greater the odds of developing SHTN at 48-week post-KT among the older age group (OR 1.06; p 0.041, 95%CI 1.002, 1.117); whereas, the risk was 2% increase in younger group (OR 1.02; p 0.400; 95%CI 0.969, 1.082). The association between PP at the 12-week post-KT and SHTN at 48-week post-KT were in the same direction, but it was attenuated (5%) in the older and strengthen the younger (7%) (OR old 1.048; p 0.033; 95%CI 1.004, 1.095 and OR young 1.087; p 0.050; 95%CI 1.000, 1.1801). There were no association between PP at 4- and 12-week post-KT and DHTN at 48-week post-KT. Conclusion: Higher early post-KT PP was associated with increased risk of long-term post-KT SHTN, but not DHTN. However, the magnitude of the association was greater among the older KTR at early post-KT, but higher in the younger at later post-KT period. Mechanism of increased PP and outcomes such as post-KT HTN in KTR needs to be further elucidated.
Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial
Authors: Paolo F Caimi, Weiyun Ai, Juan Pablo Alderuccio, Kirit M Ardeshna, Mehdi Hamadani, Brian Hess, Brad S Kahl, John Radford, Melhem Solh, Anastasios Stathis, Pier Luigi Zinzani, Karin Havenith, Jay Feingold, Shui He, Yajuan Qin, David Ungar, Xiaoyan Zhang, Carmelo Carlo-Stella
Journal: The Lancet Oncology (2021)
Abstract 15265: Trace or Mild Valvular Heart Disease With Cardiac Remodeling, Damage, and Overload in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yumin Gao, Jonathan Rubin, Susan Cheng, Lena Mathews, Ajay Kirtane, Ron C Hoogeveen, Christie Ballantyne, Elizabeth Selvin, Martin B Leon, Josef Coresh, Scott Solomon, Kunihiro Matsushita, Amil Shah
Journal: Circulation (2020)

Background: Few studies have evaluated the link between trace or mild valvular disease with measures of cardiac structure, function, and damage in a general population of older adults. Hypothesis: Three left-sided valvular conditions (aortic stenosis, aortic regurgitation, and mitral regurgitation) will be independently associated with cardiac remodeling, damage, and overload. Methods: In 4,935 ARIC participants aged 66-99 years in 2011-13, we examined the cross-sectional associations of these three valvular conditions, only in trace or mild forms, with echocardiographic measures (left ventricular mass index, left ventricular end-diastolic diameter [LVDd], ejection fraction [EF], left atrial volume index [LAVI]) and biomarkers (high sensitivity troponin-T [hs-TnT] and natriuretic peptide) using multivariable linear regression. Aortic stenosis was categorized as none or mild by peak transaortic jet velocity and mean transaortic gradient. Regurgitation was categorized as none, trace, or mild based on color Doppler signal (see the Table footnote for detailed definitions). Results: The prevalence was 4.3% for mild aortic stenosis, 10.8% for aortic regurgitation (10.3% trace, 0.5% mild), and 44.0% for mitral regurgitation (39.9% trace, 4.1% mild). Each valvular condition showed independent and graded associations with all measures tested (Table), with the exception of aortic stenosis with LVDd and aortic regurgitation with hs-TnT. There was a positive association between aortic stenosis and EF. The associations remained consistent when all three valvular conditions were modeled simultaneously. Conclusions: Three prevalent valvular conditions were independently associated with cardiac remodeling, damage, and overload. Although this study cannot determine the directionality of these associations, our results suggest the involvement of mild valvular abnormalities in the pathophysiology of functional and structural alteration of the heart.
Cbl-b deficiency prevents functional but not phenotypic T cell anergy
Authors: Trang T.T. Nguyen, Zhi-En Wang, Lin Shen, Andrew Schroeder, Walter Eckalbar, Arthur Weiss
Journal: The Journal of Experimental Medicine (2021)

T cell anergy is an important peripheral tolerance mechanism. We studied how T cell anergy is established using an anergy model in which the Zap70 hypermorphic mutant W131A is coexpressed with the OTII TCR transgene (W131AOTII). Anergy was established in the periphery, not in the thymus. Contrary to enriched tolerance gene signatures and impaired TCR signaling in mature peripheral CD4 T cells, CD4SP thymocytes exhibited normal TCR signaling in W131AOTII mice. Importantly, the maintenance of T cell anergy in W131AOTII mice required antigen presentation via MHC-II. We investigated the functional importance of the inhibitory receptor PD-1 and the E3 ubiquitin ligases Cbl-b and Grail in this model. Deletion of each did not affect expression of phenotypic markers of anergic T cells or T reg numbers. However, deletion of Cbl-b, but not Grail or PD-1, in W131AOTII mice restored T cell responsiveness and signaling. Thus, Cbl-b plays an essential role in the establishment and/or maintenance of unresponsiveness in T cell anergy.
Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart
Authors: Ge Guan, Da Huo, Yanzhao Li, Xiaolin Zhao, Yinghao Li, Zhongliang Qin, Dayu Sun, Guanyuan Yang, Mingcan Yang, Ju Tan, Wen Zeng, Chuhong Zhu
Journal: Bioactive Materials (2021)

Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI. • SpGel provides a novel platform for hiPSC culture and differentiation. • SpGel provides a proper microenvironment for cell implants against oxidant stress damage in vitro . • iEC/iCM-laden SpGel improves cell graft retention, promotes cardiac function recovery and inhibits cardiac fibrosis. • SpGel could also be used as a biocompatible bioink for 3D printing cardiac organoids in the future.
Association between up‐titration of medical therapy and total hospitalizations and mortality in patients with recent worsening heart failure across the ejection fraction spectrum
Authors: Vasiliki Bistola, Panagiotis Simitsis, John Parissis, Wouter Ouwerkerk, Dirk J. van Veldhuisen, John G. Cleland, Stefan D. Anker, Nilesh J. Samani, Marco Metra, Faiez Zannad, Eftihia Polyzogopoulou, Kalliopi Keramida, Dimitrios Farmakis, Adriaan A. Voors, Gerasimos Filippatos
Journal: European Journal of Heart Failure (2021)
Abstract 12276: A Fetal Risk Stratification Protocol for Postnatal Development of Coarctation of the Aorta: A Quality Improvement Initiative
Authors: Shiraz A Maskatia, David M Kwiatkowski, Shazia Bhombal, Alexis Davis, Doff B McElhinney, Theresa Tacy, Amy Quirin, Rajesh Punn
Journal: Circulation (2019)

Introduction: Although fetal presentation of coarctation of the aorta (CoA) varies in severity, postnatal management is typically uniform and results in unnecessarily aggressive postnatal managemen...
Abstract 15634: High-fat Diet Consumption Accelerates Cardiometabolic Impairment via Deteriorating Mitochondrial Function in Non-obese Spontaneously Type 2 Diabetic Rats
Authors: Wanpitak Pongkan, KEWARIN JINAWONG, Siriporn Chattipakorn, Nipon CHATTIPAKORN
Journal: Circulation (2020)

Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disease which is related to genetic, environmental, and lifestyle factors. In genetically-induced T2DM rats, normal diet could induce spontaneous diabetes, and induce left ventricular (LV) dysfunction over time. However, the effect of high-fat diet (HFD) in these genetically-induced T2DM rats on the cardiometabolic changes, including LV function and cardiac mitochondrial function has rarely been investigated. Hypothesis: High-fat diet (HFD) consumption accelerates the development of T2DM and LV dysfunction by inducing mitochondrial dysfunction in genetically-induced non-obese T2DM-Spontaneously Diabetic Torii (SDT) rats. Methods: Male SDT rats (n=18/group) were divided into 2 groups to receive either normal diet (ND, 19.77% fat) or HFD (57.60% fat) for 4, 8 or 12 weeks. At each time course, cardiac function determined by echocardiography and the pressure-volume loop determined by invasive intracardiac catheterization were assessed. The heart was removed to study cardiac mitochondrial function at each time-course. Results: The body weight, food intake, and visceral fat were not different between ND and HFD rats at any times. Increased blood glucose was seen earlier at week 4 in HFD rats, but later at week 12 in ND rats. The development of LV contractile dysfunction and decreased stroke volume was observed earlier at week 8 in HFD rats, compared to ND rats and HFD rats at the baseline. Increased cardiac mitochondrial ROS production and decreased mitochondrial membrane potential (i.e. mitochondrial depolarization) was observed earlier at week 8 in HFD rats, compared to ND rats (Fig). Conclusions: High-fat diet accelerates cardiometabolic impairments via impaired cardiac mitochondrial function in genetically-induced non-obese T2DM rats.
Abstract 16654: Covid - 19 - Acute Myocardial Infarction and Heart Failure Mortality Trends in a Non-epicenter Region
Authors: Mahathi Indaram, Mark Doyle, Sarah Wiswall, Indu G Poornima
Journal: Circulation (2020)

Introduction: As the novel coronavirus gained acceleration, there are several reports of a decreasing number of hospital admissions for acute myocardial infarctions (AMI) worldwide. It is unclear if this is due to an actual decrease in their incidence or due to patients avoiding hospital visits during the pandemic. We examined the trends in admissions for AMI, acute decompensated heart failure (HF) and their associated mortality in an integrated health system (7 hospitals) in Pittsburgh (Pennsylvania), a non-epicenter region. Hypothesis: If patients are presenting late due to avoiding hospitals, AMI and HF would be associated with increased mortality rates. Methods: We collected data on the total number of admissions and deaths related to AMI (ST and non-ST elevation), HF using ICD-10 codes, during the period of January-April 2020. We compared this with data from the same period in 2018, 2019. Mortality rate was calculated as deaths per 100 admissions. Results: There were 505 AMI admissions in January-April 2020 and 37 died compared to 23 deaths amongst 645 admissions in the same period of 2018 and 2019 (averaged). Similarly, there were 1030 HF admissions in January-April 2020 and 46 died in comparison to 39 deaths amongst 1280 admissions in 2018 and 2019 (averaged). The absolute number of AMI and HF admissions was lower in 2020 (p&lt;0.05, p&lt;0.01). There was no difference in absolute number of deaths attributed to HF or AMI between 2020 and the preceding years (p=0.3). However, mortality rate was higher for HF in 2020 compared to prior 2 years. Conclusions: In this non-epicenter region, there was a significant decrease in admissions for AMI and HF in 2020 compared to 2018-2019 while the absolute number of deaths were similar. Similar mortality rates for AMI across the years suggests that patients were presenting appropriately and that the true incidence was likely low. However, higher mortality rate with HF may suggest a delayed presentation albeit without accounting for confounders.
Abstract 17389: Antiplatelets Agents Decreases 30-days Mortality in Myocardial Injury After Noncardiac Surgery
Authors: Hanumantha R Jogu, Parag A Chevli, Geeth Sandeep Nadella, Tareq S Islam, Abhishek Dutta, Padageshwar Sunkara, Harsh Barot, Luqman-Arafath Thazhatuveetil-Kunhahamed, Chi-Cheng Huang, Daniel Beekman
Journal: Circulation (2020)

Introduction: Despite being frequent and associated with poor outcomes, no guidelines exist addressing the management of myocardial injury after noncardiac surgery (MINS). We hypothesized that Antiplatelets (ATP) agents reduce 30-days mortality in MINS patients. Methods: We used data from the Wake-Up T2MI registry, which is a single-center, retrospective cohort of hospitalized adults with elevated troponin (cTn) I (&gt; 99 th percentile reference upper limit is &gt;0.04 ng/dL) without acute myocardial infarction in a 2-year period. Patients with the cardiac procedures were excluded and cTn obtained during hospitalization. MINS is defined as abnormally elevated cTn levels during or within 30 days after surgery. Kaplan-Meier curve and multivariate-adjusted Cox-proportional hazard models were performed to assess all-cause mortality at 30-days, 90-days, and 1-year among patients with and without ATPs upon discharge. Results: A total of 457 patients were included in the final analysis. There was no difference in sex, race, BMI, and peak cTn, except age among patients stratified by ATP on discharge. Prevalence of mortality was significantly lower at 30-days (2.6% vs 7%, p = 0.028), it was not significant at 90-days (9.6% vs. 11.8%, p = 0.440) and at 1-year (21.4% vs. 24.6%, p=0.421) in patients who were discharged on ATPs compared to non-ATPs. Survival benefit was significant at 30-days (log-rank p = 0.022), non-significant at 90-days (log-rank p = 0.292) and at 1-year (log-rank p = 180) in ATPs group compared to non-ATPs. In a multivariate-adjusted (adjusted for age, sex, race, and peak cTn) model, patients who were discharged on ATPs had a HR of 0.31 (0.120 - 0.799; p = 0.015) at 30 days, HR of 0.64 (0.363 - 1.136; p = 0.128) at 90 days (Figure 1), and HR of 0.69 (0.472 - 1.025; p = 0.066) at 1 year. Conclusions: In conclusion, antiplatelet agents on discharge were associated with decreased 30-days mortality in MINS patients. Further studies are needed to validate our results.
Abstract 15564: What Pre-pregnancy, Pregnancy, and Inter-pregnancy Cardiometabolic Factors Contribute to Increased Risk of Recurrent Preeclampsia?: A Longitudinal Analysis in the Boston Birth Cohort
Authors: Michelle Ogunwle, Xiaobin Wang, Wendy L Bennett
Journal: Circulation (2020)

Introduction: Women with recurrent preeclampsia represent a group at uniquely high risk for maternal and perinatal morbidity, as well as future cardiovascular complications. The aim of this study is to examine the association of cardiometabolic risk factors with recurrent preeclampsia in the subsequent pregnancy. Methods: The Boston Birth Cohort is a racially/ethnically diverse birth cohort with over 8500 women. We identified 618 women with repeat pregnancies. Of those, 78 women had preeclampsia in the index pregnancy, and of those, 33 had recurrent preeclampsia in the subsequent pregnancy. We used log-binomial regression to examine the association between pre-pregnancy, pregnancy, and inter-pregnancy cardiometabolic risk factors (e.g., obesity, hypertension, diabetes mellitus, preterm birth, low birth weight, and gestational diabetes mellitus) and recurrent risk of preeclampsia. Results: Among the 78 women who had preeclampsia in their index pregnancy, the recurrence rate of preeclampsia was 42.3%. Several maternal risk factors were associated with this recurrent risk. Compared to women with pre-(index) pregnancy normal weight, the risk of recurrent preeclampsia was 3 times higher for women with pre-(index) pregnancy overweight (RR 3.0 [95% CI: 1.4 to 6.6]) or obesity (RR 3.1 [95% CI: 1.5 to 6.7). Compared to women without new inter-pregnancy chronic hypertension, women with new inter-pregnancy chronic hypertension had a 2-fold higher risk of recurrent preeclampsia (RR 2.4 [95% CI: 1.5 to 3.9]). Conclusions: Pre-(index) pregnancy obesity and new inter-pregnancy chronic hypertension was highly associated with recurrent preeclampsia in the subsequent pregnancy. Clinical and public health programs focused on reducing preconception obesity and reducing risk of hypertension in both the pre-pregnancy and inter-pregnancy periods may help reduce recurrent preeclampsia, which, in turn may help prevent or reduce subsequent cardiovascular disease.