tbuckley/cabot-search huggingface dataset:
Abstract 13066: Circulating Cellular Clusters: A Proposed Mechanism and Novel Biomarker for Immunothrombosis and Clinical Outcomes in Patients With COVID-19
Authors: Ander Dorken Gallastegi, He Li, Leon Naar, Elizabeth M Van Cott, Rachel P Rosovsky, David J Gregory, Damodaran Annamalai, Haytham M Kaafarani, George Velmahos, George E Karniadakis, Jarone Lee, Galit H Frydman
Journal: Circulation (2021)

Introduction: Circulating Cellular Clusters (CCCs) have been studied in the context of cancer; however, CCCs in other inflammatory conditions, such as COVID-19, have not been explored. Hypothesis: CCC phenotypes play a role in immunothrombosis and in the development of adverse events. Methods: Blood samples were collected from patients with a positive SARS-CoV2 PCR treated at the Massachusetts General Hospital. Imaging flow cytometry was used to characterize CCCs, including: platelet-leukocyte aggregates (PLAs), leukocyte clusters (LCs) and platelet-erythrocyte aggregates (PEAs) (Fig1A). CCC phenotypes were compared with controls and were correlated with clinical outcomes. CCCs identified to be significant were used to guide a computational model investigating the mechanism of CCC formation and their behavior in circulation (Fig1C). Results: Forty-six COVID-19 and 12 control samples were analyzed. Statistically significant positive correlations were identified between CCCs and clinical outcomes in patients with COVID-19 (Fig1B). Using these data as inputs, computational simulations illustrated that CCCs may form in the circulation and be recruited by existing thrombi and sites of inflammation, or may detach from thrombogenic sites (Fig1D). Conclusions: CCCs are correlated with the development of significant clinical outcomes and cluster phenotypes appear to be associated with specific outcomes. CCCs may form de novo in the circulation or via the detachment from a thrombus. These CCCs may subsequently attach to a second thrombus downstream or serve as their own nidus for thrombus development, resulting in vessel lumen occlusion. Computational modeling serves as a powerful tool for the exploration of the pathophysiological mechanism by which CCCs contribute to thrombus formation. These findings may serve as novel biomarkers and aid in the identification of new drug targets for immunothrombotic complications in severe inflammatory conditions.
Abstract MP250: Reduction In Endothelial Aryl Hydrocarbon Receptor Nuclear Translocator (arnt) Mediates Vascular Dysfunction In Mice With Type 2 Diabetes Mellitus
Authors: Tu Nguyen, Kaichao Pan, Maura Knapp, Mei Zheng, Nikola Sladojevic, Lizhuo Ai, Albert Sitikov, Frank Gonzalez, james K Liao, Rongxue Wu
Journal: Circulation Research (2021)

Background: Endothelial dysfunction, especially at the microvasculature level, is one of the most deleterious events in diabetes. ARNT is a transcription factor that functions as a master regulator of glucose homeostasis, but its role in diabetic vascular complications is poorly understood. Results and method: We found a reduction in ARNT expression in microvascular endothelial cells (MVECs) derived from type 2 diabetic mice (db/db). Thus, we generated an inducible, EC-specific ARNT-knockout mutation ( Arnt ΔEC, ERT2) to address the hypothesis that aberrations in ARNT expression might contribute to the vascular deficiencies associated with diabetes. We show here that loss of ARNT in the endothelium mimics diabetic phenotypes, such as impairs blood flow recovery after hindlimb ischemia, delays wound healing, and exacerbates infiltration of pro-inflammatory neutrophils after myocardial infarction. Interestedly, the degree of these impairments in the KO mice was more remarkable in diabetic animals induced with high-fat chow. In addition, the siRNA-mediated knockdown of ARNT activity reduced tube formation and cell viability measurements in HUVECs cultured under high-glucose conditions. The Arnt ΔEC, ERT2 mutation also reduced measures of cell viability while increasing the production of reactive oxygen species (ROS) in MVECs isolated from mouse skeletal muscle, and the viability of Arnt ΔEC, ERT2 MVECs under high-glucose concentrations increased when the cells were treated with a ROS inhibitor. Conclusion: Collectively, these observations suggest that declines in endothelial ARNT expression contribute to the suppressed angiogenic phenotype in diabetic mice and that the cytoprotective effect of ARNT expression in ECs is at least partially mediated by declines in ROS production. Endothelial ARNT might be a critical mediator of endothelial function and could serve as a therapeutic target for diabetic complications.
Abstract 12382: Evaluation of Tissue Engineered Human Acellular Vessels as a Blalock-Taussig-Thomas Shunt in a Juvenile Primate Model
Authors: Kevin M Nash, Brian A Boe, Sergio A Carrillo, Andrew Harrison, Ryuma Iwaki, John Kelly, Robert D Kirkton, Ramkumar Krishnamurthy, Laura E Niklason, Yuichi Matsuzaki, Heather L Prichard, Kejal Shah, Toshiharu Shinoka, christopher K breuer, Jeffrey H Lawson
Journal: Circulation (2021)

Cyanotic congenital heart disease (CCHD) due to one or more structural abnormalities causes insufficient blood oxygenation. Approximately 2 out of every 1000 infants are born with CCHD and palliative treatment for many patients involves shunting blood from the systemic to the pulmonary circuits, often through a modified Blalock-Taussig-Thomas shunt (BTTs). Synthetic vascular grafts typically used for BTTs have associated risks for intimal hyperplasia, thrombosis, and infection. Humacyte, Inc. has developed a 6mm diameter tissue-engineered blood vessel, the Human Acellular Vessel (HAV), currently being studied in adults suffering from vascular trauma, peripheral arterial disease, and renal failure requiring hemodialysis. In addition to restoring blood flow and providing arteriovenous access in these patients, the HAV has demonstrated the capacity for host cellular remodeling that transformed it into a native-like living tissue. Here the HAV production platform was modified to generate small diameter (3.5mm) vessels for preclinical evaluation. BTTs were placed from the right subclavian artery to the pulmonary artery in juvenile rhesus macaques. Post-operative imaging from 1 week to 6 months using angiography and MRI was used to confirm HAV patency, structure, and quantify blood flow. At explantation, the HAV and surrounding tissues were collected and processed for histological analyses. Results confirmed the feasibility of using the HAV BTTs, but also showed that all macaques had some immunological reactivity to the HAV human extracellular matrix in this xenogeneic animal model. Nonetheless, the HAV BTTs remained patent and performed well for up to six months in animals that had only mild host reactivity. HAV repopulation by host cells expressing smooth muscle and endothelial markers as well as the formation of neoadventitial tissue was also observed. These findings may support use of the HAV as a BTTs in CCHD and potentially other pediatric indications.
Abstract 13263: Sex Differences in Outcomes After Cardiac Surgery: Insights From a National Database
Authors: Lauren Dixon, Arnaldo Dimagli, Ettorino Di Tommaso, Shubhra Sinha, Manraj Sandhu, gianni angelini, Umberto Benedetto
Journal: Circulation (2021)

Introduction: Female sex is considered an independent risk factor for mortality and morbidity following cardiac surgery. This study is the first to review the UK national database to compare outcomes following surgical revascularisation and valvular cardiac procedures between females and males. Hypothesis: Females have worse outcomes following cardiac surgery than males. Methods: Using data from National Adult Cardiac Surgery Audit (NACSA), we identified all elective and urgent, isolated coronary artery by-pass grafting (CABG), aortic valve replacement (AVR) and mitral valve replacement/repair (MVR) procedures from 2010-2018. We compared baseline data, operative data and outcomes of mortality, stroke, renal failure, deep sternal wound infection, return to theatre for bleeding and length of hospital stay. Multivariable logistical/linear regression models were used to assess relationships between sex and our outcomes, adjusting for baseline characteristics. Results: Females, compared to males, had a greater odds of experiencing 30-day mortality in each procedure (CABG OR 1.76, CI 1.47-2.09, p&lt;0.001; AVR OR 1.59, CI 1.27-1.99, p&lt;0.001; MVR OR 1.37, CI 1.09-1.71, p=0.006). After CABG, females also experienced increased need for post-operative dialysis (OR 1.31, CI 1.12-1.52, p&lt;0.001), deep sternal wound infections (OR 1.43, CI 1.11-1.83, p=0.005) and length of stay (Beta 1.2, CI 1.0-1.4, p&lt;0.001) compared to males. Female sex was protective against returning to theatre for post-operative bleeding following CABG (OR 0.76, CI 0.65-0.87, p&lt;0.001) and AVR (OR 0.72, CI 0.61-0.84, p&lt;0.001). Conclusions: Despite advances in cardiac surgery, females in the UK have an increased risk of short-term mortality after cardiac surgery compared to males. This highlights the need to focus on the understanding of the causes behind these disparities and therefore implementation of strategies to improve this.
Reply to: “Focus on the decisions to forego life-sustaining therapies during ICU stay of patients with cirrhosis and COVID-19: A case control study from the prospective COVID-ICU database”
Authors: François Depret, Samir Bouam, Michaël Schwarzinger, Vincent Mallet, François Depret, Samir Bouam, Michaël Schwarzinger, Hélène Fontaine, Marion Corouge, Anaïs Vallet Pichard, Clémence Hollande, Philippe Sogni, Stanislas Pol, Vincent Mallet
Journal: Journal of Hepatology (2021)
Abstract 9816: Clinical and Pathophysiological Relevance of Follistatin-Like 1 in Calcific Aortic Valve Disease
Authors: Zhongli Chen, Qianru Zhang, Qing Zha, Chenxi Yu, yan liu, Ke Yang
Journal: Circulation (2021)

Introduction: CAVD is a progressive disease resulting in severe aortic valve stenosis. Recent studies unveiled protective effects of FSTL1 in various cardiovascular disorders. But its role in CAVD is uncertain. This study aims to evaluate the clinical and pathophysiological relevance of FSTL1 in CAVD. Methods: FSTL1 level was measured in blood samples fromCAVD (n = 343) and non-CAVD (n = 318) patients. The diagnosis of CAVD was based on the echocardiography report. ApoE-/- mice and primary aortic valve interstitial cells (VICs) were used as animal and cell models respectively for mechanistic studies. Results: Compared with non-CAVD group, CAVD patients exhibits lower circulating FSTL1 concentrations [Median (IQR) ng/mL: 0.91 (0.52-1.50) versus 0.78 (0.34-1.25), p=0.002]. Multivariate logistic regression indicates that circulating FSTL1 level is independently associated with CAVD (OR: 0.831, 95% CI: 0.755-0.915, p&lt;0.001) after full adjustment. Moreover, there is a non-linear relationship with threshold effect between FSTL1 level and CAVD: Below the turning point (FSTL1= 1.2ng/mL) the predicted probability of CAVD decreases significantly as FSTL1 level increases, but above 1.2ng/mL, the downtrend levels off. In ApoE-/- mice, overexpression of FSTL1 significantly reduces calcified nodule formation and structural remodeling of aortic valves. Finally, rhFSLT1 significantly alleviates calcium deposits, alkaline phosphatase activity, suppresses expression of osteogenic markers (BMP2, RUNX2, and MSX2) and inhibits phosphorylation of ERK1/2 in VICs in the osteogenic medium Conclusion: FSTL1 emerges as an important marker exhibiting inverse clinical association with CAVD and it alleviates the mineralization of murine valve and VICs. Further evaluation and manipulation of FSTL1 might provide a novel potential therapeutic opportunity for CAVD.
Abstract 10882: Validation of a Continuous Flow Pressure Gradient for Coarctation Severity Assessment
Authors: Arash Ghorbannia, Chalani D Ellepola, Ronald K Woods, John F LaDisa
Journal: Circulation (2021)

Introduction: Coarctation of the aorta (CoA) severity is assessed via trans-CoA blood pressure gradient (BPG) estimated using simplified Bernoulli equation (SBE) with indices from noninvasive Doppler echocardiography (echo). However, simplifications of the SBE and inconsistent readings through a suboptimal insonation window limit diagnostic accuracy (DA). In a rabbit model mimicking human CoA (Fig. 1A), catheter vs. Doppler comparison of BPG revealed diastolic continuous-flow pressure gradient (CFPG) was independently associated with severity. We therefore hypothesized the unique properties of CFPG would improve DA in humans. Methods: SBE and CFPG were quantified using color flow Doppler in humans and rabbits with discrete non-recurrent CoA before repair (Fig. 1B). Quantifications used peak velocity proximal to (V p ) and at the CoA (V pk ), early diastolic velocity (V d ), doppler velocity index (DVI), and normalized diastolic pressure half-time (dPHT; see Fig. 1B and C for definitions). Results were compared with measured BPG in rabbits (peak-to-peak catheter BPG) and humans (upper-lower extremity BPG). There was a total of 18 human and 26 rabbit cases; significance was defined a priori as a BPG of ≥20 mmHg. A CFPG ≥4 mmHg threshold was identified by maximizing sensitivity plus specificity in receiver operative curves (ROC). Results: Accuracy measures (Fig. 1D) revealed the superior performance of CFPG vs. SBE. Although reports suggest &lt;60% of measured BPG can be explained with SBE, CFPG yielded a specificity of 78% in humans. Similar improvements were observed in rabbits. Results confirm the potential DA of CFPG in echo-based CoA assessment. Fig. 1- (A) MRI confirming morphological similarities between rabbit and human CoA, (B) Spectral Doppler images show diastolic continuous flow, (C) indices derived from the generalized Bernoulli equation assuming exponential diastolic pressure loss, (D) diagnostic performance for CFPG vs. conventional SBE.
A Bicistronic Vector Expressing CD16 and a Membrane Bound IL-15 Construct in iPSC Derived NK Cells Increased Cytotoxicity and Persistence
Authors: Alexander G Allen, Rithu Pattali, Kaitlyn M Izzo, Jared A Getgano, Kevin M Wasko, Laura C Blaha, John A Zuris, Kate Zhang, Mark S Shearman, Kai-Hsin Chang
Journal: Blood (2021)
A Novel NGS-Based Simultaneous Detection of DNA and RNA Biomarkers Using Total Nucleic Acid (TNA) for Acute Lymphocytic Leukemia (ALL)
Authors: Archana Ramesh, Samuel Koo, Soo Jin Kang, Abhisek Ghosal, Francys Alarcon, Tibor Gyuris, Segun C Jung, Christophe Magnan, Hyunjun Nam, Brad B Thomas, Rudy Fabunan, Paris Petersen, Fernando Lopez-Diaz, Ryan Bender, Sally Agersborg, Fei Ye, Vincent Funari
Journal: Blood (2021)
Abstract 12510: Monitoring of Chemotherapy-Induced Vascular Toxicity in Pediatric, Adolescent, and Young Adult Lymphomas Using PET/CT Imaging
Authors: Kyra Deep, Dariya Hardisky, Nguyen K Tram, Ting-heng Chou, Laila Ettefagh, Adam J Bobbey, Anthony N Audino, Mitchel R Stacy
Journal: Circulation (2021)

Introduction: Lymphoma treatment with chemotherapy, alone or in combination with radiation therapy, can have off-target effects that lead to vascular toxicity, which has recently gained attention in the field of cardio-oncology. Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 ( 18 F)-fluorodeoxyglucose (FDG) is standard of care for monitoring lymphoma treatment responses and is a widely accepted tool for assessing vascular inflammation. We hypothesized that 18 F-FDG PET/CT imaging could detect and quantify chemotherapy-induced increases in vascular inflammation following the first cycle of lymphoma treatment in pediatric, adolescent, and young adult (AYA) patients. Methods: Whole-body 18 F-FDG PET/CT images were retrospectively acquired at initial staging of disease and first treatment follow-up for pediatric and AYA lymphoma patients (n=33). Regions of interest were manually drawn using each axial slice of fused PET/CT images for the femoral and popliteal arteries/veins to quantify serial changes in vascular uptake of 18 F-FDG. The changes in the average maximum standard uptake value (SUV max ) for the femoral-popliteal vessels were calculated. Results and Conclusions: The patient population consisted of Non-Hodgkin (55%) and Hodgkin (45%) lymphoma patients with a mean age of 13 years (SD=4.7). 18 F-FDG PET/CT imaging detected ( Fig. 1A ) and quantified a significant increase in the mean SUV max from baseline (0.94±0.03) to first treatment follow-up (1.06±0.02) for the femoral and popliteal arteries/veins ( Fig. 1B ). Standard of care 18 F-FDG PET/CT imaging can non-invasively quantify chemotherapy-induced vascular inflammation in young cancer patients in response to the first cycle of treatment, thus representing an approach for evaluating vascular toxicity and creating novel opportunities for personalized medicine focused on reducing cardiovascular side effects of chemotherapy.
Abstract 13773: Hyperuricemia is Associated With Increased Mortality in Heart Failure Patients With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Chol Techorueangwiwat, Panupong Hansrivijit, Chanavuth Kanitsoraphan
Journal: Circulation (2021)

Introduction: Recent data has emerged suggesting prognostic value of serum uric acid in heart failure with preserved ejection fraction (HFpEF), however, there are conflicting data. This is the first meta-analysis to assess the associations of serum uric acid and clinical outcomes in patients with HFpEF. Methods: Comprehensive literature search was conducted from MEDLINE and EMBASE through November 2020. We included cohort studies and post-hoc analyses of randomized controlled trials that investigated the associations between serum uric acid and clinical outcomes in patients with HFpEF. Data was combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate hazard ratios and 95% confidence intervals (CI). Only studies using multivariable analyses were included. Results: Six studies were included in this meta-analysis, including 12,976 patients with HFpEF. The studies dated from 2015 to 2020. We found that in patients with HFpEF, hyperuricemia was associated with an increased risk of overall mortality (pooled adjusted HR 1.236, 95% CI 1.002-1.525, p=0.048, I 2 =84.6%) and cardiac mortality (pooled adjusted HR 1.589, 95% CI 1.273-1.984, p&lt;0.05, I 2 = 0%) after multivariable adjustments. The results were significant on sensitivity analysis. Conclusions: Our meta-analysis suggested that hyperuricemia was associated with increased mortality in patients with HFpEF. Further studies are warranted to elucidate mechanism underlying this association and possible therapeutic interventions for HFpEF patients with hyperuricemia.
Impacts of Total Body Irradiation in Allogeneic Umbilical Cord Blood Hematopoietic Stem Cell Transplantation
Authors: Jeffrey J. Pu, Kristin N. Berger, Hao Wang, Wei Fu, Elizabeth L Miller, Larisa Broglie, Heiko Konig, Frederick Goldman, Julie-An Talano, Sherif S. Farag, Melanie Comito
Journal: Blood (2021)
Abstract 12294: Cardiothoracic Surgery Research Articles Supported by National Institutes of Health Grant Funding Exhibit Enhanced Scholarly Impact
Authors: Hanjay Wang, Simar Bajaj, Kiah M Williams, Y Woo, Jack Boyd
Journal: Circulation (2021)

Introduction: National Institutes of Health (NIH) grants are an essential funding source for cardiothoracic (CT) surgeon-scientists. The association between NIH funding and an article’s research impact, however, has not been explored. We hypothesized that CT surgery research articles supported by NIH funding exhibit enhanced scholarly impact. Methods: Research records and NIH funding history for all CT surgery faculty (n=992) at accredited United States CT surgery training institutions in 2018 were obtained using Scopus and Grantome, respectively. Using the NIH iCite database, all articles published by these surgeons were classified as either basic science research (BSR, iCite animal or molecular/cellular score &gt;0) or clinical research (CR, iCite animal and molecular/cellular score = 0). The relative citation ratio (RCR), an NIH-validated field-normalized metric of scholarly impact, was calculated for each article, where RCR 1.00 indicates equal impact as other NIH-funded articles in the same field, and RCR 2.00 indicates twice the impact. Data are presented as median [interquartile range] and analyzed using the Mann-Whitney test. Results: A total of 37,402 unique articles were identified, including 9,469 supported by NIH funding and 27,933 without NIH funding. CT surgery research articles with NIH funding exhibit a significantly greater median RCR than those without NIH funding (1.08 [0.53-2.19] vs 0.75 [0.28-1.72], p&lt;0.0001, Figure 1A). Among BSR articles, NIH-funded papers have a significantly greater median RCR (0.93 [0.47-1.88] vs 0.62 [0.26-1.33], p&lt;0.0001, Figure 1B). Similarly, among CR articles, NIH-funded papers also exhibit a significantly greater median RCR (1.34 [0.66-2.60] vs 0.79 [0.28-1.80], p&lt;0.0001, Figure 1C). Conclusions: At single-article resolution, CT surgery research publications supported by NIH grant funding exhibit enhanced scholarly impact and compare favorably in median RCR versus other NIH-funded biomedical research.
Abstract 11684: Meta-Analysis of Contemporary Hybrid Convergent Ablation Outcomes
Authors: suvash shrestha, Kristen Plasseraud, Kevin Makati, Nitesh Sood, David DeLurgio, Yisachar Greenberg, Felix Yang
Journal: Circulation (2021)

Introduction: Recent randomized clinical trial data demonstrated safety and effectiveness of hybrid epicardial-endocardial (convergent) ablation for persistent and longstanding persistent atrial fibrillation (PersAF/LSPAF). The objective of this study was to perform a systematic review and meta-analysis focused on contemporary hybrid convergent procedure outcomes. Methods: Predefined search terms were used in PubMed/EMBASE in May 2021. Abstracts and full text in English were reviewed for peer-reviewed, primary clinical studies of hybrid convergent procedures in PersAF/LSPAF using the current unipolar device for epicardial ablation and lesion set focused on left atrial posterior wall and pulmonary vein isolation. Meta-analysis was performed with using a random effects model with a restricted maximum likelihood estimator and forest plots. Heterogeneity was tested using Cochran’s Q-test. Results: The updated search yielded 155 unique results. Two articles from manual searching were added. Twenty-seven full text articles were assessed for inclusion. Six articles that included 551 patients were identified for qualitative and quantitative analysis. Ninety-six percent of patients had persistent or long-standing persistent AF. Mean/median pre-operative AF duration ranged from 2 to 5 years. The 30-day major adverse event rate was 6% (95% CI 3-8%, n=551, 6 studies). No atrioesophageal fistulas or periprocedural mortality events were reported. Freedom from atrial arrhythmia at one year or later was 69% (95% CI 61-78%; n=523, 6 studies) regardless of anti-arrhythmic drugs (AADs) and 50% (95% CI 42-58%; n=343; 3 studies) off AADs. Heterogeneity was insignificant for effectiveness off AADs (p=0.14) and safety (p=0.23) Conclusions: This meta-analysis found favorable effectiveness of contemporary hybrid convergent procedures at one year, even off AADs, and a reasonable safety profile in mostly persistent or long-standing persistent AF.
Reply: Methionine supplementation: potential for improving alveolar macrophage function through reverse cholesterol transport?
Authors: Alice Hadchouel, Christophe Delacourt
Journal: European Respiratory Journal (2021)

<b>This correspondence discusses the pathophysiological mechanism proposed by O9Callaghan and co-workers to explain PAP related to mutations in <i>MARS1</i> and the efficacy of methionine supplementation</b>https://bit.ly/3rrzOm8