tbuckley/cabot-search huggingface dataset:
Abstract 14625: Clinical Outcomes of Autologous Stem Cell Patch Implantation for Heart Failure Patients With Non-ischemic Dilated Cardiomyopathy
Authors: Keitaro Domae, Shigeru Miyagawa, Koichi Toda, Daisuke Yoshioka, Satoshi Kainuma, Takuji Kawamura, Ai Kawamura, Noriyuki Kashiyama, Hiroko Iseoka, Emiko Ito, Akima Harada, Maki Takeda, Tomomi Yamada, Yoshiki Sawa
Journal: Circulation (2020)

Background: Although pre-clinical researches proved that cardiac regenerative therapy with autologous skeletal stem cell (SSC) patch implantation healed non-ischemic dilated cardiomyopathy (NIDCM) animal model by anti-fibrotic effect and preservation of cytoskeletal proteins in distressed myocytes, its clinical effectiveness for NIDCM has not been clearly elucidated. We hypotheses SSC patch implantation for NIDCM is feasible, safe and have therapeutic efficacy and we aim to identify the predictor of responder of this treatment in NIDCM patients Methods: Twenty-four NIDCM patients with ejection fraction less than 35% underwent SSC patch transplantation (average: 3.9±0.4х10 8 cells) via the left thoracotomy without concomitant procedures. We identified thirteen responders (Group RP) and eleven non-responders (Group NR) using the combined indicator of major cardiac adverse event and incidence of heart failure event. Results: In Group RP, symptoms, exercise capacity and cardiac performance were improved postoperatively (NYHA functional class; 2.5±0.5 to 1.9±0.3, p&lt;0.05, six-minute walk test; 471(370-541) to 525(425-555)m, p&lt;0.05, LVSWI; 31.1(22.7-35.5) to 32.8(28-38.5)g/m 2 /beat, p=0.21). However, such improvement was not observed in Group NR. Overall survival rate was 90.9±8.7% at 5 years, which was superior to estimated survival rate using Seattle heart failure model (SHFM) of 70.9±5.4% in Group RP. However overall and estimated survival rate using SHFM was similar in Group NR (47.7±21.6% and 56.3±8.1%). Preoperative histological analysis demonstrated significant low level of hypertrophy of myocyte and interstitial fibrosis and high expression of histone methylation-related molecules in Group RP compared with Group NR. Multivariate regression model with BNP, PCWP and expression of histone H3 lysine 4 trimethylation (H3K4me3) strongly predicted the responder (BNP: OR 0.96, PCWP: OR, 0.58, H3K4me3; OR, 1.35, AUC in ROC, 0.96, p&lt;0.001). Conclusions: This clinical trial demonstrated that SSC patch implantation might promise functional recovery and good clinical outcome in selected NIDCM patients with preoperatively preserved diastolic function and ability of protein synthesis in myocytes.
Abstract 17170: Does Cardiopulmonary Bypass Provide Adequate End-Organ Perfusion?
Authors: Marijan Koprivanac, Ahmed Aly, Jonathan Magruder, Andrew Acker, Joshua Grim, michael acker, Marisa Cevasko, Nimesh Desai
Journal: Circulation (2020)

Introduction: Our clinical experience in cardiac surgery teaches us that a subset of patients show signs of unexplained end-organ hypoperfusion after an otherwise unremarkable procedure. The objective of this study is to comprehensively examine cardiopulmonary bypass (CPB) management parameters and end-organ perfusion. Hypothesis: Despite advancements in CPB management, CPB does not provide adequate end-organ perfusion. Methods: Retrospective analysis was performed using data from 1462 cardiac operations performed from 2/2019 to 4/2020, excluding circulatory arrest and non-CPB cases. CPB management parameters included cardiac index (CI), mean arterial pressure (MAP), vasopressor-phenylephrine use, lines and bladder temperatures, hemoglobin (Hgb), indexed oxygen delivery (iDO 2 ), and intravenous fluid infusion. End-organ perfusion markers included lactate levels, mixed venous oxygen saturation (SvO 2 ), oxygen consumption (VO 2 ), and arterial pH. Results were expressed as means with first standard deviation. Results: During CPB, CI, MAP, iDO 2 and Hgb were 2.2 ± 0.4 l/min/m 2 , 67 ± 16 mmHg, 270 ± 71 ml/min/m 2 , and 9.3 ± 1.6 g/dl respectively (Figure 1). Phenylephrine cumulative dose increased with CPB duration, 11 ± 9 mg at 1h and 20 ± 15 mg at 2h. Fluid administration showed similar trend. Core mean temperature was maintained with nadir being 33.5 ± 3.4°C. SvO 2 rapidly increased with institution of CPB, peaking at 85%, and then slowly declined. Inversely, VO 2 dropped and then slowly increased. Lactate continuously increased with duration of CPB. Conclusions: Our findings suggest that despite hemodynamic values being maintained at goal by continuously high vasopressor use and fluid administration during CPB, tissue perfusion was inadequate.Our study suggests that, using data-driven approaches, it may be time to revisit the assumptions regarding all aspects of managing CPB.
Abstract 14810: Left Atrial Ejection Force as a Predictor of Outcome After Catheter Ablation in an Early Stage of Atrial Fibrillation
Authors: Hideyuki Kishima, Takanao Mine, Satoshi Takahashi, Kenki Ashida, Masaharu Ishihara, Tohru Masuyama
Journal: Circulation (2017)

Introduction: Left atrium (LA) systolic dysfunction is observed in the early stages of atrial fibrillation (AF) prior to LA anatomical change. Hypothesis: We investigated whether LA systolic dysfun...
Abstract 13295: Novel Experimental Therapeutics for COVID-19 Derived From a Nitric Oxide Donor
Authors: John F Schmedtje, Zahra Assar
Journal: Circulation (2020)

Urea transport protein B, the product of the gene SLC14A1 , facilitates transport of urea, water and urea analogues across cell membranes. SLC14A1 mRNA is overexpressed in human vascular endothelial cells in culture under hypoxic (1% oxygen) conditions compared with normoxia. This leads to transport of urea out of the endothelial cell and likely contributes to the reduction in eNOS (endothelial nitric oxide synthase) pathway activity in hypoxia. NO has antiviral activity. Novel compounds were developed by binding a urea-like moiety to the backbone of the generic agent isosorbide mononitrate, a well-known NO donor, to combat vascular endothelial dysfunction in COVID-19, a disease characterized by systemic hypoxia and inflammation due to SARS-CoV-2 infection. A study of drug-protein interactions was undertaken using in silico modelling. Novel compounds were studied against 9 key SARS-CoV-2 targets using Maestro, Schrödinger Suite software (Glide docking). Docking scores and intermolecular interactions within the target’s key binding amino acid residues were studied to compare investigational compounds and known antivirals. Several novel agents tested had a better Glide Score (a prediction of ligand affinity) against the papain-like protease (PL pro ) of SARS-CoV-2 compared with known antiviral drugs. PL pro is considered to be a primary target for therapeutic inhibition of the SARS viruses. The candidate compounds CR-305, CR-607, CR-510 and CR-605 were all superior to Remdesivir, GS-441524, Lopinavir, Boceprevir, and Ribavirin. Given the known direct antiviral action of NO and evidence of specific binding of these compounds to the PL pro of SARS-CoV-2 based on the in silico results, we conclude there is a high likelihood these novel compounds will prove to be of therapeutic value against COVID-19. CR-305 appears to have a higher affinity to SARS-CoV-2 than other antivirals as it sits firmly in the PL pro catalytic pocket and makes the most of key interactions with the catalytic pocket residues: Gly163, Asp164, Gln271 and Tyr264. These data call for a new focus on these novel antiviral agents as they appear to bind with an increased avidity to PL pro (compared with other known antivirals) while targeting delivery of NO to the SARS-CoV-2 virus in COVID-19.
Calcium phosphate coatings enhance biocompatibility and degradation resistance of magnesium alloy: Correlating in vitro and in vivo studies
Authors: Julia Gao, Yingchao Su, Yi-Xian Qin
Journal: Bioactive Materials (2020)

Magnesium (Mg) and its alloys are promising biodegradable materials for orthopedic applications. However, one of the major problems is their rapid degradation rate with quick evolution of hydrogen gas. To overcome this problem, calcium phosphate (CaP) coatings have been used to improve the degradation resistance and the biocompatibility of Mg materials. This study focuses on the comparison and correlation of the
Heterodimerization With 5-HT <sub>2B</sub> R Is Indispensable for β <sub>2</sub> AR-Mediated Cardioprotection
Authors: Ying Song, Chanjuan Xu, Jianfeng Liu, Yulong Li, Huan Wang, Dan Shan, Irving W. Wainer, Xinli Hu, Yan Zhang, Anthony Yiu-Ho Woo, Rui-Ping Xiao
Journal: Circulation Research (2020)

Rationale: The β 2 -adrenoceptor (β 2 -AR), a prototypical GPCR (G protein-coupled receptor), couples to both G s and G i proteins. Stimulation of the β 2 -AR is beneficial to humans and animals with heart failure presumably because it activates the downstream G i -PI3K-Akt cell survival pathway. Cardiac β 2 -AR signaling can be regulated by crosstalk or heterodimerization with other GPCRs, but the physiological and pathophysiological significance of this type of regulation has not been sufficiently demonstrated. Objective: Here, we aim to investigate the potential cardioprotective effect of β 2 -adrenergic stimulation with a subtype-selective agonist, (R,R’)-4-methoxy-1-naphthylfenoterol (MNF), and to decipher the underlying mechanism with a particular emphasis on the role of heterodimerization of β 2 -ARs with another GPCR, 5-hydroxytryptamine receptors 2B (5-HT 2B Rs). Methods and Results: Using pharmacological, genetic and biophysical protein-protein interaction approaches, we studied the cardioprotective effect of the β 2 -agonist, MNF, and explored the underlying mechanism in both in vivo in mice and cultured rodent cardiomyocytes insulted with doxorubicin, hydrogen peroxide (H 2 O 2 ) or ischemia/reperfusion. In doxorubicin (Dox)-treated mice, MNF reduced mortality and body weight loss, while improving cardiac function and cardiomyocyte viability. MNF also alleviated myocardial ischemia/reperfusion injury. In cultured rodent cardiomyocytes, MNF inhibited DNA damage and cell death caused by Dox, H 2 O 2 or hypoxia/reoxygenation. Mechanistically, we found that MNF or another β 2 -agonist zinterol markedly promoted heterodimerization of β 2 -ARs with 5-HT 2B Rs. Upregulation of the heterodimerized 5-HT 2B Rs and β 2 -ARs enhanced β 2 -AR-stimulated G i -Akt signaling and cardioprotection while knockdown or pharmacological inhibition of the 5-HT 2B R attenuated β 2 -AR-stimulated G i signaling and cardioprotection. Conclusions: These data demonstrate that the β 2 -AR-stimulated cardioprotective G i signaling depends on the heterodimerization of β 2 -ARs and 5-HT 2B Rs.
First‐in‐man case of non‐invasive proton radiotherapy for the treatment of refractory ventricular tachycardia in advanced heart failure
Authors: Veronica Dusi, Viviana Vitolo, Laura Frigerio, Rossana Totaro, Adele Valentini, Amelia Barcellini, Alfredo Mirandola, Giovanni B. Perego, Michela Coccia, Alessandra Greco, Stefano Ghio, Francesca Valvo, Gaetano M. De Ferrari, Massimiliano Gnecchi, Luigi Oltrona Visconti, Roberto Rordorf
Journal: European Journal of Heart Failure (2020)
Abstract 15288: Mitochondrial Injury in Cardiomyopathy of Neurogenic Hypertension: Role of MiR-18a-5p/HIF-1a Axis
Authors: Shyam S Nandi, Kenichi Katsurada, Neeru M Sharma, Sushil K Mahata, Kaushik P Patel
Journal: Circulation (2020)

Hypertension increases the risk of heart disease, and key hallmark features of hypertensive heart disease is sympatho-excitation and mitochondrial injury. However, the molecular intermediary link between enhanced sympatho-excitation and cardiac mitochondrial injury remains unclear. Sprague-Dawley rats (250-300g) were subjected to a central infusion of Ang II (20ng/min for 14days, 0.5μl/h, i.c.v.; neurogenic hypertension (NG-HTN)) or isotonic saline (0.9% saline, i.c.v; Control (Con)) through osmotic mini-pumps. Mitochondrial injury and cardiac remodeling were assessed using Western blot, histology, immunocytochemistry and electron microscopy. Sympatho-excitatory effect on mitochondrial injury was examined in in vitro by administration of norepinephrine (NE) on H9c2 rat cardiomyocytes. Our NG-HTN rat model exhibited increased sympatho-excitaton and hypertension. Concomitantly, there was reduced miRNA-18a-5p (NG-HTN: 0.65±0.05 vs. Con: 1.06±0.04 vs.), but increased HIF-1α levels in the heart (NG-HTN: 1.82±0.4 vs. Con: 0.88±0.13). Increased mitochondrial untranslated protein response (UPR mt ) marker HSP60 (NG-HTN: 1.22±0.08 vs. Con: 0.81±0.07) indicated mitochondrial proteinopathy and proteotoxic stress associated with increased mito-ROS and altered mitochondrial oxidative phosphorylation. Further, there was reduced mitochondrial biogenesis and fusion, but increased mitochondrial fission, coupled with impaired mitochondrial TIM-TOM translocase performance in NG-HTN hearts. Electron microscopy revealed mitochondrial injury in NG-HTN hearts, linked with hypertrophic cardiomyopathy and fibrosis remodeling. Our In-silico data showed increased NE decreased miR-18a-5p to target HIF-1α, and corroborated mitochondrial injury and cardiomyocyte hypertrophy in, in vitro studies. In conclusion, these results demonstrate that enhanced sympatho-excitation contributes to reduced miR-18a-5p causing increased HIF-1α in the heart leading to mitochondrial proteotoxic stress and metabolic shift, which underlies mitochondrial injury. This study identifies the key molecular intermediary links that can potentially be manipulated for therapeutic benefits for pathological cardiac remodeling in clinical HTN.
Artificial Intelligence Aids Cardiac Image Quality Assessment for Improving Precision in Strain Measurements
Authors: Kuan-Chih Huang, Chiun-Sheng Huang, Mao-Yuan Su, Chung-Lieh Hung, Yi-Chin Ethan Tu, Lung-Chun Lin, Juey-Jen Hwang
Journal: JACC. Cardiovascular imaging (2020)
Abstract 13426: The Dual GIP/GLP-1 Receptor Agonist Tirzepatide Improves Cardiovascular Risk Protein Biomarkers in Patients With Type 2 Diabetes
Authors: Jonathan M Wilson, Yanzhu Lin, Gary Considine, Amy L Cox, Lenden M Bowsman, Deborah A Robins, Jeffrey S Riesmeyer, Axel Haupt, Kevin Duffin, Giacomo Ruotolo
Journal: Circulation (2020)

Introduction: The dual GIP/GLP-1 receptor agonist tirzepatide dose-dependently reduced HbA1c and body weight in patients with obesity and type 2 diabetes (T2D) in a Phase 2 trial. Hypothesis: In this post hoc analysis, additional biomarkers of inflammation, endothelial dysfunction, and cellular stress were measured to better understand possible additional effects of tirzepatide treatment on cardiovascular risk factors. Methods: Patients with T2D were randomly assigned to receive either once-weekly subcutaneous injection of tirzepatide (1, 5, 10, or 15 mg), GLP-1 receptor agonist dulaglutide (1.5 mg), or placebo for 26 weeks. Soluble ICAM-1 and VCAM-1, IL-6, NT-proBNP, hsCRP and GDF-15 were assessed by immunoassay at baseline and 26 weeks in stored serum or EDTA plasma samples. Results were analyzed in a modified intent-to-treat population using a mixed effect model for repeated measures. Results: At 26 weeks, tirzepatide dose-dependently decreased ICAM-1 levels compared to baseline (Table). ICAM-1 levels were also significantly lower with tirzepatide 15 mg than placebo or dulaglutide. Moreover, tirzepatide 15 mg significantly decreased hsCRP levels from baseline compared with placebo. GDF-15 levels were decreased from baseline with all tirzepatide doses and with dulaglutide; however, changes in GDF-15 levels with tirzepatide were not significantly different from those with placebo or dulaglutide. Levels of IL-6, VCAM-1 or NT-proBNP were unchanged in all groups. Conclusions: In a 26-week study in patients with obesity and T2D, treatment with tirzepatide dose-dependently decreased circulating levels of specific biomarkers of inflammation and endothelial dysfunction previously associated with cardiovascular events, thus suggesting a net improvement in the cardiovascular risk profile of these patients. Clinical relevance of these changes will be assessed in the planned cardiovascular outcome study SURPASS-CVOT (NCT04255433).
CRELD1 modulates homeostasis of the immune system in mice and humans
Authors: Lorenzo Bonaguro, Maren Köhne, Lisa Schmidleithner, Jonas Schulte-Schrepping, Stefanie Warnat-Herresthal, Arik Horne, Paul Kern, Patrick Günther, Rob ter Horst, Martin Jaeger, Souad Rahmouni, Michel Georges, Christine S. Falk, Yang Li, Elvira Mass, Marc Beyer, Leo A. B. Joosten, Mihai G. Netea, Thomas Ulas, Joachim L. Schultze, Anna C. Aschenbrenner
Journal: Nature Immunology (2020)
Toward real-time polyp detection using fully CNNs for 2D Gaussian shapes prediction
Authors: Hemin Ali Qadir, Younghak Shin, Johannes Solhusvik, Jacob Bergsland, Lars Aabakken, Ilangko Balasingham
Journal: Medical Image Analysis (2020)

To decrease colon polyp miss-rate during colonoscopy, a real-time detection system with high accuracy is needed. Recently, there have been many efforts to develop models for real-time polyp detection, but work is still required to develop real-time detection algorithms with reliable results. We use single-shot feed-forward fully convolutional neural networks (F-CNN) to develop an accurate real-time polyp detection system. F-CNNs are usually trained on binary masks for object segmentation. We propose the use of 2D Gaussian masks instead of binary masks to enable these models to detect different types of polyps more effectively and efficiently and reduce the number of false positives. The experimental results showed that the proposed 2D Gaussian masks are efficient for detection of flat and small polyps with unclear boundaries between background and polyp parts. The masks make a better training effect to discriminate polyps from the polyp-like false positives. The proposed method achieved state-of-the-art results on two polyp datasets. On the ETIS-LARIB dataset we achieved 86.54% recall, 86.12% precision, and 86.33% F1-score, and on the CVC-ColonDB we achieved 91% recall, 88.35% precision, and F1-score 89.65%.
Abstract 12719: Diagnostic and Prognostic Contributions of Cardiac Computed Tomography for Infective Endocarditis Surgery
Authors: Tom Kai Ming Wang, Mnahi Bin Saeedan, Nicholas Chan, Nancy Obuchowski, Nabin Shrestha, Bo Xu, Shinya Unai, Paul C Cremer, Richard A Grimm, Brian P Griffin, Scott D Flamm, Gosta B Pettersson, Zoran B Popovic, Michael A Bolen
Journal: Circulation (2020)

Background: Cardiac computed tomography (CT) is emerging as an adjunctive modality to echocardiography in the evaluation of infective endocarditis (IE) and surgical planning. CT studies in IE have, however, focused on its diagnostic rather than prognostic utility, the latter of which is important in high-risk diseases like IE. We evaluated the associations between cardiac CT and transesophageal echocardiography (TEE) findings and adverse outcomes after IE surgery. Methods: Of 833 consecutive patients with surgically proven IE during 5/1/2014-5/1/2019 at Cleveland Clinic, 155 underwent both pre-operative ECG-gated contrast-enhanced CT and TEE. Multivariable analyses were performed to identify CT and TEE biomarkers that predict adverse outcomes after IE surgery, adjusting for EuroSCORE II. Results: CT and TEE were positive for IE in 123 (75.0%) and 124 (75.6%) of patients respectively. CT identified an additional 11% of vegetations, 13% of pseudoaneurysms or abscesses, 5% of dehiscences and 14% of fistulae when TEE was negative. Thirty-day mortality occurred in 3 (1.9%) patients, and composite mortality and/or morbidities in 72 (46.5%). Pseudoaneurysm or abscess detected on TEE was the only imaging biomarker to show independent association with composite mortality and/or morbidities in-hospital, with odds ratio (95%CI) of 3.66 (1.76-7.59), P=0.001. There were 17 late deaths, and both pseudoaneurysm or abscess detected on CT and fistula detected on CT were the only independent predictors of total mortality during follow-up, with hazards ratios (95%CI) of 3.82 (1.25, 11.7), P&lt;0.001 and 9.84 (1.89, 51.0), P=0.007 respectively (Figure). Conclusion: We identified cardiac CT and TEE features that predicted separate adverse outcomes after IE surgery. Imaging biomarkers can play important roles incremental to conventional clinical factors for risk stratification in patients undergoing IE surgery.
Abstract 233: Characterizing Impact of State Legislation on Cardiac Arrest Outcomes at K-12 Schools
Authors: Edward Ford, Patrick Karabon, Clay Mann, Monica Goble, Gwen Fosse, Robert A Swor
Journal: Circulation (2020)

Background: Cardiac arrests that occur in schools are infrequent, but high-profile events. Many states have enacted school specific legislation regarding automated external defibrillators (AEDs) placement, CPR training and emergency response plans (EAP). Objective/Aim: To characterize out-of-hospital cardiac arrests (OHCA) that occur in K-12 schools; and, assess the relationship of U.S. state AED and CPR laws to outcomes of in school cardiac arrests. Methods: A retrospective review of in school OHCA was completed with data from the National EMS Information System (NEMSIS) 3.4 database, calendar years 2017-2018. Study subjects were non-traumatic OHCA occurring prior to EMS arrival on K-12 school grounds. Additionally, we conducted a search of Westlaw (Thomson Reuters) to identify current school specific AED, CPR and EAP laws for all 50 states, and created a structured taxonomy for these laws. Datasets were linked by an honest broker and the K-12 school CPR and AED provisions were compared to state legislation. Results: During the study period, there were 454 cases of in school cardiac arrest out of the 25.3 million incidents submitted to NEMSIS. We excluded 140, thus leaving 314 arrests for analysis. The average age was 46.7 (SD=24.1), most were over 18 years old (79.4%), and male 221 (70.4%). Bystander CPR (BCPR) was performed in 240 (76.4%) of cases, bystander AEDs were used in 160 (51.0%) cases, and 107 (34.1%) patients received an AED shock. State AED and CPR laws required student CPR training in 78%, school AED placement in 46%, teacher CPR certification in 14%, and school specific cardiac emergency response plans in 32%. We found no increase in BCPR or AED placement in states with school CPR, AED or EAP legislation. These findings persisted regardless of patient age, school type, or legislative mandate (all P &gt; 0.05). Conclusion: Despite the perceived benefit of legislation supporting CPR and AED use in schools, we identified no improved provision of BCPR or AED use in schools in states with such legislation. Given the high proportions of BCPR and AED in states with and without statutes, we believe this data suggests that non-legislative initiatives, which exist in many states, may be an important driver of emergency cardiac care in K-12 schools.
99mTc-Sestamibi Scintigraphy Reveals Parathyroid Adenoma Masquerading as Esophageal Diverticulum
Authors: Matthew D. Kay, Lilah F. Morris-Wiseman, Justin Caskey, Blair A. Winegar, Phillip H. Kuo
Journal: Clinical Nuclear Medicine (2020)

A 74-year-old woman with primary hyperparathyroidism diagnosed from routine laboratory tests described symptoms of fatigue and difficulty with concentration. During surgical consultation, the cervical and thoracic spine MRI scans from the preceding 10-year period, performed for relapsing-remitting multiple sclerosis, were reviewed. In this clinical context, the slowly enlarging left upper paraesophageal lesion, reported as a lateral proximal esophageal (Killian-Jamieson) diverticulum, was reevaluated for a potential parathyroid adenoma. 99mTc-sestamibi SPECT/CT demonstrated focal uptake in the paraesophageal lesion with surgical resection, confirming it to be a large parathyroid adenoma.