tbuckley/cabot-search huggingface dataset:
Abstract 254: High Shock Efficacy and Algorithm Performance for a 150J Biphasic Waveform AED Used by Lay and BLS Responders During Out-of-hospital Cardiac Arrest
Authors: Stacy Gehman, Edward Kompare, Barbara Fink, Tim Johnson, Walter Hufford, Kevin Najarian, Dawn Jorgenson
Journal: Circulation (2020)

Introduction: Effective AED defibrillation of out of hospital cardiac arrest (OHCA) depends on the safe and effective identification of shockable rhythms, and on delivery of effective defibrillation energy. This report summarizes rhythm detection performance and shock efficacy during OHCA uses of Philips HeartStart Home and OnSite AEDs using non-escalating 150 J therapy. Methods: A convenience sample of 185 OHCA AED patient uses were reviewed by clinical experts. All analysis periods that resulted in AED rhythm advisories (Shock Advised or No Shock Advised) were annotated. Shockable rhythm categories include VF and polymorphic VT/flutter. Non-Shockable rhythm categories include normal sinus rhythm, other rhythms (e.g., atrial fibrillation/flutter, bradycardia, SVT, idioventricular, bundle branch block), and asystole. Intermediate rhythms (benefits of defibrillation are limited or uncertain) were not included. Post-shock rhythm was categorized as shockable, non-shockable, or undeterminable (rhythms corrupted by CPR artifact or pads removal within 5-s of shock delivery). Shock success was defined as conversion to a non-shockable rhythm within 5-s post-shock. Results: A total of 487 analysis periods resulted in AED rhythm advisories, with 175 annotated as Shockable and 312 Non-shockable. Sensitivity and specificity (n/N, Exact 95% CI) were 97.7% (171/175, 94.3%, 99.4%) and 100% (312/312, 98.8%, 100.0%) respectively. A total of 165 shocks were delivered to 100 patients with 5 undeterminable post-shock rhythms. The remaining 160 shocks were delivered to 156 Shockable rhythm episodes. All shock efficacy was 96.9% (155/160, 92.9%, 99.0%): 150 episodes converted to non-shockable rhythms after one shock (96.2% (150/156, 91.8%, 98.6%)); 154 after two shocks (98.7% (154/156, 95.4%, 99.8%)); and 155 after three shocks, the first two of which were undeterminable (99.4% (155/156, 96.5%, 100.0%)). The remaining episode had a failed first shock, followed by an undeterminable second shock, which was the last shock of the use. Conclusion: For these 150J fixed-energy AEDs, OHCA defibrillation is safe (100% specificity), and effective (97.7% sensitivity; 96.2% single shock effectiveness; 98.7% after two shocks; 99.4% after three shocks).
Abstract 13699: Cyclohexanone Contamination of Medical Plastics is Associated With Worse Congenital Heart Surgery Outcomes
Authors: Christin Y Park, Jordan Kuiper, Jessie Buckley, Greg Ellis, David Graham, Eric M Graham, Allen D Everett
Journal: Circulation (2020)

Introduction: Cyclohexanone, an industrial medical plastic fabrication contaminant, can leach from medical plastics including the cardiopulmonary bypass (CPB) circuit. Effects of neonatal perioperative cyclohexanone exposure on hospital-based outcomes have not been explored. Hypothesis: We hypothesize that serum cyclohexanone during congenital heart surgery with CPB is associated with worse morbidity. Methods: The study was a secondary analysis of 107 neonates enrolled in the NHLBI-funded Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass trial. Blood samples were collected preoperatively, post-CPB, and 12 hours postoperatively, and concentrations of cyclohexanone and its metabolites were quantified using mass spectrometry. Using the geometric mean of cyclohexanone concentrations, the effects of an interquartile range (IQR) increase in concentration on hospital-based outcomes was assessed using adjusted linear and Poisson regression, for continuous and dichotomous outcomes, respectively. Estimates were reported as % differences (linear regression) or relative risks (Poisson regression) with 95% confidence intervals. Results: In adjusted analyses, an IQR increase in mean cyclohexanone concentration was associated with greater time spent on mechanical ventilation (40.1%: 7.34%, 82.9%), in the ICU (20.1%: 1.36%, 42.2%), and in the hospital (20.8%: 3.28%, 41.3%), and less time spent alive and out of the hospital 90 days post-surgery (-17%: -30.9%, -0.36%). An IQR increase in mean cyclohexanone was associated with a 61% (RR: 1.61; 1.19, 2.17) greater risk of the trial primary morbidity-mortality composite outcome (death, cardiac arrest, ECMO, renal or hepatic insufficiencies, and lactic acidosis). An IQR increase in mean cyclohexanone metabolites was associated with a 29% (RR: 1.29; 1.07, 1.55) greater risk of developing low cardiac output syndrome. Conclusions: This study showed that in neonates, circulating cyclohexanone was associated with unfavorable hospital-based outcomes following cardiac surgery with CPB, suggesting that medical plastic contamination may contribute to morbidity. Therefore, reducing exposure to cyclohexanone perioperatively may improve congenital heart surgery outcomes.
A Malignant Electrocardiogram
Authors: Robert T. Short, Bei Hu, Laszlo Littmann
Journal: Circulation (2020)

ECG CHALLENGEA 67-year-old woman with history of hypertension but no other cardiac history presented to the emergency department after she awoke with severe dyspnea and midsternal chest pressure.She had been experiencing mild chest discomfort, dyspnea on exertion, night sweats, nausea, and vomiting for 1 week.Before this, she was in her normal state of health.Figure 1 illustrates the ECG on presentation.A comparison ECG from 4 months before showed normal sinus rhythm without ischemic abnormalities.Chest radiography demonstrated bilateral pleural effusions with normal heart and mediastinal diameters.Computerized tomography angiogram of the chest showed
Benefit–Risk Tradeoffs in Assessment of New Drugs and Devices
Authors: Sanjay Kaul, Norman Stockbridge, Javed Butler
Journal: Circulation (2020)

Balancing benefits and risks is a complex task that poses a major challenge, both to the approval of new medicines and devices by regulatory authorities and in therapeutic decision-making in practice. Several analysis methods and visualization tools have been developed to help evaluate and communicate whether the benefit-risk profile is favorable or unfavorable. In this White Paper, we describe approaches to benefit-risk assessment using qualitative approaches such as the Benefit Risk Action Team framework developed by the Pharmaceutical Research and Manufacturers of America, and the Benefit-Risk Framework developed by the United States Food and Drug Administration; and quantitative approaches such as the numbers needed to treat for benefit and harm, the benefit-risk ratio, and Incremental Net Benefit. We give illustrative examples of benefit-risk evaluations using 4 treatment interventions including sodium glucose cotransporter 2 inhibitors in patients with type 2 diabetes; a direct antithrombin agent, dabigatran, for reducing stroke and systemic embolism in patients with nonvalvular atrial fibrillation; transcatheter aortic valve replacement in patients with symptomatic severe aortic valve stenosis; and antiplatelet agents vorapaxar and prasugrel for reducing cardiovascular events in patients at high cardiovascular risk. Regular applications of structured benefit-risk assessment, whether qualitative, quantitative, or both, enabled by easy-to-understand graphical presentations that capture uncertainties around the benefit-risk metric, may aid shared decision-making and enhance transparency of those decisions.
Soran Akram Agha Chawishly
Authors: Esma J Dogramaci
Journal: BMJ (2020)

Soran Akram Agha Chawishly was born on 4 January 1951 in Erbil, Iraq, to Akram and Rasmieh Chawishly, their second son and one of six children. After completing his primary and secondary education in Erbil, he travelled to Baghdad, where he studied medicine at the Baghdad Medical College, University of Baghdad.

After obtaining his primary degree, Soran worked and trained in several Baghdad hospitals in the specialties of general surgery, orthopaedics, general internal medicine, paediatrics, accident and emergency medicine, and otolaryngology, after which he decided to pursue specialisation in the latter. This decision led him to train at the Al-Yarmouk Teaching Hospital in Baghdad. After qualifying he worked as a specialist otolaryngologist in …
Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial
Authors: Juliane Schuhmacher, Sonja Heidu, Torben Balchen, Jennifer Rebecca Richardson, Camilla Schmeltz, Jesper Sonne, Jonas Schweiker, Hans-Georg Rammensee, Per Thor Straten, Martin Andreas Røder, Klaus Brasso, Cécile Gouttefangeas
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Peptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC) in patients with prostate cancer. RhoC is a small GTPase overexpressed in advanced solid cancers, metastases and cancer stem cells. Methods Twenty-two patients who had previously undergone radical prostatectomy received subcutaneous injections of 0.1 mg of a single RhoC-derived 20mer peptide emulsified in Montanide ISA-51 every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. The drug safety and vaccine-specific immune responses were assessed during treatment and thereafter within a 13-month follow-up period. Serum level of prostate-specific antigen was measured up to 26 months postvaccination. Results Most patients (18 of 21 evaluable) developed a strong CD4 T cell response against the vaccine, which lasted at least 10 months following the last vaccination. Three promiscuouslypresented HLA-class II epitopes were identified. Vaccine-specific CD4 T cells were polyfunctional and effector memory T cells that stably expressed PD-1 (CD279) and OX-40 (CD134), but not LAG-3 (CD223). One CD8 T cell response was detected in addition. The vaccine was well tolerated and no treatment-related adverse events of grade ≥3 were observed. Conclusion Targeting of RhoC induced a potent and long-lasting T cell immunity in the majority of the patients. The study demonstrates an excellent safety and tolerability profile. Vaccination against RhoC could potentially delay or prevent tumor recurrence and metastasis formation. Trial registration number NCT03199872 .
Abstract 15125: Insulin Therapy is Associated With Increased Cardiomyocyte Apoptosis and Cardiac Fibrosis
Authors: Fadi W Adel, Ye Zheng, Shuchong Pan, Siu-Hin Wan, Syed Ameenuddin, Horng Chen
Journal: Circulation (2019)

Introduction: Patients with diabetes mellitus (DM) are at an increased risk of heart failure (HF). While insulin therapy restores euglycemia, it does not protect against HF in DM. In fact, in a rec...
Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis
Authors: Eun Hee Koh, Ji Eun Yoon, Myoung Seok Ko, Jaechan Leem, Ji-Young Yun, Chung Hwan Hong, Yun Kyung Cho, Seung Eun Lee, Jung Eun Jang, Ji Yeon Baek, Hyun Ju Yoo, Su Jung Kim, Chang Ohk Sung, Joon Seo Lim, Won-Il Jeong, Sung Hoon Back, In-Jeoung Baek, Sandra Torres, Estel Solsona-Vilarrasa, Laura Conde de la Rosa, Carmen Garcia-Ruiz, Ariel E Feldstein, Jose C Fernandez-Checa, Ki-Up Lee
Journal: Gut (2020)

Objective Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH. Design Wild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4). Results HFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of Sms1 but not Sms2 was higher in mouse models and patients with NASH. FC in hepatocytes induced Sms1 expression, and Sms1 knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of Nlrc4 prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but Nlrp3 knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis. Conclusion SMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.
Geospatial clustering of childhood IgA vasculitis and IgA vasculitis-associated nephritis
Authors: Matej Sapina, Marijan Frkovic, Mario Sestan, Sasa Srsen, Aleksandar Ovuka, Mateja Batnozic Varga, Karolina Kramaric, Dario Brdaric, Kresimir Milas, Alenka Gagro, Marija Jelusic
Journal: Annals of the Rheumatic Diseases (2020)

Research on spatial variability of the incidence of IgA vasculitis (IgAV) in children and its potential implications for elucidation of the multifactorial aetiology and pathogenesis is limited. We intended to observe spatial variability of the incidence of IgAV and IgA vasculitis-associated nephritis (IgAVN) using modern geostatistical methods, and hypothesised that their spatial distribution may be spatially clustered.Patients' data were retrospectively collected from 2009 to 2019 in five Croatian University Hospital Centres for paediatric rheumatology, and census data were used to calculate the incidence of IgAV. Using spatial empirical Bayesian smoothing, local Morans' I and local indicator of spatial autocorrelation (LISA), we performed spatial statistical analysis.596 children diagnosed with IgAV were included in this study, of which 313 (52.52%) were male. The average annual incidence proportion was estimated to be 6.79 per 100 000 children, and the prevalence of IgAVN was 19.6%. Existence of spatial autocorrelation was observed in both IgAV and IgAVN; however, clustering distribution differed. While IgAV showed clustering in Mediterranean and west continental part around cities, IgAVN was clustered in the northern Mediterranean and eastern continental part, where a linear cluster following the Drava and Danube river was observed.IgAV incidence in Croatia is similar to other European countries. Spatial statistical analysis showed a non-random distribution of IgAV and IgAVN. Although aetiological associations cannot be inferred, spatial analytical techniques may help in investigating and generating new hypotheses in non-communicable diseases considering possible environmental risk factors and identification of potential genetic or epigenetic diversity.
Abstract 16388: Feature Selection Using Recursive Feature Elimination (RFE): Machine Learning Application in Predicting Permanent Pacemaker Implantation (PPMI) in Patients Undergoing Transcatheter Aortic Valve Replacement (TAVR)
Authors: Suleman Ilyas, Wasiq Sheikh, Anshul Parulkar, Malik B Ahmed, Gerry Ovide, Benjamin Rosen, Brian Osler, Fabio V Lima, Esseim Sharma, Anthony Chu
Journal: Circulation (2020)

Introduction: TAVR is increasingly being performed because of several recent large-scale clinical trials supporting its use across a range of patient sub-classes. Although it provides life-altering relief of severe aortic stenosis, adverse outcomes are not uncommon including paravalvular leak, life-threatening bleeding, acute kidney injury, stroke, and PPMI. RFE can help certain classification models like logistic regression in better predicting binary variables such as PPMI by creating a model based upon a set of predictors and then progressively eliminating variables to optimize the model. Objective: To determine whether RFE when applied to logistic regression would result in discriminatory ability in the prediction of PPM implantation in patients undergoing TAVR Methods: Pre- and postoperative data from a single institution were collected for all patients undergoing TAVR without a history of PPMI between January 2016 and December 2019. EKG data obtained included QRS duration, presence of atrioventricular block, left anterior and posterior fasicular block and right bundle branch block(RBBB). Data was imported into Python and a stratified 5 fold cross validation with SMOTE oversampling was run with RFE running at every fold to avoid overfitting. Upon completion, a rank score was tabulated for each predictor and a final logistic regression model with the highest optimized receiver under the operator curve was exported and applied to a test set. The receiver under the operator score was calculated for the training and test sets and the variables of importance were identified using RFE. Results: The total sample size for this cohort was 513 patients, with a PPMI incidence of 8.58%. The training set consisted of 40 variables and 384 patients, and the test set had 129 patients. The final optimized model on the training set had an ROC of 0.75 and utilized three features out of forty. The three features identified by RFE were: implanted TAVR valve size, QRS duration, and presence of RBBB. The model had a ROC of 0.63 on the test set. Conclusions: Our results show that presence of pre-op RBBB, prolonged QRS duration and valve size were risk factors for PPMI. Logistic regression classification had modest ability in predicting the need for PPMI after TAVR.
Abstract 12730: Cardiosphere-derived Cells Improve Segmental Myocardial Circumferential Strain by Magnetic Resonance Imaging: Results From the Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration Study
Authors: Mohammad R Ostovaneh, Raj Makkar, Bharath Ambale Venkatesh, Deborah Ascheim, Tarun Chakravarty, Timothy D Henry, Glen Kowalchuk, Frank V Aguirre, Dean J Kereiakes, Thomas J Povsic, Richard A Schatz, Jay H TRAVERSE, Janice Pogoda, Rachel D Smith, Linda S Marban, Eduardo Marban, Joao A Lima
Journal: Circulation (2020)

Introduction: Cell therapy failed to improve global LV ejection fraction (LVEF) in most trials of post-MI LV dysfunction. LVEF does not consider the effect of cell therapy on different segments of the myocardium, which may be heterogeneous across different myocardial regions in patients with regional MI. Hypothesis: Allogeneic cardiosphere-derived cells (CDCs) improve segmental (but not global) myocardial function indexed as circumferential strain by MRI. Methods: In this randomized double-blind trial, 142 post-MI patients with LVEF&lt;45% and 15% or greater LV scar size were randomized in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6-month was compared between CDCs and placebo groups. Results: In total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3(10.8) and 108 (87.1%) males). Segmental Ecc improvement was significantly greater in patients receiving CDC (-0.5%(4.0)) compared to placebo (0.2%(3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of -0.7% (3.5) in patients receiving CDC vs. 0.04% (3.7) in the placebo group, p=0.04). The beneficial effect of CDCs for improving segmental Ecc was greater in patients with LV ejection fraction&lt;41%, LV scar size&gt;18.8% or LV end-diastolic volume index&gt;100 [mixed effect regression coefficients of -0.92(p=0.02),-0.78(p=0.03), and -1.16(p=0.004) respectively versus -0.58(p=0.05) for the entire cohort]. Conclusions: In patients with post-MI LV dysfunction, allogeneic CDC administration resulted in improved segmental myocardial function. This CDC induced improvement in segmental myocardial function was greater in patients with severe LV dysfunction, dilated LV and greater infarct size. (clinicaltrials.gov Identifier: NCT01458405).
Abstract 13871: Plasmacytoid Dendritic Cell-derived Interferons Mediate Myocardial Ischemia-reperfusion Injury by Activating Type I Interferon Receptor
Authors: Aimee Zhang, Katherine Marsh, Irving Kron, Zequan Yang
Journal: Circulation (2020)

Introduction: We have previously demonstrated type I interferon (IFN-I) is elevated during and mediates myocardial ischemia-reperfusion injury (IRI). Hypothesis: Plasmacytoid dendritic cells (pDCs) secrete IFN-I to exacerbate myocardial IRI by activating IFN-I receptor (IFNAR). Methods: C57BL/6 (WT) and IFNAR1 knockout (KO) mice underwent 40 minutes of left coronary artery occlusion followed by 60 minutes of reperfusion. At the end of reperfusion, plasma was obtained and hearts were harvested for TTC-Phthalo-blue staining to calculate infarct size (IS), denoted as a percentage of the ischemic risk region (RR). In pDC-depleted mice, WT mice were treated with PDCA-1 antibody (250 μg via intraperitoneal injection) on days 1, 3, 5, 7 prior to undergoing IRI on day 11. Control mice were treated with isotype IgG. For IFNAR blockade, IFNAR1 antibody (MAR1-5A3 2.0 μg/g) was administered as an IV bolus to WT mice 5 minutes before reperfusion. Results: Flow cytometry demonstrated that PDCA-1 antibody treatment had no effect on the number of splenic conventional dendritic cells (1.87±0.33% vs. 1.55±0.12% in IgG control, p=NS), but significantly reduced splenic pDCs by 60% (0.47±0.01% vs. 1.41±0.29% in IgG control, p&lt;0.05. Figure). pDC-depleted mice had significantly smaller IS compared to control after IRI (31.4±2.8 vs. 51.1±6.0, p&lt;0.05. Figure). At the end of reperfusion, plasma levels of IFNα and IFNβ were significantly elevated in IgG control but not in pDC-depleted mice. RRs were comparable in WT mice with/without IFNAR1 blockade and congenic IFNAR1 KO mice following IRI. WT control and IgG control mice had similar IS (53±4 vs. 49±4, p=NS). IS was significantly reduced by greater than 30% in IFNAR1 mAb-treated mice and IFNAR1 KO mice (p&lt;0.05 vs. controls). Conclusions: pDCs are activated during myocardial IRI and secrete IFN-I, which subsequently activates IFNARs and exacerbates IS. This pathway presents potential new therapeutic targets to attenuate myocardial IRI.