tbuckley/cabot-search huggingface dataset:
Abstract 9970: Prevalence of ECG Abnormalities and Association with Arrhythmic Risk and Myocardial Fibrosis in a Large Cohort of Patients with Mitral Valve Prolapse
Authors: Gene Hu, Lisa Lim, Shalini Dixit, Thuy Nguyen, Yoo Jin Lee, Francesca N Delling
Journal: Circulation (2021)

Background: Inverted or biphasic T-waves (IBTWs) in the inferior leads on a 12-lead electrocardiogram (ECG) have been previously described in small, retrospective samples of MVP with sudden cardiac arrest (SCA) or sudden cardiac death (SCD). However, prior studies are limited by selection of bileaflet involvement, referral bias or targeted autopsies. Moreover, the association of IBTWs with focal fibrosis remains poorly defined. Objective: To assess the rates of IBTWs and their association with arrhythmic risk and late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) in an unselected, longitudinal MVP cohort. Methods: We reviewed available 12-lead ECGs from a cohort of 570 MVP patients with clinical and ambulatory ECG or telemetry monitoring evaluated at the University of California San Francisco between 2012 and 2020. IBTWs were considered clinically relevant if present in at least 2 of 3 inferior ECG leads. Complex ventricular ectopy (ComVE) was defined as &gt;5% burden of premature ventricular contractions, bigeminy, or non-sustained ventricular tachycardia. SCD cases were identified through the National Death Index. In a subset of 86 (15%) patients with available contrast CMR, we assessed the presence and location of LGE. Results: Among 570 MVP patients (52% male, mean age 64±17), 86 (15%) had IBTWs, 160 (28%) had ComVE, and 26 (5%) had severe arrhythmic events (2 sustained VT, 13 SCA, and 11 SCD). Of these 26, 15 (58%) were bileaflet. Rates of IBTWs were similar between MVPs with severe arrhythmic events (9/26, 35%), ComVE (28/160, 18%), and no ventricular arrhythmia (58/410, 14%) ( p= 0.33). Among MVPs with contrast CMR, there were higher rates of IBTWs in those with LGE (papillary muscles or basal inferolateral wall in all) versus without LGE (7/22 vs 6/64, respectively, p = 0.01). Conclusions: In a large, unselected MVP sample inclusive of all arrhythmic presentations and leaflet subtypes, the prevalence of IBTWs is overall low and similar in those with and without ventricular arrhythmia, including SCA/SCD. In those with IBTWs, LGE in the papillary muscles or basal inferolateral wall is common, suggesting focal myocardial traction/fibrosis as the underlying anatomical substrate for repolarization abnormalities in the MVP population.
Abstract 11296: The Association of the Novel Inflammatory Marker Glyc a and Incident Heart Failure and Its Subtypes of Preserved and Reduced Ejection Fraction: The Multi-ethnic Study of Atherosclerosis
Authors: Sunyoung Jang, Oluseye Ogunmoroti, Vishal N Rao, Oluwaseun E Fashanu, Di Zhao, Martin Tibuakuu, James D Otvos, Eve-Marie Benson, Chiadi E Ndumele, Pamela Ouyang, Erin D Michos
Journal: Circulation (2019)

Background: GlycA, a nuclear magnetic resonance composite marker of systemic inflammation, reflects serum concentration and glycosylation state of main acute phase reactants. Prior studies have sho...
BIOM-25. ADULT GANGLIOGLIOMA: A 4-PATIENT CASE SERIES WITH MOLECULAR PROFILING
Authors: Erica Shen, Alireza Shams, Xianyuan Song, Ahmad Daher
Journal: Neuro-Oncology (2021)

Abstract Accounting for only 2% of all primary brain tumors, ganglioglioma is a rare neoplasm that most frequently arises in the temporal lobe in children or young adults. Ganglioglioma is the most common epilepsy-associated neoplasm and is typically composed of dysplastic ganglion cells and neoplastic glial cells. Recent publications have revealed that the activating p.V600E mutation in the BRAF oncogene is seen in 20-60% of gangliogliomas. However, the genetic landscape of ganglioglioma requires further elucidation, especially in gangliogliomas that arise from outside of the temporal lobe in adults. In this case series, we describe the genetic mutations of adult gangliogliomas originating outside of the temporal lobe in four patients aged 21 to 56 years. Targeted next generation sequencing via the MSK-IMPACT panel covering ~ 500 actionable mutations was used in all cases. None of the cases had the BRAF p.V600E mutation. Case 1 describes a left cerebellar cystic ganglioglioma with NTRK2 fusion mutation (NTRK2-DST) and a tumor mutation burden (TMB) = 0 mutation/megabase (mut/Mb). Case 2 describes a right parietal lobe cystic ganglioglioma with a BRAF-CLEC2Linversion mutation and TMB = 0 mut/Mb. Case 3 describes a cerebellar vermis ganglioglioma with a BRAF fusion mutation (BRAF-KIAA1549) and TMB = 0 mut/Mb. The last case describes a right cerebellopontine angle ganglioglioma with a MAP2K1 splicing mutation and TMB = 0.9 mut/Mb. To the best of our knowledge, the mutations identified in this case series have not been previously described in adult brain gangliogliomas. The BRAF-KIAA1549 fusion mutation has been found in spinal cord gangliogliomas, but not in brain gangliogliomas. MAP2K1 splicing mutations, unlike MAP2K1 in-frame deletions, have not been found in gangliogliomas. Finally, a different NTRK2 mutation (NTRK2-TLE4) has been described in a pediatric ganglioglioma, but NTRK2-DST has not been found in any adult gangliogliomas.
Abstract 12070: Extracellular Vesicles, Derived Early After Myocardial Infarction, Inhibits Staurosporin Induced Cardiac Cell Death
Authors: Avinash Khandagale, Bertil Lindahl, Agneta G Siegbahn, Christina Christersson
Journal: Circulation (2021)

Introduction: Adverse ventricular remodeling may occur after myocardial infarction (MI) and is associated with an increased risk of heart failure and death. Extracellular vesicles (EVs) derived exogenously from pluripotent stem cells exert cardioprotective effects after injury and being tested for therapeutic efficacy for MI. However role of endogenous EVs from MI patients in this regard is not yet addressed. Hypothesis: We aim to characterize EVs derived from MI patients and explore their cardioprotective potential on human primary cardiomyocytes (HCM) upon chemically induced cell death. Methods: The EVs from plasma of MI patients with preserved or reduced left ventricular ejection fraction (LVEF) and healthy controls (HC) were purified and characterized by flow cytometry and transmission electron microscopy (TEM). HCM and human cardiac microvascular endothelial cells (hCMVECs) were used to study functional effects of EVs upon staurosporin (STS), etoposide and rapamycin induced cell death. Results: Higher concentrations of platelet-, leukocyte-, endothelial- and erythrocyte-derived EVs were found in MI patients compared to HC. TEM analysis demonstrated the presence of heterogenous vesicles of different sizes (50-1000-nm) across all tested samples. Human cardiac cells- hCMVECs and HCM when pre-incubated with both preserved and reduced LVEF MI EVs showed significant attenuation to STS-induced caspase 3 activity compared to HC EVs or mock treatment. Lactate dehydrogenase (LDH) release, as a marker for membrane integrity, upon etoposide stimulation was not affected in hCMVECs and partly increased in HCM, whereas pre-incubation with HC EVs or MI EVs did not affect eotoposide treatment outcome by these cells. While rapamycin induced cleavage of LC3-I to LC3-II in hCMVECs, the presence of EVs from either HC or MI patients did not influence autophagic response. Whereas, baseline LC3-II expression in HCM was observed to be too high to be perturbed by the presence of rapamycin. Conclusions: Diverse nature of MI EVs in terms of cells of origin can be further elaborated to consolidate their biomarker potential. Cardioprotective ability of endogenously presented heterogenous mixture of MI EVs opens new avenues to consider in preclinical EV/MI research.
Abstract 9112: Dexmedetomidine Reduces Incidences of Ventricular Arrhythmias in Adults
Authors: Qiaonan Zhong, Ashish Kumar, Abhishek Deshmukh, Courtney Bennett
Journal: Circulation (2021)

Introduction: Ventricular arrhythmias, including ventricular tachycardia (VT) and ventricular fibrillation (VF), are associated with high mortality and morbidity. Sedation through agents like benzodiazepines, propofol, and opiates are mainstays of treatment but are limited by side effects. Dexmedetomidine is a α2-presynaptic receptor agonist with a safe and efficacious sedative profile. Furthermore, it has been recently proposed as a sedative agent in VT due its additional antiarrhythmic properties. Methods: A systemic literature review was conducted of MEDLINE, EMBASE, Cochrane, and Scopus. Randomized controlled trials comparing the incidence of ventricular arrhythmias of dexmedetomidine with placebo or an alternative sedative agent were included. Two researchers independently extracted the data and performed quality assessments. Results: We identified 6 studies that met the selection criteria. Our meta-analysis demonstrated significant reduction of the overall risk of ventricular arrhythmias in patients receiving dexmedetomidine (RR 0.35, 95% CI 0.16, 0.76). Furthermore, there was no significant difference in risk of mortality (RR 0.59 95% CI 0.12, 3.02). Dexmedetomidine also significantly increased the risk of bradycardia (RR 2.78 95% CI 2.00, 3.87). There was no significant difference in risk of tachycardia (RR 0.59 95% CI 0.12, 3.02) or hypotension (RR 1.07 95% CI 0.64, 1.81). Conclusions: Our study demonstrates that the dexmedetomidine reduces the risk of VA by 65% compared to control. Further prospective research is necessary to clarify the antiarrhythmic and sedative properties of dexmedetomidine and its potential effect on patient outcomes.
Increasing Incidence of Pediatric <i>Clostridioides difficile </i>Colonization—More Exploration Is Needed—Reply
Authors: Stephen B. Freedman, Phillip I. Tarr, Sarah Tougas
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
IOTG-03. Rapid intraoperative flow cytometry of brain tumor useful for surgical decision-making
Authors: Yoshihiro Muragaki, Shunichi Koriyama, Taiichi Saito, Masayuki Nitta, Takashi Komori, Takakazu Kawamata
Journal: Neuro-Oncology (2021)

Abstract Flow cytometry is a measuring device frequently used in basic research, we have developed a fully automatic flow cytometer device that performs cell isolation, staining of cell nuclei, and measurement for intraoperative diagnosis. Placing a small specimen in a reagent containing PI calculates, the total number of cells, the DNA histogram, and the Malignancy Index (MI), which means in the proliferation phase, the ratio of the number of cells (S, G2, M) / total number of cells. The major feature of this device is that calculating takes only 10 minutes by thoroughly reviewing the process. We here introduce our study of this device, rapid diagnosis, WHO grading, prognosis in glioma, and differentiation from malignant lymphoma (PCNSL), then how to use it in decision making in the operation. In the analysis of 323 gliomas, the threshold between the peripheral brain and the tumor was 7%, and the MI value was correlated with WHO grade (II 13%, III 35%, IV 47%) (J Neurosurg 2013). A correlation was also found between the MI value and the number of residual tumors (Brain Tumor Path 2018). Furthermore, it was also useful for differentiating from PCNSL with many S-phase cells (World Neurosurg 2018). In addition, the relationship between the presence of DNA aneuploidy and poor prognosis in 102 grade II patients (Clin Neuro Neurosurg 2018), and the high MI in 102 grade IV patients showed a good prognosis and an inverse correlation with expectations (Neurosurg 2018). Intraoperative flow cytometry has enabled various intraoperative decision-making support by converting intraoperative histology, which was an analog-like transmission, into digitized histological information. In the future, the development of this research makes expectations for more accurate diagnosis and prediction by artificial intelligence and the development of other departments.
Abstract 10677: Skeletal Muscle Sirt3 Deficiency-Mediated Loxl2 Secretion in Remote Pulmonary Vascular Remodeling and Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction
Authors: Jia-rong Jheng, Kentaro Noda, Gunner Halliday, Yang Bai, Huot R Joshua, Todd Cook, Dmitry A Goncharov, Andrea L Frump, Elena Goncharova, Marc Simon, Daniel E Forman, Mauricio Rojas, Andrea Bonetto, Roberto F MacHado, Mark T Gladwin, Yen Lai
Journal: Circulation (2021)

Background: Pulmonary hypertension in the context of heart failure with preserved ejection fraction (PH-HFpEF) is the most common cause of PH worldwide. However, major pathways involved in the regulation of PH-HFpEF are still not well understood. We have recently reported on a role of skeletal muscle sirtuin-3 (SIRT3) in modulating PH-HFpEF. In this study, we attempted to define the processes by which skeletal muscle SIRT3 defects affect pulmonary vascular health in PH-HFpEF. Methods and Results: Skeletal muscle-specific Sirt3 knockout mice ( Sirt3 skm-/- ) exhibited drastically reduced pulmonary vascular density accompanied by pulmonary vascular proliferative remodeling and elevated pulmonary pressures. Using global mass spectrometry-based comparative secretome analysis, we found elevated secretion of lysyl oxidase homolog 2 (LOXL2) in SIRT3-deficeint skeletal muscle cells. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of Sirt3 skm-/- mice, rats with experimental PH-HFpEF (SU5416/Obese ZSF1, Ob-Su), and patients with PH-HFpEF. Interestingly, expression levels of the tumor suppressor WW domain-containing oxidoreductase (WWOX), which plays a housekeeping role in repressing cellular proliferation, were decreased in PASMCs from Sirt3 skm-/- mice. Reduced WWOX expression levels were also detected in PASMCs from Ob-Su rats and human subjects with obesity and diabetes. Treatment with LOXL2 recombinant protein resulted in reduced WWOX expression ex vivo in precision-cut lung slices (PCLS) and in vitro in PASMCs. Media conditioned by SIRT3-deficient skeletal muscle cells reduced WWOX expression in PASMCs, concomitant with increased PCNA levels and cellular proliferation. Finally, knockdown of both SIRT3 and LOXL2 in skeletal muscle cells or suppression of LOXL2 with β-aminopropionitrile (BAPN) restored WWOX and PCNA levels in PASMCs. Conclusions: These studies indicate a systemic pathogenic impact of skeletal muscle SIRT3 deficiency in remote pulmonary vascular remodeling and PH-HFpEF. These studies also reveal a new endocrine signaling axis that links skeletal muscle SIRT3 deficiency to remote WWOX regulation in the pulmonary vasculature through myokine LOXL2.
Abstract 11640: Longitudinal Changes in Ventricular Torsion in Adolescents with Single-Ventricle Anatomy: Long Term Follow Up
Authors: Safwat Aly, Luc L Mertens, Mark K Friedberg, Lars Grosse-Wortmann, Andreea Dragulescu
Journal: Circulation (2021)

Background: Ventricular torsion is important in assessment of the systolic and diastolic function especially in single ventricle (SV) but is poorly studied. Objective: We aimed to a) examine serial changes in SV torsion, and b) examine its association with CMR data and exercise performance. Methods: We retrospectively studied SV patients after Fontan completion. Speckle-tracking echocardiography was used to evaluate serial changes in ventricular mechanics; strain, torsion, and untwist. CMR volumetric data and cardiopulmonary exercise data closest to echocardiograms were obtained. The most recent follow up echocardiographic and CMR data were compared to data before Fontan. Results: 45 SV patients (27 LV, 12 RV, and 6 co dominant) were studied. Demographics, echocardiographic, CMR, and exercise data are shown in table 1. Mean time at follow up echo from time of Fontan was 12.8 (10.6-16.6) years. Follow up echocardiograms showed reduced global longitudinal strain [-17.5(-6.5 to-19.5) vs -19.8 (-12 to -23%), p=0.01], circumferential strain [-15.7 (-8.4 to - 20.7) vs [-18.9 (-11.2 to -25.0), p=0.009], reduced torsion [5.5°/cm (-6.1 to 17.8) vs 8.1°/cm (-9.7 to18.5) vs, p=0.03], decreased apical rotation [6.5°/cm (-11.3 to 18.1) vs 5.1°/cm (-21.2 to 19.7), p=0.02] with no significant change in basal rotation compared to the echo at time of Fontan. Single RV had lower net torsion compared to single LV [2.7°/cm (-2.5.1 to 13.1) vs 6.1°/cm (-6.3 to 19.5) vs, p=0.03]. Mean interval between echocardiograms and exercise testing and CMR were 3.5±2.2 and 5.6±1.8 months respectively. Torsion and untwist rates correlated with peak oxygen consumption (r=0.64, -0.41, p=0.01, 0.04 respectively) but did not correlate with ventricular volumes or ejection fractions. Conclusion: In long term follow up post Fontan, SV torsion is decreased due to decreased apical rotation, worse in single RV, and is associated with decreased exercise capacity.
Abstract 11074: Worsening Renal Function in Acute Heart Failure in the Context of Diuretic Response
Authors: Lisa E Emmens, Jozine M ter Maaten, Yuya Matsue, Sylwia M Figarska, Iziah Sama, Gad Cotter, John Cleland, Beth Davison, Michael Felker, Michael M Givertz, Barry Greenberg, Peter S Pang, Thomas Severin, Claudio R Gimpelewicz, Marco Metra, Adriaan A Voors, John R Teerlink
Journal: Circulation (2021)

Background: For patients with acute heart failure (AHF), a substantial diuresis after administration of loop diuretics is generally associated with better clinical outcomes but may cause creatinine to rise, suggesting a decline in renal function. We investigated the interaction between diuretic response and worsening renal function (WRF) on clinical outcomes in patients with AHF. Methods: In two cohorts of patients with AHF (PROTECT, n=1,698 and RELAX-AHF-2, n=5,586 in current analysis), the prognostic impact of WRF (creatinine ≥0.3 mg/dL increase baseline-day 4, sensitivity analyses were performed incorporating baseline renal function) by diuretic response (kg weight loss per 40 mg furosemide equivalent from baseline-day 4) was investigated with regards to (CV) death or cardiovascular/renal hospitalisation using subpopulation treatment effect pattern (STEPP) plots and survival analyses. Results: WRF occurred in 286 (16.8%) patients in PROTECT and 1,031 (18.5%) patients in RELAX-AHF-2. Patients with WRF had higher left ventricular ejection fraction and lower estimated glomerular filtration rate at baseline (P&lt;0.05). Patients with WRF also received higher doses of loop diuretics and had a worse diuretic response (all P&lt;0.001). In patients with a poor diuretic response (≤0.35 kg weight loss/40 mg furosemide equivalent as identified by STEPP), WRF was associated with a higher risk of (CV) death or cardiovascular/renal hospitalisation (P&lt;0.001 in both cohorts), but this was not the case for patients with a good diuretic response (P=0.900 for both cohorts). Conclusion: In two large cohorts of patients with AHF, WRF in the first 4 days was not associated with worse outcomes when patients had a good diuretic response. The occurrence of WRF in patients with AHF should therefore be considered in the context of diuretic response.
Influenza outcomes in patients with inflammatory joint diseases and DMARDs: how do they compare to those of COVID-19?
Authors: Hannah Bower, Thomas Frisell, Daniela Di Giuseppe, Bénédicte Delcoigne, Johan Askling
Journal: Annals of the Rheumatic Diseases (2021)

To estimate absolute and relative risks for seasonal influenza outcomes in patients with inflammatory joint diseases (IJDs) and disease-modifying antirheumatic drugs (DMARDs). To contextualise recent findings on corresponding COVID-19 risks.Using Swedish nationwide registers for this cohort study, we followed 116 989 patients with IJD and matched population comparators across four influenza seasons (2015-2019). We quantified absolute risks of hospitalisation and death due to influenza, and compared IJD to comparators via Cox regression. We identified 71 556 patients with IJD on active treatment with conventional synthetic DMARDs and biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drug (tsDMARDs) at the start of each influenza season, estimated risks for the same outcomes and compared these risks across DMARDs via Cox regression.Per season, average risks for hospitalisation listing influenza were 0.25% in IJD and 0.1% in the general population, corresponding to a crude HR of 2.38 (95% CI 2.21 to 2.56) that decreased to 1.44 (95% CI 1.33 to 1.56) following adjustments for comorbidities. For death listing influenza, the corresponding numbers were 0.015% and 0.006% (HR=2.63, 95% CI 1.93 to 3.58, and HR=1.46, 95% CI 1.07 to 2.01). Absolute risks for influenza outcomes were half (hospitalisation) and one-tenth (death) of those for COVID-19, but relative estimates comparing IJD to the general population were similar.In absolute terms, COVID-19 in IJD outnumbers that of average seasonal influenza, but IJD entails a 50%-100% increase in risk for hospitalisation and death for both types of infections, which is largely dependent on associated comorbidities. Overall, bDMARDs/tsDMARDs do not seem to confer additional risk for hospitalisation or death related to seasonal influenza.