tbuckley/cabot-search huggingface dataset:
Abstract 13695: Neighborhood Perception is Associated With Physical Activity and Nutrition Self-Efficacy Among African Americans: The Washington, DC Cardiovascular Health and Needs Assessment
Authors: Foster Osei Baah, Sam Neally, Valerie Mitchell, Gwenyth R Wallen, Tiffany Powell-wiley
Journal: Circulation (2021)

Background: Although environmental factors influence cardiovascular (CV) health behaviors, like physical activity (PA) and nutrition, relationships between neighborhood environment (NE) perception and self-efficacy related to these health behaviors is unclear. Methods: We explored associations between NE perception and self-efficacy for performing nutrition and PA behaviors aimed at weight loss in the Washington DC CV Health and Needs Assessment, a community-engaged CV health evaluation in lower-resourced DC areas. Participants completed the PA and Nutrition Self-Efficacy (PANSE) scale (higher score=greater self-efficacy) and validated NE perception questions about violence, physical/social environment, social cohesion, and safety (higher scores=more favorable perception). Linear regression models were performed to assess relationships between each neighborhood perception construct and self-efficacy, adjusting for covariates. Results: Participants (N=78) were African Americans (AA), predominantly women (84.6%), with an age range=23-84 (mean 59.5, SD±12.1) years. Perceived neighborhood violence, physical/social environment, social cohesion, and neighborhood safety were significantly and positively associated with self-efficacy (Table 1). After adjusting for socio-demographics, neighborhood violence and safety remained significantly associated with self-efficacy, where more favorable perceptions about violence and safety associated with greater self-efficacy. Perceptions of physical/social environment were marginally associated with self-efficacy. Conclusion: Favorable NE perceptions about violence and safety are associated with increased self-efficacy for performing PA and nutrition behaviors aimed at weight loss. Interventions and public health policies tailored for improving NE perceptions may enhance self-efficacy for nutrition and PA behaviors aimed at weight loss in AAs.
Abstract 13267: The Shifted Balance of Arginine Metabolites in Patients With Acute Myocardial Infarction and Its Association With the Composition of the Infarct-Related Culprit Lesion
Authors: Patrycja Molek, Aleksandra Wlodarczyk, Pawel Zmudzki, Radoslaw Rychlak, Mateusz Wnuk, Jadwiga Nessler, Jaroslaw Zalewski
Journal: Circulation (2021)

Introduction: We hypothesize that acute phase of myocardial infarction (MI) is associated with suppression of nitric oxide synthase (NOS) and enhanced arginase activity. Moreover, this altered metabolic balance might correlate with the composition of vulnerable culprit lesion in the infarct-related coronary artery (IRA). Methods: Arginine metabolites (μM) including ornithine, citrulline, proline, spermine, spermidine, agmatine, homoarginine, creatine, asymmetric dimethylarginine (ADMA) and monomethyl-L-arginine acetate were measured using liquid chromatography and tandem mass spectrometry in 85 consecutive MI patients upon admission and at 6-month follow-up and were compared with the composition of the IRA culprit lesion assessed with optical coherence tomography (OCT). Results: The concentration of ornithine in acute phase of MI was higher by 44% and homoarginine by 62% whereas level of arginine was lower by 39% and citrulline by 64% (P&lt;0.001 for all), when compared to 6-month stable conditions. Following ischemia, the ratios of citrulline/arginine (0.10 [0.08; 0.14] vs 0.22 [0.18; 0.28]) and citrulline/ornithine (0.09 [0.07; 0.12] vs 0.47 [0.36; 0.55]) were decreased while the indices of ornithine/arginine (1.48 [1.08, 2.39] vs 0.50 [0.41, 0.60]) and homoarginine/arginine (0.17 [0.12; 0.22] vs 0.04 [0.03; 0.05]) were higher as compared with 6-month results (P&lt;0.001 for all). Both, concentrations of arginine metabolites and their ratios were not associated with the mechanism of IRA occlusion, the amount of calcium or lipids and the presence of intramural hematoma. However, in patients with (n=67) versus without (n=18) thin-cap fibroatheroma (TCFA) in OCT the higher median concentrations of ornithine (10.24 [7.86; 12.52] vs 7.82 [4.38; 9.57]), ADMA (0.40 [0.29; 0.49] vs 0.29 [0.23; 0.42]), homoarginine (1.02 [0.81; 1.27] vs 0.74 [0.62; 1.00]) and a higher ornithine/arginine ratio (1.73 [1.29; 2.54] vs 1.18 [1.01; 2.07]) with a lower citrulline/ornithine ratio (0.07 [0.09; 0.11] vs 0.13 [0.09; 0.15]) were found (P&lt;0.05 for all). Conclusions: During acute phase of MI the altered balance of arginine metabolites indicates NOS suppression and enhanced arginase activation and is associated with the presence of TCFA in IRA culprit lesion.
Abstract 11216: Applicability of US Food and Drug Administration Labeling for Dapagliflozin to Patients with Chronic Kidney Disease in the National Health and Nutrition Examination Survey (NHANES) 2017-2018 Data
Authors: Joanna Huang, Juan Jose Garcia Sanchez, Stephen Nolan, John Guzek, Lise Retat, Laura Webber, Anjay Rastogi
Journal: Circulation (2021)

Introduction: Patients with chronic kidney disease (CKD) lack evidence-based therapeutic options to delay progression to end-stage kidney disease (ESKD) and reduce the risk of CV events. Dapagliflozin has been shown to reduce the risk of sustained eGFR decline, ESKD, hospitalization for heart failure, CV death and all-cause mortality, in adults with CKD at risk of progression. To determine the dapagliflozin-eligible CKD population in the US, and to understand the presence of CV comorbidities and use of key medications, NHANES was evaluated. Methods: The dapagliflozin-eligible population was extracted from NHANES 2017-2018 data. Inclusion criteria were: UACR ≥ 30 mg/g and/or an eGFR &lt; 60 mL/min/1.73 m 2 in line with the approved indications for dapagliflozin. These patients are at risk of CKD progression, CV events and premature mortality, according to KDIGO 2012 CKD guidelines. Dialysis patients were excluded. Sampling weights were generated using NHANES analytical guidance. The data set was scaled in line with the US population. Results: NHANES data indicate that, of the adult US population, 35,422,098 individuals (14.4%) are eligible for dapagliflozin treatment. Of those eligible, 64.5% are non-Hispanic white, 13.2% are Hispanic, and 12.4% are non-Hispanic black. Non-Hispanic Asian and other races account for the remaining 10%. Among the eligible population, 22,104,903 individuals (62.6%) have hypertension, 10,998,581 (32.1%) have diabetes, 3,186,685 (9.1%) have a history of stroke, 2,755,256 (7.9%) have previous myocardial infarction, and 2,688,886 (7.7%) have heart failure. Renin-angiotensin-aldosterone system (RAAS) inhibitor therapy is used in 43% of these individuals. Conclusions: NHANES 2017-2018 data indicate a substantial dapagliflozin-eligible CKD population in the US. These patients are at risk of progression to ESKD or CV complications and could benefit from the availability of effective treatment options.
Abstract 11217: Adverse Events Associated with AV Node Ablation in Patients with an Implanted Leadless Pacemaker
Authors: Robert Hauser
Journal: Circulation (2021)

Introduction: The Micra leadless intracardiac pacemaker (LICP) is an FDA-approved right ventricular pacemaker that has been available worldwide since 2016. It is frequently implanted in patients who have atrial fibrillation and who undergo atrioventricular node ablation (AVN-AB) for rate control. The potential adverse effects of AVN-AB on LICP performance and function are unknown. Hypothesis: AVN-AB may increase LICP pacing thresholds and/or cause exit block or damage the LICP's electronics. Methods: The FDA Manufacturers and User Facility Device Experience (MAUDE) database was searched for Micra LICP adverse events associated with AVN-AB that were submitted by the manufacturer and received by the Food and Drug Administration from 2016-April 2021. Results: The search found 19 cases of pacing threshold elevation following AVN-AB that were performed during (n=9) or after (n=10) LICP implantation. Exit block resulted in asystole or marked bradycardia in 12 patients (63.2%); 2 of these patients required cardiopulmonary resuscitation. In 8 patients, a persistently high threshold or exit block required LICP replacement with either a new LICP or a transvenous pacemaker. Four explanted LICPs were returned and analyzed by the manufacturer and no pulse generator electronic abnormalities were found. Conclusions: AVN-AB during or after LICP implantation may result in persistently high pacing thresholds or exit block and necessitate LICP replacement; this appears to be a local effect at the LICP electrode-tissue interface rather than effects on LICP electronic function. Additional clinical safety data are needed, especially since patients may be rendered pacemaker-dependent after AVN-AB.
Abstract 14585: Chronic Treatment With a Mavacamten-Like Myosin-Modulator (MYK-581) Blunts Disease Progression in a Mini-Pig Genetic Model of Non-Obstructed Hypertrophic Cardiomyopathy: In Vivo Evidence for Improved Relaxation and Functional Reserve
Authors: Carlos L del Rio, Aprajita Yadav, Brian S Ferguson, Christopher Zambataro, Trisha Smit, Frank Rohret, John Swart, Lee-Jae Guo, Allison Hargraves, Julie Grinde, Vidya Sridhar
Journal: Circulation (2019)

Introduction: Hypertrophic cardiomyopathy (HCM) is a heritable disease characterized by cardiac remodeling, impaired relaxation, and exertional intolerance. Direct myosin-attenuation with Mavacamte...
Abstract 13156: Acute Myocardial Infarction With Biventricular Thrombi Due to Blunt Thoracic Trauma
Authors: Jacob Mok, Saad Sikanderkhel, Hannah Moody, Dharmendra Patel, Patrick Stevens, Harish Manyam
Journal: Circulation (2021)

To our knowledge, this is the first ever reported case of biventricular thrombi with acutemyocardial infarction following blunt thoracic wall trauma. We present a case of a man who presented with non-ST segment elevation myocardial infarction with left anterior descending artery (LAD) occlusion and biventricular thrombi after a blunt thoracic wall trauma. Clinical Vignette: A 56-year-old man with past medical history of diabetes mellitus and hypothyroidism presented to our ED with dizziness after motor vehicle collision. Initial workup revealed biventricular thrombi, pulmonary embolus, and dural sinus thrombosis. 2D echocardiogram showed decreased systolic function with ejection fraction of 15% and enlargement of both ventricles with biventricular thrombi. Serial troponin I levels consistently elevated from 0.3 to 0.6. After initiating cangrelor and heparin infusion, patient underwent coronary angiography which revealed LAD occlusion with a thrombus. Patient then successfully underwent mechanical thrombectomy with restoration of TIMI grade III blood flow. Discussion: Hence, we presented the first ever reported case of biventricular thrombi with LAD occlusion resulting from blunt thoracic wall trauma. While trauma induced musculoskeletal pain may mask symptoms of myocardial infarction, a high index of suspicion for acute coronary syndrome can lead to desirable outcomes in such patients.
Abstract 10293: The Association of Fibroblast Growth Factor-23 with Cardiac Structure and Function in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yasuyuki Honda, Junichi Ishigami, Manabu Hishida, Amy Karger, Dalane W Kitzman, Josef Coresh, Elizabeth Selvin, Pamela L Lutsey, Amil M Shah, Kunihiro Matsushita
Journal: Circulation (2021)

Background: Fibroblast growth factor-23 (FGF-23), a protein regulating phosphorus levels, is associated with the risk of heart failure, particularly in patients with chronic kidney disease (CKD), and with left ventricular (LV) hypertrophy in CKD. However, few studies have explored this association in the general population, and it is unknown whether FGF23 is associated with other parameters of cardiac structure and function. Methods: Among 5,533 Black or White participants attending Visit 5 (2011-2013) of the community-based ARIC study, we quantified the cross-sectional association of serum FGF-23 levels with echocardiographic measures of cardiac structure and function after accounting for potential confounders including kidney function. Results: Mean age was 76 [SD 5] years, 58 % were women, and 21 % were Black. Among the echocardiographic parameters tested ( Table ), higher FGF-23 levels were robustly associated with LV hypertrophy (adjusted odds ratio [aOR] 1.35 [95%CI 1.02-1.79] in top vs. bottom quartile), abnormal peak longitudinal strain (aOR 1.88 [1.32-2.69]), and left atrial enlargement based on left atrium volume index (aOR 1.34 [1.05-1.70]). No association was observed with E/e’ ratio. Higher FGF-23 was also associated with end-diastolic right ventricular (RV) enlargement (aOR 1.36 [1.04-1.78]). Similar results were observed when echocardiographic measures were modeled as continuous variables and when we stratified participants by demographics (age, sex, and race) or a history of cardiovascular disease. Conclusions: In community-dwelling older adults, in addition to LV hypertrophy, FGF-23 was associated with LV systolic and diastolic function as well as RV size, independent of kidney function and other potential confounders. These findings further support the involvement of FGF-23 in the pathophysiology of cardiac remodeling.
DDRE-19. SPHINGOSINE KINASE 1 AS A THERAPEUTIC TARGET FOR IDH1-R132H mut GLIOMA
Authors: Tyrone Dowdy, Tomohiro Yamasaki, Lumin Zhang, Orieta Celiku, Adrian Lita, Victor Ruiz Rodado, Mark Gilbert, Mioara Larion
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Our study aimed to identify vulnerabilities within sphingolipid metabolism with potential to translate to therapeutics. While the vital role of sphingolipids in maintaining rheostat balance and as secondary messengers for signaling pathways (involving proliferation, invasion, migration, and angiogenesis) has been well-documented, their role has not been widely investigated in gliomas. Therefore, metabolic analysis of sphingolipid pathway for IDH1-R132H (IDH1 mut ) glioma cell lines was conducted in order to elucidate susceptible targets. METHODS Global sphingolipid quantification utilized high-throughput LCMS analysis. Pathway protein expression was measured via Western blots in vitro and derived from patients using The Cancer Genome Atlas analysis. RESULTS We probed the impact of decreasing D-2HG on the sphingolipid metabolism after treating a panel of IDH1 mut glioma cells with IDH1-R132H mut inhibitor, AGI5198. This revealed significant downregulation of N,N-dimethylsphingosine (NDMS), C17-sphingosine, and C18-sphinganine. Coincidentally, sphingosine-1-phosphate (S1P) was significantly upregulated in these gliomas. We conducted rational drug screen which revealed that inhibition of SPHK1 with N,N-dimethylsphingosine in combination with C17-sphingosine triggered biostatic dose-response across IDH1 mut gliomas and low impact on IDH WT glioblastoma (GBM) cells. Western analysis revealed that the IDH1 mut gliomas and IDH WT GBM expressed sphingosine kinase-1 (SPHK1). Data also unveiled a discovery that SPHK2 was highly expressed in the GBM cells while remarkably absent in the glioma cells. CONCLUSION Herein, we provide evidence that certain IDH1 mut gliomas present epigenetic silencing of SPHK2 which creates dependency on SPHK1 for S1P; thus, increasing sensitivity to targeting sphingolipid metabolism, and creating susceptibility to proliferation arrest and subsequent cellular death. S1P production has been reported to be elevated particularly for malignant glioblastomas in prior studies; whereas our research revealed that it is relatively low in IDH mut by comparison with IDH WT tumor cells. These findings suggest targeting the sphingolipid metabolism may present a promising strategy to improve survival for patients diagnosed with IDH1 mut gliomas.
Myostatin - A Circulating Biomarker Correlating with Disease in Myotubular Myopathy Mice and Patients
Authors: C Koch, S Buono, A Menuet, A Robe, S Djeddi, C Kretz, R G Oca, M Depla, A Monseur, L Thielemans, L Servais, J Laporte, B Cowling, M Annoussamy, A Seferian, J Baets, N Voermans, A Behin, U Schara, A D'Amico, A Hernandez, C de lattre, Arnal J-M., M Mayer, Cuisset J-M., C Vuillerot, S Fontaine, R Bellance, Grp N-Cs.
Journal: Molecular Therapy (2020)
Hospital delivery and neonatal mortality in 37 countries in sub-Saharan Africa and South Asia: An ecological study
Authors: Anna D. Gage, Günther Fink, John E. Ataguba, Margaret E. Kruk
Journal: PLoS Medicine (2021)

Widespread increases in facility delivery have not substantially reduced neonatal mortality in sub-Saharan Africa and South Asia over the past 2 decades. This may be due to poor quality care available in widely used primary care clinics. In this study, we examine the association between hospital delivery and neonatal mortality.We used an ecological study design to assess cross-sectional associations between the share of hospital delivery and neonatal mortality across country regions. Data were from the Demographic and Health Surveys from 2009 to 2018, covering 682,239 births across all regions. We assess the association between the share of facility births in a region that occurred in hospitals (versus lower-level clinics) and early (0 to 7 days) neonatal mortality per 1,000 births, controlling for potential confounders including the share of facility births, small at birth, maternal age, maternal education, urbanicity, antenatal care visits, income, region, and survey year. We examined changes in this association in different contexts of country income, global region, and urbanicity using interaction models. Across the 1,143 regions from 37 countries in sub-Saharan Africa and South Asia, 42%, 29%, and 28% of births took place in a hospital, clinic, and at home, respectively. A 10-percentage point higher share of facility deliveries occurring in hospitals was associated with 1.2 per 1,000 fewer deaths (p-value < 0.01; 95% CI: 0.82 to 1.60), relative to mean mortality of 22. Associations were strongest in South Asian countries, middle-income countries, and urban regions. The study's limitations include the inability to control for all confounding factors given the ecological and cross-sectional design and potential misclassification of facility levels in our data.Regions with more hospital deliveries than clinic deliveries have reduced neonatal mortality. Increasing delivery in hospitals while improving quality across the health system may help to reduce high neonatal mortality.
Visualising SARS-CoV-2 transmission routes and mitigations
Authors: Harry Rutter, Simon Parker, Will Stahl-Timmins, Catherine Noakes, Alexandra Smyth, Ron Macbeth, Shaun Fitzgerald, Alexandra L J Freeman
Journal: BMJ (2021)

<h3>Objectives</h3> To test the hypothesis that people with concurrent diagnosis of epilepsy and psychogenic nonepileptic seizures (PNES) are at increased risk of attempting suicide as compared to people with epilepsy or PNES alone. To report on suicide rates. <h3>Methods</h3> Retrospective cohort study from the UK largest tertiary mental health care provider, with linked nationwide admission and mortality data from the Hospital Episode Statistics and Office for National Statistics. Participants were 2460 people with a primary or secondary diagnosis of epilepsy, PNES or concurrent epilepsy and PNES attending between 1 January 2007 and 18 June 2021. The primary outcome was a first hospital admission for suicide attempt (International Classification of Diseases, version 10 X60–X84). <h3>Results</h3> 9% of participants had at least one suicide attempt-related hospital admission. For people with concurrent diagnosis of epilepsy and PNES, the odds for suicide attempt-related admissions were 2.52 times the odds of people with epilepsy alone (OR 0.40; 95% CI 0.21 to 0.79; p=0.01). Odds were comparable between people with concurrent diagnosis and people with PNES alone (OR 0.75; 95% CI 0.41 to 1.48; p=0.40). Post hoc analyses revealed that the odds of people with PNES alone were 1.93 times the odds of people with epilepsy alone (OR 0.52; 95% CI 0.38 to 0.70; p&lt;0.001). <h3>Conclusions</h3> People with concurrent diagnosis of epilepsy and PNES or PNES alone have significantly increased odds of hospitalisation due to suicide attempt as compared to people with epilepsy alone (152% and 93% increase, respectively). These findings have direct implications for the clinical management of suicide risk in people with epilepsy.
Efficacy and Safety of Eltrombopag Combined with Cyclosporine As First-Line Therapy in Adults with Severe Acquired Aplastic Anemia: Results of the Interventional Phase 2 Single-Arm Soar Study
Authors: Carlos Vallejo, Jun Ho Jang, Carlo Finelli, Efreen Montaño Figueroa, Lalita Norasetthada, Rodrigo T. Calado, Mehmet Turgut, Regis Peffault De Latour, Ulrike Kriemler-Krahn, Jens Haenig, Joan Maier, Phillip Scheinberg
Journal: Blood (2021)
Abstract 11055: Length of Anticoagulation Treatment in Provoked VTE - Lessons from the Maqi <sup>2</sup> Collaborative
Authors: Elizabeth Joyce, Brian Haymart, Xiaowen Kong, Mona Ali, Scott Kaatz, Eva M Kline-rogers, Jay Kozlowski, James B Froehlich, Mara Carrigan, Geoffrey Barnes
Journal: Circulation (2021)

Introduction: Anticoagulation (AC) with warfarin or direct oral anticoagulants (DOAC) is the core of VTE treatment. Due to lower risk of VTE recurrence, American College of Chest Physicians (ACCP) recommends three months AC in patients with provoked VTE and without other indication for long-term AC. We aimed to assess how closely “real world” practice followed guideline recommendations. Hypothesis: We hypothesize most patients taking warfarin or DOAC for provoked VTE receive no more than three months AC. Patients who get prolonged AC are more likely to be taking DOAC than warfarin. Methods: We identified patients who initiated warfarin or DOAC from a six center AC clinic registry between 2008-20. Provoked VTE was defined as VTE after a transient risk factor: surgery, lower extremity cast/immobilization, childbirth, or OCPs. AC duration was categorized as &lt;80, 80-120, or &gt;120 days. Appropriate treatment window was defined as 80-120 days to adjust for variability in clinic scheduling. Median AC length for DOAC vs. warfarin was compared with a two-sample test. Prevalence of extended AC was compared using chi-square test. Variables increasing risk of extended AC were analyzed with logistic regression, adjusted for baseline demographic and clinical characteristics. Results: At six centers, we identified 488 patients with provoked VTE on warfarin and 302 on DOAC. Average AC length was 137 days for warfarin and 180 days for DOAC (p&lt;0.0001). 266 (54.5%) patients on warfarin and 215 (71.2%) on DOAC got &gt;120 days of AC (p&lt;0.001). Variables increasing risk of &gt;120 days AC include recurrent VTE (OR 2.11; CI 1.34,3.32), prior MI (OR 4.09; CI 1.37,12.2), and DOAC use (OR 2.34; CI 1.69, 3.23) (Figure 1). Conclusions: In this multi-center analysis, most patients receive AC longer than guideline-recommended. DOAC use, recurrent VTE, and prior MI are associated with prolonged AC. Understanding the relationship between prior MI and AC duration in provoked VTE warrants future investigation.
Glucose metabolism enzymes gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer (CRC)
Authors: E. Ongaro, A. Ruzzo, E. Giacomini, T. Ricciardi, G. Aprile, F. Loupakis, P. Lorenzini, F. Zoratto, C. Cremolini, V. Catalano, D. Sarti, E. Rullia, M. De Nictolis, G. DeMaglio, A. Falcone, G. Fiorentini, M. Magnani, F. Graziano
Journal: Annals of Oncology (2015)