tbuckley/cabot-search huggingface dataset:
Abstract 343: Effect of Periodic Inspection on Maintenance of the Public Automated External Defibrillators
Authors: Tae Youn Kim, Kyoungchul Cha, Woo Jin Jung, Youngil Roh, So Yeong Kim, Sun Ju Kim, Yoon Kyung Jung, Sun Hwa Yoon, Sung Oh Hwang
Journal: Circulation (2020)

Introduction and purposes: Communities need to pay attention to the maintenance of public access defibrillators (PADs) installed in their jurisdictions to ensure that the PADs are always available. The purpose of this study is to assess the maintenance status of the PAD and to investigate the effect of periodic inspections on the maintenance status of the PAD. Methods: From 2013 to 2018, PADs installed in Seoul Metropolitan area were eligible. After an 8-hour PAD inspection training, an inspector visited the PAD site once a year to check the defibrillator. The inspector checked the maintenance status of the PAD using the checklist and conducted a questionnaire on PAD management from the PAD manager. At the end of inspection, the inspector gave an instruction on PAD maintenance and usage to the person in charge. Results: A total of 18,011 PADs including 3,134 in 2013, 3402 in 2014, 5622 in 2015, 5909 in 2016, 5552 in 2017, and 3615 in 2018 were inspected. During study period, there was a tendency to improve accessibility to PAD including obstacles around the defibrillator (from 9.3% in 2013 to 0.8% in 2018, p trend=0.006) and installation of PAD signs (from 34.3% in 2013 to 99.9% in 2018, p trend=0.007). Maintenance status of PAD was improved in terms of normal operation (from 94.0% in 2013 to 99.7% in 2018, p trend=0.010), normal battery charge status (from 95.6% in 2013 to 99.7% in 2018, p trend=0.037), and availability of valid electrodes (from 97.1% in 2013 to 99.8% in 2018, p trend=0.035). There was no difference in the frequency of actual use to the victims (from 0.7% in 2013 to 1.1% in 2018, p trend=0.803). Conclusions: Periodic inspections improve maintenance status of the PAD and its availability.
Abstract 13770: Experiences of Ethnic Discrimination and COMT Val158Met Polymorphism Are Associated With Depressive Symptoms in Hispanic Adults at Risk for Cardiovascular Disease
Authors: Kaitlin V Key, Steven Estus, Terry A Lennie, Ana Maria Linares, Gia Mudd-martin
Journal: Circulation (2020)

Introduction: There is emerging evidence that ethnic discrimination, commonly experienced among U.S. Hispanics, is associated with depressive symptoms, increasing cardiovascular disease (CVD) risk. Genetic variants in dopaminergic pathways may moderate this association. The catechol-O-methyltransferase Val158Met polymorphism is a potential candidate because the Met allele is associated with increased risk for depressive symptoms. The purposes of this study were to examine associations among ethnic discrimination, Val158Met polymorphism, and depressive symptoms, and to explore if Val158Met moderates the association between discrimination and depressive symptoms in Hispanic adults. Methods: Participants were 124 Hispanic adults with 2+ CVD risk factors. Ethnic discrimination was measured with the Experiences of Discrimination instrument, which measures discrimination experiences across 9 settings (e.g. at work). Scores range from 0 to 45; higher scores indicate more experiences of discrimination. Depressive symptoms were measured using the Patient Health Questionnaire-8. Scores range from 0 to 21; higher scores indicate more depressive symptoms. DNA was isolated from saliva and analyzed for Val158Met genotype. A hierarchical linear regression was conducted adjusting for sex, age, income, education, acculturation, and years in the U.S. Discrimination was entered in Step 1 and Val158Met in Step 2 to examine the association with depressive symptoms. To assess moderation, a discrimination*Val158Met interaction term was entered in Step 3. Results: Participants were aged 40.2 ± 9.3 years and mostly female (74.2%). Discrimination was positively associated with depressive symptoms (p = 0.041). Participants with at least one Met allele at the Val158Met polymorphism had more depressive symptoms than those with a Val-Val genotype (p = 0.049). No moderation effect was found. Conclusion: Findings suggest that discrimination and Val158Met genotype independently influence depression in Hispanic adults, which may increase risk for depression and CVD in certain individuals. This highlights the need to explore mechanisms underpinning these associations, and to address the impact of discrimination on depression and CVD disparities.
Abstract 14479: Fontan Patients With Dominant Left Ventricular Morphology Have Severe Ventricular Electromechanical Discoordination Associated With Worse Exercise Capacity
Authors: Michal Schafer, Nolan Younoszai, Benjamin Frank, Johannes von Alvensleben, Dunbar D IVY, Alexander Barker, Max B Mitchell, James Jaggers, Roni Jacobsen, Adel K Younoszai, Michael V Di Maria
Journal: Circulation (2020)

Introduction: Fontan patients with a single left ventricle (SLV) develop late systolic and diastolic dysfunction. The development of SLV dysfunction has been associated with abnormal loading conditions, myocardial ischemia and fibrosis, and compromised ventricular-aortic coupling. However, electromechanical discoordination, a prime determinant of ventricular performance, has not been adequately evaluated in patients with SLV. Hypothesis: Patients with SLV and Fontan circulation will have abnormal electromechanical discoordination compared to controls, and this will be associated with their functional status. Methods: Patients with SLV (n=20) and healthy controls (n=20) underwent MRI-based tissue deformation analysis. Circumferential strain and strain rate data were used to calculate systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF) (Figure 1). SSF is the proportion of myocardial segments undergoing relaxation in systole, while the DRF is the proportion of myocardial segments undergoing contraction in diastole. SSF and DRF were correlated with standard MRI indices and standard exercise tests. Results: Global circumferential strain was decreased in SLV compared to controls (16.4±2.7 vs 19.9±1.7, P&lt;0.001). SLV had increased median SSF when compared to the LV of controls [(0.023 (IQR: 0.006-0.036) vs. 0.007 (IQR: 0.006-0.013), P=0.023] and increased median DRF [0.39 (IQR: 0.30-0.44) vs. 0.30 (IQR: 0.26-0.32), P=0.002]. SSF correlated with the peak VO 2 index (R=-0.56, P=0.027) and DRF correlated with ejection fraction (R=-0.56, P=0.010). Conclusion: Fontan patients with SLV exhibit systolic and diastolic electromechanical discoordination, which is associated with lower peak VO 2 and reduced ejection fraction, respectively. Electromechanical discoordination might contribute to global SLV dysfunction by limiting both effective contractility and preload generation.
Abstract 14937: Evaluation of Biventricular Functions in Patients With Covid-19 Using Speckle Tracking Echocardiography
Authors: Omer F Baycan, Hasan Ali A Barman, Adem Atici, Mustafa A Tatlisu, furkan bolen, Pinar Ergen, sacit icten, Baris Gungor, Mustafa Caliskan
Journal: Circulation (2020)

Introduction: A new infectious outbreak sustained by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now spreading all around the world. The aim of this study was to evaluate the prognostic value of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) in patients with coronavirus disease 2019 (COVID-19). Hypothesis: As some studies have shown that COVID-19 could affect the cardiovascular system due to the capability of pathogenity of the virus, biventricular functions could be affected in the tissue level even though the routine evaluations of the heart functions seem normal. Methods: In this prospective, single-center study, data were gathered from patients treated for COVID-19, who had biventricular systolic function and no history of coronary artery disease. Two-dimensional echocardiography (2-DE) and speckle tracking echocardiography (STE) images were obtained for all patients. Patients were divided into three groups: those with severe COVID-19 infection, those with non-severe COVID-19 infection, and those without COVID-19 infection (the control group). Data regarding clinical characteristics and laboratory findings were obtained from electronic medical records. The primary endpoint was in-hospital mortality. Results: A total of 100 patients hospitalized for COVID-19 were included in this study. The mean age of the severe group (n = 44) was 59.1 ± 12.9, 40% of whom were male. The mean age of the non-severe group (n = 56) was 53.7 ± 15.1, 58% of whom were male. Of these patients, 22 died in the hospital. In patients in the severe group, LV-GLS and RV-LS were decreased compared to patients in the non-severe and control groups (LV-GLS: -14.5 ± 1.8 vs. -16.7 ± 1.3 vs. -19.4 ± 1.6, respectively [p &lt; 0.001]; RV-LS: -17.2 ± 2.3 vs. -20.5 ± 3.2 vs. -27.3 ± 3.1, respectively [p &lt; 0.001]). The presence of cardiac injury, D-dimer, arterial oxygen saturation (SaO2), LV-GLS (OR:1.63, 95% confidence interval [CI] 1.08-2.47; p = 0.010) and RV-LS (OR:1.55, 95% CI 1.07-2.25; p = 0.019) were identified as independent predictors of mortality via multivariate analysis. Conclusions: LV-GLS and RV-LS are independent predictors of in-hospital mortality in patients with COVID-19.
Abstract 15253: Significant Discrepancies in Quantification of Regurgitant Volume in Primary Mitral Regurgitation Observed on Multimodality Imaging: Is It Time for Reappraisal?
Authors: Agostina M Fava, Rhonda Miyasaka, Marc Gillinov, Per Wierup, Zoran B Popovic, Leonardo Rodriguez, Brian P Griffin, Milind Y Desai
Journal: Circulation (2020)

Introduction: Mitral valve regurgitation volume (RV) can be quantified using proximal isovelocity surface area (PISA) or stroke volume (SV). SV method incorporates mitral annulus (MA) diameter (assumed circular) on 2D transthoracic echo (2D TTE). However, MA area (MAA) can be precisely measured using 3D transesophageal echocardiographic (3DTEE) or computed tomography (CT). Hypothesis: We sought to compare RV obtained using a) PISA b) standard SV using MA diameter on 2D echo and c) modified SV using MAA on 3D TEE and d) MAA on CT. Methods: 37 patients (63±9 years, 81 % men) with severe primary mitral regurgitation (MR) undergoing surgery were prospectively recruited. RV was calculated using a) PISA b) standard SV method using MA diameter on 2D echo (0.785*diameter 2 MV *VTI MV -0.785*d 2 LVOT *VTI LVOT ) c) &amp; d) modified SV methods where MAA (on 3D TEE and CT) were incorporated instead of MA diameter. Results: The mean MAA (cm 2 ) by 2DTTE, 3DTEE &amp; CT were 10.7±3, 10.9 ±3 &amp; 15.9 ±3. Mean RV (cc) by standard SV method, modified SV (3D TEE &amp; CT) &amp; PISA were 294±126, 276±82, 355±127 &amp; 91±51, respectively. Correlations &amp; agreements of SV-based RV are shown in Figure 1. RV was highest using CT-based MAA. The closest agreement was between 2D TTE &amp; CT with a mean error (ME) of -61 cc. There was a large discrepancy in RV derived from PISA vs all SV methods, with a systemic overestimation using SV methods with root mean square errors (RMSE) ranging from 156 to 293 cc Figure 2. Conclusions: In severe MR,calculating RV using SV vs PISA yields vastly different values. The differences are exaggerated using modified SV method incorporating more accurate MAA on 3D TEE or CT. These techniques should not be interchanged to quantify MR.
Abstract 14374: Peripheral Artery Disease and Gait Speed in Women With and at Risk for HIV
Authors: Emily R Cedarbaum, Yifei Ma, Rebecca Scherzer, Adaora A Adimora, Marcas Bamman, Mardge Cohen, Margaret A Fischl, Deborah R Gustafson, Kunihiro Matsushita, Igho Ofotokun, Michael Plankey, Eric C Seaberg, Anjali Sharma, Phyllis C Tien
Journal: Circulation (2020)

Introduction: Peripheral artery disease (PAD) is associated with decreased physical function and increased mortality in the general population. PAD is common in women with and at risk for HIV infection, but its association with functional decline is unclear. We examined the contribution of PAD to gait speed in the Women’s Interagency HIV Study, controlling for traditional cardiovascular risk factors and HIV-related factors. Methods: 1,839 participants (72% HIV+) with measured ankle-brachial index (ABI) and 4-meter gait speed were included in analysis. ABI scores were categorized as: &lt;0.7, moderate-severe PAD; 0.7-&lt;0.9, mild PAD; 0.9-&lt;1.0, borderline PAD; 1.0-&lt;1.1, low-normal; 1.1-1.4, normal. Longitudinal regression models with repeated measures were used to examine the association of PAD category with log-transformed gait speed after controlling for demographic, behavioral, and cardiovascular disease risk factors, and HIV and HCV status. Coefficients represented percentage differences. Results: Median age was 50 years, &gt;70% were Black. Figure 1 shows median gait speed by PAD group. In univariate analysis, compared to normal ABI, each category of PAD severity was associated with slower gait speed: 6% slower for low-normal (95% confidence interval [CI]:4%, 9%), 10% for borderline (95% CI:6%, 13%), 14% for mild (95% CI:9%, 18%), and 16% for moderate-severe (95% CI:5%, 25%). In multivariate analysis, PAD severity remained associated with 6% (95% CI:4%, 9%), 10% (95%CI:7%, 14%), 12% (95%CI:8%, 17%), and 11% (95%CI: -1%, 22%) slower gait speed, respectively. HIV/HCV coinfection reduced gait speed by 9% (95%CI:4%, 14%). Among HIV+ women, neither CD4 count nor HIV viral load was associated with gait speed. Conclusions: In middle-aged women with and at risk for HIV, greater PAD severity is associated with progressively slower gait speed. ABI measurement may be a simple and clinically useful tool for early assessment of functional declines.
The return of malonyl-CoA to the brain: Cognition and other stories
Authors: Rut Fadó, Rosalía Rodríguez-Rodríguez, Núria Casals
Journal: Progress in Lipid Research (2020)

Nutrients, hormones and the energy sensor AMP-activated protein kinase (AMPK) tightly regulate the intracellular levels of the metabolic intermediary malonyl-CoA, which is a precursor of fatty acid synthesis and a negative regulator of fatty acid oxidation. In the brain, the involvement of malonyl-CoA in the control of food intake and energy homeostasis has been known for decades. However, recent data uncover a new role in cognition and brain development. The sensing of malonyl-CoA by carnitine palmitoyltransferase 1 (CPT1) proteins regulates a variety of functions, such as the fate of neuronal stem cell precursors, the motility of lysosomes in developing axons, the trafficking of glutamate receptors to the neuron surface (necessary for proper synaptic function) and the metabolic coupling between astrocytes and neurons. We discuss the relevance of those recent findings evidencing how nutrients and metabolic disorders impact cognition. We also enumerate all nutritional and hormonal conditions that are known to regulate malonyl-CoA levels in the brain, reflect on protein malonylation as a new post-translational modification, and give a reasoned vision of the opportunities and challenges that future research in the field could address.
Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial
Authors: Javier Martin-Broto, Nadia Hindi, Giovanni Grignani, Javier Martinez-Trufero, Andres Redondo, Claudia Valverde, Silvia Stacchiotti, Antonio Lopez-Pousa, Lorenzo D'Ambrosio, Antonio Gutierrez, Herminia Perez-Vega, Victor Encinas-Tobajas, Enrique de Alava, Paola Collini, Maria Peña-Chilet, Joaquin Dopazo, Irene Carrasco-Garcia, Maria Lopez-Alvarez, David S Moura, Jose A Lopez-Martin
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Sarcomas exhibit low expression of factors related to immune response, which could explain the modest activity of PD-1 inhibitors. A potential strategy to convert a cold into an inflamed microenvironment lies on a combination therapy. As tumor angiogenesis promotes immunosuppression, we designed a phase Ib/II trial to test the double inhibition of angiogenesis (sunitinib) and PD-1/PD-L1 axis (nivolumab). Methods This single-arm, phase Ib/II trial enrolled adult patients with selected subtypes of sarcoma. Phase Ib established two dose levels: level 0 with sunitinib 37.5 mg daily from day 1, plus nivolumab 3 mg/kg intravenously on day 15, and then every 2 weeks; and level −1 with sunitinib 37.5 mg on the first 14 days (induction) and then 25 mg per day plus nivolumab on the same schedule. The primary endpoint was to determine the recommended dose for phase II (phase I) and the 6-month progression-free survival rate, according to Response Evaluation Criteria in Solid Tumors 1.1 (phase II). Results From May 2017 to April 2019, 68 patients were enrolled: 16 in phase Ib and 52 in phase II. The recommended dose of sunitinib for phase II was 37.5 mg as induction and then 25 mg in combination with nivolumab. After a median follow-up of 17 months (4–26), the 6-month progression-free survival rate was 48% (95% CI 41% to 55%). The most common grade 3–4 adverse events included transaminitis (17.3%) and neutropenia (11.5%). Conclusions Sunitinib plus nivolumab is an active scheme with manageable toxicity in the treatment of selected patients with advanced soft tissue sarcoma, with almost half of patients free of progression at 6 months. Trial registration number NCT03277924 .
Abstract 17278: Mid-Term Clinical Outcomes of Functionally-Guided Treatment of Coronary Bifurcation Lesions
Authors: Dobirn Vassilev, Niya Mileva, Carlos Collet, Pavel Nikolov, Kiril Karamfiloff, Gianluca Rigatelli, Robert Gil, Patrick W Serruys
Journal: Circulation (2020)

Background: Rates of major adverse cardiac events (MACE) after functionally guided percutaneous coronary intervention (PCI) of coronary bifurcation lesions have not been specifically analysed. Methods: Patients from FIESTA registry (ClinicalTrials.govNCT01724957) with stable angina, bifurcation lesions in a coronary artery with diameter ≥ 2.5 mm and ≤ 4.5 mm and SB diameter≥2.0 mm were included in the analysis. Subjects with ST-segment elevation myocardial infarction, left main disease, hemodynamic instability were excluded. Provisional stenting was the default strategy in all patients. Fractional flow reserve (FFR) was performed using the PrimeWire or PrimeWire Prestige (Volcano Corp., USA). Bifurcation lesion with FFR above 0.80 were deferred from PCI. Follow-up for vital status at every 3-month period was performed and rates of MACE, including cardio-vascular death, nonfatal myocardial infarction and stroke, were analyzed. Results: Overall 165 patients were included, mean age was 67±10 years, 66% males, 72 (44%) had functionally significant bifurcation lesions (FSL) and 93 (56%) were with non-significant lesions (nFSL). There were no differences (FSL vs. nFSL) regarding: dyslipidemia (88% vs 96%), diabetes (44% vs. 32%), smoking (52% vs 40%), previous MI (24% vs 15%), previous PCI (54% vs 49%), atrial fibrillation (17% vs 29%), PAD (10% vs. 9%), renal failure (29% vs 31%) – all p&gt;0.05. On a median follow-up of 34±14 months there were no differences between FSL and nFSL regarding rates of cardio-vascular death -12.5% (n=9/72) vs. 7.5% (n=7/93), p=0.4, MACEs - 13.9% (n=10/72)vs 8.6 (8/93), p=0.512. On multivariate Cox-regression analysis factors associated with occurrence of MACE were: presence of cancer OR 3.692, (CI 0.955-14.269); renal failure OR 2.550, (CI 0.961-6.767) SYNTAX ≥9 OR 1.836, (CI 0.490-6.874); SB RVD ≥ 2.4mm OR 2.546, (CI 0.708-9.160); SB BARI 13.5% OR 2.013, (CI 0.652-6.211); WBC≥7OR 3.647, (CI 0.824-16.134); Platelet count ≥ 256.106/ml OR 3.814, (CI 1.220-11.925). Conclusion: Less than a half of angiographically significant coronary bifurcation lesions were functionally significant requiring stent implantation. The rates of MACE were not-significantly different in deferred and treated stenoses up to 3 years follow-up.
Abstract 16270: Genetic Susceptibility to Stress Associates With Higher Amygdalar Activity and Greater Myocardial Infarction Risk
Authors: Shady Abohashem, Michael Osborne, Karmel W Choi, Tawseef Dar, Ahmed Ghoneem, Taimur Abbasi, Hadil Zureigat, Nicki Naddaf, Zhaowen Liu, Jordan Smoller, Ahmed A Tawakol
Journal: Circulation (2020)

Introduction and Hypothesis: Chronic psychological stress is strongly linked to cardiovascular disease (CVD) risk. Metabolic activity of the amygdala, a stress-associated brain center, robustly associates with high inflammation and CVD risk. We hypothesized that a validated polygenic risk score for neuroticism (nPRS), a broad trait measure of vulnerability to stress, independently associates with 1) heightened amygdalar activity (AmygA) and 2) increased myocardial infarction (MI) risk Methods: Individuals (N=14349; median age (IQR): 64 (52, 74) yrs, 46%male) were identified from the Partners Biobank where genome wide nPRS and principle components of ancestry (PCI) were calculated. Using validated 18 FDG PET/CT imaging methods, AmygA was measured (N=995) as a target-to-background-ratio in individuals with clinical PET/CT imaging. MI was adjudicated using International Classification of Diseases (ICD) diagnoses. Traditional CVD risk factors * and psychiatric history were obtained using ICD codes and questionnaires. Independent t-tests and linear and logistic regression were employed Results: A total of 1708 (12%) individuals experienced MI. nPRS associated with AmygA (standardized β [95% CI]: 0.07 [0.01, 0.13], p=0.02 Fig A ) after adjustment for age, sex, and 10 PCI. It remained significant after additional adjustment for psychiatric history (p=0.02). AmygA also predicted MI in an adjusted model (OR: 1.50, p=0.006 * ). Importantly, after adjustment for age, sex, and 10 PCI, nPRS significantly associated with MI incidence (standardized OR [95% CI]: 1.12 [1.05, 1.17], p&lt;0.001 Fig B ) and remained significant after additional adjustment for CVD factors (p=0.006*) and psychiatric history (p=0.007) Conclusions: These findings show for the first time that a genetic susceptibility to stress (high nPRS) associates with greater stress-related neurobiological activity, and MI risk. Further, these findings suggest nPRS may serve as a novel risk marker for MI