tbuckley/cabot-search huggingface dataset:
Abstract 15246: Sex-Biased Preoperative Circulating MicroRNA Levels in Patients Who Developed Postoperative Heart Failure With Preserved Ejection Fraction
Authors: Farhan Rizvi, Stacie Kroboth, Larisa Emelyanova, Gracious Ross, Maharaj Singh, David Kress, A Jamil Tajik, Arshad Jahangir
Journal: Circulation (2020)

Introduction: Acute postoperative heart failure (PoHF) is encountered in 20-35% of elderly patients after cardiac surgery but predictors are not well defined. Circulating microRNAs (miRNAs) predict HF or postoperative atrial fibrillation, yet, their role in identifying those at risk for PoHF with preserved LV function and gender-related differences is not known. Hypothesis: miRNAs involved in CVD can identify patients who develop PoHF in gender-specific manner. Methods: Preoperative blood samples from patients with preserved LV function undergoing cardiac surgery with no prior history of HF, supraventricular, or ventricular tachycardia was used for RNA isolation. Differences in relative plasma levels of miRNA between PoHF vs. No-PoHF were assessed using qPCR. Univariate and multiple logistic regressions were performed to assess risk factors for PoHF. Results: Out of 68 patients (mean age 68.3±12.4), 13 (19%) developed PoHF (54% males; mean age 64.1±15.1; p=0.23), while 55 (51% males; mean age 69.3y ± 11.6) remained free of PoHF. Although all patients had preserved LV function, those who developed PoHF had lower LVEF, (52 vs 58; P&lt;0.05). No significant differences were observed in the prevalence of hypertension, diabetes, myocardial infarction, heart failure, stroke, COPD, or the use of cardiac medications. Out of 13 miRNAs analyzed, stepwise discriminant analysis showed miR-423 (11-fold), -187 (6-fold), -26a2 (4-fold), and -15b (-1.9-fold) were significantly (p&lt;0.05) altered in patients who developed PoHF. When miRNAs were assessed for gender differences, levels of only four miRNAs [miR-423(P&lt;0.01), -23b2(p&lt;0.05), -15b1(p&lt;0.01), and -29b (p&lt;0.05)] principally involved in TGFβ1-SMAD 2/3 regulated extracellular matrix (ECM) turnover pathways were significantly altered in male but not in female patients who developed PoHF compared to No-PoHF group. Conclusions: The differences in preoperative miRNA expression in pathways involved in ECM turnover in male patients who develop PoHF is suggestive of pathophysiological substrate differences between males and females and identifies a group at risk of PoHF with preserved LV function.
Abstract P188: Anxiety Is Associated With Six-year Blood Pressure Change And Incident Hypertension: Findings From The Hispanic Community Health Study/ Study Of Latinos
Authors: Carlos E Rosas, Amber Pirzada, Ramon A Durazo-Arvizu, Lisa A Sanchez-Johnsen, krista perreira, Linda Gallo, Gregory A Talavera, Tali Elfassy, Sylvia W Wassertheil-smoller, Maria Llabre, Jianwen Cai, Martha L Daviglus
Journal: Circulation (2021)

Introduction: Prior research on the association of anxiety with hypertension has yielded mixed results. Despite the high burden of both conditions in Hispanics/Latinos, little is known about their association in this population. This study examined the longitudinal relationship of trait anxiety with changes in BP and incidence of hypertension. Hypothesis: Higher trait anxiety at Visit 1 (V1) will be associated with greater increases in BP and incident hypertension over 6 years. Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multi-center prospective community-based study of 16,415 diverse Hispanics/Latinos ages 18-74 at V1 (2008-11). Data included 11,048 participants with complete information on BP, trait anxiety, and other variables at V1 and V2 (2014-17). Trait anxiety was measured at V1 using the 10-item Spielberger Trait Anxiety Scale, which was dichotomized into low and high using a cut-point of 20 points, the top quartile in the HCHS/SOL cohort. BP was measured using a standardized protocol and validated automated device. Hypertension was defined as systolic BP ≥ 140 or diastolic BP ≥ 90 mm Hg or self-reported antihypertensive medication use. Linear regressions were used to examine the association of anxiety with BP change; to account for medication use, 9 mmHg and 6 mmHg were added to systolic and diastolic BP of treated participants, respectively. The association of anxiety with incident hypertension at V2 was examined using Poisson regression among those without hypertension at V1 ( N = 7,878). Estimates were adjusted for complex survey design, sociodemographic factors, baseline BP, antidepressant/anxiolytic medication use, and health conditions. Results: Mean baseline age was 45.8 years and 60% were women. Mean change was 3.13 ( SE = 15.67) in systolic and 0.21 ( SE = 9.73) in diastolic BP. Individuals with high, compared to those with low, trait anxiety had greater increases in systolic ( B = 1.10, 95% CI = 0.28-1.93, p = 0.009) and diastolic BP ( B = 0.69, 95% CI = 0.11-1.27, p = 0.02) over 6 years, after adjusting for covariates. Individuals with high, relative to those with low, trait anxiety had an 18% higher risk of hypertension (RR = 1.18, 95% CI = 1.03-1.34, p = 0.012). Conclusions: Elevated trait anxiety is associated with small increases in BP over 6 years and an 18% higher risk of hypertension among diverse Hispanics/Latino adults. Research on the mechanisms underlying these relationships among Hispanics/Latinos is warranted to develop effective interventions to prevent and treat hypertension in this population.
152P Analysis of patient access to breast cancer drugs in the USA and Europe with a focus on the UK and Ireland
Authors: R.A. Mclaughlin, D. O'Reilly, C. Ronayne, E. Barrett, R. Kalachand, A.M. De Frein, B. Macanovic, R.M. Connolly, D. Power, R. Bambury, S.O. Reilly, D. Collins
Journal: Annals of Oncology (2021)
Spondylolysis of the Cervical Spine (Case Report)
Authors: V. P. Mironova, A. V. Sudarkina, A. P. Dergilev, N. A. Gorbunov, A. A. Kuzovkova
Journal: Radiology - Practice (2021)

Cervical spondylolysis is a fairly rare clinical phenomenon that is mostly asymptomatic. The article describes a case of detection of bilateral cortical defects of pars interarticularis at the level of the CVI vertebra. Methods of computed tomography and magnetic resonance imaging were used for a comprehensive assessment of morphological changes.
Abstract 16802: Economics and Outcomes of Sotalol and Dofetilide In-Patient Dosing Approaches in Patients With Atrial Fibrillation
Authors: Thomas J Bunch, Heidi T May, Tami L Bair, Benjamin A Steinberg, Ravi Ranjan, Joseph B Muhlestein, Jeffrey L Anderson, Kirk U Knowlton
Journal: Circulation (2020)

Background: Inpatient initiation of sotalol (STL) and dofetilide (DFL) for patients with symptomatic atrial fibrillation (AF) can be variable, more so for STL. Objective: Define the impact of inpatient initiation of STL and DFL approaches on patient in-hospital costs and outcomes. Methods: AF patients that were admitted for STL (n=133) or DFL (n=38) initiation at an Intermountain Healthcare Hospital in 2018 were included to provide contemporary insight. Patient and dosing characteristics were described descriptively, and the impact of dosing schedule was correlated with daily hospital costs and outcomes. The CMS reimbursement for 3-day initiation of STL or DFL is $9,263.51. Results: The average age of the complete population was 69.7±11.7 years and 64.3% were male. Baseline risk factors were similar between groups. Mean ejection fraction was 59.2±8.9% and median QTc was 455.7±38.5 ms before STL dosing and 453.7±37.6 before DFL dosing. The average length of stay was 3.7±4.2 days and was shorter for DFL (3.0±2.0) compared to the STL (3.9±4.6). Within the DFL group, most received 5-6 doses, whereas STL dosing frequency was variable (Figure A). DFL discharge dose in 22 (57%) was 500 mcg BID and 125 mcg BID in 8 (21%). STL dose was 80 mg BID in 96 (72.1%) and 40 mg BID in 29 (21.8%). Total costs per hospitalization and per day were higher for STL compared to DFL (Figure B). QTc prolongation &gt;500 ms was more common with DFL versus STL and other long-term outcomes were similar (Figure C). A 24 load of IV sotalol result in a cost savings of $871.55 vs. a 2-day load and $3,803.10 vs. a 3-day oral load. Conclusion: Routine contemporary inpatient STL dosing is markedly variable and results in the potential of both cost gain and loss to a hospital. Under dosing of STL is also common and may negatively impact long-term outcomes.
Predicting Pseudomonas aeruginosa susceptibility phenotypes from whole genome sequence resistome analysis
Authors: Sara Cortes-Lara, Ester del Barrio-Tofiño, Carla López-Causapé, Antonio Oliver, Luis Martínez-Martínez, Germán Bou, Laura Zamorano, Irina Sánchez-Diener, Fátima Galán, Irene Gracia, Manuel Antonio Rodríguez, Lina Martín, Juan Manuel Sánchez, Laura Viñuela, Ma Victoria García, José Antonio Lepe, Javier Aznar, Inma López-Hernández, Cristina Seral, Francisco Javier Castillo-García, Ana Isabel López-Calleja, Carmen Aspiroz, Pedro de la Iglesia, Susana Ramón, Elena Riera, María Cruz Pérez, Carmen Gallegos, Jorge Calvo, María Dolores Quesada, Cristina Pitart, Francesc Marco, Yannick Hoyos, Juan Pablo Horcajada, Nieves Larrosa, Juan José González, Fe Tubau, Silvia Capilla, Mar Olga Pérez-Moreno, Ma José Centelles, Emma Padilla, Alba Rivera, Beatriz Mirelis, Raquel Elisa Rodríguez-Tarazona, Noelia Arenal-Andrés, María del Pilar Ortega, Gregoria Megías, Inmaculada García, Cristina Colmenarejo, José Carlos González, Nora Mariela Martínez, Bárbara Gomila, Salvador Giner, Nuria Tormo, Eugenio Garduño, José Andrés Agulla, Alejandro Seoane, Julia Pita, Isabel Paz Vidal, David Mauricio Guzmán, Marta García, María Luisa Pérez del Molino, Gema Barbeito, Fernando Artiles, José Manuel Azcona-Gutiérrez, Yolanda Sáenz, José Antonio Oteo, Ana González, Jennifer Villa, Fernando Chaves, Emilia Cercenado, Teresa Alarcón, Nelly Daniela Zurita, Desiré Gijón, Irene Merino, María Isabel Morosini, Rafael Cantón, María Isabel Sánchez, Laura Moreno, Genoveva Yagüe, José Leiva, José Luis Barrios, Andrés Canut, Jesús Oteo
Journal: Clinical Microbiology and Infection (2021)
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity
Authors: Marcin F Osuchowski, Martin S Winkler, Tomasz Skirecki, Sara Cajander, Manu Shankar-Hari, Gunnar Lachmann, Guillaume Monneret, Fabienne Venet, Michael Bauer, Frank M Brunkhorst, Sebastian Weis, Alberto Garcia-Salido, Matthijs Kox, Jean-Marc Cavaillon, Florian Uhle, Markus A Weigand, Stefanie B Flohé, W Joost Wiersinga, Raquel Almansa, Amanda de la Fuente, Ignacio Martin-Loeches, Christian Meisel, Thibaud Spinetti, Joerg C Schefold, Catia Cilloniz, Antoni Torres, Evangelos J Giamarellos-Bourboulis, Ricard Ferrer, Massimo Girardis, Andrea Cossarizza, Mihai G Netea, Tom van der Poll, Jesús F Bermejo-Martín, Ignacio Rubio
Journal: The Lancet Respiratory Medicine (2021)

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.
Abstract 12683: Genome-wide Mrna Expression Analysis of Acute Psychological Stress Responses
Authors: Jeongok G Logan, Mihyun Jeong
Journal: Circulation (2020)

Introduction: Previous studies have examined effects of acute psychological stress in humans on selected panels of genes. This exploratory study aimed to investigate genome-wide transcriptional activity changes in responses to acute psychological stress. Methods: The sample included 40 healthy women who participated in a previous study (22 who had a stress induced experience (experimental group) and 18 who did not (control group)). The psychological stress was induced by the Trier Social Stress Test (TSST). Psychological stress levels (measured by the Subjective Units of Distress Scale (SUDS) and the state anxiety subscale of the Spielberger State-Trait Anxiety Inventory) and hemodynamic changes (measured by blood pressure (BP) and heart rate (HR)) were assessed before and after the TSST. The peripheral blood samples obtained before and after the TSST were processed for mRNA-sequencing. Results: The mean age of the participants was 31 years (SD 11.6). The psychological and hemodynamic stress parameters indicated that the TSST successfully induced moderate but statistically significant levels of acute psychological stress in the participants of the experimental group. Compared with the participants in the control group, six genes ( BCL2L14, FAM3B, HCG26, HLA-F-AS1, LOC101928710 , and SLC22A16 ) were up-regulated and 9 genes ( ATP2C2, CA1, CRYBG3, FBXO9, HBD, SLC39A9, SNCA, STRADB , and TRMT12 ) were down-regulated among those who experienced stress induction. The IPA analysis identified one network of cell-to-cell signaling and interaction, cellular function and maintenance, and hematological system development and function. Thirteen genes out of 15 were found in this network. Conclusions: The identified genes including FAM3B, BCL2L14, SLC22A16 , and SNCA , have been proposed as the therapeutic targets of diabetes-related CVDs, certain cancers, and Parkinson’s disease, but have not previously been reported to be associated with psychological stress. Future studies are suggested to examine the pathological mechanisms by which the identified genes may mediate the association between psychological stress and adverse health outcome.
Abstract 15070: Micu1 Regulates Mitochondrial Cristae Structure and Function Independent of the Mitochondrial Calcium Uniporter Channel
Authors: Dhanendra Tomar, Manfred Thomas, Joanne Garbincius, Devin Kolmetzky, Oniel Salik, pooja jadiya, Suresh K Joseph, April C Carpenter, Gyorgy Hajnoczky, John W Elrod
Journal: Circulation (2020)

Background: MICU1 is an EF-hand domain containing Ca 2+ -sensor regulating the mitochondrial Ca 2+ uniporter channel and mitochondrial Ca 2+ uptake. MICU1-null mouse and fly models display perinatal lethality with disorganized mitochondrial architecture. Interestingly, these phenotypes are distinct from other mtCU loss-of-function models ( MCU, MICU2, EMRE, MCUR1 ) and thus are likely not explained solely by changes in matrix Ca 2+ content. Using size-exclusion proteomics and co-immunofluorescence, we found that MICU1 localizes to mitochondrial complexes lacking MCU. These observations suggest that MICU1 may have additional cellular functions independent of the MCU. Methods: Biotin-based proximity labeling and proteomics, protein biochemistry, live-cell Ca 2+ imaging, electron microscopy, confocal and super-resolution imaging were utilized to identify and validate MICU1 novel functions. Results: The expression of a MICU1-BioID2 fusion protein in MCU +/+ and MCU -/- cells allowed the identification of the total vs. MCU-independent MICU1 interactome. LC-MS analysis of purified biotinylated proteins identified the mitochondrial contact site and cristae organizing system (MICOS) components Mitofilin (MIC60) and Coiled-coil-helix-coiled-coil helix domain containing 2 (CHCHD2) as MCU independent novel MICU1 interactors. We demonstrate that MICU1 is essential for proper organization of the MICOS complex and that MICU1 ablation results in altered cristae organization, mitochondrial ultrastructure, mitochondrial membrane dynamics, membrane potential, and cell death signaling. We hypothesize that MICU1 is a MICOS Ca 2+ - sensor since perturbing MICU1 is sufficient to modulate cytochrome c release independent of Ca 2+ uptake across the inner mitochondrial membrane. Conclusions: Here, we provide the first experimental evidence of an intermembrane space Ca 2+ - sensor regulating mitochondrial membrane dynamics, independent of changes in matrix Ca 2+ content. This study provides a novel paradigm to understand Ca 2+ -dependent regulation of mitochondrial structure and function and may help explain the mitochondrial remodeling reported to occur in numerous disease states.
Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population‐Based Cohort Study
Authors: Habiba Kamal, Omid Sadr‐Azodi, Lars Engstrand, Nele Brusselaers
Journal: Hepatology (2021)

Background and Aims Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation‐wide population‐based cohort in Sweden. Approach and Results Using nation‐wide registries, we identified all adults who received maintenance PPIs (≥180 days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow‐up of 5.3 years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37‐1.81), 1.77 (95% CI, 1.56‐2.00), and 1.88 (95% CI, 1.57‐2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17‐1.57) and 1.47 (95% CI, 1.19‐1.80) for extra‐ and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5 years of PPIs use, ruling out confounding by indication. Conclusions In this study, long‐term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.
Abstract 17383: Comparative Analysis of TAVR With PCI and SAVR With CABG - A Nationwide Inpatient Sample Database
Authors: Waqas Ullah, Sameer Saleem, yasar sattar, Salman Zahid, Bashar Al hemyari, Sundas Younas, Homam Moussa Pacha, Yasser Al-khadra, Mohammad Abdul-Waheed, David L Fischman, Kenton J Zehr, M Chadi M Alraies
Journal: Circulation (2020)

Introduction: For patients with coronary artery disease (CAD) and severe aortic stenosis (AS), the relative safety of percutaneous approach [transcatheter aortic valve replacement (TAVR) and percutaneous coronary intervention (PCI)] to surgical approach [SAVR and coronary artery bypass graft (CABG)] has not been studied. Hypothesis: TAVR+PCI carries a higher risk of complications. Methods: The National Inpatient Sample (NIS) from 2002-2014 was queried to identify all cases of TAVR+PCI and SAVR+CABG. Univariate and multiple logistic regression analyses were used to control the outcomes. Results: A total of 215829 (TAVR+PCI 1634, SAVR+CABG 214195) patients were included. The unadjusted odds for in-hospital mortality (5.6% vs. 9.5%, uOR 0.57;95% CI, 0.48-0.67, p=&lt;0.001), acute kidney injury (18.9% vs. 26.3%, uOR 0.65; 95% CI, 0.59-0.73, P = 0.001), major bleeding (12.3% vs. 18.6%, uOR 0.61; 95% CI, 0.53-0.69, P = &lt;0.001), vascular complications (2.2% vs. 10.7%, uOR 0.19; 95% CI, 0.16-0.22, P = &lt;0.001), cardiogenic shock (4.5% vs. 8.6%, uOR 0.51; 95% CI, 0.16-0.22, P = &lt;0.001) and septic shock (1% vs. 1.8%, uOR 0.54; 95% CI, 0.38-0.79, P &lt;0.002), were significantly lower in patients undergoing SAVR+CABG compared to TAVR with PCI, respectively. The adjusted odds ratio based on baseline comorbidities, demographic and age closely mirrored the unadjusted odds ratios. Conclusions: In patients with the concomitant severe aortic disease and coronary artery disease, TAVR with PCI might have higher odds of in-hospital complications and mortality compared to SAVR+CABG. The mean hospital charges were also lower with the open surgical approach.
Risk of miscarriage in women with chronic diseases in Norway: A registry linkage study
Authors: Maria C. Magnus, Nils-Halvdan Morken, Knut-Arne Wensaas, Allen J. Wilcox, Siri E. Håberg
Journal: PLoS Medicine (2021)

Increased risk of miscarriage has been reported for women with specific chronic health conditions. A broader investigation of chronic diseases and miscarriage risk may uncover patterns across categories of illness. The objective of this study was to study the risk of miscarriage according to various preexisting chronic diseases.We conducted a registry-based study. Registered pregnancies (n = 593,009) in Norway between 2010 and 2016 were identified through 3 national health registries (birth register, general practitioner data, and patient registries). Six broad categories of illness were identified, comprising 25 chronic diseases defined by diagnostic codes used in general practitioner and patient registries. We required that the diseases were diagnosed before the pregnancy of interest. Miscarriage risk according to underlying chronic diseases was estimated as odds ratios (ORs) using generalized estimating equations adjusting for woman's age. The mean age of women at the start of pregnancy was 29.7 years (SD 5.6 years). We observed an increased risk of miscarriage among women with cardiometabolic diseases (OR 1.25, 95% CI 1.20 to 1.31; p-value <0.001). Within this category, risks were elevated for all conditions: atherosclerosis (2.22; 1.42 to 3.49; p-value <0.001), hypertensive disorders (1.19; 1.13 to 1.26; p-value <0.001), and type 2 diabetes (1.38; 1.26 to 1.51; p-value <0.001). Among other categories of disease, risks were elevated for hypoparathyroidism (2.58; 1.35 to 4.92; p-value 0.004), Cushing syndrome (1.97; 1.06 to 3.65; p-value 0.03), Crohn's disease (OR 1.31; 95% CI: 1.18 to 1.45; p-value 0.001), and endometriosis (1.22; 1.15 to 1.29; p-value <0.001). Findings were largely unchanged after mutual adjustment. Limitations of this study include our inability to adjust for measures of socioeconomic position or lifestyle characteristics, in addition to the rareness of some of the conditions providing limited power.In this registry study, we found that, although risk of miscarriage was largely unaffected by maternal chronic diseases, risk of miscarriage was associated with conditions related to cardiometabolic health. This finding is consistent with emerging evidence linking cardiovascular risk factors to pregnancy complications.