tbuckley/cabot-search huggingface dataset:
Abstract 13526: Global and National Atrial Fibrillation Quality of Care, From 1990 to 2017: Results From the GBD Study
Authors: Mahsima Shabani, Sahar Saeedi Moghaddam, Arya Aminorroaya, Erfan Ghasemi, Nazila Rezaei, Negar Rezaei, Farshad Farzadfar
Journal: Circulation (2020)

Introduction: Afib has a drastically higher incidence and burden among elderly. Aside from cardio and cerebrovascular outcomes in these patients, Afib individually brings about a significant mortality among elderly. Scoring systems like CHA2DS2-VASc imply that female gender, advanced age, and comorbidities augment the morbidity of Afib. Hypothesis: This study aims to evaluate the global and national discrepancies in Afib quality of care (QoC) within a 38-year time among over 70-year-old population. Methods: Four key epidemiologic indices were measured using the data from the estimates of ‘Global Burden of Diseases’ study, 2017: Mortality to incidence, DALY to prevalence, YLL to YLD, and Prevalence to Incidence ratio. Principal Component Analysis was utilized to find the highest value of all eigenvectors of the 4 estimates. The adaptive component derived from this analysis was set as the QoC index (QCI), a centile-based score reflecting better QoC with inclining values. Statistical analyses were done by R software v3.6.1. Results: QCI score decreased globally in over 70-year-old population of both females (-4.61%), and males (-3.92%). The gender disparity increased in favor of higher scores for males (-0.50 in 1990, -1.19 in 2017). At the country level, majority of nations had decreased QCI within this period (Figure 1). The US had the second highest QCI in over 70-year-old population (98.30), as well as 80-84 (98.24) and 85-89 years (98.07), specifically. Although the QCI dropped 2.18 scores from 1990 to 2017, the female-male disparity decreased in age group of over 70 (4.15 to 3.44) in US. Conclusions: Predominant world-wide decline in QCI, could imply the decreased quality of care for patients with Afib. Observed gender-specific discrepancy in a disease with female-dominant morbidity calls for the necessity to adapt health policies accordingly. However, further studies with adjustment for concomitant risk factors are required to address the underlying causes.
Abstract 14559: Prognostic Utility of Cardiac Markers in Covid-19 Patients
Authors: Ahmad Damati, Kok Hoe Delcos Chan, Iyad Farouji, Amr Al-ramahi, Patel Bhavic, fayez shamoon, Slim Jihad
Journal: Circulation (2020)

Introduction: SARS-CoV-2 infection has been associated with a multiple cardiovascular complications. It is not known if cardiac markers can be used for outcome prediction in the US population. Methods: We conducted a retrospective study on patients ≥ 18 years old with confirmed COVID 19, who were admitted to our hospital between 03/15/2020 and 05/25/2020. Individuals were included if they had a baseline troponin and brain natriuretic peptide (BNP) available, and if their outcome by the end of the study period was well defined as discharge alive, or deceased. Univariate and multivariate logistic regression methods were employed to identify the cardiac markers associated with mortality in COVID-19 patients. Results: The total number of confirmed COVID-19 hospitalized patients during the study period was 348, after excluding patients who did not have cardiac markers available, 233 patients were included in the study, 75 (32%) expired, and 158 (68%) were discharged alive. The median age was 65 years old, and ranged from 22 to 101 years old. 140 males and 93 females. Comorbidities were present in 201 (86%) patients, with hypertension (65%) being the most common, followed by obesity (55%), diabetes mellitus (DM) (44%) and coronary artery disease (27%). Mechanical ventilation was required for 61 patients of whom 42 expired. In univariate analysis, we found a significant difference in history of chronic kidney disease defined by eGFR &lt;45ml/min (p=0.046), DM (p=0.043), initial SOFA (p=0.017), troponin (p=0.001), BNP (p=0.043), CRP (p=&lt;0.0001), LDH (p=&lt;0.0001) and ferritin (p=&lt;0.0001) between survivors and non-survivors. With multivariable logistic regression analysis, the only values that had an odds of survival were a low troponin (odds ratio [OR] 0.17; 95% confidence interval [CI], 0.04-0.52), a low SOFA (OR 0.72, CI 0.50-0.94) and a low CRP (OR 0.87, CI 0.87-0.94). Conclusions: This retrospective cohort study of hospitalized patients with COVID-19 suggests an independent association of increased troponin as risk factor for death in COVID-19 patients. Cardiac troponin has been reported as potential prognostic marker in the China cohort. To our knowledge, we are first to demonstrate the utilization of troponin as mortality predictor in the US population.
The BAFFling persistence of memory B cells
Authors: Jeremy F. Brooks, Julie Zikherman
Journal: The Journal of Experimental Medicine (2020)

Although BAFF/BLyS and its receptor, BAFFR, play critical roles in naive B cell survival, the pathways involved in the persistence of memory B cells are largely unknown. In this issue of JEM, two groups, Müller-Winkler et al. (https://doi.org/10.1084/jem.20191393) and Lau et al. (https://doi.org/10.1084/jem.20191167), take complementary approaches to identify an essential role for BAFFR in the survival of memory B cells.
A Notch-Dependent Inflammatory Feedback Circuit between Macrophages and Cancer Cells Regulates Pancreatic Cancer Metastasis
Authors: Yawen Geng, Jie Fan, Lianyu Chen, Chenyue Zhang, Chao Qu, Ling Qian, Kun Chen, Zhiqiang Meng, Zhen Chen, Peng Wang
Journal: Cancer Research (2020)

Notch activation has been detected in pancreatic ductal adenocarcinoma (PDAC). However, its role in PDAC metastasis remains unknown. In this study, we identify a Notch-dependent feedback circuit between pancreatic cancer cells and macrophages, which contributes to PDAC metastasis. In this circuit, miR-124 regulated Notch signaling in cancer cells by directly targeting the Notch ligand Jagged 1. Autoamplified Notch signaling promoted the recruitment and activation of macrophages to a tumor-supporting M2-like phenotype via downstream IL8, CCL2, IL1α, and uPA paracrine signaling. In turn, activated macrophage-derived IL6 activated the oncogenic transcription factor STAT3 that directly repressed miR-124 genes via a conserved STAT3-binding site in their promoters, thereby promoting cancer cell epithelial-mesenchymal transition and invasion. Disrupting this circuit suppressed liver metastasis in mouse models. Thus, our study suggests that manipulation of this Notch-dependent circuit has a therapeutic potential for the treatment of PDAC metastasis. SIGNIFICANCE: This study provided potential therapeutic targets and robust preclinical evidence for PDAC treatment by interrupting feedback signaling between cancer cells and macrophages with targeted inhibitors.
Abstract 201: Bougie-Assisted Endotracheal Intubation in the Pragmatic Airway Resuscitation Trial
Authors: Austin Bonette, Tom P Aufderheide, Graham Nichol, Jeffrey Jarvis, Matthew L Hansen, Riccardo Colella, Jason Lesnick, Jestin N Carlson, Shannon W Stephens, Henry E Wang
Journal: Circulation (2020)

Objective: Paramedics often perform endotracheal intubation (ETI) in the management of out-of-hospital cardiac arrest (OHCA). While ETI assisted by use of the gum elastic Bougie has been associated with improved first-pass intubation success in the emergency department, its influence upon out-of-hospital cardiac arrest (OHCA) ETI is unknown. We compared success rates and outcomes between Bougie-assisted and standard ETI in the Pragmatic Airway Resuscitation Trial (PART). Methods: We conducted a secondary analysis of PART, a clinical trial comparing initial-ETI vs. initial-laryngeal tube airway management strategies in adult OHCA. We included only patients receiving initial ETI attempts. The primary exposure was Bougie-assisted vs. standard ETI. The primary outcome was first-pass ETI success. Secondary outcomes included overall ETI success, time to successful ETI, 72-hour survival, hospital survival and hospital survival with favorable neurologic status. We assessed the associations between Bougie-assistance and ETI outcomes using Generalized Estimating Equations and Cox Regression, adjusting for for age, sex, race, witnessed arrest, bystander CPR and initial rhythm. Results: Of the 3,004 patients enrolled in PART, 1,227 received initial ETI, including 440 Bougie-assisted and 787 standard ETI. First-pass ETI success did not differ between Bougie-assisted and standard ETI (53.1% vs. 42.8%; adjusted OR 1.12, 95% CI: 0.97 to 1.39). Overall ETI success was slightly higher for Bougie-assisted ETI (56.2% vs. 49.1%; adjusted OR 1.19, 95% CI: 1.01 to 1.32). Time to ETI was longer for Bougie-assisted than standard ETI (median 13 vs. 11 min; adjusted HR 0.63, 95% CI: 0.45 to 0.90). While survival to hospital discharge was lower for Bougie-assisted than standard ETI (3.6% vs. 7.5%; adjusted OR 0.94, 95% CI: 0.92 to 0.96), there were no differences in 72-hour survival or hospital survival with favorable neurologic status. Conclusion: In the PART trial, Bougie assistance resulted in slightly higher overall ETI success but with longer airway placement time. Bougie assistance was not associated with first-pass ETI success. The association between Bougie-assisted ETI and OHCA survival was unclear. The role of Bougie-assisted ETI in OHCA is uncertain.
Genomic and transcriptomic correlates of Richter transformation in chronic lymphocytic leukemia
Authors: Jenny Klintman, Niamh Appleby, Basile Stamatopoulos, Katie Ridout, Toby A. Eyre, Pauline Robbe, Laura Lopez Pascua, Samantha J. L. Knight, Helene Dreau, Maite Cabes, Niko Popitsch, Mats Ehinger, Jose I. Martín-Subero, Elías Campo, Robert Månsson, Davide Rossi, Jenny C. Taylor, Dimitrios V. Vavoulis, Anna Schuh
Journal: Blood (2020)
Abstract 12788: Cardiac MicroRNA-150 Confers Cardioprotection by Directly Repressing Pro-apoptotic Small Proline-rich Protein 1a, Sprr1a in Cardiomyocytes
Authors: Tatsuya Aonuma, Bruno Moukette, Nipuni P Barupala, Il-man Kim
Journal: Circulation (2020)

Background and Aims: Cardiac injury induces dynamic changes in the expression of microRNAs (miRs). For example, the evolutionarily conserved miR-150 is downregulated in patients with multiple cardiovascular diseases such as myocardial infarction (MI) and cardiomyopathies, as well as in various mouse models of heart failure (HF). MiR-150 is significantly associated with HF severity and outcome in humans. Using a systemic miR-150 knockout (KO) mouse model, we previously showed that carvedilol (Carv)/β 1 -adrenergic receptor/β-arrestin1-responsive miR-150 confers cardiac protection against MI (Left side in Figure). However, the extent to which expression of miR-150 in cardiomyocytes (CMs) regulates MI is unknown and there is a lack of mechanistic insight by which CM miR-150 modulates cardiac protection. Methods and Results: Here, we demonstrate using a novel mouse model that conditional CM-specific miR-150 KO (miR-150 cKO) in mice worsens cardiac dysfunction, stress, fibrosis and apoptosis post-MI, without affecting mortality or inflammation. Genome-wide transcriptomic analysis in miR-150 cKO mouse hearts identifies small proline-rich protein 1a (sprr1a) as a novel regulatory target of miR-150. Our mouse and CM studies further reveal that sprr1a expression is upregulated in CMs isolated from ischemic myocardium and subjected to simulated ischemia/reperfusion. In contrast, its expression is downregulated in hearts and CMs by Carv. Our human heart data also show that left ventricular sprr1a is upregulated in patients with HF with reduced ejection fraction. Mechanistically, the cardioprotective roles of CM miR-150 during MI are in part attributed to the direct and functional repression of pro-apoptotic gene sprr1a in CMs (Right side in Figure). Conclusions: These findings reveal a pivotal role for the miR-150/sprr1a axis in regulating CM function post-MI, and this novel axis could be a therapeutic target for intervention in ischemic heart disease.
Abstract 14904: Alteration of Lipid Profile and Prognostic Value of Lipids on the Length of Hospital Stay in Covid-19 Pneumonia Patients
Authors: qin chen, Minghan Huang, yukun luo
Journal: Circulation (2020)

Background: The outbreak of the novel coronavirus SARSCoV-2 (coronavirus disease 2019; COVID-19) has spread to most of countries in the world. The tight relationship of plasma lipids and COVID-19 pneumonia (NCIP-19) has not been well invested. To observe lipid profiles and their alterations in hospitalized patients with COVID-19 and evaluated the prognostic value of lipids for the length of hospital stay (LOS). Methods: 248 NCIP-19 cases aged 18 years or older were enrolled in this study. Serum lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected at admission. In 68 severe cases, levels of serum lipids were subsequently detected every 5 ~ 10 days. Results: At admission, median levels of TG, TC, HDL-C, and LDL-C in all patients, were 1.11 mmol/L, 4.00 mmol/L, 0.89 mmol/L and 2.11 mmol/L, respectively. Compared with common cases (n=174), higher TG and HDL-C, lower LDL-C were observed in severe cases (n=74). Levels of TC and LDL-C at admission were negatively correlated with LOS. In severe cases, the average levels of serum lipids were lowest at admission and gradually increased during hospitalization. Compared with the LOS≤29d group, serum levels of TC, HDL-C, and LDL-C were significantly lower in the LOS&gt;29d group at admission; this lower trend always existed during the following tests for TC and LDL-C, but not for HDL-C and TG. Patients with LDL-C≥1.70 mmol/L at admission showed a lower risk of LOS prolongation (adjusted HR=0.557, 95% CI: 0.409-0.759, p &lt;0.001). Conclusions: In NCIP-19, serum lipid levels were low at admission. Levels of TC and LDL-C at admission were negatively correlated with LOS. LDL-C &lt;1.7 mmol/L at admission may act as the independent predictor of LOS prolongation. In severe cases, the gradual increase of TC, LDL-C, and HDL-C during the hospitalization might indicate the gradual recovery of the disease.
Abstract 15016: Peak Oxygen Consumption Achieved at the End of Cardiac Rehabilitation Predicts Survival in Patients With Coronary Heart Disease
Authors: Salvatore Carbone, Youngdeok Kim, Sergey Kachur, Alban De Schutter, Hayley E Billingsley, Richard V Milani, Carl J LAVIE
Journal: Circulation (2020)

Introduction: Several patients with coronary heart disease (CHD) present reduced survival despite completing cardiac rehabilitation (CR), suggesting that the level of cardiorespiratory fitness (CRF) achieved might remain suboptimal. The purposes of this study were: 1) to examine the independent association of peak oxygen consumption (VO 2 ), a measure of CRF, at post-CR with long-term survival; and 2) to establish an optimal cut-off for peak VO 2 at post-CR that best predicts mortality risk. Methods: 853 patients with CHD (mean age of 64±10 years old) who were referred to CR between January 1, 2000, and June 30, 2013, at Ochsner Medical Center were analyzed for this study. We measured pre- and post-CR peak VO 2 . Mortality data were collected using National Death Index. Cox proportional hazard regression model was used to examine the risk of all-cause mortality associated with peak VO 2 at post-CR, independent of peak VO 2 at pre-CR and related changes during CR. Contal and O’Quigley’s method were used to determine the optimal cut-off for peak VO 2 at post-CR based on a split-sample approach. Results: Mean peak VO 2 at post-CR was 21.01±6.25 mL/kg/min (75% and 51% predicted peak VO2 using Wasserman and FRIEND Registry equations, respectively). During a mean follow-up of 6.55 years, 106 subjects (12.4%) died. Peak VO 2 at post-CR independently predicted mortality (Hazard Ratio: 0.82 [0.77-0.87], p&lt;0.001). We identified peak VO 2 of ≥17.6 kg/mL/min as optimal cut-off best predicting survival ( Figure 1, Panel A ) and the %predicted peak VO2 at post-CR ≥62.1% using Wasserman ( Figure 1, Panel B ) and ≥41.4% using FRIEND Registry ( Figure 1, Panel C ) as the alternative optimal cut-offs. Conclusions: In patients with CHD undergoing CR, post-CR peak VO 2 independently predicts long-term survival. These results suggest that patients with CHD presenting a peak VO 2 lower than the cut-off identified herein may benefit from additional sessions of CR or higher intensity exercise training.
Abstract 15282: Right Ventricular Echocardiographic Analysis in the Critically Ill COVID-19 Population
Authors: Akshar Jaglan, Sarah Roemer, Ana C Perez Moreno, Pedro D Salinas, Bijoy K Khandheria
Journal: Circulation (2020)

Introduction: Coronavirus disease 2019 (COVID-19), has rapidly spread around the world and reached a pandemic level. The utility and benefit of echocardiographic analysis in this patient population has just started to be documented in the literature. We use this study to show the benefits of analyzing right ventricular (RV) function in this patient population. Methods: We assessed RV systolic function in 22 (mean age 63.5±4 years; 73% male) patients admitted to the ICU who tested positive for COVID-19. The transthoracic echocardiograms performed on the critically ill COVID-19 patients were focused studies done in supine position. Right ventricular free wall strain (RVFWS) was analyzed on proprietary software (EchoPac 202, GE Vingmed Ultrasound, Horten, Norway). RV systolic dysfunction was classified as tricuspid annulus peak systolic velocity (S’) &lt;9.5 cm/s or RVFWS &lt;-20%. Results: All 22 patients had either an S’ or RVFWS measurement; 20 of them had an observation for S’ and 16 had an observation for RVFWS. Median RVFWS among all patients was reduced at -18.5%. At the time of this writing, 14 of the 22 patients were being treated in the ICU or had died; median RVFWS in this subgroup was reduced at -17.5% and S’ at 12 cm/s. The 8 patients who transferred out of the ICU had a median RVFWS of -23.5 and S’ of 16 cm/s. Of the 10 patients classified as having RV dysfunction, 9 were due to RVFWS &lt;-20% and 1 to S’ of &lt; 9.5. Excluding patients who passed away, RV dysfunction was associated with a longer median ICU stay (21.5 days [interquartile range {IQR} 13-30] vs 9 days [IQR 5.5-16.5]; p=0.03). Conclusions: Of the 22 patients included in the study, currently 5 have died, 9 remain intubated in critical condition in the ICU, and 8 have been transferred to the medicine floor. In conclusion, focused, rather than point-of-care, ultrasound should be utilized to analyze RV function as there is clear evidence that RVFWS is correlated with longer ICU stay and poorer prognosis.
Abstract 14657: Intermuscular Fat is Independently Associated With Coronary Microvascular Dysfunction and Adverse Cardiovascular Outcomes in Patients With No Obstructive CAD
Authors: Ana Carolina A Souza, Amelie S Troschel, Jan P Marquardt, Sanjay Divakaran, Jenifer Brown, Leanne Barrett, Laurel Martell, Courtney Bibbo, Jon Hainer, Ron Blankstein, Sharmila Dorbala, MARCELO F DI CARLI, Florian J Fintelmann, Viviany R Taqueti
Journal: Circulation (2020)

Introduction: Intermuscular adipose tissue (IMAT) reflects skeletal muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with BMI, inflammation and risk of heart failure, myocardial infarction and death. Using a novel neural networks algorithm for body composition analysis, we sought to investigate the relationship between skeletal muscle quality, CMD and cardiovascular outcomes. Methods: Consecutive patients (N=669) undergoing evaluation for CAD with cardiac stress PET demonstrating normal perfusion and preserved LVEF were followed over median 6 years for events (MACE), including death and hospitalization for myocardial infarction or heart failure. CFR was calculated as the stress/rest myocardial blood flow ratio. Subcutaneous fat (SAT) and IMAT areas (cm 2 ) were obtained from PET attenuation correction CTs using a fully automated algorithm validated by manual segmentation at T10 and T12 levels, respectively. Results: Median age was 63 years, 70% were female and 46% nonwhite. Nearly half of patients were obese (46% with BMI 30-61) and BMI correlated closely with SAT and IMAT (r=0.8 and 0.7, respectively, p&lt;0.001). Independent of age, sex, race, BMI, LVEF and hypertension, CFR was associated with IMAT (β -0.10, p=0.047). In adjusted analyses, both CFR and increased IMAT were independently associated with MACE [HR 1.6 (1.1-2.4) per -1U CFR and 1.5 (1.2-1.7) per +10 cm 2 IMAT, p≤0.01]. Patients with both CMD and poor muscle quality demonstrated highest risk of MACE (adjusted p&lt;0.02). Conclusion: Increased intermuscular fat is associated with CMD and adverse cardiovascular outcomes independently of BMI and traditional risk factors. Combined assessment of skeletal muscle quality and coronary microvascular function may help to redefine at-risk cardiometabolic phenotypes.
Abstract 14541: Incidence, Risk Factors, and Outcomes of Heart Failure in Patients With Graves’ Disease
Authors: Jwan A Naser, Sorin Pislaru, Marius N Stan, Grace Lin
Journal: Circulation (2020)

Background: Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF). Due to the rarity of thyrotoxic HF, population-based studies are lacking, and data from smaller studies are widely variable. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. HF was defined according to Framingham criteria. GD-related HFrEF was defined by left ventricular ejection fraction of &lt;50%, while HFpEF was defined according to the Heart Failure Association of the European Society of Cardiology. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were analyzed with adjustments for age, gender, and history of coronary artery disease (CAD). 1:1 matching with controls (age, gender, and CAD) was additionally done. Results: HF occurred in 74 patients (31 HFrEF; 43 HFpEF). Incidence of GD-related HF, HFrEF, and HFpEF was 5.4%, 2.3%, and 3.1%, respectively. In HFrEF, atrial fibrillation (AF) (RR 10.05, p &lt;0.001) and thyrotropin receptor antibodies (TRAb) level (RR 1.05 per unit, p=0.005) were independent predisposing factors. In HFpEF, independent risk factors were COPD (RR 5.78, p &lt; 0.001), older age (RR 1.48 per 10 years, p = 0.003), overt hyperthyroidism (RR 5.37, p = 0.021), higher BMI (1.06 per unit, p = 0.003), and HTN (RR 3.03, p = 0.011). Rates of cardiac hospitalizations were higher in HFrEF (41.9% vs 3.2%, p &lt;0.001) and HFpEF (44.2% vs 4.7%, p &lt; 0.001) compared to controls. Furthermore, while both increased risk of strokes (HFrEF: RR 4.12, p = 0.027; HFpEF: RR 4.64, p = 0.009), only HFrEF increased risk of all-cause mortality (RR 3.78, p = 0.045). Conclusion: De novo HF occurs in 5.4% of patients with GD and increases the rate of cardiovascular events. HF occurs more frequently in GD patients with AF, higher TRAb, higher BMI, and overt hyperthyroidism, suggesting that these may be targets for treatment to prevent cardiovascular complications, especially in older multimorbid patients.