tbuckley/cabot-search huggingface dataset:
Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study
Authors: Sarah E Daugherty, Yinglong Guo, Kevin Heath, Micah C Dasmariñas, Karol Giuseppe Jubilo, Jirapat Samranvedhya, Marc Lipsitch, Ken Cohen
Journal: BMJ (2021)

To evaluate the excess risk and relative hazards for developing incident clinical sequelae after the acute phase of SARS-CoV-2 infection in adults aged 18-65.Retrospective cohort study.Three merged data sources from a large United States health plan: a large national administrative claims database, an outpatient laboratory testing database, and an inpatient hospital admissions database.Individuals aged 18-65 with continuous enrollment in the health plan from January 2019 to the date of a diagnosis of SARS-CoV-2 infection. Three comparator groups, matched by propensity score, to individuals infected with SARS-CoV-2: a 2020 comparator group, an historical 2019 comparator group, and an historical comparator group with viral lower respiratory tract illness.More than 50 clinical sequelae after the acute phase of SARS-CoV-2 infection (defined as the date of first SARS-CoV-2 diagnosis (index date) plus 21 days) were identified using ICD-10 (international classification of diseases, 10th revision) codes. Excess risk in the four months after acute infection and hazard ratios with Bonferroni corrected 95% confidence intervals were calculated.14% of adults aged ≤65 who were infected with SARS-CoV-2 (27 074 of 193 113) had at least one new type of clinical sequelae that required medical care after the acute phase of the illness, which was 4.95% higher than in the 2020 comparator group. The risk for specific new sequelae attributable to SARS-Cov-2 infection after the acute phase, including chronic respiratory failure, cardiac arrythmia, hypercoagulability, encephalopathy, peripheral neuropathy, amnesia (memory difficulty), diabetes, liver test abnormalities, myocarditis, anxiety, and fatigue, was significantly greater than in the three comparator groups (2020, 2019, and viral lower respiratory tract illness groups) (all P<0.001). Significant risk differences because of SARS-CoV-2 infection ranged from 0.02 to 2.26 per 100 people (all P<0.001), and hazard ratios ranged from 1.24 to 25.65 compared with the 2020 comparator group.The results indicate the excess risk of developing new clinical sequelae after the acute phase of SARS-CoV-2 infection, including specific types of sequelae less commonly seen in other viral illnesses. Although individuals who were older, had pre-existing conditions, and were admitted to hospital because of covid-19 were at greatest excess risk, younger adults (aged ≤50), those with no pre-existing conditions, or those not admitted to hospital for covid-19 also had an increased risk of developing new clinical sequelae. The greater risk for incident sequelae after the acute phase of SARS-CoV-2 infection is relevant for healthcare planning.
Abstract 16854: Left Atrial Dysfunction and Prediction of Atrial Fibrillation in LMNA Cardiomyopathy
Authors: Maxime Tremblay Gravel, Victoria Parikh, Yumeko Kawano, Kermshlise Picard, Brianna Tucker, Francois Haddad, Neal K Lakdawala, Matthew T Wheeler
Journal: Circulation (2020)

Introduction: LMNA cardiomyopathy is characterized by a high incidence of atrial fibrillation (AF) and an increased risk for AF-related stroke. AF commonly occurs before apparent cardiomyopathy, and the ability to predict its incidence in asymptomatic LMNA mutation carriers is limited. We sought to evaluate the presence of echocardiographic features specific to LMNA and whether they predict AF incidence. Methods: Patients harboring LMNA mutations (n=77) from two referrals centers between 2000 and 2017 were retrospectively included. Comparator groups included patients with TTN cardiomyopathy (n=35) and healthy subjects (n=36). Echocardiograms at first clinical contact were analyzed for routine metrics and LA strain and related to incident AF. Results: Patients with LMNA mutations were assessed at median age 47 years (IQR, 32-62) with median LVEF 51% (41-61). In LMNA patients with LVEF ≥55% (n=20) and healthy subjects matched for LVEF, LA contractile strain was lower in LMNA patients (-10% vs -16%, respectively; P = 0.047), whereas other parameters did not significantly differ (Figure, panel A). Comparison of LVEF-matched LMNA and TTN cardiomyopathy patients showed LA contractile strain as the only distinguishing feature (-5.8% vs -12.8%, respectively; P = 0.01) (Figure, panel B). LMNA patients without previous AF (n=35) were followed for a total of 133 patient-years during which 11 (31%) developed AF. In Cox regressions adjusted for clinical and echocardiographic variables, decreased LA contractile strain (&lt;
Abstract 12569: Analysis of Deep Learning Models for Prediction of Heart Failure Mortality
Authors: Chayakrit Krittanawong, Kipp W Johnson, Usman Baber, Mehmet Aydar, Zhen Wang, Matthew P Stewart, Jonathan Halperin, Wilson Tang
Journal: Circulation (2020)

Introduction: Heart failure (HF) is a leading cause of hospitalization, morbidity and mortality. Deep learning (DL) techniques appear to show promising results in risk stratification and prognosis in several conditions in medicine. However, few methods using DL exist to help quantitatively estimate prognosis of HF. We hypothesized that deep learning (DL) techniques could prognosis of HF using simple variables. We propose application of a custom-built deep-neural-network model to identify mortality in HF patients. Methods: Custom-built deep-neural-networks were assessed using survey data from 42,147 participants from the National Health and Nutrition Examination Survey 1999-2016 (NHANES). Variables were selected using clinical judgment and stepwise backward regressions to develop prediction models. We partitioned the data into training and testing sets and repetitive experiments. We then evaluated model performance based on discrimination and calibration including the area under the receiver-operator characteristics curve (C-statistics), balanced accuracy, probability calibration with sigmoid, and the Brier score, respectively. As sensitivity analyses, we examined results limited to cases with complete clinical information available. We validated models’ performance using Mount Sinai database. Results: Of 42,147 participants with 4,060 variables, 1,491 (3.5%) had HF and HF mortality was 51.8%. In validation cohort, of 26,333 HF patients, the mortality in HF patients was 405 (1.5%). Final model using only 20 variables (age, race, gender, BMI, smoking, alcohol consumption, HTN, COPD, SBP, DBP, HR, HDL, LDL, CRP, A1C, BUN, creatinine, hemoglobin, sodium level, on statin) was tested. A state-of-the-art deep learning models achieved high accuracy for predicting mortality in HF patients with an AUC of 0.96 (95% CI: 0.95-0.99) in the first cohort and AUC of 0.93 (95% CI: 0.91-0.96) in validation cohort. Conclusions: A deep neural network model has shown to have high predictive accuracy and discriminative and calibrative power for prediction of HF mortality. Further research can delineate the clinical implications of DL in predicting HF mortality.
Abstract 15649: Pharmacological Inhibition of Aldose Reductase by AT001 Prevents Abnormal Cardiac Energy Metabolism and Improves Heart Function in an Animal Model of Diabetic Cardiomyopathy
Authors: Keshav Gopal, Qutuba Karwi, Seyed Amirhossein Tabatabaei Dakhili, Riccardo Perfetti, Ravichandran Ramasamy, John R Ussher, Gary D Lopaschuk
Journal: Circulation (2020)

Introduction: Diabetic Cardiomyopathy (DCM) is a major cause of death in people with type 2 diabetes (T2D). Alterations in cardiac energy metabolism including increased fatty acid oxidation rates and reduced glucose oxidation rates are key contributing factors to the development of DCM. Studies have shown that Aldose Reductase (AR), an enzyme activated under hyperglycemic conditions, can modulate myocardial glucose and fatty acid oxidation, and promotes cardiac dysfunction. Hypothesis: Pharmacological inhibition of AR using a next-generation inhibitor AT-001, can mitigate DCM in mice by modulating cardiac energy metabolism and improving cardiac efficiency. Methods: Male human AR overexpressing (hAR-Tg) and C57BL/6J (Control) mice were subjected to experimental T2D (high-fat diet [60% kcal from lard] for 10-wk with a single intraperitoneal streptozotocin injection of 75 mg/kg) and treated for the last 3-wk with AT-001 (40mg/kg/day) or vehicle via oral gavage. Cardiac energy metabolism and in vivo cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Results: AT-001 treatment significantly improved cardiac energetics in a murine model of DCM (hAR-Tg mice with T2D). Particularly, AT-001-treated mice exhibited decreased cardiac fatty acid oxidation rates compared to the vehicle-treated mice (342 ± 53 vs 964 ± 130 nmol/min/g dry wt.). Concurrently, there was a significant decrease in cardiac oxygen consumption in the AT-001-treated compared to the vehicle-treated mice (41 ± 12 vs 60 ± 11 μmol/min/g dry wt.), suggesting increased cardiac efficiency. Furthermore, treatment with AT-001 prevented cardiac structural and functional abnormalities present in DCM, including diastolic dysfunction as reflected by an increase in the tissue Doppler E’/A’ ratio and decrease in E/E’ ratio. Moreover, AT-001 treatment prevented cardiac hypertrophy as reflected by a decrease in LV mass in AT-001-treated mice. Conclusions: AR inhibition with AT-001 prevents cardiac structural and functional abnormalities in a mouse model of DCM, and normalizes cardiac energetics by shifting cardiac metabolism towards a non-diabetic metabolic state.
Abstract 16696: Racial Differences in Cardiometabolic Determinants of Natriuretic Peptide Levels in Clinically Referred Patients With and Without Heart Failure
Authors: Newman Kwame Boakye Ansa, Meng Xu, Cassandra Reynolds, Eric Farber-Eger, Debra Dixon, Vineet Agrawal, Sheila Collins, Thomas Wang, Deepak K Gupta
Journal: Circulation (2020)

Background: Relative natriuretic peptide (NP) deficiencies are associated with hypertension, diabetes, and obesity. The prevalence of these conditions varies by race, affecting more black than white individuals. We assessed whether circulating NP levels and factors associated with NP levels differ by race in clinically referred patients. Methods: Using Vanderbilt University Medical Center electronic health records from 2002 to 2013, we examined plasma B-type natriuretic peptide (BNP) levels and correlates in 30,487 black (17%) or white adult patients. Multivariable-adjusted models including interaction terms by race and stratification by heart failure (HF) status were used. Results: In 18,850 patients without HF, BNP levels were lower in black [median 58 pg/ml (25 th , 75 th percentile: 23, 179)] compared with white individuals [97 pg/ml (38, 247)], p&lt; 0.001. Factors most strongly correlated with BNP differed between black (creatinine, age, chronic kidney disease, body mass index (BMI), left ventricular [LV] ejection fraction) and white (age, BMI, LV mass, chronic kidney disease, sex) patients ( Figure ). Lower BNP levels in black patients were observed across the spectrum of heart rate, blood pressure, body mass index, glucose, LV ejection fraction and mass, and renal function. The directional association of cardiometabolic risk factors with BNP levels was largely similar by race, with exceptions of significant interactions by BMI and creatinine. Higher BMI was associated with lower BNP levels in whites, while among black patients beyond a BMI of approximately 35 kg/m 2 , BNP levels did not decline any further. With higher creatinine, the rise in BNP levels was steeper in black compared with white patients. In contrast to patients without HF, among patients with HF (n = 11,637), BNP levels and its correlates were similar between black and white patients ( Figure ). Conclusion: The associations between cardiometabolic factors and BNP levels vary by race and HF status.
Abstract MP01: Effect Of The DASH-Sodium Diet On Serum Biomarkers Of Inflammation And Mineral Metabolism
Authors: Valerie K Sullivan, Lawrence J Appel, Jesse C Seegmiller, Casey M Rebholz
Journal: Circulation (2021)

Background: The blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and reduced sodium intake are well-established. The effects on other biomarkers related to vascular health are of interest and may assist in explaining cardiovascular benefits of the DASH diet. Objective: We hypothesized that a low-sodium DASH diet improves biomarkers of inflammation [i.e. reduces C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR)] and mineral metabolism [phosphorus and fibroblast growth factor-23 (FGF23)]. Methods: We conducted a post hoc analysis of the DASH-Sodium trial using stored frozen serum samples. This controlled feeding study randomized 412 adults to consume either a DASH diet or control diet representative of a typical American diet. Within each arm, participants received three sodium levels (low, intermediate, high) in random sequence, each for 30 days. To maximize contrast, samples collected at the end of the low-sodium DASH (n=198) and high-sodium control (n=194) diets were compared. Between-diet differences in biomarker concentrations were assessed by t-test or Wilcoxon rank sum test for normally distributed and skewed variables, respectively. Results: CRP concentrations did not differ between groups ( P =0.19), but suPAR was higher after the low-sodium DASH diet than the high-sodium control (median, IQR: 2473, 2127-2887 pg/mL vs. 2281, 1929-2679 pg/mL; P =0.003). FGF23 was also higher after the DASH diet (35.9, 26.9-44.8 pg/mL vs. 30.2, 23.5-37.5 pg/mL; P&lt; 0.001). Serum phosphorus was higher after the DASH diet (mean±SEM: 3.5±0.04 mg/dL) versus the control (3.4±0.04 mg/dL; P =0.02). Conclusions: Contrary to our hypothesis, biomarkers of inflammation and mineral metabolism were increased or unchanged by a low-sodium DASH diet compared to a high-sodium control diet. Potential reasons (e.g. short duration of the trial, sodium-specific effects, bioavailable phosphorus-rich dairy intake) require further investigation.
Abstract 15666: Effectiveness of Sharpsense™ Algorithms in Reducing Pause and Bradycardia Detection: Real-world Performance Before and After the Software Upgrade in Confirm Rx™ Insertable Cardiac Monitor
Authors: Rakesh Gopinathannair, Dhanunjaya Lakkireddy, Christopher Piorkowski, Muhammad Afzal, Ghulam Murtaza, Fujian Qu, Fady Dawoud, Kevin Davis, Kyungmoo Ryu, Avi Fischer, John Ip
Journal: Circulation (2020)

Background: Recent enhancements have been introduced to the Abbott Confirm Rx™ insertable cardiac monitor (ICM) arrhythmia detection algorithms (SharpSense™). This study aims to characterize the real-world performance of SharpSense™ algorithms, in the upgraded ICM devices by comparing device detected pause and bradycardia (brady) episodes before and after the SharpSense™ upgrade. Methods: Confirm Rx™ devices with at least 90 days monitoring each before and after SharpSense™ upgrade were included in the study. Brady and pause episodes were extracted from Merlin.net™ patient care network for evaluation and adjudicated by expert adjudicators. Results: A total of 197 devices were included in the analysis. Devices were implanted for syncope (35%), AF management (33%), and other indications, including cryptogenic stroke and palpitations (32%). The SharpSense™ upgrade significantly reduced the total number of detected episodes by 92% (pause: 93%, brady: 87%) and the rate of transmitted episodes by 73.6% from 50.3 to 13.3 (pause: 34.9 to 6.0, brady: 7.8 to 1.5) episodes per patient-week (p &lt; 0.001). SharpSense™ reduced false positive episodes by 82.8% and 91.5% for pause and brady, respectively. The percentage of devices with at least one false positive episode was reduced from 52% to 35% for pause and from 39% for 20% for brady. The number of devices with false positive rate greater than 1 episode per week was reduced from 39% to 20% for pause and from 23% to 8% for brady. Conclusion: SharpSense™ upgrade resulted in substantial reduction of pause and bradycardia episode detections, false positive detections, and frequency of transmitted episodes for clinic review.
Abstract P059: Prevalence And Correlates Of Co-occurring Metabolic Syndrome And Chronic Kidney Disease: Findings From The Hispanic Community Health Study/study Of Latinos (hchs/sol)
Authors: Celestin Missikpode, Sylvia E Rosas, Ana Ricardo, James Lash, Unab I Khan, Oana Klein, Leopoldo Raij, Neil Schneiderman, Martha L Daviglus
Journal: Circulation (2021)

Introduction: Metabolic syndrome (MetS) and chronic kidney disease (CKD) are highly prevalent among Hispanics/Latinos, yet data on co-occurring MetS and CKD are not available. Understanding the prevalence and correlates of MetS-CKD overlap may inform intervention programs for such subgroups. Methods: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) was used. MetS was defined as the presence of three or more of the following risk factors: abdominal obesity, high triglyceride, low high-density lipoprotein cholesterol level, elevated blood pressure, and elevated glucose level. CKD was defined as eGFR &lt;60 mL/min per 1.73 m 2 or the presence of albuminuria (urine albumin-creatinine ratio ≥17 mg/g in men and ≥25 mg/g in women). Of 16,415 HCHS/SOL participants, data from 14,527 persons with complete information on kidney function measures and covariates were analyzed using logistic regression. Potential correlates included age, sex, Hispanic/Latino background, acculturation, education, income, physical activity, alcohol use, cigarette smoking, cardiovascular disease, hemoglobin, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance (HOMA-IR). Analyses accounted for complex sampling design. Results: Average age was 41 years, 52% were women, 33% had prevalent MetS, and 14% had prevalent CKD. MetS and CKD co-occurred in 7.8% of the study population, 8.5% in men and 7.2% in women. The prevalence of co-occurring MetS and CKD was 10.4% in Puerto Rican, 9.2% in Cuban, 7.2% in Central American, 7.2% in Mexican, 6.5% in Dominican, and 5.3% in South American. Factors independently related to those co-occurring conditions were age, sex, physical activity levels, cardiovascular disease, high-sensitivity C-reactive protein, and HOMA-IR ( Table ). Conclusions: Targeted prevention efforts that address key modifiable overlapping risk factors may be especially effective in reducing metabolic syndrome and improving kidney health.
Chronic respiratory diseases are predictors of severe outcome in COVID-19 hospitalised patients: a nationwide study
Authors: Guillaume Beltramo, Jonathan Cottenet, Anne-Sophie Mariet, Marjolaine Georges, Lionel Piroth, Pascale Tubert-Bitter, Philippe Bonniaud, Catherine Quantin
Journal: European Respiratory Journal (2021)

Background Influenza epidemics were initially considered to be a suitable model for the COVID-19 epidemic, but there is a lack of data concerning patients with chronic respiratory diseases (CRDs), who were supposed to be at risk of severe forms of COVID-19. Methods This nationwide retrospective cohort study describes patients with prior lung disease hospitalised for COVID-19 (March–April 2020) or influenza (2018–2019 influenza outbreak). We compared the resulting pulmonary complications, need for intensive care and in-hospital mortality depending on respiratory history and virus. Results In the 89 530 COVID-19 cases, 16.03% had at least one CRD, which was significantly less frequently than in the 45 819 seasonal influenza patients. Patients suffering from chronic respiratory failure, chronic obstructive pulmonary disease, asthma, cystic fibrosis and pulmonary hypertension were under-represented, contrary to those with lung cancer, sleep apnoea, emphysema and interstitial lung diseases. COVID-19 patients with CRDs developed significantly more ventilator-associated pneumonia and pulmonary embolism than influenza patients. They needed intensive care significantly more often and had a higher mortality rate (except for asthma) when compared with patients with COVID-19 but without CRDs or patients with influenza. Conclusions Patients with prior respiratory diseases were globally less likely to be hospitalised for COVID-19 than for influenza, but were at higher risk of developing severe COVID-19 and had a higher mortality rate compared with influenza patients and patients without a history of respiratory illness.
Prevalence of Myocardial Hypertrophy and Double Mutations in Sarcomere Gene Mutation Carriers
Authors: Fujino Noboru, Konno Tetsuo, Hayashi Kenshi, Sakata Kenji, Fujita Takashi, Houdatsu Akihiko, Tsuda Toyonobu, Nagata Youji, Nomura Akihiro, Kawashiri Masaaki, Ino Hidekazu, Yamagishi Masakazu
Journal: Circulation (2014)
25P Investigation of TLR4 and pSTAT3 expression on circulating tumour cells (CTCs) in patients with metastatic breast cancer (mBC)
Authors: M.A. Papadaki, C.A. Apostolopoulou, A. Monastirioti, D. Aggouraki, C. Papadaki, K. Michaelidou, D. Mavroudis, S. Agelaki
Journal: Annals of Oncology (2021)
Abstract 16511: Isocaloric Fructose Restriction Improves Postprandial Chylomicron and VLDL Excursions in Adolescents With Obesity by Reducing Angiopoietin-Like Protein 3 and Apolipoprotein CIII
Authors: Yasmin Bains, Ayca Erkin-Cakmak, Russell Caccavello, Kathleen Mulligan, Susan Noworolski, Jean-Marc Schwarz, Robert Lustig, Alejandro Gugliucci
Journal: Circulation (2020)

Introduction: Delayed postprandial triglyceride-rich lipoprotein (TRL) metabolism is associated with increased atherogenic risk. Dietary fructose is a preferred lipogenic substrate which contributes to NAFLD and dyslipoproteinemia. Hypothesis: Isocaloric fructose restriction reduces postprandial TRL excursions in part by affecting the modulation of lipoprotein lipase (LPL) activity and peripheral clearance rates. Methods: We determined the effect of 9 days of isocaloric fructose restriction on fasting and postprandial TRL metabolism markers in obese Latino and African American children (9-18 years old; n=30) with high habitual sugar consumption (&gt;50 g/d). Metabolic assessments were performed on day 0 and day 10 of isocaloric fructose restriction (starch substituted for sugar, same macronutrient composition). To follow postprandial TRL metabolism, after an initial double-sized meal, single-sized meals (providing 67% of daily calories, 15% protein, 35% fat, 50% carbohydrate) were fed every 30 minutes, with blood sampled every hour for 8 hours. Fructose content of meals reduced from 12% on day 0 to 4% on day 10. Paired t-tests compared change from day 0 to day 10 within each child. Results: Fasting TG, apoCIII, and ANGPTL3 reduced by 25%, 28% and 26% respectively (p &lt;0.01). Postprandial AUC of TG, apoCIII, ANGPTL3, VLDL, chylomicrons (apoB48) reduced by 35%, 34%, 40%, 17%, 19% (p &lt;0.01), while no changes were found in fasting or AUC for ANGPTL4, ANGPTL8 nor LPL mass. Conclusions: Short-term isocaloric fructose restriction improved postprandial chylomicron and VLDL metabolism in children with obesity. Specific and selective improvements in ANGPTL3 and apoCIII suggest differential modulation of LPL activity as a putative mechanism that deserves further exploration.