tbuckley/cabot-search huggingface dataset:
Abstract 16403: Prevalence and Sex Differences in Early-onset Atrial Fibrillation - A Nation-wide Primary Care Study in Norway
Authors: Silje M Kalstø, Ståle Nygård, Arnljot Tveit, Inger Ariansen, Ingrid E Christophersen
Journal: Circulation (2020)

Background: Several studies have reported a male:female ratio of 4:1 in lone atrial fibrillation (AF) populations. However, there have been few reports on the young population with AF, and no reports from a primary care setting. Here, we describe prevalence and sex-differences in early-onset AF in a nation-wide register-based study in the primary care sector in Norway. Methods: In Norway, with a population of 5.4 million, healthcare is publicly financed and all general practitioner (GP) claims have been recorded in the Norwegian Control and Payment of Health Reimbursement (KUHR) registry, since 2006. We identified all individuals aged ≥18 and &lt;50 years registered with ≥1 AF diagnosis code (International Classification of Primary Care (ICPC) K78), from 2006-2019 in the KUHR registry. Based on population estimates from Statistics Norway, we calculated the prevalence of early-onset AF in 2019, as a total, by sex, and by age groups: 18-29, 30-39, 40-49. Results: We identified 5563 individuals (28.5% women, age 18-49 years) aged 18-49 in 2019 with AF diagnosed &lt;age 50 years. In 2019, the prevalence of early-onset AF registered in all individuals up to age 50 was 0.24% (women: 0.14% (1585/1114821), men 0.34% (3978/1176555), p=1.4x10 -205 ) with a ratio of 2.5 men:women. In individuals aged 18-29 the prevalence was 0.05% (women 0.04% (164/410367), men 0.07% (292/435001), p=79x10 -8 ). For the age group 30-39 years the prevalence was 0.19% (women 0.12% (408/349639), men 0.27% (985/367730), p=3.9x10 -49 ). For the age group 40-49 years the prevalence was 0.51% (women 0.29% (1013/354815), men 0.72% (2701/373824), p=1.39x10 -155 ). Conclusion: We show that the prevalence of early-onset AF in a nation-wide primary care population is 0.24% and that the sex-difference in prevalence is smaller than previously reported in early-onset and lone AF studies. Our findings underline the need of increased awareness of AF as a disease in the young, and particularly to women in the youngest age-groups.
Abstract 15226: The Impact of Chronic Obstructive Pulmonary Disease on In-hospital Outcomes Following Left Ventricular Assist Device Implantation
Authors: Bertrand Ebner, Jennifer Maning, Louis Vincent, Jelani Grant, neal olarte, Odunayo P Olorunfemi, Rosario A Colombo, Sandra Chaparro
Journal: Circulation (2020)

Background: Chronic obstructive pulmonary disease (COPD) is well-known cause of ventricular dysfunction. However, in the setting of patients with advanced heart failure undergoing left ventricular assist device (LVAD) implantation, there is paucity data on COPD influence on in-hospital outcomes. Methods: This retrospective cohort study based on the Nationwide Inpatient Sample included all patients above 18 years all who underwent LVAD implantation from 2011 to 2017. All data was weight as recommended by Healthcare Cost and Utilization Project.Multivariate logistic regression was used to evaluate the impact of COPD on in-hospital outcomes. Results: A total of 25,503 patients underwent LVAD implantation, of those 13.8% had a pre-existing diagnosis of COPD. Individuals with COPD were older (median 62 vs. 58 years, p&lt;0.001), more commonly male (82% vs. 76.4%, p&lt;0.001). Patient with COPD had a greater burden of comorbidities confirmed by significant higher rate of hypertension, diabetes, atrial tachyarrhythmias, dyslipidemia, prior stroke, coronary and peripheral artery diseases, pulmonary hypertension, and chronic kidney disease (p&lt;0.001 for all). No significant difference was found in in-hospital stroke, infections, short-term percutaneous mechanical circulatory support, implant related complications, and LVAD thrombosis. There was a significant higher rate of inpatient acute kidney injury, major bleeding, cardiac complications, thromboembolism, and cardiac arrest in patients without COPD (p&lt;0.05 for all outcomes). Compared to patients without COPD, individuals with COPD had a lower mortality (6.2% vs. 12.4%; OR 0.59; C.I. 0.512-0.685; p&lt;0.05). Conclusion: Patients with COPD undergoing LVAD implantation have higher comorbidities, however, it is not associated with increase in-hospital all-cause mortality.Further studies are needed to analyze the differences found between these two groups in more detail.
Rare PEG Allergy Triggered Postvaccination Anaphylaxis
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

Researchers in the UK have linked anaphylaxis in a patient who received the Pfizer-BioNTech COVID-19 vaccine with her allergy to polyethylene glycol (PEG), which stabilizes lipid nanoparticles that deliver mRNA in the vaccine to cells in the body.
Abstract 13040: Left Ventricle Dysfunction is Prevented by the Treatment With Methotrexate Carried in Lipid Nanoparticles in Lipopolysaccharide-injected Rats
Authors: Natalia M Lopes, Maria Carolina Guido, Camila Albuquerque, Leonardo Jensen, Raul C Maranhao
Journal: Circulation (2020)

Introduction: In infectious processes, left ventricle (LV) dysfunction is often associated with dysregulation of the immune response. LDE, a lipid core nanoparticle resembling LDL, is able to concentrate in inflammatory sites. We showed that methotrexate (MTX), associated with LDE, modulated inflammation and improved cardiac function in rats with myocardial infarction Hypothesis: Investigate therapeutic effects of LDE-MTX on LV function in lipopolysaccharide (LPS)-injected rats Methods: Wistar rats were submitted to 2 injections of LPS (10mg/kg ip), with 24h interval. Animals were allocated to control group (CT, without LPS) and 3 LPS groups: LDE, treated with only LDE; MTX, with commercial MTX; and LDE-MTX. LDE-MTX dose was 1mg/kg I.P. 72h after LPS, animals were submitted to echocardiographic analysis. Animals were euthanised for analysis of the LV Results: Rats treated with LDE developed diastolic dysfunction and presented decreased diastolic volume and diameter of the LV, which was prevented by LDE-MTX. Only LDE-MTX treatment elicited cardiac hypertrophy through the increase of the thickness of LV septum and posterior wall, LV mass, relative heart weight and myocyte diameter. Inflammatory and apoptotic markers were similar in LPS groups, but LDE-MTX treatment increased macrophage recruitment (CD68). Angiogenesis, represented by vascular endothelial growth factor (VEGF), was higher in LDE-MTX compared to all other groups. Hypoxia-inducible factor 1 alpha, which was remarkably higher in LDE, was normalized by LDE-MTX to CT levels. A1, A2b and A3 adenosine receptors expression was higher in LDE-MTX, compared to CT, indicating an increase in intracellular adenosine. Myocyte diameter was positively correlated with VEGF (r2= 0.52; p&lt;0.0001) Conclusions: The increased recruitment of immune cells to the LV indicates that treatment with LDE-MTX was effective in activating immune response, impaired by LPS. LDE-MTX increased intracellular adenosine availability, contributing to an adaptive LV hypertrophy, increase in angiogenesis and diminished cellular hypoxia. These mechanisms conceivably elicited the observed LV improvement of diastolic dysfunction caused by LPS challenge
Abstract 10876: Risk of Morbidity and Mortality in Takotsubo Cardiomyopathy With Right Ventricular Involvement - A Meta-analysis of Observational Trials
Authors: Suchith Shetty, Aaqib Malik, Kan Liu
Journal: Circulation (2019)

Background: The studies to date have reported conflicting results on the risk of mortality in Takotsubo cardiomyopathy (TTS) with right ventricular involvement (RV) when compared to TTS without RV....
11P A Breast Cancer Index (BCI) prognostic model for N0 HR+ breast cancer optimized for late distant recurrence
Authors: J.M.S. Bartlett, Y. Zhang, I. Ahmed, K. Treuner, T. Piper, S.J. Pirrie, A.M. Brufsky, D.C. Sgroi, C.A. Schnabel, D.W. Rea
Journal: Annals of Oncology (2021)
Training Future Health Justice Leaders — A Role for Medical–Legal Partnerships
Authors: Edward B. Healton, William M. Treanor, John J. DeGioia, Vicki W. Girard
Journal: New England Journal of Medicine (2021)

Medical–legal partnerships integrate lawyers directly into health care teams to help patients address health-harming legal needs. Schools could integrate these partnerships into education and training to support the next generation of health justice leaders.
Monoclonal Gammopathy of Renal Significance
Authors: Nelson Leung, Frank Bridoux, Samih H. Nasr
Journal: New England Journal of Medicine (2021)

Monoclonal gammopathy of renal significance is a B-cell or plasma-cell clonal disorder that does not meet the criteria for cancer but produces a monoclonal immunoglobulin that leads to kidney injury or disease. This review discusses pathogenesis, evaluation, and management.
Early intervention and prevention of allergic diseases
Authors: Helen A. Brough, Bruce Joshua Lanser, Sayantani B. Sindher, Joyce M. C. Teng, Donald Y. M. Leung, Carina Venter, Susan M. Chan, Alexandra F. Santos, Henry T. Bahnson, Emma Guttman‐Yassky, Ruchi S. Gupta, Gideon Lack, Christina E. Ciaccio, Vanitha Sampath, Kari C. Nadeau, Cathryn R. Nagler
Journal: Allergy (2021)

Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of (1) an intact epidermal barrier to prevent epicutaneous antigen presentation, (2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and (3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.
Abstract 15203: Acute Electronic Cigarette Exposure Decreases Heart Rate Variability in C57BL/6 Mice
Authors: Carson G Cornett, Jocelyn Castellanos, Karla Luna, Rajat Gupta, Dennis Ruenger, Yifang Zhu, Maria C Jordan, Xuesi M Shao, Kenneth P Roos, Jesus A Araujo
Journal: Circulation (2020)

Background: Despite a lack of empirical data, an unprecedented rise in electronic cigarettes (ECs) has been widely perceived as safe. Multiple studies support a causal link between tobacco cigarette (TC) use and a decline in cardiovascular (CV) health; however, there is a paucity of data with EC use. A study showed EC use decreased HRV in humans via increased sympathetic activation- a known mechanism predictive of CV disease from TC use. We aimed to develop a mouse model to determine if acute EC exposure modifies HRV in mice. Methods: Telemetry devices were implanted in the abdomen of 6 eight-week-old C57BL/6 mice to monitor ECG activity continuously. Mice underwent a 1-hr acclimation phase in exposure chambers followed by a 1-hour exposure to air (control). EC exposures consisted of two 15-min sessions (4-sec puff/26-sec air) to BluPlus® 2.4% nicotine (Classic Tobacco) with a 15-min period of aerosolized PBS added as a secondary control. For each exposure episode, a 45-min post-exposure event followed. Ponemah v6.20 software was used for HRV analysis of the time domain. A linear mixed-effects model with a robust estimator was used to determine the relationship between air vs. combined EC events and PBS (n = 1,109). R (Version R3.6.3) was utilized to test for statistical significance at α = 0.05. Results: EC exposures significantly decreased the standard deviation of NN intervals (SDNN) and root mean square of successive differences (RMSSD) by 5.00 and 9.34 units as compared to air exposures, suggesting reductions in total and short-term autonomic variability (Table 1). Both parameters increased in the post-EC periods as compared with the EC exposures. Conversely, PBS vs. air exposure showed a marked increase in SDNN and RMSSD. Conclusion: Short-term exposures to ECs decreased HRV in mice, consistent with similar results in human studies, suggesting that ECs could increase cardiovascular risk in an acute manner.
Abstract 17055: Novel Dual mTOR Inhibitor/AMPK Activator Mitigates Doxorubicin Cardiotoxicity and Potentiates Its Chemotherapeutic Efficacy Against Triple Negative Breast Cancer
Authors: Anindita Das, Sahak Hovsepian, Sayantanee Das, Arun Samidurai, Adolfo G Mauro, Chad Cain, Donatas Kraskauskas, Laura Corral, Leah Fung, Robert Sullivan, Kyle W Chan, Cathy A Swindlehurst, Fadi N Salloum
Journal: Circulation (2020)

Background: Doxorubicin (DOX) is a first-line anticancer drug for the treatment of triple negative breast cancer (TNBC). However, its dose-dependent delayed and progressive cardiotoxicity limits its therapeutic application. NovoMedix (NM922) is a novel dual mTOR inhibitor/AMPK activator that was shown to attenuate adverse cardiac remodeling and fibrosis in a pressure-overload mouse model of heart failure. We investigated whether combination therapy with DOX and NM922 exhibits synergistic chemotherapeutic effect while mitigating DOX cardiotoxicity. Methods &amp; Results: Tumors were generated in athymic female BALB/cAnNCr-nu/nu mice by implanting MDA-MB-231 cells into the rear right flank. Mice with tumors (volume≈200mm 3 ) were randomized into 6 groups and treated as follows: 1) Control (n=10); 2) DOX (3 mg/kg; i.p. twice weekly, total 15 mg/kg; n=10); 3) NM922 (25 mg/kg/d; p.o. n=5); 4) DOX+NM922 (25 mg/kg/d; p.o. n=15); 5) NM922 (100 mg/kg/d; p.o. n=5); 6) DOX+NM922 (100 mg/kg/d; p.o. n=15). Tumor size, body weight and cardiac function were assessed throughout the study. DOX alone, and to a significant extent when in combination with NM922 (25 mg/kg) reduced tumor growth compared to control. NM922 (100 mg/kg) with/without DOX significantly reduced tumor growth as compared to DOX alone (Fig A). DOX caused reduction in body weight and survival of tumor-bearing mice. NM922 did not prevent DOX-induced cachexia, but significantly improved survival in DOX-treated mice (Fig B). DOX treatment caused a significant decline in left ventricular ejection fraction compared to control over 3 weeks, which was ameliorated with NM922 (100 mg/kg) co-treatment (Fig C&amp;D). Conclusion: Our results suggest that NM922 may potentiate the chemotherapeutic efficacy of DOX in TNBC, while mitigating its cardiotoxicity. Moreover, these findings advocate the potential efficacy of utilizing lower DOX dosages when combined with NM922, which would have significant clinical implications.
Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study
Authors: Mercedes Martinez, Emily R. Perito, Pamela Valentino, Cara L Mack, Madeleine Aumar, Annemarie Broderick, Laura G. Draijer, Eleonora D.T. Fagundes, Katryn N. Furuya, Nitika Gupta, Simon Horslen, Maureen M. Jonas, Binita M. Kamath, Nanda Kerkar, Kyung Mo Kim, Kaija‐Leena Kolho, Bart G.P. Koot, Trevor J. Laborda, Christine K. Lee, Kathleen M. Loomes, Tamir Miloh, Douglas Mogul, Saeed Mohammed, Nadia Ovchinsky, Girish Rao, Amanda Ricciuto, Alexandre Rodrigues Ferreira, Kathleen B. Schwarz, Vratislav Smolka, Atsushi Tanaka, Mary E.M. Tessier, Venna L. Venkat, Bernadette E. Vitola, Marek Woynarowski, Melissa Zerofsky, Mark R. Deneau
Journal: Hepatology (2021)

Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children.We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05).The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.
Abstract P137: Association Of Equol Producing Capacity With Aortic Calcification In Middle-aged Japanese Men
Authors: Xiao Zhang, Akira Fujiyoshi, Aya Kadota, Vasudha Ahuja, Abhishek Vishnu, Lewis H Kuller, Hirotsugu Ueshima, Katsuyuki Miura, Akira M Sekikawa
Journal: Circulation (2021)

Background: Soy isoflavones (ISFs) are regularly consumed in Japan and other Asian countries where some studies showed a significant inverse association of ISFs intake with incident coronary heart disease (CHD). However, a US randomized clinical trial did not find ISFs as anti-atherogenic. This discrepancy may be due to the higher capacity of people in Japan than in the US to produce equol, a metabolite of ISF by the gut microbiome. Equol may have greater anti-atherogenic properties than ISFs. It is unknown whether equol producers (EP), people who produce equol after consuming ISF, have lower aortic calcification (AC), a biomarker of atherosclerosis, as compared to non-EP. Aim: To determine the association between equol producing status and AC in Japanese men. Method: This cross-sectional, population-based study included 302 Japanese men aged 40-49, free of CHD. EP was defined as participants with serum levels of equol ≥20 nM. AC was measured in the entire aorta and quantified by the Agatston method. The presence of AC was defined as AC score ≥10. We analyzed the association between equol producing status and AC using the Tobit and the logistic regressions. Result: We observed 125 participants as EP. In multivariable analyses, EP had non-significantly lower AC score by 147 (95% confidence interval (CI): -386, 92) units and an odds ratio of 0.71 (95% CI: 0.40, 1.26) for the AC presence as compared to non-EP. As significant interaction of equol producing status with age was present, we stratified the analyses by the median age. In men aged 45-49 years, EP had non-significantly lower AC score by 246 units and a non-significant 0.62 times the odds of AC presence as compared to non-EP; the corresponding values in men aged 40-44 were 12 units and 0.91 times (Table). Such an association was not observed with serum ISFs (data not shown). Conclusion: Japanese middle-aged men who were EP had non-significantly lower AC than non-EP and such association was stronger in men aged 45-49 than 40-44 years. Further study with much larger sample size is warranted.
SpatialDWLS: accurate deconvolution of spatial transcriptomic data
Authors: Rui Dong, Guo-Cheng Yuan
Journal: Genome biology (2021)

Abstract Recent development of spatial transcriptomic technologies has made it possible to characterize cellular heterogeneity with spatial information. However, the technology often does not have sufficient resolution to distinguish neighboring cell types. Here, we present spatialDWLS, to quantitatively estimate the cell-type composition at each spatial location. We benchmark the performance of spatialDWLS by comparing it with a number of existing deconvolution methods and find that spatialDWLS outperforms the other methods in terms of accuracy and speed. By applying spatialDWLS to a human developmental heart dataset, we observe striking spatial temporal changes of cell-type composition during development.
Abstract 15334: Increased Physical Activity is Associated With Lower Prevalence of Cardiac Symptoms in Adolescents: An Analysis of the Heartbytes Screening Registry
Authors: Abhinav Nair, Max Weiss, Sean Dikdan, Jennifer Wellings, Drew Johnson, Prashant Rao, Renee Langstaff, David M Shipon
Journal: Circulation (2020)

Background: The ACC/AHA currently recommend performing a 14-point cardiovascular (CV) evaluation when screening healthy student-athletes for CV disease. This includes a focused history to assess for cardiac symptoms including exertional chest pain, dyspnea, fatigue, palpitations, and syncope. Though the presence of these symptoms may suggest underlying CV disease, additional factors including hours of weekly physical activity may influence the prevalence of reported symptoms. The relationship between physical activity level and the prevalence of cardiac symptoms has not been fully studied in an adolescent population. Methods: We analyzed the results of 10683 consecutive athlete screenings (median age 15 years) from HeartBytes, a data registry of pre-participation youth CV screenings utilizing the 14-point AHA evaluation. Cardiac symptoms and hours of weekly physical activity were self-reported. Weekly activity level was reported as less than 2 hours, between 2 and 5 hours, between 5 and 10 hours, or as greater than 10 hours. A chi-squared analysis for independence was performed to evaluate the relationship between physical activity level and each cardiac symptom. Results: Chest pain was reported in 5.1% of athletes, and increasing hours of physical activity was associated with less reported pain ( X 2 = 73.01, p &lt;.001). Exertional dyspnea was reported in 11.7% of individuals, and increasing activity was associated with less reported dyspnea ( X 2 = 120.53, p &lt;.001). Easy fatigability was reported in 7.5% of individuals, with more activity associated with less reported fatigue ( X 2 = 376.61, p &lt;.001). Palpitations were reported in 5.1% of those screened, with increasing activity was associated with less reported palpitations ( X 2 = 95.34, p &lt;.001). Finally, syncope was reported in 1.1% of athletes, though there was no relationship between activity level and syncope ( X 2 = 5.53, p = 0.24). Conclusion: Increased physical activity is associated with lower rates of reported chest pain, exertional dyspnea, easy fatigability, and palpitations in adolescents. Further studies are needed to clarify the relationship in youth athletes between symptoms and CV health.