tbuckley/cabot-search huggingface dataset:
Abstract P196: Insomnia Symptoms And Ideal Cardiovascular Health In Older Women: Data From The Women’S Health Study
Authors: Cameron Hicks, Jonathan Butler, Natalie B Slopen, David Williams, Dayna A Johnson, Susan Redline, Julie E Buring, Michelle A Albert
Journal: Circulation (2021)

Introduction: While insomnia is associated with an increased risk of incident cardiovascular disease (CVD), its relationship with ideal cardiovascular health (ICH) is less certain. Given that sleep disturbances increase with age, we examined the relationship between insomnia symptoms and ICH in older women. Methods: Among women participating in the ongoing Women’s Health Study stress cohort with no apparent history of CVD [N= 2588; Mean age= 72.5 ± 6.3], insomnia symptoms were characterized as self-reported difficulty falling asleep or waking up multiple times a night, three or more times per week. Ideal cardiovascular health, as defined by the American Heart Association’s 2020 Impact goals, included standard optimal targets for blood pressure, total cholesterol, glucose, body mass index, physical activity, diet, and smoking. We examined the relationship between insomnia symptoms and ICH using logistic regression, adjusting for clinical and demographic variables. Results: Of the 26588 participants, 52% reported insomnia symptoms, and 38% had ICH. Women with insomnia symptoms had significantly lower odds of ICH after full adjustment for age, race/ethnicity, education, income, depression/anxiety, marital status, and sleep duration (OR [95% CI]: 0.73 [0.64-0.83]). Moreover, compared to women without insomnia symptoms, those with insomnia symptoms were significantly more likely to have hypertension, diabetes, hypercholesterolemia, depression, anxiety, currently smoke, drink one or more alcoholic beverages per day, have a BMI &gt;30, or exercise less frequently. Conclusion: In older women, insomnia symptoms were significantly associated with lower odds of ideal cardiovascular health even after adjusting for socioeconomic status, psychosocial factors, and sleep duration. These results suggest insomnia screening may be an important component of cardiovascular health promotion in this patient population. Further research is needed to evaluate the effects of sleep behavioral interventions on improving ICH.
Abstract 15274: Social Determinants of Suboptimal Cardiovascular Health Among Pregnant Women in United States
Authors: Garima Sharma, Gowtham R Grandhi, Isaac Acquah, Reed Mszar, Laxmi S Mehta, Martha Gulati, Priyanka Bhugra, Priyanka Satish, Tamer Yahya, Roger S Blumenthal, Miguel Cainzos-Achirica, Khurram Nasir
Journal: Circulation (2020)

Introduction: Cardiovascular health (CVH) and social determinants of health (SDOH) have a significant impact on maternal morbidity and mortality. We assessed the association and cumulative effects of SDOH on CVH among a nationally representative sample of pregnant women in the United States. Methods: We included cross-sectional data of pregnant women aged 18 to 49 years from the National Health Interview Survey (2013-2017). We ascertained CVH based on the following CV risk factors: hypertension, diabetes mellitus, dyslipidemia, smoking, obesity, and physical activity; classifying participants into optimal (0-1) and suboptimal (≥2) CVH. For each individual, SDOH risk score was calculated that represents the cumulative number of distinct variables (present vs absent) identified on 39 sub-components for 6 domains (economic stability, neighborhood and physical environment, community and social context, food, education, and healthcare system access). SDOH risk score was aggregated and divided into 4 quartiles. Results: Among 1,433 (3.3%, representing 2.2 million) pregnant women in US, one third (33%) of pregnant women (mean age: 33 years, 13% non-Hispanic black) had suboptimal CVH. The prevalence of hypertension, smoking, obesity and physical inactivity across the increasing SDOH quartiles were noted. Overall, 52% pregnant women with unfavorable (4 th quartile) vs 27% with favorable (1 st quartile) SDOH had suboptimal CVH. In multivariable analyses, accounting for demographics and co-morbid conditions, pregnant women with unfavorable SDOH in 4 th quartile had nearly 3-fold higher odds of suboptimal CVH. (Figure). Conclusions: Aggregate SDOH risk score provides significant discrimination of CVH in pregnant women. In pregnant women, suboptimal CVH is common and more than 1 in 2 women with highest risk of SDOH inequities have suboptimal CVH, highlighting the public health urgency for intervention in young high risk women.
Epidemiology of Heart Failure: A Contemporary Perspective.
Authors: Véronique L. Roger
Journal: Circulation Research (2021)

Designated as an emerging epidemic in 1997, heart failure (HF) remains a major clinical and public health problem. This review focuses on the most recent studies identified by searching the Medline database for publications with the subject headings HF, epidemiology, prevalence, incidence, trends between 2010 and present. Publications relevant to epidemiology and population sciences were retained for discussion in this review after reviewing abstracts for relevance to these topics. Studies of the epidemiology of HF over the past decade have improved our understanding of the HF syndrome and of its complexity. Data suggest that the incidence of HF is mostly flat or declining but that the burden of mortality and hospitalization remains mostly unabated despite significant ongoing efforts to treat and manage HF. The evolution of the case mix of HF continues to be characterized by an increasing proportion of cases with preserved ejection fraction, for which established effective treatments are mostly lacking. Major disparities in the occurrence, presentation, and outcome of HF persist particularly among younger Black men and women. These disturbing trends reflect the complexity of the HF syndrome, the insufficient mechanistic understanding of its various manifestations and presentations and the challenges of its management as a chronic disease, often integrated within a context of aging and multimorbidity. Emerging risk factors including omics science offer the promise of discovering new mechanistic pathways that lead to HF. Holistic management approaches must recognize HF as a syndemic and foster the implementation of multidisciplinary approaches to address major contributors to the persisting burden of HF including multimorbidity, aging, and social determinants of health.
Response to Comment on Piccinini and Bergman The Measurement of Insulin Clearance. Diabetes Care 2020;43:2296–2302
Authors: Richard N. Bergman, Francesca Piccinini
Journal: Diabetes Care (2020)

We thank Dr. Gastadelli and colleagues for their interest in our review article (1) and their comments (2) on the limitations of different approaches to assessing insulin clearance in humans and putative limitations of the hypothesis (3) that lower insulin clearance might cause type 2 diabetes (T2D). In fact, many of their comments relate to a series of articles from our group, and in addition to the article they refer to (1), several others (4–6) are also relevant to their comments.

Concerning the Polidori/Bergman model (4), they are correct that the approach used by Polidori et al. (4) assumes either linear or saturable hepatic insulin extraction and chooses the model that best fits the data. We believe these are reasonable assumptions and that there is little support for the claim by Gastadelli et al. (2) that a saturable model of hepatic insulin extraction is not justified based on experimental data. The articles they cite claiming that hepatic insulin extraction does not reach saturability until insulin concentrations are in the 300–500 mU/L range are based on comparisons between groups of …
Sunburn Injuries Admitted to Burn Services in Australia and New Zealand
Authors: Siobhan Connolly, Monique Bertinetti, Warwick J. Teague, Belinda J. Gabbe, Lincoln M. Tracy
Journal: JAMA Dermatology (2021)

This cohort study uses data from the Burns Registry of Australia and New Zealand to describe patients with sunburns severe enough to warrant admission to specialist burn services across Australia and New Zealand.
Abstract 069: Sporadic Step Accumulation And All-cause Mortality In The Women’S Health Study: Do All Steps Count?
Authors: Christopher C Moore, Kelly R Evenson, Eric J Shiroma, Annie G Howard, Carmen C Cuthbertson, Julie E Buring, I-Min Lee
Journal: Circulation (2021)

Background: With the popularity of step counting and feasibility of accumulating physical activity (PA) through sporadic spurts (e.g., taking the stairs), the 2018 PA Guidelines Committee called for research to inform step-based PA recommendations by quantifying relationships between patterns of stepping and health. Purpose: To examine the relationship between daily steps accumulated outside of “bouts” (sporadic steps/d) and all-cause mortality, before and after accounting for bouted steps/d. Methods: From 2011-2015, 16,732 women (mean 72 [standard deviation 6] years) wore a hip-worn accelerometer for 7 days to assess steps and met wear time criteria. Stepping bouts were defined as ≥10 consecutive minutes at ≥40 steps/min (purposeful stepping or faster), allowing for ≤20% of time and ≤5 mins at &lt;40 steps/min. Total steps/d were partitioned into steps accrued outside of bouts (sporadic steps/d; SS) and in bouts (bouted steps/d; BS). We estimated hazard ratios (HRs) for mortality through Dec 31, 2019 using Cox proportional hazard models fitted to SS in quartiles and using restricted cubic splines. Analyses were adjusted for covariates and repeated with further adjustment for BS, categorized as 0, 1-2000, and &gt;2000 steps/d in bouts. Results: Adjusted HRs (95% confidence intervals) in increasing quartiles of SS were 1.00 (reference); 0.63 (0.52, 0.76); 0.60 (0.49, 0.74); 0.54 (0.42, 0.70). In spline analyses, initial increases in SS corresponded to the greatest mortality reductions (Figure 1), with HRs of 0.69 (0.64, 0.76) per additional 1000 SS below 3200. After further adjusting for BS, initial 1000 steps/d increases in SS were association with HRs of 0.72 (0.66, 0.78). In increasing categories of BS, HRs adjusted for SS were 1.00 (reference); 0.91 (0.76, 1.09); 0.69 (0.56, 0.84). Conclusion: Daily step counts were inversely associated with mortality, regardless of how they were accumulated. These results can help inform step-based target PA volumes that communicate the benefits of increasing everyday walking behaviors.
Abstract 16966: A p53-Toll-Like Receptor 3-Bone Morphogenic Protein Interaction Regulates the Endothelial Phenotype and Function in Pulmonary Hypertension
Authors: Aneel Roy Bhagwani, Daniela Farkas, Ali Mehboob, Elena Goncharova, Laszlo Farkas
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by complex remodeling of pulmonary arteries. In addition to impaired bone morphogenic protein (BMP) signaling, deficiency of the cell cycle regulator p53 has been implicated in PAH pathogenesis. Endothelial cells (ECs) from PAH patients have reduced levels of toll-like receptor 3 (TLR3), impairing EC function. This study investigated whether the p53, TLR3 and BMP pathways regulate endothelial phenotype and function in PAH. Methods: Human pulmonary artery ECs (PAECs) and rat CD117 + ECs were used. Knockdown experiments were carried out by targeting p53 and TLR3. Cells were further treated with the MDM2 antagonist Nutlin 3a, reducing p53 degradation, and with the TLR3 agonist Poly(I:C). Rats received CD117 + EC clones or SU5416 and were subjected to chronic hypoxia and then treated with Nutlin-3a, Poly(I:C) or vehicle. Results: We detected reduced p53 levels in PAECs from PAH patients. Clonal expansion of rat CD117 + ECs resulted in hyperproliferative cells with reduced p53 and TLR3 levels and evidence for histone methylation. Then, knockdown of p53 or TLR3 increased tube formation in surviving human and rat ECs. In addition, knockdown or activation of p53 indicated regulation of TLR3 mRNA by p53. TLR3 knockdown reduced expression of BMP2, whereas the TLR3 agonist Poly(I:C) induced BMP receptor 2 expression. Upstream, reduced p53 degradation by Nutlin 3a not only increased TLR3, but also BMP2 expression and increased BMP signaling in rat ECs. Interestingly, clonal selection resulted in EC clones with high BMP2 expression. TLR3 knockdown caused partial endothelial mesenchymal transition with increased expression of Snail, which was ameliorated by Poly(I:C). In vivo, Nutlin-3a treatment reduced PH while increasing TLR3 expression in rats. Poly(I:C) reduced PH and Smad2 phosphorylation in rats, and the protective effects were abolished in TRIF KO mice. Conclusion: The RNA receptor and p53 transcriptional target TLR3 regulates the BMP pathway in ECs and this interaction may explain some of the protective effects of TLR3 stimulation in PH. However as clonally selected ECs retain high BMP2 expression, differences between EC subpopulations can be suggested and are under investigation.
127TiP Phase II, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine (CX 2009) in metastatic HR-positive/HER2 non-amplified breast cancer (mHR+/HER2− BC) and CX-2009 as monotherapy and in combination with pacmilimab in metastatic triple-negative breast cancer (mTNBC)
Authors: K.D. Miller, L.A. Emens, S.M. Tolaney, S.A. Hurvitz, E. Hamilton, V. Paton, A.L. Hannah, V. Boni
Journal: Annals of Oncology (2021)
CD1a autoreactivity: When size does matter
Authors: Laurent Gapin
Journal: The Journal of Experimental Medicine (2021)

CD1a-autoreactive T cells represent a significant proportion of circulating αβ T cells in humans and appear to be enriched in the skin. How their autoreactivity is regulated remains unclear. In this issue of JEM, Cotton et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202699) show that CD1a molecules do not randomly survey cellular lipids but instead capture certain lipid classes that broadly interfere with the binding of autoreactive T cell antigen receptors to the target CD1a. These findings provide new potential therapeutic avenues for manipulating CD1a autoreactive T cell responses.
Abstract 16565: Intramyocardial Tbx18 Gene Delivery in a Radiopaque Medium Enables Real-Time Assessment of Gene Transfer, and is Compatible With Biological Pacemaker Function
Authors: Nam Kyun Kim, Ki Hong Lee, Jonathan Langberg, Jared Beyersdorf, Natasha Fernandez, Minji Shin, Philip Santangelo, Hee Cho
Journal: Circulation (2020)

Introduction: The efficacy and specificity of myocardial gene transfer depends on retention of the injectate at the site of gene delivery. However, no direct method exists to confirm myocardial retention of a biologic delivered via an intracardiac transvenous catheter. We tested feasibility of a radiographic contrast media as a gene delivery vehicle, and fluoroscopic assessment of intramyocardial retention as well as proper function of a transgene. Methods and Results: Synthetic mRNA expressing GFP in saline was mixed with an iodine-based radiopaque contrast agent, iopamidol, at 2, 5, 20, 30 and 40%. The minimum content of iopamidol that allowed unequivocal radiographic identification ex vivo was 20%. To validate functional expression of the transgene, GFP mRNA was injected focally into the left ventricular apex of the rat heart upon thoracotomy at 0, 2, 5 or 20% iopamidol solution. On day 5, the hearts were harvested and examined for GFP expression, which illustrated comparable and focal GFP expression in all animals. To test whether gene delivery in a contrast media is compatible with intended disease-modifying activity, we employed TBX18 gene transfer via the right femoral vein in a porcine model of complete heart block. We have previously demonstrated that TBX18 could convert ventricular myocytes to pacemaker cells, and create de novo ventricular pacing in situ. Intracardiac delivery of TBX18 or GFP (n=6 or 2 pigs, respectively) mRNA dissolved in 20% iopamidol to the high His bundle region revealed clear, real-time visualization of the injectate in all pigs. In one of the 8 pigs, the injectate diffused rapidly into the ventricular circulation, which necessitated a repeat injection. The maximum heart rate of TBX18-injected pigs was faster than that of GFP-injected pigs upon β-adrenergic stimulation at 77±12 vs. 43±13 BPM at week 2 ( P =0.08), and at 93±19 vs. 48±3BPM at week 4 ( P &lt;0.05), respectively. Conclusion: Radiographic contrast agent can serve as an effective gene delivery vehicle, allowing real-time and non-invasive assessment of the retention of intramyocardial gene delivery. This approach may be generalizable to other focal gene therapy applications, and minimize suboptimal gene delivery.
Abstract 14783: Association of Daily Step Count and Resting Heart Rate With Right Ventricular Function in Pulmonary Arterial Hypertension
Authors: Grant E MacKinnon, Carolyn Whitmore, Rashundra Oggs, Shi Huang, RAVINDER MALLUGARI, Anna R Hemnes, Evan Brittain
Journal: Circulation (2020)

Introduction: Remote activity monitoring may provide new insight into behavioral choices and exercise capacity in pulmonary arterial hypertension (PAH). Here, we report baseline data from a randomized behavioral intervention (NCT03069716) to increase step counts in PAH. Hypothesis: Higher daily step count and lower resting heart rate (RHR) are associated with better right ventricular (RV) function. Methods: We recruited functional class I-III patients with idiopathic, heritable, or connective tissue disease-associated PAH on stable therapy. Participants were provided a Fitbit Charge 3 device and monitored for two weeks as a run-in period to the trial. The 6MWD test and echocardiogram were performed at baseline. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). We conducted linear regression to examine associations between daily step count and RHR with RV function, adjusted for age, sex, and BMI. Results: In total, 42 subjects completed the run-in period (48 ± 11 years, 86% female, 64% functional class II). PAH etiology was 76% idiopathic, 17% heritable, and 7% connective tissue disease. Average daily step count, RHR, and 6MWD were 4718 ± 3521 steps, 72 ± 10 beats per minute, and 424 ± 106 meters, respectively. Only 2.9% of days monitored had missing data. Daily step count (Beta 0.37mm per 1,000 steps; p = 0.039) and RHR (Beta -0.19mm per beat; p = 0.017) were associated with TAPSE ( Figure ), and daily step count was associated with FAC (Beta 1.1% per 1,000 steps; p = 0.01). The 6MWD was modestly associated with daily step count (r = 0.35; p = 0.028) but not associated with RV function (p &gt; 0.05). Conclusions: Remote activity monitoring is feasible in PAH and may provide important clinical information as an adjunct to clinic-based assessments of exercise capacity. Lower daily step count and a higher RHR are associated with poorer RV function. Interventions to increase daily activity warrant further investigation in PAH.
Abstract 15695: Contemporary Trends and Outcomes of Prosthetic Valve Infective Endocarditis in the United States: Insights From the Nationwide Inpatient Sample
Authors: Muhammad KHAN, Muhammad Munir, Muhammad U Khan, Sudarshan Balla
Journal: Circulation (2020)

Introduction: Prosthetic valve endocarditis (PVE) carries high mortality and morbidity as compared to native valve endocarditis (NVE). Hypothesis: Hospital outcomes have shown improvement over the years in PVE Methods: We used the National Inpatient Sample from 2000 to 2017 to identify patients admitted with PVE who 18 years and older using ICD-9-CM and ICD-10 codes (421.0,421.1,421.9, V433.0, I33.0, I33.9, and Z95.2). Patients with prior history of prosthetic valve were identified using the respective ICD-9. Risk-adjusted rates were calculated using an Analysis of Covariance (ANCOVA) with the Generalized Linear Model (GLM). Trends were assessed with linear regression and Pearson’s Chi-square when appropriate. Binomial logistic regression was used to assess predictors of in-hospital mortality. Results: We identified 43,602 hospitalizations for PVE. PVE increased from 1803 in 2000 to 3450 in 2017. Risk-adjusted mortality decreased from 10.7% in 2002 to 7.3% in 2017 (P&lt;0.01)(Figure). Logistic regression analysis on mortality showed increase association with age (OR, 1.021[1.017-1.024], Hispanics (OR, 1.493[1.296-1.719],p&lt;0.01) and patients with drug abuse(OR, 1.233[1.05-1.449],p=0.01). co-morbid conditions like congestive heart failure (OR, 1.511[1.366-1.673],p&lt;0.01), renal failure (OR, [1.572[1.427-1.732],p&lt;0.01) and weight loss (OR, 1.425[1.093-1.419],p&lt;0.01) were also associated with higher mortality. Conclusions: Adjusted in-hospital mortality from PVE has trended down over the years. The findings reflect improved health care delivery over the study years for patients with PVE.
Abstract 16647: Left Ventricular Electro-Mechanical Discoordination is Present in Patients With Tetralogy of Fallot Not Meeting Conventional Criteria for Pulmonary Valve Replacement
Authors: Alexis L Gerk, Michal Schafer, Benjamin Frank, Johannes von Alvensleben, Dunbar D IVY, Max B Mitchell
Journal: Circulation (2020)

Introduction: Pulmonary regurgitation (PR) and RV dilation influence timing of pulmonary valve replacement (PVR) in patients with repaired Tetralogy of Fallot (rTOF). LV function is an independent marker of TOF patient outcomes. New markers of electromechanical discoordination (EMD) have recently been described. Systolic stretch fraction (SSF) quantifies the ratio of ventricular myocardium inappropriately relaxing during systole. Diastolic relaxation fraction (DRF) quantifies inappropriate myocardial contraction during diastole. We analyzed LV EMD using SSF and DRF in rTOF patients with PR who do not meet commonly used criteria for PVR with mild to moderate RV dilation (&lt;150 mL/m 2 ). Hypothesis: Patients with rTOF will have abnormal LV EMD. Methods: Patients (n=18) and healthy controls (n=20) with rTOF and PR underwent cardiac MRI. LV EMD was analyzed using SSF and DRF (Figure) derived from strain and strain rate analysis considering individual LV myocardial segments. Rank-sum test was used to compare groups. SSF and DRF were assessed for linear correlations with RVEDVi by Pearson method. Results: There were 9 male and 9 female TOF patients (Mdn age 15, range 9-55). TOF patients had increased RVEDVi (118±23 ml/m 2 , p&lt;0.001) and increased RVESVi (56±13 ml/m 2 , p&lt;0.001) compared to controls. RV EF was lower in TOF patients but within normal physiologic range (53±6%, p=0.008). LV size indices and EF did not differ. TOF patients had increased SSF (Mdn 0.035, IQR 0.015-0.052, p=0.002) and significantly decreased DRF (Mdn 2.735, IQR 2.358-2.959, p&lt;0.0001). RVEDVi correlated with increased SSF (R=0.51, p=0.011) and decreased DRF (R=0.62, p=0.007). Conclusions: TOF patients with PR and mild to moderate RV dilation have significant LV EMD during both systole and diastole. The degree of systolic and diastolic EMD correlate with RV dilation. SSF and DRF are unique and sensitive early markers of LV dysfunction compared to conventional MRI metrics.