tbuckley/cabot-search huggingface dataset:
Abstract 17469: Comparing the Effect of CRT Implantation on Quality of Life in Older Patients Compared With Younger Patients: Systematic Review and Meta-Analysis
Authors: Praveen Ponnamreddy, Saeed Juggan, Lauren Gilstrap
Journal: Circulation (2020)

Background: CRT had been accepted as standard of care for patients with HFrEF who qualify for the therapy. The pivotal CRT trials enrolled patients significantly younger than the typical HFrEF patients seen in the community. Benefits of CRT in older HFrEF patients is largely unknown. We sought to evaluate the change in quality of life in older patients undergoing CRT in comparison to younger patients. Hypothesis: CRT implantation is associated with comparable improvements in quality of life in younger patients (age &lt;70) and older patients (age 70 and above). Methods: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older HFrEF patients. We gathered data for Quality of life measurements including improvement in NYHA class, MLHFQ, Six minute walk test. MLHFQ, Six minute walk test data was analyzed qualitatively as data was insufficient to impute Standard deviation for mean change. Changes in NYHA class was analyzed quantitatively. Random effects meta-analysis of improvement in NYHA class and relative risk (RR) is reported along with estimates of heterogeneity Results: Seven studies [n=2494 for younger group and n=1035 for older group] were included in changes in NYHA class meta-analysis. Older age group patients had similar improvement in NYHA class compared to younger age group patients. Relative risk 0.99 with 95%CI 0.93-1.06 (figure). Five studies reported Baseline and follow up MLHFQ scores for both the groups. All the five studies reported improvements in MLHFQ in both the groups. Three studies reported change in six minute walk test in meters before and after CRT implantation. All the studies reported improvement in six minute walk test both in younger and older group. Conclusions: People older than 70 years of age with heart failure with reduced ejection fraction who qualify for CRT derive similar benefits with improvement in quality of life compared to patients aged less than 70 years of age.
Abstract MP44: Adolescent Predictors Of Changes In Weight Status From Adolescence To Adulthood: Evidence From The Addhealth Study
Authors: Liliana Aguayo, Solveig Argeseanu Cunningham
Journal: Circulation (2021)

Introduction: The persistence of obesity from adolescent to adult ages is associated with risk of cardiovascular disease later in life. Data from cohorts that passed through childhood before 1980 show that when obesity is first observed in youth it often persists into adulthood. However, less is known about current weight trajectories of adolescents transitioning to adulthood. We examined the changes in weight status from adolescence to adulthood and baseline predictors of normal weight in adulthood. Methods: Study used data from the National Longitudinal Study of Adolescent Health (AddHealth) (n=14,135), a nationally representative sample of adolescents recruited in 1994 and followed up in 1996, 2001, and 2008. Weight and height measurements collected at each visit were used to classify weight status; we identified 4 trajectories between mean ages 16 and 30: 1) maintained normal weight, 2) achieved normal weight, 3) gained weight to enter the obesity category, and 4)maintained overweight or obesity. Logistic regression models included individual and family characteristics. Results: Among adolescents with normal weight, 56% gained weight to enter overweight or obesity categories 14 years later. Of those with overweight at baseline, 68% gained weight to enter obesity and 8% achieved normal weight; among adolescents with obesity, 89% maintained obesity, and only 2% achieved normal weight. After controlling for sex, age, race-ethnicity, and baseline weight status, adolescents who were trying to lose weight, skipped breakfast, ate dinner with their parents, had a mother with diabetes or obesity, a father with obesity, parents with less than high-school education, or married in high-school were less likely to have normal weight as adults. Independent of baseline weight status, adolescents who reported feeling loved were more likely to have normal weight in adulthood. Conclusion: Findings shed light on individual and family factors associated with normal weight outcomes after the transition from adolescence to adulthood.
Abstract P046: Prevalence Of Covid-19 Related Concerns And The Association With Participant Characteristics Among Adults With Heart Disease Engaged In Telebehavioral Therapy During The Pandemic
Authors: Nicole Kashine, Heidi M Greenberger, Evie Andreopoulos, Reena L Pande
Journal: Circulation (2021)

Introduction: Individuals with cardiac conditions may be at increased risk for behavioral health issues, as well as for adverse COVID-19 outcomes. The purpose of this study was to examine the prevalence and types of COVID-19 related concerns, and associated characteristics, among U.S. adults with heart disease engaged in a telebehavioral therapy program during the COVID-19 pandemic. Methods: The analytic sample comprised de-identified data from a consecutive cohort of 480 adults with heart disease (62% female, 27% non-white race/ethnicity, mean age 70.9 ± 12.6 years) that completed an initial consultation for an evidence-based telebehavioral therapy program between March 23 - April 11, 2020. Baseline characteristics including age, sex, race/ethnicity, U.S. region, marital status, living alone, employment status, self-rated health (from the 36-Item Short Form Health Survey), and psychological symptom severity (Depression Anxiety Stress Scales 21) were obtained through standardized assessment conducted by a licensed therapist. COVID-19 related concerns were abstracted from clinical notes and characterized using qualitative research methods. Associations between participant characteristics and the presence of a COVID-19 concern were evaluated using chi-square statistics and logistic regression. Results: Forty percent of participants (191/480) reported at least one COVID-19 related concern at their initial consultation. The three most prevalent concerns were anxious feelings associated with the pandemic (14.2%), isolation (11.9%), and health-related concerns (e.g., contracting COVID-19; 11.9%). Depression (39.9%), anxiety (40.1%), and stress (26.3%) symptoms were prevalent among participants. There were no significant associations between having a COVID-19 concern and age &gt;=65 years, U.S. region, unmarried/unpartnered status, living alone, unemployed status, poor/fair self-rated health (p&gt;.05). Female vs. male sex (45% vs. 32%; p=.006) and white vs. non-white race/ethnicity (43% vs. 30%; p=.006) were each associated with higher odds of having a COVID-19 related concern; after multivariate adjustment these associations remained significant (OR female sex = 1.8, 95%CI 1.2-2.7; OR white race/ethnicity = 1.9, 95%CI = 1.2-3.0). Conclusion: COVID-19 related concerns were common among adults with heart disease engaged in telebehavioral health care during the COVID-19 pandemic, and more common among female and white participants.
Long-Term Complications After Aortic Coarctation Stenting
Authors: Maria Alvarez-Fuente, Ana Ayala, Elvira Garrido-Lestache, Ramon Bermudez-Cañete, Ana Garcia-De Vicente, Maria Toledano, Inmaculada Sanchez, Cesar Abelleira, Isabel Molina, Maria Jesus del Cerro
Journal: Journal of the American College of Cardiology (2021)
Abstract MP11: Systematic Discovery Of Thousands Of Gene-Environment Interactions For Cardiometabolic Serum Biomarkers
Authors: Kenneth E Westerman
Journal: Circulation (2021)

Background: Gene-environment interaction (GEI) analysis enables us to understand how genetic variants modify the effects of environmental exposures on cardiometabolic risk factors, providing a foundation for genome-based precision medicine. Ideally, these interactions could be mapped comprehensively across all measured genetic variants, exposures, and outcomes, but this approach is computationally intensive and statistically underpowered. Recent studies have shown that variance-quantitative trait loci (vQTLs), or genetic variants that associate with differential variance of an outcome, are substantially enriched for underlying GEIs. Here, we sought to first identify vQTLs for cardiometabolic traits, then use this smaller genetic search space to uncover novel gene-environment interactions across thousands of environmental exposures. Methods: A two-stage, multi-ancestry analysis was conducted in 355,790 unrelated participants from the UK Biobank. First, we performed a genome-wide vQTL scan for each of 20 serum metabolic biomarkers, including but not limited to lipids, lipoproteins, and glycemic measures. This scan used Levene’s test to identify genetic markers whose genotypes are associated with the variance, rather than the mean, of the biomarker. Next, we collected over 2000 variables corresponding to socioeconomic, dietary, lifestyle, and clinical exposures, and conducted an interaction analysis for each combination of exposure and vQTL-biomarker pair. For each stage, the analysis was initially stratified by ancestry then meta-analyzed to generate the primary set of results. Results: vQTLs were identified at 514 independent regions in the genome, with most of these genetic variants already known to affect the mean biomarker level. In the subsequent gene-environment interaction analysis, we found 2,162 significant interactions passing a stringent significance threshold adjusted for multiple testing ( p &lt; 0.05 / 578 vQTL-biomarker pairs / 2140 exposures = 4х10 -8 ). Some of these expanded on existing findings; for example, genetic marker rs2393775 in the HNF1A gene interacted with education level (as a proxy for socioeconomic status) to influence hsCRP ( p = 1.3х10 -10 ), building on a previous finding that HNF1A variants modify the effect of perceived stress on cardiovascular outcomes. Others highlighted novel biology, such as an interaction between variants near the fatty liver-associated gene TM6SF2 and oily fish intake on total and LDL-cholesterol levels ( p = 6.6х10 -9 ). Conclusions: Our systematic GEI discovery effort identified thousands of interactions that may impact cardiometabolic risk, both expanding on previous research and identifying novel biological mechanisms. This catalog of vQTLs and interactions can inform future mechanistic studies and provides a knowledge base for genome-centered precision approaches to cardiometabolic health.
Abstract 13027: Differential Direct Effects of Equal Hypotensive Natriuretic Peptides (NPs) of ANP, BNP and CNP on Left Ventricular Contractile Performance in Heart Failure: Assessment by Left Ventricular Pressure-Volume Analysis
Authors: Che Cheng, Zhi Zhang, Tiankai Li, Xiaowei Zhang, Xiaoqiang Sun, Jing Cao, David M Herrington, David X Zhao, Heng Jie Cheng
Journal: Circulation (2020)

Background: Natriuretic peptides (NPs) play a crucial role in maintaining cardiovascular homeostasis. NPs stimulate the production and release of cGMP, leading to the vasodilating and natriuretic actions. In heart failure (HF), circulating and cardiac ANP, BNP, and CNP are increased and exhibit a range of actions. However, although they serve as therapeutic agents, their direct cardiac effects in HF are uncertain due to the confounding influence of NPs-produced changes in loading condition on conventional measures of LV function. We test the hypothesis that equal hypotensive 3 NPs may have different inotropic effects on LV contractility and relaxation in HF. Methods: We assessed the cardiac effects of intravenous infusion (20 min) of ANP (2 μg/kg plus 0.5 μg/kg/min), BNP (2 μg/kg plus 0.04 μg/kg/min) and CNP (2 μg/kg plus 0.4 μg/kg/min) on different days in 6 instrumented conscious dogs with pacing-induced HF by using pressure (P)-volume (V) analysis, a load-independent measure of LV contractility. Results: Versus baselines, 3 NPs produced arterial vasodilation with similar and significant decreases in LV end-systolic pressure (10 to 12 mmHg) with relatively unchanged heart rate. ANP caused significant reductions (13%) of E ES (4.2 vs 4.8 mmHg/ml) and M SW (54.6 vs 62.8 mmHg). The time constant of LV relaxation (τ, 45.1 vs 37.6 ms) was lengthened. The LV-arterial coupling, E ES / E A (arterial elastance) (0.57 vs 0.58) was unaltered. The peak mitral flow, dV/dt max was only increased by 7% (178 vs 166 ml/s). With BNP, there were no significant changes in E ES (5.1 vs 4.9 mmHg/ml) and M SW, but E ES /E A was improved 30% (0.74 vs 0.57) due to decreased E A . τ (33.4 vs 37.9 ms) was significantly shortened and dV/dt max increased 15% (189 vs 165 ml/s). In contrast, CNP produced significant increases (~30%) in E ES (6.3 vs 4.8 mmHg/ml) and M SW (80.5 vs 62.4 mmHg) with enhanced increase in E ES /E A (50%, 0.87vs 0.58), but decrease in τ (25%, 28.4 vs 38.1 ms) and significantly greater augmented dV/dt max (25%, 205 vs 164 ml/s). Similar observations of NPs were made at constant heart rate, or after autonomic blockade. Conclusion: In conscious dogs with HF, equal hypotensive ANP, BNP and CNP have negative, no effect, and positive inotropic effects on LV contractility and relaxation, respectively.
Efficacy and safety of tildrakizumab in patients with active psoriatic arthritis: results of a randomised, double-blind, placebo-controlled, multiple-dose, 52-week phase IIb study
Authors: Philip J Mease, Saima Chohan, Ferran J Garcia Fructuoso, Michael E Luggen, Proton Rahman, Siba P Raychaudhuri, Richard C Chou, Alan M Mendelsohn, Stephen J Rozzo, Alice Gottlieb
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To evaluate efficacy and safety of the anti-interleukin-23p19 monoclonal antibody tildrakizumab in patients with psoriatic arthritis (PsA). Methods In this randomised, double-blind, placebo-controlled, phase IIb study, patients with active PsA were randomised 1:1:1:1:1 to tildrakizumab 200 mg every 4 weeks (Q4W); tildrakizumab 200, 100 or 20 mg Q12W; or placebo Q4W. Patients receiving tildrakizumab 20 mg or placebo switched to tildrakizumab 200 mg Q12W at W24; treatment continued to W52. The primary efficacy endpoint was proportion of patients with ACR20 response (≥20% improvement by American College of Rheumatology criteria) at W24. Secondary efficacy endpoints were assessed without adjustment for multiplicity. Safety was evaluated from treatment-emergent adverse events (TEAEs). Results 391/500 patients screened were randomised and treated. At W24, 71.4%–79.5% of tildrakizumab-treated versus 50.6% of placebo-treated patients achieved ACR20 (all p&lt;0.01). Patients receiving tildrakizumab versus placebo generally achieved higher rates of ACR50, Disease Activity Score in 28 joints with C reactive protein &lt;3.2, minimal disease activity and 75%/90%/100% improvement from baseline Psoriasis Area and Severity Index responses at W24 and through W52. Improvement in dactylitis and enthesitis was not observed; results were mixed for other outcomes. Responses in patients switched to tildrakizumab 200 mg at W24 were consistent with treatment from baseline. TEAEs and serious TEAEs occurred in 64.5% and 3.3%, respectively, of all patients through W52 and were comparable among treatment arms. Conclusions Tildrakizumab treatment significantly improved joint and skin manifestations of PsA other than dactylitis and enthesitis. Treatment was generally well tolerated through W52. Clinicaltrials.gov NCT02980692 .
Abstract 025: Mediterranean Diet Trajectories And Changes In Cardiovascular Risk Factors And Inflammation Markers Over A 12.7 Years Follow-up: Prospective Findings From The Moli-sani Study Cohort
Authors: Marialaura Bonaccio, Simona Costanzo, Augusto F Di Castelnuovo, Alessandro Gialluisi, Amalia De Curtis, Mariarosaria Persichillo, Claudio Tabolacci, Francesco Facchiano, Chiara Cerletti, Maria Benedetta Donati, Giovanni De Gaetano, Licia Iacoviello
Journal: Circulation (2021)

Introduction: Trends in diet quality worldwide indicate a progressive decline in adherence to Mediterranean diet (MD), but data on longitudinal individual-level changes are still limited, especially in Mediterranean countries. Hypothesis: We assessed the hypothesis of an association, in a Mediterranean population, between life course trajectories in MD and concurrent long-term modifications of risk factors for cardiovascular disease (CVD) and inflammatory markers. Methods: We followed 2,107 men and women (mean age at baseline 54.6±8.8 y) from the Moli-sani Study (Italy) between 2005 and 2020. Dietary data were measured at baseline and at a re-examination (after an average of 12.7 years) and were collected by a 188-item food frequency questionnaire. Adherence to MD was estimated by a Mediterranean diet score based on 9 food groups, ranging from 0 to 9 points. MD trajectories were identified as downward (-6 to -2 points in MDS), relatively stable (-1 to 0) and upward (1 to 6). Inflammation was measured by both an INFLA-score including C-reactive protein and cellular markers ( e.g ., leukocyte count) and a CYTO-score including 14 selected analytes (cytokines, chemokines and growth factors). Regression models were used to examine changes in MDS, CVD risk factors and inflammation markers within the same period. Results: Overall, adherence to MD decreased by an average of 6.5% over follow-up. As opposed to the downward, an upward trajectory in MD adherence was inversely associated with the INFLA-score (β=-0.177; 95%CI -0.296, -0.058) and the CYTO-score (β=-0.311; 95%CI -0.548, -0.073). No significant changes were observed for CVD risk factors, with the exception of an increase in blood glucose (β=0.121; 95%CI 0.001, 0.241) and systolic blood pressure (β=0.110; 95%CI 0.003, 0.217) associated with an upward MD trajectory. Conclusions: In a large sample of Mediterranean individuals, diet quality, as reflected by adherence to an MD, has been declining over the last decade. However, in the group of subjects who improved their adherence to an MD, a significant reduction of markers of an inflammatory status was documented, possibly predisposing to a better duration and quality of life.
Bedside Detection and Follow-Up of Pulmonary Artery Stenosis after Lung Transplantation
Authors: Francesco Zarantonello, Nicolò Sella, Tommaso Pettenuzzo, Giulio Andreatta, Andrea Dell’Amore, Chiara Giraudo, Federico Rea, Paolo Navalesi
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Bedside Detection and Follow-Up of Pulmonary Artery Stenosis after Lung Transplantation." American Journal of Respiratory and Critical Care Medicine, 204(9), pp. 1100–1102
Abstract 13155: Differences in Cardiovascular Prescription Drug Utilization Among Medicaid Beneficiaries in Early Expander vs. Non-expander States From 2011 to 2018
Authors: Andrew Sumarsono, Hussain Lalani, Matthew W Segar, Ambarish Pandey
Journal: Circulation (2020)

Introduction: Cardiovascular disease remains the leading cause of death in the United States. In 2014, the Affordable Care Act expanded Medicaid eligibility allowing low-income adults to access healthcare. It remains unclear how Medicaid expansion affected access to cardiovascular prescription drugs. Methods: We used the publicly available Medicaid State Drug Utilization dataset to evaluate the utilization of statins, P2Y12 receptor blockers (P2Y12-RB), and seven classes of oral antihypertensives. We used a difference-in-differences analysis to compare quarterly prescriptions per 1,000 Medicaid beneficiaries for each drug class among Medicaid expansion states versus non-expansion states during the three years before and five years after the 2014 Medicaid expansion. Results: Between 2011 and 2018, the number of annual prescriptions of statins, P2Y12-RB, and antihypertensives increased by 89.7% (11.0 to 20.8 million), 37% (1.7 to 2.3 million), and 76% (35.3 to 62.2 million). Medicaid expansion states had higher quarterly prescriptions per 1000 Medicaid beneficiaries compared to non-expansion states for statins (22.54 [CI 95%: 15.5 to 28.58], p&lt;0.001), antiplatelets (1.68 [CI 95%: 1.15 to 2.21], p&lt;0.001), and antihypertensives (63.21 [CI 95%: 47.31 to 79.11], p&lt;0.001). Conclusion: National Medicaid use of statins, P2Y12-RB, and antihypertensives increased between 2011 to 2018. The Medicaid expansion was associated significant increases in per-capita utilization of all cardiovascular prescription drugs. These gains in utilization are likely providing long-term cardiovascular benefits to lower-income and previously underinsured populations. Figure 1: Trends in Quarterly Prescriptions/1000 Beneficiaries of statins, anti-platelets, and antihypertensives between 2011 to 2018 between expander and non-expander states. 1A: statins. 1B: P2Y12 inhibitors. 1C: Antihypertensives
Infections in Sézary syndrome: A retrospective cohort study of 113 patients
Authors: Caterina Cariti, Pietro Quaglino, Tommaso Lupia, Mauro Novelli, Elena Marra, Paolo Fava, Virginia Caliendo, Luca Tonella, Francesco Giuseppe De Rosa, Maria Teresa Fierro, Simone Ribero
Journal: Journal of the American Academy of Dermatology (2021)
An antibody-like peptidic network for anti-angiogenesis
Authors: Kuo Zhang, Hui Zhang, Xiao-Ran Zou, Ying Hu, Da-Yong Hou, Jia-Qi Fan, Chao Yang, Zi-Ming Chen, Shi-Fang Wen, Hui Cao, Pei-Pei Yang, Lei Wang
Journal: Biomaterials (2021)
An innovative NRF2 nano-modulator induces lung cancer ferroptosis and elicits an immunostimulatory tumor microenvironment
Authors: Chih-Hsiung Hsieh, Hung-Chia Hsieh, Fu-Hsuan Shih, Pei-Wen Wang, Li-Xing Yang, Dar-Bin Shieh, Yi-Ching Wang
Journal: Theranostics (2021)

Simultaneous targeting of both the tumor microenvironment and cancer cells by a single nanomedicine has not been reported to date. Here, we report the dual properties of zero-valent-iron nanoparticle (ZVI-NP) to induce cancer-specific cytotoxicity and anti-cancer immunity. Methods: Cancer-specific cytotoxicity induced by ZVI-NP was determined by MTT assay. Mitochondria functional assay, immunofluorescence staining, Western blot, RT-qPCR, and ChIP-qPCR assays were used to dissect the mechanism underlying ZVI-NP-induced ferroptotic cancer cell death. The therapeutic potential of ZVI-NP was evaluated in immunocompetent mice and humanized mice. Immune cell profiles of allografts and ex vivo cultured immune cells were examined by flow cytometry analysis, RT-qPCR assay, and immunofluorescence. Results: ZVI-NP caused mitochondria dysfunction, intracellular oxidative stress, and lipid peroxidation, leading to ferroptotic death of lung cancer cells. Degradation of NRF2 by GSK3/β-TrCP through AMPK/mTOR activation was enhanced in such cancer-specific ferroptosis. In addition, ZVI-NP attenuated self-renewal ability of cancer and downregulated angiogenesis-related genes. Importantly, ZVI-NP augmented anti-tumor immunity by shifting pro-tumor M2 macrophages to anti-tumor M1, decreasing the population of regulatory T cells, downregulating PD-1 and CTLA4 in CD8+ T cells to potentiate their cytolytic activity against cancer cells, while attenuating PD-L1 expression in cancer cells in vitro and in tumor-bearing immunocompetent mice. In particular, ZVI-NPs preferentially accumulated in tumor and lung tissues, leading to prominent suppression of tumor growth and metastasis. Conclusions: This dual-functional nanomedicine established an effective strategy to synergistically induce ferroptotic cancer cell death and reprogram the immunosuppressive microenvironment, which highlights the potential of ZVI-NP as an advanced integrated anti-cancer strategy.