tbuckley/cabot-search huggingface dataset:
Abstract 055: Neighborhood-Wide Association Study Of Hypertension In The Health And Retirement Study
Authors: Kendra D Sims, Perry W Hystad, G. D Batty, Ellen Smit, Jessina C McGregor, Michelle C Odden
Journal: Circulation (2022)

Background: Systematic evaluation of neighborhood factors which capture an array of characteristics -analogous to genome-wide-association studies- may identify important patterns in spatial determinants of blood pressure control. Methods: Our sample included Health and Retirement Study participants (N=13180; 58% women, 13% non-Hispanic Black, 4% Hispanic/Latino) with at least one sphygmomanometer reading taken between 2006 and 2016. Our main study outcome was at least one hypertensive blood pressure measurement over the study period. Participants were randomly assigned to either a training or test dataset. Using generalized estimating equations, we summarized multivariable associations between each of 51 standardized American Community Survey sociodemographic, housing, and income-related census tract variables (2005-09) and the period prevalence of measured hypertension. We adjusted for individual factors and accounted for multiple comparisons in the training set using the Simes significance test. Neighborhood-based factors that revealed statistically significant associations (Simes-adjusted p-value&lt;=0.05) with hypertension in the training dataset were rerun in the test dataset to replicate findings. Lastly, in the full cohort, we evaluated main and race/ethnicity-stratified independent effects of each significant neighborhood factor on the likelihood of at least one hypertensive sphygmomanometer reading between 2006 and 2016. We hypothesized that residence in neighborhoods with worse housing or socioeconomic characteristics would be associated with a higher odds of hypertension, and that associations in the full sample would differ by racial/ethnic designation. Results: Thirty-two percent (4218 out of 13180) of participants had at least one hypertensive sphygmomanometer reading between 2006 and 2016. In the training set, two of the 51 census-tract level variables were independently associated with period prevalence of hypertension. In the full sample, we observed a lower likelihood of prevalent hypertension (OR: 0.95; 95% CI: 0.92, 0.99) among participants residing in a census tract with recent (since 2000) in-migration. A higher proportion of relatively recent (since 2000) renters in the census tract was associated with a lower hypertension prevalence (OR: 0.95; 95% CI: 0.91, 0.98). When stratified by racial/ethnic designation, these patterns were apparent among Non-Hispanic White and to some extent Hispanic/Latino but not Non-Hispanic Black participants. However, differences were not statistically significant by race or ethnicity. Conclusion: In conclusion, relatively more recent relocation to an area appears to be modestly associated with reduced prevalence of hypertension. These findings support possible differential cardiovascular health impacts of gentrification. Further investigation is needed to confirm these findings.
Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy
Authors: Ren Jie Phang, Rebecca H Ritchie, Derek J Hausenloy, Jarmon G Lees, Shiang Y Lim
Journal: Cardiovascular Research (2022)

Abstract Patients with Type 2 diabetes mellitus (T2DM) frequently exhibit a distinctive cardiac phenotype known as diabetic cardiomyopathy. Cardiac complications associated with T2DM include cardiac inflammation, hypertrophy, fibrosis, and diastolic dysfunction in the early stages of the disease, which can progress to systolic dysfunction and heart failure. Effective therapeutic options for diabetic cardiomyopathy are limited and often have conflicting results. The lack of effective treatments for diabetic cardiomyopathy is due in part, to our poor understanding of the disease development and progression, as well as a lack of robust and valid preclinical human models that can accurately recapitulate the pathophysiology of the human heart. In addition to cardiomyocytes, the heart contains a heterogeneous population of non-myocytes including fibroblasts, vascular cells, autonomic neurons, and immune cells. These cardiac non-myocytes play important roles in cardiac homeostasis and disease, yet the effect of hyperglycaemia and hyperlipidaemia on these cell types is often overlooked in preclinical models of diabetic cardiomyopathy. The advent of human-induced pluripotent stem cells provides a new paradigm in which to model diabetic cardiomyopathy as they can be differentiated into all cell types in the human heart. This review will discuss the roles of cardiac non-myocytes and their dynamic intercellular interactions in the pathogenesis of diabetic cardiomyopathy. We will also discuss the use of sodium-glucose cotransporter 2 inhibitors as a therapy for diabetic cardiomyopathy and their known impacts on non-myocytes. These developments will no doubt facilitate the discovery of novel treatment targets for preventing the onset and progression of diabetic cardiomyopathy.
Efficacy and Safety of Edoxaban 15 mg According to Renal Function in Very Elderly Patients With Atrial Fibrillation: A Subanalysis of the ELDERCARE-AF Trial
Authors: Tetsuro Yoshida, Akihiro Nakamura, Junichi Funada, Mari Amino, Wataru Shimizu, Masayuki Fukuzawa, Saori Watanabe, Takuya Hayashi, Takeshi Yamashita, Ken Okumura, Masaharu Akao
Journal: Circulation (2022)
Abstract P019: Compensatory Hyperinsulinemia Is An Independent Risk Factor For Atherosclerotic Cardiovascular Disease: CARDIA 30-year Follow Up
Authors: Sarah Farooq, Alok Dwivedi, David P Cistola
Journal: Circulation (2022)

Introduction: Compensatory hyperinsulinemia (CH) is the heightened response of thepancreas and liver to early insulin resistance. Elevated blood insulin compensates for insulin resistance in tissues, maintainingfasting glucose, triglycerides and HDL-cholesterol within normal limits. Individuals with CH, as defined here, do notmeet the harmonized criteria for metabolic syndrome and elude screening for cardiovascularrisk. Previously, we reported that CH isprevalent in the U.S., especially in teenagers, young adults, Hispanic andBlack populations. However, it wasunclear whether CH increases the risk of future atherosclerotic cardiovasculardisease (ASCVD) or simply is a benign adaptation to energy imbalance. Hypothesis: Compensatory hyperinsulinemia is an independentrisk factor for ASCVD. Methods: We conducted a retrospectivecohort study of CARDIA: Coronary ArteryRisk Development in Young Adults. Theparent study enrolled 5,113 participants, ages 18-30 at baseline, with studyvisits every five years for a mean follow up of 30 years. In our study, the baseline exclusion criteriawere hyperglycemia, hypertriglyceridemia and low HDL-C (all using metabolicsyndrome cutpoints), as well as pregnancy, fasting &lt;8 hours, baseline diabetesor cardiovascular disease. The resulting 3,292 participants wereanalyzed using Cox models that included CH, as well as the 2019 ACC/AHA riskfactors for ASCVD: hypertension, LDL ≥160mg/dL, family history of premature ASCVD, elevated waist circumference or BMI, fitness,race, nicotine use (serum cotinine) and estimated glomerular filtration rate (eGFR)&lt;60 mL/min/1.73 m 2 . Theprimary outcome was time to incident ASCVD. The effect size was hazard ratio (HR) with 95% confidence intervals (CI). Results: In an adjusted Cox model that included CH, waistcircumference and the other ACC/AHA risk factors mentioned above, CH atbaseline was an independent risk factor for ASCVD: HR 1.86, 95% CI: 1.32, 2.61, p=0.0004. The other risk factors were significantexcept for race, eGFR, fitness and waist circumference. In an adjusted Cox model that substituted BMIcategory (≥25 vs. &lt;25 kg/m 2 ) for elevated waist circumference, CHremained significant: HR 1.74, 95% CI:1.23, 2.46, p=0.0017. In that model, overweight/obesewas statistically significant as well (p=0.0289). To assess possible effect modificationbetween CH and BMI, a Cox model incorporating an interacting categorical variablerevealed that CH is a significant risk factor in overweight/obese participants (HR3.52, 95% CI: 1.76, 7.03, p=0.0004), but not those with BMI&lt;25 (HR 1.23, 95%CI: 0.79, 1.94, p=0.3476). Thisobservation was confirmed using Cox models stratified by BMI category. Conclusion: After adjusting for canonical risk factors, compensatoryhyperinsulinemia is an independent risk factor for future ASCVD among CARDIA participantswho were overweight or obese at baseline.
<i>ABO</i> O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia
Authors: Jason H. Karnes, Jerome Rollin, Jason B. Giles, Kiana L. Martinez, Heidi E. Steiner, Christian M. Shaffer, Yukihide Momozawa, Chihiro Inai, Andrei Bombin, Mingjian Shi, Jonathan D. Mosley, Ian Stanaway, Kathleen Selleng, Thomas Thiele, Taisei Mushiroda, Claire Pouplard, Nancy M. Heddle, Michiaki Kubo, Elizabeth J. Phillips, Theodore E. Warkentin, Yves Gruel, Andreas Greinacher, Dan M. Roden
Journal: Blood (2022)

Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. We performed a genome-wide association study (GWAS) with positive functional assay as the outcome in a large discovery cohort of patients divided into 3 groups: (1) functional assay-positive cases (n = 1269), (2) antibody-positive (functional assay-negative) controls (n = 1131), and (3) antibody-negative controls (n = 1766). Significant associations (α = 5 × 10-8) were investigated in a replication cohort (α = 0.05) of functional assay-confirmed HIT cases (n = 177), antibody-positive (function assay-negative) controls (n = 258), and antibody-negative controls (n = 351). We observed a strong association for positive functional assay with increasing PF4/heparin immunoglobulin-G (IgG) level (odds ratio [OR], 16.53; 95% confidence interval [CI], 13.83-19.74; P = 1.51 × 10-209) and female sex (OR, 1.15; 95% CI, 1.01-1.32; P = .034). The rs8176719 C insertion variant in ABO was significantly associated with positive functional assay status in the discovery cohort (frequency = 0.41; OR, 0.751; 95% CI, 0.682-0.828; P = 7.80 × 10-9) and in the replication cohort (OR, 0.467; 95% CI, 0.228-0.954; P = .0367). The rs8176719 C insertion, which encodes all non-O blood group alleles, had a protective effect, indicating that the rs8176719 C deletion and the O blood group were risk factors for HIT (O blood group OR, 1.42; 95% CI, 1.26-1.61; P = 3.09 × 10-8). Meta-analyses indicated that the ABO association was independent of PF4/heparin IgG levels and was stronger when functional assay-positive cases were compared with antibody-positive (functional assay-negative) controls than with antibody-negative controls. Sequencing and fine-mapping of ABO demonstrated that rs8176719 was the causal single nucleotide polymorphism (SNP). Our results clarify the biology underlying HIT pathogenesis with ramifications for prediction and may have important implications for related conditions, such as vaccine-induced thrombotic thrombocytopenia.
Empagliflozin Changes Urine Supersaturation by Decreasing pH and Increasing Citrate
Authors: Dusan Harmacek, Menno Pruijm, Michel Burnier, Marie-Eve Muller, Arlène Ghajarzadeh-Wurzner, Olivier Bonny, Anne Zanchi
Journal: Journal of the American Society of Nephrology (2022)

Clinical Trial registry name and registration number: Empagliflozin and Renal Oxygenation in Healthy Volunteers (EMPA-REIN), NCT03093103.
Survival outcomes in men with unfavorable intermediate-risk and high-risk prostate cancer treated with prostate-only versus whole pelvic radiation therapy.
Authors: Neal Andruska, Benjamin Walker Fischer-Valuck, Elizabeth Juarez Diaz, Temitope Agabalogun, Randall Brenneman, Hiram Alberto Gay, Jeff M. Michalski, Brian C. Baumann
Journal: Journal of Clinical Oncology (2022)

264 Background: Men with unfavorable intermediate-risk (UIR-PCa) or high-risk prostate cancer (HR-PCa) are often treated with definitive external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT). Treatment is frequently intensified by electively treating the pelvic lymph nodes with whole pelvis radiotherapy (WPRT), but practice patterns differ and the benefits of WPRT are not clearly defined, with mixed results from clinical trials. The recent POP-RT trial showed improved biochemical control with WPRT but most patients were staged with PET/CT scan. We hypothesized that men treated with WPRT would have improved overall survival (OS) relative to men treated with prostate-only radiotherapy in patients staged using conventional imaging. Methods: Men diagnosed between 2008-2015 with UIR or high-risk prostate cancer were retrospectively reviewed from the National Cancer Database (n = 28,724). Patients with involved nodes or distant metastases were excluded. Men received EBRT to a dose of 72-86.4 Gy and either prostate-only RT ± ADT (n = 13,549) or WPRT plus prostate RT ± ADT (n = 15,175). WPRT was delivered using a dose range of 40-50.4 Gy (1.8 – 2.0 Gy/fraction). The MSKCC nomogram was used to calculate risk of lymph node involvement. Unweighted or inverse probability of treatment weighting (IPTW) was used to perform multivariable analysis (MVA) using Cox regression modeling to compare OS hazard ratios, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, education, income, treatment facility type, PSA, Gleason score, clinical T-stage, use of ADT, lymph node risk score, and radiation dose. Results: 53% of men received WPRT, with national utilization of WPRT increasing from 2008 to 2015. For every 1% increase in risk of lymph node involvement, there was a 1% increased risk of death ( P&lt;.001). WPRT trended toward improved OS in all men with UIR or high-risk (Hazard Ratio (HR): 0.95 [95% Confidence Interval: 0.90-1.006], P=.07). WPRT correlated with improved OS in men with grade group 5 (GG5) disease (HR: 0.87 [0.78-0.98]. P=.02) or risk of lymph node involvement ≥ 10% (HR: 0.93 [0.87-0.99], P=.03). Conclusions: WPRT is associated with improved OS in men with a lymph node risk score ≥ 10% or GG5 disease. These results complement the recent POP-RT randomized trial in mostly PET/CT-staged patients, demonstrating that a more heterogenous population of men staged without functional imaging appears to benefit from WPRT.
Aldosterone and cardiovascular diseases
Authors: Wasita W Parksook, Gordon H Williams
Journal: Cardiovascular Research (2022)

Aldosterone's role in the kidney and its pathophysiologic actions in hypertension are well known. However, its role or that of its receptor [minieralocorticoid receptor (MR)] in other cardiovascular (CV) disease are less well described. To identify their potential roles in six CV conditions (heart failure, myocardial infarction, atrial fibrillation, stroke, atherosclerosis, and thrombosis), we assessed these associations in the following four areas: (i) mechanistic studies in rodents and humans; (ii) pre-clinical studies of MR antagonists; (iii) clinical trials of MR antagonists; and (iv) genetics. The data were acquired from an online search of the National Library of Medicine using the PubMed search engine from January 2011 through June 2021. There were 3702 publications identified with 200 publications meeting our inclusion and exclusion criteria. Data strongly supported an association between heart failure and dysregulated aldosterone/MR. This association is not surprising given aldosterone/MR's prominent role in regulating sodium/volume homeostasis. Atrial fibrillation and myocardial infarction are also associated with dysregulated aldosterone/MR, but less strongly. For the most part, the data were insufficient to determine whether there was a relationship between atherosclerosis, stroke, or thrombosis and aldosterone/MR dysregulation. This review clearly documented an expanding role for aldosterone/MR's dysregulation in CV diseases beyond hypertension. How expansive it might be is limited by the currently available data. It is anticipated that with an increased focus on aldosterone/MR's potential roles in these diseases, additional clinical and pre-clinical data will clarify these relationships, thereby, opening approaches to use modulators of aldosterone/MR's action to more precisely treat these CV conditions.
Extensive-Stage Small-Cell Lung Cancer: First-Line and Second-Line Treatment Options
Authors: Jon Zugazagoitia, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2022)

Extensive-stage small-cell lung cancer is a therapeutically challenging disease. After more than two decades without clinical progress, the addition of programmed cell death protein 1 axis blockade to platinum-based chemotherapy has demonstrated sustained overall survival benefit and represents the current standard of care in the first-line setting. Despite this benefit, resistance emerges relatively rapidly in virtually all patients. Although newer treatments are being incorporated in the relapse setting, marked therapeutic resistance is typically observed in patients with relapsed small-cell lung cancer (SCLC), underscoring the need of developing more effective therapies in this setting. Notably, recent progress in the understanding of the molecular biology of SCLC might bring possibilities toward molecularly informed therapeutic strategies for patients with SCLC, which could have a significant impact for improving outcomes in this disease. Here, we review current treatment options and recent progress made in the first-line and relapsed SCLC, including the role of biomarkers and new evolving therapeutic strategies.
Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials
Journal: BMJ (2022)

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Abstract P205: Long-term Changes In Proteomic Levels And The Risk Of Incident Atrial Fibrillation In Older Adults: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Jeffrey R Misialek, Faye L Norby, Alvaro Alonso, Lin Y Chen, Christie M Ballantyne, Eric Boerwinkle, Josef Coresh, Jim S Pankow, Pamela L Lutsey
Journal: Circulation (2022)

Background: Previous studies examining proteomic markers and atrial fibrillation (AF) have used protein measurements at one time point; however, few have studied these protein changes over time. Using data from the Atherosclerosis Risk in Communities (ARIC) study, we examined the association of long-term protein changes with AF in white and Black participants. Methods: Of 4877 plasma proteins measured at visits 3 (1993-1995) and 5 (2011-2013) using an aptamer-based proteomic profiling platform, we examined 17 proteins previously associated with AF. Protein changes between visits 3 and 5 were log base 2 transformed, corresponding to the log base 2 of the ratio [log 2 (protein5/protein3)]. AF was ascertained from hospital discharge codes, ECGs, and death certificates. We used Cox proportional hazards to assess the association of protein changes and AF. Results: This study included 3552 participants (mean age 75±5 years; 58% female; 17% Black) who had proteomic measures and were free of AF at visit 5. Over a mean follow-up of 6.4±2 years, 486 participants developed AF. After adjustment for clinical factors of AF, medication use, estimated glomerular filtration rate, and protein level at visit 5 (Model 2), changes in natriuretic peptides B and spondin-1 were associated with the risk of AF (HR: 1.57; 95%CI: 1.25-1.98; p-value=0.0001; and HR: 1.82; 95%CI: 1.23-2.70; p-value=0.0027, respectively) after Bonferroni correction. Although changes in NT-proBNP were not associated with AF risk, adjustment for visit 5 NT-proBNP attenuated associations for natriuretic peptides B and spondin-1 to non-significance. Conclusion: Examining protein changes over time may provide additional information about mechanistic pathways of AF development.
Reclaiming traditional, plant-based, climate-resilient food systems in small islands
Authors: Abrania Marrero, Josiemer Mattei
Journal: The Lancet Planetary Health (2022)

Small island developing states face challenges in cultivating healthy food systems and are currently bearing substantial burdens of obesity and type 2 diabetes. Local food production—rooted in collective local and Indigenous traditions, self-sufficiency, and climate-adaptive agricultural practices—has long emphasised a fibre-rich, plant-based diet; however, common histories of dietary colonialism have replaced local, small-scale farming and fisheries with non-nutritive cash crops, intensive livestock operations, and high-quality food exportation. Along with declines in traditional food availability, the resulting food import dependence has fostered a diabetogenic ecosystem composed of energy-dense cereal products, animal-based fats, and processed foods. The destabilisation of local food sectors undermines small island social and cultural systems, contributes to impoverishment and food insecurity during natural disasters, and, ultimately, can reduce diet quality and increase type 2 diabetes risk. Despite ongoing marginalisation of traditional local food systems, locally produced foods such as starchy roots, legumes, fruits, and seafood persist as nutritious and ecologically relevant cornerstones of self-determined local economic productivity and dietary health. Findings from community and epidemiological work suggest that local food production—bolstered by local and Indigenous agroecological knowledge, cultural preservation, and collective agency—can aid in reclaiming healthy and climate-resilient small island food systems.
Acute Myeloid Leukemia Patients Requiring Two Cycles of Intensive Induction for Attainment of Remission Experience Inferior Survival Compared with Patients Requiring a Single Course of Induction Chemotherapy
Authors: Gal Sharvit, Gabriel Heering, Maya Zlotnick, Arnon Nagler, Abraham Avigdor, Avichai Shimoni, Jonathan Canaani
Journal: Blood (2021)