A Randomized Controlled Trial of the Implementation of BREASTChoice, a Multilevel Breast Reconstruction Decision Support Tool With Personalized Risk Predictiona.

OBJECTIVE: To implement the BREASTChoice decision tool into the electronic health record and evaluate its effectiveness. BACKGROUND: BREASTChoice, is a multilevel decision tool that: 1) educates patients about breast reconstruction; 2) estimates personalized risk of complications; 3) clarifies patient preferences; and 4) informs clinicians about patients' risk and preferences. METHODS: A multisite randomized controlled trial enrolled adult women with stage 0-III breast malignancy undergoing mastectomy. Participants were randomized to BREASTChoice or a control website. A survey assessed knowledge, preferences, decisional conflict, shared decision-making, preferred treatment, and usability. We conducted intent-to-treat (ITT), per-protocol (PP) analyses (those randomized to BREASTChoice who accessed the tool), and stratified analyses. RESULTS: 23/25 eligible clinicians enrolled. 369/761 (48%) contacted patients enrolled and were randomized. Patients' average age was 51 years; 15% were older than 65. BREASTChoice participants had higher knowledge than control participants (ITT: mean 70.6 vs. 67.4, P=0.08; PP: mean 71.4 vs. 67.4, P=0.03), especially when stratified by site (ITT: P=0.04, PP: P=0.01), age (ITT: P=0.04, PP: P=0.02), and race (ITT: P=0.04, PP: P=0.01). BREASTChoice did not improve decisional conflict, match between preferences and treatment, or shared decision-making. In PP analyses, fewer high-risk patients using BREASTChoice chose reconstruction. BREASTChoice had high usability. CONCLUSIONS: BREASTChoice is a novel decision tool incorporating risk prediction, patient education, and clinician engagement. Patients using BREASTChoice had higher knowledge; older adults and those from racially minoritized backgrounds especially benefitted. There was no impact on other decision outcomes. Future studies should overcome implementation barriers and specifically examine decision outcomes among high-risk patients.

SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure.

BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses. METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined. DISCUSSION: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov on 5/31/2023 (NCT05881135). TRIAL STATUS: Currently enrolling.

Patient-Reported Experience in Colorectal Disease is Predicted by Cleanliness.

BACKGROUND: Children with colorectal diseases such as anorectal malformations (ARM), Hirschsprung disease (HD), and functional constipation (FC) undergo bowel management programs (BMPs) to achieve cleanliness. While patient outcomes, such as cleanliness and quality of life, are well understood, patient experience, such as relationships, ability to participate in sports, and independence and self-confidence is less well understood. We aimed to assess the relationship between BMP and patient experience. METHODS: A cross-sectional survey was administered to 295 patients ≥3 years old with ARM, HD, and FC completing BMP. The survey contains 22 questions regarding patient-reported experience measures (PREMs) and 11 regarding patient-reported outcomes measures (PROMs). Each was graded on a Likert scale, with higher scores meaning better experience. Scores were compared by demographics and clinical characteristics and logistic regression was performed controlling for clinically significant variables. A p-value of ≤0.05 was significant. RESULTS: There were 205 eligible respondents (69.5%) with a median age of 8.9 years [IQR: 6.1-12.4]. ARM was most common (51.2%) and most achieved cleanliness on BMP (69.3%). There were no differences in experience scores by age, diagnosis, or bowel regimen. Patients that were clean had significantly higher PREM scores (67.7 [IQR: 64.0-83.0] vs. 64.8 [IQR: 55.0-70.1], p = 0.0002) and PROM scores (36.8 [IQR: 33.0-41.0] vs. 34.0 [31.0-38.5], p = 0.005). On regression analysis, cleanliness remained a strongly significant predictor of positive experience scores (ß 7.37, SE 1.86, p < 0.0001). CONCLUSIONS: Achieving cleanliness was associated with positive patient experience of bowel management programs. This finding suggests that achieving cleanliness, regardless of regimen, may allow patients the best functional and experiential outcomes.

A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome.

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.

Association of Socioeconomic Status With Life's Essential 8 in the National Health and Nutrition Examination Survey: Effect Modification by Sex.

BACKGROUND: Higher scores for the American Heart Association Life's Essential 8 (LE8) metrics, blood pressure, cholesterol, glucose, body mass index, physical activity, smoking, sleep, and diet, are associated with lower risk of chronic disease. Socioeconomic status (SES; employment, insurance, education, and income) is associated with LE8 scores, but there is limited understanding of potential differences by sex. This analysis quantifies the association of SES with LE8 for each sex, within Hispanic Americans, non-Hispanic Asian Americans, non-Hispanic Black Americans, and non-Hispanic White Americans. METHODS AND RESULTS: Using cross-sectional data from the National Health and Nutrition Examination Survey, years 2011 to 2018, LE8 scores were calculated (range, 0-100). Age-adjusted linear regression quantified the association of SES with LE8 score. The interaction of sex with SES in the association with LE8 score was assessed in each racial and ethnic group. The US population representatively weighted sample (13 529 observations) was aged ≥20 years (median, 48 years). The association of education and income with LE8 scores was higher in women compared with men for non-Hispanic Black Americans and non-Hispanic White Americans (P for all interactions <0.05). Among non-Hispanic Asian Americans and Hispanic Americans, the association of SES with LE8 was not different between men and women, and women had greater LE8 scores than men at all SES levels (eg, high school or less, some college, and college degree or more). CONCLUSIONS: The factors that explain the sex differences among non-Hispanic Black Americans and non-Hispanic White Americans, but not non-Hispanic Asian Americans and Hispanic Americans, are critical areas for further research to advance cardiovascular health equity.

Improving mental health in black men through a 24-week community-based lifestyle change intervention: the black impact program.

BACKGROUND: Poor mental health is a leading cause of morbidity and mortality among Black men in the United States. Efforts to improve mental health among Black men have been hampered by a lack of access and utilization of mental health services. Physical activity and social networks have been shown to improve mental health. Thus, we examined the effect of a community team-based physical activity, health education and social needs intervention among Black men on mental health over 24 weeks. METHODS: Black adult males (n = 74) from a large Midwestern city participated in Black Impact, a 24-week community-based lifestyle change program adapted from the Diabetes Prevention Program and American Heart Association's (AHA) Check, Change, Control Blood Pressure Self-Management Program, which incorporates AHA's Life's Simple 7 (LS7) framework. Measures of mental health including the Center for Epidemiological Studies Depression Scale (CES-D), Patient Health Questionnaire 2-question depression screener (PHQ-2), and Perceived Stress Scale-10 (PSS-10) were completed at baseline, 12 and 24 weeks. The change in mental health scores from baseline to 12 and 24 weeks were evaluated using linear mixed-effects models adjusting for age, education, and income. The change in cardiovascular health scores, defined as objective metrics of LS7 (LS5 [blood pressure, total cholesterol, fasting glucose, body mass index and smoking]), by baseline mental health were evaluated using linear mixed-effects models with an interaction term (time*baseline mental health variable) and a random intercept for each participant. RESULTS: Among 71 Black men (mean age 51, 85% employed) at 24 weeks, CES-D scores decreased from 10.54 to 7.90 (-2.64, 95%CI:-4.74, -0.55), PHQ-2 decreased from 1.04 to 0.63 (-0.41, 95%CI: -0.75, -0.07), and PSS-10 decreased from 14.62 to 12.91 (-1.71, 95%CI: -3.53, 0.12). A 1-unit higher CES-D at baseline was associated with less improvement in LS5 scores by -0.04 (95%CI: -0.076, -0.005) and - 0.032 (95%CI:-0.067, 0.003) units at week 12 and 24, respectively, with similar findings for PSS. CONCLUSIONS: The Black Impact community-based lifestyle program has the potential to reduce depressive symptoms and stress in Black men. There is a dire need for larger, randomized studies to test the impact of Black Impact on mental health in Black men to advance health equity. TRIAL REGISTRATION: Retrospectively Registered, ClinicalTrials.gov Identifier: NCT04787978.

Evidence for the Association Between Adverse Childhood Family Environment, Child Abuse, and Caregiver Warmth and Cardiovascular Health Across the Lifespan: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: This study aimed to quantify the association between childhood family environment and longitudinal cardiovascular health (CVH) in adult CARDIA (Coronary Artery Risk Development in Young Adults) Study participants. We further investigated whether the association differs by adult income. METHODS: We applied the CVH framework from the American Heart Association including metrics for smoking, cholesterol, blood pressure, glucose, body mass index, physical activity, and diet. CVH scores (range, 0-14) were calculated at years 0, 7, and 20 of the study. Risky Family environment (range, 7-28) was assessed at year 15 retrospectively, for childhood experiences of abuse, caregiver warmth, and family or household challenges. Complete case ordinal logistic regression and mixed models associated risky family (exposure) with CVH (outcome), adjusting for age, sex, race, and alcohol use. RESULTS: The sample (n=2074) had a mean age of 25.3 (±3.5) years and 56% females at baseline. The median risky family was 10 with ideal CVH (≥12) met by 288 individuals at baseline (28.4%) and 165 (16.3%) at year 20. Longitudinally, for every 1-unit greater risky family, the odds of attaining high CVH (≥10) decreased by 3.6% (OR, 0.9645 [95% CI, 0.94-0.98]). Each unit greater child abuse and caregiver warmth score corresponded to 12.8% lower and 11.7% higher odds of ideal CVH (≥10), respectively (OR, 0.872 [95% CI, 0.77-0.99]; OR, 1.1165 [95% CI, 1.01-1.24]), across all 20 years of follow-up. Stratified analyses by income in adulthood demonstrated associations between risky family environment and CVH remained significant for those of the highest adult income (>$74k), but not the lowest (<$35k). CONCLUSIONS: Although risky family environmental factors in childhood increase the odds of poor longitudinal adult CVH, caregiver warmth may increase the odds of CVH, and socioeconomic attainment in adulthood may contextualize the level of risk. Toward a paradigm of primordial prevention of cardiovascular disease, childhood exposures and economic opportunity may play a crucial role in CVH across the life course.

Association Between Marijuana Laws and Suicide Among 12- to 25-Year-Olds in the United States From 2000 to 2019.

OBJECTIVE: Cannabis use is associated with suicide-related outcomes in both adolescents and adults, and may be increasing amid shifting cannabis policies. However, little is known about the impact of medical marijuana legalization (MML) and recreational marijuana legalization (RML) policies on youth suicide. Using 20 years of national data, we examined associations between MML, RML, and suicide-related mortality among US individuals aged 12 to 25 years, and assessed whether they varied based on age and sex. METHOD: Suicide deaths (N = 113,512) from the 2000-2019 National Vital Statistics System Multiple Cause of Death files for age groups 12 to 13, 14 to 16, 17 to 19, 20 to 22, and 23 to 25 years were examined in relation to time-varying cannabis law status using a staggered adoption difference-in-difference (DiD) approach with a negative binomial regression to determine associations between MML, RML, and suicide rates, controlling for individual- and state-level covariates and accounting for the varying effective dates of MML and RML by state. RESULTS: The overall unadjusted annual suicide rate was 10.93/100,000, varying from 9.76 (states without marijuana laws (ML)) to 12.78 (MML states) to 16.68 (RML states). In multivariable analysis, both MML (incidence rate ratio [IRR] = 1.10, 95% CI: 1.05-1.15) and RML (IRR = 1.16, 95% CI: 1.06-1.27) were associated with higher suicide rates among female youth compared to those in states without ML. Youth aged 14 to 16 years had higher rates of suicide in states with RML compared to states with MML (IRR = 1.14, 95% CI: 1.00-1.30) and states without ML (IRR = 1.09, 95% CI: 1.00-1.20). Findings were consistent across sensitivity analyses. CONCLUSION: MML and RML were associated with increased suicide-related mortality in female youth and 14- to- 16-year-old individuals of both sexes. Mechanisms through which cannabis policies are related to increased youth suicide warrant further study and should inform legislative reform.

Textbook outcome: A novel metric in heart transplantation outcomes.

OBJECTIVE: Assessing heart transplant program quality using short-term survival is insufficient. We define and validate the composite metric textbook outcome and examine its association with overall survival. METHODS: We identified all primary, isolated adult heart transplants in the United Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files from May 1, 2005, to December 31, 2017. Textbook outcome was defined as length of stay 30 days or less; ejection fraction greater than 50% during 1-year follow-up; functional status 80% to 100% at 1 year; freedom from acute rejection, dialysis, and stroke during the index hospitalization; and freedom from graft failure, dialysis, rejection, retransplantation, and mortality during the first year post-transplant. Univariate and multivariate analyses were performed. Factors independently associated with textbook outcome were used to create a predictive nomogram. Conditional survival at 1 year was measured. RESULTS: A total of 24,620 patients were identified with 11,169 (45.4%, 95% confidence interval, 44.7-46.0) experiencing textbook outcome. Patients with textbook outcome were more likely free from preoperative mechanical support (odds ratio, 3.504, 95% confidence interval, 2.766 to 4.439, P < .001), free from preoperative dialysis (odds ratio, 2.295, 95% confidence interval, 1.868-2.819, P < .001), to be not hospitalized (odds ratio, 1.264, 95% confidence interval, 1.183-1.349, P < .001), to be nondiabetic (odds ratio, 1.187, 95% confidence interval, 1.113-1.266, P < .001), and to be nonsmokers (odds ratio, 1.160, 95% confidence interval,1.097-1.228, P < .001). Patients with textbook outcome have improved long-term survival relative to patients without textbook outcome who survive at least 1 year (hazard ratio for death, 0.547, 95% confidence interval, 0.504-0.593, P < .001). CONCLUSIONS: Textbook outcome is an alternative means of examining heart transplant outcomes and is associated with long-term survival. The use of textbook outcome as an adjunctive metric provides a holistic view of patient and center outcomes.

A Pilot Study: Free Flap Atrophy in Tongue Reconstruction Using 3D Volumetric Analysis.

OBJECTIVE: To identify factors influencing volume change in non-osseous oral free flap reconstruction using postoperative cross-sectional imaging and 3-dimensional segmentation of the free flap's muscular and adipose tissue content. METHODS: Oral tongue free flap reconstruction cases (2014-2019) were reviewed with inclusion of patients with 3 postoperative, cross-sectional imaging studies with 1 within 6 months, 1 within 1 year, and 1 that spanned 2 years post-reconstruction. Exclusion criteria included recurrence, significant dental artifact, bony reconstruction, and flap failure. Demographics, risk factors, and surgical/clinical treatments were identified. Flap volumes were measured using Materialise MIMICS. RESULTS: Twenty-two patients met strict inclusion criteria. Four flaps were anterolateral thighs and 18 radial forearms. Median percent volume loss greater than 2 years post-reconstruction was 53.2% overall, 58.1% for radial forearms, and 45.4% for ALTs (21.4% for adipose tissue and 57.4% for muscular tissue). Univariate analysis revealed glossectomy amount was associated with percent volume loss (P = .0417). Each successive postoperative month, the flap decreased by 1.54% (P < .0001). Checking for the interaction effect, the percent of flap loss across time was different for glossectomy amount (P = .0093), obesity status (P = .0431), and base of tongue involvement (P = .0472). CONCLUSION: Glossectomy type, and thus flap size, is a positive predictor for flap atrophy. Obesity and base of tongue involvement are negative predictors for flap atrophy. The amount of tissue loss may differ from classical teachings with median atrophy 53.2% greater than 2 years post-reconstruction.

Role of Sex in the Association of Socioeconomic Status With Cardiovascular Health in Black Americans: The Jackson Heart Study.

BACKGROUND: Socioeconomic status (SES) is associated with cardiovascular health (CVH). Potential differences by sex in this association remain incompletely understood in Black Americans, where SES disparities are posited to be partially responsible for cardiovascular inequities. The association of SES measures (income, education, occupation, and insurance) with CVH scores was examined in the Jackson Heart Study. METHODS AND RESULTS: American Heart Association CVH components (non-high-density-lipoprotein cholesterol, blood pressure, diet, tobacco use, physical activity, sleep, glycemia, and body mass index) were scored cross-sectionally at baseline (scale: 0-100). Differences in CVH and 95% CIs (Estimate, 95% CI) were calculated using linear regression, adjusting for age, sex, and discrimination. Heterogeneity by sex was assessed. Participants had a mean age of 54.8 years (SD 12.6 years), and 65% were women. Lower income, education, occupation (non-management/professional versus management/professional occupations), and insurance status (uninsured, Medicaid, Veterans Affairs, or Medicare versus private insurance) were associated with lower CVH scores (all P<0.01). There was heterogeneity by sex, with greater magnitude of associations of SES measures with CVH in women versus men. The lowest education level (high school) was associated with 8.8-point lower (95% CI: -10.2 to -7.3) and 5.4-point lower (95% CI: -7.2 to -3.6) CVH scores in women and men, respectively (interaction P=0.003). The lowest (<25 000) versus highest level of income (≥$75 000) was associated with a greater reduction in CVH scores in women than men (interaction P=0.1142). CONCLUSIONS: Among Black Americans, measures of SES were associated with CVH, with a greater magnitude in women compared with men for education and income. Interventions aimed to address CVH through SES should consider the role of sex.

Exome sequencing in the pediatric neuromuscular clinic leads to more frequent diagnosis of both neuromuscular and neurodevelopmental conditions.

INTRODUCTION/AIMS: Exome sequencing (ES) has proven to be a valuable diagnostic tool for neuromuscular disorders, which often pose a diagnostic challenge. The aims of this study were to investigate the clinical outcomes associated with utilization of ES in the pediatric neuromuscular clinic and to determine if specific phenotypic features or abnormal neurodiagnostic tests were predictive of a diagnostic result. METHODS: This was a retrospective medical record review of 76 pediatric neuromuscular clinic patients who underwent ES. Based upon clinical assessment prior to ES, patients were divided into two groups: affected by neuromuscular (n = 53) or non-neuromuscular (n = 23) syndromes. RESULTS: A diagnosis was made in 28/76 (36.8%), with 29 unique disorders identified. In the neuromuscular group, a neuromuscular condition was confirmed in 78% of those receiving a genetic diagnosis. Early age of symptom onset was associated with a significantly higher diagnostic yield. The most common reason neuromuscular diagnoses were not detected on prior testing was due to causative genes not being present on disease-specific panels. Changes to medical care were made in 57% of individuals receiving a diagnosis on ES. DISCUSSION: These data further support ES as a powerful diagnostic tool in the pediatric neuromuscular clinic and highlight the advantages of ES over gene panels, including the ability to identify diagnoses regardless of etiology, identify genes newly associated with disease, and identify multiple confounding diagnoses. Rapid and accurate diagnosis by ES can not only end the patient's diagnostic odyssey, but often impacts patients' medical management and genetic counseling of families.

Association of Socioeconomic Status With Life's Essential 8 Varies by Race and Ethnicity.

Background The American Heart Association's Life's Essential 8 (LE8) are 8 risk factors for cardiovascular disease, with poor attainment across all racial, ethnic, and socioeconomic groups. Attainment is lowest among Americans of low socioeconomic status (SES). Evidence suggests the association of SES with LE8 may vary by race and ethnicity. Methods and Results The association of 4 SES categories (education, income-to-poverty line ratio, employment, insurance) with LE8 was computed in age-adjusted linear regression models, with an interaction term for race and ethnicity, using National Health and Nutrition Examination Survey data, years 2011 to 2018. The sample (n=13 529) had a median age of 48 years (51% female) with weighting to be representative of the US population. The magnitude of positive association of college education (relative to ≤high school) with LE8 was greater among non-Hispanic White Americans (NHWA) compared with non-Hispanic Black Americans, Hispanic Americans, and non-Hispanic Asian Americans (all interactions P<0.001). NHWA had a greater magnitude of positive association of income-to-poverty line ratio with LE8, compared with non-Hispanic Black Americans, Hispanic Americans, and non-Hispanic Asian Americans (all interactions P<0.001). NHWA with Medicaid compared with private insurance had a greater magnitude of negative association with LE8 compared with non-Hispanic Black Americans, non-Hispanic Asian Americans, or Hispanic Americans (all interactions P<0.01). NHWA unemployed due to disability or health condition (compared with employed) had a greater magnitude of negative association with LE8 than non-Hispanic Black Americans, non-Hispanic Asian Americans, or Hispanic Americans (all interactions P<0.05). Conclusions The magnitude of association of SES with LE8 is greatest among NHWA. More research is needed on SES's role in LE8 attainment in minority group populations.

Adiposity, aldosterone and plasma renin activity among African Americans: The Jackson Heart Study.

Objective: To analyze associations between adiposity and the renin-angiotensin-aldosterone system (RAAS) in a large African American (AA) cohort. Methods: Cross-sectional associations of adiposity (body mass index [BMI], waist circumference [WC], waist:height ratio, waist:hip ratio, leptin, adiponectin, leptin:adiponectin ratio [LAR], subcutaneous [SAT] and visceral adipose tissue [VAT], and liver attenuation [LA]) with aldosterone, plasma renin activity (renin), and aldosterone:renin ratio (ARR) were assessed in the Jackson Heart Study using adjusted linear regression models. Results: A 1-SD higher BMI was associated with a 4.8 % higher aldosterone, 9.4 % higher renin, and 5.0 % lower ARR (all p < 0.05). Log-leptin had the largest magnitude of association with renin (30.2 % higher) and ARR (9.6 % lower), while the strongest association of aldosterone existed for log-LAR (15.3 % higher) (all 1-SD, p < 0.05). SAT was only associated with renin. VAT was associated with higher aldosterone, renin, and ARR. Liver fat was associated with aldosterone and renin, but not ARR. Associations of WC, BMI, and SAT with aldosterone were greater in men while the association with VAT was greater in women (p-interactions < 0.05). Conclusion: Multiple measures of adiposity are associated with the RAAS in AAs. Further studies should examine the role of RAAS in obesity-driven cardiometabolic diseases.

The association of aldosterone and endothelin-1 with incident diabetes among African Americans: The Jackson Heart Study.

Introduction: African Americans (AAs) have the highest prevalence of hypertension among United States racial/ethnic groups. Regulators of blood pressure, such as aldosterone and endothelin-1, impact glucose regulation. The relationship between these factors and incident diabetes is not well elucidated among AAs. Methods: Among 3914 AA participants without prevalent diabetes in the Jackson Heart Study, linear regression models were used to examine cross-sectional associations of exposures (aldosterone, endothelin-1, and a combined aldosterone-endothelin-1 score [2-8]) with glycemic measures (fasting plasma glucose [FPG], HbA1c, homeostatic model assessments of beta cell function [HOMA-ß] and insulin resistance [HOMA-IR]). Longitudinal associations of exposures with incident diabetes were examined using Cox proportional hazard models. Models were adjusted for age, sex, education, occupation, systolic blood pressure, smoking, physical activity, dietary intake, alcohol use and adiponectin. Results: Aldosterone and the combined aldosterone-endothelin score were positively associated with FPG, HOMA-IR, and HOMA-ß (all p < 0.05). Endothelin-1 was negatively associated with FPG but positively associated with HOMA-ß (both p < 0.05). Only the aldosterone-endothelin score was positively associated with HbA1c (p < 0.01). A 1-SD higher serum aldosterone and endothelin-1 was associated with a 22 % and 14 % higher risk of incident diabetes, respectively, while a 1-point higher aldosterone-endothelin score was associated with a 13 % higher risk of incident diabetes after adjustment for diabetes risk factors (all p < 0.01). Conclusions: Aldosterone and endothelin-1, factors integral in blood pressure regulation, may play a significant role in the development of diabetes among AAs.

Plasma Thermogram Parameters Differentiate Status and Overall Survival of Melanoma Patients.

Melanoma is the fifth most common cancer in the United States and the deadliest of all skin cancers. Even with recent advancements in treatment, there is still a 13% two-year recurrence rate, with approximately 30% of recurrences being distant metastases. Identifying patients at high risk for recurrence or advanced disease is critical for optimal clinical decision-making. Currently, there is substantial variability in the selection of screening tests and imaging, with most modalities characterized by relatively low accuracy. In the current study, we built upon a preliminary examination of differential scanning calorimetry (DSC) in the melanoma setting to examine its utility for diagnostic and prognostic assessment. Using regression analysis, we found that selected DSC profile (thermogram) parameters were useful for differentiation between melanoma patients and healthy controls, with more complex models distinguishing melanoma patients with no evidence of disease from patients with active disease. Thermogram features contributing to the third principal component (PC3) were useful for differentiation between controls and melanoma patients, and Cox proportional hazards regression analysis indicated that PC3 was useful for predicting the overall survival of active melanoma patients. With the further development and optimization of the classification method, DSC could complement current diagnostic strategies to improve screening, diagnosis, and prognosis of melanoma patients.

Outcomes After Deceased Donor Kidney Transplantation Using Kidney Allografts With Marginal Perfusion Parameters.

BACKGROUND: This study examines outcomes of deceased donor kidney transplantation (DDKT) in recipients of kidney allografts with marginal perfusion parameters. METHODS: Allografts with marginal perfusion parameters (resistance index [RI] >0.4 and pump flow rate [F] <70 mL/min; MP group) were compared with those with good parameters (RI <0.4 and F >70 mL/min; GP group) for DDKT recipients between January 1996 and November 2017 after hypothermic pulsatile perfusion. Demographics, creatinine, cold ischemia times (CIT), delayed graft function (DGF), and recipient glomerular filtration rate at pre- and post-transplant were noted. The primary outcome was graft survival post-transplant. RESULTS: In the MP (n = 31) versus GP (n = 1281) group, the median recipient was aged 57 years versus 51 years; the median donor was aged 47 versus 37 years; terminal creatinine was 0.9 versus 0.9 mg/dL; CIT was 10.2 versus 13 hours, and the RI and flow were 0.46 and 60 mL/min versus 0.21 and 120 mL/min. The DGF rate was 19% (MP) versus 8% (GP). The graft survival in the MP versus GP group was 81% versus 90% (1 year), 65% versus 79% (3 years), 65% versus 73% (4 years), and 45% versus 68% (5 years). CONCLUSION: Carefully selected kidney allografts after comprehensive donor and recipient evaluation may allow for the use of these routinely discarded kidneys with marginal perfusion parameters.

Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study.

BACKGROUND: Insulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA. METHODS: This was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations. RESULTS: RA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ = - 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03). CONCLUSIONS: Mitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.

The role of aldosterone and ideal cardiovascular health in incident cardiovascular disease: The Jackson heart study.

Background: Higher levels of ideal cardiovascular health (ICH) are associated with lower levels of aldosterone and incidence of cardiovascular disease (CVD). However, the degree to which aldosterone mediates the association between ICH and CVD incidence has not been explored. Thus, we investigated the mediational role of aldosterone in the association of 5 components of ICH (cholesterol, body mass index (BMI), physical activity, diet and smoking) with incident CVD and the mediational role of blood pressure (BP) and glucose in the association of aldosterone with incident CVD in a cohort of African Americans (AA). Methods: The Jackson Heart Study is a prospective cohort of AAs adults with data on CVD outcomes. Aldosterone, ICH metrics and baseline characteristics were collected at exam 1 (2000-2004). ICH score was developed by summing 5 ICH metrics (smoking, dietary intake, physical activity, BMI, and total cholesterol) and grouped into two categories (0-2 and ≥3 metrics). Incident CVD was defined as stroke, coronary heart disease, or heart failure. Cox proportional hazard regression models were used to model the association of categorical ICH score with incident CVD. The R Package Mediation was utilized to examine: 1) The mediational role of aldosterone in the association of ICH with incident CVD and 2) The mediational role of blood pressure and glucose in the association of aldosterone with incident CVD. Results: Among 3,274 individuals (mean age: 54±12.4 years, 65% female), there were 368 cases of incident CVD over a median of 12.7 years. The risk of incident CVD was 46% lower (HR: 0.54; 95%CI 0.36, 0.80) in those with ≥3 ICH metrics at baseline compared to 0-2. Aldosterone mediated 5.4% (p = 0.006) of the effect of ICH on incident CVD. A 1-unit increase in log-aldosterone was associated with a 38% higher risk of incident CVD (HR 1.38, 95%CI: 1.19, 1.61) with BP and glucose mediating 25.6% (p<0.001) and 4.8% (p = 0.048), respectively. Conclusion: Aldosterone partially mediates the association of ICH with incident CVD and both blood pressure and glucose partially mediate the association of aldosterone with incident CVD, emphasizing the potential importance of aldosterone and ICH in risk of CVD among AAs.

Associations of minor histocompatibility antigens with outcomes following allogeneic hematopoietic cell transplantation.

The role of minor histocompatibility antigens (mHAs) in mediating graft versus leukemia and graft versus host disease (GvHD) following allogeneic hematopoietic cell transplantation (alloHCT) is recognized but not well-characterized. By implementing improved methods for mHA prediction in two large patient cohorts, this study aimed to comprehensively explore the role of mHAs in alloHCT by analyzing whether (1) the number of predicted mHAs, or (2) individual mHAs are associated with clinical outcomes. The study population consisted of 2249 donor-recipient pairs treated for acute myeloid leukemia and myelodysplastic syndrome with alloHCT. A Cox proportional hazard model showed that patients with a class I mHA count greater than the population median had an increased hazard of GvHD mortality (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.01, 1.77, p = .046). Competing risk analyses identified the class I mHAs DLRCKYISL (GSTP), WEHGPTSLL (CRISPLD2), and STSPTTNVL (SERPINF2) were associated with increased GVHD mortality (HR = 2.84, 95% CI = 1.52, 5.31, p = .01), decreased leukemia-free survival (LFS) (HR = 1.94, 95% CI = 1.27, 2.95, p = .044), and increased disease-related mortality (DRM) (HR = 2.32, 95% CI = 1.5, 3.6, p = .008), respectively. One class II mHA YQEIAAIPSAGRERQ (TACC2) was associated with increased risk of treatment-related mortality (TRM) (HR = 3.05, 95% CI = 1.75, 5.31, p = .02). WEHGPTSLL and STSPTTNVL were both present within HLA haplotype B*40:01-C*03:04 and showed a positive dose-response relationship with increased all-cause mortality and DRM and decreased LFS, indicating these two mHAs contribute to the risk of mortality in an additive manner. Our study reports the first large-scale investigation of the associations of predicted mHA peptides with clinical outcomes following alloHCT.