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Importance The prevalence of cardiovascular disease differs substantially across neighborhoods. However, few studies have examined the contribution of neighborhood-level structural racism to inequities in cardiovascular health. Objective To investigate the association between neighborhood-level manifestations of structural racism and the prevalence of cardiovascular clinical and behavioral risk factors and cardiovascular diseases. Design, Setting, and Participants This cross-sectional study consisted of 71 915 US census tracts. The Structural Racism Effect Index (SREI) was appended to the 2020 Centers for Disease Control and Prevention’s PLACES dataset. Race and ethnicity were self-reported and obtained from the 2019 American Community Survey 5-year estimates. Data analysis was conducted from June 2024 to October 2024. Exposure The SREI is a composite score of census tract measures within 9 domains affected by structural racism (built environment, criminal justice, education, employment, housing, income and poverty, social cohesion, transportation, and wealth). The SREI scores were categorized into distribution-based quintiles, where higher quintiles represented greater neighborhood structural racism. Main Outcomes and Measures Neighborhood-level prevalence of cardiovascular clinical (high blood pressure, high cholesterol, obesity, and diabetes) and behavioral (current cigarette smoking and no leisure-time physical activity) risk factors and cardiovascular disease (coronary heart disease and stroke). Multilevel-linear mixed models, adjusting for confounders, were used to estimate adjusted prevalence rate ratios (aPRR). Results Among 71 915 census tracts, neighborhoods in the highest quintiles of structural racism were more likely than neighborhoods in the lowest quintile to be in the southern region (quintile 1, 19.9% vs quintile 5, 56.8%). The proportion of the population that was Black was largest in neighborhoods in the highest quintile of structural racism (quintile 1, 2.2% vs quintile 5, 23.0%). After adjustment, compared with the lowest quintile of structural racism, the highest quintile had significantly higher prevalence rates of cardiovascular clinical risk factors, including high blood pressure (aPRR, 1.37; 95% CI, 1.37-1.38), obesity (aPRR, 1.40; 95% CI, 1.39-1.40), and diabetes (aPRR, 1.80; 95% CI, 1.79-1.81). Similarly, for cardiovascular behavioral risk factors, the highest quintile of structural racism had significantly higher prevalence rates of current cigarette smoking (aPRR, 1.84; 95% CI, 1.83-1.85) and no leisure-time physical activity (aPRR, 1.88; 95% CI, 1.87-1.89). Additionally, for cardiovascular diseases, the highest quintile of structural racism had higher prevalence rates of coronary heart disease (aPRR, 1.80; 95% CI, 1.79-1.82) and stroke (aPRR, 1.99; 95% CI, 1.98-2.00). Conclusions and Relevance In this cross-sectional study, structural racism was associated with inequities in neighborhood cardiovascular health, highlighting opportunities for place-based prevention efforts.

Abstract Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported. Experimental Design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts. Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a diagnosis of pineoblastoma (n = 8) or Wilms tumor (n = 1). A somatic second hit in DROSHA was detected in all eight tumors analyzed. All pineoblastoma tumors analyzed were classified as miRNA processing–altered 1 subtype. We estimate the population prevalence of germline DROSHA loss-of-function variants to be 1:3,875 to 1:4,843 but find no evidence for increased adult cancer risk. Conclusions: This is the first report of DROSHA-related tumor predisposition. As pineoblastoma and Wilms tumor are also associated with DICER1 GPVs, our results suggest that the tissues of origin for these tumors are uniquely tolerant of general miRNA loss. The miRNA processing–altered 1 pineoblastoma subtype is associated with older age of diagnosis and better outcomes than other subtypes, suggesting DROSHA GPV status may have important clinical and prognostic significance. We suggest that genetic testing for DROSHA GPVs be considered for patients with pineoblastoma, Wilms tumor, or other DICER1-/DGCR8-related conditions and propose surveillance recommendations through research studies for individuals with DROSHA GPVs.

Introduction: Oral glucose tolerance testing is recommended for all children with CF older than 9 years, yet compliance remains poor across centers. Methods: We performed a small pilot study assessing the glycemic curves and participant satisfaction in seven children and adolescents. Results: We chose a dextrose-based candy (Nerds®) free of any fat, fiber, gelatin, or corn syrup and performed the candy OGTT 1–4 days following the standard oral dextrose solution OGTT. Glucose values at 120 min were similar between the candy and oral dextrose solution (p = 0.8986). Conclusions: Our small pilot suggests that a carefully selected candy alternative may result in similar glycemic OGTT when compared to the standard oral dextrose solution. However, some participants preferred the oral dextrose solution to candy due to having to consume a large volume in a short period of time. This may have significant implications as centers consider candy alternatives to increase OGTT adherence rates.

AbstractBackgroundWe sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID‐19) infection.MethodsMultiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID‐19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission.ResultsSeventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50–4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40–7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48–3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25–0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut‐offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends.ConclusionsVitamin D deficiency is associated with greater severity of COVID‐19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID‐19.

Key Points The ClinGen MM-VCEP has specified RUNX1-specific curation rules to address gene function, gene-specific domains, and phenotypic criteria. RUNX1-specific criteria resulted in a reduction in CONF and VUS variants by 33%, emphasizing the need for expert variant curation.