Self-identified African Americans Research Articles

Characterizing heart failure and its subtypes in people living with HIV.

People living with HIV have an increased risk of heart failure (HF). There are different subtypes of HF. Knowledge about the factors differentiating HF subtypes in people with HIV is limited but necessary to guide preventive measures and treatment. A retrospective review of medical records was undertaken in people with HIV aged ≥18 years who received care at the University of Miami/Jackson Memorial HIV Clinic between January 2017 and November 2019 (N = 1166). Patients with an echocardiogram available for review (n = 305) were included. HF was defined as a documented diagnosis of any HF subtype (n = 52). We stratified those with HF by their ejection fraction (EF) into HF with preserved EF (HFpEF), HF with borderline EF, or HF with reduced EF (HFrEF). The prevalence of HF was 4.5%. The cohort included 46.2% females and 75% self-identified African Americans. Those with HF had a higher prevalence of hypertension, prior myocardial infarction, angina, coronary artery disease, percutaneous coronary intervention, coronary artery bypass grafting, diastolic dysfunction, and left ventricle hypertrophy. People with HIV with HF with borderline EF exhibited more coronary artery disease than those with HFpEF. We characterize HF in people with HIV in South Florida and report the prevalence of HF and HF subtypes. Only a small percentage of patients had echocardiograms performed, suggesting an ongoing need for recognition of the increased risk of HF in people living with HIV, and raising the concern about lack of awareness contributing to underdiagnosis and missed treatment opportunities in this population.

Understanding the safety and toxicity profile of durvalumab for Black patients with lung cancer.

e20051 Background: Constituting 12.2% of all new cancer diagnosis in 2023,Lung cancer continues to be among the most common cancers in the US. According to statistics 1 in 16 black males and1 in 20 black females are likely to develop lung cancer in their lifetime.The results of the PACIFIC trial changed the paradigm of management in non-resectable NonSmall Cell Ca and made Durvalumab the standard of care. The toxicity profile of the drug were extensively studied in the study however, only 2% (n-14) of the study population was Black. More studies are required to understand the tolerability and toxicity profile of the drug in the Black population. Methods: This is a retrospective study. Study population consisted of 55 self-identified African Americans diagnosed with stage 3 Non-small Cell Ca who received Durvalumab for consolidation therapy after chemo radiation at a large safety net hospital between 2018-2023.Their charts were reviewed to study: 1. The development of any grade- known adverse side effects of the drug. 2. The tolerability of the drug- assessed as the lack of severe toxicities resulting in discontinuation of the drug. 3. Appearance of any peculiar adverse effects not previously known. 4. Adverse side effects warranting the use of more healthcare resources, like ED visits and hospital admissions for adverse effects. The results were then compared to the results of the PACIFIC trial. Results: 52.7% (n=29) developed known adverse effects of the drug-any grade.20 % (n=11) developed severe adverse effects leading to discontinuation of therapy.32.7%(n=18) were able to tolerate completion of therapy in-spite of adverse effects. 16.3% ( n=9) required ED visits/ hospital visit due to immunotherapy adverse effects. ADRs leading to discontinuation of therapy-pneumonitis -9%, Debilitating Chest Pain-1.8%, Hyperglycemia- 1.8%, severe fatigue-1.8%, atrial fibrillation-1.8%, Autoimmune hepatitis -1.8% and Pan uveitis -1.8%. Other adverse effects are listed in the table. Conclusions: Based on our results, AA are more likely to develop any grade adverse effects than was estimated in the PACIFIC trial, however, the percentage of the AA population discontinuing therapy due to severe adverse effect was lower. While the occurrence of most common adverse effects including Pneumonitis was comparable to the PACIFIC trial, thyroid dysfunction – both hypo and hyperthyroidism was about 3 times more in the AA population. All the thyroid dysfunctions noted were G1 and G2, and did not require discontinuation of therapy. We therefore, recommend providers to be more watchful for signs and symptoms suggestive of thyroid dysfunction when treating AA patients with Durvalumab. [Table: see text]

Gun Violence Exposure and Suicide Among Black Adults.

Black individuals are disproportionately exposed to gun violence in the US. Suicide rates among Black US individuals have increased in recent years. To evaluate whether gun violence exposures (GVEs) are associated with suicidal ideation and behaviors among Black adults. This cross-sectional study used survey data collected from a nationally representative sample of self-identified Black or African American (hereafter, Black) adults in the US from April 12, 2023, through May 4, 2023. Ever being shot, being threatened with a gun, knowing someone who has been shot, and witnessing or hearing about a shooting. Outcome variables were derived from the Self-Injurious Thoughts and Behaviors Interview, including suicidal ideation, suicide attempt preparation, and suicide attempt. A subsample of those exhibiting suicidal ideation was used to assess for suicidal behaviors. The study sample included 3015 Black adults (1646 [55%] female; mean [SD] age, 46.34 [0.44] years [range, 18-94 years]). Most respondents were exposed to at least 1 type of gun violence (1693 [56%]), and 300 (12%) were exposed to at least 3 types of gun violence. Being threatened with a gun (odds ratio [OR], 1.44; 95% CI, 1.01-2.05) or knowing someone who has been shot (OR, 1.44; 95% CI, 1.05-1.97) was associated with reporting lifetime suicidal ideation. Being shot was associated with reporting ever planning a suicide (OR, 3.73; 95% CI, 1.10-12.64). Being threatened (OR, 2.41; 95% CI, 2.41-5.09) or knowing someone who has been shot (OR, 2.86; 95% CI, 1.42-5.74) was associated with reporting lifetime suicide attempts. Cumulative GVE was associated with reporting lifetime suicidal ideation (1 type: OR, 1.69 [95% CI, 1.19-2.39]; 2 types: OR, 1.69 [95% CI, 1.17-2.44]; ≥3 types: OR, 2.27 [95% CI, 1.48-3.48]), suicide attempt preparation (≥3 types; OR, 2.37; 95% CI, 2.37-5.63), and attempting suicide (2 types: OR, 4.78 [95% CI, 1.80-12.71]; ≥3 types: OR, 4.01 [95% CI, 1.41-11.44]). In this cross-sectional study, GVE among Black adults in the US was significantly associated with lifetime suicidal ideation and behavior. Public health efforts to substantially reduce interpersonal gun violence may yield additional benefits by decreasing suicide among Black individuals in the US.

Multi-ethnic variation in the ties that bind rumination and heart rate variability: Implications for health disparities.

Higher self-reported rumination, a common form of trait perseverative cognition, is linked with lower resting heart rate variability (HRV), which indicates poorer cardiac function and greater disease risk. A meta-analysis and systematic review indicated that in samples with fewer European Americans, the association of rumination with both heart rate and blood pressure was stronger. Thus, trait rumination may be more strongly associated with resting HRV among ethnically minoritized populations. The current study investigated whether differences in the association of self-reported rumination with resting HRV varied by ethnicity in a sample (N=513; Mage=19.41; 226 Women) of self-identified African Americans (n=110), Asian Americans (n=84), and European Americans (n=319). Participants completed a five-minute baseline period to assess resting HRV, followed by the Ruminative Responses Scale, which contains three facets of rumination including brooding, depressive, and reflective rumination. On average, Asian Americans reported higher levels of rumination relative to European Americans. African Americans had higher resting HRV than Asian Americans. Adjusting for covariates, higher self-reported rumination was significantly associated with lower resting HRV in both African and Asian Americans, but not significantly so in European Americans. This finding was consistent for brooding and reflective, but not depressive rumination. Overall, this study lends insight into a psychological mechanism-rumination-that may impact health disparities among ethnically minoritized individuals, contributing to an understanding of how stress gets under the skin among such minoritized populations.

FC9: Ethno-racial identity and cognitive impairment: A population-based study

Objective:Health disparities between communities with greater and lesser advantages are a global concern. In the USA, self-identified race as African American (AA) is consistently associated with mild cognitive impairment (MCI) and dementia, compared to Americans of European descent. In a prospective population-based study, we sought to confirm this association and investigate potential explanatory factors.Methods:The Monongahela-Youghiogheny Healthy Aging Team (MYHAT) and Seniors Project 15104 (SP15104) studies recruited adults aged 65+ years from a group of small towns of lower socioeconomic status in the US. MYHAT recruited by age-stratified random sampling from the voter registration list for all towns; SP15104 recruited by intensive community engagement from three towns with populations that are 60% AA. Based on the Clinical Dementia Rating (CDR), MCI was defined as CDR=0.5 and dementia as CDR > 1. Using Cox proportional hazard models, we modeled time to incident CDR > 0.5 from baseline as a function of race (AA vs. all other), other demographics, and several other covariates at baseline.Results:The sample of 2120 individuals was 8% AA, and 62% female, with median age of 73y, and median educational level of partial college. During follow up of up to 14.5 years, 499 participants developed new-onset MCI/dementia (CDR >0.5). Cox models revealed that being AA was significantly associated with incident CDR > 0.5 (HR=1.45. 95% CI:1.01,2.10). Inclusion of age, sex, and education in the model increased the HR for race to 1.63 (1.1, 2.3). Adding number of regularly taken prescription drugs (reflecting overall morbidity), depression symptoms, preceding year alcohol consumption, and number of visits to emergency or urgent care together reduced the HR to 1.4 (0.96, 2.0), no longer statistically significantConclusions:In this population-based cohort study, self-identified African Americans had an about 40% elevated risk of developing MCI/dementia. Adjusting for demographics, the significant association between race and incident MCI/dementia was attenuated by variables reflecting depression, greater general morbidity, and lesser access to regular health services. These variables possibly reflect downstream effects of historic discrimination, but couldstill be modifiable risk factors for MCI/dementia. Addressing them could potentially mitigate ethno-racial disparities in cognitive impairment.

Contribution of smoking, disease history, and survival to lung cancer disparities in Black individuals.

Lung cancer is the leading cause of cancer deaths and disproportionately affects self-identified Black or African American ("Black") people, especially considering their relatively low self-reported smoking intensity rates. This study aimed to determine the relative impact of smoking history and lung cancer incidence risk, histology, stage, and survival on these disparities. We used 2 lung cancer models (MichiganLung-All Races and MichiganLung-Black) to understand why Black people have higher rates of lung cancer deaths. We studied how different factors, such as smoking behaviors, cancer development, histology, stage at diagnosis, and lung cancer survival, contribute to these differences. Adjusted for smoking history, approximately 90% of the difference in lung cancer deaths between the overall and Black populations (born in 1960) was the result of differences in the risk of getting lung cancer. Differences in the histology and stage of lung cancer and survival had a small impact (4% to 6% for each). Similar results were observed for the 1950 and 1970 birth cohorts, regardless of their differences in smoking patterns from the 1960 cohort. After taking smoking into account, the higher rate of lung cancer deaths in Black people can mostly be explained by differences in the risk of developing lung cancer. As lung cancer treatments and detection improve, however, other factors may become more important in determining differences in lung cancer mortality between the Black and overall populations. To prevent current disparities from becoming worse, it is important to make sure that these improvements are available to everyone in an equitable way.

The Collaborative Study on the Genetics of Alcoholism: Overview.

Alcohol use disorders (AUD) are commonly occurring, heritable and polygenic disorders with etiological origins in the brain and the environment. To outline the causes and consequences of alcohol-related milestones, including AUD, and their related psychiatric comorbidities, the Collaborative Study on the Genetics of Alcoholism (COGA) was launched in 1989 with a gene-brain-behavior framework. COGA is a family based, diverse (~25% self-identified African American, ~52% female) sample, including data on 17,878 individuals, ages 7-97 years, in 2246 families of which a proportion are densely affected for AUD. All participants responded to questionnaires (e.g., personality) and the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) which gathers information on psychiatric diagnoses, conditions and related behaviors (e.g., parental monitoring). In addition, 9871 individuals have brain function data from electroencephalogram (EEG) recordings while 12,009 individuals have been genotyped on genome-wide association study (GWAS) arrays. A series of functional genomics studies examine the specific cellular and molecular mechanisms underlying AUD. This overview provides the framework for the development of COGA as a scientific resource in the past three decades, with individual reviews providing in-depth descriptions of data on and discoveries from behavioral and clinical, brain function, genetic and functional genomics data. The value of COGA also resides in its data sharing policies, its efforts to communicate scientific findings to the broader community via a project website and its potential to nurture early career investigators and to generate independent research that has broadened the impact of gene-brain-behavior research into AUD.

Bone Mineral Density During and After Lactation: A Comparison of African American and Caucasian Women

During lactation, changes in maternal calcium metabolism are necessary to provide adequate calcium for newborn skeletal development. The calcium in milk is derived from the maternal skeleton through a process thought to be mediated by the actions of parathyroid hormone-related protein (PTHrP) in combination with decreased circulating estrogen concentrations. After weaning, bone lost during lactation is rapidly regained. Most studies of bone metabolism in lactating women have been performed in Caucasian subjects. There are well-documented differences between African American (AA) and Caucasian (C) bone metabolism, including higher bone mineral density (BMD), lower risk of fracture, lower 25-hydroxyvitamin D (25(OH) D), and higher PTH in AA compared to C. In this prospective paired cohort study, BMD and markers of bone turnover were compared in self-identified AA and C mothers during lactation and after weaning. BMD decreased in both AA and C women during lactation, with similar decreases at the lumbar spine (LS) and greater bone loss in the C group at the femoral neck (FN) and total hip (TH), demonstrating that AA are not resistant to PTHrP during lactation. BMD recovery compared to the 2 week postpartum baseline was observed 6 months after weaning, though the C group did not have complete recovery at the FN. Increases in markers of bone formation and resorption during lactation were similar in AA and C. C-terminal telopeptide (CTX) decreased to 30% below post-pregnancy baseline in both groups 6 months after weaning, while procollagen type 1 N-terminal (P1NP) returned to baseline in the AA group and fell to below baseline in the C group. Further investigation is required to determine impacts on long term bone health for women who do not fully recover BMD before a subsequent pregnancy.

Lipidomic Profiling Reveals Biological Differences between Tumors of Self-Identified African Americans and Non-Hispanic Whites with Cancer.

In the US, the incidence and mortality of many cancers are disproportionately higher in African Americans (AA). Yet, AA remain poorly represented in molecular studies investigating the roles that biological factors might play in the development, progression, and outcomes of many cancers. Given that sphingolipids, key components of mammalian cellular membranes, have well-established roles in the etiology of cancer progression, malignancy, and responses to therapy, we conducted a robust mass spectrometry analysis of sphingolipids in normal adjacent uninvolved tissues and tumors of self-identified AA and non-Hispanic White (NHW) males with cancers of the lung, colon, liver, and head and neck and of self-identified AA and NHW females with endometrial cancer. In these cancers, AA have worse outcomes than NHW. The goal of our study was to identify biological candidates to be evaluated in future preclinical studies targeting race-specific alterations in the cancers of AA. We have identified that various sphingolipids are altered in race-specific patterns, but more importantly, the ratios of 24- to 16-carbon fatty acyl chain-length ceramides and glucosylceramides are higher in the tumors of AA. As there is evidence that ceramides with 24-carbon fatty acid chain length promote cellular survival and proliferation, whereas 16-carbon chain length promote apoptosis, these results provide important support for future studies tailored to evaluate the potential roles these differences may play in the outcomes of AA with cancer.

Three-dimensional Anthropometric Analysis of Racial and Ethnic Differences in Unilateral and Bilateral Cleft Nasal Deformity.

This study used three-dimensional measurements to provide a nasolabial analysis of patients with unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), and controls across different races and ethnicities. A retrospective comparative study. Tertiary care pediatric institution. The study included 90 patients with UCLP, 43 patients with BCLP, and 90 matched controls. Patients are separated as self-identified Caucasian, Hispanic, or African American. Nasal length, nasal protrusion, columellar height, columellar width, tip width, alar width, alar base width, nasolabial angle, upper lip length, philtrum length, nostril height, and nostril width. All UCLP groups had significantly greater columella and tip widths and decreased nasolabial angles than controls. All BCLP groups had significantly greater columella width, tip width, nasolabial angle, and nostril widths. Upper lip length, philtrum length, and nostril height were significantly decreased in BCLP compared to controls. Across UCLP groups, African Americans had significantly decreased nasal protrusion and columella height and a significantly increased columella width compared to Caucasians and Hispanics. Alar and alar base widths were significantly different between all groups. Across BCLP groups, the Caucasian nostril width was significantly less than the African Americans. These findings suggest that when correcting nasolabial characteristics in patients with cleft lip, it is important to consider racial and ethnic differences to achieve a normal appearance. Specifically, goals for alar width, alar base width, nasal tip, and projection should be tailored to the patient's race and ethnicity.

Systemic Inflammation Indices and Association with Prostate Cancer Survival in a Diverse Patient Cohort

There is a lack of investigations assessing the performance of systemic inflammation indices as outcome predictive tools in African Americans with prostate cancer. This study aims to assess the relationships between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation (SII), and systemic inflammation response index (SIRI) with survival outcomes among 680 diverse men with prostate cancer. Routine blood results were collected from self-identified African American and European American patients. We applied multivariable Cox regression modeling to examine the associations of systemic inflammation indices with overall and prostate cancer-specific survival. The median survival follow-up was 5.9 years, with 194 deaths. NLR, SII, and SIRI, but not PLR, showed associations with all-cause and prostate cancer-specific mortality when coded as dichotomized and continuous variables. NLR and SIRI were significantly associated with prostate cancer-specific mortality among all men (hazard ratio (HR) 2.56 for high vs. low NLR; HR 3.24 for high vs. low SIRI) and African American men (HR 2.96 for high vs. low NLR; HR 3.19 for high vs. low SIRI). Among European Americans, only SII showed an association with prostate cancer-specific survival. These observations suggest that inflammation indices merit further study as predictors of prostate cancer mortality.

Protein Markers of Diabetes Discovered in an African American Cohort.

Proteomics has been used to study type 2 diabetes, but the majority of available data are from White participants. Here, we extend prior work by analyzing a large cohort of self-identified African Americans in the Jackson Heart Study (n = 1,313). We found 325 proteins associated with incident diabetes after adjusting for age, sex, and sample batch (false discovery rate q < 0.05) measured using a single-stranded DNA aptamer affinity-based method on fasting plasma samples. A subset was independent of established markers of diabetes development pathways, such as adiposity, glycemia, and/or insulin resistance, suggesting potential novel biological processes associated with disease development. Thirty-six associations remained significant after additional adjustments for BMI, fasting plasma glucose, cholesterol levels, hypertension, statin use, and renal function. Twelve associations, including the top associations of complement factor H, formimidoyltransferase cyclodeaminase, serine/threonine-protein kinase 17B, and high-mobility group protein B1, were replicated in a meta-analysis of two self-identified White cohorts-the Framingham Heart Study and the Malmö Diet and Cancer Study-supporting the generalizability of these biomarkers. A selection of these diabetes-associated proteins also improved risk prediction. Thus, we uncovered both novel and broadly generalizable associations by studying a diverse population, providing a more complete understanding of the diabetes-associated proteome.

Mixed meal tolerance testing highlights in diabetes altered branched-chain ketoacid metabolism and pathways associated with all-cause mortality

BackgroundElevated BCAA levels are strongly associated with diabetes, but how diabetes affects BCAA, branched-chain ketoacids (BCKAs), and the broader metabolome after a meal is not well known. ObjectiveTo compare quantitative BCAA and BCKA levels in a multiracial cohort with and without diabetes after a mixed meal tolerance test (MMTT) as well as to explore the kinetics of additional metabolites and their associations with mortality in self-identified African Americans. MethodsWe administered an MMTT to 11 participants without obesity or diabetes and 13 participants with diabetes (treated with metformin only) and measured the levels of BCKAs, BCAAs, and 194 other metabolites at 8 time points across 5 h. We used mixed models for repeated measurements to compare between group metabolite differences at each timepoint with adjustment for baseline. We then evaluated the association of top metabolites with different kinetics with all-cause mortality in the Jackson Heart Study (JHS) (N = 2441). ResultsBCAA levels, after adjustment for baseline, were similar at all timepoints between groups, but adjusted BCKA kinetics were different between groups for α-ketoisocaproate (P = 0.022) and α-ketoisovalerate (P = 0.021), most notably diverging at 120 min post-MMTT. An additional 20 metabolites had significantly different kinetics across timepoints between groups, and 9 of these metabolites—including several acylcarnitines—were significantly associated with mortality in JHS, irrespective of diabetes status. The highest quartile of a composite metabolite risk score was associated with higher mortality (HR:1.57; 1.20, 2.05, P = 0.00094) than the lowest quartile. ConclusionsBCKA levels remained elevated after an MMTT among participants with diabetes, suggesting that BCKA catabolism may be a key dysregulated process in the interaction of BCAA and diabetes. Metabolites with different kinetics after an MMTT may be markers of dysmetabolism and associated with increased mortality in self-identified African Americans.

Abstract A009: Survival disparities in lung squamous cell carcinoma: Clinical and genomic correlates with genetic ancestry

Abstract Many studies show racial and ethnic survival disparities in lung squamous cell carcinoma (LSCC), and self-identified African-Americans have significantly lower overall survival and progression-free survival than self-identified Caucasians. However, survival models based on genetic ancestry, rather than self-identified race, are needed to assess whether genetic ancestry influences this survival disparity or whether the cause of the disparity is largely socioeconomic. Using clinically annotated genomic data from 501 LSCC tumor samples in the Cancer Genome Atlas (TCGA), we compared clinical data, gene expression profiles, mutations, and copy number changes of tumors across ancestral groups to identify significantly differential events. We then applied the Cox Proportional Hazards model to predict overall survival as a function of genetic ancestry alongside other genetic, molecular, and clinical variables. We found a significant difference in metastatic stage between tumors from patients of African (AFR) and European (EUR) ancestry, which was significant in predicting survival. We identified increased copy number of chromosome arm 8q and locus chr8q24, as well as increased expression of MYC targets in AFR samples relative to EUR samples, all of which suggest a role for the MYC pathway in differential cancer progression. In addition, we found enrichment of amplifications at chr22q11 and chr16p11 in AFR samples compared to EUR samples. We identified top differentially mutated genes between groups, of which mutant SPRR3, PDGFA, FRS3, and C21orf62 correlate with survival. Notably, when survival was modeled as a function of both genetic ancestry and SPRR3 mutation, genetic ancestry was no longer significant as a predictor of survival. The PDGFRA receptor is also significantly differentially expressed between groups, suggesting a possible role of the PDGF axis in differential tumor growth. These results suggest potential genetic and clinical factors implicated in racial survival disparities. Further studies and more diverse sampling of cancer patient populations would allow validation of these differences and future elucidation of patient-specific treatment modalities. Citation Format: Sejal Jain, Alexandria Yao, Diane Allen-Gipson, Fatemeh Momen-Heravi, Alison M. Taylor. Survival disparities in lung squamous cell carcinoma: Clinical and genomic correlates with genetic ancestry [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A009.

Genetic Testing and Other Healthcare Use by Black and White Individuals in a Genomic Sequencing Study

Introduction: Early adopters play a critical role in the diffusion of medical innovations by spreading awareness, increasing acceptability, and driving demand. Understanding the role of race in the context of other characteristics of potential early adopters can shed light on disparities seen in the early implementation of genomic medicine. We aimed to understand the association between self-identified race and individual experience with genetic testing outside of the research context. Methods: We assessed factors associated with the odds of having ever received genetic testing prior to enrollment in a genomic sequencing study among 674 self-identified white and 407 self-identified African, African American, or Afro-Caribbean (“Black”) individuals. Results: Controlling for individual determinants of healthcare use (demographics, personality traits, knowledge and attitudes, and health status), identifying as Black was associated with lower odds of prior genetic testing (OR = 0.43, 95% CI [0.27–0.68], p < 0.001). In contrast, self-identified race was not associated with the use of non-genetic clinical screening tests (e.g., echocardiogram, colonoscopy). Black and white individuals were similar on self-reported personality traits tied to early adoption but differed by sociodemographic and resource facilitators of early adoption. Conclusion: Persistent racial disparities among early adopters may represent especially-entrenched disparities in access to and knowledge of genomic technologies in clinical settings.

HFE hemochromatosis in African Americans: Prevalence estimates of iron overload and iron overload-related disease

BackgroundLittle is known about the prevalence of HFE (homeostatic iron regulator) hemochromatosis in African Americans (AA). MethodsWe defined AA as self-identified AA, blacks, or non-Hispanic blacks. We defined hemochromatosis-associated HFE genotypes as p.C282Y/p.C282Y and p.C282Y/p.H63D. We compiled prevalences of these genotypes in AA using published population and cohort data and numbers of men and women ≥18 y‬ in 2018 U.S. Census estimates. We defined iron overload (IO) and IO-related disease by genotype as previously reported in population and cohort studies of hemochromatosis in whites of European ancestry. We used these definitions to estimate prevalences and numbers of AA with IO and IO-related disease associated with hemochromatosis-associated HFE genotypes. ResultsThere were ∼16,287,599 men and ∼17,644,898 women. HFE genotypes and their respective prevalences were: p.C282Y/p.C282Y, 0.00017 (6/34,905) [95% confidence interval 0.000034, 0.00031] and p.C282Y/p.H63D, 0.0012 (41/33,596) [0.000084, 0.0016]. IO prevalences were: men 0.000076 [0.000072, 0.000081] and women 0.0000061 [0.0000050, 0.0000073]. IO-related disease prevalences were: men 0.000063 [0.000059, 0.000067] and women 0.0000021 [0.0000014, 0.0000027]. There were ∼1021 [961, 1091] men and ∼36 [25, 48] women with IO-related disease. ConclusionsWe conclude that ∼1/25,061 AA >18 y have a hemochromatosis-associated HFE genotype and IO and that ∼1/32,103 AA >18 y have a hemochromatosis-associated HFE genotype and IO-related disease.

Pulse Oximetry Error in Patients With Single-Ventricle Palliation

Pulse Oximetry Error in Patients With Single-Ventricle Palliation

Relative impact of genetic ancestry and neighborhood socioeconomic status on all-cause mortality in self-identified African Americans

Self-identified race/ethnicity is a correlate of both genetic ancestry and socioeconomic factors, both of which may contribute to racial disparities in mortality. Investigators often hold a priori assumptions, rarely made explicit, regarding the relative importance of these factors. We studied 2,239 self-identified African Americans (SIAA) from the Prostate, Lung, Colorectal and Ovarian screening trial enrolled from 1993–1998 and followed prospectively until 2019 or until death, whichever came first. Percent African genetic ancestry was estimated using the GRAF-Pop distance-based method. A neighborhood socioeconomic status (nSES) index was estimated using census tract measures of income, housing, and employment and linked to participant residence in 2012. We used Directed Acyclic Graphs (DAGs) to represent causal models favoring (1) biomedical and (2) social causes of mortality. Hazard ratios were estimated using Cox models adjusted for sociodemographic, behavioral, and neighborhood covariates guided by each DAG. 901 deaths occurred over 40,767 person-years of follow-up. In unadjusted (biomedical) models, a 10% increase in percent African ancestry was associated with a 7% higher rate of all-cause mortality (HR: 1.07, 95% CI: 1.02, 1.12). This effect was attenuated in covariate adjusted (social) models (aHR: 1.01, 95% CI: 0.96, 1.06). Mortality was lower comparing participants in the highest to lowest nSES quintile following adjustment for covariates and ancestry (aHR: 0.74, 95% CI: 0.57, 0.98, Ptrend = 0.017). Higher African ancestry and lower nSES were associated with higher mortality, but African ancestry was not associated with mortality following covariate adjustment. Socioeconomic factors may be more important drivers of mortality in African Americans.

Race and Ethnicity of Pediatric Trainees and the Board-Certified Pediatric Workforce

Race and Ethnicity of Pediatric Trainees and the Board-Certified Pediatric Workforce

Tumor immune microenvironment of self-identified African American and non-African American triple negative breast cancer

Differences in the tumor immune microenvironment may result in differences in prognosis and response to treatment in cancer patients. We hypothesized that differences in the tumor immune microenvironment may exist between African American (AA) and NonAA patients, due to ancestry-related or socioeconomic factors, that may partially explain differences in clinical outcomes. We analyzed clinically matched triple-negative breast cancer (TNBC) tissues from self-identified AA and NonAA patients and found that stromal TILs, PD-L1 IHC-positivity, mRNA expression of immune-related pathways, and immunotherapy response predictive signatures were significantly higher in AA samples (p < 0.05; Fisher’s Exact Test, Mann–Whitney Test, Permutation Test). Cancer biology and metabolism pathways, TAM-M2, and Immune Exclusion were significantly higher in NonAA samples (p < 0.05; Permutation Test, Mann–Whitney Test). There were no differences in somatic tumor mutation burden. Overall, there is greater immune infiltration and inflammation in AA TNBC and these differences may impact response to immune checkpoint inhibitors and other therapeutic agents that modulate the immune microenvironment.