African American Females Research Articles

Whole Exome Sequence Study of Mild Cognitive Impairment in African and European Americans; the Atherosclerosis Risk in Communities‐Neurocognitive Study

AbstractBackgroundMild cognitive impairment (MCI) encompasses cognitive deficits beyond normal aging that minimally impact daily functioning. Uncovering the genetic architecture of MCI, which can progress to Alzheimer’s disease in some individuals, may facilitate the development of lifestyle and pharmacologic interventions to minimize cognitive impairment or prevent dementia. We conducted a whole exome sequence study of MCI in 1,144 African American (AA) and 3,358 European American (EA) participants aged 67‐90 years from the Atherosclerosis Risk in Communities‐Neurocognitive Study.MethodsFor both single‐variant and gene‐based tests, we employed seqMeta to perform race‐stratified analyses of functional (nonsynonymous, splicing, stopgain, stoploss, or frameshift) variants in each sex alone and both sexes combined. Models were adjusted for age, sex (except sex‐stratified models), field center, and population substructure (the first ten principal components). Logistic regression models were fit on autosomal single‐variants with minor allele frequency (MAF) ≥0.01 while SKAT‐O, T1 burden, and SKAT (beta weights and MAF ≤ 0.05) gene‐based tests were conducted. The significance and suggestive p‐value thresholds were 1.13E‐06 and 2.27E‐05 for single‐variant tests and 2.81E‐06 and 5.63E‐05 for gene‐based tests, respectively, after Bonferroni correction.ResultsThe analysis sample contained 993 MCI cases and 3,509 cognitively normal participants; Table 1 contains the count for each race and sex subgroup. One significant (p‐value=1.06E‐7) single‐variant association (chr6:51712759:T:C in PKHD1) was detected in AA males (Figure 1). This variant had MAF=0.025 in AA males but was monomorphic in EA males. Four significant gene‐based associations with minor allele counts (MAC) ≥ 10 were discovered: CDC27 in AA females (SKAT‐O p‐value=6.63E‐07), C19orf18 in AA males (SKAT‐O p‐value=1.26E‐07), SLC16A10 in EA males and females combined (SKAT p‐value=1.90E‐06), and ZNF804A in EA females (T1 p‐value=2.69E‐07). Twenty‐three suggestive single‐variant and gene‐based associations with MAC ≥ 10 were identified (Figure 2).ConclusionsMCI‐associated genes have diverse biological functions including cell division, sodium‐independent transportation of amino acids, and zinc finger binding. Our findings imply that the genetic underpinnings of MCI may differ by race and sex. External replication of our findings, as well as investigations using large samples in consortia, will provide insight into the pervasiveness of sex‐specific genetic effects in dementia‐related traits.

Race and sex based disparities in sepsis

BackgroundStudies of sepsis evaluating sex- and race-related disparities in treatment and outcome have been limited by using administrative databases, which may not adequately capture sepsis diagnosis, used limited number and types of races, or not included both sex and race in the analyses. ObjectiveTo determine if patients of different races and sexes with sepsis have different mortality, receipt of mechanical ventilation or renal replacement therapy, or time to antibiotics? MethodsWe retrospectively analyzed clinical data from 34,999 patients with sepsis, defined by Sepsis-3 criteria, using logistic regression and linear regression. ResultsAfter adjustments for confounders, Asian females had the lowest adjusted 90-day mortality (OR=0.656, 95% CI=0.385–1.118, p<0.001 compared to White males). Similarly, compared to White males, African-American males had a lower adjusted mortality (OR=0.790, 95% CI=0.648–0.963, p = 0.019), while Asian males (OR=1.185, 95% CI=0. 828–1.696, p = 0.354) and both African-American (OR=0.972, 95% CI=0.800–1.182, p = 0.779) and Caucasian (OR=1.054, 95% CI=0.960–1.158, p = 0.270) females had similar mortality. Both male and female patients with Other/unknown race had higher mortality (OR=1.776, 95% CI=1.395–2.261, p<0.001 and OR=1.658, 95% CI=1.359–2.021, p<0.001), respectively. In the secondary analyses for new-onset mechanical ventilation and new-onset renal replacement therapy post-sepsis, we found no association between any of the race-sex groups and receipt of these therapies. ConclusionWe found that Asian females had the lowest adjusted 90-day mortality for patients with sepsis. Understanding the reasons for disparities in outcome after sepsis may improve care and outcomes in diverse populations.

Non-Hodgkin Lymphoma Mortality in the Elderly Population By Race, Gender, and Region in the United States

Background: Over the past decades, non-Hodgkin lymphoma (NHL) patients have significant improvement in the 5-year relative survival rate. In elderly NHL patients, comorbidities play a major role in mortality. Studies have shown that lower survival rates are multifactorial and strongly associated with certain races, gender, socioeconomic status, and availability of rituximab. Therefore, we aim to assess the differences in causes of mortality among races and genders. To better understand environmental contributions to one-year survival rate in NHL patients state-wise in the US, we examined the mortality-to-incidence rate (MIR) in senior NHL patients characterized by race, gender, and American health ranking (AHR) index.Methods: This is a retrospective study using the Centers for Disease Control and Prevention database from 2008 to 2017. Patients ≥65 years with non-Hodgkin lymphoma were included. AHR assesses the nation's health on a state-by-state basis to determine state health rankings with a composite index of health measures. AHR consists of five weighted core measures (four groups of health determinants and one health outcome): (1). Behaviors including excessive drinking, obesity, smoking, (2). Community and environment including air pollution, poverty, infectious disease, violent crime, (3). Policy including immunization, public health funding, uninsured rate, (4). Clinical care including primary care physicians, mental health providers, preventable hospitalizations, and (5). Outcomes including cancer deaths, cardiovascular deaths, diabetes, disparity in mental status. A ten-year (2008-2017) average of all-determinants value from AHR were reported and MIR, a parameter that can serve as a proxy for survival, was compared between US states. We analyzed the association between NHL mortality and state health disparities using linear regression. Multiple-cause-of-death data is based on death certificates for US residents. Each death certificate contains a single underlying cause of death, up to twenty additional multiple causes, and demographic data. We analyzed the multiple cause age-adjusted mortality rate in White males and females versus African American males and females. All data were analyzed using R version 4.0.5, with p-values <0.05 in two-sided t-tests to indicate statistical significance.Results: In this 10-year analysis, the mean age-adjusted mortality rate (AAMR) in Whites, African Americans, and all populations were 38.2, 21.4, and 36.7 per 1,000,000 population, respectively. Among all 50 states, Idaho had the highest AAMR for all populations (42.7/1,000,000) and Whites (43.1/1,000,000); Minnesota had the highest AAMR for African Americans (29/1,000,000). District of Columbia had the lowest AAMR for all populations (26.4/1,000,000); New Mexico had the lowest AAMR for Whites (30.6/1,000,000) and New York had the lowest AAMR for African Americans (Table 1). Our results demonstrated that elderly NHL patients in states with better health all-determinants index had significantly lower MIR in all populations (R 2=0.2654, p <0.001, Figure 1). The three lowest MIR states in the US were Florida (0.319), Connecticut (0.348), and New York (0.348) (Figure 2). Whites were more likely to have underlying comorbidities than African Americans, especially ischemic heart disease (Male: OR 87.16, 95% CI 74.23-102.34; Female: 26.10, 95% CI 22.01-30.94), congestive heart failure (Male: OR 53.31, 95% CI 45.35-62.66; Female: OR 25.98, 95% CI 22.25-30.34), and chronic obstructive pulmonary disease (Male: OR 54.55, 95% CI 45.27-65.73; Female: OR 45.98, 95% CI 36.48-57.95) (Table 2,3).Conclusions: States of better health index in terms of all determinants had lower MIR for elderly NHL patients in the US. Factors contributing to the difference in MIR possibly include variations in socioeconomic status, insurance coverage, and healthcare access. Our results highlight the need to focus on secondary prevention to decrease morbidities and health disparities in NHL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

What is the Orbital Volume of African-Americans?

PurposeMeasurements of orbital volume (OV) are important for reconstructive operations of orbits such as congenital deformities, trauma, and pathology. Successful orbital reconstruction relies on an accurate restoration of OV. The purpose of this study was to identify the OV in the African-American (AA) population. The specific aims were to compare OV of AAs to Caucasians and right-to-left OV in the same racial group. This is the first project in available literature that calculates these OVs. Materials and methodsThe authors implemented a retrospective observational study of successive subjects who received a maxillofacial computed tomography (CT) scan at Grady Memorial Hospital between 2017 and 2020. The primary predictor variable was race. The primary outcome was orbital volume. Two independent examiners calculated OV with an open access OsiriX MD software (version 10.0.5; Pixmeo, Switzerland). All CT scans were acquired using a departmental-based max-face CT scan protocol; 0.6mm slice thickness, 0.5mm slice increment, 100-120kV, 80-440mA, 200-220 FOV, 0.656 Pitch, and a 512 × 512 image matrix. All CT scan data sets were anonymized. The CT images was exported in the digital imaging and communication in medicine (DICOM) format file from Philips Intellispace PACS Enterprise 4.4 software to an external hard drive WD My Passport for Mac. Computer-assisted manual segmentation of OV was performed using an open-access OsiriX MD (software version 10.0.5 [Pixmeo, Switzerland]). The anterior and posterior boundary of the orbit was defined by posterior lacrimal crest and anterior aspect of the optic canal, respectively. Inter-rater reliability was calculated. Differences in means between races, genders, and sides were tested using an independent samples T-test. ResultsSixty subjects (120 orbits) with an average age of 36.7 years (range 22 to 78) met the inclusion criteria. Male-to-female ratio was 1:1. Racial distribution represented 30 AA (50%) and 30 Caucasian patients (50%). Inter-examiner reliability was 0.973. The mean OV of AA and Caucasians was 22.375 cm3 and 23.225 cm3, respectively (P = .07). The mean OV in AA and Caucasian males was 23.919 cm3 and 24.168 cm3, respectively (P = .71). The mean OV in AA and Caucasian females was 20.832 cm3 and 22.282cm3, respectively (P = .013). Gender analysis revealed that AA males had a statistically significant larger OV than AA females (P = <.0001). ConclusionIn conclusion, this study showed that the mean OV for AAs was 22.38 cm3 (male 23.919 cm3; female 20.832 cm3). Caucasian males and females had a larger OV than AA males and females. Caucasian and AA males had a larger OV than Caucasian and AA females. The study findings provide normative values for race and gender between AA and Caucasians. Understanding the average value for OV based on race and gender will assist in preoperative surgical planning of orbital trauma repair and therefore will improve surgical outcome.

Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans

Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3′hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3′hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e−8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e−22, 21.8% variation explained; males: beta = 0.75, P = 1.2e−37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3′), for C vs. T: beta = − 0.71, P = 6.6e−26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3′), for G vs. T: beta = 0.64, P = 1.9e−19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e−9, TMEM132C (~ 1 Mb 5′), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e−9, SLC17A2 (~ 8 kb 5′), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e−8, ZNF469 (~ 92 kb 5′), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.

TWO CASES OF ARTERIAL THROMBUS IN COVID-19 INFECTION

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Several studies have observed thrombotic complications in COVID-19 patients with rates as high as 30%. We present two COVID-19 cases of arterial and venous thrombotic complications. CASE PRESENTATION: A 64-year-old African American female was admitted for worsening respiratory failure due to COVID-19. HIT panel was obtained due to worsening thrombocytopenia, as the patient was on heparin for venous thrombosis prophylaxis, which was negative. Duplex of the lower extremities performed on hospital day 12 showed an acute non-occlusive deep vein thrombosis of the left common femoral vein, for which therapeutic heparin was initiated. On hospital day 25, the patient was found to have right digit ischemia with no flow to the right ulnar artery secondary to an occlusive arterial thrombus. Hematology was consulted for severe thrombocytopenia and considered to treat empirically for ITP with IVIG;however, the patient continued to decompensate and the family elected for comfort care measures. The patient expired on hospital day 30.Our second case report is a 64-year-old African American male presented from a local prison with worsening shortness of breath and was found to have COVID-19. Shortly after arrival from the ED to ICU, the patient went into cardiac arrest, ACLS was initiated and ROSC was achieved. The patient was in torsades and Vfib rhythm. He underwent left heart catheterization on hospital day 1 and was found to have 100% occlusion of obtuse marginal and underwent successful percutaneous coronary intervention with a drug-eluting stent to OM2. On hospital day 8, the patient was found to have digit ischemia of the right first through third digits. Arterial and venous duplex showed thrombotic occlusion of the right radial artery from the mid-forearm to the wrist and an acute deep vein thrombus of the left subclavian and axillary veins. DISCUSSION: COVID-19 can be associated with arterial and venous thrombosis as highlighted by our two cases. Even though the pathophysiology of thromboembolic complications in COVID-19 is not reported in the literature, it is implicated due to inflammation, hypoxia, immobilization, and DIC. In a study done by Klok et al in COVID-19 ICU patients, 27% of the study population had CTPE/Ultrasonography confirmed venous thromboembolism and 3.7% had arterial thrombosis compared to 12% of venous thrombosis in the ICU. The mechanism for hyper-coagulability in COVID infection is not known, it has been linked to the inflammatory response rather than specific properties of the virus. This association of excess inflammation and COVID-19 with subsequent activation of coagulation has been implicated in the pathogenesis of thrombosis. CONCLUSIONS: Intermediate to therapeutic anticoagulation may be necessary to prevent venous and arterial thromboembolic events in ICU patients admitted with COVID-19 given their excessive inflammatory state. REFERENCE #1: Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood, The Journal of the American Society of Hematology. 2020 Jun 4;135(23):2033-40. REFERENCE #2: Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Medicine. 2020 Apr 28:1-4. REFERENCE #3: Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Muller MC, Bouman CC, Beenen LF, Kootte RS, Heijmans J, Smits LP. Incidence of venous thromboembolism in hospitalized patients with COVID-19. Journal of Thrombosis and Haemostasis. 2020 May 5. DISCLOSURES: No relevant relationships by Sarenthia Epps, source=Web Response No relevant relationships by Harmeen Goraya, source=Web Response No relevant relationships by Raga Deepak Reddy Palagiri, source=Web Response

A RARE CASE OF ENDOBRONCHIAL GRANULAR CELL TUMORS

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Granular cell tumors are rare neoplasms primarily of neuroendocrine origin. They account for only 0.5% of soft tissue tumors. They most commonly occur in the head and neck region, with less than 10% of cases involving the respiratory tract. Due to their low prevalence, granular cell tumors are easily mistaken for more common tumors. This case highlights the presentation, diagnosis, and management of a patient with these rare tumors using a multidisciplinary approach. CASE PRESENTATION: A 41-year-old African American female smoker presented with atypical chest pain and dyspnea. Associated symptoms included fevers, chills, fatigue, cough productive of green sputum, and a 20 pound unintentional weight loss. She was hemodynamically stable with excellent oxygen saturation on room air. Physical exam was remarkable for slightly diminished breath sounds over the lower right lung field. CT chest demonstrated right hilar lymphadenopathy and a bulky, heterogenous 5.9 x 6.1 x 5.6 cm mass in the posterior medial right lower lobe. Bronchoscopy revealed several yellow, lobulated endobronchial lesions located in the right upper and lower lobes. Biopsies were obtained from both locations, resulting in PAS+, S100+, and SOX10+ stains. Fine needle aspiration (FNA) of hilar and mediastinal adenopathy was performed via endobronchial ultrasound (EBUS) and was negative for malignancy. The combined morphologic and immunohistochemical findings were determined to be consistent with a granular cell tumor.The case was presented at the hospital center's multidisciplinary thoracic conference with a recommendation for formal surgical evaluation. Cardiothoracic surgery performed a right video-assisted thoracoscopic surgery (VATS) exploration and second biopsy of the right upper lobe mass, with pathology again consistent with granular cell tumor. Definitive treatment for this patient concluded with a right pneumonectomy. DISCUSSION: Granular cell tumors are rare, slow growing tumors presenting most often in the head and neck region. Persons in their 4th-6th decade of life are most commonly affected, with an increased incidence in African American females. When pulmonary involvement occurs, granular cell tumors may present as an endobronchial lesion or small solitary lung mass less. Diagnosis requires tissue acquisition and immunohistochemical staining. Granular cell tumors are typically benign, with a malignancy rate of less than 3%. There is little evidence to support the use of chemoradiation in treatment of these tumors. Surgical resection offers the best therapeutic option for curative treatment. CONCLUSIONS: Granular cell tumors are rarely occurring pulmonary neoplasms with a lack of standardized management recommendations. This case illustrates a multidisciplinary approach to identification, evaluation, and management of these rare neoplasms. REFERENCE #1: Jobrack AD, Goel S, Cotlar AM. Granular Cell Tumor: Report of 13 Cases in a Veterans Administration Hospital. Military medicine. 2018 Sep 1;183(9-10):e589-e593. REFERENCE #2: Becelli R, Perugini M, Gasparini G, Cassoni A, Fabiani F. Abrikossoff's tumor. The Journal of craniofacial surgery. 2001 Jan;12(1):78-81. REFERENCE #3: Farooqui SM, Khan MS, Adhikari L, Doshi V. Multifocal Pulmonary Granular Cell Tumor Presenting with Postobstructive Pneumonia. Merrick DT, ed. Case Reports in Pulmonology. 2017:8513702 DISCLOSURES: No relevant relationships by Emily Breeding, source=Web Response No relevant relationships by Kelly Hill, source=Web Response No relevant relationships by Kari McCoy, source=Web Response No relevant relationships by Caroline Mears, source=Web Response no disclosure on file for Billur Samli

An Examination of Risk Profiles among Justice-Involved Girls: Do Race and Place Matter?

ABSTRACT Studies addressing risk factors among justice-involved girls in rural areas remain a neglected area of research. Following an intersectional framework, the current study examines the patterning of a broad range of risk factors and health needs, across urban and rural contexts, among arrested African American, Hispanic, and white females who participated in a public health service. Results from a latent class analysis suggest significant differences in substance use, physical health, depression, and trauma experiences among the racial/ethnic groups and across geographic setting. This study has implications for prevention, screening and assessment procedures of arrested youths, and intervention services in the juvenile justice system.

Association of the SNP rs112369934 near TRIM66 Gene with POAG Endophenotypes in African Americans

We investigated the association of the single nucleotide polymorphism (SNP) rs112369934 near the TRIM66 gene with qualitative and quantitative phenotypes of primary open-angle glaucoma (POAG) in African Americans (AA). AA subjects over 35 years old were recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study in Philadelphia, PA. Glaucoma cases were evaluated for phenotypes associated with POAG pathogenesis, and the associations between rs112369934 and phenotypes were investigated by logistic regression analysis and in gender-stratified case cohorts: The SNP rs112369934 was found to have a suggestive association with retinal nerve fiber layer (RNFL) thickness and cup-to-disc ratio (CDR) in 1087 male AA POAG cases, individuals with the TC genotype having thinner RNFL (95% CI 0.85 to 6.61, p = 0.01) and larger CDR (95% CI −0.07 to −0.01, p = 0.02) than those with wildtype TT. No other significant associations were found. In conclusion SNP rs112369934 may play a role in POAG pathogenesis in male AA individuals. However, this SNP has been implicated in higher POAG risk in both male and female AA POAG cases.

Outcomes of upfront autologous hematopoietic cell transplantation in patients with multiple myeloma who are 75 years old or older.

Consolidative autologous hematopoietic stem cell transplantation (AHCT) is commonly used for patients with multiple myeloma (MM). We studied AHCT use and outcomes in patients with MM ≥75 years old. Patients with MM ≥75 years old receiving AHCT between 2013 and 2017 in the United States were identified using the Center for International Blood and Marrow Transplant Research database. Relapse and/or progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. Covariates used were age, sex, Karnofsky performance score (KPS), HCT-comorbidity index (HCT-CI), International Staging System and/or Durie-Salmon stage, high-risk cytogenetics, melphalan dose, and disease status at and 1 year after transplant. AHCT utilization rate using the Surveillance, Epidemiology, and End Results database was used to estimate specific incidence among ≥75 years old by race and gender. Of 360 patients, 63% were male, 84% were White, 56% had KPS <90, and 57% had HCT-CI ≥3. The 100-day transplant-related mortality was 1% (0%-2%) with a 2-year REL rate of 27% (95% confidence interval [CI], 22%-33%), PFS of 66% (95% CI, 60%-72%), and OS of 83% (95% CI, 78%-87%). On multivariate analysis, only high-risk cytogenetics was associated with REL risk and decreased PFS. In White males, transplant utilization rate was 5.2%-5.8% compared to 3.5%-4.0% in African American males (P = .02). There was 3.37-3.79% transplant utilization in White females compared to 1.88-2.12% in African American females (P < .01). The use of AHCT was associated with excellent 2-year outcomes in this selected MM population ≥75 years old. Transplant utilization for patients ≥75 years old remains low with significant racial and gender disparities.

Do Racial Differences in Orbital Volume Influence the Reconstruction of Orbital Trauma

Successful orbital reconstruction relies on an accurate restoration of orbital volume (OV). The purpose of this study was to determine if the OV of African American (AA) subjects differs from that of Caucasian subjects. The authors implemented a retrospective observational study of successive subjects who received a maxillofacial computed tomography (CT) scan at a level I trauma center between 2017 and 2020. The primary predictor variable was race (AA/Caucasian). The primary outcome variable was orbital volume. Two independent examiners calculated OV with an open access OsiriX MD software version 10.0.5 (Pixmeo, Switzerland). Inter-rater reliability was calculated. Differences between races, genders, and sides were tested using independent samples t test with a significance of P < .05. Sixty subjects (120 orbits) were included in the study. The mean age was 36.7 (SD ± 13.2) years with a range of 22 to 78 years. Gender distribution was equal with 30 male (50%) and 30 female (50%) subjects. Inter-examiner reliability was 0.973. The mean OV of AA and Caucasians was 22.38 and 23.23 cm3, respectively (P=.07). The mean OV of AA and Caucasian males was 23.92, and 24.17cm3, respectively (P=.71). The mean OV in AA and Caucasian females was 20.84 and 22.28cm3, respectively (P=.013). African-American female subjects appear to have a smaller OV when compared with Caucasians which may influence orbital reconstruction. Laterality does not appear to be associated with any differences in OV.

Tryptophan, kynurenine pathway, and diabetic ketoacidosis in type 1 diabetes.

Diabetic ketoacidosis (DKA) is a serious complication of complete insulin deficiency and insulin resistance in Type 1 diabetes (T1D). This results in the body producing high levels of serum ketones in an attempt to compensate for the insulin deficiency and decreased glucose utilization. DKA’s metabolic and immunologic dysregulation results in gradual increase of systemic and cerebral oxidative stress, along with low grade systemic and cerebral inflammation and the development of pretreatment subclinical BE. During treatment the early progression of oxidative stress and inflammation is hypothesized to advance the possibility of occurrence of crisis of clinical brain edema (BE), which is the most important cause of morbidity and mortality in pediatric DKA. Longitudinal neurocognitive studies after DKA treatment show progressive and latent deficits of cognition and emphasize the need for more effective DKA treatment of this long-standing conundrum of clinical BE, in the presence of systemic osmotic dehydration, metabolic acidosis and immune dysregulation. Candidate biomarkers of several systemic and neuroinflammatory pathways prior to treatment also progress during treatment, such as the neurotoxic and neuroprotective molecules in the well-recognized tryptophan (TRP)/kynurenine pathway (KP) that have not been investigated in DKA. We used LC-MS/MS targeted mass spectrometry analysis to determine the presence and initiation of the TRP/KP at three time points: A) 6–12 hours after initiation of treatment; B) 2 weeks; and C) 3 months following DKA treatment to determine if they might be involved in the pathogenesis of the acute vasogenic complication of DKA/BE. The Trp/KP metabolites TRP, KYN, quinolinic acid (QA), xanthurnenic acid (XA), and picolinic acid (PA) followed a similar pattern of lower levels in early treatment, with subsequent increases. Time point A compared to Time points B and C were similar to the pattern of sRAGE, lactate and pyruvic acid. The serotonin/melatonin metabolites also followed a similar pattern of lower quantities at the early stages of treatment compared to 3 months after treatment. In addition, glutamate, n-acetylglutamate, glutamine, and taurine were all lower at early treatment compared to 3 months, while the ketones 3-hydroxybutaric acid and acetoacetate were significantly higher in the early treatment compared to 3 months. The two major fat metabolites, L-carnitine and acetyl-L-carnitine (ALC) changed inversely, with ALC significantly decreasing at 2 weeks and 3 months compared to the early stages of treatment. Both anthranilic acid (AA) and 3-OH-anthranilic acid (3OH-AA) had overall higher levels in the early stages of treatment (A) compared to Time points (B and C). Interestingly, the levels of AA and 3OH-AA early in treatment were higher in Caucasian females compared to African American females. There were also differences in the metabolite levels of QA and kynurenic acid (KA) between genders and between races that may be important for further development of custom targeted treatments. We hypothesize that the TRP/KP, along with the other inflammatory pathways, is an active participant in the metabolic and immunologic pathogenesis of DKA’s acute and chronic insults.

Abstract LB083: Characterizing colon and prostate cancers with comorbid chronic kidney disease in NHANES

Abstract In the US, the prevalence of chronic kidney disease (CKD) is estimated at 30 million, or approximately 15% of the population. Compared to Caucasians (CA), African Americans (AAs) have a higher prevalence of CKD, and faster decline in kidney function. Relationships between low socio-economic status (SES), area-level social disadvantages, and CKD are well documented. In cancer patients, CKD impedes overall survival, treatment, and surgical outcomes. Given the link between kidney disease preceding cancer, as well as the higher risk of mortality for cancer patients with CKD, the goals of this research were to identify the tumor types most associated with CKD prevalence and to elucidate the modifying effects of age, race, gender, and lifestyle/environmental measures on these relationships. Using the National Health and Nutrition Examination Survey (NHANES), we generated cross-sectional associations between CKD and various cancer types for the years of 2007-2018. After exclusion for age under 18 years, non-AA or non-CA race, or incomplete information for exposure (CKD) or outcome (cancer), a nationally representative, weighted sample of ~25,000 subjects was included in the analysis. CKD was defined as estimated glomerular function (eGFR) &amp;lt;60 ml/min/1.73 m2. Self-reported measures of ever having any type of cancer and type of cancer were used for tumor variables. CKD was present in 15% of all NHANES subjects, and 21% of those with CKD reported having any cancer versus 12% of those without CKD. In a cancer-only analysis, overrepresented tumor types in CKD vs. non-CKD patients were prostate (23% vs. 6%) and colon (7% vs. 4%). Cases of colon cancer were significantly higher for CKD patients of all races, with the largest CKD-related difference for female AAs (28% in CKD vs. 7% in non-CKD). For both races, prostate cancer had higher CKD comorbidity, strongest for male AAs. While eGFR normally decreases with age, AAs had low eGFR in younger cases (50-60years), for both prostate and colon cancers, notably in female AAs with colon cancer. Body mass index (BMI) was higher for those with CKD (29.4) versus non-CKD (28.9). In a gender/race stratified analysis, AA women with colon cancer who were obese (BMI 30+) had 1.66 times the odds of also having CKD relative to all other BMI categories. Men with colon cancer also showed increased odds of CKD in obese versus all other BMI categories (AA 1.98, CA 1.21). There was no effect of BMI on prostate cancer. Overall, CKD is a more frequent in cancer patients than for cancer-free patients even when accounting for age. This relationship is modified by tumor type, race, and gender. Prostate and colon cancers have strong associations with CKD which are independent of age in AAs. Obesity is linked to CKD-comorbid colon cancers for AAs and males. These findings identify high-risk subgroups for colon cancer and suggest dietary/metabolic/environmental etiology and intervention strategies. Citation Format: Michael Behring, Dawna Nelson, Tina Vazin, Ram Alagan, Seela Aladuwaka, Manoj Mishra, Tariq Shafi, Orlando Gutierrez, Upender Manne. Characterizing colon and prostate cancers with comorbid chronic kidney disease in NHANES [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB083.

Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention

Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. HIV disease. The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

Exploring Attitudes, Beliefs and Behavior Towards Hormonal Birth Control Among Female Patients with Sickle Cell Disease through Semi-Structured Interviews

▪Background: Sickle cell disease (SCD) is an inherited, autosomal recessive disorder and one way to decrease the risk of transmission of the disease is through informed reproductive choices. The U.S. Medial Eligibility Criteria for Contraceptive Use advises that the benefits of using hormonal contraceptives usually outweigh the risks for women with SCD. Recommendations for contraceptive use for individuals with sickle cell disease do not discourage the use of any specific contraceptives and identify sickle cell disease as a condition that exposes the woman to increased risk as a result of unintended pregnancy. Research indicates that women with SCD use hormonal contraceptives at lower rates than women without SCD.Objective: We sought to understand women with SCD knowledge, attitudes, and practices around hormonal contraceptives.Methods: African American females 18 and older with SCD were recruited from a sickle cell clinic in Atlanta, Georgia. We administered semi-structured interviews to examine the intersection of sickle cell and reproductive health. These semi-structured interviews explored participants' knowledge and attitudes towards hormonal contraceptives, as well as their personal experiences using hormonal contraceptives.Results: Seventeen women were interviewed on this topic. All but two of the participants indicated they had previously used hormonal contraceptives, but most of the women were not currently using hormonal birth control. Some of the participants had positive thoughts towards hormonal birth control because it prevents pregnancy.Birth control period. I am all for it. I feel like that is a good prevention of having unplanned pregnancies and whatever.Women cited positive experiences with hormonal birth control because it helped with heavy menstrual bleeding and decreased the number of sickle cell pain crises they experienced.I had depo before. It just made me gain weight and my cycles were off balance but it kind of helped with the Sickle Cell crisis a little bit.I would have pain crisis every time I had a menstrual cycle so my doctor told me to go to a gynecologist to get onto a birth control so that kind of decreased the amount of crisis that I was getting.Some of the participants had negative perceptions of hormonal birth control. Some were wary of it altogether. Most of them cited the side effects associated with hormonal birth control as the main reason they did not use them.I don't think any women should be on them just because of all the stuff in it. Some stuff they do not tell you what is in it and the weight gain and all the side effects I don't like them.That's why I don't like them because of the symptoms that I had. I wason Depo and I bleed for two months straight. And then I tried another one.Some green pill I don't know. I tried the implant. Like I said all the side effectsI didn't like them. I didn't like when I had side effects with it.Participants had specific concerns about the side effects related to menstrual bleeding and the intersection between contraceptive and sickle cell.I know they can just regulate your menstrual cycle. I kind of feel like that's unnatural. I think God put that in place for a reason and it needs to clean your body out. I just kind of think that part of it is unnatural and it shouldn't happen.I actually had to get one of them took out. The Nexplanon it actually caused a blood clot which is dangerous for a Sickle Cell patient.Right now I have an IUD and at first it was giving me back problems but I think it was just associated with Sickle Cell. So I think maybe it can trigger a Sickle Cell crisis sometimes.Conclusion: Our study findings indicate that women with SCD have low utilization of hormonal birth control with concerns for side effects caused by, and a general distrust of, hormonal contraception. However, some women also acknowledge that hormonal contraception can help prevent unplanned pregnancy, which not only may lead to unintended transmission of SCD, but also increased health risks to the woman. Providers caring for women with SCD may be able to better support them by adopting a patient-centered approach to contraceptive counseling. Seeking to clarify women's reproductive goals, contraceptive priorities and concerns, as well as correcting misinformation and reassuring women about hormonal contraceptive safety for women with SCD may be beneficial. DisclosuresNo relevant conflicts of interest to declare.

Ameliorating Prediabetes With Healthy Lifestyles: A Stage-Tailored Motivational Interviewing Pilot

This study assessed the feasibility, acceptability, and preliminary efficacy of a nurse-led, 3-session, stage-tailored motivational interviewing (MI) program in modifying the lifestyles of 23 primarily African American (52%) females who were overweight/obese and had prediabetes. All participants attended all 3 MI sessions. More than 90% were satisfied with the program. The participants (baseline mean age = 45, BMI = 39.2, and A1C = 5.98) demonstrated significant decreases in waist circumferences and systolic/diastolic blood pressures, and improvements in exercise self-efficacy, readiness for behavioral changes, eating patterns, and moderate-intensity physical activity (PA). This pilot was well-accepted and efficacious in promoting healthy lifestyle among overweight/obese female adults with prediabetes.

OR1. Frailty, Quality of Life, and Renal Dysfunction in African Americans with Preserved Ejection Fraction Heart Failure

<h3>Background</h3> African Americans (AA) are at a higher risk for heart failure with preserved ejection fraction (HFpEF) and renal impairment. They are predisposed to several shared risk factors for both syndromes at a younger age. HFpEF is associated with frailty and poor health-related quality of life (HRQOL). Renal impairment amplifies the inflammatory state in HFpEF, worsens ventricular function, and leads to increased frailty and poorer HRQOL. In HFpEF trials, AAs are often underrepresented and patients with renal impairments are often excluded. As such, little is known about HRQOL and frailty in AA with HFpEF. <h3>Objectives</h3> We aimed to examine HRQOL scores and frailty in AA with HFpEF, and to explore the moderation effect of estimated glomerular filtration rate (eGFR) on the relationship between frailty and HRQOL. <h3>Methods</h3> This was a cross-sectional study. Sixteen AA with HFpEF were recruited between September 2019 and March 2020 from an outpatient heart failure clinic in Chicago. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used to measure HRQOL. Frailty was evaluated using Fried's frailty criteria, which included assessment of unintentional weight loss, weakness (hand-held dynamometer), slowness (walking speed), physical activity (Minnesota Leisure Time Activity questionnaire), and exhaustion (2 questions from Center for Epidemiological Studies Depression scale). Subjects meeting 3 or more criteria were classified as frail, 1 to 2 criteria were classified as pre-frail, and 0 criterion were classified as non-frail. eGFR was calculated according to CKD-EPI equation based on the latest creatinine levels from the participants' medical records. Diagnosis of Chronic Kidney Disease was obtained from participants' medical records. Comorbidities were determined by the functional comorbidity index (FCI). Multiple regression and ordinal logistic regression were used, with robust standard error and Bayesian method. Data were analyzed using Stata software (version 16) with the significance value set at p-value ≤ 0.05. <h3>Results</h3> The sample consisted of 7 males and 9 females with a mean age of 56 ±7 years. They had 5±3 comorbid conditions and 3 had Chronic Kidney Disease. The mean calculated eGFR was 62.25 ± 26 ml/min/1.73m2. The mean HRQOL score was 59 indicating poor HRQOL. There was 1 non-frail, 10 pre-frail, and 5 frail subjects. Sex and the comorbidity score explained 36.36 % of the variance in HRQOL (p=0.03). Females had worse HRQOL scores than males (coefficient= -15.81, p=0.04, CI = -31.49, -0.15). Frailty was not associated with age (p=0.27). eGFR was a predictor for HRQOL (p=0.03), but it was not a moderator of the relationship between frailty and HRQOL (p=0.06). <h3>Conclusion</h3> In this sample, African Americans with HFpEF had poor HRQOL. AA females and AA with higher numbers of comorbidities reported worse HRQOL. Most subjects were either pre-frail or frail indicating frailty may be an issue for AA with HFpEF. eGFR may be a clinically useful marker for early detection of poor HRQOL in this population.

Hidradenitis suppurativa in skin of colour.

Hidradenitis suppurativa/acne inversa (HS) more prevalent and disproportionally affects African American females. Although there are limited studies in HS skin of colour populations in the USA, there is more scarcity of HS skin of colour studies in other countries, which limits the overall understanding of the disease among these patients. Herein, our overview of the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference provided a crude example of the limited number of skin of colour physicians, physician scientists and inclusion of skin of colour patients highlighting the need to increase awareness of this important issue. We summarized the epidemiology, pathogenesis, clinical picture and focused on treatment options from southeast Asia and Africa. Our outlined general recommendations for diagnosis will render better clinical care and outcomes for diverse patient populations.

PCN124 Potential for Earlier Cancer Diagnosis to Reduce Cancer Deaths:Differences By Sex and Race/Ethnicity

To examine absolute disparities in stage IV cancer and quantify potential benefits of detection before metastasis for US subpopulations defined by sex and race/ethnicity. Annual cancer incidence and five-year probabilities of cancer deaths were obtained from the Surveillance, Epidemiology and End Results (SEER) Program for persons aged 50-79 diagnosed with invasive cancer between 2006-2015 for eight subpopulations defined by sex and race/ethnicity (Hispanic, non-Hispanic: African-American, Asian/Pacific Islander, White). Hypothetical five-year deaths and percentage deaths averted were calculated under two scenarios: (1) death rates of stage IV cancers were assigned mortality rates associated with stage III detection, and (2) death rates were assigned for stage IV as a mix of stage I, II, and III. The proportion of all cancer that was metastatic was generally similar in all subpopulations (16-21%). Case-mix adjusted probability of death within five years was ∼79% with stage IV and ∼35% with any stage diagnosis, though absolute numbers of deaths varied between groups. Among males, Asian/Pacific Islanders had the lowest (177) and African-Americans the highest (337) incidence of stage IV cancer per 100,000. Among females, Asian/Pacific Islanders had the lowest (117) and African-Americans the highest (203) incidence of stage IV cancer per 100,000. When hypothetical 5-year deaths were calculated using scenario 1, ∼13% of all cancer deaths were averted across all groups; in African-Americans, this corresponded to 56 females and 80 males per 100,000. In scenario 2, ∼21% of all deaths were averted, corresponding to 91 African-American females and 126 African-American males. This model predicts that detection of cancer before metastasis could result in comparable relative reductions in mortality across the eight subpopulations, but that the absolute number of deaths averted would be highest among African-Americans, who have the highest incidence of stage IV cancer.

Racial differences in incidence, outcomes, and genomic alterations in small cell lung cancer.

8514 Background: While the incidence of small cell lung cancer (SCLC) has been decreasing in recent years, an increasing proportion of our patients are younger African American (AA) women. There have been no studies describing these changes as well its impact on outcome and potential genomic differences amongst white and AA populations. Methods: We maintain a clinical/genomic/pathological database of all patients with SCLC treated at our comprehensive cancer center starting from 1998. We compared the baseline characteristics and outcomes (Overall survival [OS] and progression-free survival [PFS]) between AA and white patients, and between females and males. In addition, we looked at genomic alterations in &gt;350 cancer-related genes and compared the frequency and types of mutations in our study population. Results: A total of 917 patients with SCLC were included (median age 66 years, 486 female, 179 African American). Amongst the African American patients, 67.6% were female, a striking difference compared to the white population, where only 49.1% were women (P&lt;0.001). In multivariable analysis, there was no association between gender or race with OS or PFS (P&gt; 0.05). There was an increase in mutational frequency in AA women compared to both AA men and white patients. PIK3CA and KIT mutations were more frequent in females while APC mutations were more frequent in males (P=0.041 for all comparisons). There was a trend toward increased mutational frequencies in TP53, PTEN, and NOTCH1 in AA patients. The relative frequency of gene alterations is shown in the table. In univariable analysis, NOTCH1 mutation was associated with improved OS (HR 0.24 [0.06-0.96], P=0.04). Conclusions: In this large cohort of patients with SCLC followed over 2 decades, there was a striking 2-fold higher incidence of SCLC in AA females than in AA males, although there were no differences in OS or PFS by sex or race. Several genomic alterations occur in higher frequencies in AA patients and AA women, in particular, have higher mutational frequencies.[Table: see text]