A Large Irritation Fibroma of the Hard Palate: A Rare Clinical Entity.

An irritative fibroma of the oral cavity can be defined as a benign tumor of connective tissue. They usually occur in the oral cavity, with the most common sites being the buccal mucosa and tongue. However, reported cases over the hard palate are few. Irritant or reactive fibromas are brought upon by recurrent, mildly intense stimulation of the oral mucosa. This can be because of repeated tobacco chewing, ill-fitted dentures, intentional or unintentional biting, sharp teeth, and so on. Because, clinically, fibromas resemble the features of other benign or reactive tumors, histological examination is required for the appropriate management of the same. Here, we describe a case of an irritative fibroma of the hard palate in a 61-year-old female. The patient had a history of betel nut and tobacco chewing for 30 years. The patient was evaluated and underwent complete excision for the same. The base of the lesion was cauterized to prevent recurrence.

Paid Leave Mandates and Care for Older Parents.

Policy Points We examined the effect of the Paid Family Leave policy (PFL) and Paid Sick Leave policy (PSL) on care provision to older parents. We found that PSL adoption led to an increase in care provision, an effect mainly attributable to respondents in states/periods when PSL and PFL were concurrently offered. Some of the strongest effects were found among women and unpartnered adult children. PFL adoption by itself was not associated with care provision to parents except when PFL also offered job protection. Paid leave policies have heterogeneous effects on eldercare and their design and implementation should be carefully considered. CONTEXT: Family caregivers play a critical role in the American long-term care system. However, care responsibilities are known to potentially conflict with paid work, as about half of family caregivers are employed. The federal Family and Medical Leave Act passed by the US Congress in 1993 provides a nonuniversal, unpaid work benefit. In response, several states and localities have adopted the Paid Family Leave policy (PFL) and Paid Sick Leave policy (PSL) over the last two decades. Our objective is to examine the effect of these policies on the probability of personal care provision to older parents. METHODS: This study used longitudinal data from the Health and Retirement Study (1998-2020). Difference-in-differences regression models were estimated to examine associations between state- and local-level PFL and PSL mandates and personal care provision to older parents. We analyzed heterogeneous effects by the type of paid leave exposure (provision of job protection with PFL and availability of both PSL and PFL [with or without job protection] concurrently). We also examined results for different population subgroups. FINDINGS: PSL implementation was associated with a four- to five-percentage point increase in the probability of personal care provision. These effects were mainly attributable to respondents in states/periods when PSL and PFL were concurrently offered. The strongest effects were found among adult children who were employed at baseline, women, younger, unpartnered, and college educated. PFL implementation by itself was not associated with care provision to parents except when the policy also offered job protection. CONCLUSIONS: Paid leave policies have heterogeneous impacts on personal care provision, potentially owing to differences in program features, variation in caregiving needs, and respondent characteristics. Overall, the results indicate that offering paid sick leave and paid family leave, when combined with job protection, could support potential family caregivers.

Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats.

BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.

Innate and adaptive immune responses in subjects with CPA secondary to post-pulmonary tuberculosis lung abnormalities.

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%-25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. METHODS: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. RESULTS: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets. CONCLUSION: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.

Universal germline genetic testing in patients with hematologic malignancies using DNA isolated from nail clippings.

Not available.

Dual Drug Delivery for Augmenting Bacterial Wound Complications via Tailored Ultradeformable Carriers.

Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 µg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 µg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries.

RE-AIM for rural health innovations: perceptions of (mis) alignment between the RE-AIM framework and evaluation reporting in the Department of Veterans Affairs Enterprise-Wide Initiatives program.

Background: The Department of Veterans Affairs (VA) Office of Rural Health (ORH) supports national VA program offices' efforts to expand health care to rural Veterans through its Enterprise-Wide Initiatives (EWIs) program. In 2017, ORH selected Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM), an implementation science framework, to structure the EWI evaluation and reporting process. As part of its mandate to improve EWI program evaluation, the Center for the Evaluation of Enterprise-Wide Initiatives conducted a qualitative evaluation to better understand EWI team' perceptions of, and barriers and facilitators to, the EWI evaluation process. Methods: We conducted 43 semi-structured interviews with 48 team members (e.g., evaluators, program office leads, and field-based leads) representing 21 EWIs from April-December 2020. Questions focused on participants' experiences using strategies targeting each RE-AIM dimension. Interviews were inductively analyzed in MAXQDA. We also systematically reviewed 51 FY19-FY20 EWI annual reports to identify trends in misapplications of RE-AIM. Results: Participants had differing levels of experience with RE-AIM. While participants understood ORH's rationale for selecting a common framework to structure evaluations, the perceived misalignment between RE-AIM and EWIs' work emerged as an important theme. Concerns centered around 3 sub-themes: (1) (Mis)Alignment with RE-AIM Dimensions, (2) (Mis)Alignment between RE-AIM and the EWI, and (3) (Mis)Alignment with RE-AIM vs. other Theories, Models, or Frameworks. Participants described challenges differentiating between and operationalizing dimensions in unique contexts. Participants also had misconceptions about RE-AIM and its relevance to their work, e.g., that it was meant for established programs and did not capture aspects of initiative planning, adaptations, or sustainability. Less commonly, participants shared alternative models or frameworks to RE-AIM. Despite criticisms, many participants found RE-AIM useful, cited training as important to understanding its application, and identified additional training as a future need. Discussion: The selection of a shared implementation science framework can be beneficial, but also challenging when applied to diverse initiatives or contexts. Our findings suggest that establishing a common understanding, operationalizing framework dimensions for specific programs, and assessing training needs may better equip partners to integrate a shared framework into their evaluations.

Acceptability and Satisfaction of Patients and Providers With Telemedicine During the COVID-19 Pandemic: A Systematic Review.

COVID-19, also known as coronavirus disease 2019, is an extremely contagious viral sickness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After the first cases of this primarily respiratory viral illness were recorded in Wuhan, Hubei Province, China, in late December 2019, SARS-CoV-2 rapidly disseminated across the globe. Consequently, on March 11, 2020, the World Health Organization (WHO) declared it a global pandemic. The rapid spread of the COVID-19 virus, coupled with subsequent lockdowns and social distancing measures, profoundly disrupted traditional healthcare delivery systems. Amidst the COVID-19 pandemic, telemedicine emerged as a pivotal solution for delivering healthcare services while minimizing exposure to the virus. This study aims to assess patient and provider satisfaction with telemedicine during this unprecedented period. A systematic literature search was conducted on PubMed and Google Scholar using specific MeSH terms and Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) guidelines to summarize patient and provider satisfaction concerning telemedicine using all the facts, evidence, and published literature. The analysis showed that although providers were generally satisfied with telemedicine, they were less satisfied than patients due to technical issues and difficulties transmitting documents. Patients reported high satisfaction with telemedicine, citing convenience and cost savings as major benefits. However, a lack of provider compensation was identified as a potential barrier to adoption. Most providers believed that telemedicine was only necessary in emergencies while a few recognized its potential for routine care. The study concludes that telemedicine has the potential to improve healthcare access and efficiency, but more research is needed to address technical and reimbursement issues and to determine the appropriate scope of telemedicine use. Overall, the findings of this study can inform future healthcare policies and regulations to ensure that telemedicine is used effectively and to the satisfaction of both patients and providers.

Exploring glycans as vital biological macromolecules: A comprehensive review of advancements in biomedical frontiers.

This comprehensive review delves into the intricate landscape of glycans and glycoconjugates, unraveling their multifaceted roles across diverse biological dimensions. From influencing fundamental cellular processes such as signaling, recognition, and adhesion to exerting profound effects at the molecular and genetic levels, these complex carbohydrate structures emerge as linchpins in cellular functions and interactions. The structural diversity of glycoconjugates, which can be specifically classified into glycoproteins, glycolipids, and proteoglycans, underscores their importance in shaping the architecture of cells. Beyond their structural roles, these molecules also play key functions in facilitating cellular communication and modulating recognition mechanisms. Further, glycans and glycoconjugates prove invaluable as biomarkers in disease diagnostics, particularly in cancer, where aberrant glycosylation patterns offer critical diagnostic cues. Furthermore, the review explores their promising therapeutic applications, ranging from the development of glycan-based nanomaterials for precise drug delivery to innovative interventions in cancer treatment. This review endeavors to comprehensively explore the intricate functions of glycans and glycoconjugates, with the primary goal of offering valuable insights into their extensive implications in both health and disease. Encompassing a broad spectrum of biological processes, the focus of the review aims to provide a comprehensive understanding of the significant roles played by glycans and glycoconjugates.

Wiskott-Aldrich syndrome protein expression in female WAS carriers: A flow cytometry study from North India.

INTRODUCTION: Wiskott-Aldrich syndrome (WAS) is a rare X-linked inborn error of immunity characterized by microthrombocytopenia, infections, eczema, and increased predisposition to develop autoimmunity and malignancy. Flow cytometric assay for determining WAS protein (WASp) is a rapid and cost-effective tool for detecting patients. However, very few studies described WASp expression in female carriers. Most WAS carriers are clinically asymptomatic. Active screening of female family members helps identify female carriers, distinguish de novo mutations, and to select appropriate donor prior to curative stem cell transplantation. This study was undertaken to evaluate the diagnostic capability of flow cytometry-based WASp expression in peripheral blood cells to identify carriers and compare WASp expression in different blood cell lineages. PATIENTS AND METHODS: Female patients, heterozygous for WAS gene, were enrolled in this study conducted at Pediatric Allergy Immunology Unit, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Flow cytometric assessment of WASp expression in lymphocytes, monocytes, and neutrophils was carried out and compared with healthy control and affected patients. The results were expressed in delta (Δ) median fluorescence intensity (MFI) as well as stain index (SI), which is the ratio of ΔMFI of patient and ΔMFI of control. RESULTS: Thirteen mothers and two sisters of genetically confirmed WAS patients were enrolled in the study. All enrolled females were clinically asymptomatic and did not have microthrombocytopenia. Low WASp expression (SI < 1) was seen in lymphocytes and monocytes in 10 (66.6%) carriers. Females with variants in proximal exons (exons 1 and 2) were found to have lesser expression than those with distal (exons 3-12) variants. CONCLUSION: Flow cytometry is a rapid, easily available, cost-effective tool for WASp estimation. Lymphocytes followed by monocytes are the best cell lineages for WASp estimation in carrier females. However, genetic testing remains the gold standard, as carrier females with variants in distal exons may have normal WASp expression.

Unrelenting Growth and Diversification: Using the Health and Retirement Study to Illuminate Cannabis Use Among Aging Americans.

BACKGROUND AND OBJECTIVES: Cannabis use among aging Americans continues to increase. We examine correlates of cannabis use including attitudes, state of residence, health status, and service use. RESEARCH DESIGN AND METHODS: Using the 2018 Health and Retirement Study Cannabis module completed by 1,372 respondents aged 50 and older, we distinguished current cannabis users from those who have never used or have some prior use. We linked 2018 and 2016 core HRS data and used multinomial regressions to identify associations among current use, attitudes, place of residence, as well as current (2018) and past (2016) medical conditions, pain, and sleep issues. We also examined associations among cannabis use, hospital stays, and outpatient medical visits. RESULTS: Past-year cannabis use reached 10.3% among aging Americans. Attitudes toward cannabis have changed over time with 4 of 5 survey respondents currently holding a favorable attitude. Attitude and state of residence were associated with current use. Cannabis users reported higher levels of pain, were more likely to use prescription opioids, and report activity limitations in both 2016 and 2018. Associations between cannabis use and sleep issues or concurrent healthcare use were not observed. DISCUSSION AND IMPLICATIONS: Changing attitudes and state legalization appear important for late middle-aged and older persons, and as many as 1 of every 5 persons over 50 may be using cannabis by 2030. Cannabis use among aging Americans warrants increased attention from care providers, program administrators, and policymakers, especially as a prevention or harm reduction strategy relative to prescription opioids.

Pathogenic germline variants in patients with endometrial cancer of diverse ancestry.

BACKGROUND: Racial disparities in outcomes exist in endometrial cancer (EC). The contribution of ancestry-based variations in germline pathogenic variants (gPVs) is unknown. METHODS: Germline assessment of ≥76 cancer predisposition genes was performed in patients with EC undergoing tumor-normal Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets sequencing from January 1, 2015 through June 30, 2021. Self-reported race/ethnicity and Ashkenazi Jewish ancestry data classified patients into groups. Genetic ancestry was inferred from Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets. Rates of gPV and genetic counseling were compared by ancestry. RESULTS: Among 1625 patients with EC, 216 (13%) had gPVs; 15 had >1 gPV. Rates of gPV varied by self-reported ancestry (Ashkenazi Jewish, 40/202 [20%]; Asian, 15/124 [12%]; Black/African American (AA), 12/171 [7.0%]; Hispanic, 15/124 [12%]; non-Hispanic (NH) White, 129/927 [14%]; missing, 5/77 [6.5%]; p = .009], with similar findings by genetic ancestry (p < .001). We observed a lower likelihood of gPVs in patients of Black/AA (odds ratio [OR], 0.44; 95% CI, 0.22-0.81) and African (AFR) ancestry (OR, 0.42; 95% CI, 0.18-0.85) and a higher likelihood in patients of Ashkenazi Jewish genetic ancestry (OR, 1.62; 95% CI; 1.11-2.34) compared with patients of non-Hispanic White/European ancestry, even after adjustment for age and molecular subtype. Somatic landscape influenced gPVs with lower rates of microsatellite instability-high tumors in patients of Black/AA and AFR ancestry. Among those with newly identified gPVs (n = 114), 102 (89%) were seen for genetic counseling, with lowest rates among Black/AA (75%) and AFR patients (67%). CONCLUSIONS: In those with EC, gPV and genetic counseling varied by ancestry, with lowest rates among Black/AA and AFR patients, potentially contributing to disparities in outcomes given implications for treatment and cancer prevention. PLAIN LANGUAGE SUMMARY: Black women with endometrial cancer do worse than White women, and there are many reasons for this disparity. Certain genetic changes from birth (mutations) can increase the risk of cancer, and it is unknown if rates of these changes are different between different ancestry groups. Genetic mutations in 1625 diverse women with endometrial cancer were studied and the lowest rates of mutations and genetic counseling were found in Black and African ancestry women. This could affect their treatment options as well as their families and may make disparities worse.

Genomic ancestry in kidney cancer: Correlations with clinical and molecular features.

INTRODUCTION: Genetic ancestry (GA) refers to population hereditary patterns that contribute to phenotypic differences seen among race/ethnicity groups, and differences among GA groups may highlight unique biological determinants that add to our understanding of health care disparities. METHODS: A retrospective review of patients with renal cell carcinoma (RCC) was performed and correlated GA with clinicopathologic, somatic, and germline molecular data. All patients underwent next-generation sequencing of normal and tumor DNA using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, and contribution of African (AFR), East Asian (EAS), European (EUR), Native American, and South Asian (SAS) ancestry was inferred through supervised ADMIXTURE. Molecular data was compared across GA groups by Fisher exact test and Kruskal-Wallis test. RESULTS: In 953 patients with RCC, the GA distribution was: EUR (78%), AFR (4.9%), EAS (2.5%), SAS (2%), Native American (0.2%), and Admixed (12.2%). GA distribution varied by tumor histology and international metastatic RCC database consortium disease risk status (intermediate-poor: EUR 58%, AFR 88%, EAS 74%, and SAS 73%). Pathogenic/likely pathogenic germline variants in cancer-predisposition genes varied (16% EUR, 23% AFR, 8% EAS, and 0% SAS), and most occurred in CHEK2 in EUR (3.1%) and FH in AFR (15.4%). In patients with clear cell RCC, somatic alteration incidence varied with significant enrichment in BAP1 alterations (EUR 17%, AFR 50%, SAS 29%; p = .01). Comparing AFR and EUR groups within The Cancer Genome Atlas, significant differences were identified in angiogenesis and inflammatory pathways. CONCLUSION: Differences in clinical and molecular data by GA highlight population-specific variations in patients with RCC. Exploration of both genetic and nongenetic variables remains critical to optimize efforts to overcome health-related disparities.

Adenoid cystic carcinoma metastatic to the kidney: a series of 10 patients emphasizing unilateral presentation and long time interval from primary diagnosis.

Adenoid cystic carcinoma (AdCC) metastasis to kidney is rare. We identified 10 patients with metastatic AdCC in multi-institutional collaboration. Core needle biopsy was the most common specimen (n = 6). Patients were predominately female (n = 7) with a median age of 48 years (35-62 years). The most common primary location of the AdCC was head and neck (n = 6, among them parotid gland = 4), followed by lung (n = 2), breast (n = 1), and vulva (n = 1). Median lapse between primary AdCC and renal metastasis was almost 13 years (154 months, range 1-336 months). Moreover, all but one patient had unilateral kidney metastasis. The majority of metastatic AdCC within the kidney demonstrated mixed growth patterns, frequently cribriform, and tubular morphology. Follow-up available for 8 patients showed 6 alive with disease and 2 died of disease (the longest survival was 4 years past the diagnosis of renal metastasis). A systematic literature review including 29 patients revealed that kidney metastasis by AdCC is usually a late event, is typically unilateral, and is usually composed of one to three foci, and thus has clinical features which mimic a primary renal tumor.

Bioactive Compound-Loaded Nanocarriers for Hair Growth Promotion: Current Status and Future Perspectives.

Hair loss (alopecia) has a multitude of causes, and the problem is still poorly defined. For curing alopecia, therapies are available in both natural and synthetic forms; however, natural remedies are gaining popularity due to the multiple effects of complex phytoconstituents on the scalp with fewer side effects. Evidence-based hair growth promotion by some plants has been reported for both traditional and advanced treatment approaches. Nanoarchitectonics may have the ability to evolve in the field of hair- and scalp-altering products and treatments, giving new qualities to hair that can be an effective protective layer or a technique to recover lost hair. This review will provide insights into several plant and herbal formulations that have been reported for the prevention of hair loss and stimulation of new hair growth. This review also focuses on the molecular mechanisms of hair growth/loss, several isolated phytoconstituents with hair growth-promoting properties, patents, in vivo evaluation of hair growth-promoting activity, and recent nanoarchitectonic technologies that have been explored for hair growth.

Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers.

Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.

Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer.

PURPOSE: To evaluate rates of germline pathogenic/likely pathogenic variants (PVs) and genetic counseling by ancestry in patients with epithelial ovarian cancer (EOC). METHODS: Patients with pathologically confirmed EOC who underwent clinical tumor-normal sequencing from January 1, 2015, to December 31, 2020, inclusive of germline analysis of ≥76 genes were included. Patients with newly identified PVs were referred for Clinical Genetics Service (CGS) counseling. Ancestry groups were defined using self-reported race/ethnicity and Ashkenazi Jewish (AJ) heritage. Genetic ancestry was inferred computationally using validated algorithms. Logistic regression models were built. RESULTS: Of 1,266 patients, self-reported ancestry (AJ, 17%; Asian, 10%; Black/African American, 5.4%; Hispanic, 6.2%; non-Hispanic White, 57%; other, 0.16%; unknown, 4.0%) correlated with genetic ancestry (AJ ancestry, 18%; admixed, 10%; African, 4%; East Asian [EAS], 6%; European, 56%; Native American, 0.2%; South Asian [SAS], 4%; unknown, 2%). Germline PVs were observed in 313 (25%) patients, including 195 (15%) with PVs in EOC-associated genes. Those with PVs were younger at diagnosis (59 v 62 years; P < .001) and more likely to have high-grade serous ovarian cancer (83% v 72%; P = .009). PV prevalence varied between ancestry groups (P < .001), with highest rates in the AJ (39.9%) and Asian (26.5%) groups and similar rates (>10%) across other ancestry groups. Use of genetic ancestry demonstrated similar findings and further characterized high rates of PV in EAS/SAS groups. Younger age, high-grade serous histology, and self-reported AJ or Asian ancestry were associated with PV in an EOC-associated gene. Rates of CGS counseling for newly identified PVs were high (80%) across ancestry groups. CONCLUSION: Rates of PV, particularly in EOC-associated genes, were high regardless of ancestry, with similar rates of counseling between groups, emphasizing the importance of universal genetic testing in all patients with EOC.

Molecular Characterization of Endometrial Carcinomas in Black and White Patients Reveals Disparate Drivers with Therapeutic Implications.

Although the incidence of endometrial carcinoma (EC) is similar in Black and White women, racial disparities are stark, with the highest mortality rates observed among Black patients. Here, analysis of 1,882 prospectively sequenced ECs using a clinical FDA-authorized tumor-normal panel revealed a significantly higher prevalence of high-risk histologic and molecular EC subtypes in self-identified Black (n = 259) compared with White (n = 1,623) patients. Clinically actionable alterations, including high tumor mutational burden/microsatellite instability, which confer benefit from immunotherapy, were less frequent in ECs from Black than from White patients. Ultramutated POLE molecular subtype ECs associated with favorable outcomes were rare in Black patients. Results were confirmed by genetic ancestry analysis. CCNE1 gene amplification, which is associated with aggressive clinical behavior, was more prevalent in carcinosarcomas occurring in Black than in White patients. ECs from Black and White patients display important differences in their histologic types, molecular subtypes, driver genetic alterations, and therapeutic targets. SIGNIFICANCE: Our comprehensive analysis of prospectively clinically sequenced ECs revealed significant differences in their histologic and molecular composition and in the presence of therapeutic targets in Black versus White patients. These findings emphasize the importance of incorporating diverse populations into molecular studies and clinical trials to address EC disparities. This article is featured in Selected Articles from This Issue, p. 2293.