Citations

The immune tumor microenvironment (iTME) plays a crucial role in disease biology of plasma cell (PC) dyscrasias, but remains poorly characterized in self-identified Black individuals, a population at increased risk. Mass cytometry and scRNA-seq of 128 bone marrow aspirates revealed significant changes in immune cell composition across the disease spectrum, including shifts from naïve to effector T cells with declines in B cells, MAIT, pDCs, and increases in monocytes with disease progression. Self-identified Black patients had higher relative proportions of terminally differentiated T cells and lower monocytes in newly diagnosed and treated multiple myeloma (MM). ScRNA-seq revealed genes overexpressed in self-identified Black individuals were enriched for E2F targets and G2-M checkpoints, while reduced genes were enriched for TNF-α/NF-kB, interferon and inflammatory responses pathways. These findings were supported by genetic ancestry and validated in an independent dataset of 286 patients with MM from the MMRF Immune Atlas. Self-identified race and African genetic similarity are significantly associated with remodeling the MM iTME, with potential implications for disease biology and treatment response.

BACKGROUND: With evolving therapy for heart failure with reduced ejection fraction, the benefits of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT) remain unclear, particularly for nonischemic cardiomyopathy (NICM). This study evaluates long-term survival among patients with NICM treated with CRT defibrillator (CRT-D) versus CRT pacemaker (CRT-P). METHODS: DECIDE-CRT (Cardiac Resynchronization With or Without Defibrillator in Non-Ischemic Cardiomyopathy) is a multicenter cohort study across 170 US Veterans Affairs hospitals. We identified patients with NICM receiving primary-prevention CRT-P or CRT-D between January 1, 2006, and December 31, 2020. Using a propensity score approach, we applied inverse probability of treatment weighting to balance baseline characteristics between the CRT-P and CRT-D groups. An inverse probability of treatment weighting–weighted Cox model estimated hazards for all-cause mortality. Secondary outcomes included generator replacement, device-related infections, hospitalization for heart failure, and ventricular arrhythmias. RESULTS: Of 16 609 CRT recipients, 3965 met NICM primary-prevention criteria (CRT-D=3158; CRT- P =807). At baseline, patients with NICM receiving CRT-P were much older, with more cardiovascular and noncardiovascular comorbidities compared with the CRT-D group. During the median follow-up of 5.2 years, the mortality rate for CRT-P versus CRT-D was 9.46 versus 9.21 per 100 person-years (RR, 0.97 [95% CI, 0.71–1.13]; P =0.66). The adjusted hazard ratio for all-cause mortality using the inverse probability of treatment weighting-Cox model was 0.90 (95% CI, 0.71–1.13; P =0.34). There was no difference in adjusted hazard for heart failure hospitalization (hazard ratio, 1.27 [95% CI, 0.86–1.87]), while the CRT-D group had higher rates of generator replacement and device-related infections. CONCLUSIONS: This nationwide observational study from the Veterans Affairs Health system did not demonstrate a clear survival advantage with the addition of a defibrillator among patients with NICM receiving CRT although residual confounding cannot be excluded. Given the uncertainty surrounding the incremental benefit of the defibrillator in this setting, a randomized trial is needed to test the incremental value of CRT-D over CRT-P in NICM.

Abstract Black/African American populations, globally, bear the greatest prostate cancer (CaP) burden compared to other racial/ethnic groups. Addressing CaP disparities in Black men is complex, requiring a patient-centered, community-centric and comprehensive approach. This study integrates iCCaRE Consortium findings and broader literature to address unmet needs in survivorship care. The iCCaRE Consortium implemented five complementary pilot studies using mixed-methods designs, including feasibility trials, qualitative research, and observational analyses across the United States and sub-Saharan Africa. Descriptive statistics, subgroup analyses, and qualitative thematic analyses were performed across these studies. Collectively, projects addressed multilevel determinants including social, behavioral, and biological drivers of disparities. Project 1 implemented a Virtual Reality Assistant (ViRA) across clinical and community settings, with ongoing evaluation in pragmatic trials. Project 2 showed strong patient preference for home-based cancer care. Project 3 enrolled demonstrated trends toward improved health-related quality of life. Project 4 identified key themes influencing survivorship experiences. Project 5 identified biological mechanisms linking stress, immune modulation, and symptom burden. The iCCaRE pilot projects demonstrate the feasibility and early impact of a consortium-based, transdisciplinary approach to addressing CaP disparities in Black men. These findings highlight the importance of integrating patient-centered interventions, community engagement, and biological insights to inform scalable strategies aimed at improving survivorship outcomes and advancing health equity. The iCCaRE Consortium demonstrates that a transatlantic, patient-centered, and multidisciplinary approach integrating social, clinical, and biological factors can generate scalable strategies to improve survivorship outcomes and advance equity in CaP care for Black men.

Introduction: Systemic racism continues to shape maternal health care in the United States, contributing to higher rates of adverse outcomes for Black women and other women of color. Doulas have emerged as important advocates, yet little is known about how doulas’ own racial identities influence their work in challenging inequities. Methods: This qualitative study used a phenomenological approach to explore doulas’ perspectives on racism in maternal health care. Ten doulas in Northeast Florida participated in in-depth interviews and focus groups between 2021 and 2022. Data were transcribed verbatim and analyzed thematically using established qualitative methods. Results: Four major themes were identified: (1) challenging differential racial treatment, (2) leveraging privilege, (3) anti-racist doula training, and (4) advocating for Black doula recruitment and engagement. White doulas described using their privilege to support clients of color, while Black doulas described navigating heightened scrutiny and exclusion. Across participants, there was consensus that current training inadequately prepares doulas to address racism and that greater racial diversity within the profession is essential. Discussion: Findings highlight how doulas both confront and adapt to systemic racism in maternal health care. Their accounts point to gaps in training and structural barriers to equitable practice, while also illustrating how advocacy can both protect clients and, at times, reproduce inequities through unequal access to power and privilege. Health Equity Implications: Addressing how race and privilege shape advocacy pathways, reforming training to include racial justice, expanding recruitment and support for Black doulas, and integrating doulas into perinatal care models are important strategies for advancing maternal health equity and advocating for Black racial justice in health.

Abstract Rural and low-socioeconomic status women face social determinants of health barriers leading to disproportionately low rates of breast cancer screening and markedly reduced participation in clinical trials. To address this gap, we developed the WeCARE (Women’s Engagement for Cancer Awareness, Resources, and Education) intervention using a community-engaged approach. This paper describes how Community Advisory Board feedback informed the development of Mayo Clinic Health System’s WeCARE intervention components. Their input was systematically analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0) to identify determinants of acceptability, appropriateness, and feasibility and to guide actionable refinements to intervention content and delivery.

Abstract Genetic studies have significantly advanced our understanding of tauopathies, yet the genetic aetiology of Pick’s disease, a rare 3-Repeat tauopathy, remains unclear. The MAPT p.A152T variant has been identified as a risk factor for Alzheimer’s disease and progressive supranuclear palsy, but its role in Pick’s disease is unknown. In this study, we examined the prevalence of MAPT p.A152T in the largest series of neuropathologically confirmed Pick’s disease cases to date (n = 401). Through genotyping, we identified a single mutation carrier in the Pick’s disease cohort (minor allele frequency = 0.12%). We previously reported MAPT p.A152T at a 0.20% frequency in healthy controls (n = 2456), suggesting that it does not associate with 3-Repeat tauopathy risk. To further investigate the effect of the variant on MAPT transcript expression, we used bulk RNA sequencing in Alzheimer’s disease and progressive supranuclear palsy A152T mutation carriers. We did not detect significant differences in 4-Repeat tau levels, though preliminary trends may indicate more nuanced effects that need to be examined with long-read sequencing in a larger series. Overall, our study suggests that MAPT p.A152T does not increase Pick’s disease risk and may instead be linked to 4-Repeat or mixed tau pathologies, warranting further functional investigation.

Abstract Background Black women are more likely to develop and die from early‐onset breast cancer. Hereditary breast cancer (HBC) is strongly associated with early age of onset. Accordingly, HBC characteristics in young Black women were evaluated. Methods Black women diagnosed with invasive breast cancer at age 50 years or younger between 2005 and 2018 were recruited through the state cancer registries in Florida and Tennessee. Participants were asked to complete a questionnaire, sign medical records releases, and donate a saliva sample for free genetic testing to identify HBC germline pathogenic or likely pathogenic variant (GPV). Women with sporadic versus hereditary breast cancer were compared, based on age distribution, clinical characteristics, and family cancer history. Results Among 686 participants with confirmed genetic testing, 15.3% had GPVs in breast and/or ovarian cancer predisposition genes, including BRCA1 (7.7%), BRCA2 (4.5%), PALB2 (0.9%), and ATM (0.7%), with 1.5% in other genes. Compared to the sporadic group, triple‐negative breast cancers were overrepresented among BRCA1 carriers (23.6% vs. 75.5%; p < .001), and family history of breast cancer was significantly more frequent among BRCA1 , BRCA2 , and PALB2 carriers (all p < .05). The majority of breast cancers occurred by age 40 years in BRCA1 carriers (52.8%), compared to other genes, where age was more evenly distributed. Conclusion Among unselected young Black women with breast cancer, our findings demonstrate that the highest frequency of HBC GPVs are in BRCA1 , BRCA2, and PALB2, with identification of distinct histopathologic and demographic characteristics across HBC genes, underscoring the critical need for genetic testing in all populations.

INTRODUCTION: Alcohol-associated hepatitis (AH) is a severe condition with high short-term mortality. Identifying key predictors of poor outcomes is critical for guiding therapeutic strategies. Mean arterial pressure (MAP), a key determinant of tissue perfusion and systemic hemodynamics, may play a pivotal role in prognosis. METHODS: We analyzed a multicenter, prospective cohort of 323 patients hospitalized with AH, with validation in an independent cohort of 290 patients. Survival was evaluated using Kaplan-Meier curves and compared with the log-rank (Mantel-Cox) test. Cox proportional hazards models were used to estimate hazard ratios for mortality, adjusted for Model for end stage liver disease score. Mechanistic insights were explored through assessment of cardiovascular biomarkers. RESULTS: A baseline MAP <80 mm Hg was associated with significantly higher mortality at both 28 days (27.3% vs 8.0%) and 90 days (40.3% vs 15.6%; P < 0.001 for both). This association persisted after adjusting for Model for end stage liver disease score, age, and baseline hepatic encephalopathy. The incidence of infections during follow-up was similar across MAP groups (27.6% vs 22.8%), but acute kidney injury occurred more frequently in the MAP <80 mm Hg group (62% vs 38%, P < 0.001). In the validation cohort, patients with MAP <80 mm Hg also demonstrated significantly lower 28-day transplant-free survival. Although B-type natriuretic peptide and plasma renin levels were altered in patients with AH, they did not correlate with MAP values. DISCUSSION: A baseline MAP <80 mm Hg is an independent predictor of short-term and mid-term mortality in patients with AH. Strategies aimed at restoring hemodynamic stability may improve outcomes in this high-risk population.

ABSTRACT Cancer mortality is inequitably distributed across the U.S. and globally, with historically marginalized groups, particularly racial and ethnic minorities, being disproportionately affected. Disproportionate representation in clinical cancer research is a consequence of inequitable access as well as a central factor contributing to outcome disparities; it limits efficacy and safety data for underrepresented groups while directing drug development to be most beneficial for those enrolled. To tackle this problem and improve the efficacy and safety of commercially available therapies, a consensus conference on strategies to promote Diversity, Equity, Inclusion, and Accessibility (DEIA) in cancer research was empaneled in September 2022. The resulting “Indianapolis Black Paper” presented here is an international collaborative white paper with authors from industry, academia, and the government, as well as patient advocacy and community health groups. First, it outlines the roles and responsibilities of key groups involved in clinical cancer research, as they relate to representation and equity. The Black Paper then delineates five steps to promote diversity in clinical research. This actionable strategy is called “DRIVE,” and it involves: incorporating a Diversity officer into clinical research studies, Ranking clinical studies for diversity, developing an Individual diversity, equity, inclusion, and access plan, a process for Verifying study diversity, and Elevating and Enhancing training of minority investigators and research team members. Finally, we outline the timeline and milestones of implementation. Purposefully ambitious and crosscutting industry, academia, and governmental policy, the Black Paper aims to address “injustices in health” with enhanced safety, purpose, and humanity.