Citations

Abstract Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive forms of pancreatic cancer, is associated with poor survival outcomes and currently ranks as the third leading cause of cancer-related death in the United States. Despite its clinical significance, the mechanisms of PDAC development and progression remain, in part, poorly understood. In this study, we provide evidence of a novel role of sorting nexin 10 (SNX10), a member of the sorting nexin family, in the regulation of KRAS-induced pancreatic carcinogenesis. We demonstrate that SNX10 is downregulated in PDAC, especially in advanced cases. Furthermore, mutational analysis revealed SNX10 genetic alterations in PDAC cases. Functional studies demonstrated that SNX10 overexpression in human PDAC cells inhibited cell proliferation and colony formation. Moreover, SNX10 overexpression induced G1-phase cell-cycle arrest and decreased KRAS signaling activity. Using a novel Snx10 knockout mouse crossed with a Kras-driven PDAC model, we observed reduced survival, increased tumor cell proliferation, enhanced aggression, and heightened inflammation. Collectively, these findings highlight SNX10 as a tumor suppressor candidate in PDAC and underscore its promise as a foundation for new therapeutic approaches. Significance: SNX10 plays a crucial role in reducing pancreatic tumorigenesis. This discovery offers valuable insights into PDAC’s biology and the development of new effective treatments.

Prostate cancer represents a significant health disparity among Black men, who experience higher rates of both incidence and mortality compared to other racial groups. Understanding the complex interplay of cultural, familial, and socioeconomic factors that shape health behaviors is essential for the development of effective interventions. This study sought to explore the lived experiences of ethnically diverse Black men with prostate cancer, focusing on how cultural context, family history, and spirituality influence health decisions and engagement with care. Through a secondary analysis of existing data, personal narratives from 32 Black prostate cancer survivors, primarily U.S.-born Black men, were examined to identify recurring themes that revealed the multifaceted challenges and motivations these men face. The analysis uncovered eight key themes that reflect a complex landscape, including medical distrust fueled by cultural perceptions and past negative experiences, the dual influence of family history on seeking early care versus hesitation, and the role of spirituality as a guiding force in health decisions. Additionally, financial constraints and limited access to comprehensive health information emerged as critical factors affecting engagement with preventive care. The findings underscore the need for culturally sensitive approaches that acknowledge the diverse experiences of Black men in their prostate cancer journey. By understanding the influence of family dynamics, spirituality, and socioeconomic challenges, future research can create targeted interventions that promote informed decision-making and help reduce disparities in prostate cancer outcomes.

Background: The American opioid use disorder (OUD) and overdose epidemic require physicians and advanced care providers to be prepared to care for patients with this life-threatening condition. Learning to identify, engage, and treat patients with OUD with medications is an essential skill for providers, as is developing requisite confidence and therapeutic attitudes regarding the care of patients with OUD (CP-OUD). To address the need for improved OUD treatment education, our team built and implemented a 12-module asynchronous course entitled, “Care of Patients with Opioid Use Disorder”, in 3 Doctor of Medicine (MD) programs and a Graduate School of Nursing (GSN) program. Methods: Students self-reported their attitudes and confidence regarding the CP-OUD before and after each module. Twelve questions assessed confidence, and 12 questions assessed attitude. Students’ change in confidence and attitudes before and after training was calculated. Results: Responses were collected between January 2021 and November 2024. The number of students completing each module ranged from 552 to 967 MD students and 81 to 149 GSN students. Students reported improved confidence after completing each of the 12 modules (<0.0001). Students reported improved attitudes after completing 10 of the 12 modules (<0.0001). Differences ranging from small to medium size were observed between MD and GSN student’s baseline confidence for 4 modules, and baseline attitudes for 6 modules. Conclusions: Asynchronous learning modules can be effectively implemented in medical and nursing education to improve confidence and attitudes regarding the CP-OUD. The use of asynchronous training modules allows for flexible deployment, as evidenced by their use in 3 MD programs and a GSN program. Future research should investigate whether improved confidence and attitudes during medical and nursing education result in more graduates caring for patients with OUD post-training.

Introduction Alzheimer’s disease and related dementias (ADRD) are conditions with progressive cognitive decline. Still, people living with late-stage ADRD (PLWD) have been reported to exhibit transient recovery of communication or behavioural abilities that had seemingly been lost. These lucid episodes (LEs) are underinvestigated and poorly understood. This study aims to advance scientific understanding of the incidence, prevalence and predictors of LEs and assess from family caregivers if LEs are associated with changes they make in care planning or experiences with burden, distress or grief. Methods This study recruited 545 caregivers from five ADRD-related registries in the USA. Eligibility included caregivers over 18 years who currently provide care to someone with moderate to very severe ADRD and can complete online questionnaires. Using a longitudinal observational study design, consented caregivers will be assessed monthly for 1 year using online questionnaires that inquire about witnessing LEs. If witnessed, the context and content of the LE is reported. Changes in caregiver decision-making about care for the PLWD, and caregiver burden, distress and grief are assessed at baseline, 6 and 12 months. Analysis Analysis of baseline data will assess descriptive aspects of LEs that are currently unknown (eg, prevalence, content, antecedents, duration). Longitudinal analysis will examine the incidence of LEs, characteristics of PLWD and caregivers that are predictors of episodes, and the associations between LEs and caregiver outcomes (eg, burden, distress, grief). Ethics and dissemination This study is being conducted in accordance with all Federal Policies for the Protection of Human Subjects. The protocol has been approved by the Mayo Clinic Institutional Review Board (ID 22-006861). Findings will be presented at scientific conferences and disseminated through journal publications and outreach efforts with collaborating partners invested in brain health and caregiver support.

Background and Objectives: Evidence on the relationship between formative assessment engagement and summative assessment outcomes in practicing physicians is sparse. We evaluated the relationship between engagement in the American Board of Family Medicine (ABFM) formative Continuous Knowledge Self-Assessment (CKSA) and performance on high-stakes summative assessments. Methods: This retrospective cohort study included 24,926 ABFM diplomates who completed CKSA modules and summative assessments between 2017 and 2023. We analyzed CKSA engagement metrics—such as the number of quarters completed, time of completion, and self-reported confidence—against performance on summative assessments, measured by z scores. Multivariable regression models controlled for demographic factors and prior assessment performance. Results: The overall cohort summative assessment pass rate during the study period was 90.3%. Greater CKSA engagement was strongly associated with higher summative assessment performance. Diplomates who completed all four CKSA quarters had significantly higher summative assessment z scores than those completing fewer quarters (P&lt;.001). Early CKSA completion and spending more time on low-confidence questions were also positively correlated with both CKSA and summative assessment scores (P&lt;.001). These effects were observed across different levels of prior exam performance. Conclusions: Engagement in formative assessments like CKSA, particularly early and consistent participation and reviewing incorrect or low-confidence questions, is linked to better outcomes on high-stakes assessments. Future research should explore the mechanisms underlying these associations and consider developing an index of engagement to identify physicians at risk of poor performance. Incorporating structured, longitudinal self-assessments like CKSA into certification requirements could enhance continuous learning and improve summative exam readiness.

ABSTRACTBackgroundRenal medullary carcinoma (RMC) is an aggressive tumor associated with sickle cell trait. Despite treatment advances for other rare renal tumors, RMC survival remains poor. We aimed to describe the contemporary management and survival of children and adults with RMC.ProcedureIn this multicenter retrospective cohort study, Pediatric Surgical Oncology Research Collaborative sites searched their databases for patients diagnosed with RMC (2000–2022). Descriptive statistics were calculated and survival analyses performed using Kaplan–Meier and Cox regression.ResultsThirty‐four patients with RMC were identified. Median age was 19 years (IQR: 15–28; range: 7–52). Most were male (24/34; 71%), Black (27/32; 84%), had sickle cell trait or disease (30/33; 91%), presented with metastatic disease (27/34; 79%), and were symptomatic at presentation (32/34; 94%). Median overall survival (OS) was 24 months from diagnosis (16 months for children, 28 months for adults, p = 0.6). Receipt of platinum‐based chemotherapy (23/34; 68%) was associated with significantly higher OS than other regimens (35 vs. 5 months, p < 0.001). Nephrectomy (24/34; 71%) was associated with significantly improved OS compared with non‐operative management (34 vs. 7 months, p = 0.001). Immunotherapy, targeted therapy, or radiation therapy were not associated with significant differences in OS, nor were age, sex, race, sickle cell status, SMARCB1/INI‐1, stage, nephrectomy approach, retroperitoneal lymph node dissection, gross residual disease, margins, or tumor size.ConclusionsRMC survival remains poor despite newer therapies. Nephrectomy and platinum‐based chemotherapy should be considered in locally advanced and metastatic disease. Coordinated international cooperative group studies are needed to meaningfully improve RMC survival.

Introduction: A person’s sex and/or gender may influence the pathogenesis, presentation, and therapeutic response to disease; yet, the impact of sex and gender is not routinely evaluated in medical research, nor adequately emphasized in medical school curricula. Little is known about medical school faculty knowledge and attitudes regarding sex and gender-based medicine (SGBM). Methods: We administered an online survey to 158 faculty members at WMU Homer Stryker M.D. School of Medicine. The survey of knowledge on SGBM was adapted from two prior surveys used in medical student and resident populations and modified for faculty participants. Hidden curriculum theory, which proposes students learn through formal curriculum as well as through passive perceptions of faculty and institutional attitudes, was used as a theoretical lens. Results: Thirty-eight of 158 recipients completed the survey, for a 24% response rate. Respondents answered an average of 48.53% of the knowledge questions correctly; percent correct did not differ significantly between men and women faculty members (P= .2732). Seventy one percent of respondents indicated it was important or very important to consider sex and gender when providing patient care. Only 24% indicated they had some formal or continuing education on the topic. Respondents indicated interest in educational opportunities for SGBM in the form of online modules or lectures. Conclusion: Though faculty respondents endorsed SGBM, few have had formal education related to the topic. Faculty development on SGBM may close knowledge gaps and facilitate integration of this curriculum. The survey tool developed through this project may be useful for other institutions engaged in similar efforts related to SGBM.

Abstract RATIONALE: 4G4G/4G5G SERPINE1 genotypes produce high concentrations of plasminogen activator inhibitor-1 and are associated with worse asthma outcomes. A secondary analysis of the American Lung Association (ALA) SOYA trial showed that soy isoflavones significantly reduced asthma exacerbations versus placebo among patients with 4G4G/4G5G SERPINE1 genotypes. We hypothesized that baseline characteristics predict optimal responders to soy isoflavones among this subgroup. METHODS: ALA-SOYA was a randomized controlled trial that tested the efficacy of soy isoflavones vs. placebo for reducing asthma exacerbations among adolescents and adults with symptomatic asthma. In this responder analysis among participants with 4G4G/4G5G SERPINE1 genotypes, baseline demographic and clinical characteristics were tested for effect modification of the treatment assignment (soy/placebo) on the primary outcome of annualized number of asthma exacerbations using interaction terms in negative binomial regression models, with a significance threshold of p-interaction=0.15. RESULTS: Data were available for n=168 participants. Soy reduced the annualized number of asthma exacerbations relative to placebo among patients with 4G4G/4G5G SERPINE1 genotypes (incident rate ratio (IRR)=0.37, 95% confidence interval (CI): 0.15-0.90, p=0.028). Self-reported adherence to baseline controller therapy was the only significant effect modifier of this association (interaction p=0.115), with those using inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA) controller therapy at least twice weekly experiencing reductions in asthma exacerbations with soy versus placebo (IRR = 0.25, 95% CI: 0.09-0.69; p= 0.007) but not among those using ICS/LABA controller therapy less frequently (IRR = 1.33, 95% CI: 0.22-8.02; p= 0.757). CONCLUSION: Soy isoflavones reduce asthma exacerbations among patients with the 4G4G/4G5G SERPINE1 genotypes and are most effective in those with greater adherence to asthma controller therapy regimens.

Introduction: Hypertension (HTN) is highly prevalent among patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), uncontrolled HTN as well as high blood pressure variability (BPV) can significantly impact cardiovascular health. This study aims to understand the impact of BPV in patients with ESKD following arteriovenous fistula (AVF) creation for hemodialysis, to better understand its association with age, sex, BMI, and cardiovascular risk. Methods: A retrospective analysis was conducted on 83 patients who underwent AVF creation between February 2019 and October 2020 at University of Miami Hospital. During 20 months, blood pressure measurements were collected from medical records at four different times during AVF access creation process, and BPV was quantified using machine learning clustering techniques. Results: The study identified three distinct clusters among the 83 patients with ESKD who underwent AVF creation. Cluster 1 ( n = 28) was characterized by high blood pressure variability, with a mean systolic blood pressure standard deviation of 16.2 mmHg. This cluster exhibited a significantly higher cardiovascular risk rate of 42.9% compared to Cluster 2 ( n = 30) and Cluster 3 ( n = 25), which had lower variability with mean systolic blood pressure standard deviations of 10.3 and 8.7 mmHg, respectively, and cardiovascular risk rates of 16.7% and 12.0%. Age, sex, and BMI did not differ significantly across the clusters. Conclusion: This study underscores the association between blood pressure variability and the increased risk of cardiovascular events, including myocardial infraction, stroke or heart failure in patients with ESKD undergoing AVF creation. Our findings highlight the critical need for vigilant monitoring of blood pressure fluctuations in this population and demonstrate how these variations are influenced by individual demographic factors. Further research is needed to develop targeted interventions to mitigate this risk.