Faculty Bibliography

BACKGROUND:Population-based studies have linked progestin exposure to increased meningioma risk. However, the molecular basis of meningiomas associated with depot medroxyprogesterone acetate (DMPA) - a common injectable contraceptive-remains undefined. METHODS:We performed an integrated clinicopathologic and genomic analysis of meningiomas from 10 women with long-term DMPA exposure. Tumors underwent histopathological analysis, targeted sequencing, and DNA methylation profiling. Data were integrated with reference cohorts (Baylor and Heidelberg) and analyzed through classifier assignment, consensus clustering, copy number analysis, differential methylation testing, and dimensionality reduction. RESULTS:DMPA-associated meningiomas were all newly diagnosed, WHO grade 1 tumors with a predilection for the anterior and central skull base (n = 6). Nine patients harbored multiple meningiomas. Four experienced regression of untreated meningiomas following DMPA cessation, while five demonstrated stabilization. Histopathology demonstrated relative overrepresentation of metaplastic morphology, an uncommon meningioma subtype. All DMPA-associated meningiomas mapped to benign molecular groups, and most exhibited low copy number alteration burden. Targeted sequencing revealed enrichment for TRAF7 mutations (n = 5), with no NF2 mutations detected. Eight tumors shared consensus cluster identity, with cohesive grouping on principal component analysis and t-distributed stochastic neighbor embedding. No differential methylation was identified at the progesterone receptor locus. CONCLUSIONS:DMPA-associated meningiomas represent a recognizable phenotype within the broader NF2-wildtype/TRAF7-enriched spectrum of benign meningiomas, characterized by chromosomal stability, a shared methylation profile, tumor multiplicity, and regression or stabilization following DMPA cessation. While derived from a small single-institution cohort, these findings provide a molecular framework for understanding progestin-associated meningioma biology, re-interpreting epidemiologic literature, and informing population-level risk stratification.

BACKGROUND/UNASSIGNED:Osteoporosis (OP) is a common comorbidity in patients undergoing total hip arthroplasty (THA) and is a known risk factor for poor postoperative outcomes such as periprosthetic fracture (PPF). The impact of preoperative OP medications in patients with OP undergoing THA remains unclear. This study aimed to compare THA outcomes by OP diagnosis and preoperative bone strengthening medication usage. METHODS/UNASSIGNED:This was a retrospective review of primary elective THAs from June 2011-January 2024. Patients were stratified by OP diagnosis and OP medication usage, then propensity matched in a 1:2:3 ratio by age, sex, body mass index, and comorbidities. The resulting cohorts: (1) OP and medication usage for at least 1 year preoperatively and within 7 years of the procedure (n = 296), (2) OP and no medication usage (n = 592), and (3) no diagnosis of OP and no medication usage (n = 888) were then compared for postoperative outcomes. RESULTS/UNASSIGNED:= .009). Of the 12 revisions due to periprosthetic femoral fracture in cohorts 1 and 2 combined, 11 (91.7%) occurred around an uncemented implant. CONCLUSIONS/UNASSIGNED:Osteoporotic patients on OP medications did not have improved outcomes after THA compared with nonmedicated osteoporotic patients or those without a diagnosis of OP. PPF in osteoporotic patients overwhelmingly occurred around uncemented femoral implants. Surgeons should use caution when operating on osteoporotic patients, regardless of utilization of preoperative medications, and strongly consider using cemented femoral implants to decrease the risk of PPF.

Clinical equipoise-genuine uncertainty within the expert community regarding the relative merits of competing treatments-forms the ethical and scientific foundation of randomized controlled trials. The growing adoption of thoracic endovascular aortic repair (TEVAR) for uncomplicated type B aortic dissection (uTBAD) has increasingly challenged the principle of clinical equipoise in the treatment algorithm of uTBAD. Optimal medical therapy remains the accepted standard in the treatment of uTBAD. However, the expanding role of TEVAR has led some clinicians and institutions to view early intervention as beneficial, despite the lack of definitive comparative data. Randomized controlled trials, such as INSTEAD, INSTEAD-XL, and ADSORB, have demonstrated that TEVAR promotes false-lumen thrombosis and remodeling, but have not shown a clear survival benefit over optimal medical therapy. Retrospective studies frequently suggest favorable aortic remodeling and improved survival with TEVAR, yet these associative findings cannot establish causality and fall short of the evidentiary strength required to resolve treatment uncertainty. Contemporary guidelines reflect this ambiguity by endorsing aggressive medical therapy with selective TEVAR for anatomically high-risk patients. In the absence of definitive data, practice patterns have been shaped by institutional culture. Persistent uncertainties underscore the need for a definitive randomized trial. These unresolved questions underscore the persistence of clinical equipoise and the ethical necessity for a definitive randomized trial. Equipoise is challenged by institutional culture, specialty bias, referral patterns, patient expectations, and device marketing. Clinical equipoise in uTBAD will be resolved by adequately powered trials demonstrating improvement in patient-centered outcomes. Surrogate measures of aortic remodeling are insufficient.

Many individuals hospitalized due to severe viral infections develop mental and physical sequelae, which could potentially be prevented by targeted interventions for those at risk. Our goal was to develop and externally validate an algorithm for predicting mental and physical symptoms after SARS-CoV-2 hospitalization utilizing routinely collected clinical data. Participants were included from two independent samples of the German National Pandemic Cohort Network (NAPKON): a model development sample (SUEP; N = 451; mean age: 55.6 ± 15.3; 36.2% female) and an external validation sample (HAP: N = 158; mean age: 55.1 ± 12.1; 39.9% female). Machine learning models leveraging demographic, clinical and biological variables collected at the time of admission were employed to predict Patient-Reported Outcomes Measurement Information System scores (PROMIS) across 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain) three months after SARS-CoV-2 hospitalization. Shapley Additive exPlanation values were used to provide interpretable information about key predictive factors. Approximately 15-20% of participants reported moderate to severe impairment in at least one PROMIS domain three months after hospitalization. For the mental health composite score, the best-performing model achieved RMSE = 1.833 ± 0.341 and R² = 0.927 ± 0.031 in SUEP and RMSE = 3.131 and R² = 0.893 in HAP. For the physical health composite, the best-performing model achieved RMSE = 2.908 ± 0.703 and R² = 0.824 ± 0.052 in SUEP and RMSE = 3.019 and R² = 0.850 in HAP. Furthermore, the models achieved high predictive performance across all individual PROMIS domain scores in both samples. We provide an externally validated methodology for accurately predicting mental and physical symptomatology following hospitalization due to a severe viral infection. This approach may facilitate the development of a brief risk stratification tool at the point of hospitalization, enabling early identification of at-risk patients, improving the prediction accuracy of subsequent psychological and physical sequelae, and supporting timely preventive interventions.

BACKGROUND/UNASSIGNED:This paper provides an overview of adapting a micro-savings program originally developed in the United States to a resource-limited setting in Uganda, highlighting this specific case of adapting a program from one country to another. The program involved opening Child Development Accounts (CDAs) to support saving among adolescents girls and their families. Guided by the asset theory and institutional theory, the paper discusses the challenges and opportunities faced during the adaptation and implementation process. The findings offer insights that can inform efforts to expand similar micro-savings programs in other resource-limited communities. METHODS/UNASSIGNED:This paper utilizes data from the Suubi4Her study (2017-2022), a longitudinal intervention involving 1,260 adolescent girls in Southern Uganda. The analysis focused on saving behaviors among the entire sample and a subsample of 690 participants who opened CDAs. We examined self-reported and administrative savings outcomes over 30 months, encompassing bank savings behavior and savings beyond the initial deposit. Analyses also addressed key sociodemographic and psychosocial factors. A mixed-effect and adjusted logistic regression model were applied. RESULTS/UNASSIGNED:At enrollment, the participant's mean age was 15.37 years. The intervention improved bank saving behavior, evidenced by significant intervention-by-time interaction effects [χ2(2) = 43.38, p < 0.01], demonstrating a substantial increase in the odds of bank saving behavior in the intervention group at Wave 2 (OR = 78.85, 95% CI: 18.76, 331.51, p < 0.01) and Wave 3 (OR = 80.95, 95% CI: 19.31, 339.26, p < 0.01) compared to baseline within the control group. In the analysis of additional saving beyond the initial deposit, participants whose schools were located within 2 km of their home had significantly higher odds of saving (OR = 2.74, 95% CI: 1.72-4.37, p < 0.01), while older participants had lower odds (OR = 0.83, 95% CI: 0.68-0.99, p = 0.04). Living nearer to a bank was associated with increased odds of additional saving (OR = 1.74, 95% CI: 0.84-3.62, p = 0.13), though this association did not reach statistical significance. CONCLUSIONS AND IMPLICATIONS/UNASSIGNED:These findings suggest that, overall, CDA-based micro-saving programs implementation is possible even in resource limited communities like Uganda, and when given the opportunity, families living in low-income households can utilize the CDA "infrastructure" to save. Overall, for the saving intervention to yield its intended benefits, institutional barriers need to be addressed, including bringing the bank services to the people and providing financial literacy training to instill the culture of saving from a young age.