Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Cornerstone therapies for metastatic prostate cancer include androgen deprivation and androgen receptor pathway inhibition, but cognitive impairment is a recognized, life-altering potential adverse effect of this treatment. Abiraterone acetate (AA), an androgen receptor pathway and CYP17A1 inhibitor, suppresses androgen synthesis and may contribute to cognitive changes. This cell culture-based study uses the BE(2)M17 human male neuroblastoma model to investigate AA-induced alterations in gene and protein expression that may underlie cognitive decline, laying the foundation for a mechanistic investigation aimed at identifying molecular targets to mitigate cognitive impairment in men with prostate cancer receiving androgen-directed therapies. MATERIALS AND METHODS/METHODS:BE(2)M17 cells were pretreated for 12 h with dihydrotestosterone (DHT; 5 nM) or vehicle control, then exposed to AA (0, 5, 10 µM, 24 h). RNA and protein were analyzed by qRT-PCR and Western blot for markers of amyloid processing, neuronal health, and mitochondrial function. RESULTS:= 0.0003). CONCLUSIONS:AA, alone or combined with DHT, disrupts key pathways involved in neuronal health, amyloid processing, and mitochondrial function. These findings suggest a potential mechanistic link between AA treatment and cognitive impairment.

IMPORTANCE/UNASSIGNED:Remote patient monitoring (RPM), including self-measured blood pressure monitoring with clinician review and telehealth-supported feedback, can support hypertension management. However, RPM use and related care continuity after switching from Medicare fee-for-service (FFS) to Medicare Advantage (MA) remain unclear. OBJECTIVE/UNASSIGNED:To compare RPM adoption, clinician continuity, and hypertension-related acute care utilization among beneficiaries who remained in Medicare FFS vs switched to MA plans, categorized as value-based contract (VBC) proxy or non-VBC. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study with an observational difference-in-differences design with propensity score matching used data from 2016 to 2022 Medicare enrollment, FFS claims, and MA encounter data. Beneficiaries were aged 65 years or older with prevalent diagnosed hypertension in 2018 and continuous enrollment in Parts A and B in 2018. Treated groups switched from FFS to MA in January 2019 and remained enrolled through 2022; comparators remained in FFS. Follow-up extended from January 1, 2019, through December 31, 2022. Data analysis was conducted from April to July 2025. EXPOSURE/UNASSIGNED:Switching from Medicare FFS to MA-VBC proxy or MA non-VBC in 2019. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was annual RPM adoption during hypertension-related visits; secondary outcomes included clinician loss without replacement, clinician switching or substitution, and hypertension-related emergency department (ED) visits and hospitalizations. RESULTS/UNASSIGNED:Matched samples included 281 620 beneficiaries, with 46 833 MA-VBC proxy plan switchers and 46 833 FFS comparators (27 920 [59.6%] aged 71 years or older and 27 685 female [59.1%] in each group) and 93 977 MA non-VBC switchers and 93 977 FFS comparators (67 188 [71.5%] aged 71 years or older; 53 122 female [56.5%] in each group). Common comorbidities included diabetes, chronic kidney disease, and heart failure. Switching to MA was associated with lower RPM adoption in 2022 (MA-VBC proxy: odds ratio [OR], 0.55; 95% CI, 0.42-0.72; -0.63 percentage points; non-VBC: OR, 0.73; 95% CI, 0.54-0.99; -0.52 percentage points), greater clinician loss without replacement (MA-VBC proxy: OR, 1.27; 95% CI, 1.23-1.32; 3.41 percentage points; MA non-VBC: OR, 1.09; 95% CI, 1.06-1.12; 0.83 percentage points), and higher hypertension-related hospitalizations (MA-VBC proxy: OR, 1.75; 95% CI, 1.48-2.06; MA non-VBC: OR, 1.94; 95% CI 1.71-2.19; 1.56 percentage points in both comparisons). Event-study analyses showed postswitch divergence through 2022. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of older Medicare beneficiaries with hypertension, switching from FFS to MA was associated with lower RPM adoption, greater clinician discontinuity, and higher hypertension-related acute care use. These findings suggest that continuity safeguards and clearer payment or quality incentives during MA transitions may support remote monitoring and clinician follow-up for hypertension.

New onset refractory status epilepticus and febrile infection-related epilepsy syndrome are rare and devastating entities in the pediatric population. While no known therapies have formally been established as the "gold standard" for management of the acute phase, consensus guidelines do establish interleukin therapies such as anakinra and tocilizumab as safe and effective second-line immunotherapeutic options. Despite the use of interleukin therapies, many patients continue to have super refractory status epilepticus. A number of publications (mainly case reports and case series) have described various adjunctive therapies in the management of new onset refractory status epilepticus/febrile infection-related epilepsy syndrome, including neuromodulatory therapies (such as vagal nerve stimulation, deep brain stimulation, and electroconvulsive therapy), surgical resection, noninterleukin immunotherapies (such as intrathecal dexamethasone, intravenous rituximab, and cyclophosphamide), infusions (such as lidocaine and magnesium), and anesthetic agents (such as sevoflurane). Utilizing a modified Preferred Reporting Items for Systematic reviews and Meta-Analyses approach, this narrative review summarizes the effectiveness and safety of second-line immunotherapies such as tocilizumab and anakinra, as well as the various adjunctive third-line therapies that aim to abort seizures and mitigate comorbidities within an intensive care setting, such as prolonged sedation and secondary systemic complications.

Mechanical thrombectomy (MT) is superior to medical therapy for anterior circulation proximal large-vessel occlusion (LVO) stroke, including in imaging-selected patients treated 6 to 24 h after their last known well (LKW) time. Beyond 4.5 h, the role of intravenous thrombolysis (IVT) has become more relevant because many health systems lack the ability to provide timely thrombectomy access for eligible late-window patients. Recent late-window IVT trials, including TRACE-III and HOPE, have demonstrated benefit in imaging-selected patients in whom thrombectomy was not planned or not effectively deliverable, addressing a critical systems-of-care gap. We review these trials alongside emerging evidence and situate each within a systems-of-care framework, distinguishing bridging scenarios from settings where MT is unavailable or substantially delayed. However, we argue that their results should not be taken to imply therapeutic equivalence with MT, a comparison that is misleading on methodological grounds. No randomized, head-to-head late-window trial of IVT versus MT exists. Comparing treated-arm outcomes across these separate trials as a proxy for therapeutic equivalence is vulnerable to differences in baseline prognosis, occlusion site, imaging selection, access to rescue therapy, and control-group outcomes. In this Perspective, we argue that these trials should be read one at a time. Each treated arm should be judged against its own control group and against the clinical and angiographic profile of the patients enrolled, not against treated arms from trials that enrolled very different strokes.

BACKGROUND:Gastroparesis is a chronic disorder characterized by delayed gastric emptying without mechanical obstruction, significantly impacting patient quality of life. Management of refractory gastroparesis remains challenging, with both gastric electrical stimulation (GES) and prokinetic medications used as treatment options. This systematic review synthesizes the available evidence on GES clinical outcomes, the role of continued prokinetic therapy after GES, and indirect comparative data relevant to symptom management in adult patients with refractory gastroparesis. METHODS:A comprehensive systematic review was conducted following PRISMA guidelines. Multiple databases were searched for studies published between 2000 and 2011 focusing on GES for gastroparesis. This window was selected to capture the period from initial FDA Humanitarian Device Exemption approval of the Enterra system (2000) through publication of cohorts with mature, multi-year follow-up (up to 10 years), maximizing the durability evidence available for analysis. Inclusion criteria required adult patients with refractory gastroparesis, GES as primary intervention, symptom-related outcomes, and minimum 6-week follow-up. Eight studies met eligibility criteria with follow-up periods ranging from 6 weeks to 10 years. Quality assessment utilized the Newcastle-Ottawa Scale for cohort studies and Cochrane risk-of-bias tools for controlled trials. RESULTS:Gastric electrical stimulation (GES) demonstrated significant symptom improvement in patients with treatment-resistant gastroparesis. Controlled studies showed vomiting frequency reduction of 57% at 6 weeks, improving to 67.8% after one year (p < 0.001). Long-term data revealed ≥ 50% reduction in Total Symptom Scores in 58% of diabetic gastroparesis patients, 53% of post-surgical cases, and 48% of idiopathic gastroparesis patients (p < 0.05) (Fig. 3; Table 2). Combination therapy (GES plus prokinetics) yielded significantly better symptom scores (1.35) compared to GES alone (2.20, p = 0.02). Device-related infection requiring removal occurred in approximately 7% of cases. No direct head-to-head comparisons between GES and prokinetic medications alone were identified. CONCLUSION/CONCLUSIONS:GES provides substantial symptom relief for treatment-resistant gastroparesis, particularly in diabetic gastroparesis. Combination therapy with GES plus prokinetics appears superior to GES monotherapy. However, the absence of direct comparative studies limits definitive conclusions regarding relative effectiveness versus prokinetic medications alone. Future randomized controlled trials are needed to establish optimal treatment protocols and patient selection criteria along with the role of other surgical approaches. Planned next steps include direct comparisons of GES with pyloric-directed interventions - namely gastric per-oral endoscopic myotomy (G-POEM) and surgical pyloroplasty - to clarify the optimal positioning of GES within the contemporary treatment algorithm for refractory gastroparesis.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Accelerated 3-year programs (A3YPs) for an MD degree offer a condensed medical education pathway to residency, often with directed pathways in primary care. Many programs aim to address workforce shortages and decrease debt. As these programs expand, assessing whether A3YP graduates are as prepared for residency as their peers from traditional 4 year programs is critical. This study evaluates milestone attainment of A3YP postgraduates in Year 1 (PGY-1s) compared to non-A3YP PGY-1s within family medicine residency programs. METHODS:We analyzed the Accreditation Council for Graduate Medical Education milestone ratings for family medicine PGY-1s from 2021 to 2023. The study included 109 A3YP graduates across 51 family medicine programs and 1,638 non-A3YP PGY-1s (MD, DO, international medical graduate) in those same programs. PGY-1s were compared across milestone competency domains using mixed-effects regression that accounted for clustering by program and subcompetency. RESULTS:At midyear, A3YP PGY-1s scored significantly higher in medical knowledge, systems-based practice, and practice-based learning and improvement. Differences were statistically significant but modest. Coefficients ranged from 0.05 for patient care and medical knowledge to 0.10 for practice-based learning and improvement (PBLI; P&lt;0.01). At end-year, A3YP PGY-1s maintained slightly higher scores in medical knowledge, professionalism, PBLI, and communication (coefficients ranged from 0.07 to 0.10; P&lt;0.01). CONCLUSIONS:A3YP graduates demonstrate equal or minimally higher milestone attainment compared to non-A3YP peers during PGY-1, supporting the viability of accelerated pathways. These findings reassure residency programs of A3YP readiness and highlight their potential to address workforce shortages and reduce student debt without compromising educational outcomes.

BACKGROUND/OBJECTIVES/OBJECTIVE:Peritoneal metastases (PMs) arise from gastrointestinal, gynecologic, hepatobiliary, and colorectal origins and are associated with poor outcomes. Cytoreductive surgery (CRS) with intraperitoneal (IP) chemotherapy offers benefit for select patients, but survival remains limited. This review aims to summarize recent insights into the molecular and tumor microenvironmental (TME) changes characteristic of PMs and the impact of IP chemotherapy. METHODS:A literature review was performed using recent clinical, translational, and preclinical studies examining alterations in molecular signaling, DNA repair alterations, metabolic pathways, and angiogenic factors in PMs before and after IP therapy. RESULTS:Peritoneal metastases exhibit distinct biology after being treated with IP chemotherapy. Treatment induces alterations in gene expression, mutational patterns, and immune infiltrates. Heated intraperitoneal chemotherapy (HIPEC) has been associated with increased CD8+ T-cell activity, macrophage and NK cell shifts, and modulation of PD-1/PD-L1 signaling, which correlate with treatment response and survival. Emerging data on PIPAC similarly suggests induction of favorable gene expression changes with repeated treatment, though supporting evidence remains more limited than for HIPEC. Angiogenic pathways-particularly VEGF and HIF1α-remain key drivers of PM progression and predictors of post-operative outcomes. Early findings suggest potential synergy between IP chemotherapy and immunotherapy though clinical trials are ongoing. CONCLUSIONS:IP chemotherapy induces tumor microenvironmental changes that have potential to shape therapeutic response. Characterizing these measurable biologic changes may allow clinicians to improve patient selection and support the development of combination therapies to enhance outcomes.

Psychological distress among persons living with HIV (PLWH) can negatively impact behavioral and clinical outcomes. There is need for additional data surrounding mental health status in resource-constrained settings to inform intervention. We assessed social and economic factors associated with symptoms of depression and anxiety among PLWH in western Kenya. Baseline data from the Harambee cluster randomized trial were collected from May 2021 through March 2022 among 1040 PLWH (≥ 18 years of age) receiving care through the Academic Model Providing Access to Healthcare program. Self-reported physiological distress (defined as non-specific symptoms of depression, anxiety and stress) was measured via the four-item Patient Health Questionnaire for Anxiety and Depression (PHQ-4). Multivariable logistic regression analysis was used to identify factors associated with psychological distress. At study baseline, 24% of participants reported severe psychological distress (PHQ-4 summary score ≥ 6). Compared to participants earning <$7 USD per month, those with a monthly income of ≥$35 USD had reduced odds of reporting severe psychological distress (adjusted Odds Ratio (aOR): 0.50; 95% Confidence Interval (CI): 0.27-0.93). Participants in the highest (versus lowest) wealth quintile (aOR: 0.36; 95% CI: 0.18-0.70), and those reporting moderate or high (versus low) levels of social support (aOR: 0.46; 95% CI: 0.46-0.98) were less likely to report severe psychological distress. Among PLWH in rural Kenya, higher monthly income, greater household wealth, and higher levels of social support were negatively associated with severe psychological distress. Multilevel interventions that provide both economic and social support may be essential for improving their mental health.Trial Registry ClinicalTrials.gov Identifier: NCT04417127.