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.

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.

OBJECTIVE:The objectives of this study were to determine 1) the prevalence of perceived mistreatment, 2) the source of mistreatment, and 3) the location where mistreatment occurred among obstetrics and gynecology residents. METHODS:We conducted a national survey of obstetrics and gynecology residents using an adapted validated questionnaire. RESULTS:Over half of participating obstetrics and gynecology residents reported mistreatment. The most common type of mistreatment reported was verbal or emotional abuse (57%). Patients/patients' families, attendings, nurses, and other residents were all common sources of mistreatment. The most frequent location was labor and delivery. Female, gender-diverse, Black, and lesbian, gay, bisexual, queer+ (LGBQ+) residents experienced mistreatment at higher rates. CONCLUSION/CONCLUSIONS:Obstetrics and gynecology residents report a high prevalence of mistreatment. Interventions to reduce mistreatment, especially on labor and delivery, will prove important to promote the respectful work environment necessary for optimal learning and patient care.

Trauma from explosions is among the most serious injuries faced by healthcare professionals. There are few studies that describe the risk factors for mortality, or the patterns of blast injuries in the civilian compared to the military population. Review of articles extracted from Medline, PubMed, and Scopus published (01/2014-03/2024). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Data on mortality and injury patterns were extracted from the articles that met the inclusion criteria to describe the type of injuries and to identify risk factors for mortality. Sixteen articles were included. Average age of civilians was 40.0 years ± 3.7, with men representing 79.4% compared to a mean age of 24.5 ± 1.4 and 79.0% for the military patients. While there was no difference in the distribution of injuries by body regions, the civilian population was more likely to sustain severe cranial and thoracic injuries (31.9% and 20.4% vs. 18.1% and 9.9%, respectively). Civilian population had a non-statistically significant lower risk of death (odds ratio = 0.96; 95% confidence interval = 0.82, 1.13). The findings of this review indicate that clinical experience derived from explosions occurring in one setting may not be fully generalizable to explosions occurring in other contexts, as demographic, environmental, and contextual factors contribute to distinct injury patterns.

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.

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.

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.

BACKGROUND:Robotic hiatal hernia repair (RHHR) has emerged as an innovative alternative to conventional laparoscopic techniques, offering potential advantages in visualization, dexterity, and ergonomics. However, predictors of revision surgery following RHHR remain incompletely understood. This systematic review investigates key surgical and patient factors associated with revision within 5 years following RHHR. METHODS:We systematically searched PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science from inception through July 2025 for studies reporting revision or recurrence after RHHR, following PRISMA 2020 guidance. Eligible studies enrolled adults undergoing primary RHHR (≥ 10 patients) and reported revision or recurrence with at least 12 months of follow-up. Two reviewers independently screened records and extracted data, with disagreements resolved by a third reviewer; methodological quality was appraised using the Newcastle-Ottawa Scale. Because of substantial clinical and methodological heterogeneity (variable hernia size criteria, fundoplication and crural closure techniques, outcome definitions, and follow-up duration), a formal quantitative meta-analysis was judged inappropriate; we therefore performed a structured descriptive synthesis with sample size-weighted pooled estimates where data permitted. RESULTS:), advanced age (> 70 years), and comorbidities (diabetes, chronic steroid use) showed inconsistent associations with revision risk, with only 6 of 14 cohorts performing multivariate analysis to control for confounding variables. CONCLUSION/CONCLUSIONS:Hernia size consistently emerges as the primary determinant of revision following RHHR, with larger hernias demonstrating substantially higher revision rates regardless of surgical approach. Based on available data, the 5-year revision rate for RHHR ranges from 0 to 5.7%, with an estimated weighted average of 3.2%. Technical considerations including mesh reinforcement and reconstruction methods remain incompletely understood due to significant reporting variations across studies. Patient-specific factors require further investigation through adequately powered prospective studies. Future research demands rigorous prospective designs with standardized documentation of surgical techniques, hernia characteristics, and patient profiles to better identify and stratify revision risk factors after RHHR. The development of consensus guidelines for reporting outcomes in hiatal hernia surgery would facilitate meaningful comparison across studies and improve our understanding of optimal surgical approaches.