Faculty Bibliography

BACKGROUND/UNASSIGNED:Advancements in surgical techniques and immunosuppressive therapies have transformed care for patients through vascularized composite allotransplantation (VCA). However, lifelong systemic immunosuppression (SI) carries significant risks, specifically during acute rejection (AR), which typically requires increasing SI dosages. Mitigating such risks may be achieved through topical tacrolimus (TT). Although TT shows promise for VCA in preclinical studies, robust clinical data are lacking. This systematic review aims to evaluate the clinical use of TT in VCA. METHODS/UNASSIGNED:A systematic review was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines using Cochrane, PubMed, Scopus, and Web of Science. Studies included patients who underwent VCA and received TT treatment. Study details, patient demographics, VCA characteristics, Banff grade, induction and SI maintenance protocols, complications, AR episodes, and treatment plans following these episodes were collected. RESULTS/UNASSIGNED:The search yielded 271 articles; 11 met inclusion criteria, encompassing 15 VCA recipients (mean age 39.9 y). Thirty-two AR episodes were reported; 22 (68.8%) involved TT. TT was mostly used in Banff grade I-II AR episodes. Resolution occurred in 65.5% of TT-treated episodes, though this finding was not statistically significant. TT was frequently used with steroids and adjunct therapies. CONCLUSIONS/UNASSIGNED:This systematic review highlights the potential role that TT may play in mitigating the need for increased doses of SI during AR episodes. As clinical data continue to grow, further research is essential to establish the potential benefits and efficacy of TT use in VCA.

BACKGROUND/UNASSIGNED:Librarians providing feedback on Evidence-Based Medicine (EBM) assignments face time constraints. This case report describes implementing a semi-automated rubric - defined here as a tool that automatically calculates scores from grader-selected ratings while narrative feedback is still written by the instructor - to reduce grading time for an EBM capstone assignment for first-year medical students. CASE PRESENTATION/UNASSIGNED:Two cohorts of approximately 100 students completed the same EBM assignment. The 2023 cohort received manual feedback, while the 2024 cohort received feedback using the semi-automated rubric. Grading time was logged for both cohorts. The rubric, adapted from a template, automatically calculates scores based on selected criteria, streamlining the feedback process. CONCLUSIONS/UNASSIGNED:The semi-automated rubric reduced grading time by 30%, from an average of seven minutes per assignment to five minutes. This simple, adaptable intervention can help reduce educator workload, improve feedback timeliness, and enhance assessment consistency. While limited by its single-grader and single institution design, this case report offers practical insights for educators seeking to improve feedback efficiency in EBM and other disciplines.

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.

Platelet-rich plasma (PRP) has emerged as a regenerative treatment option for various foot and ankle pathologies, containing growth factors and anti-inflammatory proteins to promote tissue healing. The most consistent clinical evidence supports PRP use for plantar fasciitis and osteochondral lesions of the talus, with significant improvements in pain and function observed. In contrast, outcomes for Achilles tendon pathologies and ankle osteoarthritis are mixed, demonstrating heterogeneity in PRP preparation and implementation. Future high-quality, standardized studies are necessary to determine the efficacy, optimal protocols, and long-term outcomes of PRP in foot and ankle pathologies.

The United States overdose crisis is driven in large part by an increasingly unpredictable and contaminated drug supply, including fentanyl and its analogs and emerging adulterants such as xylazine and nitazenes. Drug checking interventions such as fentanyl test strips and Fourier Transform Infrared Spectroscopy are essential for harm reduction, yet they also highlight a central policy failure: they place the burden of safety on people who use drugs (PWUD) and frontline programs after drugs have already entered an unregulated market. We argue for a more pragmatic upstream public health response, authorizing pilots of a safer, regulated drug supply ("safer supply"), broadly defined as legal and regulated access to psychoactive substances or close pharmaceutical alternatives intended to reduce reliance on the unregulated drug market. International experience, particularly models in Switzerland, Canada, and the United Kingdom, demonstrates feasibility and suggests potential benefits, including improved health and social stability, reduced reliance on unregulated supply, and reduced acute care utilization in some settings. For the United States context, we propose a portfolio approach: near-term, healthcare-based pilots leveraging existing controlled-substance infrastructure (eg, opioid treatment programs, clinics, pharmacies, and tech-enabled dispensing) while preserving space for community-governed models with legal protections and longer-horizon, state-regulated pathways. We address predictable concerns (secondary sharing, youth initiation, community impact, mixed population-level findings) and outline guardrails and evaluation strategies that are PWUD-led, nonpunitive, and methodologically rigorous. We conclude with concrete policy actions to authorize pilots, establish legal protections, fund independent evaluation, and scale models that demonstrably reduce harm while integrating with harm reduction and treatment services.

Dermatophytoses (synonymous with tinea) are superficial fungal infections of the skin, hair, and nails, typically caused by dermatophytes in the genera of Trichophyton and Microsporum. Dermatophyte infections are common and are estimated to affect roughly 20-25% of the global population. Historically, tinea infections have been treated with short courses of topical and/or oral antifungal therapies, however, the last decade has seen increasing antifungal treatment failure. Trichophyton (T.) indotineae (previously termed Trichophyton mentagrophytes-genotype VIII) has emerged as the primary species driving antifungal treatment failure worldwide. Clinically, T. indotineae infection may present as a typical dermatophyte infection, or atypically may mimic eczema, psoriasis, or other inflammatory dermatoses. Patients are often strikingly itchy and may be using topical steroid creams inappropriately in combination with antifungal and antibiotic agents. Terbinafine, once considered a first-line oral agent for tinea infections, often fails against T. indotineae, for which prolonged courses of itraconazole (often at higher than typical dermatophyte dosing) are now regarded as the treatment of choice. Fluconazole and griseofulvin demonstrate limited efficacy. Antifungal susceptibility testing may guide treatment choices but is not well established for dermatophytoses. Dermatologists should be aware of an approach to evaluating and treating refractory dermatophyte infections. Increased awareness among clinicians, including in infectious diseases, primary care, and the emergency room, is also important to facilitate early recognition, appropriate management, and timely referral. Dermatologists may play a key role in promoting antifungal stewardship and educating other clinician groups about emerging dermatophyte infections. In this review, we detail T. indotineae with a focus on clinical presentation, diagnostic confirmation, and treatment.

Scans constitute an important role in cancer management. "Scanxiety", or scan-associated anxiety, is commonly experienced by patients undergoing cancer-related scans. Although more patients are turning to the internet and social media platforms such as YouTube for health information, few studies have evaluated the scanxiety content presented in these online resources. This study aims to evaluate YouTube videos and webpages available to patients relating to scanxiety. YouTube was searched using pre-defined scanxiety search terms and a Google search analysis for the term scanxiety was carried out and results from the first two pages were collected in August 2024. YouTube videos and webpages were evaluated using the validated DISCERN quality criteria for consumer health information and the Agency for Healthcare Research and Quality Patient Education Materials Assessment Tool (PEMAT). To assess accessibility of reading content, the Flesch-Kincaid reading level was determined for each webpage. Three independent reviewers performed video and webpage analysis. There were 82 videos and 18 webpages included in the analysis. Videos had a mean independent-reviewer rated quality DISCERN score of 1.8 out of 5, which was between low and moderate quality. Websites showed a higher mean quality DISCERN score of 2.7 out of 5. Despite better quality of information, websites were written at a higher reading level than that of the general population, limiting accessibility. Both videos and webpages had low actionability as patient education materials. Efforts are needed to improve scanxiety-related patient education as the number of patients living with cancer and requiring cancer-related scans has significantly increased.

Squamous cell carcinomas (SCCs) are common epithelial malignancies frequently associated with EZH2 upregulation, which correlates with aggressive growth and poor prognosis. EZH2 functions as the catalytic subunit of Polycomb repressive complex 2 (PRC2), which deposits the repressive H3K27me3 histone mark, yet PRC2 function in SCC pathogenesis remains unresolved. Here, we uncover a paradox: although EZH2 is elevated, the PRC2-catalyzed H3K27me3 is profoundly reduced in human SCC and complementary murine models. Mechanistically, we identify that oncogenic Ras signaling causes degradation of the PRC2 subunit EED, destabilizing PRC2 and depleting H3K27me3. Loss of EED reprograms keratinocytes into an aggressive tumor-specific cell state and induces paracrine factors that remodel the tumor microenvironment, driving metastasis. Remarkably, reintroducing EED suppresses tumor growth via restoring PRC2 integrity and H3K27me3 levels, revealing the reversibility of this epigenetic collapse. These findings link oncogenic signaling to epigenetic reprogramming and uncover PRC2 reconstitution as a potential therapeutic option in epithelial cancers.