Faculty Bibliography

Segmental peripheral nerve injuries, particularly those involving long nerve gaps, pose a significant challenge in reconstructive surgery. Conventional strategies, such as nerve autografts or processed allografts, are often limited by inadequate length or poor regenerative outcomes, especially in traumatized wound beds. Nerve flaps offer the theoretical advantage of enhanced axonal regeneration through improved perfusion and support of Schwann cell viability but are rarely used due to technical complexity and limited donor options. We present a unique case of a free sural nerve flap used to reconstruct a 7-cm segmental defect of the tibial nerve following blast trauma in a 23-year-old man. A composite flap consisting of the sural nerve and lesser saphenous vein was harvested with preservation of the bridging adipofascial tissue to maintain perfusion to the nerve. The lesser saphenous vein was anastomosed to the retrograde peroneal artery distally and ligated proximally, whereas the sural nerve was divided and used as a double-barrel cable graft across the defect. Intraoperative Doppler and SPY angiography confirmed perfusion of the nerve through the preserved adipofascial connections. The patient was recently seen in our clinic at 17 weeks postoperation. He demonstrated undetectable 2-point discrimination in all nerve distributions of his foot but is ambulatory. This case demonstrates the feasibility and potential utility of a free vascularized sural nerve flap for reconstructing extensive peripheral nerve defects, particularly in cases where standard techniques are inadequate.

BACKGROUND/UNASSIGNED:Umbrella reviews, or overviews of reviews, synthesize information using systematic reviews (SRs) as their unit of analysis. Although a formal guideline exists for reporting umbrella reviews of healthcare interventions (i.e. Preferred Reporting Items for Overviews of Reviews [PRIOR]), no formal guideline exists for conducting and/or reporting umbrella reviews of observational studies that examine epidemiological associations. OBJECTIVE/UNASSIGNED:To review the existing guidance on conducting and/or reporting umbrella reviews of observational studies on epidemiological associations, as part of the process of developing a formal reporting guideline. METHODS/UNASSIGNED:We reviewed the scoping review conducted in the context of PRIOR development and identified documents through forward citation search in PubMed, Scopus, and manual search in Google Scholar, Google Search up to December 22, 2024. Documents, regardless of format, were included if they provided guidance for conducting and/or reporting umbrella reviews of observational studies (including meta-research studies of their features). Title/abstract screening and data extraction were performed independently and in duplicate and summarized narratively by stages of the umbrella review process. RESULTS/UNASSIGNED:The search retrieved 4491 unique records, with 96 full texts assessed and eight documents included. These documents, published between 2014 and 2023, offered guidance across seven topic areas, but overall guidance on conducting and/or reporting is limited. These areas include the answerable questions, prerequisite considerations, the scope of umbrella reviews, searching for SRs, primary data collection, analysis, presentation, and assessing the certainty/quality of the body of evidence. CONCLUSION/UNASSIGNED:There is a need for dedicated, practical, and evidence-based formal reporting guidelines for umbrella reviews of observational studies on epidemiological associations. This review lays the groundwork for developing the PRIOR-extension for such studies: the Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control, and Cohort Studies.

BACKGROUND/UNASSIGNED:To examine the relationships between state Medicaid total Long-Term Services and Supports (LTSS) expenditures and the LTSS rebalancing ratio (i.e., the proportion allocated to Home- and Community-Based Services [HCBS]) with the self-reported health of spousal caregivers of community-dwelling older adults with dementia. METHODS/UNASSIGNED:This study used multiple data sources, including the Health and Retirement Study (HRS) and annual Medicaid LTSS user and expenditure reports. The analytic sample included 1,232 respondent-waves of spousal caregivers who participated in at least one of the seven HRS waves between 2008 and 2020 and provided care for their community-dwelling spouse with dementia. We employed generalized linear models (GLMs) for both bivariate and multivariable analyses, with the outcome of interest being a dichotomous variable for self-reported poor health. RESULTS/UNASSIGNED:Each additional $1,000 of annual LTSS spending per older adult was associated with a marginally significant 4.2-percentage point reduction in the probability of reporting poor health (Average Marginal Effect [AME] in percentage points [PP] = -4.21, 95 % Confidence Interval [CI] = -9.12-0.70, p = 0.093). However, no statistically significant association was observed between the LTSS rebalancing ratio and spousal caregivers' self-reported health (AME in PP = 2.22, 95 % CI = -2.07-6.49, p = 0.310). CONCLUSIONS/UNASSIGNED:Higher state Medicaid LTSS spending per older adult was moderately associated with better self-reported health among spousal caregivers of individuals with dementia. As the demand for informal caregiving continues to rise, this study underscores the importance of state investments in protecting caregivers' health and highlights the need to incorporate caregiver-focused assessments into the design and evaluation of LTSS policies.

BACKGROUND:While immune checkpoint inhibitors (ICI) induce potent responses against several systemic malignancies, clinical efficacy against high-grade glioma has been limited by immunosuppression, low mutational burden and limited lymphocyte infiltration into tumors. Laser interstitial thermal therapy (LITT) induces coagulative necrosis and disrupts the peritumoral blood-brain barrier (BBB), creating a potentially antigenic milieu. We hypothesized that neoadjuvant and adjuvant ICI would synergize with LITT to potentiate antitumor immune responses and enhance survival. METHODS:This retrospective study is an exploratory case series that includes 9 adult patients with recurrent IDH wild-type glioblastoma (GBM, n = 6), IDH mutant high-grade astrocytoma (n = 2) and H3K27M mutant diffuse midline glioma (n = 1). All patients received neoadjuvant anti-PD1 ICI prior to LITT and most received adjuvant ICI (8/9). Disease burden was followed through radiographic volume segmentation of gadolinium-enhancing disease. Patients were followed for progression-free (PFS) and overall survival (OS). RESULTS:). There were no perioperative complications. All patients showed an initial increase in gadolinium-enhancing volume after LITT. Seven of 9 (78 %) patients demonstrated subsequent regression in total gadolinium-enhancing volume. Three non-contiguous satellite lesions naïve to laser ablation exhibited complete or near-complete regression in 2 patients. Median PFS was 5.90 months (range 1.00-41.23), and median OS was 9.97 months (range 1.20-41.23). CONCLUSIONS:Combination therapy with neoadjuvant and adjuvant pembrolizumab and LITT is feasible and safe in recurrent high-grade glioma. Responses may be more robust in certain molecular subtypes of glioma. Further studies are needed to investigate this potential synergy.

T-cell lymphomas are a heterogeneous group of lymphoid neoplasms with a variable prognosis. They can be further divided into cutaneous T-cell lymphomas and peripheral T-cell lymphomas. Treatment options are relatively limited for patients with relapsed or refractory disease. Janus kinase (JAK) inhibitors have emerged as promising new drugs for these lymphomas, as increasing evidence supports the JAK and signal transducer and activator of transcription (STAT) pathway as a potential target. The objective of this review is to summarize the current evidence supporting the use of JAK inhibitors in the treatment of T-cell lymphomas and highlight areas for future research. Although many JAK inhibitors have been developed for the treatment of autoimmune conditions, only a subset of these have been tested in T-cell lymphomas and reported in the literature. These include abrocitinib, cerdulatinib, golidocitinib, ruxolitinib, tofacitinib, and upadacitinib. Other drugs are currently being tested in clinicals trials, including pacritinib and ivarmacitinib, but results are not yet available. Most of the published data are for ruxolitinib, which was found to have a clinical benefit rate of up to 53% in patients with PTCL with activating JAK and/or STAT mutations. Response durations are limited, which may be overcome through combination therapies in the future. JAK inhibitors are associated with multiple adverse effects, including cytopenias and infections, and long-term safety data are lacking for newer agents. Future studies will need to clarify long-term safety and efficacy through well-designed clinical trials involving larger groups of patients.

Cytology cell block specimens are essential for diagnosing patients with advanced-stage malignancy and often represents the only available strategy for therapeutic biomarker evaluation. The use of cell blocks preserves tumor cells, captures high-grade or metastatic populations, and retains meaningful microenvironmental context, making them well suited for IHC analysis. With the rapid expansion of computational pathology, deep learning-assisted biomarker interpretation in cell blocks is emerging as a promising frontier for improving reproducibility, reducing interobserver variability, and enabling quantitative assessment of spatial tumor-immune interactions. Because many treatment-defining biomarkers are routinely assessed on cytology cell blocks, this mini-review highlights artificial intelligence-based applications for PD-L1, HER2, ER/PR, Ki-67, ALK/ROS1, BRAF V600E, and p16 markers that directly inform decisions about immunotherapy, targeted therapy, and hormone therapy. Also reviewed are emerging predictive models that convey biomarker status directly from morphology, extending the utility of artificial intelligence beyond conventional IHC interpretation. Finally, spatial pathobiology-related opportunities afforded by cell block preparations are discussed, and future directions for integrating artificial intelligence-enabled analysis into cytology workflows are outlined. Together, these advances position cytology cell blocks as an important platform for computational biomarker interpretation and morphology-driven precision oncology.

Improving long-term protective immunity elicited by prime-boost vaccinations requires a deeper understanding of the immunologic outcomes of different vaccine platforms. Given the variety of platforms used to develop vaccines against SARS-CoV-2, we reasoned that SARS-CoV-2 offered an opportunity to compare vaccine platforms in humans. We used flow cytometry and single-cell transcriptomics to explore the B cell response to different homologous and heterologous vaccine regimens. We found that an adenovirus vector prime followed by a messenger RNA (mRNA) vaccine boost showed the greatest short-term B cell expansion and preferentially elicited an activated atypical B cell subset that was associated with antibody binding titers against spike protein. In contrast, an mRNA primary series followed by homologous boost induced a different activated B cell subset with more proliferative potential and high frequencies of a long-lived resting memory subset. Moreover, immunoglobulin A (IgA)-expressing memory B cells had more somatic hypermutations than the predominant IgG-expressing B cell population. This heterogeneity in vaccine-elicited B cell responses underscores the potential of tailoring vaccine regimens that combine different platforms to achieve potent and durable protection against infectious diseases.

BACKGROUND:Ischemic/anoxic brain injury is often assumed to occur within minutes of severe cerebral ischemia. However, emerging evidence suggests brain tissue may be more resilient, with important implications for resuscitation. We hypothesized that during prolonged cardiac arrest, cortical electrical activity may be restorable if cerebral oxygenation thresholds are met and may be associated with return of spontaneous circulation (ROSC). METHODS:) during cardiopulmonary resuscitation (CPR). RESULTS:≥16%, and alpha at >40%. Alpha activity was seen up to 35 min, and delta/theta up to 60 min into CPR. Suppression reverted to near-normal in 12% of transitions. Alpha activity was associated with ROSC (OR 5.4; 95% CI 1.08-29.20; p = 0.045), while suppression predicted lower ROSC odds (OR 0.12; 95% CI 0.02-0.53; p = 0.002). Survival analysis was limited by small sample size. CONCLUSION/CONCLUSIONS:Near-physiologic brain activity may be restored during prolonged CPR if oxygenation thresholds are met and is associated with ROSC. Further research is needed to evaluate survival outcomes.

End-stage renal disease and the number of patients relying on hemodialysis are increasing. Hemodialysis access, such as autogenous arteriovenous (AV) fistulas, prosthetic AV grafts, and tunneled catheters, is essential yet also a major source of morbidity. This focused narrative review summarizes the best practices for access planning. Complications after AV fistulas are reviewed, including stenosis, thrombosis, infection, central venous stenosis, steal syndrome, ischemic monomelic neuropathy, high-output cardiac failure, and aneurysmal degeneration. Multidisciplinary collaboration between nephrology, vascular surgery, and clinicians taking care of dialysis patients is essential to optimize long-term outcomes for patients dependent on hemodialysis. This review is intended for non-nephrologists taking care of dialysis-dependent patients in their practice.