Faculty Bibliography

BACKGROUND:2-octyl cyanoacrylate (2-OCA) topical skin adhesives are widely used for surgical wound closure but are increasingly associated with allergic contact dermatitis (ACD). We conducted a systematic review and meta-analysis to define the incidence, clinical features, and risk factors for 2-OCA-associated ACD. STUDY DESIGN/METHODS:A PRISMA systematic review of PubMed, Embase, and Web of Science (2008-2025) identified studies reporting cutaneous hypersensitivity to 2-OCA in human wound closure. Randomized, observational, and case-based reports were included. Risk of bias was assessed using ROBINS-I and RoB 2. Incidence from analytic cohorts was pooled using a random-effects model with prespecified subgroup analyses by surgical specialty. RESULTS:Seventy-four studies comprising 26,330 exposed patients were included; 20 analytic cohorts (25,442 patients) contributed to meta-analysis. The pooled ACD incidence was 4% (95% CI 3-5%) with substantial heterogeneity (I²=94.5%; prediction interval 0-12%). Incidence was 4% in orthopedic cohorts and 8% in plastic surgery cohorts, with lower rates in dermatology and obstetrics/gynecology (p=0.015 for subgroup differences). Re-exposure markedly increased risk, with reaction rates rising from 1-3% after initial exposure to >20% in staged or repeat procedures in several cohorts. Prior adhesive/contact allergy and cosmetic acrylate exposure were also strong risk factors. Diagnosis was primarily clinical, with selective patch testing. Management typically involved adhesive removal and topical corticosteroids; systemic therapy was reserved for severe cases. CONCLUSIONS:ACD to 2-OCA is a clinically meaningful and likely under-recognized complication of surgical wound closure. Re-exposure is strongly associated with increased postoperative reaction rates, supporting preoperative risk assessment and caution in repeat adhesive use.

UNLABELLED:Inflammation, particularly mediated through interleukin-6 (IL-6) signaling, plays a critical role in stroke pathophysiology. High levels of IL-6 are associated with poor outcomes in stroke patients. Therapeutic inhibition of IL-6 signaling may offer a novel strategy to mitigate post-stroke damage and improve recovery. This study evaluated the efficacy of tocilizumab (TCZ), a clinically approved monoclonal antibody that blocks IL-6 receptor signaling, using data from the Stroke Preclinical Assessment Network (SPAN), a multi-center, randomized, blinded, placebo-controlled trial in preclinical stroke models. METHODS:We analyzed behavioral and MRI morphometry data from 701 rodents (both males and females; 1:1), including healthy young mice, diet-induced obese mice, aging mice, and spontaneously hypertensive rats (SHR) treated with saline (N = 348) or TCZ (N = 353) at a dose of 100 mg/kg for mice, 10 mg/kg for rats after middle cerebral artery occlusion (MCAO). RESULTS:In the overall mouse cohort, TCZ did not significantly improve long-term sensorimotor recovery or reduce brain tissue loss measured by MRI. However, aging mice exhibited modest motor function improvements. In SHRs, TCZ treatment resulted in improved sensory-motor function, particularly in male rats, as demonstrated by enhanced corner test scores on days 7 and 28 post-MCAO. While TCZ in SHRs provided early (day 2) cerebroprotection with reduced lesion volume, it did not alter subsequent tissue loss, as measured by tissue atrophy at day 30. CONCLUSIONS:These results suggest that IL-6R blockade with TCZ was associated with functional improvement in aging mice (modest) and hypertensive rats (notably males), without durable effect of brain tissue loss. No benefit was observed in the overall mouse cohort. These findings support IL-6 signaling as a viable therapeutic target and warrant further investigation into IL-6 receptor inhibition as a potential treatment strategy for stroke recovery.

OBJECTIVE:We discuss implications of potential ascertainment biases for studies examining diabetes risk following SARS-CoV-2 infection using electronic health records (EHRs). We quantitatively explore sensitivity of results to misclassification of COVID-19 status using data from the U.S.-based Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network on children (≤17 years) and young adults (18-44 years). MATERIALS AND METHODS/METHODS:In our retrospective case study from the DiCAYA Network, SARS-CoV-2 was identified using labs and diagnoses from June 1, 2020 to December 31, 2021. Patients were followed through December 31, 2022 for new diabetes diagnoses. Sites examined incident diabetes by COVID-19 status using Cox proportional hazards models. Results were pooled in meta-analyses. A bias analysis examined potential impact of COVID-19 misclassification scenarios on results, guided by hypotheses that sensitivity would be <50% and would be higher among those who developed diabetes. RESULTS:Prevalence of documented COVID-19 was low overall and variable across sites (children: 4.4%-7.7%, young adults: 6.2%-22.7%). Individuals with documented COVID-19 were at higher risk of incident diabetes compared to those with no documented infection, but results were heterogeneous across sites. Findings were highly sensitive to COVID-19 misclassification assumptions. Observed results could be biased away from the null under several differential misclassification scenarios. DISCUSSION/CONCLUSIONS:Although EHR-based documentation of COVID-19 was associated with incident diabetes, COVID-19 phenotypes likely had low sensitivity, with considerable variation across sites. Misclassification assumptions strongly impacted interpretation of results. CONCLUSION/CONCLUSIONS:Given the potential for low phenotype sensitivity and misclassification, caution is warranted when interpreting analyses of COVID-19 and incident diabetes using clinical or administrative databases.

PURPOSE/OBJECTIVE:This prospective, non-randomized phase II single-arm pilot trial aimed to explore favorable mid-treatment nodal response (FMNR) through CT imaging to guide de-escalated chemoradiation therapy (CRT) in patients with favorable risk, node-positive HPV-associated oropharyngeal cancer (OPC). MATERIALS AND METHODS/METHODS:. At week 4, CT imaging evaluated nodal response: ≥40% reduction warranted de-escalation to 60 Gy, while <40% reduction continued standard CRT. Primary endpoint was 2-year PFS from initiation of dose de-escalated CRT. Tissue tumor modified viral (TTMV) HPV DNA samples and DW-MRI were collected at baseline and week 4. MDADI questionnaires were collected at baseline, 1, 3, 6, 12, and 24 months. RESULTS:Of 39 patients, 26 had FMNR and underwent de-escalated treatment. 13 pts had slow mid-treatment nodal shrinkage and received standard dose. At a median follow-up of 47.4 months, the 2-year PFS was 92.1% (95% CI: 0.72-0.98) for the deescalated dose group and 92.3% for the standard dose patients (95% CI: 0.57-0.99), p=0.96. With a median survival follow up of 48.9 months (range: 16.7-77.8 months), there were no deaths or distant failures. FMNR was associated with rapid TTMV HPV DNA clearance, reduced TTMV HPV DNA flare, lower baseline and week 4 MRI diffusivity, and higher baseline and week 4 MRI diffusional kurtosis. No differences in acute or late maximum grade 3-4 toxicity by patient were noted. MDADI composite scores showed minimal clinical important difference (MCID) in the de-escalated group at 1-month post-treatment while the standard group had MCID up to 1-year post-treatment. No patients required feeding tube placement. CONCLUSIONS:De-escalated CRT using CT-based mid-treatment nodal response in favorable risk, node-positive HPV-associated OPC achieved excellent 2-year PFS and OS rates and represents a potential approach in better selecting patients for treatment de-escalation.

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.

OBJECTIVES/BACKGROUND/OBJECTIVE:This study was undertaken to review the published literature and provide a position statement from the American Headache Society regarding the safety, efficacy, and impact on access to care of telemedicine for the clinical management of patients with headache disorders. Access to specialized care in headache medicine is severely limited in the United States and worldwide. Telemedicine has been used as an approach to care delivery in headache medicine for more than a decade, with accelerated adoption during the COVID-19 pandemic. There is now uncertainty regarding the extent to which telemedicine will be accepted by health systems and reimbursed by payers moving forward. The purpose of this position statement is to summarize evidence and clinical experience supporting the utility of telemedicine in headache medicine. METHODS:Evidence regarding the safety and efficacy of telemedicine, and patient and clinician satisfaction with the use of telemedicine for headache specialty care, was gathered from a variety of sources, including PubMed, Google Scholar, and ClinicalTrials.gov. The results and conclusions based upon these results were reviewed and discussed by the authors and the Board of Directors of the American Headache Society to confirm consistency with clinical experience and to achieve consensus. RESULTS:Several randomized clinical trials and observational studies have been performed to compare telemedicine with in-person visits in the management of patients with headache disorders. These studies showed consistently that telemedicine is noninferior to in-person care based upon multiple outcome measures, including disability measures, patient satisfaction, and clinician satisfaction. In addition, these studies found that telemedicine rarely leads to a missed diagnosis of secondary headache or mismanagement of primary headache. Telemedicine has substantial advantages for patients, including improved access to care and reduced costs associated with obtaining care. Studies evaluating health care utilization indicate no significant differences between patients evaluated and treated virtually versus in person. Obvious limitations of telemedicine include the inability to perform an in-person physical exam or to perform injections. For a substantial number of patients, however, these limitations are outweighed by its advantages. The experience with telemedicine reported in the literature is consistent with the experience of the Board of Directors of the American Headache Society, who endorse its use for patients when feasible and appropriate. CONCLUSION/CONCLUSIONS:Telemedicine has significantly advanced the care of patients with headache disorders. Its further development and deployment should be supported and reimbursed.

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.

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.