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.

IMPORTANCE/UNASSIGNED:Spending benchmarks in the Medicare Shared Savings Program previously only considered an accountable care organization's (ACO) historical spending, potentially disadvantaging efficient organizations in favor of inefficient ones. To more sustainably reward efficient ACOs, benchmark calculation has evolved, such as the incorporation of average regional spending in 2017, but how benchmarking policy, and its changes, have affected the financial performance of ACOs across the efficiency spectrum remains unclear. OBJECTIVE/UNASSIGNED:To measure the association between ACO efficiency on entry (ie, the ratio of observed to expected spending) with earning a shared savings bonus. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study used a 20% national sample of Medicare claims to identify ACOs that participated in the Shared Savings Program for a minimum of 4 years between January 2013 and December 2020. ACOs were sorted in quartiles based on their observed to expected spending ratio in their first year of participants. Data analysis was conducted from July 2024 to May 2025. EXPOSURE/UNASSIGNED:Quartiles of ACO efficiency with a higher spending ratio denoting lower efficiency. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was receipt of a shared savings bonus in the second, third, and fourth agreement years. Multivariable logistic regression was used to estimate the association between ACO efficiency quartiles and earning a bonus and how the regional benchmark adjustment in 2017 affected this association across measured agreement years. RESULTS/UNASSIGNED:Across 402 ACOs, the median (IQR) spending ratio was 1.000 (0.993- 1.005). After adjustment, the most efficient ACOs (ie, lowest quartile of the spending ratio) had an increased probability of earning a bonus from 24.4% (95% CI, 15.3%-33.4%) to 45.2% (95% CI, 35.4%-55.0%) after the 2017 introduction of the regional benchmark adjustment. However, the least efficient ACOs (ie, top quartile of the spending ratio) were significantly more likely to earn bonuses prior to (43.8%; 95% CI, 33.7%-53.9%) and after (60.7%; 95% CI, 51.3%-70.1%) the benchmarking change, without evidence that this gap narrowed. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study, ACOs across the range of efficiency on entry had greater odds of earning bonuses after the introduction of the regional benchmark adjustment in 2017. However, less efficient ACOs had significantly greater odds of earning bonuses compared with more efficient ACOs, before and after the policy change.

Childhood adversity is increasingly recognized as a critical modifier of neurologic disorder development and disease severity, including in the neuroimmune disorder multiple sclerosis (MS). While previous studies have linked early-life adversity to increased MS susceptibility and more severe disease, the underlying biological mechanisms remain poorly understood. This study investigated associations between childhood adversity and MS clinical features, with a focus on two potential pathogenic mechanisms: allostatic load and epigenetic modifications. We evaluated 60 consecutively enrolled young adults with MS; 30 with paediatric-onset MS (POMS) and 30 with adult-onset MS (AOMS). At time of enrolment in this cross-sectional study, participants had MS disease duration of 6 years on average. POMS participants were mean 22.09 (2.66) years and AOMS participants were mean 32.41 (2.19) years old. 62% of participants were female. Childhood adversity was defined using a composite index of individual, family and socioeconomic measures captured by the adverse childhood experiences questionnaire, parental education level and estimated household income during childhood. Clinical outcomes included patient-reported SymptoMScreen questionnaire regarding MS symptom burden and MS neurologist-assessed disability using the Expanded Disability Status Scale (EDSS) of the participant's neurologic exam at the time of enrolment. Circulating biomarkers of allostatic load and genome-wide epigenetic profiles (DNA methylation via RRBS; reduced representation bisulfite sequencing) were also assessed. A history of high childhood adversity was associated with significantly greater patient-reported MS symptom burden (P = 0.001) and higher neurologist-reported EDSS disability scores (P = 0.028), independent of disease duration or timing of treatment initiation. There were no differences between childhood adversity and circulating biomarkers of allostatic load. While childhood adversity was not associated with global epigenetic changes across the entire cohort, stratified analysis revealed divergent methylation patterns by age of MS onset: POMS participants with childhood adversity had increased DNA methylation, whereas AOMS participants with childhood adversity showed decreased methylation compared to individuals without childhood adversity. None of the observed clinical and biologic differences were explained by differences in disease duration or the interval between symptom onset and treatment initiation. Our findings suggest that childhood adversity is associated with increased MS symptom burden and neurologic disability in young adults with MS. Childhood adversity may differentially shape the epigenome, depending on the age of MS onset, with potential implications for disease trajectory and therapeutic vulnerability. These results support the biological embedding of childhood adversity in MS and highlight the need for age- and exposure-sensitive approaches to understanding MS pathogenesis across the lifespan.

BACKGROUND:Glioblastoma intramedullary spinal cord metastasis (GISCM) is a rare sequela of high-grade astrocytoma and glioblastoma multiforme (GBM). Discrete intramedullary spinal cord metastases are less common than spinal leptomeningeal spread and may follow a more indolent course. Once identified as GISCM, palliative maximal safe resection of the tumor may be considered to alleviate neurological symptoms. Reports describing the surgical management of these rare lesions, including the use of emerging technologies that may aid in maximal safe resection, are sparse. A further understanding is also required regarding the course of disease and factors contributing to mortality in GISCM. METHODS:We reviewed the intraoperative management and clinical course of three patients treated for GISCM at our institution between 2015 and 2024. We additionally conducted a PRISMA-guided systematic literature review of PubMed Central, MEDLINE, and Bookshelf databases through May 26th, 2025, including original patient reports of GISCM from cranial astrocytoma or GBM. The disease course, management strategies, and causes of mortality in previously reported cases were analyzed. RESULTS:Our institutional cohort had a mean time to spinal metastasis of 26.2 months from diagnosis of cranial disease (range 17.5-40.5 months), with a mean survival of 9.2 months following maximal safe resection of extramedullary components (range 7-12 months). In two cases, intraoperative Stimulated Raman Histology (SRH) was employed to facilitate the rapid identification of metastatic GBM, thereby influencing surgical strategy. In one case, 5-aminolevulinic acid (5-ALA) was used to differentiate between tumor and spinal cord parenchyma, facilitating maximal safe debulking without neurological injury. Literature review identified 38 prior reported cases of GISCM, with a median time to spinal diagnosis of 11.0 months and a median survival of 3.5 months thereafter. The cause of death in the review cohort often involved multiple factors, and when analyzed for contributing factors to death, 38.7% involved cranial progression, 38.7% involved progression of spinal disease, and 29.0% involved medical complications. Gait ataxia at presentation was associated with shorter survival in review patients, potentially reflecting advanced disease with extramedullary cord compression. CONCLUSION/CONCLUSIONS:GISCM represents an entity distinct from leptomeningeal disease and may be managed in conjunction with recurrent cranial disease. Surgical debulking is a technically feasible strategy that can be safely facilitated using tools employed in the management of intracranial GBM, facilitating maximal safe resection without compromising survival.

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.

BACKGROUND/UNASSIGNED:The Standard of Care (SOC) for treating significant spinal epidural abscesses (SEA) is STAT surgery for patients with the new-onset of neurological deficits following STAT contrast MR studies confirming significant neural (i.e. mild/moderate, moderate, or marked cord/nerve root) compression. Too many health care professionals, including physicians, and select spine surgeons still wrongly believe delaying "acute" spinal decompressions in patients with SEA for up to 8, 12, and even 24 hours is acceptable even in paralyzed patients. METHODS/UNASSIGNED:Here we review the fact that the standard of care for treating SEA is STAT surgery for patients demonstrating the new-onset of neurological deficits following STAT contrast MR scans confirming significant neural compression. RESULTS/UNASSIGNED:STAT surgery for newly neurologically symptomatic patients with SEA following STAT contrast MR scans documenting significant neural compression yields the best results. Notably, select patients without neural deficits or significant MR neural compression may be considered for non-surgical treatment. The "gold standard" for diagnosing SEA is the contrast MR, while non-contrast CT studies almost uniformly fail to diagnose SEA, and Myelogram-CT studies have significant limitations (i.e. risk of causing meningitis, and may fail to document cephalad extent of SEA if there is a distal total block to intrathecal contrast). CONCLUSION/UNASSIGNED:STAT surgery is the SOC and treatment of choice for patient with SEA demonstrating significant new-onset neurological deficits with significant STAT contrast MR findings of neural compression. Further, STAT means STAT, no waiting period is acceptable (i.e. 8, 12 or up to < 24 hours) particularly in paralyzed patients.

OBJECTIVES/OBJECTIVE:The 1st Global Consensus for Clinical Guidelines (GCCG) in Implant Dentistry introduced an innovative, evidence-based approach to developing patient-centered and practical recommendations for the rehabilitation of the edentulous maxilla. Within this framework, Group 1 aimed to formulate clinical recommendations on the number of implants required, timing of implant placement, and timing of loading. MATERIALS AND METHODS/METHODS:Group 1 followed the S2k-level guideline framework of the Association of the Scientific Medical Societies in Germany (AWMF), using a structured nominal group technique. The evidence base included three systematic reviews evaluating clinician-reported outcomes (ClinROs) and patient-reported outcomes (PROs), supplemented by structured single-round international surveys involving expert clinicians, patients, and cross-disciplinary experts. Survey content covered diagnostics, treatment planning, clinical procedures, and maintenance care. Draft recommendations were discussed during the in-person consensus meeting in Boston (June 16-18, 2025) and finalized through anonymous plenary voting. Consensus was defined as ≥ 75% and ≤ 95% agreement and strong consensus as > 95% agreement. RESULTS:Group 1 formulated 12 clinical recommendations across the workflow domains of diagnostic tools, treatment planning, and treatment procedure. During plenary voting, three of these recommendations reached strong consensus, and nine achieved consensus. The number of voters per recommendation ranged from 61 to 90, with an average of 83. CONCLUSIONS:This consensus report provides structured, evidence-based recommendations on implant number, placement timing, and loading protocols for rehabilitation of the edentulous maxilla. These guidelines are intended to support individualized, patient-centered care while also identifying priority areas for future research.