Faculty Bibliography

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.

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.

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.

PURPOSE/OBJECTIVE:To evaluate the effectiveness and safety of current surgical modalities for nephrolithiasis in ectopic pelvic kidneys, a rare congenital anomaly with limited available evidence. METHODS:A multicenter retrospective study was conducted across 11 high-volume international centers, including 45 patients with congenital pelvic kidneys who underwent flexible ureteroscopy, multimodal-guided percutaneous nephrolithotomy, and laparoscopic pyelolithotomy. Stone-free rate (defined as 0 mm), need for ancillary procedures, and complications (Clavien-Dindo) were assessed. RESULTS:Stones were classified as GUYS II in 51.1% of patients and GUYS III-IV in 48.9%. flexible ureteroscopy was the most common primary treatment (51.1%), followed by multimodal guided - PCNL (33.3%). Multimodal-guided PCNL achieved the highest stone free rate (86.7%) and the lowest requirement for ancillary procedures (OR 9.7; 95% CI 1.8-51 compared with other modalities). The overall final stone free rate for the cohort was 65.9% after a mean of 1.38 procedures per patient. Complications occurred in 13.3% of cases, with only one major event (Clavien-Dindo IVa). CONCLUSIONS:Our findings indicate that multimodal-guided PCNL achieved the highest success rates and required fewer ancillary procedures than other approaches when treating stones in ectopic pelvic kidneys. In contrast, flexible ureterorenoscopy showed lower efficacy and required more ancillary interventions. Complication rates were low and comparable to those observed in anatomically normal kidneys. Although larger cohorts would strengthen these observations, the very low incidence of ectopic pelvic kidneys inherently limits the ability to accumulate large patient numbers.

INTRODUCTION/UNASSIGNED:Immune checkpoint inhibitors have become an increasingly effective treatment for various malignancies, although their use is associated with a range of organ toxicities. As these therapies become more prevalent, it is critical to establish appropriate management and long-term surveillance strategies for patients who develop immune-related adverse events. AREAS COVERED/UNASSIGNED:This review explores the chronic sequelae that may result from immune-related adverse events and focuses specifically on their persistence, outcomes, and implications for future research. A literature review was conducted using PubMed to identify relevant articles from within the last 10 years. EXPERT OPINION/UNASSIGNED:While acute management of irAEs has improved over the past decade, there is a major gap in understanding and addressing their chronic sequelae. Challenges in studying these sequelae include the complexity of cancer care, overlapping clinical presentations, and previously, a lack of long-term data. Continued research from large multicenter studies and dedicated databases can identify high-risk patients, inform risk-benefit discussions, refine management strategies, and pave the way for evidence-based, long-term care.

This study draws on repeated-measures data on a diverse (51% female; 54% Latine, 20% Black, and 11% White), low--income cohort of children (N = 618) whose academic skills were assessed before and after COVID-19-induced school closures. Longitudinal models predicted changes in children's literacy and math trajectories from before school closures (ages 4-6; 2017-2019) to after school reopening (ages 8-11; 2021-2023) and tested whether remote learning participation moderated these changes. Results suggest that academic growth stagnated during school closures, with "losses" ranging from 3 months of literacy growth to 14 months of math growth. Sufficient participation in remote learning was only slightly protective. After schools reopened, children's growth rates were slower than before school closures, but this may reflect normal developmental deceleration.

PURPOSE/OBJECTIVE:We aimed to determine time trends in incidence, treatment and survival of patients with adrenocortical carcinoma in the Netherlands. METHODS:All 685 adult patients with adrenocortical carcinoma diagnosed between 1993 and 2020 in the Netherlands were included, using the nation-wide prospective Netherlands Cancer Registry. RESULTS:The median age-adjusted incidence rate based on the European Standard Population was 1.62 per million person-years [0.83-2.11] and was stable over time. We saw a gradual increase in stage III on diagnosis (13 to 25%) with a stable proportion of stage IV (40%). The five-year survival remained stable over time for stage I-II at 65% and stage III at 35%, while the survival for stage IV increased from 3% in 1993-1996 to 11% in 2017-2020. Since the Dutch Adrenal Network was founded in 2004, more patients were referred to an expert center (p<0.001), which was associated with increased survival (adjusted HR 0.70, 95%CI[0.57-0.85]). Multivariate cox-regression showed increased survival in all stages when treated with adrenalectomy (adjusted HR 0.53, 95%CI[0.43-0.65]) and mitotane therapy (adjusted HR 0.73, 95%CI[0.55-0.98]). In stage IV disease, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy were associated with increased survival. However, only 58% of mitotane users reached a therapeutic drug level and 59.5% discontinued treatment prematurely. CONCLUSIONS:The incidence of adrenocortical carcinoma is stable over time. The five-year survival for stage I-III remained stable, while the survival for stage IV increased. Factors associated with increased survival are centralization of care, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy.

BACKGROUND:Upper airway stimulation (UAS) is an emerging neuromodulatory treatment for obstructive sleep apnea (OSA). It involves stimulating the motor fibers of the hypoglossal nerve to prevent airway collapse. Patients with OSA and pain may require radiofrequency ablation (RFA) or electrocautery during surgery. Due to the proximity of UAS leads to cervical facet joints, careful procedural considerations are necessary to prevent complications. This report summarizes best practices for performing RFA or electrocautery in patients with UAS implants, guided by manufacturer safety recommendations and expert consensus statements. CASE PRESENTATION/METHODS:An elderly patient with OSA, successfully treated with Inspire UAS, and chronic cervical facet-mediated pain presented for repeat cervical RFA. The procedure followed manufacturer safety recommendations, including turning off the UAS device prior to the intervention, positioning the grounding pad to avoid current passage through the implant, maintaining distance from the device leads, and using bipolar RFA. The RFA was performed without complications, and the patient experienced significant pain relief without adverse effects. CONCLUSION/CONCLUSIONS:This case underscores the importance of thorough preprocedural planning when performing RFA in patients with implanted neuromodulation devices. Adhering to manufacturer guidelines can reduce the risk of device interference and associated complications.

BACKGROUND/UNASSIGNED:Lateral ankle sprains are the most common lower extremity injury in athletes, most often involving the anterior talofibular ligament (ATFL). Although ATFL repair outcomes are well studied, optimal management for patients with generalized ligamentous laxity (GLL) remains less understood. PURPOSE/UNASSIGNED:To (1) evaluate the radiographic findings, clinical measures, and complications in patients with GLL undergoing modified Broström-Gould repair and to (2) assess the role of suture augmentation in optimizing outcomes. STUDY DESIGN/UNASSIGNED:Systematic review; Level of evidence, 4. METHODS/UNASSIGNED:During July 2025, the PubMed, EMBASE, and Cochrane library databases were systematically searched to identify studies examining outcomes and complications in GLL patients who underwent modified Broström-Gould repair. RESULTS/UNASSIGNED:= .03). When suture augmentation was performed, no significant difference in complication rates existed between cohorts. CONCLUSION/UNASSIGNED:Patients with GLL experienced significantly higher rates of complication and failure following modified Broström-Gould repair compared with patients without ligamentous laxity. Suture augmentation may lower complication rates in GLL patients, but its effect on failure rates remains undetermined, as no studies directly compared augmented and nonaugmented GLL patients. Importantly, both GLL patients and patients without ligamentous laxity experienced clinical improvements from the modified Broström-Gould repair. While GLL increases the risk of mechanical complications, it should not be considered a contraindication to undergoing the modified Broström-Gould procedure. However, suture augmentation may be beneficial for GLL patients to reduce the risk of complications after undergoing ATFL repair. REGISTRATION/UNASSIGNED:CRD420251182303 (PROSPERO identifier).

PURPOSE/OBJECTIVE:We aim to inform the design of new diffusion MRI (dMRI) approaches for microvasculature quantification that enhance the biological specificity of imaging towards cancer. METHODS: RESULTS: CONCLUSIONS: