Faculty Bibliography

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.

Kidney Disease: Improving Global Outcomes (KDIGO) develops evidence-based clinical practice guidelines to improve care for people with kidney disease worldwide. KDIGO has produced 17 guidelines across kidney care, and 7 of these have been updated comprehensively at least once. Historically, guidelines were revised in their entirety when novel therapies or treatment paradigms emerged-a process requiring years to complete. To respond more dynamically to accelerated clinical trial results and drug approvals, KDIGO recently adopted a modular update approach for some guidelines. For example, the 2021 Glomerular Diseases Guideline is being updated chapter by chapter, with 4 chapters published since 2024. To support guideline development and promote implementation, additional KDIGO initiatives include Controversies Conferences, which convene global experts to synthesize current knowledge and identify research priorities, and implementation activities such as regional presentations and summits. The pace of scientific advances in kidney disease has never been faster, and KDIGO continues to adapt its programmatic approach to meet the need for trusted, timely guidance.

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.

INTRODUCTION/BACKGROUND:We examined obstructive sleep apnea (OSA) severity's association with Alzheimer's disease (AD) plasma biomarkers, independent or synergistic with cerebrospinal fluid (CSF) amyloid, and as a proof of concept, whether plasma amyloid beta (Aβ)42/Aβ40 with OSA severity improves detection of amyloidosis and tau pathology. METHODS:In 120 cognitively normal older adults (70 with CSF data) from New York University sleep and aging studies (2013-2021), OSA severity was measured using apnea/hypopnea index with 4% desaturation; plasma Aβ40, Aβ42, tau, and neurofilament light chain (NfL) via single molecule array; CSF amyloid and tau via enzyme-linked immunosorbent assay. Associations evaluated adjusted correlations and generalized models; receiver operating characteristic analyses evaluated diagnostic accuracy. RESULTS:OSA severity correlated with plasma Aβ40 (r = 0.21), Aβ42 (r = 0.26), and Aβ42/Aβ40 (r = 0.20). Plasma tau and NfL associations depended on CSF-Aβ42. OSA severity with Aβ42/Aβ40 improved CSF amyloidosis (area under the curve [AUC] = 0.78) and tau pathology (AUC = 0.71) detection. DISCUSSION/CONCLUSIONS:OSA severity relates to elevated plasma Aβ and, with CSF amyloid, to tau/NfL. Combined plasma and OSA measures aid non-invasive AD associations' detection.

PURPOSE/UNASSIGNED:To quantify the economic burden of vision loss in U.S. children and adolescents aged 0 to 18 years. METHODS/UNASSIGNED:This was a cross-sectional economic analysis study using publicly available data sources from the Centers for Disease Control and Prevention (CDC). This study employed a comprehensive data analysis using the American Community Survey, Medical Expenditure Panel Survey, American Time Use Survey, Bureau of Labor Statistics, National and State Health Expenditure Accounts, and the National Health Interview Survey. Total costs attributed to vision loss among children were categorized into medical expenses, nursing home care, supportive services, and productivity losses. Data were stratified by state to investigate regional differences in economic burden within the continental United States. RESULTS/UNASSIGNED:The study found that in 2017, the average economic burden per-child with vision loss in the United States was $15,150 annually, with a total cost of approximately $9.4 billion annually. This compares to a cost of $13,110 per-person affected age 19 to 64 years and $21,560 per-person affected age 65 years or older. The per-affected child cost for males ($15,210) was slightly higher than for females ($15,090) and generally uniform across geographies. Productivity loss due to informal care requirements represented the largest cost driver at 73.2%. CONCLUSIONS/UNASSIGNED:Vision loss in children and adolescents imposes a significant economic burden, particularly through productivity losses due to informal caregiving. The findings underscore the need for targeted public health strategies that consider the regional disparities in economic impact and focus on preventive measures to reduce the long-term economic and social consequences of pediatric vision loss.