Citations

Objective To characterize regional brain atrophy patterns, evaluate their association with regional leucine‐rich glioma‐inactivated‐1 ( LGI1 ) gene expression, and identify clinical predictors of hippocampal atrophy in LGI1 autoimmune encephalitis (AE). Methods This study compared regional brain volumes in LGI1‐AE patients versus age‐ and sex‐matched healthy controls (HC) and Alzheimer's disease (AD) patients. LGI1 gene expression was derived from the Allen Human Brain Atlas. Multivariable linear regression and generalized linear models were utilized. Results A total of 55 LGI1‐AE patients were included. Median age was 68 years (IQR 62.5–74.2 years) at volumetric analysis, after 19 months (IQR 11–45 months) from symptom onset. Compared with HC ( n = 55) and AD patients ( n = 55), LGI1‐AE patients had greater regional atrophy of the hippocampus, insula, caudate, and putamen ( p < 0.002). Longitudinal analyses demonstrated hippocampal and pallidal atrophy after covariate adjustment. Among those who did not fulfill limbic encephalitis criteria and/or had non‐lesional magnetic resonance imaging, limbic and striatal atrophy were identified compared with HC ( p < 0.01). Regions with the greatest differential atrophy corresponded to higher LGI1 gene expression (Spearman ρ = 0.7, p = 0.005). Severe cognitive deficits at diagnosis ( β = −0.56; p = 0.002) and longer disease duration ( β = −0.01; p = 0.001) independently predicted total hippocampal volume ( R 2 = 0.31). Interpretation LGI1‐AE demonstrates a distinct pattern of limbic and striatal atrophy that differs from AD and aligns with regional LGI1 expression, supporting a model of selective network vulnerability. Greater baseline cognitive impairment and longer disease duration independently associated with hippocampal atrophy, underscoring the potential importance of early diagnosis and treatment to limit structural brain injury. ANN NEUROL 2026

Importance Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. Objective To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). Design, Setting, and Participants This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. Exposures Tocilizumab or satralizumab. Main Outcomes and Measures Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. Results A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). Conclusions and Relevance In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.

Background: Understanding drivers of supply and labor cost variation in orthopaedic surgery is crucial to provide value-based care. Time-driven activity-based costing (TDABC) is a more accurate methodology for capturing costs of care than traditional methods. Anterior cruciate ligament reconstruction (ACLR) is one of the most performed outpatient procedures within orthopaedic surgery. The purpose of this study was to characterize the cost composition of ACLR and identify factors that drive cost variation. Methods: Cost data for supplies and time-based personnel usage were extracted from electronic health records and were used to calculate costs using TDABC. TDABC methodology was applied to calculate the cost of personnel usage by multiplying the duration and associated cost per minute. Descriptive statistics and mixed-effects modeling were used to determine cost drivers. Results: This study included 861 patients who underwent ACLR at 8 hospitals. The mean patient age (and standard deviation) was 31.1 ± 11.6 years. Of the 861 patients, 350 were male and 511 were female; 85.6% of patients were White, 8.1% were Asian, and 3.4% were Black. There was 3.2-fold variation in supply costs ($2,950) and 1.6-fold variation in labor costs ($940) between the 10th and 90th percentiles. Overall, supply costs accounted for 58.2% of total costs, whereas labor costs comprised the remaining 41.8%. The intraoperative phase was the greatest generator of total cost (89.7%). After adjusting for surgeon and hospital variability, variation in total cost was most effectively explained by graft type, primary surgery status, and meniscal repair (conditional R 2 = 0.84; marginal R 2 = 0.27). On subanalysis, patients undergoing allograft ACLR had significantly higher total costs, implant costs, and age compared with those undergoing ACLR with any autograft type (all p < 0.01). Conclusions: The most notable drivers of labor and supply cost variation were graft type, surgeon, surgery center, primary surgery status, and concomitant meniscal repair. Understanding modifiable cost drivers may aid health systems in designing value-based pathways, implant formularies, and surgeon education programs. Future studies may integrate cost with outcome measures for a more holistic view of value. Level of Evidence: Economic and Decision Analysis Level III . See Instructions for Authors for a complete description of levels of evidence.

Background Psychiatric comorbidities are increasingly recognised in demyelinating diseases, yet their frequency and timing in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well defined. We aimed to characterise the spectrum and temporal pattern of psychiatric illness in MOGAD and compare to multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-IgG). Methods We conducted a cross-sectional study of patients with MOGAD (n=388), age-matched and sex-matched MS (n=257) and AQP4-IgG-positive NMOSD (n=58) evaluated at Mayo Clinic (1991–2025). Psychiatric diagnoses, timing relative to the first attack and patient-reported outcomes were extracted from electronic health records (EHRs). Complementary analyses were conducted using the NeuroBlu real-world EHR database. Results Among 388 patients with MOGAD, 54.8% had ≥1 psychiatric disorder, most commonly anxiety (47.7%), depression (36.6%) and attention-deficit/hyperactivity disorder (ADHD, 9%). After the first attack, 33.3% of patients with MOGAD developed a new psychiatric disorder, often within the first year. MOGAD showed a lower frequency of depression versus MS (36.6% vs 47.5%, p=0.02) but similar rates of anxiety and ADHD. Temporal patterns differed: psychiatric disorders often appeared years before onset in MS but clustered shortly after onset in MOGAD. NeuroBlu analyses supported high rates of psychiatric disorders across the three conditions. Conclusion Psychiatric comorbidities are common in MOGAD, particularly depression and anxiety, typically emerging close after onset, whereas in MS they often preceded onset by years. These findings underscore the need for routine psychiatric screening in MOGAD and highlight unresolved questions regarding whether, and to what extent, MOG-IgG-mediated inflammatory demyelination contributes to psychiatric vulnerability.

Background: Amid mounting pressure to reduce health care spending, strategies for identifying and eliminating unwarranted variation in costs have garnered significant attention. Previous studies have characterized intersurgeon variation in costs for common orthopaedic procedures, but such variation remains unexplored in the context of hip arthroscopic surgery. Purpose: To (1) characterize variation in the cost of hip arthroscopic surgery between surgeons using time-driven activity-based costing (TDABC) and (2) identify patient characteristics, intraoperative findings, and operative procedures underlying such intersurgeon variation in costs. Study Design: Cohort study; Level of evidence, 3. Methods: Employing TDABC, the authors determined the intraoperative cost of 890 outpatient hip arthroscopic surgery cases performed by 5 surgeons at 4 surgery centers from 2015 to 2022. All costs were calculated in United States dollars. Costs were normalized to protect the confidentiality of internal hospital cost data. Surgeon-specific mean costs were calculated with and without adjustment for patient characteristics, surgical personnel, operative factors, and surgery center. Finally, to elucidate the sources of surgeon-driven cost variation, the authors estimated the proportion of variation attributable to different cost subcategories, including labor, implant/allograft, and other supply costs. Results: The intraoperative cost per patient ranged from 38.2 to 212.8 normalized cost units (mean, 100.0 ± 26.5), with a 1.6-fold variation in the mean cost between the highest and lowest cost surgeons. Operating surgeon alone explained 53.4% of the observed variation in costs. Controlling for case-specific features significantly improved the explanatory power to 91.8% ( P < .001), but the adjusted variation in costs between surgeons remained essentially unchanged (decreased by <3%). Each of the 5 surgeons generated costs that deviated significantly from those predicted based on case-specific factors, with mean surgeon deviations ranging from −5.0% to 21.8% ( P < .001 for all). Drivers of cost variation differed substantially between surgeons but generally stemmed from labor or other supply costs rather than implant/allograft costs. Conclusion: The cost of outpatient hip arthroscopic surgery varied widely between surgeons; the cause of this deviation was multifactorial and surgeon specific. While within-surgeon cost variation was effectively explained by patient and operative characteristics, most between-surgeon variability remained unexplained by observable factors. These insights may support individual surgeons in cost reduction efforts and, more importantly, may enable the alignment of reimbursement rates with costs.

Purpose To characterize variation in the value of hip arthroscopy for femoroacetabular impingement and explore associations between value and patient‐specific demographic characteristics, comorbidities, preoperative patient‐reported outcome measures (PROMs), and intraoperative variables. Methods We included all patients aged 18 years or older who underwent primary arthroscopic acetabular labral repair or debridement between 2015 and 2020 with minimum 2‐year follow‐up. The exclusion criteria were hip dysplasia, advanced hip osteoarthritis (TÖnnis grade >1), or unreconcilable documenting errors. Value was calculated by dividing 2‐year postoperative International Hip Outcome Tool 33 scores by time‐driven activity‐based costs. To protect the confidentiality of internal hospital cost data, the study average for value was normalized to 100. Multivariable linear mixed‐effects models were used to identify factors underlying variation in value. Results This study included 161 patients. There were 76 women (47.2%) and 85 men, with a mean age of 36.0 years (standard deviation [SD], 10.9 years) and mean body mass index (BMI) of 25.8 (SD, 4.3). Most patients were white (92.5%), were not Hispanic (93.8%), and were commercially insured (92.5%). Preoperatively, 57.1% of hips were classified as Tönnis grade 1 (57.1%) whereas the remainder were grade 0. The normalized value of hip arthroscopy ranged from 25.4 to 216.4 (mean ± SD, 100 ± 38.4), with a 3.0‐fold variation between patients in the 10th and 90th percentiles. Higher value was significantly associated with Tönnis grade 0 (12.2‐point increase, P = .025), no prior contralateral hip arthroscopy (17.3‐point increase, P = .039), higher preoperative PROMs (0.52‐point increase per 1‐unit increase, P < .001), and no bone marrow aspirate concentrate or microfracture (33.8‐point increase, P < .001). Value was also significantly associated with osteoplasty type and labral treatment technique ( P < .05 for both). In contrast, operative year, age, sex, BMI, race, ethnicity, Outerbridge grade, and American Society of Anesthesiologists score were not independently associated with value. A model incorporating these factors as fixed effects and the surgery center as a random effect explained 42.3% of the observed variation in value. Sensitivity analyses revealed that value drivers may vary slightly across PROMs. Conclusions This study revealed wide variation in the value of hip arthroscopy that was most strongly explained by osteoplasty type, labral management technique, and preoperative PROMs. In contrast, patient demographic characteristics such as age, sex, and BMI contributed minimal independent variability. Level of Evidence Level IV, economic and decision analysis.