Citations

Importance Seizure-induced brain injury is central to the treatment urgency of new-onset refractory status epilepticus (NORSE). Identifying biomarkers that reflect ongoing neuronal damage could inform therapeutic timing and improve outcomes. Objective To quantify acute brain injury in patients with cryptogenic NORSE (cNORSE), etiology-defined status epilepticus (eSE), and chronic epilepsy. Design, Setting, and Participants This was an international cross-sectional study conducted between 2013 and 2025. Patients were enrolled at 36 hospitals in the US, 2 in Canada, and 1 in Italy, France, and Belgium. Patients with cNORSE and eSE for which biological samples were obtained during ongoing seizure activity were enrolled in the study. Comparison groups without status epilepticus comprised individuals with chronic epilepsy and healthy participants. None were excluded. Exposures Neurofilament light chain (NfL) and S100-beta (S100B) protein concentrations in serum and cerebrospinal fluid (CSF). Main Outcomes and Measures Degree of neuronal and glial damage, indexed by NfL and S100B levels, and their association with short-term functional outcomes. Results A total of 78 patients with cNORSE (mean [95% CI] age, 37 [30-41] years; 44 female [56%]) and 2 independent cohorts of 211 patients (mean [95% CI] age, 69 [66-71] years; 128 female [61%]) and 73 patients (mean [95% CI] age, 56 [45-65] years; 39 male [53%]) with eSE were included. NfL concentrations were markedly elevated in cNORSE—approximately 10-fold higher in CSF and 4-fold higher in serum—compared with the eSE cohorts (CSF: median [IQR], 6408 [1503-22 963] pg/mL compared with 694 [219-2389] pg/mL; serum: median [IQR], 231 [99-855] pg/mL compared with 55 [20-135] pg/mL; P <.001). Serum NfL levels were nearly 20-fold higher in cNORSE than in the cohort with epilepsy and in healthy controls (median [IQR], 11 [7-19 ] and 7 [5-14 ] pg/mL, respectively). Serum and CSF NfL levels were strongly correlated (Spearman ρ = 0.75; P < .001) and rose sharply between week 1 (median [IQR], 101 [51-137] pg/mL), week 2 (median [IQR], 197 [117-324] pg/mL), and week 3 (median [IQR], 598 [163-1000] pg/mL) after onset ( P < .001). In contrast, S100B concentrations did not differ between groups and showed no consistent temporal pattern. NfL discriminated cNORSE from eSE (area under the receiver operating characteristic curve [AUROC], 0.79; 95% CI, 0.68-0.90) and from cohorts without status epilepticus (AUROC, 0.99; 95% CI, 0.78-1.00). Higher serum NfL was independently associated with poor functional outcome at discharge (Glasgow Outcome Scale extended score, 1-4; odds ratio, 1.01; 95% CI, 1.00-1.03; P = .03). Conclusions and Relevance Results of this cross-sectional study suggest that acute neuroaxonal injury, as reflected by elevated NfL levels, was substantially greater in cNORSE than in the cohorts with eSE and in controls without status epilepticus. The rapid early rise in NfL highlights a narrow therapeutic window, emphasizing the need for prompt, effective, and potentially neuroprotective interventions in cNORSE.

ABSTRACT Background Fall risk screening and prevention interventions initiated from the Emergency Department (ED) are endorsed by current national guidelines. We aimed to evaluate the effectiveness of ED‐based multi‐factorial and multi‐component interventions to prevent falls. Methods We conducted a systematic review and meta‐analysis of interventions for fall prevention initiated in the ED for older patients (age ≥ 60 years). Multi‐component and multi‐factorial interventions were included. We excluded studies without a control or comparison group. The published literature was searched from 2019 to May 2024. Risk of bias was assessed with the Newcastle Ottawa tool for observation studies and the Cochrane Risk of Bias v2 for randomized trials. A meta‐analysis was completed for the outcomes with multiple studies. Results The search resulted in 6312 abstracts with 2571 duplicates, for 3741 unique citations. A total of 18 studies were included in the systematic review; 5 were rated as high risk of bias/low quality. The articles were heterogenous in the intervention type (8 multi‐factorial and 8 multi‐component), setting (ED focused vs. outpatient), intervention components (i.e., nurses, physicians, therapists), and size (103–1435 participants). The interventions did not decrease risk of falls at 3 months (risk difference 0.05 95% CI [0.00; 0.09]), 6 months (0.07 [−0.04; 0.18]) or 12 months (−0.02 [−0.11; 0.07]). ED revisits at 1 month (−0.01 [−0.03; 0.00]), 3 months (−0.04 [−0.14; 0.06]), and 12 months (0.02 [−0.05; 0.25]) were also unchanged. Mortality and hospitalization rates were also unaffected. Improvement in functional status was noted in 4 of 5 studies reporting this outcome. Conclusions Multi‐factorial and multi‐component fall prevention interventions initiated from the ED did not decrease falls or recurrent healthcare use. These interventions may improve functional status in older adults at fall risk. Comparisons are limited by the heterogeneity in types of interventions, intervention compliance, and timing of outcomes.

Purpose To project the future utilization of open and arthroscopic rotator cuff repair (RCR) in the Medicare population through 2050, incorporating post‐COVID recovery data to provide insight into evolving surgical preferences, economic pressures, and implications for health care delivery. Methods We analyzed 2003‐2024 data from the Centers for Medicare and Medicaid Services Medicare Part‐B National Summary, which captures all Medicare beneficiaries undergoing open or arthroscopic RCR as identified by Current Procedural Terminology codes. Projections were based on 2003‐2019 and 2023‐2024 data, reflecting post‐COVID‐19 recovery and avoiding distortions from 2020 to 2022 pandemic‐related disruptions. Statistical models evaluated included log‐linear, Poisson, negative binomial, and autoregressive integrated moving average. Autoregressive integrated moving average was selected based on the lowest normalized root mean square error, reflecting superior predictive accuracy and its ability to capture time‐dependent trends, and was used to forecast RCR volumes through 2050. Results In 2024, there were 23,154 open and 188,700 arthroscopic RCR procedures, which served as the baseline for modeling. Open RCR is projected to decline on average by 5.91% annually, while arthroscopic RCR is projected to grow by 2.88% annually. By 2050, arthroscopic RCR volume is expected to reach 394,434 procedures (95% forecast interval: 363,424‐425,321), whereas open RCR is expected to decline to 4748 procedures (95% forecast interval: 1243‐43,747). Conclusions Autoregressive integrated moving average modeling projects that by 2050 arthroscopic RCR utilization will increase by 2‐fold and open RCR will decline to one‐fifth compared with 2024 baseline volumes. Level of Evidence Level III, retrospective cohort study.

Enteroblastic, hepatoid, and clear cell carcinomas are rare subtypes of colorectal carcinoma (CRC) with histologic and immunohistochemical (IHC) overlap. We assessed 37 CRCs that possibly represent these subtypes. Provisional criteria for each subtype, along with case photomicrographs and IHC data, were circulated among the authors to provide diagnostic interpretations. Based on plurality consensus, the carcinomas were classified as enteroblastic (n=13), hepatoid (n=6), and clear cell (n=18). Unanimous agreement was reached in 18% (3 clear cell, 3 hepatoid). Interobserver analysis revealed a mean pairwise Cohen κ of 0.63 (range: 0.32 to 0.91), with the hepatoid subtype eliciting the greatest consensus. Clear cell areas were the most likely to intermix with areas of conventional CRC ( P <0.001). Seven patients (20%) had inflammatory bowel disease (mostly linked to enteroblastic CRC). Twenty-three of 34 patients (68%) had nodal metastasis, and 12 (32%) had distant metastasis (mostly to the liver) at presentation. Median recurrence-free survival was 17 months, with enteroblastic cases the most likely to recur (54%, P =0.015). Median follow-up length was 27 months, with 14 patients (40%) dying of disease (representing 7 enteroblastic, 4 hepatoid, and 3 clear cell CRC). Mutations were identified in TP53 (n=8) , APC (n=3) , FBXW7 (n=2), and KRAS (n=1). Inflammatory bowel disease significantly worsened recurrence-free survival on multivariate analysis, while distant metastasis significantly worsened both recurrence-free and overall survival on multivariate analysis. Enteroblastic, hepatoid, and clear cell CRC demonstrate morphologic and IHC overlap, leading to interobserver variability in diagnosis. Given potential differences in clinical correlations and outcomes, more refined criteria are likely necessary.

Abstract Purpose The aim of this systematic review and meta‐analysis was to quantify and compare the evidence on the results obtained with the surgical treatments for meniscal lesions in athletes. Methods A literature search was conducted on PubMed, Cochrane and Web of Science in August 2025 according to the PRISMA guidelines. Inclusion criteria were clinical studies (randomised controlled trials [RCTs], non‐randomised comparative studies and case series), ≥6 patients, in the English language, on the surgical treatment of meniscal lesions in athletes. A meta‐analysis was conducted on the rate of patients returning to sport, the time to return to sport, and the rate of patients returning to the pre‐injury level of sport. Patient‐reported outcome measures, adverse events, failures and reoperation rates, as well as risk of bias and quality of evidence, were also documented. The risk of bias was assessed using the Cochrane RoB 2.0 tool, the Cochrane ROBINS‐I tool, and the JBI Critical appraisal checklist. The quality of evidence was assessed using a modified Coleman score and the GRADE tool. Result The mean time to return to sport was 2.1 months for meniscectomy, 5.8 months for meniscal repair, and 8.9 months for meniscal allograft transplantation (MAT). Statistically significant differences were observed between meniscectomy and repair and between meniscectomy and MAT (both p < 0.001). Meniscectomy showed a return to sport rate of 98.2%, meniscal repair of 96.9%, and MAT of 94.2%, while return to the same pre‐injury level of sport was reported as 84.4% for meniscectomy, 81.3% for meniscal repair, and 77.4% for MAT, with no statistically significant differences between groups. The mean modified Coleman Methodology Score for the included studies was 66.6 ± 7.0. Conclusion Meniscectomy, meniscal repair, and MAT are all able to provide high rates of return to sport in athletes. In the investigated treatment cohorts, meniscectomy presented the shortest pooled time to return to sport, followed by meniscal repair and MAT. Importantly, all treatments offered good rates of return to the same level of athletic performance. The treatment choice should be guided by an individualised, multidisciplinary approach aimed at providing a patient‐tailored treatment strategy to optimise both athletic recovery and joint preservation. Level of Evidence Level I.

Morel-Lavallee lesions (MLLs) are traumatic closed degloving injuries with operative intervention (OI), especially excisional debridement, remaining the mainstay of treatment. However, high-quality evidence describing operative techniques and outcomes remains limited. This study aimed to characterize current OI practices and associated outcomes, especially among patients undergoing excisional debridement, hypothesizing an increased risk of wound complications with this approach for MLLs. Methods This prospective (2021-2024), multicenter, observational study was conducted across 15 trauma centers and included patients diagnosed with MLL who underwent OI. The association between operative technique (eg, excisional debridement) and the primary outcome of wound complications was evaluated. Wound complications were defined as cellulitis, deep wound infection, skin necrosis, necrotizing soft tissue infection (NSTI), and/or organized hematoma. Results Of 88 MLL patients undergoing OI, 36 (40.9%) had excisional debridement, with 4 (11.1%) limited excision to skin, 20 (55.6%) extended to subcutaneous tissue, and 12 (33.3%) down to muscle. Excisional debridement had higher rates of skin necrosis (22.2% vs. 1.9%, P = .002). Although overall rates of wound complications were statistically similar between cohorts (33.3% vs. 17.3%, P = .098), univariate analysis demonstrated excisional debridement had increased risk of wound complications (OR 2.52, CI 1.07-5.97, P = .035). Conclusion This prospective multicenter study over three years demonstrated that a fifth of MLLs undergoing excisional debridement developed postoperative skin necrosis. Excisional debridement also had a more than two-fold increased risk of wound complications compared to other OIs. These findings underscore the importance of investigating alternative operative techniques, such as incision and drainage or minimally invasive debridement methods.

In a large, multicenter cohort of HIV and non–HIV immunocompromised patients with Pneumocystis jirovecii pneumonia, chest CT most commonly demonstrated diffusely distributed ground-glass opacity, with no imaging features distinguishing between immunocompromise etiology.

BACKGROUND: The metabolic mechanisms underlying right ventricular (RV) dysfunction are poorly understood, particularly outside of group 1 pulmonary hypertension (PH). We aimed to identify metabolites and pathways associated with RV systolic function and explored whether associations differed by pulmonary vascular resistance, PH group 1 status, and sex. METHODS: We analyzed data from the multicenter PVDOMICS (Pulmonary Vascular Disease Phenomics) cohort. RV systolic function metrics included fractional area change (echo), global longitudinal strain (echo), and ejection fraction (cardiac magnetic resonance). We used linear regression adjusted for age, sex, body mass index, and PH group to assess associations between metabolites and RV function. Pathway enrichment analyses were used to identify pathways significantly associated with RV function. Interaction terms were assessed to determine whether metabolite associations were modified by pulmonary vascular resistance, group 1 PH status, or sex. Least absolute shrinkage and selection operator regression was used to develop metabolite-based scores for RV function, and prognostic performance was assessed. RESULTS: There were 979 participants with plasma metabolomics and RV function data. Linear regression identified 170 metabolites that were significantly associated with all 3 RV metrics. Androgenic steroid, gamma-glutamyl amino acid, polyamine, vitamin A, fatty acid, and sterol pathways are most strongly associated with RV systolic function. Two metabolites interacted with group 1 PH status, and 6 interacted with pulmonary vascular resistance. Four androgenic steroids are associated more strongly with RV systolic function in women compared with men. Metabolite-based scores were prognostically equivalent to RV systolic function metrics and less accurate than REVEAL Lite 2 scores. CONCLUSIONS: We provide a blueprint of metabolites and metabolic pathways associated with RV systolic function across the spectrum of PH. Novel links to vitamin A and glutathione metabolites were observed. We detected few metabolites that associated with RV systolic function differentially by group 1 PH status or degree of pulmonary vascular resistance elevation. Androgenic steroids may associate more strongly with RV systolic function in women compared with men.