Citations

Introduction Krackow Type II valgus deformity is defined by attenuation of the medial collateral ligament (MCL). However, little quantitative information exists about associated intra-operative MCL laxity. Furthermore, a corollary may exist in varus deformity with associated lateral ligament laxity but is poorly described. Robotic-assisted total knee arthroplasty (raTKA) includes quantitative assessment of intraoperative ligament function. This study evaluated whether increased preoperative medial or lateral radiographic joint space width (JSW) in valgus or varus knees, was associated with increased intraoperative soft tissue laxity of the respective compartment. Methodology Intraoperative data from 348 consecutive raTKAs with 270 varus knees (hip-knee-ankle angle [HKA]<-2°), and 78 valgus knees, (HKA>2°) were retrospectively reviewed. For varus knees, lateral JSW was measured on preoperative, standing anteroposterior radiographs to determine lateral widening (threshold 8.0mm). For valgus knees, medial JSW was evaluated to determine medial widening (threshold 7.0mm). Intraoperative medial and lateral gaps at 0° and 90° had been recorded during manual stress testing. Linear regression was performed to determine associations between intra-operative gaps, radiographic JSW, and HKA. Results 51 varus knees demonstrated lateral widening and 15 valgus knees had medial widening. In varus knees, lateral JSW was positively associated with the lateral extension (β=0.76, P <0.001) and flexion (β=0.74, P <0.001) gaps. Similarly, for valgus knees, medial JSW was positively associated with the medial extension (β=0.75, P <0.001) and flexion (β=0.77, P <0.001) gaps. Conclusion Increased preoperative radiographic JSW of the medial and lateral compartment in valgus and varus knees, predicted increased intraoperative gaps of that compartment, consistent with ligament attenuation.

Transcranial magnetic stimulation can provide noninvasive measures of cortical excitability and plasticity, but relationships between these measures and clinically observable features of autism are not fully characterized. Nineteen autistic participants aged 15 to 40 years were included in the analysis of a left primary motor cortex continuous theta-burst stimulation (cTBS) biomarker protocol. Motor evoked potentials were measured at baseline and at seven assessments from 5 to 60 min after stimulation. Linear mixed-effects models evaluated whether clinical measures moderated the post-stimulation motor evoked potential log-response ratio over time. Aberrant Behavior Checklist (ABC) and Attenuated Behavior Questionnaire (ABQ) analyses were restricted to the same 15 participants with caregiver-informant assessments. Catatonia severity, social impairment, ABQ Motor Total, ABQ Total, and cognitive ability did not significantly moderate the post-stimulation response. ABC Inappropriate Speech was associated with progressively greater post-stimulation facilitation (standardized Time-by-Inappropriate Speech interaction: beta = +0.688, SE = 0.210, 95% CI +0.276 to +1.099; Holm-adjusted P = .008 across eight informant-rated models). Two individual speech-related items ("Talks excessively" and "Talks to self loudly") survived false-discovery-rate correction. An exploratory eight-item ABC phenotype showed a large descriptive in-sample association (beta = +0.904, SE = 0.200, P less than .001) and directionally positive held-out performance. However, full-pipeline permutation tests were nonsignificant for both Pearson (r = .357, two-sided empirical P = .360) and Spearman correlations (rho = .446, two-sided empirical P = .261). Caregiver-rated inappropriate speech may be associated with altered post-cTBS motor cortical facilitation in autism. The candidate phenotype remains hypothesis-generating and requires independent validation.

Purpose To compare lower extremity soft tissue injury and revision surgery rates for patients with anorexia nervosa (AN) and bulimia nervosa (BN) compared with matched controls. Methods This retrospective cohort study used a deidentified claims database. Patients were included if they carried an International Classification of Diseases code for AN or BN. Respective matched cohorts for AN and BN were created using propensity score matching. Primary and revision surgeries for anterior cruciate ligament (ACL) reconstruction, posterior cruciate ligament reconstruction, knee collateral ligament reconstruction, meniscus repair or meniscectomy, and any ankle ligament reconstruction were identified by their CPT codes. Patients over the age of 40 and without a minimum 2‐year follow‐up after primary surgery were excluded. Differences in prevalence and revision rates were analyzed. Results A total of 56,146 patients with AN and 42,630 patients with BN were included in this study with equal numbers in respective matched cohorts. Patients with BN showed an increased risk of ACL injury (relative risk = 1.32, P = .019), medial collateral ligament injury (1.17, 0.04), calcaneofibular sprain (1.92, <0.001), deltoid sprain (1.41, 0.004), and unspecified ankle sprain (1.44, <0.001). Patients with AN showed an increased risk for calcaneofibular sprain (1.25, 0.007), deltoid sprain (1.28, 0.015), and unspecified ankle sprain (1.17, <0.001). Patients with BN were more likely to have revision ACL repair (1.89, 0.02), partial meniscus revision (3.44, <0.001) and any meniscus revision (4.74, <0.001) while patients with AN were more likely to have an ACL revision (2.81, <0.001), partial meniscus (4.37, <0.001), and any meniscus (4.52, <0.001). Conclusions In this study, patients with AN and BN had a significantly increased risk for various knee and ankle injuries and revision surgeries compared with matched controls. Additionally, patients with AN and BN who sustained these injuries were more likely to undergo a revision surgical procedure within the first 5 years of the primary procedure. Level of Evidence Level III, retrospective comparative study.

Background Competition for urgent and emergent operating-room access is a significant challenge in many hospitals. Evidence-based benchmarks for early intervention are well established for emergencies like acute appendicitis or hip fracture. In contrast, laparoscopic cholecystectomy for acute cholecystitis or symptomatic cholelithiasis is often delayed. The purpose of this study was to evaluate the clinical and economic impact of delays in laparoscopic cholecystectomy across the US. Methods The Nationwide Readmissions Database was queried for patients aged ≥18 years admitted between 2021 and 2022 undergoing urgent or emergent laparoscopic cholecystectomy. Patients were stratified based on operative timing (<3 vs ≥ 3 days). The primary outcome was 30-day readmission. Secondary outcomes included VTE, SSI, and total cost. Propensity score matching (1:1) was performed using 46 covariates. Linear regression assessed the cost associated with each additional hospital day prior to surgery, with a subgroup analysis of safety-net hospitals. Results Among 136,893 patients, 24,496 (17.9%) experienced delayed laparoscopic cholecystectomy. After matching (n = 48,992), delays were associated with increased odds of readmission (9.5%; OR 1.22 [1.15-1.29], P < 0.001) and VTE (1.5%; OR 1.51 [1.30-1.77], P < 0.001). SSI (0.2%) was not significantly different. The mean total cost was $25,957 ± $21,609 for delayed patients vs $20,784 ± $20,027 for early surgery. Linear regression revealed an incremental cost of $1,695 per additional hospital day prior to surgery, rising to $2071 per day in safety-net hospitals ( P < 0.001). Discussion Delays in laparoscopic cholecystectomy have significant clinical and economic impacts, underscoring the urgent need for national benchmarks to standardize operative timing and reduce disparities for patients in safety-net hospitals.

Abstract Objective The goal of this study was to synthesize the evidence on how “status migrainosus” is defined in research studies in comparison to established International Classification of Headache Disorders (ICHD) criteria. Background Current ICHD‐3 criteria define status migrainosus as a headache attack occurring in a patient with a history of migraine with or without aura that is typical of previous attacks except for its duration (>72 h) and severity (debilitating). Despite the ICHD criteria, there are varying inclusion criteria noted in studies enrolling patients with status migrainosus. With this diagnostic uncertainty, there remains difficulty in studying this patient population. Methods This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. Ovid MEDLINE, Ovid EMBASE, All Evidence‐Based Medicine Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform were searched with the end search date of August 29, 2025. We included studies that were original research focused on status migrainosus, published in English after January 1, 1988, and also included diagnostic criteria to define this condition. The abstracts and full texts were screened by independent reviewers, with a third independent reviewer remaining available to settle disputes. There were 45 studies that underwent full text review, with 19 of these studies included. Data extraction was conducted recording the criteria used to define status migrainosus, headache characteristics, and goals of each study. Results We identified four common domains among studies of status migrainosus, including use of ICHD criteria, headache duration, symptom severity, and treatment response. Reference to ICHD criteria was variable, with only 68% (13/19) of studies specifying an edition of ICHD criteria applied in recruiting or studying patients with status migrainosus. The majority of studies (16/19; 84%) used a headache duration greater than 72 h to define status migrainosus. The use of symptom severity with “debilitating” or “severe” was present in 63% (12/19) of studies and depended on the edition of ICHD criteria that was referenced. Treatment response was rarely used as a condition in defining status migrainosus, with only 15% (3/19) of studies utilizing this stipulation in diagnostic criteria. Conclusion The results of this systematic review show inconsistent application of ICHD criteria in research studies focusing on status migrainosus. These inconsistencies lead to ambiguity in how status migrainosus is defined in the research setting and limit the ability to replicate or compare studies. Guidelines outlining best practices for research of status migrainosus are necessary. For prospective studies, consistent utilization of ICHD criteria is necessary, with potential need to revise these criteria to better reflect the clinical realities of this entity. For retrospective studies, implementation of a standardized International Classification of Diseases code for status migrainosus would be of benefit to improve diagnostic clarity because the current codes are lengthy, cumbersome, and unclear.

Background New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency evaluation and treatment of patients on AAT who develop acute neurological symptoms. Methods The American Heart Association convened 75 multidisciplinary experts for the Amyloid‐Related Imaging Abnormalities Summit: Cardiovascular and Stroke Considerations for β‐Amyloid Immunotherapy in AD in July 2025. These experts were divided into 8 work groups to evaluate the current evidence related to AAT usage in patients with cardiovascular risk factors and conditions and develop consensus‐based guidance for clinicians. Results This statement outlines the outcomes of the Summit, including considerations for prescribers, primary care professionals, emergency personnel, and health care system stakeholders. These considerations are intended to improve identification of patients as appropriate candidates for AAT, management of patients with co‐occurring AD and cardiovascular conditions, and their emergency evaluation and treatment. The statement also includes guidance for shared decision‐making, implementation of system changes for improving dementia care, and recommendations for future research and data collection to add to the body of evidence for treating patients with concomitant AD and cardiovascular conditions. Conclusions Building on lessons learned from the establishment of stroke systems of care, the consensus‐based considerations outlined in this document can serve as a foundation for AD systems of care aimed at ensuring optimal use of these ground‐breaking therapies.

Chimeric antigen receptor (CAR) T-cell therapy is a transformative modality for refractory hematologic malignancies; however, its adoption in Latin America and the Caribbean (LAC) is severely constrained by prohibitive manufacturing costs, limited specialized infrastructure, and fragmented regulatory frameworks. To address this translational gap, we propose a pragmatic, cost-adapted model for establishing Good Manufacturing Practice (GMP) laboratories tailored to the socioeconomic realities of LAC. This model advocates for decentralized, modular cleanroom facilities that integrate fully closed automated manufacturing platforms with risk-based quality management systems. Furthermore, we emphasize the strategic implementation of artificial intelligence (AI) and digital health tools—such as electronic batch records and predictive analytics—to optimize resource utilization and ensure stringent regulatory compliance. Essential to this framework is the cultivation of a specialized local workforce and the promotion of regional regulatory harmonization through initiatives like PAHO’s Red PARF. Ultimately, this scalable approach provides a realistic roadmap to democratize CAR T-cell therapy in LAC, fostering regional biomanufacturing autonomy and promoting equitable patient access.

Abstract INTRODUCTION Plasma p‐tau217 and p‐tau217/Aβ42 reliably identify non‐Hispanic White individuals with symptomatic and pre‐clinical AD. However, performance across ethnoracially diverse groups remains unknown. METHODS Cognitively normal Black, Hispanic, and non‐Hispanic White participants completed cognitive evaluations, brain magnetic resonance imaging (MRI), amyloid and tau positron emission tomography (PET), and measures of kidney function. Plasma p‐tau217 and Aβ42 were measured using Fujirebio Lumipulse assays. Pre‐clinical AD detection was evaluated using symptomatic and cohort‐derived optimized cutoffs. RESULTS Among 191 participants (57 Black, 46 Hispanic White, 88 non‐Hispanic White), age‐adjusted plasma p‐tau217 and p‐tau217/Aβ42 performed similarly in detecting amyloid‐positive individuals (≥ 25 Centiloids), regardless of race/ethnicity. Both measures independently correlated with amyloid deposition, whereas estimated glomerular filtration rate (eGFR) correlated solely with p‐tau217. Pre‐clinical AD optimized cutoffs (p‐tau217 ≥ 0.132 pg/ml; p‐tau217/Aβ42 ≥ 0.0059) outperformed cutoffs established in symptomatic individuals (sensitivity: 83% vs. 57%; 77% vs. 63%; negative predictive value [NPV] > 93%). DISCUSSION Plasma biomarkers performed similarly across ethnoracially diverse cohorts. Optimized cutoffs may improve early detection and trial enrollment.

Obesity is common among critically ill adults, but its association with outcomes during venovenous extracorporeal membrane oxygenation (VV ECMO) remains controversial. We evaluated associations of body mass index (BMI) with mortality and Extracorporeal Life Support Organization (ELSO)–defined complications in adults supported with VV ECMO. We conducted a retrospective multicenter cohort study of adults receiving VV ECMO at four centers (2017–2025). The primary outcome was in-hospital mortality; secondary outcomes were ELSO-defined complications. Multivariable logistic regression was adjusted for age, sex, and hospital site; BMI was evaluated as continuous, dichotomized (≥30 vs . <30 kg/m 2 ), and World Health Organization (WHO) obesity class exposures, with interaction testing by coronavirus disease 2019 (COVID-19) status. Among 420 patients (median BMI, 31 kg/m 2 ), in-hospital mortality was 62%. Higher BMI was associated with mortality in non–COVID-19 acute respiratory distress syndrome (ARDS; odds ratio [OR] = 1.06 per 1 kg/m 2 , 95% confidence interval [CI] = 1.02–1.10, p = 0.003) but not in COVID-19 ARDS (OR = 1.00, 95% CI = 0.94–1.05); there was insufficient evidence of interaction between BMI and COVID-19 ( p = 0.07). Higher BMI was associated with renal complications in both groups and infectious complications in non–COVID-19 ARDS (OR = 1.05, 95% CI = 1.02–1.09, p = 0.003). No significant BMI × COVID-19 interaction was detected for any outcomes. These findings do not support an obesity survival paradox during VV ECMO.