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Background: Despite the growing clinical relevance of obesity in the context of multiligament knee injuries, there remains a paucity of data evaluating patient-reported outcomes in this population. Purpose: To compare clinical and functional outcomes, including postoperative patient-reported outcome measures (PROMs) and complication/revision rates, of multiligament knee reconstruction (MLKR) in individuals with a body mass index (BMI) >30 kg/m 2 versus <30 kg/m 2 at a minimum 2-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed to identify all patients who underwent MLKR between 2001 and 2022 at a single institution. Patients with a BMI >30 kg/m 2 were propensity-matched to patients with a BMI <30 kg/m 2 on a 1:1 basis by age, sex, laterality, and Schenck classification (knee dislocation). Medical records were reviewed for patient characteristics, time to surgery, year of surgery, number and type of ligament interventions, graft choice, single versus staged reconstruction, and concomitant injuries. Postoperative clinical examination findings and PROMs for each cohort, including visual analog scale score, Tegner activity scale score, Lysholm score, and International Knee Documentation Committee (IKDC) subjective score, were analyzed and compared. Postoperative complication and revision rates were evaluated and compared. Results: Of 158 patients, 79 patients with a BMI <30 kg/m 2 (mean age, 31.0 ± 11.5 years; mean BMI, 25.8 ± 3.0 kg/m 2 ) were matched to 79 patients with a BMI >30 kg/m 2 (mean age, 32.8 ± 9.5 years; mean BMI, 37.1 ± 5.8 kg/m 2 ). There were no significant differences between cohorts regarding age, sex, laterality, and Schenck classification ( P ≥ .100); however, patients in the BMI >30 kg/m 2 group had greater numbers of posterior cruciate ligament reconstruction. The mean follow-up was 7.5 ± 4.8 years for the BMI <30 kg/m 2 cohort and 7.2 ± 4.8 years for the BMI >30 kg/m 2 cohort ( P = .229). Patients with a lower BMI (<30 kg/m 2 ) had significantly better postoperative mean IKDC (79.3 ± 18.7 vs 67.9 ± 21.2; P = .004), Lysholm (85.1 ± 17.1 vs 75.7 ± 21.0; P = .007), and Tegner (5.1 ± 2.0 vs 4.4 ± 1.7; P = .041) scores. The BMI >30 kg/m 2 group also had significantly more postoperative complications ( P = .028). However, there was no significant difference between the 2 cohorts in terms of reoperation rate or conversion to total knee arthroplasty ( P ≥ .189). Conclusion: Patients who undergo MLKR and have a BMI >30 kg/m 2 demonstrate significantly decreased postoperative PROMs when compared to patients with a BMI <30 kg/m 2 . Increasing BMI significantly increased the incidence of complication rates after MLKR.

BACKGROUND: Atherothrombosis, which underlies most acute coronary syndromes and is driven by intraplaque thrombosis, preferentially occurs in regions of disturbed blood flow (d-flow). Although LATS1/2 (large tumor suppressor kinases 1 and 2) are known regulators of endothelial mechanotransduction, the mechanisms by which d-flow connects endothelial senescence, proliferation, and intraplaque thrombosis remain poorly understood. METHODS: We investigated endothelial cell (EC)-specific roles of Lats1/2 using inducible EC-specific knockout mice in a partial carotid ligation model. Spatial multiomics of human and mouse plaques was performed using imaging mass cytometry, COMET sequential immunofluorescence, and spatial metabolomics. RESULTS: Tamoxifen-induced deletion of both Lats1 and Lats2 (homozygous) in ECs caused fatal edema and increased vascular permeability. In contrast, Lats1 het ( ± ) / Lats2 homo ( −/−) -EC-specific knockout mice survived and developed spontaneous atherothrombotic plaques with neovascularization. Spatial proteomics revealed that LATS1/2 loss induced a senescence-associated stemness phenotype driven by CD38 upregulation. Spatial metabolomics showed sulfite and taurine accumulation, indicating SUOX (sulfite oxidase) deficiency. CD38 suppressed SUOX, demonstrated a switch into the reverse mode of mitochondrial complex V, increased succinate dehydrogenase activity, and promoted ATP consumption. Despite ATP depletion, glutamate metabolism and the citric acid cycle flux increased, sustaining EC proliferation under energetic stress. This senescence-associated stemness state promoted both proliferation and senescence, leading to fragile, leaky neovessels and intraplaque thrombotic lesions. Pharmacological CD38 inhibition attenuated these phenotypes. Similar EC states were observed in human plaques. CONCLUSIONS: Loss of Lats1/2 in ECs induces a CD38-associated senescence-associated stemness-like phenotype that promotes intraplaque thrombosis through mitochondrial metabolic reprogramming, including changes consistent with reverse-mode operation of mitochondrial complex V. These findings define a mechanistic link between disturbed flow, endothelial metabolic reprogramming, and intraplaque thrombosis and hemorrhage.

OBJECTIVE Historically, craniopharyngioma (CP) was divided into adamantinomatous CP (ACP) and papillary CP (PCP) subtypes based on histopathological features. However, each harbors a unique genetic profile and progressively differing treatment paradigms, leading to their reclassification by the WHO in 2016 as two distinct entities. Descriptive in nature, this large multi-institutional study aimed to establish current differences between the presentation, treatment patterns, and clinical course of these pathologies to serve as a baseline for future studies as new treatment paradigms emerge. METHODS The authors queried the Registry for Adenomas of the Pituitary and Related Disorders (RAPID) database, which encompassed patients from 14 participating institutions across the United States between 2000 and 2024. The database was screened for adult patients who underwent initial CP treatment with a confirmed histopathological diagnosis of ACP or PCP. Patient demographic characteristics, clinical course, tumor treatment, and outcomes data were collected and compared by CP type. RESULTS The final analysis included 273 ACP and 99 PCP adult patients who underwent initial surgical treatment. ACP patients presented younger on average (mean 48.3 vs 52.8 years, p = 0.034). PCP patients were more likely to present with hypothyroidism (33.3% vs 20.5%, p = 0.010), hyperlipidemia (25.3% vs 15.8%, p = 0.036), fatigue (28.3% vs 17.6%, p = 0.024), temperature intolerance (9.1% vs 1.5%, p < 0.001), and cardiac arrhythmia (6.1% vs 1.1%, p = 0.006). The groups demonstrated similar postsurgical and neuroendocrinological outcomes. Postoperative median (IQR) progression-free survival did not significantly differ between groups (19.0 [7.0–37.0] for ACP vs 5.0 [3.5–7.5] months for PCP, p = 0.972). ACP patients were more likely to receive radiation after surgery (27.8% vs 15.2%, p = 0.012). CONCLUSIONS This large multicenter descriptive study aimed to characterize similarities and differences between the clinical courses of molecularly distinct ACP and PCP, which has not previously been described. The findings should serve as a baseline to inform future studies, particularly with the recent introduction of targeted therapy for PCP.

OBJECTIVE Craniopharyngiomas are benign intracranial tumors that can be difficult to manage operatively and often result in postoperative complications and prolonged recovery. Understanding the factors that influence length of stay (LOS), discharge disposition, and readmission can guide perioperative planning and patient counseling. The authors examined the clinical, radiographic, and surgical predictors of extended LOS (eLOS), nonhome discharge, 90-day readmission, and hospitalization ratio (HR) after craniopharyngioma resection using a large, multicenter cohort. METHODS A retrospective analysis was conducted using the Registry of Adenomas of the Pituitary and Related Disorders database, encompassing 469 patients who underwent craniopharyngioma resection at 14 US academic centers from 2011 to 2025. Patients were stratified by 4 outcomes: eLOS (> 75th percentile), discharge to home versus skilled nursing facility/rehabilitation, 90-day hospital readmission, and hospitalization ratio (i.e., integration of initial and readmission LOS). Multivariable logistic regression models identified independent predictors for each outcome among patient and surgical variables. RESULTS An eLOS (> 10 days) was independently associated with preoperative memory loss (OR 3.75, 95% CI 1.95–7.21), gait imbalance (OR 5.90, 95% CI 1.53–22.70), and postoperative complications (OR 4.07, 95% CI 2.34–7.06). The use of a nasoseptal flap was protective against an eLOS (OR 0.52, 95% CI 0.28–0.93). Discharge to home was predicted by an endoscopic approach (OR 3.87, 95% CI 1.78–8.44) and postoperative intact thirst (OR 2.22, 95% CI 1.05–4.66) and negatively predicted by preoperative diabetes mellitus (OR 0.21, 95% CI 0.09–0.50), LOS (OR 0.87, 95% CI 0.84–0.91), and postoperative cognitive dysfunction (OR 0.30, 95% CI 0.13–0.72). Among 385 patients with follow-up data, a 90-day readmission was independently associated with postoperative complications (OR 5.62, 95% CI 3.12–10.13), preexisting coronary artery disease (OR 4.30, 95% CI 1.46–12.69), and postoperative cognitive dysfunction (OR 3.33, 95% CI 1.76–6.44). A higher HR was associated with diabetes mellitus (unstandardized B 0.059, 95% CI 0.010–0.108, p = 0.02), postoperative complications (unstandardized B 0.054, 95% CI 0.021–0.086, p = 0.001), and postoperative cognitive dysfunction (unstandardized B 0.049, 95% CI 0.006–0.092, p = 0.02). Tumor pathologic subtype and size, prior treatment, extent of resection, and surgeon experience were not directly predictive of outcomes. CONCLUSIONS Cognitive and functional status, systemic comorbidities, and postoperative complications, in addition to surgical approach, are important predictors of the early clinical course after craniopharyngioma surgery. Early identification of high-risk patients may help to guide treatment decisions, improve discharge planning, and reduce healthcare utilization.

Introduction Geriatric distal femur fractures are associated with mortality rates exceeding 20%, comparable to hip fractures. Traditional single implant fixation often requires weight-bearing restrictions that delay recovery. This pilot study aims to assess the feasibility of conducting a multicentre randomised controlled trial comparing dual vs single implant fixation for geriatric distal femur fractures. Methods and analysis This multicentre, prospective, randomised controlled pilot trial will enrol 80 participants aged 60 years or older with displaced distal femur fractures at five US level 1 trauma centres. Patients will be randomly allocated 1:1 to receive either single implant (lateral plate or retrograde nail) or dual implant (nail-plate or dual plate) fixation. All patients will be permitted immediate weight-bearing. The primary outcome is feasibility assessed through enrolment rate (80 patients in 12 months), protocol adherence (≥90%) and follow-up retention (≥85% at 12 months). Secondary outcomes include post-surgical mobility (AM-PAC, TUG), patient-reported outcomes (PROMIS-PF, PROMIS-29), mortality (90-day and 1 year) and complication rates. Analyses will be on an intention-to-treat basis. Ethics and dissemination The protocol was approved by the University of Utah Institutional Review Board (IRB_00149119) and IRBs at all participating centres. Written informed consent will be obtained from participants or legally authorised representatives. Findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT05292313 .

ABSTRACT Objective Management of vestibular schwannoma (VS) remains controversial. Very small VSs represent a pivotal group: on one hand, they pose the least risk to the patient from the perspective of being small; yet, not recommending treatment may result in missing a critical window for achieving the best outcome. This debate fundamentally hinges on whether treatment improves upon the natural history of the disease. There is an unproven assumption that very small tumors behave similarly to the broader observed population. To address this central question, we conducted a multicenter retrospective review to compare the natural history of tumor growth and hearing for patients with very small VS (1–3 mm) with a referent cohort with larger tumors. Methods All patients diagnosed with sporadic VS 1–3 mm were reviewed at 3 large skull base referral centers and compared with a referent cohort of patients with tumors > 3 mm. Tumor growth‐free survival rates, treatment‐free survival rates, and rates of maintenance of class A, B, or C hearing were estimated using the Kaplan–Meier method. Results In total, 123 patients with very small VS and a referent cohort of 326 patients were studied. Seventeen patients with very small VS experienced tumor growth at a median of 3.2 years after diagnosis (IQR 2.6–5.1), demonstrating a median growth rate of 1.0 mm per year (IQR 0.9–1.8). In comparison, 167 of the patients in the referent cohort experienced tumor growth at a median of 1.7 years after diagnosis (IQR 0.8–3.1). Tumor growth‐free survival rates (95% CI, number still at risk) at 5 years after diagnosis for the 2 cohorts were 84% (75–93, 39) and 45% (40–52, 100), respectively ( p < 0.001). Six patients with very small VS underwent treatment after tumor growth at a median of 3.2 years after diagnosis (IQR 3.2–3.8), compared with 138 patients in the referent cohort at a median of 2.2 years after diagnosis (IQR 1.4–3.6). Treatment‐free survival rates (95% CI, number still at risk) at 5 years after diagnosis for the 2 cohorts were 92% (86–98, 55) and 54% (49–61, 125), respectively ( p < 0.001). Among the 105 patients with very small VS and class A, B, or C hearing at diagnosis, 3 progressed to class D. Comparatively, among the 225 patients in the referent cohort with class A, B, or C hearing at diagnosis, 70 progressed to class D at a median of 2.6 years after diagnosis (IQR 1.0–4.8). Rates of maintenance of class A, B, or C hearing (95% CI, number still at risk) at 5 years after diagnosis were 96% (92–100, 28) for patients with very small VS and 65% (57–73, 70) for the referent cohort ( p < 0.001). Conclusions The natural history of tumor growth and hearing for very small VS diverges favorably from the cumulative natural history data and provides a more appropriate benchmark to compare clinical outcomes of upfront surgery or radiosurgery for this population. At 5 years after diagnosis, 96% of very small VS maintained class A, B, or C hearing and only 8% received treatment for growth within this multicenter cohort. Cumulatively, these data substantiate initial wait‐and‐scan management via size threshold surveillance in this population. Level of Evidence 3.

ABSTRACT The Burkholderia cepacia complex (BCC) is comprised of 24 species of Gram-negative bacteria that cause opportunistic infections. While antimicrobial susceptibility testing (AST) has historically been used to guide treatment for BCC infections, recent work highlighting problems with AST for these organisms led the Clinical and Laboratory Sciences Institute (CLSI) to remove disk diffusion (DD) and minimal inhibitory concentration (MIC) breakpoints for BCC from its M100 standards document. Epidemiological cut-off values (ECVs) may be helpful to clinicians in the absence of breakpoints, as they may be used to determine whether an isolate has a wild-type or non-wild-type phenotype. Here we present an analysis of BCC ECVs for ceftazidime (CAZ), levofloxacin (LVX), meropenem (MEM), minocycline (MIN), and trimethoprim-sulfamethoxazole (TMP-SMX). ECVs were calculated using MIC data from 3 previous studies and 3 independent laboratories for 1,896 BCC isolates. ECVs were 16 μg/ml for CAZ, 8 μg/ml for LVX, 16 μg/ml for MEM, and 8 μg/ml for MIN. The ECV for TMP-SMX varied depending on the analysis from 2 μg/ml, 8 μg/ml, and 16 μg/ml and therefore could not be reliably established. Challenges with establishing ECVs for BCC include limitations with the pooled MIC dataset, broad MIC distributions, and high ECVs that are above the obsolete susceptible MIC breakpoints. These challenges limit the clinical utility of ECVs for these organisms and supported removal of ECVs from the CLSI M100 standards document. IMPORTANCE The Burkholderia cepacia complex is a group of bacterial species that cause difficult-to-treat opportunistic infections. Recently, clinical breakpoints, which are used to determine whether organisms are susceptible to certain antimicrobials, were removed from Clinical and Laboratory Standards Institute (CLSI) standards for these organisms due to problems with antimicrobial susceptibility testing performance. Clinicians are now faced with the challenge of how to treat these complex infections without clinical breakpoints. Here we determine epidemiological cut-off values (ECVs) for relevant antimicrobials for the B. cepacia complex. While we established ECVs for four antimicrobials, we encountered significant challenges in our analyses, including limitations with data for these organisms and high ECVs that are not clinically useful. These challenges limit the practical use of these ECVs in helping guide clinicians on treatment and supported the eventual removal of ECVs from the CLSI M100 standards document.