Citations

Background: Acute traumatic patellar dislocations may cause intra-articular derangements of the knee in the setting of acute and chronic instability which may not always be appropriately identified on magnetic resonance imaging (MRI). Purpose: To determine the rates of coexisting intra-articular pathology in patients with patellar instability requiring medial patellofemoral ligament (MPFL) reconstruction and to report discrepancies between preoperative magnetic resonance imaging (MRI) findings and diagnostic arthroscopy results. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: Patients who underwent MPFL reconstruction at a single institution between 2010 and 2023 were identified. Operative reports and preoperative MRIs were reviewed. Records without full MRI reports as read by a radiologist or cases in which a diagnostic arthroscopy was not conducted were excluded. Intra-articular pathologies noted on MRI and confirmed by arthroscopy were documented. MRI findings were considered to be discordant from arthroscopic findings if a lesion was identified on diagnostic arthroscopy that was not present in the full MRI report and that lesion resulted in additional surgical procedures. Results: There were 331 arthroscopic procedures conducted within the study population of 508 patients who underwent diagnostic arthroscopy at the time of their patellar stabilization procedures. These procedures included 180 loose body removals, 95 osteochondral lesions treated via a variety of interventions including open reduction and internal fixation (26 cases), particulated allograft chondral grafting (30 cases), osteochondral allograft transplantation (9 cases), and microfracture (30 cases), and 39 meniscal tears resulting in 33 partial meniscectomies and 6 meniscal repairs. Among these 508 patients, 105 (21%) demonstrated discordance of preoperative MRI and arthroscopic findings that necessitated additional procedures. This discordance was responsible for a total of 109 (33%) of the 331 arthroscopic procedures. These included 75 loose body removals, 2 osteochondral fracture fixation procedures, 2 microfractures for full-thickness cartilage loss, 16 partial meniscectomies, and 2 meniscal repairs, among others. Conclusion: Among patients undergoing patellar stabilization, 21% had intra-articular lesions not identified on preoperative MRI detected at the time of diagnostic arthroscopy that resulted in surgical intervention. This study, representing the largest cohort to date of patellar stabilization surgeries with both MRI and arthroscopy findings, underscores the importance of diagnostic arthroscopy for improving diagnostic accuracy and addressing associated intra-articular pathology.

Abstract Purpose: Knowledge of prognostic factors and long-term survival in patients with diffuse hemispheric glioma, H3 G34–mutant (DHG, H3 G34), remains limited in this tumor with a poor prognosis. Experimental Design: This retrospective, multi-institutional study investigated prognostic variables for patients with DHG, H3 G34, and their association with progression-free survival (PFS) and overall survival (OS). Uni- and multivariable Cox proportional hazard models were applied with multiple imputed datasets. Results: A total of 153 patients (142 G34R, 9 G34V, 2 via DNA methylation) were included. The median age at diagnosis was 17 years (range, 2–45). Initial gross/near total resection (GTR/NTR) was achieved in 43% of patients. Radiation was given in 91% (85% focal irradiation), and initial chemotherapy was given in 87% [70% temozolomide-based (TMZ), 25% TMZ/lomustine, 5% non-TMZ]. Median OS was 24 months [interquartile range (IQR), 22–28] with a median PFS of 14 months (IQR, 12–19). Twelve patients (8%) were found to be long-term survivors (≥5 years). Exploratory multivariable analysis showed that adjuvant radiotherapy [HR, 0.076; 95% confidence interval (CI), 0.033–0.17] and achieving GTR/NTR compared with < NTR (HR, 0.51; 95% CI, 0.33–0.78) were associated with improved PFS. Multivariable analysis showed improved OS with increasing age at diagnosis (HR, 0.70; 95% CI, 0.57–0.87), initial radiotherapy (HR, 0.38; 95% CI, 0.15–0.96), and initial GTR/NTR compared with < NTR (HR, 0.60; 95% CI, 0.37–0.97). Conclusions: This cohort highlights prognostic factors for patients with DHG, H3 G34, and describes relapse patterns and therapy approaches. Clinical trials and prospective registries are needed to improve outcomes.

ABSTRACT Background Primary lateral sclerosis (PLS) is an ultrarare upper motor neuron syndrome with a prognosis unique from classical ALS. The study of PLS is complicated by its rarity and the difficulty distinguishing PLS from ALS. We present data from a 1‐year prospective follow‐up study on PLS and efforts to distinguish it from ALS. Methods Seventy‐six PLS participants enrolled in this prospective natural history study. EMG studies, blood neurofilament light chain levels (NfLs), and demographic characteristics were obtained at baseline. At 1‐year follow‐up, repeat EMG studies were conducted to determine which participants fulfilled criteria for ALS. Baseline characteristics were then compared to determine features that predict reclassification. Results Seventy participants completed 1‐year follow‐up. Five of the 70 were reclassified to ALS (7.1%). Those reclassified had higher trends in baseline blood NfL levels (91.4 vs. 34.0 pg/mL, p = 0.13) and shorter symptom duration (39 vs. 69 months in the PLS group, p = 0.15). Reclassification was noted in both probable and definite PLS participants. All cases with a symptomatic duration of less than 2 years retained the PLS phenotype (5 of 5). NfL levels over 90 pg/mL predicted reclassification with 94% specificity and 60% sensitivity. No other features predicted reclassification to ALS. Conclusions In our population, reclassification of PLS to ALS occurred at a low frequency at 1 year follow‐up (7.1%). Baseline NfL was the strongest predictor in differentiating UMN dominant ALS from PLS at 1‐year follow‐up. Based on our data, we propose EMG and NfL criteria for enrollment in future PLS trials.

Abstract Current assessments of brain permeability rely predominantly on drug delivery to contrast-enhancing tumor regions. However, substantial portions of central nervous system (CNS) tumors reside within non-enhancing brain (NEB), where drug concentrations frequently remain subtherapeutic. This collaborative Adult Brain Tumor Consortium and Food and Drug Administration workshop aimed to identify criteria for defining NEB permeability to accomplish 2 critical objectives: (1) allocate clinical trial resources toward agents achieving therapeutic NEB concentrations and (2) minimize systemic toxicity when CNS benefit is improbable. The workshop systematically evaluated permeability assessment modalities, including drug physicochemical properties, in vitro blood-brain barrier models, and penetration into cerebrospinal fluid and normal rodent brain. Methodological approaches to determine requisite NEB drug concentrations and approaches to measuring NEB pharmacokinetics and pharmacodynamics were examined. This culminated in developing the Non-Enhancing Brain Permeability Index (NEBPI), which assigns therapeutic agents to 3 categories: sufficiently permeable, insufficiently permeable, or impermeable. The NEBPI provides a standardized framework to assist investigators and regulatory agencies to evaluate NEB penetration before human efficacy studies are initiated for agents that require direct tumor contact. Assessing NEB drug penetration is critical to improving outcomes in CNS tumors and reducing the incidence of brain metastases in systemic malignancies.

Abstract Introduction Left atrial-to-coronary sinus (LA-to-CS) shunting through the APTURE transcatheter shunt system aims to unload the LA while preserving the interatrial septum. This article aims to examine the 3-year health status, functional capacity, and clinical outcomes of the ALT-FLOW Early Feasibility Study (EFS). Methods Device safety, patency, and echocardiographic parameters, but also symptoms, health status, and exercise capacity were assessed in patients with left ventricular ejection fraction (LVEF) > 40% (n & 95). Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score predicted 3-year all-cause mortality was compared with observed mortality assessed by Kaplan–Meier analysis using adjudicated events. Predicted and observed HF hospitalization (HFH)-free survival rates were also compared. Results At 3 years, the safety profile remained stable with no new safety signals, and all implanted shunts remained patent. 76.3% of patients improved by at least one NYHA class, and mean KCCQ Overall Summary Scores increased by 25 points from baseline (P < .0001). The 6-min walk distance improved by an average of 39 m (P & .002). These benefits were consistent regardless of baseline pulmonary vascular resistance (PVR). Right heart echocardiographic parameters after 3 years were stable, though a reduction in TAPSE was observed, primarily in the high PVR subgroup. The observed 3-year survival was significantly higher than the MAGGIC-predicted survival (84.4% vs 70.2, respectively; P & .009), as well as the HFH-free survival (68.0% vs 24.0%, respectively; P < 0001). Conclusion In patients with HF and LVEF >40%, the APTURE LA-to-CS shunting confirmed an acceptable safety profile with stable right heart parameters and sustained improvements in symptoms, quality of life, and functional capacity at 3 years. Observed survival and HFH were superior to MAGGIC predictions.

Since the early 21st century, team science has significantly influenced emerging perspectives, processes, and expectations across various industries, human development, and scholarly activities. Research over the past 25 years—drawing on psychology, management, social psychology, anthropology, organizational sciences, and sociology—has shaped best practices and redefined how academics and practitioners approach collaborative work. Despite substantial progress in understanding team dynamics, a critical gap remains: the absence of a clearly defined professional pathway for team scientists and science workers. Specifically, there is a lack of a secure, structured pipeline that supports training, recognition, and career advancement in team science roles. This paper addresses the limited presence of systematic organizational strategies that help science workers from the early stages of their careers through long-term professional growth. As higher education confronts a shifting paradigm, institutions must now prepare students not only as disciplinary experts but also as collaborators equipped to thrive in a cross-disciplinary, problem-solving environment that embraces the workforce competencies employers seek. We examine the organizational requirements and challenges necessary to ensure success in science careers, emphasizing developmental training, robust mentorship, the professionalization and institutionalization of team structures, and sustaining collaboration. These elements are essential for preparing a workforce that is capable, resilient, and ready for the demands of future collaborative scientific endeavors.

Introduction Translating findings from cell and animal models to the clinic is difficult because these systems insufficiently capture human disease biology. Computational approaches, notably pathways modeling, have overcome interspecies differences by mapping shared signaling pathways between species. We considered whether this approach could be generalized to bridge animal and virtual drug screening data to effects measured in patients. We emphasized translational psychiatry datasets because of the unmet need for effective therapies. Methods We conducted three parallel analyses using published drug screening data in zebrafish, structure-function computational screening data, and clinically-reported efficacy data for experimental and approved antipsychotic drugs and predicted drug pathways using the PathFX algorithm Results Despite choosing screens developed for unique aspects of psychiatry and without careful curation of shared drugs, we found pathways associated with drugs that performed “well” across these distinct platforms—specifically, among drugs measured as favorable (expected to improve disease) or unfavorable (expected to aggravate disease) across screens, these drugs connected to distinct pathway proteins; however, these drugs are connected to similar protein families and shared Gene Ontology functional terms. By comparing screens, we discovered that favorable drugs may influence G-proteins, solute carrier family proteins, adrenoceptors, and steroid hydroxylase activity and that unfavorable drugs affect serotonin receptors and phosphodiesterase activity. Discussion This suggests that predictive platforms could emphasize functional information as features that could overcome differences in distinct screening platforms to eventually improve translational approaches.