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Multicentre Analysis of Seizure Outcome Predicted by Removal of High-Frequency Oscillations
In drug-resistant focal epilepsy, planning surgical resection can involve presurgical intracranial EEG (iEEG) recordings to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high-frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. In eight international epilepsy centres, iEEG was recorded during the presurgical evaluation of patients. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis, we applied a fully automated definition of HFO that was independent of the dataset. Using an observational cohort design that was blinded to postsurgical seizure outcome, we analysed HFO rates during non-rapid-eye-movement sleep. If channels had consistently high rates over multiple epochs, they were labelled the \u27HFO area\u27. After HFO analysis, centres provided the electrode contacts located in the resected volume and the seizure outcome at follow-up ≥24 months after surgery. The study was registered at www.clinicaltrials.gov (NCT05332990). We received 160 iEEG datasets. In 146 datasets (91%), the HFO area could be defined. The patients with a completely resected HFO area were more likely to achieve seizure freedom in comparison to those without [odds ratio 2.61, 95% confidence interval (CI) 1.15-5.91, P = 0.02]. Among seizure-free patients, the HFO area was completely resected in 31 and not completely resected in 43. Among patients with recurrent seizures, the HFO area was completely resected in 14 and not completely resected in 58. When predicting seizure freedom, the negative predictive value of the HFO area (68%, CI 52-81) was higher than that for the resected volume as a predictor by itself (51%, CI 42-59, P = 4 × 10-5). The sensitivity and specificity for complete HFO area resection were 0.88 (CI 0.72-0.98) and 0.39 (CI 0.25-0.54), respectively, and the area under the curve was 0.83 (CI 0.58-0.97), indicating good predictive performance. In a blinded cohort study from independent epilepsy centres, applying a previously validated algorithm for HFO marking without the need for adjusting to new datasets allowed us to validate the clinical relevance of HFOs to plan the surgical resection
Solute Transport From Synovial Fluid to Articular Cartilage and Subchondral Bone at Different Stages of Osteoarthritis in a Live Mouse Model
OBJECTIVE: This study aims to (1) identify a simplified method to preserve sample integrity and maintain original fluorescence distribution; (2) assess the diffusivity of small and large molecules within articular cartilage (AC), calcified cartilage (CC), and subchondral bone (SB); and (3) investigate the changes in solute transport at various stages of osteoarthritis (OA) in a destabilization of the medial meniscus (DMM) murine model.
METHODS: Fluorescent dyes of small and large molecules were injected into the knee joints of live mice. Joints were harvested and rapidly frozen immediately post-euthanasia. Optimal dye concentrations and dwelling times were determined through exploratory studies. Mice underwent either DMM or sham surgery and were evaluated at 2 and 8 weeks postoperatively. Relative fluorescence intensity was quantified within the AC, CC and SB, complemented by micro-CT, safranin O staining, and collagen II immunohistochemistry staining.
RESULTS: The methodology successfully preserved sample integrity and original dye distribution. Fluorescent imaging revealed that small solute was mainly restricted by the tidemark, while large solute showed limited permeability in AC. Permeability of AC remained elevated in the DMM group at both time points. Increased permeability in CC and SB was observed only at 8 weeks post-DMM surgery, accompanied by reduced collagen II amount.
CONCLUSIONS: In live mice, the tidemark serves as a barrier to small molecule diffusion, while the cartilage surface restricts larger molecules; however, both structures exhibit increased permeability in OA. These findings advance the understanding of OA pathogenesis and suggest potential therapeutic targets related to cartilage permeability.
TRANSLATIONAL POTENTIAL: The findings of this study advance the understanding of osteoarthritis pathogenesis by elucidating the role of solute transport alterations in cartilage and subchondral bone, thereby suggesting potential therapeutic targets aimed at modulating cartilage permeability to improve joint health in osteoarthritis
Frozen Section Mohs: A Hybrid Technique and One Plastic Surgeon\u27s Experience With 1714 Consecutive Skin Cancer Removals
While US nonmelanoma skin cancer (NMSC) mortality rate has decreased in the past decade, its incidence is rising. Traditional surgical treatments include wide local excision, intraoperative frozen section analysis (IFSA), and Mohs micrographic surgery (MMS). IFSA and MMS are techniques that provide intraoperative analysis allowing the surgeon to confirm margins clear of malignancy and minimize tissue damage, especially in cosmetically sensitive subunits. MMS, with cure rates up to 99%-100%, is considered the gold standard but is limited geographically and financially because of specialized training. We report a hybrid surgical technique that effectively excises cutaneous malignancy but can be utilized by plastic surgeons. This hybrid technique is called frozen section Mohs (FSM), which combines both techniques utilized in IFSA and MMS. FSM is similar to IFSA in that the middle breadloaf visualizes the central deep margin but is similar to MMS in that the entire periphery is also analyzed. This paper is a retrospective review of all patients who have undergone the FSM procedure by one plastic surgeon from September 2017 to June 2023. The primary outcomes were 1) recurrence, determined by excision of skin cancer demonstrated to be arising from postexcision scar tissue, and 2) concordance between intraoperative and final pathology. There were 1714 FSM procedures performed with a cohort averaging 73.8 years old and 57% male. Zero recurrences were identified (100% cure rate). Two cases (0.11%) were false negatives and the patients returned for re-excision. About 48.2% of cases were basal cell carcinoma while 40.7% were squamous cell carcinoma. The average number of stages per FSM procedure was 1.17. The mean defect size was 1.83 cm.2 Complication rate was 2.28% (n = 39), with the most common issue being bleeding that required suturing or cautery. Our proposed FSM technique\u27s results demonstrate effective carcinoma removal comparable to MMS. Plastic surgeons may therefore utilize this technique to meet the growing demands of skin cancer surgery in the United States with equally effective outcomes
Echocardiography and Heart Failure: An Echocardiographic Decision Aid for the Diagnosis and Management of Cardiomyopathies.
PURPOSE OF REVIEW: The purpose of this review is to highlight the utility of echocardiography in the diagnosis and management of cardiomyopathies.
RECENT FINDINGS: Echocardiographic parameters function synergistically to guide decision-making ranging from early detection of disease and screening to risk stratification of complex disease. The collective wealth of information available from 2D/3D assessment, Doppler, diastology and strain makes echocardiography an invaluable decision aid
Multiparametric MRI Along With Machine Learning Predicts Prognosis and Treatment Response in Pediatric Low-Grade Glioma
Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free survival and correlates with treatment response. We also identify genetic variants and transcriptomic pathways associated with progression risk, highlighting links to tumor growth and immune response. This radiogenomic study in pLGGs provides a framework for the identification of high-risk patients who may benefit from targeted therapies
Shoulder Musculature Model, Separable
For further information and availability, please visit the model\u27s catalogue record: https://jefferson.primo.exlibrisgroup.com/permalink/01TJU_INST/1ckporg/alma991000901184003866.https://jdc.jefferson.edu/scottlibrary_anatomy_models/1052/thumbnail.jp
Lung Model
For further information and availability, please visit the model\u27s catalogue record: https://jefferson.primo.exlibrisgroup.com/permalink/01TJU_INST/1ckporg/alma991000098469703866.https://jdc.jefferson.edu/scottlibrary_anatomy_models/1038/thumbnail.jp
The Loss of OPA1 Accelerates Intervertebral Disc Degeneration and Osteoarthritis in Aged Mice
Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling an