Citations

This international multicenter study seeks to determine the frequency and characteristics of meningitis in myelin oligodendrocyte glycoprotein antibody (MOGAD)–associated disease and highlight its pathology.

ABSTRACT Nicotinamide adenine dinucleotide (NAD) is a key coenzyme involved in energy metabolism, DNA repair, and cellular signaling. While the effects of acute NAD depletion have been better characterized, the consequences of chronic NAD deficiency remain unclear. Here, we investigated the impact of chronic NAD depletion in cultured cells by removing the availability of nicotinamide (NAM), a key precursor for NAD synthesis, from the culture media. In NIH3T3 fibroblasts, NAM depletion caused a dramatic drop in intracellular NAD levels within 2 days. Remarkably, the cells remained viable even after 7–14 days of NAM depletion, despite NAD + levels falling to less than 10% of control conditions. This chronic NAD depletion led to distinct metabolic alterations. Mitochondrial basal respiration remained unchanged, but cells exhibited reduced spare respiratory and maximal capacities, along with significantly impaired glycolysis. Notably, NAD depletion triggered an interferon‐dependent inflammatory response, resembling viral infections. This was driven by cytosolic leakage of mitochondrial DNA (mtDNA) through voltage‐dependent anion channel 1 (VDAC1), which activated the cGAS‐STING signaling pathway. Inhibition of VDAC oligomerization with VBIT‐4, STING signaling with H‐151, or mtDNA depletion blocked the upregulation of interferon genes induced by NAM depletion. Similar interferon responses triggered by NAD depletion were observed in IMR90 human fibroblasts and HS5 stromal cells. Our findings reveal a novel link between chronic NAD deficiency, VDAC‐mediated mtDNA release to the cytoplasm, and the activation of the inflammatory response, providing new insight into how NAD decline affects cellular metabolic and inflammatory processes.

Purpose Part-two of this consensus aimed to provide recommendations for the prevention of meniscus injuries, non-operative treatment of acute tears and degenerative lesions, return to sports, and patient-reported outcome measures. Methods This consensus followed the European Society of Knee Surgery, Sports Traumatology and Arthroscopy (ESSKA) formal consensus methodology. For this combined ESSKA- American Orthopedic Society for Sports Medicine (AOSSM) - American Academy of Sports Physical Therapy (AASPT) initiative, 67 experts from 14 countries, including orthopedic surgeons and physiotherapists, were involved. The 26 Steering Group members established guiding questions, screened the existing evidence, and proposed statements, and provided Grades of recommendations. The 41 Rating Group members assessed the statements according to a Likert scale (1-9). Final documents were assessed by an international peer review group for geographical adaptability. Results Low to moderate scientific level of evidence was available, so that grades of recommendations were low (three Grade A ratings, four Grade B, three Grade C and 13 Grade D), underlining the relevance of this consensus. One strong and 17 relative agreements with overall median of 8 (8-9) and a mean of 7.92 +/- 0.37 were achieved for 23 statements on 18 questions. Prevention of meniscus injuries is possible with general knee injury reduction programs and through avoidance of certain activities. Non-Operative treatment including physical therapy is the first line approach for degenerative meniscus lesions and may be an option for some acute tears. Return to sports after meniscus tear surgery should be both criterion-based and time-based. Patient reported outcomes in combination with performance-based measures are recommended to evaluate the rehabilitation process. Conclusion This international EU-US consensus established recommendations for prevention strategies, describes rehabilitation of non-operated patients and of patients after partial meniscectomy, meniscus repair and meniscus reconstruction, and establishes return to sport criteria. These updated and structured recommendations may be applied by surgeons and physiotherapists. Level of Evidence I, Formal Consensus.

Purpose: Part II of this consensus aimed to provide recommendations for the prevention of meniscus injuries, nonoperative treatment of acute tears and degenerative lesions, return to sports and patient-reported outcome measures. Methods: This consensus followed the European Society of Knee Surgery, Sports Traumatology and Arthroscopy (ESSKA) formal consensus methodology. For this combined ESSKA—American Orthopedic Society for Sports Medicine (AOSSM)—American Academy of Sports Physical Therapy (AASPT) initiative, 67 experts from 14 countries, including orthopedic surgeons and physiotherapists, were involved. The 26 Steering Group members established guiding questions, screened the existing evidence, and proposed statements, and provided Grades of recommendations. The 41 Rating Group members assessed the statements according to a Likert scale (1–9). Final documents were assessed by an international peer review group for geographical adaptability. Results: Low to moderate scientific level of evidence was available, so that grades of recommendations were low (3 Grade A ratings, 4 Grade B, 3 Grade C and 13 Grade D), underlining the relevance of this consensus. One strong and 17 relative agreements with overall median of 8 (8–9) and a mean of 7.92 ± 0.37 were achieved for 23 statements on 18 questions. Prevention of meniscus injuries is possible with general knee injury reduction programs and through avoidance of certain activities. Non-operative treatment including physical therapy is the first line approach for degenerative meniscus lesions and may be an option for some acute tears. Return to sports after meniscus tear surgery should be both criterion-based and timebased. Patient reported outcomes in combination with performance-based measures are recommended to evaluate the rehabilitation process. Conclusion: This international EU–US consensus established recommendations for prevention strategies, describes rehabilitation of nonoperated patients and of patients after partial meniscectomy, meniscus repair and meniscus reconstruction, and establishes return to sport criteria. These updated and structured recommendations may be applied by surgeons and physiotherapists. Level of Evidence: Level I, consensus.

AbstractPurposePart two of this consensus aimed to provide recommendations for the prevention of meniscus injuries, non‐operative treatment of acute tears and degenerative lesions, return to sports and patient‐reported outcome measures.MethodsThis consensus followed the European Society of Knee Surgery, Sports Traumatology and Arthroscopy (ESSKA) formal consensus methodology. For this combined ESSKA—American Orthopedic Society for Sports Medicine (AOSSM)—American Academy of Sports Physical Therapy (AASPT) initiative, 67 experts from 14 countries, including orthopedic surgeons and physiotherapists, were involved. The 26 Steering Group members established guiding questions, screened the existing evidence, and proposed statements, and provided Grades of recommendations. The 41 Rating Group members assessed the statements according to a Likert scale (1–9). Final documents were assessed by an international peer review group for geographical adaptability.ResultsLow to moderate scientific level of evidence was available, so that grades of recommendations were low (three Grade A ratings, four Grade B, three Grade C and 13 Grade D), underlining the relevance of this consensus. One strong and 17 relative agreements with overall median of 8 (8–9) and a mean of 7.92 ± 0.37 were achieved for 23 statements on 18 questions. Prevention of meniscus injuries is possible with general knee injury reduction programmes and through avoidance of certain activities. Non‐operative treatment including physical therapy is the first line approach for degenerative meniscus lesions and may be an option for some acute tears. Return to sports after meniscus tear surgery should be both criterion‐based and time‐based. Patient reported outcomes in combination with performance‐based measures are recommended to evaluate the rehabilitation process.ConclusionThis international EU–US consensus established recommendations for prevention strategies, describes rehabilitation of non‐operated patients and of patients after partial meniscectomy, meniscus repair and meniscus reconstruction, and establishes return to sport criteria. These updated and structured recommendations may be applied by surgeons and physiotherapists.Level of EvidenceLevel I, consensus.

The NCCN Guidelines for Survivorship include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from adult-onset cancer and its treatment and provide a framework for coordination of survivorship care. They also include recommendations to help cancer survivors enhance their wellness and maintain a healthy lifestyle. These NCCN Guidelines Insights summarize the panel’s current recommendations and recent updates regarding physical activity, nutrition, and weight management for cancer survivors.

Introduction. Increased steatosis on preimplant liver frozen section is associated with delayed graft function and primary nonfunction. Efforts to standardize histologic assessment have proven difficult. Frozen section artifact and lipopeliosis complicate the detection of steatosis. We aimed to develop and validate an AI model to recognize large droplet fat and fat induced artifact (FIA)/lipopeliosis on preimplantation frozen section and to correlate the AI results with post-transplant clinical parameters. Methods. The model was applied to 161 consecutive liver transplant specimens with preimplant slides. Results were correlated with traditional and Banff histologic assessment and clinical parameters. Results. By traditional assessment, steatosis ranged from 0%–40%. The AI model identified a range of 0 to 15.9% steatosis. There was no difference in patient survival by any measures of steatosis. AI steatosis correlated with increased risk of early allograft dysfunction (OR = 1.63, P < .001), respiratory failure (OR = 1.21, P = .003), and more advanced fibrosis (OR = 1.18, P = .030), but was not correlated with graft or patient survival. FIA/lipopeliosis were identified in a range of 0 to 6.42%. In univariate analysis the percentage of FIA/lipopeliosis correlated with both graft and patient survival ( P = .044 and P = .009, respectively), but was not associated with increased risk of early allograft dysfunction, respiratory failure, or advanced fibrosis. Conclusions. We developed an AI model that quantitates large droplet fat and FIA/lipopeliosis on frozen section slides and found a correlation with post-transplant outcomes. Further studies on larger, multi-institutional cohorts with higher fat containing donors are necessary to determine the role this model may have in organ acceptance decisions.

Abstract INTRODUCTION Robust plasma-based biomarkers to distinguish Lewy body disease (LBD) and Alzheimer’s disease (AD) are currently lacking. We applied track-etch magnetic nanopore (TENPO) sorting for enrichment of brain-derived extracellular vesicle (EV) signatures as potential biomarkers to address this gap. METHODS We analyzed plasma from 137 autopsy-confirmed patients [30 LBD, 31 AD, 30 AD/LBD, 19 AD with amygdala Lewy bodies (AD/ALB), and 27 controls], sequencing miRNAs from TENPO-isolated GluR2-positive (neuron-enriched) and GLAST-positive (astrocyte-enriched) EVs, and measuring plasma proteins (Aβ40, Aβ42, tau, p-Tau181, p-Tau231) via SIMOA. RESULTS We identified 16 GluR2+, 8 GLAST+, and 4 protein biomarkers with differential expression (false discovery rate-corrected P value < .1) between LBD and AD. A multimodal 15-feature panel classified LBD versus AD with 10-fold cross-validated accuracy = 0.95 and area under the curve (AUC) = 0.96. DISCUSSION Brain-derived EVs offer accurate and accessible miRNA biomarkers for the differential diagnosis of LBD and AD.