Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers.

Over the past two decades, increased research has highlighted the connection between endosomal trafficking defects and neurodegeneration. The endo-lysosomal network is an important, complex cellular system specialized in the transport of proteins, lipids, and other metabolites, essential for cell homeostasis. Disruption of this pathway is linked to a wide range of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and frontotemporal dementia. Furthermore, there is strong evidence that defects in this pathway create opportunities for diagnostic and therapeutic intervention. In this Opinion piece, we concisely address the role of endo-lysosomal dysfunction in five neurodegenerative diseases and discuss how future research can investigate this intracellular pathway, including extracellular vesicles with a specific focus on exosomes for the identification of novel disease biomarkers. This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.

Lower re-rupture rates but higher complication rates following surgical versus conservative treatment of acute achilles tendon ruptures: a systematic review of overlapping meta-analyses.

PURPOSE: To systematically review and evaluate the current meta-analyses for the treatment of acute Achilles tendon rupture (AATR). This study can provide clinicians with a clear overview of the current literature to aid clinical decision-making and the optimal formulation of treatment plans for AATR. METHODS: Two independent reviewers searched PubMed and Embase on June 2, 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Assessment of evidence was twofold: level of evidence (LoE) and quality of evidence (QoE). LoE was evaluated using published criteria by The Journal of Bone and Joint Surgery and the QoE by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scale. Pooled complication rates were highlighted for significance in favour of one treatment arm or no significance. RESULTS: There were 34 meta-analyses that met the eligibility criteria, with 28 studies of LoE 1, and the mean QoE was 9.8 ± 1.2. Significantly lower re-rupture rates were reported with surgical (2.3-5%) versus conservative treatment (3.9-13%), but conservative treatment was favoured in terms of lower complication rates. The re-rupture rates were not significantly different between percutaneous repair or minimally invasive surgery (MIS) compared to open repair, but MIS was favoured in terms of lower complication rates (7.5-10.4%). When comparing rehabilitation protocols following open repair (four studies), conservative treatment (nine studies), or combined (three studies), there was no significant difference in terms of re-rupture or obvious advantage in terms of lower complication rates between early versus later rehabilitation. CONCLUSION: This systematic review found that surgical treatment was significantly favoured over conservative treatment for re-rupture, but conservative treatment had lower complication rates other than re-rupture, notably for infections and sural nerve injury. Open repair had similar re-rupture rates to MIS, but lower complication rates; however, the rate of sural nerve injuries was lower in open repair. When comparing earlier versus later rehabilitation, there was no difference in re-rupture rates or obvious advantage in complications between open repair, conservative treatment, or when combined. The findings of this study will allow clinicians to effectively counsel their patients on the postoperative outcomes and complications associated with different treatment approaches for AATR. LEVEL OF EVIDENCE: IV.