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'.

Similar outcomes following scarf-Akin osteotomy compared to scarf-alone osteotomy for the treatment of hallux valgus: A systematic review and meta-analysis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to compare the clinical and radiographic outcomes between patients undergoing scarf osteotomy and scarf-Akin osteotomy for the management of hallux valgus deformity. METHODS: A systematic review of the MEDLINE, EMBASE and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting clinical data following scarf osteotomy and scarf-Akin osteotomy for the treatment of hallux valgus were included and assessed. The level and quality of evidence of the included studies were also evaluated. RESULTS: Four studies were included. In total, 388 patients (408 toes) underwent scarf osteotomy alone and 287 patients (295 toes) underwent scarf-Akin osteotomy for the treatment of hallux valgus deformity. There was no difference in postoperative American orthopedic foot and ankle society scores (p = 0.7828), visual analog scale scores (p = 0.4558), hallux valgus angle (p = 0.5116), intermetatarsal angle (p = 0.4830), proximal to distal phalangeal articular angle (p = 0.2411) between the scarf alone cohort and the scarf-Akin cohort. Similarly, there was no difference in complication rates (p = 0.6881) nor secondary surgical procedure rates (p = 0.3678) between the 2 cohorts. Finally, there was a higher recurrence rate in the scarf-alone cohort (11.4%) compared to the scarf-Akin cohort (5.7%), but this was not statistically significant (p = 0.4414). CONCLUSION: This systematic review demonstrates lower recurrence rates following scarf-Akin osteotomy compared to scarf osteotomy alone for the treatment of hallux valgus deformity. No difference in complication rates were noted between the 2 cohorts. Our review demonstrates that both the scarf osteotomy and the scarf-Akin osteotomy may be effective and safe procedures, however, the scarf-Akin osteotomy may provide more long-term benefit in the setting of moderate to severe hallux valgus.

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.

Associations between the Trauma Memory Quality Questionnaire and posttraumatic stress symptoms in youth: A systematic review and meta-analysis .

Cognitive models of posttraumatic stress disorder (PTSD) propose that trauma memory characteristics are implicated in the etiology of the disorder. Empirical support for cognitive models in youth is necessary to ensure psychological interventions are based on appropriate theory. This meta-analysis was conducted to quantitatively investigate the strength of the associations between self-reported trauma memory characteristics (e.g., sensory and temporal features), measured using the Trauma Memory Quality Questionnaire (TMQQ), and posttraumatic stress symptoms (PTSS) in children and adolescents. PsycINFO, MEDLINE, CINAHL, PTSDPubs, and ProQuest Dissertations and Theses Global were searched for relevant literature. In total, 11 studies (N = 1,270 participants) met the inclusion criteria for the random-effects meta-analysis. A large effect size was observed for the association between trauma memory characteristics and PTSS, r = .51, 95% CI [.44, .58], and was maintained in subgroup analyses of the prospective association between trauma memory characteristics and later PTSS (k = 5, n = 6 28), r = .51, 95% CI [.42, .59]. A slightly larger effect size was observed in subgroup analyses of the cross-sectional association between trauma memory characteristics and concurrent PTSS (k = 11, N = 1,270), r = .62, 95% CI [.53, .70]. Sensitivity analyses on study quality, TMQQ alteration, chronic trauma exposure, geographical location, and PTSS measure supported the robustness of these results. These findings provide empirical support for the role of trauma memory characteristics in PTSS, congruent with cognitive models, suggesting this theoretical framework is appropriate for youth populations. Limitations and recommendations for future research are discussed.