John McDonald

Background Ankle fractures are among the most prevalent injuries in the general population, and the timing of surgical fixation may influence postoperative wound complications. This systematic review and meta-analysis investigated the impact of surgical timing on postoperative wound complications, specifically investigating the significance of a 24-hour cutoff point. Materials and methods The comprehensive literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using PubMed, Embase, Web of Science, and Cochrane databases. Research evaluating and comparing clinical outcomes following ankle fracture treatment between early versus delayed surgical fixation groups, specifically using a 24-hour cutoff point, were reviewed. Evaluated data for the meta-analysis included total wound complications: divided into major and minor wound complications, length of stay, and other complications such as fixation failure. Results A total of eight studies were included in this systematic review and meta-analysis. In total, 1,183 patients were analyzed, with 572 in the early fixation group and 611 in the delayed fixation group. Compared to the delayed fixation group, the early fixation group significantly reduced total wound complications and length of stay, with a relative ratio of 0.37 (95% CI, 0.22 to 0.60) and − 0.88 (95% CI, -1.07 to -0.70), respectively. When analyzed as separate groups of major and minor wound complications, there was a trend showing lower rate of major and minor wound complication in the early fixation group than the delayed fixation group, but without reaching statistically significant differences. Conclusions Based on our review, early surgical intervention within the first 24 h may be considered to minimize the risk of postoperative wound complications and reduce the length of stay in ankle fractures. Level of evidence Level 3.

Background: Current literature lacks comprehensive information comparing primary tibiotalocalcaneal (TTC) hindfoot nailing and open reduction internal fixation (ORIF) in the ankle fractures in the elderly population. This systematic review and meta-analysis was conducted to evaluate and compare the clinical outcomes of 2 surgical techniques, primary TTC nailing and ORIF, for ankle fractures in the elderly. Methods: Our comprehensive literature review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and used databases including PubMed, Embase, Web of Science, and the Cochrane Library. Data investigated in this study included total infection, deep infection, superficial infection, hardware problems such as painful hardware, and hardware protrusion/pullout, nonunion/delayed union, reoperation, length of stay, and return to preoperative mobility level. Results: Total 5 studies were included in this study. In aggregate, 127 patients (42.9%) underwent TTC nailing, whereas 169/296 patients (57.1%) underwent ORIF. A lower rate of superficial infection was reported for the TTC nailing group: 2.1% (2/95) in TTC nailing vs 10.2% (14/137) in ORIF, with a relative ratio of 0.26 (95% CI, 0.08-0.85). The other outcome measures were not significantly different between groups. Conclusion: Based on our review of these studies that reported mostly early follow-up data, it appears that primary TTC nailing may be a viable alternative to ORIF for ankle fracture fixation in the elderly population. However, these findings should be interpreted cautiously because of heterogeneity across the included studies.

Introduction There is still a lack of information on the role of Tranexamic acid (TXA) in total ankle arthroplasty (TAA). The purpose of this study is to comprehensively review, consolidate, and analyze findings from existing research on the effectiveness and safety of TXA in TAA. Materials and methods The comprehensive literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using PubMed, Embase, Web of Science, and Cochrane databases, for original, English-language studies investigating the efficacy and safety of TXA in TAA, through February 2023. Evaluated data for the meta-analysis included estimated blood loss (EBL), change in perioperative hemoglobin, need for transfusion, and complications including DVT/PE, and wound complications. Results A total of nine studies were included in this study. In total, 450 TAA were included, with 244 receiving TXA (54.2%) and 206 not receiving TXA (45.8%). TXA in TAA significantly decreased EBL. A significantly lower rate of wound complications in the TXA group with the relative risk (RR) of 0.51. We classified wound complications into wound infection and delayed wound healing/dehiscence. A significant decrease in the rate of wound infection and a tendency showing a decrease in the rate of delayed wound healing/dehiscence in the TXA group were noted: the RR of 0.29, and 0.63, respectively. TXA did not increase the incidence of DVT/PE following TAA. Conclusions In conclusion, the utilization of TXA during TAA demonstrated a statistically significant reduction in EBL and relative risk for wound complications. However, further RCTs with larger sample sizes will be necessary to establish a more robust conclusion regarding the efficacy and safety of TXA in TAA. Level of evidence Level III, systematic review and meta-analysis.

Background: AAV-based gene therapy is an attractive approach to treat Duchenne muscular dystrophy (DMD) patients. Although the long-term consequences of a gene therapy approach for DMD are unknown, there is evidence in both DMD patients and animal models that dystrophin replacement by gene therapy leads to an anti-dystrophin immune response that is likely to limit the long-term use of these therapeutic strategies. Objective: Our objective is to test whether the anti-dystrophin immune response is affected by immunomodulatory drugs in mdx mice after rAAV gene therapy. Methods: mdx mice were treated with rAAV microdystrophin alone or in combination with immunomodulatory drugs. Dystrophin expression in skeletal muscle was assessed by mass spectrometry. Immune responses were assessed by immunophenotyping, western blot for anti-dystrophin antibodies and flow cytometry assays for antigen-specific T-cell cytokine expression. The impact on muscle was measured by grip strength assessment, in vivo torque, optical imaging for inflammation and H&E staining of sections to assess muscle damage. Results: We found that AAV-9-microdystrophin gene therapy induced expression of microdystrophin, anti-dystrophin antibodies, and T-cell cytokine responses. Immunomodulatory treatments, rituximab and VBP6 completely abrogated the anti-dystrophin antibody response. Prednisolone, CTLA4-Ig, and eplerenone showed variable efficacy in blocking the anti-dystrophin immune response. In contrast, none of the drugs completely abrogated the antigen specific IFN-γ response. AAV-microdystrophin treatment significantly reduced inflammation in both forelimbs and hindlimbs, and the addition of prednisolone and VBP6 further reduced muscle inflammation. Treatment with immunomodulatory drugs, except eplerenone, enhanced the beneficial effects of AAV-microdystrophin therapy in terms of force generation. Conclusions: Our data suggest that AAV-microdystrophin treatment results in anti-dystrophin antibody and T-cell responses, and immunomodulatory treatments have variable efficacy on these responses.

Spinal cord injury (SCI) results in a series of severe dysfunction of sensory and motor functions, while the molecular mechanisms that cause these dysfunctions remain elusive. Using proteomics technology, Western blot (WB), and immunohistochemistry (IHC), we found endoplasmic reticulum protein 29 (ERp29) was substantially downregulated in the motor cortex 3 days postoperation (dpo) after spinal cord transection (SCT, T10) followed by a gradual recovery 28 dpo. IHC showed that ERp29 is expressed in cortical neurons. In order to investigate the role of ERp29 in axotomized cortical neurons, we developed an in vitro axotomy injury model. ERp29 overexpression in cortical neurons after axotomy protected them from apoptosis; prevented the reduction of the number of neurons, and prevented reduction of neurite length. Moreover, we found that ERp29 overexpression increased neuronal regeneration assessed by neurite number and length. Furthermore, overexpression of ERp29 in cortical neurons after axotomy increased expression of Erk-1 and PI3K while decreasing the expression of caspase-3 expression. The present data therefore provides evidence to address the role of ERp29 in axotomized cortical neurons and identifies new therapeutic targets for the treatment of SCI.

Transforming growth factor β1 (TGF-β1) is a multi-functional cytokine implicated in many aspects of mammalian wound healing and scar tissue formation. However, few experiments have so far addressed the potential biological effects of TGF-β1 in the nervous system after injury, in addition to the immune system. In the present study, expressional silencing TGF-β1 was achieved by selecting predesigning hairpins targeting mouse TGF-β1 genes. Four homozygous transgenic offspring were generated and designed as Founder 90, Founder 12, Founder 41 and Founder 46. The down-regulated rates of TGF-β1 in different transgenic mice were also determined. To investigate the potential roles of TGF-β1, we observed changes in the neurological behavior of TGF-β1-knockdown (TGF-β1-kd) mice after spinal cord transection (SCT). Moreover, mRNA levels of inflammatory cytokines, including IL-1, IL-6, IL-10, NF-κB and TNF, were also detected in nucleate cells from blood by real-time PCR. Consequently, different TGF-β1 expressions were detected in multiple tissues, and protein levels of TGF-β1 decreased at different rates relative to that of wild type (WT) ones. The levels of TGF-β1 proteins in TGF-β1-kd mice decreased at most by 57% in Founder 90, which showed a significant recovery in Basso, Beattie, Bresnahan (BBB) scores after SCT compared with that of WT. However, expressions of immune relative genes showed no dramatic difference compared with WT ones. This study is the first to generate TGF-β1 down regulated mice and determine the possible roles of TGF-β1 in vivo in different conditions.