Project description:BackgroundDiabetic foot ulcer (DFU) is frequently difficult to heal and finally leads to amputation, resulting in high mortality rate in diabetic patients. To date, effective and optimal therapies are still lacking. This study aims to investigate the efficacy of integrated surgical wound treatment (ISWT) mode on diabetic foot wound.MethodsFrom January 2021 to December 2021, 13 diabetic foot patients with Wagner grade 3 to 4 were treated with ISWT mode, which combined TTT technique with debridement, induced membrane technique, vacuum sealing drainage (VSD) technique and skin grafting technique. The time of wound healing, the skin temperature at midpoint of dorsum of affected foot (T), visual analogue scale (VAS) score and ankle-brachial index (ABI) was measured before and after surgery. CTA examination of the lower extremity arteries was performed at the end of the cortex transport to evaluate the small arteriolar formation of the lower extremity. The complications occurred in each patient were recorded.Results13 patients with age ranging from 45 to 66 years were followed up for 3 to 13 months. All patients healed completely without amputation being performed, no serious complications were found except for one case of nail channel infection. The mean healing time was 25.8 ± 7.8 days, with a range of 17 to 39 days. The mean time of carrying external fixation scaffolds and resuming walking was 71.8 ± 10.0 and 30.8 ± 9.1 days, with a range of 56 to 91 days and 18 to 45 days, respectively. The skin temperature at midpoint of dorsum of affected foot (T), VAS and ABI was all improved significantly at 3 months after surgery. Furthermore, CTA examination showed an increase in the number of lower extremity arteries and a thickening in the size of small arteriolar compared with those of pre-operative, and the collateral circulation of lower extremity was established and interweaved into a network.ConclusionIntegrated surgical treatment of diabetic foot wound can achieve satisfactory clinical results.
Project description:BackgroundTibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT.MethodsWe established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes.ResultsThe TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity.ConclusionOur innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.
Project description:Background Management of recalcitrant diabetic foot ulcer (DFU) remains difficult. Distraction osteogenesis mediates new bone formation and angiogenesis in the bone itself and the surrounding tissues. Recently it was reported that tibial cortex transverse transport (TTT) was associated with neovascularization and increased perfusion at the foot in patients with recalcitrant DFUs and facilitated healing and limb salvage. However, the findings were from several single-center studies with relatively small populations, which need to be confirmed in multicenter cohort studies with relatively large populations. Furthermore, the effect of this technique on patient's health-related quality of life is still unclear. Methods We treated patients with recalcitrant (University of Texas wound grading system 2-C to 3-D and not responding to prior routine conservative and surgical treatments for at least 8 weeks) DFUs from seven centers using TTT (a 5 cm × 1.5 cm corticotomy followed by 4 weeks of medial and lateral distraction) between July 2016 and June 2019. We analyzed ulcer healing, major amputation, recurrence, health-related quality of life (physical and mental component summary scores), and complications in the 2-year follow-up. Foot arterial and perfusion changes were evaluated using computed tomography angiography and perfusion imaging 12 weeks postoperatively. Results A total of 1175 patients were enrolled. Patients who died (85, 7.2%) or lost to follow-up (18, 1.7%) were excluded, leaving 1072 patients for evaluation. Most of the patients were male (752, 70.1%) and with a mean age of 60.4 ± 9.1 years. The mean ulcer size was 41.0 ± 8.5 cm2 and 187 (16.6%) ulcers extended above the ankle. During the follow-up, 1019 (94.9%) patients healed in a mean time of 12.4 ± 5.6 weeks, 53 (4.9%) had major amputations, and 33 (3.1%) experienced recurrences. Compared to preoperatively, the patients had higher physical (26.2 ± 8.3 versus 41.3 ± 10.6, p = 0.008) and mental (33.6 ± 10.7 versus 45.4 ± 11.3, p = 0.031) component summary scores at the 2-year follow-up. Closed tibial fracture at the corticotomy site was found in 8 (0.7%) patients and was treated using external fixation and healed uneventfully. There were 23 (2.1%) patients who had pin site infections and were treated successfully with dressing changes. Compared to preoperatively, the patients had more small arteries and higher foot blood flow (8.1 ± 2.2 versus 28.3 ± 3.9 ml/100 g/min, p = 0.003) and volume (1.5 ± 0.3 versus 2.7 ± 0.4 ml/100 g, p = 0.037) 12 weeks postoperatively. Conclusion TTT promotes healing, limb salvage, and health-related quality of life in patients with recalcitrant DFUs as demonstrated in this multicenter cohort study. The surgical procedure was simple and straightforward and the complications were few and minor. The effect of this technique was associated with neovascularization and improved perfusion at the foot mediated by the cortex distraction. The findings are required to confirm in randomized controlled trials. The Translational Potential of this Article: TTT can be used as an effective treatment in patients with recalcitrant DFUs. The mechanism is associated with neovascularization and consequently increased perfusion in the foot after operation.
Project description:To investigate mRNA Expression profile and associated signaling pathways in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction. Methods: Tissue samples were collected from the wound edge before and after the surgery. After reference genome transcriptome sequencing and subsequent bioinformatics analysis, the differentially expressed genes and related pathways were explored, and functional analysis of important genes and pathways was conducted.
Project description:IntroductionDiabetic foot (DF) is one of the most serious chronic complications of diabetes. In recent years, the use of the tibial cortex transverse transport (TTT) technique has enabled great progress in microcirculation reconstruction and achievement of good outcomes in DF treatment. The objective of this systematic review protocol is to evaluate the efficacy and safety of TTT for DF.MethodsLiterature search was conducted using the Cochrane Library, Embase, PubMed, Web of Science, China Science Technology Journal Database (VIP), Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Service System (SinoMed), and Chinese Biomedical Literature Service System (CBM) from inception until March, 1st 2022. In addition, our reviewers will retrieve dissertations, grey literature, systematic reviews, and reference lists of the relevant studies. Randomized controlled trials (RCTs) which compared the TTT for DF with conventional treatment will be included. Our reviewers will perform subgroup analysis, sensitivity analysis, and publication bias analysis to evaluate the heterogeneity and robustness. RevMan 5.3 software and Stata V.16.0 software will be used to analyze the available data.Ethics and disseminationEthical approval was not required because this protocol neither collected private information, nor involved animal experiments. The research was disseminated by academic journals or related meetings.Prospero registration numberCRD42021279717.
Project description:The antagonism of CXC-chemokine receptor 4 (CXCR4) with AMD3100 improves cardiac performance after myocardial infarction by augmenting the recruitment of endothelial progenitor cells (EPCs) from the bone marrow to the regenerating vasculature. We investigated whether AMD3100 may accelerate diabetes-impaired wound healing through a similar mechanism. Skin wounds were made on the backs of leptin receptor-deficient mice and treated with AMD3100 or saline. Fourteen days after treatment, wound closure was significantly more complete in AMD3100-treated mice (AMD3100: 87.0 ± 2.6%, saline: 33.1 ± 1.8%; P<0.0001) and was accompanied by greater collagen fiber formation, capillary density, smooth muscle-containing vessel density, and monocyte/macrophage infiltration. On day 7 after treatment, AMD3100 was associated with higher circulating EPC and macrophage counts, and with significantly upregulated mRNA levels of stromal cell-derived factor 1 and platelet-derived growth factor B in the wound bed. AMD3100 also promoted macrophage proliferation and phagocytosis and the migration and proliferation of diabetic mouse primary dermal fibroblasts and 3T3 fibroblasts, which express very little CXCR4. In conclusion, a single topical application of AMD3100 promoted wound healing in diabetic mice by increasing cytokine production, mobilizing bone marrow EPCs, and enhancing the activity of fibroblasts and monocytes/macrophages, thereby increasing both angiogenesis and vasculogenesis. Not all of the AMD3100-mediated effects evolved through CXCR4 antagonism.
Project description:Diabetes produces a chronic inflammatory state that contributes to the development of vascular disease and impaired wound healing. Despite the known individual and societal impacts of diabetic ulcers, there are limited therapies effective at improving healing. Stromal cell-derived factor 1α (SDF-1α) is a CXC chemokine that functions via activation of the CXC chemokine receptor type 4 (CXCR4) receptor to recruit hematopoietic cells to locations of tissue injury and promote tissue repair. The expression of SDF-1α is reduced in diabetic wounds, suggesting a potential contribution to wound healing impairment and presenting the CXCR4 receptor as a target for therapeutic investigations. We developed a high-throughput β-arrestin recruitment assay and conducted structure-activity relationship (SAR) studies to screen compounds for utility as CXCR4 agonists. We identified CXCR4 agonist UCUF-728 from our studies and further validated its activity in vitro in diabetic fibroblasts. UCUF-728 reduced overexpression of miRNA-15b and miRNA-29a, negative regulators of angiogenesis and type I collagen production, respectively, in diabetic fibroblasts. In vivo, UCUF-728 reduced the wound closure time by 36% and increased the evidence of angiogenesis in diabetic mice. Together, this work demonstrates the clinical potential of small molecule CXCR4 agonists as novel therapies for pathologic wound healing in diabetes.
Project description:BackgroundThe clinical treatment of patients with severe diabetic foot (DF) is difficult. Recently, the First Affiliated Hospital of Guangxi Medical University began to apply tibial transverse transport (TTT) in patients with DF. This treatment has achieved significant effects, but its mechanism of action is unclear. Recently, microcirculation and the pathogenesis of diabetes have become the foci of research in this field. The evaluation of the possible mechanism of microcirculation reconstruction requires relevant indicators. The aim of this study was to investigate the value of computed tomography perfusion in evaluations of the curative effects of TTT and establish corresponding quantitative evaluation indicators.MethodsTwelve patients with DF treated with TTT were recruited as the research participants. All diabetic feet were divided into the transport foot (TF) group and nontransport foot (NTF) group according to whether the patients underwent TTT. All patients underwent CT shuttle scanning preoperatively and 8 weeks after surgery. The shuttle scan data were transferred to Siemens VPCT body software and postprocessed with Customized Tumor2. We chose the TF posterior tibial artery from a distance of approximately 15 cm to the bifurcation of the plantar medial artery and the lateral plantar artery as the input artery. We selected the centre of the bilateral medial plantar muscle group on the coronal and axial regions of interest. We applied a deconvolution approach to obtain data from both sides of the plantar tissue perfusion. Skin temperature (ST) detection was performed with an ST gun to measure the average ST values in the dorsal and plantar areas, the first and fifth heads of the phalanges, and the medial and lateral malleolus points of both feet of patients with DF preoperatively and 8 weeks after surgery.ResultsThe preoperative and postoperative ST values of the patients in the TF group were 30.73 ± 1.86 °C and 32.22 ± 1.51 °C, respectively. The preoperative and postoperative ST values for the patients in the NTF group were 30.93 ± 2.65 °C and 32.07 ± 2.09 °C, respectively. There were significant differences in the preoperative and postoperative data between the TF (P = 0.001) and NTF (P = 0.013) groups. In the patients with DF who underwent TTT, there were both preoperative and postoperative differences inside the medial plantar muscle group in the relative blood volume (rBV) value and relative mean transit time (rMTT) (P = 0.027, P = 0.026, respectively). The postoperative BV in the NTF group was increased compared with the preoperative BV (P = 0.006).ConclusionThere were significant differences in relative BV, relative mean transit time, and ST between the two groups before and after surgery, and the postoperative BV in the NTF group and ST values in the two groups were increased compared with the preoperative values. The BV in the NTF group and the ST values in the two groups were effective indicators in evaluating the changes between preoperative and postoperative perfusion. These results indicate that TTT could increase plantar tissue perfusion as assessed by BV and ST; this increase was among the reasons for the surface healing of severe DF ulcers.Translational potential of this articlePreoperative CT perfusion evaluation can provide relevant information of blood vessels and microcirculation for clinical operation, and postoperative CT perfusion evaluation can provide postoperative efficacy evaluation for clinical operation. All patients received information about the study and signed a specific informed consent. Approval for this study was granted by the regional ethics committee [Regional Ethics Committee of the First Affiliated Hospital of Guangxi Medical University, China [(2018-(KY-E-069].