Objective
To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers.
Methods
The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly.
Results
DPP-4 inhibitors can accelerated the ulcer healing. The mechanisms probably include inhibiting the expression of the matrix metalloproteinase (MMP) and restoring the balance of the wound MMP and the tissue inhibitors of MMP; promoting recruitment of endothelial progenitor cells and augmenting angiogenesis; optimizing extracellular matrix construction and the immune response to persistent hypoxia in chronic diabetes wounds, and so on. At present, clinical researches show that DPP-4 inhibitors may be considered as an adjuvant treatment for chronic diabetic foot ulcers.
Conclusion
DPP-4 inhibitors show promise in the local wound healing of chronic diabetic foot ulcers. However, more strictly designed, adequately powered, long-term follow-up, and high-quality randomized control trials are needed to further verify their efficacy and safety for chronic diabetic foot ulcers.
ObjectiveTo explore the causes and management of the complications in diabetic foot treated with tibial transverse transport (TTT). MethodsBetween September 2015 and September 2019, 196 patients with diabetic foot were treated with TTT. There were 109 males and 87 females, with an average age of 67.6 years (range, 45-86 years). According to Wagner’s classification, there were 124 cases of grade 3, 62 cases of grade 4, and 10 cases of grade 5; the course of disease was 1-12 months, with an average of 2.6 months. All patients underwent the minimally invasive tibial osteotomy. The osteotomy site was the middle and lower tibia in 62 cases and the middle and upper tibia in 134 cases. The area of osteotomy was 20 cm2 in 83 cases and 7.5 cm2 in 113 cases. The osteotomy block was moved back and forth once in 92 cases and twice in 104 cases. The complications were recorded, including secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection. ResultsAmong 196 patients, 41 cases (20.9%) had complications. Nine cases (4.6%) had secondary fracture at tibial osteotomy, among which 6 cases (9.6%) of middle and lower segment osteotomies and 3 cases (2.2%) of middle and upper segment osteotomies. The incidence between the patients with different osteotomy sites was significant (χ2=5.354, P=0.021). The area of osteotomy was 20 cm2 in 5 cases (6.0%) and 7.5 cm2 in 4 cases (3.5%). There was no significant difference in the incidence between patients with different areas (χ2=0.457, P=0.499). Skin necrosis occurred in the osteotomy area in 12 cases (6.1%), all of which were moved back and forth once. There was a significant difference in the incidence between patients who were treated with transport once and twice (P=0.001). There were 18 cases (9.1%) with pin tract infection, including 12 cases (6.1%) with mild infection and 6 cases (3.0%) with severe infection. There was no significant difference in the incidence between the patients with mild and severe infections (P=0.107).ConclusionTTT is an effective method to treat diabetic foot, but there are complications such as secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection during transport. Preoperative evaluation of indication, standardization of osteotomy mode, size and position of osteotomy block, establishment of individualized removal plan, and strengthening of pin track nursing after operation can effectively reduce complications.
ObjectiveTo summarize the research progress of tibial transverse transport in the treatment of diabetic foot.MethodsThe domestic and foreign literature on the tibial transverse transport for diabetic foot in recent years was summarized, and the advantages and disadvantages of the technique were analyzed.ResultsThe tibial transverse transport was an innovation based on Ilizarov technique. At present, the treatment of diabetic foot by the tibial transverse transport is in the initial stage and has achieved good results, but there are also problems such as ulcer recurrence and re-fracture. And its biological mechanism to promote tissue regeneration, clinical technical points (such as the selection of incision and bone window size), the technical parameters of postoperative removal program, and the postoperative effectiveness are still in dispute and exploration. More clinical studies and practices are needed in the future to develop a standard protocol for this technique.ConclusionTibial transverse transport is a hot spot for microcirculation reconstruction of lower extremity. Significant progress has been made in the treatment of diabetic foot, which provides a new direction for limb salvage treatment. However, the technique is not mature, there are still many disputes and difficulties to be further studied clearly.
ObjectiveTo investigate the effectiveness of local injection of autologous platelet-rich plasma (PRP) in treatment of diabetic foot ulcer.MethodsBetween October 2017 and October 2018, 90 diabetic foot ulcer patients who met the selection criteria were randomly divided into 3 groups: PRP injection group (group A, PRP was injected and hydrogel dressing covered the wounds), PRP covered group (group B, PRP gel and hydrogel dressing covered the wounds), and the control group (group C, hydrogel dressing covered the wounds), 30 cases in each group. There was no significant difference in gender, age, injured side, disease duration, preoperative glycosylated hemoglobin, wound size, and Wagner grading between groups (P>0.05). The frequency of treatments and hospitalization day in all groups and the total amount of PRP application in groups A and B were recorded. The wound healing condition was recorded during the treatment, and the wound healing rate was calculated at 3 months after the first debridement.ResultsThe frequency of treatments in groups A, B, and C were (10.2±0.8), (11.4±0.6), (12.5±0.5) times, respectively. The total amount of PRP application of groups A and B were (306±24) and (342±18) mL, respectively. There was no significant difference in the frequency of treatments and the total amount of PRP application between groups (P>0.05). The hospitalization days of groups A, B, and C were (40.5±1.8), (62.1±2.3), and (88.6±1.4) days, respectively, showing significant differences between groups (P<0.05). In the course of treatment, the necrosis and exudation of the wounds gradually reduced, the areas of wounds gradually reduced; and the above conditions of group A were significantly better than groups B and C, and group B was better than group C. At 3 months after the first debridement, the wound healing rates of groups A, B, and C were 93.2%±0.8%, 52.1%±1.1%, and 21.3%±1.3%, respectively, with significant differences between groups (P<0.05).ConclusionPRP can effectively promote the repair of diabetic foot ulcer. The effectiveness of local injection of PRP is superior to the local coverage.
ObjectiveTo review the research progress of adrenergic β-antagonists on wounds and diabetic chronic cutaneous ulcers healing in recent years, and to investigate its application prospect in diabetic foot ulcer (DFU).MethodsThe latest literature about the role of adrenergic β-antagonists in wounds and diabetic chronic cutaneous ulcers healing was extensively reviewed, and the mechanisms of adrenergic β-antagonists for wounds and its potential benefit for DFU were analyzed thoroughly.ResultsThe adrenergic β-antagonists can accelerate the wound healing. The possible mechanisms include accelerating re-epithelialization, promoting angiogenesis, improving neuropathy, and regulating inflammation and growth factors, etc. At present clinical research data showed that the adrenergic β-antagonists may be an adjuvant treatment for diabetic chronic cutaneous ulcers.ConclusionAdrenergic β-antagonists maybe promote the healing of wounds and diabetic chronic cutaneous ulcers. However, more long-term follow-up and high-quality randomized control studies are needed to further verify their efficacy and safety for DFU.
The 8th World International Symposium on the Diabetic Foot (ISDF) Conference which was sponsored by the International Working Group on Diabetic Foot (IWGDF) was held in the Hague between May 22nd and May 25th, 2019. The conference issued the 2019 IWGDF guidelines on the prevention and management of diabetic foot disease. The update to the 2015 edition of the guidelines involves the following 6 chapters: prevention of foot ulcers in patients with diabetes; offloading foot ulcers in patients with diabetes; diagnosis, prognosis, and management of peripheral arterial disease in patients with a foot ulcer and diabetes; diagnosis and treatment of foot infection in patients with diabetes; interventions to enhance healing of foot ulcers in patients with diabetes; classification of diabetic foot ulcers. This guideline has been changed more than the previous edition. In this paper, the guidelines will be interpreted to provide cutting-edge information for domestic diabetic foot researchers.
ObjectiveTo evaluate the effectiveness of transverse tibial bone transport in treatment of diabetic foot ulcer. MethodsBetween June 2014 and December 2017, 17 patients with diabetic foot ulcer were treated. There were 11 males and 6 females, with a median age of 57 years (range, 46-72 years). The duration of diabetes was 2.4-32.0 years (mean, 16.0 years). According to the Wagner grading criteria, 7 cases were rated as grade 2, 8 cases as grade 3, and 2 cases as grade 4. The CT angiography (CTA) showed the arterial occlusion or stenosis of varying degrees below knee joint. All cases were treated with transverse tibial bone transport. Bone transport started at 3 to 5 days after placing external fixator and lasted 14 days (1 mm per day), and then reverse transport started. The total transport time was 28-30 days. ResultsAll 17 patients were followed up 5-12 months (mean, 8.5 months). During transportation, 4 cases had screw orifice infection, and 3 cases had liquefaction and seepage. And other 15 cases ulcers healed and the healing time was 35-72 days (mean, 48 days). There were significant differences in visual analogue scale (VAS) scores, skin temperature, ankle brachial index (ABI) between before and after ulcer healed (P<0.05). The CTA showed that the collateral circulation was established. The foot ulcer of 2 cases (Wagener grade 3 in 1 case and grade 4 in 1 case) still progressed after treatment, and amputation was performed. ConclusionTransverse tibial bone transports has good effectiveness for diabetic foot ulcer.
ObjectiveTo provide a comprehensive summary of the technological evolution, clinical protocols, mechanisms of action, and current research progress of tibial transverse transport (TTT), with the goal of facilitating its standardized application in clinical practice. Methods A systematic review of both domestic and international literature on TTT for the treatment of diabetic foot was conducted. The analysis encompassed technical developments, surgical protocols, combination therapies, regenerative mechanisms, and clinical outcomes. Results Diabetic foot is one of the most severe complications of diabetes mellitus. Conventional treatments show limited efficacy in patients with advanced stages, such as Wagner grade 3/4 or Texas grade C and above. TTT, an evolution of the Ilizarov technique, promotes tissue regeneration through the “tension-stress principle”. The procedure for the treatment of diabetic foot has evolved from an open large cortical window (120 mm×20 mm) to a minimally invasive small window (50 mm×15 mm), with incision length reduced to 10 mm and simplified external fixators. A dual-incision technique (10 mm apart) is now applied at 5 cm distal to the tibial tuberosity. Bone transport typically begins 3-5 days postoperatively at a rate of 1 mm/day, incorporating the “accordion technique” (2 weeks distraction+3 days stabilization+reverse transport). Multicenter studies report a limb salvage rate of 96.1%, wound healing rate of 96.3%, and amputation rate of less than 5%. Combining TTT with vascular reconstruction and antibiotic-loaded bone cement further enhances outcomes. There are also a series of studies on the mechanism of TTT in treating diabetic foot. TTT has been shown to activate the hypoxia-inducible factor 1α-vascular endothelial growth factor/stromal cell-derived factor 1 (HIF-1α-VEGF/SDF-1) signaling pathway to facilitate microcirculatory reconstruction; mobilize immune cells and rebalance macrophage polarization, thereby improving the inflammatory microenvironment; recruit stem cells via chemotaxis to accelerate re-epithelialization; and promote the release of regenerative small extracellular vesicles. Conclusion TTT demonstrates promising clinical potential in the treatment of diabetic foot, particularly in improving limb perfusion and promoting tissue repair. However, the underlying mechanisms have not been fully elucidated. Further in-depth investigations are required. In addition, the current lack of high-quality randomized controlled trials highlights the urgent need for rigorously designed randomized controlled trial to validate the efficacy and safety of this technique.
ObjectiveTo investigate the effect of transverse tibial bone transport on the expression of angiogenesis-related growth factors in the serum of diabetic foot patients.MethodsBetween January 2018 and December 2018, 10 patients who suffered from diabetes mellitus accompanied with Wagner stage 4 diabetic foot underwent transverse tibial bone transport. There were 5 males and 5 females with an average age of 59.2 years (range, 51-70 years). The duration of diabetes was 2-60 months, with an average of 24.2 months. The duration of diabetic foot was 30-120 days, with an average of 54.1 days. Peripheral venous blood was taken at 1 day before operation and at 1, 4, 11, 18, 28, and 35 days after operation. The serum was centrifuged and subjected to ELISA test to detect the expression levels of serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF).ResultsThe levels of serum VEGF, bFGF, and EGF increased rapidly at 11 days after operation, and the expression levels of the factors at 11, 18, 28, and 35 days were significantly higher than those before operation (P<0.05). The expression level of PDGF increased suddenly at 18 days after operation, and the expression level of PDGF at 18, 28, and 35 days was significantly higher than that before operation (P<0.05).ConclusionTransverse tibial bone transport for the treatment of diabetic foot can significantly increase the expression of serum angiogenesis-related growth factors in early stage, which may be the mechanism of promoting the healing of diabetic foot wounds.
Tibial transverse transport (TTT) was firstly applied to treat thromboangiitis obliterans successfully by Professor QU Long in China in 2000. Based on this, the team of Professor HUA Qikai in the First Affiliated Hospital of Guangxi Medical University applied this technique to treat diabetic foot since 2013, and until now, more than 500 patients underwent this treatment with excellent effectiveness including a salvage rate as high as 96.1%. Our team also improved this technique in many aspects, and developed a TTT-based classification system and treatment for diabetic foot. We also explored the underlying mechanism of TTT treatment using imaging, histology, and other basic research methods. To further promote the application of this technique in clinic, we reported the findings from our cases and reviewed our previous findings in this study.
