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.
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 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.
ObjectiveTo study the effectiveness of tibial transverse transport combined with the antibiotics embedded bone cement in the treatment of chronic infection of foot and ankle with lower extremity ischemic diseases.MethodsA retrospective analysis was performed on 28 patients with ischemic diseases of lower extremities associated with chronic foot and ankle infection who were treated with tibial transverse transport combined with antibiotic bone cement between August 2015 and October 2019. There were 22 males and 6 females, with an average age of 65.6 years (range, 41-86 years). There were 25 cases of diabetic foot, 2 cases of arteriosclerosis obliterans, and 1 case of thromboangiitis obliterans. The course of infection ranged from 1 to 27 years, with an average of 14.9 years. The healing condition and time of foot and ankle in all patients were recorded and compared, and the Wagner grading and WIFi (W: lower extremity wound classification; I: ischemic classification; Fi: foot infection classification) grading were compared before and at last follow-up.ResultsThe wound surface of 1 diabetic foot patient improved at 111 days after operation, without purulent secretion, and lost follow-up. The remaining 27 cases were followed up 5 to 21 months (mean, 8.4 months). There was no necrosis in the tibial osteotomy incision and the local flap. After operation, 21 cases showed needle reaction of external fixator, but the needle infection gradually improved after the corresponding treatment. Among the 24 patients with diabetic foot, 1 died of multiple organ failure due to pulmonary infection. Acute lower extremity vascular embolism occurred in 1 case, and the foot was amputated due to acute gangrene. In the remaining 22 cases, the wound healing time of foot and ankle was 2.5-11.0 months (mean, 4.6 months). At last follow-up, Wagner grading and WIFi grading of the patients were significantly improved when compared with those before operation (P<0.05). One patient with thromboangiitis obliterans had foot and ankle healing at 6 months after operation. Two patients with lower extremity arteriosclerosis obliterans had foot and ankle healing at 16 and 18 months after operation, respectively.ConclusionTibial transverse transport combined with the antibiotics embedded bone cement is effective in treating chronic infection of foot and ankle with lower extremity ischemic diseases.
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.
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.
Ilizarov first reported the tibial transverse transport (TTT) for limb regeneration and functional reconstruction. The law of tension-stress could activate and enhance the regenerative potentials of living tissues, leading to growth or regeneration of muscles, fascia, blood vessels, and nerves simultaneously. Ilizarov discovered the phenomenon of rich vascular network formation during distraction osteogenesis process, but he did not apply this technique purposely to reconstruct microcirculation. Chinese orthopedic surgeons first used the TTT to treat lower extremity vascular lesions and diabetic foot ulcers. At present, some small sample clinical studies showed that the TTT could reconstruct microvascular network in the lower limbs of diabetic foot and promote the healing of foot ulcers. The use of TTT could significantly reduce the overall risk of diabetic foot complication especially the amputation risk. This expert consensus is initiated by the Chinese Association of Orthopaedic Surgeons (CAOS), Taskforce Group of Tibial Cortex Transverse Transport Technique for the Treatment of Diabetic Foot Ulcers. This expert consensus provides clear recommendations for indications, contraindications, principles for surgical procedures, preoperative and postoperative management, which maximize the success rate for TTT surgery in treatment of severe diabetic foot ulcers.
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.
ObjectiveTo evaluate the effectiveness of Ilizarov technique-based transverse tibial bone transport on the treatment of severe diabetic foot ulcer (Wagner grades 3 to 5) complicated with systemic inflammatory response syndrome (SIRS).MethodsBetween August 2014 and December 2017, 33 patients with severe diabetic foot and SIRS were treated with Ilizarov technique-based transverse tibial bone transport. There were 27 males and 6 females, with a mean age of 60.6 years (range, 34-79 years). All of them suffered from type 2 diabetes mellitus. The duration of diabetes was 1-28 years (mean, 10 years) and the duration of diabetic foot was 1-12 months (mean, 2.7 months). According to Wagner classification, there were 8 cases in grade 3, 23 cases in grade 4, and 2 cases in grade 5. The wound healing condition was observed after operation, and the limb salvage rate was calculated. The changes in body temperature, heart rate, respiratory rate, white blood cell count, erythrocyte sedimentation rate, and C-reactive protein concentration were assessed. The skin temperature of the dorsum of the foot was measured, and the visual analogue scale (VAS) score was used to evaluate the improvement of foot pain.ResultsAll 33 patients were followed up 3-30 months (mean, 14.1 months). All ulcers healed and the healing time was 3-12 months (mean, 5.3 months); the limb salvage rate was 100%. Postoperative body temperature, heart rate, respiratory rate, white blood cell count, erythrocyte sedimentation rate, and C-reactive protein concentration were significantly lower than those before operation (P<0.05). The skin temperature of the dorsum of the foot was (32.64±2.17)℃ at 1 month after operation, which was significantly improved when compared with preoperative value [(31.28±1.99)℃] (t=0.05, P=0.00); but there was no significant difference in skin temperature compared with healthy side [(32.46±2.10)℃] (t=2.04, P=0.41). The VAS score was 2.4±0.7 at 1 month after operation, which was significantly improved when compared with preoperative score (4.3±0.8) (t=3.10, P=0.00).ConclusionIlizarov technique-based transverse tibial bone transport is an effective way to treat severe diabetic foot complicated with SIRS. It can promote foot ulcer healing and avoid amputations.