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.
Objective To provide a clinical basis for the prevention of diabetic foot ulcers by analyzing the clinical data and prognosis of high-risk diabetic foot patients. Methods A retrospective analysis was performed on high-risk diabetic foot patients who were hospitalized in West China Hospital of Sichuan University between January 1, 2012 and December 31, 2018. Patients were divided into high-risk group and low-risk group according to whether they hada history of foot ulcer or amputation. The clinical characteristics of the two groups of patients were compared. The patients were followed up from hospital discharge to January 31, 2021, and their survival and ulcer recurrence or new-onset status were evaluated. Results Finally, 123 patients were included, including 29 patients in the high-risk group and 94 patients in the low-risk group. There was no statistical difference in the duration of diabetes, smoking history, drinking history, education level, proportion of receiving regular treatment, proportion of regular blood glucose monitoring, body mass index, proportion of diabetic peripheral neuropathy, callus, foot deformity, diabetic nephropathy, diabetic retinopathy, diabetic cardiac autonomic neuropathy, diabetic gastrointestinal autonomic neuropathy, hypertension, coronary heart disease and laboratory test results between the two groups (P>0.05). The proportion of women (51.7% vs. 29.8%), age [(69.8±10.3) vs. (64.4±11.3) years], proportion of lower extremity arterial disease (62.1% vs. 34.4%), proportion of hyperuricemia (27.6% vs. 10.6%) in the high-risk group were higher than the low-risk group (P<0.05). After follow-up (67±20) months, 25.8% of the patients had ulcer recurrence or new onset, and 24.2% of the patients died. The most common cause of death was diabetes complications (43.8%). The overall 1-, 3-, and 5-year cumulative mortality rates of the patients were 4.5%, 12.7%, and 20.6%, respectively. The 3- and 5-year recurrence or new ulcer rates were 8.3% and 18.2%, respectively. The 5-year recurrence or new ulcer rates in the low-risk group and high-risk group were 10.3% and 40.3%, respectively, and there was a difference in ulcer recurrence between the two groups (P=0.004). Conclusions Compared with high-risk diabetic foot patients without ulcer or amputation, patients with a history of ulcer or amputation have higher rates of lower extremity arterial disease and hyperuricemia. Patients with a history of ulceration or amputation have a higher risk of recurrent or new ulceration than patients without a history of ulceration or amputation.
ObjectiveTo investigate the effectiveness of modified tibial transverse bone transport technique combined with vancomycin calcium phosphate bone cement local filling and covering in the treatment of diabetic foot (DF). MethodsThe clinical data of 22 DF patients treated with modified tibial transverse bone transport technique combined with vancomycin calcium phosphate bone cement local filling and covering between October 2019 and December 2021 were retrospectively analyzed. There were 13 males and 9 females with an average age of 61.3 years (range, 41-74 years). The duration of diabetes mellitus was 8-30 years, with an average of 12.5 years, and the duration of DF was 10-42 days, with an average of 28.2 days. There were 2 cases of grade 3 and 20 cases of grade 4 according to Wagner classification. CT angiography was performed on both lower extremities of the patients, and the blood vessels of the affected extremities were narrowed to varying degrees and the blood supply was poor. The preoperative skin temperature of affected foot was (28.27±0.91)°C, the ankle brachial index (ABI) was 0.42±0.11, and the visual analogue scale (VAS) score was 7.7±0.6. Preoperative size of DF ulcer ranged from 2.5 cm×2.0 cm to 3.5 cm×3.0 cm. The skin temperature of affected foot, ABI, VAS score, and skin wound healing of the affected foot were recorded and compared between before operation and at 3 months after operation. ResultsAll patients were followed up 3-18 months, with an average of 10.5 months. The infection of 1 patient with Wagner grade 4 did not improve significantly after operation, and there was a trend of further deterioration, and the amputation of the left leg was finally performed at 22 days after operation.The remaining 21 patients recovered well after operation, the external fixator was removed at 1 month after operation, the wound healed at 3 months after operation, and there was no recurrence of ulcer in situ or other sites during follow-up. At 3 months after operation, the skin temperature of affected foot was (31.76±0.34)°C, the ABI was 0.94±0.08, and the VAS score was 2.1±0.3, which significantly improved when compared with those before operation (t=25.060, P<0.001; t=32.412, P<0.001; t=–51.746, P<0.001). ConclusionModified tibial transverse bone transport technique combined with vancomycin calcium phosphate bone cement local filling and covering for DF patients can effectively improve the blood supply of the affected limb, promote wound healing, and improve effectiveness.
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.
Objective To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. Methods The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). Results All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation (P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation (P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation (P<0.05), while it was higher at other time points than that before operation, but the difference was not significant (P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation (P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation (P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation (P>0.05). Conclusion TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
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.
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.