Patient Selection
From July 2012 to December 2016, 148 type 2 diabetic patients underwent TMA in our diabetic foot unit. All the patients had forefoot gangrene with more than one toe involved and 30 of them had undergone toectomy but failed to heal. One hundred two patients who were not candidates for revascularization because of severe comorbidity, nonambulatory status, inadequate outflow vessels, patients’ refusal or other conditions not accepted by vascular surgeons were selected.
As this was a follow-up observational study, and there was no intervention during the procedure, it was not registered. All procedures performed were in accordance with the ethical standards of the institutional review board of Ruijin Hospital affiliated with the Shanghai Jiao Tong University School of Medicine and the 1964 Helsinki Declaration and its later amendments. Informed consent was obtained from each enrolled patient.
Recorded Demographic, Clinical Variables and Assessed Comorbidities
All the enrolled patients were evaluated within 24 h after being admitted to identify medical conditions, which included: duration, therapy of diabetes, duration of foot ulcer, a past history of hypertension, coronary heart disease, stroke or other chronic diseases. A careful overall physical examination was finished and recorded by an experienced physician. The clinical laboratory variables included glycated hemoglobin (HbA1c) level on admission, serum albumin, hemoglobin, serum creatinine, serum lipids, leukocyte count and 24-h micro-albuminuria quantification. The eGFR value was calculated using the MDRD equation for Chinese adults [16].
The diagnosis of comorbidities was based on a clear history record or through the following methods. PAD was diagnosed if lower limb artery occlusions were spotted by Doppler ultrasound and/or ankle-brachial pressure index (ABI) < 0.9 with an automatic arteriosclerosis detector (Omron, BP-203RPEIII, Japan) [17]. Degree of severity of PAD was subdivided according to measured ABI and classified as mild (ABI, 0.7–0.9), moderate (ABI, 0.41–0.69) or severe (ABI, ≤ 0.4). Diabetic peripheral neuropathy (DPN) was diagnosed by a combination of neuropathic symptoms and signs with abnormal result of the 10-g monofilament test or vibration test using a 128-Hz tuning fork [17]. The diagnosis of heart failure was made according to European Society of Cardiology categories [18].
Treatment
All the foot care and treatments were performed by the same treatment team according to the guidelines for diabetic foot management [19, 20]. TMA surgery was performed by an experienced orthopedic surgeon. All the patients received improved medical treatment, wound care plans, medical nutrition therapy and rehabilitation exercise.
Antibiotic therapy was immediately administered according to the guidelines [20]. The antibiotic therapy was adjusted as soon as the results of the susceptibility tests were available, but not altered if infection was well controlled. Vasodilators were used, mostly assisted by Chinese patent medicines with the role of accelerating blood circulation to improve patient’s ischemic symptoms and help antibiotic transport to the wound, and cardiotonic drugs were used in patients with heart failure when appropriate. We paid attention to the improvement of nutritional status and major organ functions, with relaxed glucose control (maintain HbA1c 7.5–8.5%).
Following TMA, the patient was kept in bed with the stump elevated. The dressing was changed every 1–4 days until the stump was out of danger of ischemia and sepsis. Negative pressure wound therapy was done if needed. Rehabilitation through double-leg empty pedal bicycle movement 3000–5000 times per day was confirmed in our study.
Outcomes and Follow-Up
The primary end point of the study was wound healing after TMA. The foot was considered healed when complete re-epithelialization of the surgical wound had occurred. The healing times were calculated, considering the interval between the day of TMA and the day of complete re-epithelialization. A midfoot amputation or an above-the-ankle amputation was proposed and performed in patients in whom the lesion was extended, for stump infarction or for severe infection after TMA. An above-the-ankle amputation was considered a major amputation.
One hundred two patients were followed up at clinic after discharge, generally twice a month for the first 3 months, then every month for the second 3 months and every 3 months after half a year until March 2017 or until death (adjusting the follow-up time when necessary). For patients receiving therapy elsewhere, the follow-up was done by telephoning.
Statistical Analysis
Quantitative variables were described by the mean ± SD or median (range). Discontinuous variables were expressed using frequency. Kaplan-Meier survival analysis and the log-rank test were performed to analyze variables that affected end points (wound healing, above-the-ankle-amputation and death). Variables of p < 0.5 were included in the Cox regression analysis model to analyze the independent influencing factors of end points. All the statistical analyses were performed using the IBM SPSS statistical system (version 23.0). p < 0.05 was considered statistically significant.