This retrospective cohort study included 245 patients with diabetic ulcers who had undergone a minor amputation followed by physical therapy between January 2015 and February 2018. All subjects were patients admitted at the Oita Oka Hospital. We excluded patients with (1) infections after minor amputation, (2) major amputations (below and above the knee), (3) death or discharge due to systemic complications, (4) use of a wheelchair for mobility before hospitalization, (5) severe progression of dementia, (6) missing data, (7) and no follow-up survey data. Finally, 129 patients were enrolled in this study (Fig. 1).
Major and minor amputations were defined as those proximal and distal, respectively, to the ankle joints, including the toes. Reamputation was defined as occurring in the ipsilateral limb within 1 year after the first amputation.
Measurement items included participants’ basic and medical information, physical function, and the presence or absence of reamputation. Basic information included age, sex, body mass index (BMI), hospitalization, physical therapy period, average length of daily physical therapy in minutes, foot offloading period, comorbidities (hypertension, hyperlipidemia, and heart disease, cerebrovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease), and presence or absence of hemodialysis. The medical information included laboratory parameters (serum albumin, serum hemoglobin, blood glucose, C-reactive protein, white blood cell counts, and estimated glomerular filtration rate), lower limb blood flow data (skin perfusion pressure and ankle-brachial pressure index), wound ischemia foot infection (WIfI) classification system, amputation region (toe, ray, and transmetatarsal), and foot deformation (Charcot joint, hallux valgus, hammer toe, and claw toe). The physical function included knee extension muscle strength, ankle dorsiflexion angle, ankle plantarflexion angle, plantar sensory disorder, and Functional Independence Measure (FIM) ambulation. BMI was calculated by dividing the body weight (kg) by the square of the height (m) and was reported in kg/m2. The offloading period started from the minor amputation to the start of loading.
The average length of daily physical therapy was calculated by dividing total hours of physical therapy by the number of days in the hospital. The estimated glomerular filtration rate (eGFR) was calculated based on the new Japanese coefficient Modification of Diet in Renal Disease study equation: eGFR (mL/min/1.73 m2) = 194 × (serum creatinine) − 1.094 × (age) − 0.287 (× 0.739 for females) .
Participants were categorized into the following four groups according to the estimated eGFR (1) ≥ 60 mL/min/1.73 m2, (2) 45–59.9 mL/min/1.73 m2, (3) 30–44.9 mL/min/1.73 m2, and (4) < 30 mL/min/1.73 m2 .
We considered angina pectoris, myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting as cardiovascular condition-related history and transient ischemic attack, cerebral infarction, or cerebral hemorrhage as cerebrovascular condition-related history. Lower limb blood flow data with skin perfusion pressure as a measure of blood flow were evaluated using a Laser Doppler (SensiLase PAD4000, KanekaMedix, Osaka, Japan). The ankle-brachial index was measured with an automated oscillometric device provided by Omron Colin Co., Ltd. (Tokyo, Japan). We evaluated the wound data using the WIfI and the ischemia and foot infection data using three factors. Severity was classified by the depth, location, and presence or absence of necrotic tissue . Amputation region and foot deformation were evaluated using simple radiography and computed tomography images before and after surgery.
For physical function evaluation, we examined the maximum voluntary isometric knee extension muscle strength using a hand-held dynamometer (µ-tasF-1, Anima, Tokyo, Japan). For knee extensor strength measurements, participants were asked to sit on a chair with the knee flexed at 90 degrees and push at maximum strength against the dynamometer pad for 5 s. Isometric knee extensor strength was measured twice per side, and the highest value for the right and left legs was used to represent the knee extensor muscle strength.
The range of motion in the ankle joint was evaluated by measuring dorsiflexion and plantarflexion on the wound side with a goniometer and the angle that allowed maximum pain-free movement. The presence or absence of plantar sensory impairment was considered as neuropathy when the evaluator size of the Semmes-Weinstein-monofilament was 5.07.
Based on previous studies, we performed three-site tests involving the plantar aspects of the great toe, third metatarsal, and fifth metatarsal . The ambulation status was evaluated using the movement parameter of the FIM score .
Characteristic data were compared using the Mann–Whitney U test, t-test, and χ2 test, as appropriate. A univariate Cox proportional hazards analysis was used to calculate the reamputation hazard ratio (HR) and its 95% confidence interval. A multivariate Cox regression analysis was used to determine the factors associated with reamputation. We selected the following factors for univariate analysis: age, sex, serum albumin, knee extension muscle strength, hemodialysis, ankle dorsiflexion angle, and FIM ambulation. Subsequently, a multivariate Cox regression analysis with stepwise selection was carried out to identify significant independent factors.
The incidence of reamputation presence and absence was calculated using the Kaplan–Meier curves for the extracted factors. The intergroup differences were estimated using the log-rank test. All analyses were performed with R version 3.2.5 (R Foundation for Statistical Computing, Vienna, Austria). The level of significance was set at P < 0.05.