Heterogeneity in major amputation risk among patients with WIfI (wound, ischemia, foot infection) Stage 4 diabetic foot ulcers

Abstract

Although the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification stratifies limb threat, reported 1-year major amputation rates for WIfI Stage 4 vary widely across institutions. Whether patient-level factors provide prognostic information beyond limb severity in advanced disease remains unclear. We conducted a retrospective single-center cohort study of 296 patients with diabetic foot ulcers (DFUs) admitted to a tertiary referral center between 2017 and 2024. Because all major amputations occurred among patients classified as WIfI Stage 4, subsequent analyses focused on the WIfI Stage 4 subgroup ( n  = 195). Major amputation was defined as amputation at or above the ankle. Variables demonstrating potential associations in univariate comparisons within the WIfI Stage 4 cohort ( p  < 0.10), together with clinically relevant covariates, were considered for multivariable logistic regression analysis. Among WIfI Stage 4 patients, 38 (19.5%) underwent major amputation. Compared with the limb salvage group, patients who underwent amputation had significantly higher rates of peripheral artery occlusive disease (PAOD), chronic kidney disease, and dialysis dependence and lower hemoglobin and albumin levels. In multivariate analysis, PAOD was independently associated with higher odds of major amputation (OR 4.26, 95% CI 1.06–17.15, p  = 0.041), whereas higher serum albumin was independently associated with lower odds of major amputation (OR 0.18, 95% CI 0.07–0.49, p  < 0.001). In patients with WIfI Stage 4 DFUs, major amputation risk appeared heterogeneous despite uniformly advanced limb threat. PAOD and serum albumin were associated with clinical outcome in this cohort. These findings suggest that patient-level physiological assessment may complement limb-based staging when evaluating prognosis in advanced diabetic foot disease.