Critical limb ischemia (CLI) is considered the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events and death. In this review, we presented a complete overview about physiopathology, diagnosis and holistic management of CLI. Revascularization is the first-line treatment, but several challenging cases are not treatable by conventional techniques. Unconventional techniques for the treatment of complex below-the-knee arterial disease are described. Furthermore, the state-of-the-art on gene and cell therapy for the treatment of no-option patients is reported.

This study aims to evaluate clinical and ulcer characteristics as well the outcomes of patients with diabetic foot ulcers (DFUs). The study group was composed of DFUs patients managed by a limb salvage protocol according to guidance. Clinical and ulcers findings were described, and 1-year outcomes defined as limb salvage, healing, healing time, major amputation and death were compared between neuropathic and ischemic DFUs. One thousand, one hundred and ninety-eight subjects were included; 386 (32.2%) neuropathic and 812 (67.8%) ischemic DFUs. Neuropathic patients were younger (69.5 ± 11.5 vs. 74.5 ± 11.5, p < 0.0001) and reported less cases of nephropathy (22.8 vs. 39.6%, p < 0.0001), ischemic heart disease (22.8 vs. 36.9, p = 0.0004), cerebrovascular disease (8.3 vs. 17.2%, p = 0.002), heart failure (10.1 vs. 24.7%, p = 0.0002) and end-stage-renal-disease (ESRD) (5.4 vs. 27%, p = 0.0001) than ischemic patients; they also showed less cases of large (>5 cm²) (10.3 vs. 22.9%, p = 0.0007), infected (40.4 vs. 55.7%, p = 0.0005) and deep to the bone (22.3 vs. 39.2, p = 0.0002) ulcers, as well less multiple ulcerations (21.8 vs. 32.8%, p = 0.006) than patients with ischemic DFUs. The outcomes for neuropathic and ischemic DFUs were limb salvage (98.4 vs. 82.3%, p < 0.0001), healing (97.3 vs. 79.6%, p < 0.0001), healing time (34.9 vs. 35.6 weeks, p = 0.8), major amputation (0.5 vs. 6.6%, p = 0.0001), death (1.1 vs. 11%, p < 0.0001) respectively. Revascularization failure and ESRD were independent predictors of major amputation, while heart failure and number of co-morbidities (≥5) were independent predictors of death. Ischemic DFUs patients showed more severe clinical and ulcers features as well worse outcomes than neuropathic DFUs patients.

OBJECTIVE: We describe the long-term outcomes of 510 diabetic patients with critical limb ischemia (CLI) and an active foot ulcer or gangrene, seen at the University Hospital of Rome Tor Vergata, a tertiary care clinic. RESEARCH DESIGN AND METHODS: These patients were seen between November 2002 and November 2007 (mean follow-up 20 ± 13 months [range 1–66 months]). The Texas Wound Classification was used to grade these wounds that were either class C (ischemia) and D (ischemia+infection) and grade 2–3 (deep–very deep). This comprehensive treatment protocol includes rapid and extensive initial debridement, aggressive use of peripheral percutaneous angioplasty, empirical intravenous antibiotic therapy, and strict follow-up. RESULTS: The protocol was totally applied (with percutaneous angioplasty [PA+]) in 456 (89.4%) patients and partially (without percutaneous angioplasty [PA−]) in 54 (10.6%) patients. Outcomes for the whole group and PA+ and PA− patients are, respectively: healing, n = 310 (60.8%), n = 284 (62.3%), and n = 26 (48.1%); major amputation, n = 80 (15.7%), n = 67 (14.7%), and n = 13 (24.1%); death, n = 83 (16.25%), n = 68 (14.9%), and n = 15 (27.8%); and nonhealing, n = 37 (7.25%), n = 37 (8.1%), and n = 0 (0%) (χ2 5 cm2 indicates a reduced chance of healing and increased risk of major amputation. It was thought that all ulcers warrant aggressive treatment including percutaneous angioplasty and that treatment should be considered even for small ischemic ulcers.

Monocytes and lymphocytes play a key role in physiologic wound healing and might be involved in the impaired mechanisms observed in diabetes. Skin wound macrophages are represented by tissue resident macrophages and infiltrating peripheral blood recruited monocytes which play a leading role during the inflammatory phase of wound repair. The impaired transition of diabetic wound macrophages from pro-inflammatory M1 phenotypes to anti-inflammatory pro-regenerative M2 phenotypes might represent a key issue for impaired diabetic wound healing. This review will focus on the role of immune system cells in normal skin and diabetic wound repair. Furthermore, it will give an insight into therapy able to immuno-modulate wound healing processes toward to a regenerative anti-inflammatory fashion. Different approaches, such as cell therapy, exosome, and dermal substitute able to promote the M1 to M2 switch and able to positively influence healing processes in chronic wounds will be discussed.

Diabetic foot (DF) is a chronic and highly disabling complication of diabetes. The prevalence of peripheral arterial disease (PAD) is high in diabetic patients and, associated or not with peripheral neuropathy (PN), can be found in 50% of cases of DF. It is worth pointing out that the number of major amputations in diabetic patients is still very high. Many PAD diabetic patients are not revascularised due to lack of technical expertise or, even worse, negative beliefs because of poor experience. This despite the progress obtained in the techniques of distal revascularisation that nowadays allow to reopen distal arteries of the leg and foot. Italy has one of the lowest prevalence rates of major amputations in Europe, and has a long tradition in the field of limb salvage by means of an aggressive approach in debridement, antibiotic therapy and distal revascularisation. Therefore, we believe it is appropriate to produce a consensus document concerning the treatment of PAD and limb salvage in diabetic patients, based on the Italian experience in this field, to share with the scientific community.