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This paper describes important aspects of the diabetic foot which the vascular surgeon needs to understand to efficiently manage the diabetic foot. Firstly, it emphasises the three main pathologies which come together in the diabetic foot, namely neuropathy, ischemia and immunopathy, the latter predisposing to infection. As a result of neuropathy, the signs and symptoms of tissue breakdown, infection and ischemia may be minimal. Nevertheless the pathology emanating from such clinical events proceeds rapidly without the body being aware of it and the end stage of tissue death and necrosis is quickly reached. It is important to have a prompt system of evaluation and intervention to prevent the rapid progression to necrosis. Thus, secondly, the paper describes a simple rapid assessment of the diabetic foot, which comprises inspection, palpation and sensory testing and leads on to a modern classification and staging of the diabetic foot. This classifies six subdivisions of the diabetic foot: foot with neuropathic ulceration, Charcot foot, neuroischemic foot, critically ischemic foot, acutely ischemic foot and renal ischemic foot and six stages in the natural history of each of these subdivisions: normal foot, high risk foot, ulcerated foot, infected foot, necrotic foot and unsalvageable foot. Thirdly, it describes modern management of the diabetic foot, emphazising wound care and revascularization within the context of a multidisciplinary care team that provides integrated care focused in a diabetic foot clinic, to which patients with diabetes should have easy and rapid access. Members of the team include podiatrist, nurse, orthotist, physician, radiologist and surgeons.

Objective: CTX0E03 (CTX) is a clinical-grade human neural stem cell (hNSC) line that promotes angiogenesis and neurogenesis in a preclinical model of stroke and is now under clinical development for stroke disability. We evaluated the therapeutic activity of intramuscular CTX hNSC implantation in murine models of hindlimb ischemia for potential translation to clinical studies in critical limb ischemia., Approach and Results: Immunodeficient (CD-1 Fox(nu/nu)) mice acutely treated with hNSCs had overall significantly increased rates and magnitude of recovery of surface blood flow (laser Doppler), limb muscle perfusion (fluorescent microspheres, P<0.001), and capillary and small arteriole densities in the ischemic limb (fluorescence immunohistochemistry, both P<0.001) when compared with the vehicle-treated group. Hemodynamic and anatomic improvements were dose related and optimal at a minimum dose of 3×10(5) cells. Dose-dependent improvements in blood flow and increased vessel densities by hNSC administration early after ischemia were confirmed in immunocompetent CD-1 and streptozotocin-induced diabetic mice, together with marked reductions in the incidence of necrotic toes (P<0.05). Delayed administration of hNSCs, 7 days after occlusion, produced restorative effects when comparable with acute treatment of 35 days after hindlimb ischemia. Histological studies in hindlimb ischemia immunocompetent mice for the first 7 days after treatment revealed short-term hNSC survival, transient elevation of early host muscle inflammatory, and angiogenic responses and acceleration of myogenesis., Conclusions: hNSC therapy represents a promising treatment option for critical limb ischemia.

Background: The aim of our study was to compare the effect of bone marrow mononuclear cell and peripheral blood progenitor cell therapies in patients with diabetic foot disease and critical limb ischaemia unresponsive to revascularization with conservative therapy., Methods: Twenty-eight patients with diabetic foot disease (17 treated by bone marrow cells and 11 by peripheral blood cell) were included into an active group and 22 patients into a control group without cell treatment. Transcutaneous oxygen pressure and rate of major amputation, as the main outcome measures, were compared between bone marrow cells, peripheral blood cell and control groups over 6 months; both cell therapy methods were also compared by the characteristics of cell suspensions. Possible adverse events were evaluated by changes of serum levels of angiogenic cytokines and retinal fundoscopic examination., Results: The transcutaneous oxygen pressure increased significantly (p < 0.05) compared with baseline in both active groups after 6 months, with no significant differences between bone marrow cells and peripheral blood cell groups; however, no change of transcutaneous oxygen pressure in the control group was observed. The rate of major amputation by 6 months was significantly lower in the active cell therapy group compared with that in the control group (11.1% vs. 50%, p = 0.0032), with no difference between bone marrow cells and peripheral blood cell. A number of injected CD34+ cells and serum levels of angiogenic cytokines after treatment did not significantly differ between bone marrow cells and peripheral blood cell., Conclusions: Our study showed a superior benefit of bone marrow cells and peripheral blood cell treatments of critical limb ischaemia in patients with diabetic foot disease when compared with conservative therapy. There was no difference between both cell therapy groups, and no patient demonstrated signs of systemic vasculogenesis., (Copyright © 2013 John Wiley & Sons, Ltd.)

We treated foot ulcerations in diabetics with limb-threatening ischemia using percutaneous balloon dilatation (44) and popliteodistal vein grafts (94). After revascularization, we observed in 12% an increase in the infection which necessitated major amputation despite open bypass or successful dilatation. A diabetic local immunodeficiency leads to cellular and humoral alterations which may cause severe tissue damage although the perfusion has been improved.