OBJECTIVEWe 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 METHODSThese 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.RESULTSThe 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 <0.0009). Predicting variables at multivariate analysis were the following: for healing, ulcer dimension, infection, and ischemic heart disease; and for major amputation, ulcer dimension, number of minor amputations, and age. Additional predicting variables for PA+ patients were the following: for healing, transcutaneous oxygen tension [ΔTcPo2]; and for major amputation, basal TcPo2, basal A1C, ΔTcPo2, and percutaneous angioplasty technical failure.CONCLUSIONSEarly diagnosis of CLI, aggressive treatment of infection, and extensive use of percutaneous angioplasty in ischemic affected ulcers offers improved outcome for many previously at-risk limbs. Ulcer size >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.
Medical knowledge about wound management has improved as recent studies have investigated the healing process and its biochemical background. Despite this, foot ulcers remain an important clinical problem, often resulting in costly, prolonged treatment. A non-healing ulcer is also a strong risk factor for major amputation. Many factors can interfere with wound healing, including the patient's general health status (i.e., nutritional condition indicated by albumin levels) or drugs such as steroids that can interfere with normal healing. Diabetic complications (i.e., renal insufficiency) may delay healing and account for higher amputation rates observed in diabetic patients under dialysis treatment. Wound environment (e.g., presence of neuropathy, ischaemia, and infection) may significantly influence healing by interfering with the physiological healing cascade and adding local release of factors that may worsen the wound. The timely and well-orchestrated release of factors regulating the healing process, observed in acute wounds, is impaired in non-healing wounds that are blocked in a chronic inflammatory phase without progressing to healing. This chronic phase is characterised by elevated protease activity (EPA) of metalloproteinases (MMPs) and serine proteases (e.g., human neutrophil elastase) that interfere with collagen synthesis, as well as growth factor release and action. EPA (mainly MMP 9, MMP-8 and elastase) and inflammatory factors present in the wound bed (such as IL-1, IL-6, and TNFa) account for the catabolic state of non-healing ulcers. The availability of wound dressings that modulate EPA has added new therapeutic options for treating non-healing ulcers. The literature confirms advantages obtained by reducing protease activity in the wound bed, with better outcomes achieved by using these dressings compared with traditional ones. New technologies also allow a physician to know the status of the wound bed environment, particularly EPA, in a clinical setting. These may be helpful in guiding a clinician's options in treating very difficult-to-heal ulcers.
OBJECTIVEDespite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed.RESEARCH DESIGN AND METHODSThe immune phenotype of peripheral monocytes was studied by fluorescence-activated cell sorter analysis comparing patients with acute Charcot (n = 10) in both the active and recovered phase, diabetic patients with neuropathy (with or without osteomyelitis), and normal control subjects.RESULTSWhen compared with diabetic control subjects and healthy subjects, monocytes from acute Charcot patients showed a proinflammatory immune phenotype characterized by increased production of proinflammatory cytokines, reduced secretion of anti-inflammatory cytokines, increased expression of surface costimulatory molecules, and increased resistance to serum withdrawal-induced apoptosis. In addition, the pattern of circulating cytokines confirmed activation of proinflammatory cytokines. No modulation of the monocyte phenotype was documented in diabetic control subjects and healthy subjects, thus indicating that the proinflammatory alterations of monocytes are specific and causative of acute Charcot.CONCLUSIONSTogether, these data provide evidence for the role of proinflammatory changes in the immune phenotype of monocytes in the pathogenesis of acute Charcot. These alterations may explain the abnormally intense and prolonged inflammatory response that characterizes this disorder and may represent a potential therapeutic target for specific pharmacological interventions.
Diabetic foot (DF) is a common complication of diabetes and the first cause of hospital admission in diabetic patients. In recent years several guidelines have been proposed to reinforce the the management of DF with a notable increase in diabetes knowledge and an overall reduction of amputations. Significant improvements have been reached in the treatment of diabetic foot ulcers (DFUs) and nowadays clinicians have several advanced medications to apply for the best local therapy. Among these, negative pressure wound therapy (NPWT) is a useful adjunct in the management of chronic and complex wounds to promote healing and wound bed preparation for surgical procedures such as skin grafts and flap surgery. NPWT has shown remarkable results although its mechanisms of action are not completely understood. In this paper, we offer a complete overview of this medication and its implication in the clinical setting. We have examined literature related to NPWT concerning human, animal and in vitro studies, and we have summarized why, when and how we can use NPWT to treat DFUs. Further we have associated our clinical experience to scientific evidence in the field of diabetic foot to identify a defined strategy that could guide clinician in the use of NPWT approaching to DFUs. Core tip: This paper represents a summary of the mechanism of action of negative pressure wound therapy and its effectiveness. Further, according to scientific findings and our experience, we propose a flow chart about its use addressed to the field of diabetic foot.Meloni M, Izzo V, Vainieri E, Giurato L, Ruotolo V, Uccioli L. Management of negative pressure wound therapy in the treatment of diabetic foot ulcers.
Diabetic foot ulceration remains one of the most common and most serious consequences of diabetes. Persistently high levels of matrix metalloproteases (MMPs) contribute to wound chronicity. Our aim was to assess the concentrations of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in neuropathic and ischemic diabetic foot ulcers by analyzing biopsy samples. In this study, biopsies were taken from 35 diabetic foot ulcers of type 2 diabetes mellitus patients and distinguished in neuropathic (n = 14) or ischemic (n = 21). Zymography assay was utilized for the analysis of MMP-2 and MMP-9 activity. TACE activity was evaluated by a specific fluorimetric assay. mRNA levels of MMPs as well as TIMPs were detected using quantitative real-time polymerase chain reaction. The activity of MMP9 and A Disintegrin and A MetalloProtease Domain 17/TNF-Alpha Converting Enzyme (ADAM17/TACE) was significantly increased in ischemic compared to neuropathic biopsies. No differences were detected between both groups for the mRNA levels of MMPs as well as of ADAMs. However, TIMP3 mRNA expression was decreased in ischemic samples. The combination of increased activity of MMP9 and ADAM17/TACE with decreased concentrations of TIMP-3 mRNA expression in ischemic diabetic foot ulcers compared to neuropathic samples suggests that the increased proteolytic environment may represent a causative factor in the ulcer progression. New treatment strategies for healing diabetic foot ulcers could be directed toward increasing levels of TIMP3.
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