Outcomes after Emergency Admission with a Diabetic Foot Attack Indicate a High Rate of Healing and Limb Salvage But Increased Mortality: 18-Month Follow-up Study.

AIM: The diabetic foot attack (DFA) is perhaps the most devastating form of diabetic foot infection, presenting with rapidly progressive skin and tissue necrosis, threatening both limb and life. However, clinical outcome data in this specific group of patients are not available. METHODS: Analysis of 106 consecutive patients who underwent emergency hospitalisation for DFA (TEXAS Grade 3B or 3D and Infectious Diseases Society of America (IDSA) Class 4 criteria). Outcomes evaluated were: 1) Healing 2) major amputation 3) death 4) not healed. The first outcome reached in one of these four categories over the follow-up period (18.4±3.6 months) was considered. We also estimated amputation free survival. RESULTS: Overall, 57.5% (n=61) healed, 5.6% (n=6) underwent major amputation, 23.5% (n=25) died without healing and 13.2% (n=14) were alive without healing. Predictive factors associated with outcomes were: Healing (age<60, p=0.0017; no Peripheral arterial disease (PAD) p= 0.002; not on dialysis p=0.006); major amputation (CRP>100 mg/L, p=0.001; gram+ve organisms, p=0.0013; dialysis, p= 0.001), and for death (age>60, p= 0.0001; gram+ve organisms p=0.004; presence of PAD, p=0.0032; CRP, p=0.034). The major amputation free survival was 71% during the first 12 months from admission, however it had reduced to 55.4% by the end of the follow-up period. CONCLUSIONS: In a unique population of hospitalised individuals with DFA, we report excellent healing and limb salvage rates using a dedicated protocol in a multidisciplinary setting. An additional novel finding was the concerning observation that such an admission was associated with high 18-month mortality, almost all of which was after discharge from hospital.

Pharmacological Treatments for Diabetic Foot Disease: Current State and Future Perspectives.

The care of the individual with diabetic foot disease (DFD) represents a significant challenge. In addition to the primary foot pathology, individuals with DFD are frequently compromised by multiple co-existent medical complications. Successful management of DFD, therefore requires simultaneous addressal of these issues alongside high-quality foot care. We explore the pharmacological treatments in DFD with an emphasis on the emerging putative technologies centred on addressing the pathobiology of wound healing but also discuss developments in infection control, Charcot neuroarthropathy, cardiovascular and diabetes care. Many of these will have a significant impact on future treatment paradigms and how we amalgamate these novel technologies may help shape the standard of care in DFD hereafter. However, there is a need for better quality of evidence and cost-effectiveness data prior to widespread adoption into routine care is considered.

Surgical Diabetic Foot Debridement: Improving Training and Practice Utilizing the Traffic Light Principle.

Comprehensive management of a severe diabetic foot infection focus on clear treatment pathways. Including rapid, radical debridement of all infection in addition to intravenous antibiotics and supportive measures. However, inexperienced surgeons can often underestimate the extent of infection, risking inadequate debridement, repeated theatre episodes, higher hospital morbidity, and hospital length of stay (LOS). This study aims to assess protocolized diabetic-foot-debridement: Red-Amber-Green (RAG) model as part of a value-based driven intervention. The model highlights necrotic/infected tissue (red-zone, nonviable), followed by areas of moderate damage (amber-zone), healthy tissue (green-zone, viable). Sequential training of orthopedic surgeons supporting our emergency service was undertaken prior to introduction. We compared outcomes before/after RAG introduction (pre-RAG, n = 48; post- RAG, n = 35). Outcomes measured included: impact on number of debridement/individual admission, percentage of individuals requiring multiple debridement, and length-of-hospital-stay as a function-of-cost. All-patients fulfilled grade 2/3, stage-B, of the Texas-Wound-Classification. Those with evidence of ischemia were excluded. The pre-RAG-group were younger (53.8 ± 11.0 years vs 60.3 ± 9.2 years, P = .01); otherwise the 2-groups were matched: HbA1c, white blood cell count, and C-reactive protein. The post-RAG-group underwent significantly lower numbers of debridement's (1.1 ± 0.3 vs 1.5 ± 0.6/individual admission, P = .003); equired fewer visits to theatre (8.6% vs 38%, P = .003), their LOS was reduced (median LOS pre-RAG 36.0 vs post-RAG 21.5 days, P = .02). RAG facilitates infection clearance, fewer theatre-episodes, and shorter LOS. This protocolized-management-tools in acute severely infected diabetic foot infection offers benefits to patients and health-care-gain.

Management of negative pressure wound therapy in the treatment of diabetic foot ulcers.

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.

Non-healing foot ulcers in diabetic patients: general and local interfering conditions and management options with advanced wound dressings.

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.

High matrix metalloproteinase levels are associated with dermal graft failure in diabetic foot ulcers.

The aim of our study is to analyze factors, including matrix metalloproteinase (MMP) levels, that could influence the integration of dermal grafts in diabetic foot ulcers. From September 2012 to September 2013, 35 diabetic patients with IIA lesion (Texas Wound Classification) and an extensive foot tissue loss were considered suitable for dermal graft. Before the enrollment we ensured the best local conditions: adequate blood supply, control of infection, and offloading. The MMP level of each lesion was evaluated blindly before the application of dermal substitutes. At 1-month follow-up, we analyzed the correlation between clinical patient characteristics, local wound features including MMP levels, dermal substitute applied, and the outcome expressed in terms of dermal graft integration. We observed dermal graft integration in 28/35 patients (80% of our population). In multivariate analysis high MMP level was the only negative predictor for dermal graft integration (P < .0007). In addition, we divided the patients into 2 groups according to MMP levels: group 1 with low protease activity (24 patients) and group 2 with elevated protease activity (11 patients). The integration of the dermal graft was 100% in group 1 (n = 24 patients) and 36.4% in group 2 (n = 4patients), P < .0001. According to our data, the evaluation of MMP levels may be useful to choose the right strategy to get the best results in terms of clinical success and cost saving. However, further studies are necessary to confirm these findings.

Long-term outcomes of diabetic patients with critical limb ischemia followed in a tertiary referral diabetic foot clinic.

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%) (chi(2) <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 [DeltaTcPo(2)]; and for major amputation, basal TcPo(2), basal A1C, DeltaTcPo(2), and percutaneous angioplasty technical failure. CONCLUSIONS: Early 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 cm(2) 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.

Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot.

OBJECTIVE: Despite 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 METHODS: The 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. RESULTS: When 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. CONCLUSIONS: Together, 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.