Marco Meloni

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 patients 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 clinicians options in treating very difficult-to-heal ulcers.

A new natural history of Charcot foot: clinical evolution and final outcome of stage 0 Charcot neuroarthropathy in a tertiary referral diabetic foot clinic.

Purpose The purpose of this study is to describe the usefulness of 18F-FDG PET/CT scanning in the diagnosis and follow-up of stage 0 Charcot foot (CNO) and CNO outcomes when therapeutic options are driven by this image modality. Patients and Methods We selected 25 out of 40 diabetic patients with an acute CNO, without any bone involvement at x-ray (stage 0 CNO). Diagnostic criteria were inflammatory clinical signs of the affected foot and skin temperature difference greater than 2°C compared with the contralateral foot (&Dgr;T). All patients underwent x-ray, MRI, and 18F-FDG PET/CT scanning (expressed as standardized uptake value, SUVmax) at baseline (T0). All patients underwent another 18F-FDG PET/CT within 1 month after &Dgr;T was less than 2°C [clinical recovery (T1)] and again every 3 months until SUVmax was less than 2 [final recovery (T2)]; at this time, MRI confirmed the end of the inflammatory condition. Results T0 &Dgr;T was 3.04 ± 1.65°C. All patients showed T0 SUVmax of the affected foot higher than the contralateral one (3.83 ± 1.087 vs. 1.24 ± 0.3; P < 0.001). At clinical recovery (T1), defined by &Dgr;T below 2°C, the inflammatory signs were no longer present (T0 vs. T1 &Dgr;T = 3.04 ± 1.65 vs. 0.9 ± 0.55°C; P < 0.0001). At T1, SUVmax was unchanged from T0 (3.80 ± 1.69 vs. 3.83 ± 1.09; P = ns). At final recovery (T2), &Dgr;T was 0.74 ± 0.29°C (similar to T1 &Dgr;T), while the SUVmax dropped from T1 to T2 (3.8 ± 1.69 vs. 1.72 ± 0.52; P < 0.0001). Standard therapy was total contact cast and removable cast walker until T2 (15.12 ± 5.45 mo). No patient developed foot bone fractures nor had relapses during follow-up (21.75 ± 16.7 mo). Discussion PET/CT scan allows the quantification of the inflammatory process; therefore, it may drive clinical decisions in the management of acute CNO better than clinical criteria. None of our patients developed foot bone fractures or had relapses during follow-up driven by PET/CT scan.

Long term outcomes of diabetic haemodialysis patients with critical limb ischemia and foot ulcer

AIM To evaluate the outcomes of diabetic dialysis patients with critical limb ischemia and foot ulcer. METHODS The study group included 599 diabetic, 99 dialyzed (Ds) (16.5%) and 500 not dialyzed (NDs) (83%) patients with critical limb ischemia and foot ulcers identified as stage C (ischemia) or D (ischemia plus infection) of Texas Wound Classification. All patients were treated by endovascular revascularization. Outcomes were expressed as healing, major amputation, death and non healing after 12months. The mean follow-up was 15±13months. RESULTS The outcomes of the whole population were: 48.9% healing, 11.3% major amputation, 12.7% death, 27.1 non healing. At the multivariate analysis dialysis was a negative predictor of healing and a positive predictor of major amputation. Outcomes for Ds and NDs were respectively: healing (30.3 vs 52.6%), major amputation (14.4 vs 10.8%), death (21.1 vs 11%) and non-healing (34.2 vs 25.6%) (X=0.0004). Amputation occurred earlier in Ds than in NDs. According to the multivariate analysis in Ds ischemic heart disease and lower ΔTcPO2 were negative predictors for healing. Successful revascularization was a negative predictor for major amputation. HDL and carotid artery disease were predictive factors of death among NDs. Among Ds high blood pressure values were the only predictor of amputation while no variable resulted predictive of healing or death. CONCLUSIONS Our study shows that our limb salvage protocol ensures a good rate of limb salvage in Ds even if they have a higher risk of amputation and death compared to NDs.

Limb Salvage in Patients With Diabetes Is Not a Temporary Solution but a Life-Changing Procedure

Our limb salvage protocol for patients with diabetes at risk for amputation due to critical limb ischemia, foot ulcer, or gangrene includes early and aggressive surgical debridement, immediate broad-spectrum antibiotic therapy, and peripheral transluminal angioplasty as the first-choice revascularization procedure (1). In 2010 (2), we described the long-term outcomes (mean follow-up 20 ± 13 months) of 456 patients treated with this protocol: ulcers were healed in 62.3% (group A), major amputations performed in 14.7% (group B), death occurred in 14.9% (group C), and ulcers remained unhealed for >12 months in 8.1% (group D). As the long-term efficacy of this approach is still controversial (3), we have now evaluated the limb- or life-related outcomes in the same cohort of patients after a further …

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.

Osteomyelitis in diabetic foot: A comprehensive overview

Foot infection is a well recognized risk factor for major amputation in diabetic patients. The osteomyelitis is one of the most common expression of diabetic foot infection, being present approximately in present in 10%-15% of moderate and in 50% of severe infectious process. An early and accurate diagnosis is required to ensure a targeted treatment and reduce the risk of major amputation. The aim of this review is to report a complete overview about the management of diabetic foot osteomyelitis. Epidemiology, clinical aspects, diagnosis and treatment are widely described according to scientific reccomendations and our experience.

Risk of contrast induced nephropathy in diabetic patients affected by critical limb ischemia and diabetic foot ulcers treated by percutaneous transluminal angioplasty of lower limbs

The aim of this study is to evaluate the risk of contrast induced nephropathy (CIN) in diabetic patients with critical limb ischemia (CLI) and foot ulcers (FUs) treated by percutaneous transluminal angioplasty of lower limbs.

Comment on Hoffstad et al. Diabetes, Lower-Extremity Amputation, and Death. Diabetes Care 2015;38:1852–1857

We have read with interest the article by Hoffstad et al. (1), as lower-extremity amputation (LEA) is a topic in which we have had a long-standing interest (2,3). Thus, we would like to share some of our thoughts about its findings. This article focuses its attention on the large increase in the incidence of death among patients with diabetes who underwent a LEA, as has been previously reported by several authors, including ourselves (1,3). This article further highlights the incomplete relationship between mortality and known diabetic complications, such as cardiovascular disease or renal insufficiency, and suggests that the presence of other unspecified factor(s) may be …

Critical limb ischemia: current challenges and future prospects

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.

A Complication of the Complications: The Complexity of Pathogenesis and the Role of Co-Morbidities in the Diabetic Foot Syndrome

Diabetic foot syndrome (DFS) is considered the most severe and complicated framework of 2 diabetes-related long-term complications, peripheral neuropathy and peripheral arterial disease, and foot ulce