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 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic foot ulcers (DFUs) consist of an interaction of neuropathy, ischemia and infection. Neuropathy affects sensory, motor and autonomic pathways. Pathogenic factors for neuropathy include hyperglycemia, nonenzymatic glycosylation, oxidative stress, ischemic and hypoxic factors, nerve growth factor anomalies, activation of polyol pathway and immunologic abnormalities. All these factors are stated to contribute to microvascular disease and neural dysfunction. Peripheral neuropathy and ischemia combined with repetitive traumas can lead to diabetic foot ulceration. Fifteen percent of diabetic patients develop foot ulcers during their lifetime and nonhealing ulcers are responsible for 85% of nontraumatic lower extremity amputation. On the other hand, the treatment cost of foot disease in diabetic patients is estimated at $1 billion annually. When these conditions are considered, it is very important to design improved and novel strategies for treatment and prevention of diabetic foot disease. Lipid-lowering agents, such as statins, have been shown to prevent cardiovascular events in patients with diabetes. However, in addition, to preventing macrovascular diseases, statins may also be able to retard the progression of microvascular complications of diabetes. Statins alter the balance between vasodilatation and vasoconstriction in favor of vasodilatation by increasing nitric oxide (NO) synthesis, by downregulating endothelin 1 (ET-1) synthesis and reducing vascular response to angiotensin-2 (AT-2). These agents have been shown to augment cerebral blood flow by upregulating endothelial nitric oxide synthase (eNOs) and to reduce cerebral infarct size in a murine model of cerebral ischemia. In addition, recent in vivo and in vitro investigations have evidenced that statins have a favorable effect on diabetic peripheral neuropathy independent of its lipid-lowering effect by demonstrating restoration or preservation of microcirculation of the sciatic nerve. We hypothesized that statins can be useful for the prevention and treatment of diabetic foot. Possible mechanisms include the reduction of neuropathy and ischemia or through growth factors, the effectiveness of which has been shown for fracture healing in animal models.
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PMID:Statins may be useful in diabetic foot ulceration treatment and prevention. 1749 47

Diabetic foot lesions remain a major cause of morbidity in patients with renal failure, especially those on dialysis. Foot complications are encountered at a more than twofold frequency in diabetic patients with end-stage renal disease, and the rate of amputations is 6.5-10 times higher in comparison to the general diabetic population. The causal pathways of the diabetic foot in renal failure are multiple and inter-related. Three major pathologies--neuropathy, ischemia, and infection--are the main contributory factors. Increased awareness of this condition and careful clinical examination are indispensable to avoid serious complications. Appropriate management needs to address all contributory factors. Treatment options include revascularization, off-loading to relieve high-pressure areas, and aggressive control of infection. Equally important is the collaboration between health care providers in a multidisciplinary foot care setting. Moreover, patient education on the measures required to achieve both primary and secondary prevention is of great value. Certainly, technical innovations have made considerable progress possible, but there is a need for further improvement to reduce the number of amputations.
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PMID:The diabetic foot in end stage renal disease. 1765 12

Diabetic foot ulcers remain a major cause of morbidity. Significant progress has been accomplished in ulcer healing by improved management of both ischemia and neuropathy in the diabetic foot. Nevertheless, there is a vital need for further improvement. Becaplermin gel represents an important therapeutic advance for diabetic neuropathic foot ulcers with adequate blood supply. Randomized controlled trials have shown that it is effective in increasing healing rates. However, this efficacy has not translated to positive clinical experience, and the drug is not widely used. Moreover, becaplermin is an expensive medication. Even though it has repeatedly been estimated as cost-effective, its high cost may be prohibitive for some clinicians, especially in developing countries. Clearly, further work is needed to clarify whether use of becaplermin is justified in everyday clinical practice. Future research also needs to assess the potential room for improvement with becaplermin, for instance by combination with other growth factors or by exploring alternative modes of drug delivery.
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PMID:Becaplermin gel in the treatment of diabetic neuropathic foot ulcers. 1868 46

Diabetic foot ulcers are a major health care problem. Complications of foot ulcers are a leading cause of hospitalization and amputation in diabetic patients. Diabetic ulcers result from neuropathy or ischemia. Neuropathy is characterized by loss of protective sensation and biomechanical abnormalities. Lack of protective sensation allows ulceration in areas of high pressure. Autonomic neuropathy causes dryness of the skin by decreased sweating and therefore vulnerability of the skin to break down. Ischemia is caused by peripheral arterial disease, not by microangiopathy. Poor arterial inflow decreases blood supply to ulcer area and is associated with reduced oxygenation, nutrition and ulcer healing. Necrotic tissue is laden with bacteria apt to grow in such an environment, which also impairs general defence mechanisms against infection. Infections often complicate existing ulcers, but are seldom the cause for ulcers. Protective footwear helps to reduce ulceration in diabetic feet at risk. Relieving pressure on the ulcer area is necessary to allow healing. Blood supply needs to be improved by revascularisation whenever compromised. Systemic antibiotics are helpful in treating acute foot infections, but not uninfected ulcers. Osteomyelitis may underlie a diabetic ulcer and is often treated by resection of the infected bone and always by antibiotics, the mode and length of treatment depending on the adequacy of the debridement. The aim of ulcer bed preparation is to convert the molecular and cellular environment of the chronic ulcer to that of an acute healing wound by debridement, irrigating and cleaning. Moist dressings maintain wound environment favorable for healing. All attempts should be done to prevent diabetic foot ulceration and treat existing ulcers by multidisciplinary teams in order to decrease amputations. Indeed, improvement in ulcer healing has been observed with primary healing rates of 65-85% in mixed series. Even when healed, diabetic foot should be regarded as a life-long condition and treated accordingly to prevent recurrence. Long-term efforts have reduced amputation 37-75% in different European countries over 10-15 years.
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PMID:Treatment of diabetic foot ulcers. 1954 89

Peripheral arterial occlusive disease (PAOD) of lower extremities is becoming more prevalent worldwide. The general prognosis is particularly negative with a high prevalence of coronary heart disease and cerebrovascular disease. Diabetic foot ulcers occur in 15% of all the patients with diabetes and proceed to lower-leg amputations. In diabetic ulcers, wound healing is impaired because of delayed angiogenesis. In both pathological conditions, therapeutic angiogenesis using angiogenic growth factors, particularly Vascular Endothelial Growth Factor VEGF, is expected to be a valuable treatment. The most used approaches are based on VEGF local delivery or gene therapy, but they failed to meet the expected primary goals of therapy. Adenosine receptor stimulation can induce VEGF expression in many types of cells and this may be achieved by stimulating the A(2A) or A(2B) receptor or both, following the signalling pathways activated by hypoxia. Polideoxyribonucleotide (PDRN) is obtained from sperm trout by an extraction process. The compounds hold a mixture of deoxyribonucleotides polymers with chain lengths ranging between 50 and 2000 bp. PDRN is able to stimulate VEGF production during pathological conditions of low tissue perfusion. It likely acts through the stimulation of A(2A) receptors. Furthermore, acute and chronic toxicity studies showed a good safety profile. PDRN has been shown to be effective in an experimental model of PAOD, hind limb ischemia, impaired wound healing and burn injury. Preliminary studies and ongoing clinical trials predict a significant therapeutic efficacy in patients. These data lead to hypothesize a role for PDRN in therapeutic angiogenesis.
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PMID:Polydeoxyribonucleotide (PDRN): a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers. 1986 Jun 58

Diabetic foot is one of the challenging diseases in vascular surgery, especially in patients with end-staged renal disease due to diabetic nephropathy. This disease is based on the neuropathic gangrene due to microangiopathy as well as on the macroangiopathy such as peripheral arterial occlusive disease. Therefore, the strategy for diabetic foot is as follows: the first step is the infection control by minor amputation and/or drainage, the second step is the assessment of the limb ischemia, and the final is the complete vascular reconstruction such as distal bypass to the crural arteries. To salvage the diabetic foot, it is important that doctors, who concern to diabetics, understand these strategies and also that they have a settled opinion for the diabetic foot.
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PMID:[Revascularization in patients with diabetes]. 2044 96

The present study has 3 aims: (a) to characterize the clinical and pathological features of diabetic foot infections, (b) to show the range of clinical presentations of moderate infections, and (c) to analyze the different behavior of diabetic foot osteomyelitis regarding to its clinical presentation. A definitive diagnosis of the type of infection was made based on intraoperative findings and histopathology. Diabetic foot infections were classified into 2 types: soft tissue and bone infections. Mild infections were always superficial. Severe infections included 75% of necrotizing soft tissue infections. Moderate infections showed ample range of clinical presentations. Eighty-one patients presented osteomyelitis. Osteomyelitis was further classified as follows: osteomyelitis without ischemia and without soft tissue involvement (class 1), osteomyelitis with ischemia without soft tissue involvement (class 2), osteomyelitis with soft tissue involvement (class 3), and osteomyelitis with ischemia and soft tissue involvement (class 4). Forty-eight patients (59.3%) with osteomyelitis underwent conservative surgery, 32 (39.5%) had minor amputations including 9 open transmetatarsal amputations, and there was 1 (1.2%) major amputation. The characterization of osteomyelitis into 4 classes showed a statistically significant trend toward increased severity and increased amputation rate and mortality. In conclusion, the clinical presentation of foot infections in diabetic patients is very heterogeneous and can be classified into soft tissue infections (cellulitis, superficial and deep abscesses, and necrotizing soft tissue infections) and osteomyelitis, which was the most frequent type of infection found in the author's series. Their division into 4 classes showed a statistically significant trend toward increased severity, amputation rate, and mortality. The diagnosis of deep soft tissue infections associated with osteomyelitis may be difficult to achieve before surgery.
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PMID:Clinical-pathological characterization of diabetic foot infections: grading the severity of osteomyelitis. 2258 44

Diabetes is one of the major challenges of modern medicine, as it is considered a global epidemic of the XXI century. The disease often leads to the development of serious, health threatening complications. Diabetic foot syndrome is a characteristic set of anatomical and molecular changes. At the macroscopic level, major symptoms are neuropathy, ischemia and chronic ulceration of the lower limb. In every third patient, the neuropathy develops into Charcot neuroarthropathy characterized by bone and joints deformation. Interestingly, all these complications are a result of impaired healing processes and are characteristic for diabetes. The specificity of these symptoms comes from impaired molecular mechanisms observed in type 1 and type 2 diabetes. Decreased wound and fracture healing reflect gene expression, cellular response, cell functioning and general metabolism. Here we present a comprehensive literature update on the molecular factors contributing to diabetic foot syndrome.
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PMID:Molecular factors involved in the development of diabetic foot syndrome. 2325 10

Diabetic foot ulcers and their consequences do not only represent a major tragedy for the patient and his/her family, but also place a significant burden on the healthcare systems and society in general. Diabetic patients may develop foot ulcers due to neuropathy (autonomic, sensory, and motor deficits), angiopathy or both. As a result of the additional immunopathy associated with diabetes, the probability of these wounds to become infected is extremely high. Diabetic foot infections can be classified in mild, moderate and severe according to local and systemic signs. Their identification should lead to a prompt and systematic evaluation and treatment, ideally performed by a multidisciplinary team. Decisions concerning empirical initial antibiotic agent(s), desirable route of administration, duration and need of hospitalization should be based on the more likely involved pathogen(s), the severity of the infection, the ulcer chronicity and the presence of significant ischemia. Wound cultures, ideally from ulcer tissue, are strongly advisable and can help guiding and narrowing the antibiotic spectrum. Appropriate wound care and off-loading should not be neglected. When revascularization is required, the correct timing can be crucial for limb salvage. Since the recurrence of ulcer and infection is high, the implementation of appropriate preventive measures can be critical. Ultimately, the definitive goal in the treatment of diabetic foot infections is to prevent the amputation catastrophe.
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PMID:Guidelines for treatment of patients with diabetes and infected ulcers. 2344 4

The implementation of an inpatient diabetic foot service should be the goal of all institutions that care for patients with diabetes. The objectives of this team are to prevent problems in patients while hospitalized, provide curative measures for patients admitted with diabetic foot disorders, and optimize the transition from inpatient to outpatient care. Essential skills that are required for an inpatient team include the ability to stage a foot wound, assess for peripheral vascular disease, neuropathy, wound infection, and the need for debridement; appropriately culture a wound and select antibiotic therapy; provide, directly or indirectly, for optimal metabolic control; and implement effective discharge planning to prevent a recurrence. Diabetic foot ulcers may be present in patients who are admitted for nonfoot problems, and these ulcers should be evaluated by the diabetic foot team during the hospitalization. Pathways should be in place for urgent or emergent treatment of diabetic foot infections and neuropathic fractures/dislocations. Surgeons involved with these patients should have knowledge and interest in limb preservation techniques. Prevention of iatrogenic foot complications, such as pressure sores of the heel, should be a priority in patients with diabetes who are admitted for any reason: all hospitalized diabetic patients require a clinical foot exam on admission to identify risk factors such as loss of sensation or ischemia. Appropriate posthospitalization monitoring to reduce the risk of reulceration and infection should be available, which should include optimal glycemic control and correction of any fluid and electrolyte disturbances.
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PMID:Inpatient management of diabetic foot disorders: a clinical guide. 2397 Jul 16


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