A novel native collagen dressing with advantageous properties to promote physiological wound healing.

OBJECTIVE: Chronic hard-to-heal wounds generate high costs and resource use in western health systems and are the focus of intense efforts to improve healing outcomes. Here, we introduce a novel native collagen (90 %):alginate (10 %) wound dressing and compare it with the established oxidised dressings Method: Matrices were analysed by atomic force microscopy (AMF), scanning electron microscopy (SEM), and immunoelectron microscopy for collagen types I, III and V. Viability assays were performed with NIH-3T3 fibroblasts. Matrix metalloproteinase (MMP) binding was analysed, and the effect of the wound dressings on platelet-derived growth factor B homodimer (PDGF-BB) was investigated. RESULTS: Unlike oxidised regenerated cellulose (ORC)/collagen matrix and ovine forestomach matrix (OFM), the three-dimensional structure of the native collagen matrix (NCM) was found to be analogous to intact, native, dermal collagen. Fibroblasts seeded on the NCM showed exponential growth whereas in ORC/collagen matrix or OFM, very low rates of proliferation were observed after 7 days. MMP sequestration was effective and significant in the NCM. In addition, the NCM was able to significantly stabilise PDGF-BB in vitro. CONCLUSION: We hypothesise that the observed microstructure of the NCM allows for an effective binding of MMPs and a stabilisation and protection of growth factors and also promotes the ingrowth of dermal fibroblasts, potentially supporting the re commencement of healing in previously recalcitrant wounds. DECLARATION OF INTEREST: This work was supported by BSN Medical, Hamburg, Germany.

Evaluation of tissue engineering products for the management of neuropathic diabetic foot ulcers: an interim analysis.

OBJECTIVE: The objective of this prospective, multicentre clinical study is to assess the application of MatriStem MicroMatrix (MSMM) and MatriStem Wound Matrix (MSWM) (porcine urinary bladder derived extracellular matrix) compared with Dermagraft (DG) (human fibroblast-derived dermal substitute) for the management of non-healing diabetic foot ulcers (DFUs). METHOD: A randomised, multicentre study was conducted at thirteen centers throughout the US. It was designed to evaluate the incidence of ulcer closure, rate of ulcer healing, wound characteristics, patient quality of life, cost-effectiveness, and recurrence. Those subjects whose DFUs decreased in size by ≤30% or increased by ≤50% during the standard of care (SOC) phase were randomised into the treatment phase of the study. The study evaluated complete wound closure by eight weeks with weekly device application. A two-week post treatment SOC phase followed the treatment phase for any wounds that did not heal by the end of eight weeks, and wound closure was also evaluated at the end of that period. Ulcer recurrence at 6 months post-treatment was evaluated in the subjects that showed wound healing by the end of the post-treatment SOC phase. Standard adjunctive therapy, including debridement, saline irrigation and foot off-loading, was provided to both arms during the four-week screening period, after which eligible subjects were randomised in a 1:1 ratio, to either the MatriStem (MS) or DG treatment arm. This study was developed to evaluate the hypothesis that the wound outcomes observed after wound management with MS were non-inferior to those of DG after eight weeks. The authors present the planned interim results of this study after one half of the projected enrolment was completed. RESULTS: There were 95 subjects consented and entered into the SOC four-week screening phase of the trial and 56 were randomised into the treatment phase. At the planned interim analysis, there was a significantly lower cost per subject and significant improvement in patient quality of life for the subjects treated with MS compared with those managed with DG. However, there was not a statistically significant difference found during the analysis of the interim data between the two study groups for rate of wound healing or number of subjects with complete wound closure. CONCLUSION: The data from this interim analysis show that MSMM and MSWM provide results for healing DFUs that are similar to the results obtained for DG at a significant quality of life and economic advantage. DECLARATION OF INTEREST: The opinions expressed are those of the authors and not necessarily those of the Department of Veterans Affairs or the United States Government. T.W. Gilbert is employed as the Chief Science Officer and is a stockholder in ACell, Inc., which commercializes MatriStem Wound Matrix and MicroMatrix. None of the other authors have a conflict of interest to declare.

Unstable acute and chronic Charcot's deformity: staged skeletal and soft-tissue reconstruction.

Acute and chronic Charcot's foot deformity is a progressive, disabling and disfiguring condition that is prone to ulceration and infection. If conservative treatment is ineffective, bone and soft-tissue reconstruction is a viable option.

Classifying diabetic foot surgery: toward a rational definition.

The purpose of this manuscript was to describe a classification of diabetic foot surgery performed in the absence of critical limb ischaemia. The basis of this classification is centered on three fundamental variables which are present in the assessment of risk and indication: 1) the presence or absence of neuropathy (loss of protective sensation); 2) the presence or absence of an open wound; 3) the presence or absence of acute, limb-threatening infection. The conceptual framework for this classification is to define distinct classes of surgery in an order of theoretically increasing risk for high-level amputation. These classes include: Class I: Elective Diabetic Foot Surgery (procedures performed to treat a painful deformity in a patient without loss of protective sensation); Class II: Prophylactic (Procedure performed to reduce risk of ulceration or reulceration in person with loss of protective sensation but without open wound); Class III: Curative (Procedure performed to assist in healing open wound) and Class IV: Emergent (Procedure performed to limit progression of acute infection). The presence of critical ischaemia in any of these classes of surgery should prompt a vascular evaluation to consider a) the urgency of the procedure being considered and b) possible revascularization prior or temporally concomitant with the procedure. It is our hope that this system begins a dialogue amongst physicians and surgeons which can ultimately facilitate communication, enhance perspective, and improve care.

Management of the diabetic Charcot foot.

The diabetic Charcot foot is a major limb-threatening complication of long-term diabetes mellitus and neuropathy. Although first described over 100 years ago, we are still lacking definitive studies regarding its prevalence in this population, precise etiology, or most effective treatments. Trauma in the presence of peripheral sensory neuropathy and abundant arterial perfusion seem to be the primary causal factors leading to this severe foot deformity. Misdiagnosis or delayed diagnosis of osteoarthropathy allows the destructive phase of this disorder to continue with resultant further destruction of the foot architecture. The authors discuss the natural history of this entity as well as potential treatment options and recommendations. Through a better understanding of the underlying pathogenesis, Charcot arthropathy can be more effectively managed and thereby limit the development of severe deformity, ulceration, infection and limb loss.

Diabetic foot disorders. A clinical practice guideline. For the American College of Foot and Ankle Surgeons and the American College of Foot and Ankle Orthopedics and Medicine.

Foot ulcerations, infections, and Charcot neuropathic osteoarthropathy are three serious foot complications of diabetes mellitus that can too frequently lead to gangrene and lower limb amputation. Consequently, foot disorders are one of the leading causes of hospitalization for persons with diabetes and can account for expenditures in the billions of dollars annually in the U.S. alone. Although not all foot complications can be prevented, dramatic reductions in their frequency have been obtained through the implementation of a multidisciplinary team approach to patient management. Using this concept, the authors present a Clinical Practice Guideline for diabetic foot disorders based on currently available evidence. The underlying pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are thoroughly reviewed. Although these guidelines cannot and should not dictate the standard of care for all affected patients, they are intended to provide evidence-based guidance for general patterns of practice. The goal of a major reduction in diabetic limb amputations is certainly possible if these concepts are embraced and incorporated into patient management protocols.

Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons.

Foot ulcerations, infections, and Charcot neuropathic osteoarthropathy are three serious foot complications of diabetes mellitus that can too frequently lead to gangrene and lower limb amputation. Consequently, foot disorders are one of the leading causes of hospitalization for persons with diabetes and can account for expenditures in the billions of dollars annually in the U.S. alone. Although not all foot complications can be prevented, dramatic reductions in their frequency have been obtained through the implementation of a multidisciplinary team approach to patient management. Using this concept, the authors present a Clinical Practice Guideline for diabetic foot disorders based on currently available evidence. The underlying pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are thoroughly reviewed. Although these guidelines cannot and should not dictate the standard of care for all affected patients, they are intended to provide evidence-based guidance for general patterns of practice. The goal of a major reduction in diabetic limb amputations is certainly possible if these concepts are embraced and incorporated into patient management protocols.

Diabetic foot ulcers: current concepts.

Foot ulcerations and their sequelae remain a major source of morbidity for patients with diabetes mellitus. Often leading to infection, osteomyelitis, or gangrene, these lesions have consistently been ascertained as significant risk factors for subsequent lower extremity amputation. Hence education, appropriate foot care, and early intervention have assumed important roles in programs focused on amputation prevention. Multidisciplinary cooperation has been demonstrated as the most successful approach to the management and prevention of foot lesions in patients with diabetes. This article reviews the epidemiology, current understanding of the underlying pathophysiology, and treatment rationale for diabetic foot ulcerations. Such knowledge is essential in the overall management of these complicated patients and, when incorporated into daily practice, can significantly reduce the incidence and morbidity of foot disease in diabetes.

Role of neuropathy and high foot pressures in diabetic foot ulceration.

OBJECTIVE: High plantar foot pressures in association with peripheral neuropathy have been ascertained to be important risk factors for ulceration in the diabetic foot. Most studies investigating these parameters have been limited by their size and the homogeneity of study subjects. The objective of this study was therefore to ascertain the risk of ulceration associated with high foot pressures and peripheral neuropathy in a large and diverse diabetic population. RESEARCH DESIGN AND METHODS: We studied a cross-sectional group of 251 diabetic patients of Caucasian (group C) (n=121), black (group B) (n=36), and Hispanic (group H) (n=94) racial origins with an overall age of 58.5+/-12.5 years (range 20-83). There was an equal distribution of men and women across the entire study population. All patients underwent a complete medical history and lower extremity evaluation for neuropathy and foot pressures. Neuropathic parameters were dichotomized (0/1) into two high-risk variables: patients with a vibration perception threshold (VPT) > or =25 V were categorized as HiVPT (n=132) and those with Semmes-Weinstein monofilament tests > or =5.07 were classified as HiSWF (n=190). The mean dynamic foot pressures of three footsteps were measured using the F-scan mat system with patients walking without shoes. Maximum plantar pressures were dichotomized into a high-pressure variable (Pmax6) indicating those subjects with pressures > or =6 kg/cm2 (n=96). A total of 99 patients had a current or prior history of ulceration at baseline. RESULTS: Joint mobility was significantly greater in the Hispanic cohort compared with the other groups at the first metatarsal-phalangeal joint (C 67+/-23 degrees, B 69+/-23 degrees, H 82+/-23 degrees, P=0.000), while the subtalar joint mobility was reduced in the Caucasian group (C 21+/-8 degrees, B 26+/-7 degrees, H 27+/-11 degrees, P=0.000). Maximum plantar foot pressures were significantly higher in the Caucasian group (C 6.7+/-2.9 kg/cm2, B 5.7+/-2.8 kg/cm2, H 4.4+/-1.9 kg/cm2, P=0.000). Univariate logistic regression for Pmax6 on the history of ulceration yielded an odds ratio (OR) of 3.9 (P=0.000). For HiVPT, the OR was 11.7 (P=0.000), and for HiSWF the OR was 9.6 (P=0.000). Controlling for age, diabetes duration, sex, and race (all P < 0.05), multivariate logistic regression yielded the following significant associations with ulceration: Pmax6 (OR=2.1, P=0.002), HiVPT (OR=4.4, P=0.000), and HiSWF (OR=4.1, P=0.000). CONCLUSIONS: We conclude that both high foot pressures (> or =6 kg/cm2) and neuropathy are independently associated with ulceration in a diverse diabetic population, with the latter having the greater magnitude of effect. In black and Hispanic diabetic patients especially, joint mobility and plantar pressures are less predictive of ulceration than in Caucasians.

The team approach in diabetic foot management.

A significant reduction in the incidence of ulceration, infection, and lower extremity amputation can be realized through the institution of an organized foot care service in community and major academic medical centers. A multidisciplinary team approach has proven to be the most effective means of providing treatment and preventing foot lesions in the diabetic patient. Aside from prevention and early intervention, education is an essential component in overall patient management. In the scheme presented in this article, outpatient management is optimized through the services of numerous specialists dedicated to limb preservation. Risk factors must be evaluated, risk status determined, and preventive measures taken to preserve an intact foot. Ulcers must be thoroughly evaluated and appropriately treated through established protocols utilizing all members of the team. When acute problems present, they are more efficiently managed and coordinated by this approach, thereby reducing lengths of hospital stay, morbidity, and loss of limbs.

Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy.

OBJECTIVE: We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects. RESEARCH DESIGN AND METHODS: We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44 degrees C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response). RESULTS: The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 +/- 4 vs. 55 +/- 10 [mean +/- SEM]; P < 0.01)], the non-neuropathic group (33 +/- 6 vs. 88 +/- 14; P < 0.01), and the control subjects (43 +/- 6 vs. 93 +/- 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 +/- 0.24; non-neuropathic group, 2.55 +/- 0.35; and control subjects, 2.11 +/- 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 +/- 0.27; non-neuropathic group, 2.08 +/- 0.33; and control subjects, 2.77 +/- 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups. CONCLUSIONS: In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.

Functional outcome in the elderly following lower extremity amputation.

Data regarding functional outcome in the elderly following major lower extremity amputation (LEA) are minimal. In the general diabetic population there is a significant mortality associated with these procedures, with the 5-year survival rates approaching only 40%. Contrasts between this group and the nondiabetic population will help to clarify the morbidity of these procedures and substantiate efforts at limb salvage. The authors review their experience with patients 80 years of age and above undergoing major LEA between 1990 and 1995 with a specific focus on postoperative mortality and functional status. Forty-one patients were studied, 67% of whom had diabetes mellitus. Postoperative functional status remained unchanged in 40% and worsened in 55% of patients, while residential status was unchanged in 68% and worsened in 32%. The median survival for patients with and without diabetes was 19 and 49 months, respectively. The 5-year survival for the entire group was 25% and was not statistically different in the two subgroups. The authors conclude that major LEA in the very elderly is associated with a considerable mortality and deterioration of functional and residential status.

Diabetic foot infections: evaluation and management.

Management of diabetic foot infections requires a thorough knowledge of the pathophysiology involved, the associated microbiological characteristics, and current diagnostic and treatment regiments. Management of the infected diabetic foot requires a combination of therapies including antimicrobial agents, surgical drainage, local wound care, and avoidance of weight-bearing. The complexities of this problem often require the input of multiple specialists working cohesively to manage the concurrent complications of the disease in general, as well as the foot lesion in particular.

Team approach toward lower extremity amputation prevention in diabetes.

Through a discussion of the etiology and pathology of diabetic foot lesions with particular emphasis on ulceration and osteoarthropathy, the author will develop a plan for treatment and prevention using a multidisciplinary approach to such problems. Underlying risk factors including neuropathy, ischemia, infection, and, especially high pressures must be evaluated and appropriately ameliorated in order to promote resolution and avoidance of recidivism. Accordingly, conservative management with pressure-relieving devices, topical therapies, and prophylactic surgery on structural deformities plays an integral part in the overall podiatric management of the high-risk foot in diabetes mellitus.

Difference in treatment of foot ulcerations in Boston, USA and Pisa, Italy.

Primary care of the diabetic patient with foot ulcer can be provided by medically or surgically trained practitioners. We have prospectively followed 90 sequential patients with newly developed foot ulcers from two major centers. One in the USA where the primary doctor was a podiatrist and one in Europe with a diabetologist. Thirty-four patients from Boston and 56 from Pisa (mean age, 55.6; range, 26-75 years; vs. 66.5; range, 35-94; P < 0.001), matched for sex, weight, type, duration of diabetes, renal impairment and retinopathy took part. Boston patients had more severe neuropathy, assessed with clinical examination utilizing a neuropathy disability score (NDS) (16 +/- 6 vs. 6 +/- 3 (mean +/- S.D.) P < 0.001) and vibration perception threshold (46 +/- 8 vs. 35 +/- 12 V: P < 0.001) while no difference existed in the number of patients with clinical infection, a history of lower extremity by-pass operation (6 (18%) vs. 3 (5%); P = NS) and in the size and the severity of the ulcer, according to the Wagner classification. Initial treatment was similar in both centers with emphasis on outpatient ulcer debridement, pressure relieving foot-wear and topical wound care. Hospitalization was needed in five (15%) Boston and 12 (21%) Pisa patients (P = NS) while surgery was performed on five (15%) Boston and 16 (29%) Pisa patients (P = NS). The in-hospital stay was similar in both centers (1.4 +/- 4.4 vs. 2.1 +/- 5.9 days; P = NS). The most common operations in both centers were incision, drainage and bone debridement. Ulcers healed in all patients but the amount of healing time was shorter in Boston patients (6.7 +/- 4.2 vs. 10.5 +/- 6.5 weeks; P < 0.02). We conclude that despite the differences in the two systems similar success rates were achieved in the two centers while a more surgically oriented strategy may have resulted in a slightly shorter healing time.