Continuum of care in hard-to-heal wounds by copper dressings: a case series.

OBJECTIVE: The quest for an ideal wound dressing has been a longstanding challenge due to the complex nature of wound healing, including stages of haemostasis, inflammation, maturation and remodelling, with overlapping timelines. This makes it difficult to find a single dressing that optimally supports all phases of wound healing. In addition, the ideal wound dressing should possess antibacterial properties and be capable of effectively debriding and lysing necrotic tissue. Copper is an essential trace element that participates in many of the key physiological wound healing processes. METHOD: Copper stimulates secretion of various cytokines and growth factors, thus promoting angiogenesis, granulation tissue formation, extracellular matrix proteins secretion and re-epithelialisation. Harnessing this knowledge, we have used copper oxide-impregnated wound dressings in numerous cases and observed their benefits throughout the entire wound healing process. RESULTS: This led us to postulate the 'continuum of care' hypothesis of copper dressings. In this study we describe four cases of hard-to-heal wounds of various aetiologies, in which we applied copper dressings consistently across all stages of wound healing, with rapid uneventful healing. CONCLUSION: We believe we have successfully implemented the continuum of care principle.

Stimulation of Healing of Non-Infected Stagnated Diabetic Wounds by Copper Oxide-Impregnated Wound Dressings.

Background and Objective: Copper, a wide spectrum biocide, also plays a key role in angiogenesis and wound healing. Antibacterial wound dressings impregnated with copper oxide microparticles (COD) have been recently cleared by the U.S. FDA and other regulatory bodies for the treatment of acute and chronic wounds, including diabetic wounds. Our objective was to evaluate the capacity of COD in stimulating the healing of non-infected stagnated wounds in diabetic patients initially treated with standard of care (SOC) dressings. Materials and Methods: The trial was divided into the three following phases: 1-2 weeks of screening, during which the patients were treated with SOC dressings; 4 weeks of treatment, during which the COD was applied twice weekly; and 2 weeks of follow-up, during which the patients were again treated with SOC dressings. The wound conditions and sizes were assessed by clinical evaluation and a wound imaging artificial intelligence system. Results: Following 1 month of COD treatment, there was a clear reduction in the mean wound area (53.2%; p = 0.003), an increase in granulation tissue (43.37; p < 0.001), and a reduction in fibrins (47.8%; p = 0.002). In patients with non-weight-bearing wounds, the reduction in wound size was even more dramatic (66.9%; p < 0.001). Conclusions: The results of this study, showing a statistically significant influence of COD on wound healing of hard-to-heal wounds in diabetic patients, strongly supports the notion that copper oxide-impregnated dressings enhance wound healing directly. Further larger controlled studies should be conducted to substantiate our findings.

Healing of Chronic Wounds by Copper Oxide-Impregnated Wound Dressings-Case Series.

Novel antimicrobial wound dressings impregnated with copper oxide micro-particles have been cleared for treatment of acute and chronic wounds. Our objective is to provide preliminary data regarding the potential benefit of using these novel wound dressings including in non-infected wounds. Methods involved the treatment of wounds that responded partially or poorly to conventional wound healing treatments with copper oxide impregnated wound dressings in patients with a range of etiologies. Ten cases of patients with etiologies such as diabetes mellitus, sickle cell disease, renal failure, and necrotizing fasciitis, in which the application of copper oxide impregnated wound dressings in infected and non-infected wounds, which resulted in significant enhanced wound healing, are presented. This was exemplified by clearing of the wound infections, reduction of the fibrous and/or necrotic tissue and by intense granulation, epithelialization, and wound closure. The described 10 case reports support our hypothesis that the copper oxide-containing wound dressing not only confers protection to the wound and the dressing from microbial contamination, and in some cases may help clear the wound infections, but in addition and more importantly, stimulate skin regeneration and wound healing. Our findings are in line with previous animal and in vitro studies showing that copper plays a key role in angiogenesis and skin regeneration. These case reports support the notion that the use of copper oxide impregnated wound dressings may be an important intervention in the arsenal of wound treatment modalities, especially in hard to heal wounds.

Heparanase procoagulant activity as a predictor of wound necrosis following diabetic foot amputation.

BACKGROUND: Trans-metatarsal operation to diabetic foot necrosis is a common procedure although only half of the patients do not need a second amputation due to surgery wound ischemia. No current tools are available for early prediction of surgery success and the clinical decision for a second operation may take weeks. Heparanase protein is involved in inflammation, angiogenesis and coagulation activation. The aim of the study was to evaluate heparanase level and procoagulant activity as an early predictor for success or failure of diabetic foot trans-metatarsal surgery. METHODS: The study group included 40 patients with diabetic foot necrosis requiring trans-metatarsal surgical intervention. Eighteen patients designated as necrotic group, developed post-surgery necrosis at the surgery wound within the first month, requiring a second more proximal amputation. Skin biopsies from the proximal surgery edge were stained for heparanase, tissue factor (TF), TF pathway inhibitor (TFPI) and by hematoxylin and eosin. Plasma samples were drawn pre-surgery and at 1h, 1week and 1month post-surgery. Samples were tested for heparanase levels by ELISA and TF+heparanase activity, TF activity and heparanase procoagulant activity. RESULTS: Skin biopsy staining did not predict subsequent necrosis. In the non-necrotic group a significant rise in TF+heparanase activity, heparanase activity and heparanase levels were observed 1h and 1week post-surgery. The most significant increase was in heparanase procoagulant activity at the time point of 1h post-surgery (P<0.0001). Pre-surgery TF activity was significantly lower in the non-necrotic group compared to the necrotic group (P<0.05). CONCLUSIONS: Measuring heparanase procoagulant activity pre-surgery and 1h post-surgery could potentially serve as an early tool to predict the procedure success. The present results broaden our understanding regarding early involvement of heparanase in the wound healing process.

Deviations in gait metrics in patients with chronic ankle instability: a case control study.

BACKGROUND: Gait metric alterations have been previously reported in patients suffering from chronic ankle instability (CAI). Previous studies of gait in this population have been comprised of relatively small cohorts, and the findings of these studies are not uniform. The objective of the present study was to examine spatiotemporal gait metrics in patients with CAI and examine the relationship between self-reported disease severity and the magnitude of gait abnormalities. METHODS: Forty-four patients with CAI were identified and compared to 53 healthy controls. Patients were evaluated with spatiotemporal gait analysis via a computerized mat and with the Short Form (SF) - 36 health survey. RESULTS: Patients with CAI were found to walk with approximately 16% slower walking velocity, 9% lower cadence and approximately 7% lower step length. Furthermore, the base of support, during walking, in the CAI group was approximately 43% wider, and the single limb support phase was 3.5% shorter compared to the control group. All of the SF-36 8-subscales, as well as the SF-36 physical component summary and SF-36 mental component summary, were significantly lower in patients with CAI compared to the control group. Finally, significant correlations were found between most of the objective gait measures and the SF-36 mental component summary and SF-36 physical component summary. CONCLUSIONS: The results outline a gait profile for patients suffering from CAI. Significant differences were found in most spatiotemporal gait metrics. An important finding was a significantly wider base of support. It may be speculated that these gait alterations may reflect a strategy to deal with imbalance and pain. These findings suggest the usefulness of gait metrics, alongside with the use of self-evaluation questionnaires, in assessing disease severity of patients with CAI.

FDG PET/CT imaging in the diagnosis of osteomyelitis in the diabetic foot.

PURPOSE: Osteomyelitis, the most serious complication of the diabetic foot, occurs in about 20 % of patients. Early diagnosis is crucial. Appropriate treatment will avoid or decrease the likelihood of amputation. The objective of this study was to assess the value of FDG PET/CT in diabetic patients with clinically suspected osteomyelitis. METHODS: Enrolled in this prospective study were 39 consecutive diabetic patients (29 men and 10 women, mean age 57 years, range 28-71 years) with 46 suspected sites of foot infection. Of these 39 patients, 38 had type 2 and 1 type 1 diabetes for 4-25 years, and 28 were receiving treatment with insulin. FDG PET/CT was interpreted for the presence, intensity (SUVmax) and localization of increased FDG foci. Final diagnosis was based on histopathology and bacteriology of surgical samples, or clinical and imaging follow-up. RESULTS: Osteomyelitis was correctly diagnosed in 18 and excluded in 21 sites. Of 20 lesions with focal bone FDG uptake, 2 were false-positive with no further evidence of osteomyelitis. Five sites of diffuse FDG uptake involving more than one bone on CT were correctly diagnosed as diabetic osteoarthropathy. FDG PET/CT had a sensitivity, specificity and accuracy of 100 %, 92 % and 95 % in a patient-based analysis and 100 %, 93 % and 96 % in a lesion-based analysis, respectively, for the diagnosis of osteomyelitis in the diabetic foot. CONCLUSION: FDG PET/CT was found to have high performance indices for evaluation of the diabetic foot. The PET component identified FDG-avid foci in sites of acute infection which were precisely localized on fused PET/CT images allowing correct differentiation between osteomyelitis and soft-tissue infection.

Antibiotic impregnated cement spacer for salvage of diabetic osteomyelitis.

BACKGROUND: Florid infection and osteomyelitis of the forefoot in patients with diabetic neuropathy often requires minor amputation, with risk of subsequent reulceration, reamputation, and patient dissatisfaction. We investigated use of an antibiotic-impregnated cement spacer (ACS) to release antibiotic locally to resolve residual infection and to fill the cavity created by debridement. METHODS: We report 23 cases of osteomyelitis and associated severe infection of forefoot joints in 20 consecutive patients, age 60.3 +/- 13.4 years. Antibiotic-impregnated cement, extensive meticulous debridement, and ACS placement to fill the gap were employed in all cases. Deep cultures were taken routinely. Fixation with Kirschner wires was used as necessary. Mean followup was 21.2 +/- 10.2 months. A successful result was resolution of infection and wound healing to full skin closure without amputation. RESULTS: Of 23 cases, 21 (91.3%) healed and two required toe amputation. ACS was left permanently in 10 patients, removed with arthrodesis in six, and removed without arthrodesis in five. One patient recovered but subsequently underwent transtibial amputation due to infection of a different site. CONCLUSION: Severe infection associated with osteomyelitis of the foot in diabetic patients was successfully treated with extensive debridement and use of ACS, which filled the void created by debridement. Amputation was avoided in most patients. This procedure allowed extensive debridement through filling large voids with ACS, with prolonged antibiotic release.

[Plantar fasciitis and extracorporeal shock wave therapy--essence, diagnosis and treatment methods].

Heel pain is a very common foot complaint, usually caused by inflammation at the origin of the plantar fascia in the heel, termed plantar fasciitis (PF). The diagnosis is based on patient history and physical examination. Treatment of PF is mainly conservative. In recent years, extracorporeal shock wave therapy (ESWT) for a variety of orthopedic pathologies has become more acceptable and is increasing in popularity. Treating PF with ESWT is effective and should be considered before steroid injections and definitely prior to surgical intervention.

Involvement of microparticles in diabetic vascular complications.

Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and vascular complications. Circulating microparticles (MPs) are involved in thrombosis, inflammation, and angiogenesis. However, the role of MPs in T2DM vascular complications is unclear. We characterised the cell origin and pro-coagulant profiles of MPs obtained from 41 healthy controls and 123 T2DM patients with coronary artery disease, retinopathy and foot ulcers. The effects of MPs on endothelial cell coagulability and tube formation were evaluated. Patients with severe diabetic foot ulcers expressed the highest levels of MPs originated from platelet and endothelial cells and negatively-charged phospholipid-bearing MPs. MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor (TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients (<0.7) but high in patients with coronary artery disease and foot ulcers (>1.8, p≥0.002). MPs of all T2DM patients induced a more than two-fold increase in endothelial cell TF (antigen and gene expression) but did not affect TFPI levels. Tube networks were longest and most stable in endothelial cells that were incubated with MPs of healthy controls, whereas no tube formation occurred in MPs of diabetic patients with coronary artery disease. MPs of diabetic retinopathy and diabetic foot ulcer patients induced branched tube networks that were unstable and collapsed over time. This study demonstrates that MP characteristics are related to the specific type of vascular complications and may serve as a bio-marker for the pro- coagulant state and vascular pathology in patients with T2DM.

The diabetic foot: initial experience with 18F-FDG PET/CT.

UNLABELLED: Osteomyelitis complicates up to one third of diabetic foot infections, is often due to direct contamination from a soft-tissue lesion, and represents a clinical challenge. Early diagnosis is important since antibiotic therapy can be curative and may prevent amputation. The present study assessed the role of PET/CT using 18F-FDG for the diagnosis of diabetic foot osteomyelitis. METHODS: Fourteen diabetic patients (10 men and 4 women; age range, 29-70 y) with 18 clinically suspected sites of infection underwent PET/CT after the injection of 185-370 MBq of 18F-FDG for suspected osteomyelitis complicating diabetic foot disease. PET, CT, and hybrid images were independently evaluated for the diagnosis and localization of an infectious process. Additional data provided by PET/CT for localization of infection in the bone or soft tissues were recorded. The final diagnosis was based on histopathologic findings and bacteriologic assays obtained at surgery or at clinical and imaging follow-up. RESULTS: PET detected 14 foci of increased 18F-FDG uptake suspected as infection in 10 patients. PET/CT correctly localized 8 foci in 4 patients to bone, indicating osteomyelitis. PET/CT correctly excluded osteomyelitis in 5 foci in 5 patients, with the abnormal 18F-FDG uptake limited to infected soft tissues only. One site of mildly increased focal 18F-FDG uptake was localized by PET/CT to diabetic osteoarthropathy changes demonstrated on CT. Four patients showed no abnormally increased 18F-FDG uptake and no further evidence of an infectious process on clinical and imaging follow-up. CONCLUSION: 18F-FDG PET can be used for diagnosis of diabetes-related infection. The precise anatomic localization of increased 18F-FDG uptake provided by PET/CT enables accurate differentiation between osteomyelitis and soft-tissue infection.

Can complex regional pain syndrome be painless?

While spontaneous and stimulus-evoked pain are the hallmarks of complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy, autonomic abnormalities, motor dysfunction, and trophic changes in the affected limb are additional clinical characteristics distinguishing this syndrome. Even though the exact underlying mechanisms of the syndrome remain obscure, a recent hypothesis suggests that the abnormal response of neural nociceptive tissue plays a major role in the pathogenesis of CRPS via the mechanism known as 'neurogenic inflammation'. The group of patients presented here exhibited all the clinical characteristics of CRPS but had no pain, thereby indicating that ongoing or evoked pain is not a necessary condition for CRPS to be maintained. We suggest the term complex regional painless syndrome to describe this syndrome.

Two modifications of the Weil osteotomy: analysis on sawbone models.

Second metatarsal osteotomies (30 degrees angle to shaft) were performed in 40 sawbones with: 1. head shifted proximally 5 mm; 2. head shifted proximally 10 mm; 3. 5-mm slice resected and head shifted proximally 5 mm; or 4. 5-mm dorsally based wedge resected and head shifted proximally 5 mm. Bone slice resection resulted in shortening (16.4+/-1.7 mm) and mild plantar displacement of the head (3.5+/-0.8 mm). Bone wedge excision resulted in moderate shortening (7.8+/-0.9 mm) and essentially no plantar displacement of the head (0.8+/-1.4 mm).

A biomechanical study of two postoperative prostheses for transtibial amputees: a custom-molded and a prefabricated adjustable pneumatic prosthesis.

We evaluated an adjustable pneumatic prefabricated prosthesis and a rigid custom-molded prosthesis for immediate postoperative use. Twelve transtibial amputations were performed on cadaver limbs. Differential variable reluctance transducers were placed subcutaneously across the wound edge medially and laterally. The limbs were then placed in either the pneumatic prosthesis (five limbs) or the rigid prosthesis (seven limbs). The specimens underwent static and cyclic loading to simulate weight bearing. The strain readings for static and cyclic loading were greater in the rigid prosthetic group. Only the mean medial strain measurement after cyclic loading was statistically significant. The results demonstrate that the pneumatic prosthesis places less strain across the wound than a rigid prosthesis.

Arthrodesis of the first metatarsophalangeal joint: a biomechanical study comparing memory compression staples, cannulated screws, and a dorsal plate.

Arthrodesis of the first metatarsophalangeal joint of 21 matched pairs of cadaver toes was performed in order to compare the strength of three methods of internal fixation: 1. two crossed cannulated screws, 2. a dorsal plate with an oblique 0.062 K-wire, and 3. two compression staples with an oblique 0.062 K-wire. Biomechanical testing with plantar force was carried out, and gapping across the fusion site was measured. Stiffness, load to 1-mm displacement, and force to failure was determined for each specimen. Both the plate and screw constructs were statistically stronger in force to failure and initial stiffness than the compression construct. Compression staples have an advantage in their ease of insertion and theoretical continuous compressive force across an arthrodesis site, but should be supplemented with a cast or other external immobilization until union is achieved.