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The epidermis is maintained by epidermal stem cells (ESCs) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the nonhealing edges of venous ulcers (VUs) are healing-incompetent, hyperproliferative, and nonmigratory, suggesting deregulation of ESCs. To date, genes which regulate ESC niches have been studied in mice only. Utilizing microarray analysis of VU nonhealing edges, we identified changes in expression of genes harboring regulation of ESCs and their fate. In a prospective clinical study of 10 VUs, we confirmed suppression of the bone morphogenetic protein receptor (BMPR) and GATA binding protein 3 (GATA3) as well as inhibitors of DNA-binding proteins 2 and 4 (ID2 and ID4). We also found decreased levels of phosphorylated glycogen synthase kinase 3 (GSK3), nuclear presence of β-catenin, and overexpression of its transcriptional target, c-myc, indicating activation of the Wnt pathway. Additionally, we found down-regulation of leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1), a gene important for maintaining ESCs in a quiescent state, and absence of keratin 15 (K15), a marker of the basal stem cell compartment suggesting local depletion of ESCs. Our study shows that loss of genes important for regulation of ESCs and their fate along with activation of β-catenin and c-myc in the VU may contribute to ESC deprivation and a hyperproliferative, nonmigratory healing incapable wound edge., (© 2014 The Wound Healing Society.)

Chronic wounds are an important health problem because they are difficult to heal and treatment is often complicated, lengthy and expensive. For a majority of sufferers the most common outcomes are long-term immobility, infection and prolonged hospitalisation. There is therefore an urgent need for effective therapeutics that will enhance ulcer healing and patient quality of life, and will reduce healthcare costs. Studies in our laboratory have revealed elevated levels of purine catabolites in wound fluid from patients with venous leg ulcers. In particular, we have discovered that uric acid is elevated in wound fluid, with higher concentrations correlating with increased wound severity. We have also revealed a corresponding depletion in uric acid precursors, including adenosine. Further, we have revealed that xanthine oxidoreductase, the enzyme that catalyses the production of uric acid, is present at elevated levels in wound fluid. Taken together, these findings provide evidence that xanthine oxidoreductase may have a function in the formation or persistence of chronic wounds. Here we describe the potential function of xanthine oxidoreductase and uric acid accumulation in the wound site, and the effect of xanthine oxidoreductase in potentiating the inflammatory response.

Purpose: To provide information on the Five-Times-Sit-to-Stand (FTSTS) and Timed-Up-and-Go (TUG) tests in persons with injection-related venous ulcers (VU+) and persons without venous ulcers (VU-)., Target Audience: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care., Objectives: After participating in this educational activity, the participant should be better able to:, Objective: To examine functional mobility using Five-Times-Sit-to-Stand (FTSTS) and Timed-Up-and-Go (TUG) tests in persons with injection-related venous ulcers (VU+) and compare these findings to persons without venous ulcers (VU-)., Design: Cross-sectional, comparative design., Setting: Outpatient clinic.PARTICPANTS: Participants (n = 61) were 31 persons VU+ and 30 persons VU-; 57.4% men; mean age, 54 years; 93% African American., Main Outcome Measures: Five-Times-Sit-to-Stand, TUG, physical activity, quality of life, comorbidities, falls, and body mass index., Results: Participants VU+ were 36.8% slower on completion of the TUG test (P = .012) and 26.5% slower on completion of the FTSTS test (P = .081). Five-Times-Sit-to-Stand and TUG were strongly correlated with each other, r = 0.93, 0.87, P < .001 for VU- and VU+, respectively. Test-retest reliabilities for the FTSTS and TUG tests were high (intraclass correlation coefficient = 0.89-0.94) for the VU+ and VU-. Within each group, correlations of FTSTS and TUG were similar for each of the variables examined. Across groups, correlations showed that the time to complete FTSTS and TUG increased as a function of comorbidities in the VU+ group; the correlations in the VU- group were not significantly different from zero., Conclusions: The VU+ group exhibited poorer physical performance than the VU- group. The high correlation between FTSTS and TUG and the similarity of correlations with other variables suggest that these physical performance measures may be interchangeable in their ability to predict physical functioning in these clinical groups despite differences in test demands. Clinicians need easy-to-perform reliable clinical tests such as FTSTS and TUG to assess mobility of aging injection users with venous ulcers.

An increasing number of compression systems available for treatment of venous leg ulcers and limited evidence on the relative effectiveness of these systems are available. The purpose of this study was to conduct a randomised controlled trial to compare the effectiveness of a four-layer compression bandage system and Class 3 compression hosiery on healing and quality of life (QL) in patients with venous leg ulcers. Data were collected from 103 participants on demographics, health, ulcer status, treatments, pain, depression and QL for 24 weeks. After 24 weeks, 86% of the four-layer bandage group and 77% of the hosiery group were healed (P = 0·24). Median time to healing for the bandage group was 10 weeks, in comparison with 14 weeks for the hosiery group (P = 0·018). The Cox proportional hazards regression found participants in the four-layer system were 2·1 times (95% CI 1·2-3·5) more likely to heal than those in hosiery, while longer ulcer duration, larger ulcer area and higher depression scores significantly delayed healing. No differences between groups were found in QL or pain measures. Findings indicate that these systems were equally effective in healing patients by 24 weeks; however, a four-layer system may produce a more rapid response., (© 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

This is the seventh article in the series of Clinical Updates on Nursing Home Care. The topics covered are antiresorptive drugs, hip fracture, hypertension, orthostatic hypotension, depression, undernutrition, anorexia, cachexia, sarcopenia, exercise, pain, and behavioral and psychological symptoms of dementia., (Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The goals of this study were to analyze the 2010 update of the Association for the Advancement of Wound Care (AAWC) Venous Ulcer Guideline (VUG) and examine recommendations with less than A-level evidence to identify important research questions., Data Sources: The AAWC VUG may be found at http://aawconline.org/professional-resources/resources and at the National Guideline Clearinghouse, http://www.guideline.gov. Supporting references for each recommendation, compiled by the AAWC Guideline Task Force from MEDLINE, CINAHL, and EMBASE databases, may be viewed at the first website., Study Selection: The literature identified in support of the AAWC VUG recommendations with less than A-level evidence was evaluated and is summarized below., Data Extraction: Questions requiring further research in venous ulcer (VU) care were developed from recommendations having less than A-level support and that fall under the following topics: diagnosis, documentation, prevention, wound care, adjunctive interventions, and palliation., Data Synthesis: Practitioners lack strong evidence for several generally accepted recommendations of this synthesis of VU guidelines concerning the following: diagnostic or screening validity of varicosities, timing of biopsies for differential diagnosis, clinic visit frequency, criteria for changing VU care plans, and effective VU preventive parameters. Bedside surgical debridement, several biologic interventions, certain types of grafting, and the comparative efficacy of intravascular surgical procedures also require rigorous examination. Adjunctive interventions to be investigated include systemic pain management, topical biophysical treatments, novel devices, pharmaceuticals, timing, methods and procedures for some surgical interventions., Conclusions: Better evidence for recommendations with less than A-level support may improve the quality and consistency of VU care, reduce costs, and improve resource use.

Background: Some prognostic markers of venous leg ulcer (VLU) healing have been evaluated, mostly in retrospective studies., Objectives: To identify which clinical characteristics, among those known as possible prognostic factors of VLU healing, and which VLU-associated sociodemographic and psychological factors, are associated with complete healing at week 24 (W24)., Methods: A prospective, multicentre, cohort study was conducted in 22 French dermatology departments between September 2003 and December 2007. The end point was comparison between healed and nonhealed VLUs at W24, for patient clinical and biological characteristics; psychological, cognitive and social assessments; affected leg inclusion characteristics; venous insufficiency treatment and percentage of initial wound area reduction during follow-up., Results: In total, 104 VLUs in 104 patients were included; 94 were analysed. The mean VLU area and duration were 36.8 ± 55.5 cm2 and 24.8 ± 45.7 months, respectively. At W24, 41/94 VLUs were healed. Univariate analysis significantly associated complete healing with superficial venous surgery (P = 0.001), adherence to compression therapy at W4 (P = 0.03) and W24 (P = 0.01), ankle-joint ankylosis (P = 0.01) and mean percentage of VLU area reduction at W4 (P = 0.04). Multivariate analysis retained superficial venous surgery during follow-up [odds ratio (OR) 8.4, 95% confidence interval (CI) 1.9-48.2] and percentage reduction of the VLU area at W4 (OR 1.6, 95% CI 1.0-2.14) as being independently associated with healing., Conclusions: These results indicate that complete healing of long-standing, large VLUs is independently associated with ablation of the incompetent superficial vein and percentage of wound area reduction after the first 4 weeks of treatment., (© 2013 British Association of Dermatologists.)

To achieve good patient outcomes, clinicians must ensure that clinical decision making is informed by valid and reliable evidence. This review examines the evidence on the clinical efficacy and reproducibility of compression applied by the KTwo bandage system. Its aim is to describe the evidence, not critique it. However, it clearly shows there is a body of evidence, from simple comparative evaluations to a randomised controlled trial, demonstrating the effectiveness of this system

Background: Nonhealing ulcers affect patient quality of life and impose a substantial financial burden on the health care system., Purpose: To systematically evaluate benefits and harms of advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers., Data Sources: MEDLINE (1995 to June 2013), the Cochrane Library, and reference lists., Study Selection: English-language randomized trials reporting ulcer healing or time to complete healing in adults with nonhealing ulcers treated with advanced therapies., Data Extraction: Study characteristics, outcomes, adverse events, study quality, and strength of evidence were extracted by trained researchers and confirmed by the principal investigator., Data Synthesis: For diabetic ulcers, 35 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with a biological skin equivalent (relative risk [RR], 1.58 [95% CI, 1.20 to 2.08]) and negative pressure wound therapy (RR, 1.49 [CI, 1.11 to 2.01]) compared with standard care and low-strength evidence for platelet-derived growth factors and silver cream compared with standard care. For venous ulcers, 20 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with keratinocyte therapy (RR, 1.57 [CI, 1.16 to 2.11]) compared with standard care and low-strength evidence for biological dressing and a biological skin equivalent compared with standard care. One small trial of arterial ulcers reported improved healing with a biological skin equivalent compared with standard care. Overall, strength of evidence was low for ulcer healing and low or insufficient for time to complete healing., Limitations: Only studies of products approved by the U.S. Food and Drug Administration were reviewed. Studies were predominantly of fair or poor quality. Few trials compared 2 advanced therapies., Conclusion: Compared with standard care, some advanced wound care therapies may improve the proportion of ulcers healed and reduce time to healing, although evidence is limited., Primary Funding Source: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

Patients who participated in a Phase 2 trial of HP802-247 for venous leg ulcers were invited to participate in this 24-week follow-up study to assess the durability of healing, document additional ulcer closures, and evaluate posttreatment safety. Consent was given by 90% (206/228), with 80% (183/228) completing all visits. Blinding was retained from the previous trial in which subjects had been randomized to vehicle or one of four cell therapy regimens. Visits were every 8 weeks. Among the 183 subjects, 43% (21/49) previously treated with cells and entering follow-up with an open wound achieved closure, compared with 35% (7/20) previously treated with vehicle, while 10% (11/106) and 17% (3/18), respectively, experienced reopening of a previously closed wound. Subjects previously treated with cells closed more open wounds than those previously treated with vehicle (OR 1.39, 95% CI 0.47-4.10; p = 0.739), and less subjects with a previously closed wound reopened (OR 0.65, CI 0.16-2.60; p = 0.821); however, these findings were not statistically significant. At the final visit, the difference in proportion of subjects with wounds closed continued to favor the best dose from the prior trial (83% closed vs. 58%, delta 25%). Follow-up beyond 12 weeks is necessary to evaluate the full benefit of this therapy, as treatment with cells may provide stimulus toward healing that persists for up to several weeks following the last application. The results show that the greater proportional benefit achieved by HP802-247 relative to standard care after 12 weeks of treatment persists over a meaningful timeframe., (© 2013 by the Wound Healing Society.)

Compression therapy--including inelastic, elastic, and intermittent pneumatic compression--is the standard of care for venous ulcers (VLUs) and chronic venous insufficiency, but there is no consensus in the literature regarding the most effective type of compression therapy. A prospective, randomized, clinical pilot study was conducted among 70 patients with unilateral VLUs treated in a hospital dermatology department in Poland to compare three types of compression therapy (intermittent pneumatic compression, stockings, and short-stretch bandages) in persons with superficial deep venous reflux alone or combined with the segmental variety. Study endpoints were change in ulcer dimensions and proportions healed. Patients with superficial or combined superficial and deep vein insufficiency were randomly allocated to receive one of the three therapies (one of each vein type for each treatment option, six groups total). All patients received saline-soaked gauze dressings along with micronized purified flavonoid fraction, diosmin, hesperidin, and Daflon 500 once daily. Compression treatments were changed or pneumatic compression provided daily for 15 days. Wound size reduction and percentage of wounds healed were significantly higher in groups receiving intermittent pneumatic compression or stockings than in groups using short-stretch bandages (for percentage change of ulcer surface area, P = 0.02; for healing rates P = 0.01). These results warrant additional randomized controlled clinical studies with a larger sample size and longer patient follow-up.

This study aimed to assess the feasibility of a home-based exercise programme and examine the effects on the healing rates of venous leg ulcers. A 12-week randomised controlled trial was conducted investigating the effects of an exercise intervention compared to a usual care group. Participants in both groups (n = 13) had active venous ulceration and were treated in a metropolitan hospital outpatients clinic in Australia. Data were collected on recruitment from medical records, clinical assessment and questionnaires. Follow-up data on progress in healing and treatments were collected fortnightly for 12 weeks. Calf muscle pump function data were collected at baseline and 12 weeks from recruitment. Range of ankle motion data were collected at baseline, 6 and 12 weeks from recruitment. This pilot study indicated that the intervention was feasible. Clinical significance was observed in the intervention group with a 32% greater decrease in ulcer size (P = 0·34) than the usual care group, and a 10% (P = 0·74) improvement in the number of participants healed in the intervention group compared to the usual care group. Significant differences between groups over time were observed in calf muscle pump function parameters [ejection fraction (P = 0·05), residual volume fraction (P = 0·04)] and range of ankle motion (P = 0·01). This pilot study is one of the first to examine and measure clinical healing rates for participants involved in a home-based progressive resistance exercise programme. Further research is warranted with a larger multi-site study., (© 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.)

Objective: The aim of this study was to investigate the feasibility to measure microcirculatory blood flow changes in patients with venous ulcers, by using the laser speckle imaging., Methods: Nine patients with a leg ulcer were measured with the laser speckle imager in a sitting position before and after mimicking venous hypertension, with the legs raised, by applying a blood pressure cuff and inflating it to 60 mmHg., Results: The results were inconclusive, due to the fact that a lot of practical problems interfered with the measurements, e.g. movement artefacts and inadequate wound visualisation., Conclusion: The additional value of laser speckle imaging in daily practice for wound care still remains an important question for further research. A reliable, reproducible microcirculation measurement in venous ulcers might predict venous ulcer healing and recurrence and therefore would be a valuable diagnostic tool in daily practice.

Compression therapy is considered to be the most important conservative treatment of venous leg ulcers. Until a few years ago, compression bandages were regarded as first-line therapy of venous leg ulcers. However, to date medical compression stockings are the first choice of treatment. With respect to compression therapy of venous leg ulcers the following statements are widely accepted: 1. Compression improves the healing of ulcers when compared with no compression; 2. Multicomponent compression systems are more effective than single-component compression systems; 3. High compression is more effective than lower compression; 4. Medical compression stockings are more effective than compression with short stretch bandages. Healed venous leg ulcers show a high relapse rate without ongoing treatment. The use of medical stockings significantly reduces the amount of recurrent ulcers. Furthermore, the relapse rate of venous leg ulcers can be significantly reduced by a combination of compression therapy and surgery of varicose veins compared with compression therapy alone.

Our objective was to study the prevalence and clinical pattern of chronic venous disease (CVD) in the Pakistani population. This was a multicentre cross-sectional study in which 100 primary care physicians examined 3000 subjects. The study population was aged 18-95 years (mean ± SD = 39 ± 13.2) comprised 47.4% women and 52.6% men. The prevalence of CVD was 34.8%, being significantly higher (P < 0.04) among men (36.4%) than women (33.0%). The maximum prevalence was of C3 (36.7%), followed by C2 (15.8%). The most frequent symptom was pain in the legs (59.2%) followed by heavy legs (42.7%) and night cramps (34.4%). The prevalence of symptoms increased with age but was similarly distributed between men and women. Family history of CVD, blood clots in veins and lack of exercise were significant risk factors. The roles of age or gender as risk factors could not be established. In conclusion, the prevalence and presentation of CVD in Pakistan is similar to most other countries.

In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well-defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1·35; lower-upper quartiles 0·71-1·83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2·22; 1·12-2·33; P = 0·0024) when compared with NGTA, in combination with a significant increase in CD (1·75; 0-3; P = 0·0054). In scar, the LDP was similar to that in the NGTA (1·03; 0·77-1·83; P = 0·278), combined with the highest CD (5·75; 4·5-8) in comparison with the previous stages of the area (for both pairs, P < 0·0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low., (© 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

A patient-specific finite-element (FE) model of the human leg is developed to model the stress distribution in and around a vein wall in order to determine the biomechanical response of varicose veins to compression treatment. The aim is to investigate the relationship between the local pressure on the soft tissues induced by wearing the compression garment and the development and evolution of varicose veins and various skin-related diseases such as varicose veins and ulcers. Because experimental data on the mechanical properties of healthy superficial veins and varicose veins are scarce in literature, ultrasound images of in vivo varicose veins are acquired and analysed to extract the material constants using Finite Element Model Updating. The decrease in trans-mural pressure, which conditions the effectiveness of compressive treatments, is computed from the simulation results. This constitutes the original added value of the developed model as decrease in trans-mural pressures cannot be assessed experimentally by any other means. Results show that external compression is effective in decreasing the trans-mural pressure, thereby having a positive effect in the control and treatment of vein-related diseases., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Non-healing venous leg ulcers are a cumbersome problem for the patient and the physician. Adequate compression therapy that reduces venous pressure is the cornerstone of treatment. For each patient treatment of superficial venous insufficiency should be considered. Adjuvant surgical, physical or biologic interventions can stimulate healing in case of refractory ulcers Treatment of a venous ulcer needs a tailored approach.

Presented in the article is an original version of the development of vascular-genesis trophic ulcers. The authors have for the first time come out with a suggestion on the relationship between the lobular structure of tissues and microcirculation. To describe this relationship they introduce the notion of the haemodynamic module (HM). The HM is considered to mean a limited by the fibrous capsule functional tissue fragment including haemic and lymphatic vessels. The HM including only the capillary network belongs to the 1st level, that including arterioles belongs to the 2nd level, and the HM including arteries belongs to the 3rd level. The HMs respond by altering their internal pressure on arterial vasomotion and create a significant addition to the vis a tergo. Impairments of arterial or venous circulation are accompanied and followed by pathological changes in HMs, inducing alterations of the epithelium-matrix communications and the development of trophic ulcers.

Objective: To determine the effect of topically applied amelogenin extracellular matrix protein(AEMP) in patients with non-healing venous leg ulcers combined with atrophie blanche., Method: This retrospective case series of patients with non-healing venous leg ulcers with atrophie blanche of the distal proportion of their lower legs, where non-healing was defined as no progress toward healing for 3 months previously, under standard therapy. Patient records were reviewed for associated diseases, wound diagnoses, distal blood pressure, previous treatments and changes in wound area. Patients were treated with AEMP once a week, for a period of 12 weeks, or until full healing., Results: Eleven patient records were reviewed retrospectively. The median age of the patients was 81 years (range 40-95 years), with a mean wound size of 4.7 ± 3.Scm2 and median wound duration of 6 months (range 3-444 months).AII patients had venous or combined arterial/venous insufficiency. After 12 weeks' treatment with AEMP, complete healing, defined as I 00% re-epithelialisation, was documented in four patients (36%), marked improvement(> SO% epithelialisation) in three patients (54%, 55% and 83% wound closure, respectively), slight improvement in one patient (9.4% wound closure), no change for two patients and worsening in one.AEMP was well tolerated, and no patients reported side effects., Conclusion: The results of this retrospective study suggest that AEMP improves healing in chronic venous leg ulcers combined with atrophie blanche.

The safety and efficacy of three-layer (3L) tubular bandaging as a treatment for venous ulcer healing has not been evaluated despite its use in many clinical settings to treat people with venous leg ulcers. We evaluated the safety and efficacy of 3L tubular bandage compared with short-stretch compression bandage to heal venous ulcers in a multicenter, open-label, parallel-group, randomized controlled trial. We randomized 45 patients with venous leg ulcers of up to 20 cm(2) area and an ankle brachial pressure index of >0.8 from hospital outpatient wound clinics in Victoria and Queensland, Australia. We measured time to healing and percentage reduction of wound size from baseline to week 12. Secondary outcomes were proportion of ulcers healed, self-reported compliance of compression bandage, and health-related quality of life, costs, recurrence rates, and adverse events. A total of 27 ulcers healed, the proportion of healed ulcers was higher for the 3L group (17/23 [74%] vs. 10/22 [46%]) (p = 0.05). Reported bandage tolerance at all treatment visits was 21 (91%) in 3L group vs. 17 (73%) (p = 0.10). There was no difference between the groups in adverse events. Costs were substantially less in 3L group., (© 2012 by the Wound Healing Society.)

Leg ulceration can be defined as any chronic ulcer of the lower leg excluding those on the forefoot or toes (Lees & Lambert, 1992). Venous or stasis ulcers account for 80%-85% of all leg ulcers with an overall prevalence of approximately 1% in the United States (Collins & Seraj, 2010; O'Meara, Al-Kurdi, & Ovington, 2008). Venous ulcers are more common in women and the older population (Abbade & Lastoria, 2005; Bergqvist, Lindholm, & Nelzen, 1999). Venous ulcers are often recurrent and chronic and can persist from weeks to even years. Severe complications include cellulitis, osteomyelitis, and malignant changes (Collins & Seraj, 2010). This column discusses the pathophysiology of venous insufficiency and ulcerations, presentation, diagnosis, and current treatment.

Background: Many patients with venous leg ulcers do not heal with standard care. HP802-247 is a novel spray-applied cell therapy containing growth-arrested allogeneic neonatal keratinocytes and fibroblasts. We compared different cell concentrations and dosing frequencies of HP802-247 for benefit and harm when applied to chronic venous leg ulcers., Methods: We enrolled adult outpatients from 28 centres in the USA and Canada with up to three ulcers, venous reflux confirmed by doppler ultrasonography, and adequate arterial flow in this phase 2, double-blind, randomised, placebo-controlled trial if at least one ulcer measured 2-12 cm(2) in area and had persisted for 6-104 weeks. Patients were randomly assigned by computer-generated block randomisation in a 1:1:1:1:1 ratio to 5·0×10(6) cells per mL every 7 days or every 14 days, or 0·5×10(6) cells per mL every 7 days or every 14 days, or to vehicle alone every 7 days. All five groups received four-layer compression bandages. The trial sponsor, trial monitors, statisticians, investigators, centre personnel, and patients were masked to treatment allocation. The primary endpoint was mean percentage change in wound area at the end of 12 weeks. Analyses were by intention to treat, excluding one patient who died of unrelated causes before first treatment. This trial is registered with ClinicalTrials.gov NCT00852995., Findings: 45 patients were assigned to 5·0×10(6) cells per mL every 7 days, 44 to 5·0×10(6) cells per mL every 14 days, 43 to 0·5 ×10(6) cells per mL every 7 days, 46 to 0·5 ×10(6) cells per mL every 14 days, and 50 to vehicle alone. All required visits were completed by 205 patients. The primary outcome analysis showed significantly greater mean reduction in wound area associated with active treatment compared with vehicle (p=0·0446), with the dose of 0·5 ×10(6) cells/mL every 14 days showing the largest improvement compared with vehicle (15·98%, 95% CI 5·56-26·41, p=0·0028). Adverse events were much the same across all groups, with only new skin ulcers and cellulitis occurring in more than 5% of patients., Interpretation: Venous leg ulcers can be healed with a spray formulation of allogeneic neonatal keratinocytes and fibroblasts without the need for tissue engineering, at an optimum dose of 0·5×10(6) cells per mL every 14 days., Funding: Healthpoint Biotherapeutics., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Problem wounds represent a significant and growing challenge to our healthcare system. The incidence and prevalence of these wounds are increasing in the population, resulting in growing utilization of healthcare resources and dollars expended. Venous leg ulcers represent the most common lower-extremity wound seen in ambulatory wound care centers, with recurrences frequent and outcomes often less than satisfactory. Pressure ulcers are common in patients in long-term institutional care settings adding significant increases in cost, disability and liability. Foot ulcers in patients with diabetes contribute to more than half of lower-extremity amputations in the United States in a group at risk, representing only 3 percent of the population. In response to this challenge, specialized programs have emerged designed to identify and manage these patients, using standardized protocols and a variety of new technologies to improve outcomes. Hyperbaric oxygen treatment (HBO2T) has been increasingly utilized in an adjunctive role in the care of many of these patients, coinciding with optimized patient and local wound care.

Chronic wounds are common and lead to significant patient morbidity. A better understanding of their pathogenesis and relevant biomarkers are required. We compared acute and chronic wounds in the same individual using noninvasive imaging including spectrophotometric intracutaneous analysis (SIAscopy) and full-field laser perfusion imaging. Gene expression analysis was also performed on sequential biopsies. Whole genome gene expression microarray analysis (44k), quantitative polymerase chain reaction, and immunohistochemistry were carried out to determine gene expression levels in tissue biopsies. Fifteen Caucasian patients with chronic venous ulcers had biopsies of the wound edges and simultaneously had an acute wound created on their upper arm on days 0, 7, and 14. SIAscopy revealed increased levels of melanin (p < 0.001), reduced levels of collagen (p < 0.001), and hemoglobin (p = 0.022) in chronic wounds. Microarray and subsequent quantitative polymerase chain reaction analysis confirmed an overall differential expression in acute and chronic wounds for several genes. Significantly higher levels of inhibin, beta A (INHBA) expression were confirmed in the dermis of chronic wounds (p < 0.05). Additionally, INHBA and thrombospondin 1 messenger RNA levels significantly correlated with SIAscopy measurements (p < 0.05). This unique study has showed aberrant expression of INHBA in chronic wounds using a sequential biopsy model of chronic vs. acute wounds in the same individual., (© 2012 by the Wound Healing Society.)

Since the establishment of the guidelines for the treatment of venous ulcers by the Wound Healing Society in 2006, there has been an abundance of new literature, both in accord and discord with the guidelines. The goal of this update is to highlight new findings since the publication of these guidelines to assist practitioner and patient in appropriate health care decisions, as well as to drive future research endeavors., (© 2012 by the Wound Healing Society.)

Both chronic and acute dermal wounds are susceptible to infection due to sterile loss of the innate barrier function of the skin and dermal appendages, facilitating the development of microbial communities, referred to as biofilms, within the wound environment. Microbial biofilms are implicated in both the infection of wounds and failure of those wounds to heal. The aim of this review is to provide a summary of published papers detailing biofilms in wounds, the effect they have on infection and wound healing, and detailing methods employed for their detection. The studies highlighted within this paper provide evidence that biofilms reside within the chronic wound and represent an important mechanism underlying the observed, delayed healing and infection. The reasons for this include both protease activity and immunological suppression. Furthermore, a lack of responsiveness to an array of antimicrobial agents has been due to the biofilms' ability to inherently resist antimicrobial agents. It is imperative that effective strategies are developed, tested prospectively, and employed in chronic wounds to support the healing process and to reduce infection rates. It is increasingly apparent that adoption of a biofilm-based management approach to wound care, utilizing the "antibiofilm tool box" of therapies, to kill and prevent reattachment of microorganisms in the biofilm is producing the most positive clinical outcomes and prevention of infection., (© 2012 by the Wound Healing Society.)

This article reviews published data on the effects of surgery and compression in the treatment of venous ulcers and the best options for compression therapy. Randomized controlled studies reveal that surgery and compression have similar effectiveness in healing ulcers but surgery is more effective in preventing recurrence. Most leg ulcers have a venous pathophysiology and occur because of venous ambulatory hypertension caused by venous reflux and impairment of the venous pumping function. Proposed surgical interventions range from crossectomy and stripping to perforator vein interruption and endovascular procedures (laser, radiofrequency). More conservative procedures (foam sclerotherapy, conservative hemodynamic treatment) have also been proposed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Venous leg ulcers (VLUs) are the most prevalent chronic wounds in western countries with a heavy socioeconomic impact. Compression therapy is the etiologic treatment of VLU but until now no wound dressing has been shown to be more effective than another. The aim of this study was to assess the efficacy of a new dressing in the management of VLU. Adult patients presenting a noninfected VLU and receiving effective compression therapy were enrolled in this randomized, controlled, double-blind trial. The VLUs were assessed every 2 weeks for 8 weeks. The primary study outcome was the relative Wound Area Reduction (WAR, in %), and the secondary objectives were absolute WAR, healing rate, and percentage of wounds with >40% surface area reduction. One hundred eighty-seven patients were randomly allocated to treatment groups. Median WAR was 58.3% in the Lipido-Colloid Technology-Nano-OligoSaccharide Factor (TLC-NOSF) dressing group (test group) and 31.6% in the TLC dressing group (control group) (difference: -26.7%; 95% confidence interval: -38.3 to -15.1%; p = 0.002). All other efficacy outcomes were also significant in favor of the TLC-NOSF dressing group. Clinical outcomes for patients treated with the new dressing are superior to those patients treated with the TLC dressing (without NOSF compound), suggesting a strong promotion of the VLU healing process., (© 2012 by the Wound Healing Society.)

This article reviews the literature on quality of life of people with venous leg ulcers. Research indicates that, in most people, chronic ulceration is a continuous cycle of skin breakdown over a period of decades and is associated with impaired quality of life. Management of leg ulceration represents a major component of the community nursing workload, with community nurses spending approximately half of their time treating patients with leg ulcers. However, the complex psychological and social effects of ulceration on the patient are often overlooked as the nurse's main focus is on clinical aspects of wound care. This article identifies the importance of adopting a holistic approach to the care of patients with venous leg ulcers to improve outcomes and quality of life.

Chronic venous disease encompasses a range of venous disorders, including those involving the lower limbs resulting from venous hypertension. The spectrum of chronic venous disease signs and symptoms shows variable severity, ranging from mild (aching, pain, and varicose veins) to severe (venous ulcers). The pathophysiology of chronic venous disease is characterized by venous hypertension, which triggers endothelial dysfunction and inflammation leading to microcirculatory and tissue damage, and eventually to varicose veins and venous ulcers. Sulodexide is an orally active mixture of glycosaminoglycan (GAG) polysaccharides with established antithrombotic and profibrinolytic activity. The agent is used in the treatment of a number of vascular disorders with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarction. Sulodexide differs from heparin because it is orally bioavailable and has a longer half-life and a smaller effect on systemic clotting and bleeding. An increasing body of preclinical evidence shows that sulodexide also exerts anti-inflammatory, endothelial-protective, and pleiotropic effects, supporting its potential efficacy in the treatment of chronic venous disease. Clinical studies of sulodexide have shown that the agent is associated with significant improvements in the clinical signs and symptoms of venous ulcers, and is therefore a recommended therapy in combination with local wound care and bandages for patients with persistent venous leg ulcers. Preliminary evidence supports the use of sulodexide in the prevention of recurrent deep venous thrombosis. Sulodexide was generally safe and well tolerated in clinical trials, without hemorrhagic complications. Sulodexide therefore appears to be a favorable option for the treatment of all stages of chronic venous disease and for the prevention of disease progression.

Previously, we demonstrated the effectiveness of a research grade recombinant chymotrypsin, derived from the larvae of Lucilia sericata, in "debriding" slough/eschar from venous leg ulcers ex vivo. Furthermore, we were able to formulate this enzyme for successful delivery to in vitro wound healing assays, from a prototype hydrogel wound dressing, and showed that enzyme delivered in this way could degrade wound tissue ex vivo. Recently, to progress biotechnological development of the enzyme as a potential therapeutic product, we explored expression using current good manufacturing practice (cGMP) guidelines, and now report that a recombinant chymotrypsin I zymogen from L. sericata can be expressed in the cGMP acceptable strain of Escherichia coli (BLR-DE3). In addition, the conditions required for purification, refolding and activation of the chymotrypsinogen have been determined. The activated enzyme was stable, and effective in digesting wound slough/eschar tissue. To summarise, we have successfully initiated the production and characterisation of a novel cGMP compatible product for use in future clinical trials., (Copyright © 2012 American Institute of Chemical Engineers (AIChE).)

Background: Venous outflow obstruction may play a role in patients with chronic venous stasis symptoms who fail to improve despite conventional modalities of treatment that focus on the reflux component of the disease with little attention to the possibility of an obstructive component. The introduction of minimally invasive venous stenting using venography and intravenous ultrasonography (IVUS) provides the ability to treat the "obstructive" component of the disease., Methods: We undertook a retrospective review of 56 limbs in 53 patients with chronic venous stasis symptoms. Initial transcutaneous Doppler ultrasonographic evaluation of the inferior vena cava, iliac, femoral, greater saphenous, and perforator veins was performed looking for any evidence of deep venous thrombosis, superficial venous thrombosis, perforator veins, and reflux (location and degree). Afterword, the patients were managed in the conventional fashion (leg elevation, compression, and great saphenous vein (GSV) and perforator ablation, if present) for a period of 3 months. If ulcer healing was not noted, iliac-femoral venography and IVUS were undertaken. A significant stenosis was defined as a 50% reduction in vein cross-sectional area as measured by IVUS.(1,2,3) Stenotic lesions were managed with stenting followed by balloon angioplasty. Patients were followed up for ulcer healing or improvement of stasis symptoms., Results: Of the 56 limbs, 10 (17.8%) had postthrombotic changes, 7 (12.5%) had incompetent perforators, and 27 (48.2%) had an incompetent superficial venous system. In the stented group (n = 29), 3 limbs had perforator ablation alone, 13 limbs had GSV ablation alone, and 1 limb had both perforator and GSV ablation. In the unstented group (n = 27), 10 limbs had GSV ablation alone, and 3 limbs had both perforator and GSV ablation. The overall incidence of deep reflux was 51.8%; 17 of 29 limbs (58.6%) in the stented group had evidence of deep reflux, and 12 of 27 limbs (44.4%) in the unstented group had deep reflux. All venograms except one (98.2%) were performed under local anesthesia with sedation. The procedure was performed in an ambulatory setting in 69.6% (39 of 56) of the limbs. CEAP clinical severity class distribution was as follows: C2, 4%; C3, 16%; C4, 18%; C5, 5%; C6, 57%. Over half of the limbs (29 of 56) were found to have stenotic lesions and required stenting. Eight patients (11 limbs) did not return for ulcer healing assessment. The majority (19 of 29) of limbs in the stented group had a CEAP of 6. Among the patients with CEAP 6 who returned for follow-up (n = 26), 7 had no evidence of stenosis and required no stenting. Only one of those (14.3%) healed his ulcers after 3 months (average follow-up of 4.8 months). The remainder 19 limbs were found to have stenotic lesions and underwent stenting. The ulcers healed in 11 of those (58%) over a period of 1 week to 8 months (average of 5 months), with average follow-up of 3.6 months (p = 0.08). The cumulative primary and secondary patency rates were 93.1% (27 of 29) and 100% (29 of 29), respectively. Two stent thromboses occurred within 4 weeks of the initial procedure. Both occurred in patients with postthrombotic obstruction. One patient developed a superficial femoral artery pseudoaneurysm., Conclusion: Over half of our patients with open ulcers had stenotic lesions. The ulcers healed in 58% of the stented limbs. That indicates that outflow obstruction may play a significant role in patients with chronic venous stasis symptoms, especially those with open ulcers who failed to respond to other treatment modalities. The procedure itself is relatively safe and simple and can be performed on an ambulatory basis., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Background: Venous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available., Principal Findings: In wound edge biopsies from human venous leg ulcers we found a striking upregulation of dermal N-cadherin, Zonula Occludens-1 and the gap junction protein Connexin43 (Cx43) compared to intact skin, and in stark contrast to the down-regulation of Cx43 expression seen in acute, healing wounds. We targeted the expression of these proteins in 3T3 fibroblasts to evaluate their role in venous leg ulcers healing. Knockdown of Cx43 and N-cadherin, but not Zonula Occludens-1, accelerated cell migration in a scratch wound-healing assay. Reducing Cx43 increased Golgi reorientation, whilst decreasing cell adhesion and proliferation. Furthermore, Connexin43 and N-cadherin knockdown led to profound effects on fibroblast cytoskeletal dynamics after scratch-wounding. The cells exhibited longer lamelipodial protrusions lacking the F-actin belt seen at the leading edge in wounded control cells. This phenotype was accompanied by augmented activation of Rac-1 and RhoA GTPases, as revealed by Förster Resonance Energy Transfer and pull down experiments., Conclusions: Cx43 and N-cadherin are potential therapeutic targets in the promotion of healing of venous leg ulcers, by acting at least in part through distinct contributions of cell adhesion, migration, proliferation and cytoskeletal dynamics.

Background: Plastic surgeons are often approached for wound management and closure of chronic venous ulcers that fail to heal despite multimodal management. The authors present a retrospective analysis of a large series of venous ulcers to determine factors predicting nonhealing and recurrence., Methods: Consecutive patients with chronic venous ulcers (≥ 2-cm diameter) were examined for the presence of superficial, perforating, or deep venous disease, including reflux and/or obstruction. Treatment included compression, venous ligation, stripping, thermal ablation, sclerotherapy, and local wound care. Ulcers refractory to 6 months of treatment were defined as nonhealing ulcers. Data were analyzed for differences in baseline patient and ulcer characteristics and clinical course of nonhealing ulcers. Data were compared using Wilcoxon rank sum, chi-square, and Fisher's exact tests using Sigma Stat and SPSS, with α set at p < 0.05., Results: The authors identified 153 ulcers in 127 patients. Factors associated with ulcer nonhealing included advanced age, increased body mass index, history of deep venous thrombosis, noncompliance with compression therapy, and large ulcer area. One hundred thirty-one of the ulcers (85.6 percent) healed within 6 months and 147 (96 percent) of the ulcers ultimately healed without the need for operative plastic surgical intervention., Conclusions: A thorough understanding of risks and expected clinical course is required for assessment of the nonhealing venous ulcer. The authors recommend identification and correction of underlying venous abnormality and a minimum of at least 6 months of compression and local wound care followed by reassessment of venous function before operative plastic surgical intervention should be considered., Clinical Question/level of Evidence: Risk, III.

Objectives: This study was conducted to define bandage pressures that are safe and effective in treating leg ulcers of mixed arterial-venous etiology., Methods: In 25 patients with mixed-etiology leg ulcers who received inelastic bandages applied with pressures from 20 to 30, 31 to 40, and 41 to 50 mm Hg, the following measurements were performed before and after bandage application to ensure patient safety throughout the investigation: laser Doppler fluxmetry (LDF) close to the ulcer under the bandage and at the great toe, transcutaneous oxygen pressure (TcPo(2)) on the dorsum of the foot, and toe pressure. Ejection fraction (EF) of the venous pump was performed to assess efficacy on venous hemodynamics., Results: LDF values under the bandages increased by 33% (95% confidence interval [CI], 17-48; P < .01), 28% (95% CI, 12-45; P < .05), and 10% (95% CI, -7 to 28), respectively, under the three pressure ranges applied. At toe level, a significant decrease in flux of -20% (95% CI, -48 to 9; P < .05) was seen when bandage pressure >41 mm Hg. Toe pressure values and TcPo(2) showed a moderate increase, excluding a restriction to arterial perfusion induced by the bandages. Inelastic bandages were highly efficient in improving venous pumping function, increasing the reduced ejection fraction by 72% (95% CI, 50%-95%; P < .001) under pressure of 21 to 30 mm Hg and by 103% (95% CI, 70%-128%; P < .001) at 31 to 40 mm Hg., Conclusions: In patients with mixed ulceration, an ankle-brachial pressure index >0.5 and an absolute ankle pressure of >60 mm Hg, inelastic compression of up to 40 mm Hg does not impede arterial perfusion but may lead to a normalization of the highly reduced venous pumping function. Such bandages are therefore recommended in combination with walking exercises as the basic conservative management for patients with mixed leg ulcers., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: In Hong Kong, at the time of the study, compression treatment was not considered usual care for venous leg ulcer patients., Aim: This randomized controlled trial compared quality of life (QOL) aspects in venous leg ulcer patients of over 55-years of age, of short-stretch compression (SSB), four-layer compression bandaging (4LB) and usual care (UC) (moist wound healing dressing, no compression)., Method: Study period was 24-weeks, the primary outcome was the patient functional status, disease-specific and generic health-related QOL measures and ulcer healing rates, comparing week 1 vs. week 24 (end) results. Assessments included photogrammetry, Brief Pain Inventory, SF-12 Health Survey, Charing Cross Venous Ulcer Questionnaire and Frenchay Activity Index. Data analysis was performed using, where appropriate; Kaplan Meier and log rank chi-square and the repeated measures analysis of variance test., Results: A total of 321 patients participated in the study, 45 (14%) withdrew for various reasons. Compression bandaging in both groups significantly reduced pain (P < 0.0001) and improved functional status and QOL. Healing rate at 24 weeks for both compression groups was significant (P < 0.001); for SSB this was 72.0% (77/107) vs. 67.3% in the 4LB group (72/107) and 29.0% (31/107) with usual care. The reduction in ulcer area from weeks 12 to 24 was significant only for SSB (P < 0.047)., Conclusion: Compression was shown to be feasible for elderly community care patients in Hong Kong and is currently implemented as part of standard venous leg ulcer treatment., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Objective: To use in vitro biofilm models of wound bacterial isolates and compare the biofilms produced for different combinations of wound bacterial species., Method: In vitro biofilms, generated by Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus oralis and Micrococcus luteus in microtitre plates and a constant depth film fermentor (CDFF), were studied. The tested isolates all originated from chronic venous leg ulcers. Biofilms of individual and dual combinations of these species were generated in microtitre plate wells at 37°C for 24-96 hours and also in the CDFF for 7 days. The extent of biofilm formation from these systems was then measured using crystal violet staining and/or total viable counts., Results: All the chronic wound bacteria formed biofilms (both individually and in mixed culture) in these models. In mixed species microtitre plate biofilms, both P. aeruginosa and S. aureus appeared to antagonise biofilm formation by S. oralis and M. luteus, with P. aeruginosa completely inhibiting the growth of these organisms. Similar effects were evident in the CDFF model, when all four bacterial species were added simultaneously, with M. luteus being 'out-competed' by the other organisms present and occurring at numbers at the limits of detection; however, there was an apparent increase in the numbers of S. oralis compared with its single culture equivalent., Conclusion: The study highlighted differences in biofilm formation ability for the tested species in both closed and open model systems. Using dual species biofilms, distinct species antagonism was observed with apparent antagonism of pathogenic species over 'commensal' ones. Such a finding provides insight into possible bacterial interactions during development of 'non-healing' wound biofilms.

Venous leg ulcers are a major health issue in terms of financial burden to the NHS, nurses' input, and physical, psychological and social impact to the patient. The best practice management of leg ulcers is the application of high compression, which is a complex task and requires substantial skill and knowledge. Healing and recurrence rates are poor in some cases and this adds to the physical and psychosocial impact, as well as the financial burden. Many of the sequelae of ulceration hinder patients' ability to tolerate treatment. Nurses must acknowledge the difficulties patients face and become skilled in holistic assessment, care planning and the delivery of patient-focused best practice.

Introduction: Chronic venous disease has been shown to have a significant impact on patients' quality of life (QoL)., Objective: The aim of this study was to estimate the impact of chronic venous insufficiency (CVI) on QoL in patients with terminal stages of HVI, classified according to the CEAP clinical classification into classes C5 (healed ulcers) and C6 (active ulcers), on admission and after applied therapy., Methods: A cross-sectional study performed between October 2007 and June 2008 in a Belgrade outpatient clinic involved a total of 82 patients with venous ulcers (38 C5 and 44 C6) examined at the beginning of therapy. Of these, 14 C5 and 15 C6 patients in remission were re-examined after therapy from November 2007 to January 2010. QoL was assessed using a standard short-form (SF-36) questionnaire, and additionally by a brief CVD questionnaire specific for chronic venous disease., Results: At the beginning of therapy the SF-36 scores showed significant (p < 0.05) reductions in all QoL domains of C5 and C6 patients regarding physical, general health, and vitality in C5 and C6 patients. After therapy QoL was significantly improved in both classes of patients, but remained unchanged in the domain of emotional functioning suggesting the patients' fear and worry of HVI progression., Conclusion: In patients with terminal stages of CVI QoL was decreased at the beginning of therapy, but with the remission of the disease and ulcer healing it was significantly improved. This indicates the significance of prevention and timely treatment, and the need for patients' education about the chronic nature of the disease.

Objectives: Endovenous closure of incompetent saphenous veins has been reported to facilitate venous ulcer healing; however, there is little information about the effectiveness of perforator ablation (PA) in healing recalcitrant venous ulcers. We report our experience with PA with venous ulcers unresponsive to prolonged compression therapy., Methods: Patients with nonhealing venous ulcers of >3 months' duration underwent duplex ultrasound to assess their lower extremity venous system for incompetence of superficial, perforating, and deep veins. Patients who had either no saphenous incompetence or persistent ulcers after saphenous ablation underwent PA of incompetent perforating veins >3 mm that demonstrated reflux; initial treatment was performed on the perforator vein adjacent to the ulcer with additional incompetent veins treated if ulcer healing failed., Results: Seventy-five ulcers with 86 associated incompetent perforating veins were treated with PA in 45 patients with CEAP 6 recalcitrant venous ulcers. Treated incompetent perforator veins were located in the medial ankle (61%), calf (37%), and lateral ankle (2%). Initial success of PA, assessed by postprocedure duplex ultrasound, was 58%; repeat ablation was 90% successful and 71% had eventual successful perforator closure. No complications (skin necrosis, infection, or nerve injury) occurred. Failure of ulcer healing with successful perforator closure occurred in 10% and was due to intercurrent illness, patient noncompliance, and patient death due to unrelated causes. Of patients who healed their ulcers, the healing occurred at a mean of 138 days; an average PA of 1.5 incompetent veins per ulcer was required for healing. Ninety percent of ulcers healed when at least one perforator was closed; no ulcer healed without at least one perforator being closed., Conclusions: This experience demonstrates both the feasibility and effectiveness of PA for a selected group of patients with venous ulcers who fail conventional therapy with compression., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Aim: Venous ulcers are a common, chronic medical and social problem. These ulcers are difficult to heal in most patients with sustained venous hypertension. This pilot product evaluation registry study has evaluated the efficacy and safety of an antimicrobial silver oxide wound dressing ointment ("Silver Oxide Ointment") as part of the treatment of 'difficult' venous ulcerations., Methods: The study was conducted measuring the variations in the area of the ulceration and microcirculatory parameters., Results: After four weeks, treatment with the Silver Oxide Ointment proved more effective than the 'best management' used in controls. Transcutaneous PO2 was increased (improved); Laser Doppler skin flux and transcutaneous PCO2 were improved (decreased). Also in the silver oxide group a significantly higher number of venous ulcers were completely healed at four weeks. The silver oxide ointment improved both the microcirculation and the healing rate of their ulcers. No significant tolerability problems were observed., Conclusion: In difficult venous ulcerations, local treatment with this Silver Oxide Ointment, as one component of the total wound dressing, improved microcirculation measurements and healing rate. Most of the treatments were done at home by the patients or by their tutors. This study indicates the important role of this type of treatment and indicates the need to plan larger and more prolonged studies.

In chronic wounds, exudate is believed to prolong the inflammatory phase and is detrimental to healing (Trengove et al, 1999; Vowden and Vowden, 2004). Poor exudate management can have important management cost implications, and may result in increased patient morbidity (White and Cutting, 2006). Accurate assessment of wound exudate is a key component of wound healing and management is achieved through different methods depending on the cause of the excessive exudate production. Superabsorbent dressings have been designed to treat highly exuding wounds; they have a greater fluid-handling capacity than traditional dressings and require changing less frequently (Tadej, 2009). This case study reports on the combined use of a superabsorbent dressing with an antibacterial dressing in a 102-year-old patient who presented with a painful infected venous ulcer complicated by some arterial disease. The combination of the superabsorbent KerraMax® (Crawford Healthcare) with the antibacterial honey Algivon® (Advancis Medical) created the ideal dressing for the treatment of this infected mixed aetiology ulcer, as manuka honey has a strong antibacterial effect (Molan, 1992), and the dressing absorbs the excessive exudate. The dressings worked together to reduce the bacterial load on the wound bed surface, with the honey selectively destroying the bacteria (Molan, 1992), and KerraMax absorbed and locked away the bacteria-containing exudate, which helped to reduce further exudate production, prevent maceration and reduce the potential for a wound to become malodorous (Hampton, 2011).

Venous leg ulceration is the most common type of ulceration. Incompetency of the valves in the leg results in raised venous pressure which gives rise to the signs and symptoms of venous hypertension. The application of compression bandage therapy remains the cornerstone of treatment in the healing of venous leg ulceration. Application of the correct level of pressure to reverse venous hypertension is essential for such therapy to be successful and practitioners need to be trained in assessment and application techniques to ensure that the recommended level of pressure is applied without causing adverse problems and risks to the patient.

Background: Knowledge on the underlying mechanisms for nonhealing chronic wounds is fragmentary., Objectives: To increase our understanding of the pathogenesis, the relationship between healing ability and a large panel of proteins was studied using a specially designed wound-healing antibody-based microarray., Methods: Wound fluid from nondiabetic patients with nonhealing venous leg ulcers was compared with that from patients with healing open granulating acute wounds. The high-throughput method enabled simultaneous measurement of the relative levels of 48 different proteins representing major categories of wound-healing modulators., Results: Unexpectedly, several of the examined proteins, including various proinflammatory cytokines, proteinases and antiproteinases, were not significantly (P>0·001) changed in chronic wound fluid. For example, levels of matrix metalloproteinase-9 and one of its substrates type IV collagen were similar in the two groups. The wound fluid samples displayed similar degrees of fragmentation of fibronectin by Western blot analysis and the total fibronectin levels were doubled (P<0·001) in chronic compared with acute wounds. The increased fibronectin originated from α-smooth muscle actin-positive myofibroblasts and not from the circulation. S100A8/A9 was the sole protein that was reduced (P<0·001) in wound fluid from venous ulcers [median 226 μg mL(-1) (interquartile range 213-278)] compared with healing wounds [455 μg mL(-1) (382-504)], probably reflecting a difference in inflammatory cell composition., Conclusion: The molecular anomalies in chronic wounds are more subtle than the current paradigm and neither excessive proteinase activity nor deficiencies of examined extracellular matrix proteins, growth factors or angiogenic/angiostatic factors appear to contribute significantly to the nonhealing state of venous leg ulcers., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.)

To assess relationships among food intake, anthropometrics, and wound severity, we studied 31 home care clients with pressure ulcers (PUs) or venous stasis ulcers (VSUs). Anthropometric variables (weight, height, waist circumference [WC]) were measured according to standard methodologies. Risk for PU development was assessed using the Braden Pressure Ulcer Risk Assessment score and wound severity according to the National Pressure Ulcer Advisory Panel. Three-day food records were analyzed to assess dietary adequacy. Adults with VSUs (65.8 ± 18.4 years) had a higher body mass index (48.1 vs. 25.9), WC (146.6 vs. 98.4 cm), and Braden score (20.2 vs. 17.5) than did those with PUs (67.8 ± 17.9 years) (p <0.05). Energy, protein, and zinc intake by diet alone did not meet estimated requirements in 41%, 32%, and 54.5% of clients, respectively. Intake by diet alone met the Estimated Average Requirement/Adequate Intake for all nutrients except fibre, vitamin D, vitamin E, vitamin K, folate, calcium, magnesium, and potassium. Nutrient supplementation resolved this for all nutrients except fibre, vitamin K, and potassium. In multivariate analysis, increasing wound severity was associated with decreased intakes of vitamin A, vitamin K, magnesium, and protein (r2=0.90, p<0.001). Optimizing nutrient intake may be an important strategy to promote wound healing and decrease wound severity in home care clients with chronic wounds.

Background: Chronic venous insufficiency (CVI) ulcers represent a major medical problem worldwide. Current theories concerning the pathogenesis of CVI ulcers focus on abnormalities in the blood vascular system. Other abnormalities, such as chronic leg edema, may also play pathogenic roles in CVI ulcer development and further understanding of such alterations may lead to better treatments., Objective: To gain insight into lymphatic abnormalities occurring in CVI, we compared dermal lymphatics in histologic sections from CVI ulcers and normal controls., Methods: We compared global and architectural features of dermal lymphatics in D2-40-stained histologic sections from CVI ulcer tissue and from normal controls. D2-40 recognizes podoplanin, a transmembrane glycoprotein that is constitutively expressed in lymphatic endothelial cells, allowing us to distinguish dermal blood vessels from lymphatic vessels., Results: Our analyses reveal that CVI ulcer specimens have more dermal lymphatic vessels per unit area than controls (5.71 vs 4.08 per mm(2), respectively; P = .0281); a higher percentage of lymphatic vessels with collapsed lumina compared with controls (30.5% vs 8.1%, respectively; P < .0001); and a higher percentage of competent lymphatic vessels displaying open inter-endothelial junctions compared with controls (5.7% vs 2.9%, respectively; P < .0369)., Limitations: Our study is limited by its retrospective nature and relatively small sample size., Conclusions: Lymphatic vessels in CVI ulcer specimens display global and architectural differences compared with lymphatic vessels in control specimens. These findings further implicate lymphatic dysfunction in the pathogenesis of CVI ulcers and allow for the formulation of a hypothesis concerning lymphatic changes that may be tested in future studies., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)