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Objective: Biofilm infections in chronic wounds are common and pose a significant clinical challenge. This challenge was addressed by developing the SoftOx Biofilm Eradicator (SBE) composed of hypochlorous acid (HOCl) and acetic acid with strong broad-spectrum antimicrobial activity. Approach: First-in-human study investigating the safety and tolerability as primary endpoints and wound size effect and antimicrobial efficacy as secondary endpoints of SBE treatment in chronic leg wound patients. The study was divided into two as follows: a randomized, double-blinded, Single Ascending Dose (SAD) phase ( n = 16 SBE; n = 4 placebo), where patients were treated with SBE or saline (placebo) only once, followed by an open-label, Multiple Ascending Dose (MAD) phase ( n = 8), where patients were treated with SBE once daily or twice daily over five days. Reporting is according to CONSORT guidelines. Results: SBE was safe and well-tolerated in chronic leg wound patients. There were no significant differences in pain during and after treatment with SBE or the placebo. The SBE treatment reduced bioburden in wounds compared to baseline, with 98% and 49% median reduction after SBE or placebo treatment, respectively. A dose-dependent trend in absolute wound size reduction was observed in the MAD groups with a median (min, max) change of -2.99 (-14.25, -1.5) cm 2 in the once-daily and -10.48 (-17.95, -0.38) cm 2 in the twice-daily group, respectively. Innovation and Conclusion: This study demonstrated the safe use of HOCl-based SBE in chronic leg wounds with promising trends of immediate antimicrobial action and beneficial effect on wound healing.

The presence of Kerstersia gyiorum in lower leg wounds has been reported in case studies from several countries., Objective: This study evaluated the antimicrobial susceptibility profile of K gyiorum isolated from a chronic wound., Methods: An 85-year-old woman with chronic venous insufficiency presented to an intermediate care unit in Niteroi City, Rio de Janeiro, Brazil, with an instep chronic wound of 14 cm² with wound duration of 6 months. K gyiorum was identified by matrix-assisted laser desorption ionization-time of flight, confirmed by 16S rRNA partial sequence analysis, and classified as resistant for ciprofloxacin by reagent strips(minimum inhibitory concentration [MIC] = 32 µg/mL) and the broth macrodilution method (MIC = 8 µg/mL). Intermediate resistance for ciprofloxacin was verified by microscan (MIC = 2 µg/mL)., Conclusion: The authors identified the first, to their knowledge, lower leg wound with K gyiorum in Brazil and verified that it was ciprofloxacin resistant.

This study was aimed to evaluate whether silver-containing dressings were superior to other types of dressings in the treatment of venous leg ulcers (VLU) and their specific advantages.Eight databases (Cochrane Library, PubMed, Web of Science, Ovid-Medline, Wanfang, VIP, China Biology Medicine, and China National Knowledge Infrastructure) were systematically reviewed from inception to May 2019 for randomized controlled trials (RCTs). The primary outcome was complete wound healing, and the secondary outcomes included absolute wound size changes (change of cm area since baseline), relative changes (percentage change of area relative to baseline), and healing rate. Two reviewers independently evaluated the risk of bias using the Cochrane Collaboration assessment tool and extracted the data according to the predesigned table. All analyses were performed using the latest Review Manager Software (version 5.3).A total of 8 studies qualified and were included in the meta-analysis, including 1057 patients (experiment: 526, control: 531). Both complete wound healing and wound healing rates were reported in 5 studies. Two and 3 studies reported the effect of silver dressings on absolute and relative wound size changes, respectively. Most of the studies used intention-to-treat analysis.There was sufficient evidence that silver-containing dressings can accelerate the healing rate of chronic VLU and improve their healing in a short duration of time. However, compared with other dressings, clinical trials with long-term follow-up data are needed to confirm whether silver dressings have advantages regarding complete wound healing.

Introduction: Venous leg ulcers (VLUs), the most common leg ulceration worldwide, are caused by venous hypertension due to venous reflux, the failure of the calf muscle to pump, and venous flow obstruction. They are associated with a reduced quality of life, particularly in relation to pain and physical function. Hibiscus rosa-sinensis is commonly employed because of its many medicinal properties, and studies have shown Hibiscus contains phytochemicals that have antimicrobial, antioxidant, and anti-inflammatory properties that promote wound healing., Objective: The authors evaluate the efficacy and safety of 4% gumamela leaf extract ointment in the closure of VLUs among patients seen in a dermatology outpatient department in the Philippines., Materials and Methods: The study included male or female patients with leg ulcers confirmed by duplex scan to be venous in origin and willing to have elastic compression therapy. Patients were instructed to clean the wound with normal saline solution and to apply the extract twice daily. The study was conducted for 12 weeks or until wound closure. Wounds were evaluated and photographed at baseline and every subsequent 2 weeks. Efficacy of therapy was evaluated based on ulcer area size using planimetry method at each visit. Safety was assessed using a 4-point grading system to monitor possible adverse reactions, namely pruritus, rash, burning, and urticaria., Results: Twelve patients were included in the study; 5 patients had an initial ulcer area of ⟩ 10 cm2 and 7 had an initial ulcer area of ≤ 10 cm2. By the end of the study, 10 patients (83.3%) achieved complete ulcer closure in ⟨ 12 weeks, 1 patient (8.3%) had a decrease in ulcer area ⟩ 50% by week 12, and 1 patient (8.3%) had ⟨ 50% decrease in ulcer area at the end of the study., Conclusions: Data showed compression stockings with 4% gumamela leaf extract ointment application could close VLUs in ⟨ 12 weeks. Applied with compression stockings, the ointment shows potential use in VLU management.

The aim of this study was to observe the curative effect and mechanism of Shengji Yuhong ointment in the healing of chronic ulcer of lower limbs. 400 patients were equally divided into treatment group and control group. The treatment group was covered with a piece of Shengji Yuhong ointment gauze, while the control group was covered with a piece of Vaseline gauze. Both groups changed dressings every other day for 4 weeks. On the 3rd, 7th, 14th, 21st, and 28th days of treatment, the reduction rate of wound area and the growth of wound granulation were observed and the levels of hydroxyproline and hemoglobin in wound granulation tissue were measured. The total effective rate was 99.00% in the treatment group and 71.00% in the control group. The treatment group was significantly better than the control group ( P < .01). The ulcer area reduction rate of the treatment group was significantly higher than that of the control group ( P < .01). The scores of ulcer depth, granulation color, and coverage area on the 7th, 14th, 21st, and 28th days after treatment in the treatment group were significantly lower than those before treatment ( P < .05). After treatment, the levels of hydroxyproline and hemoglobin in granulation tissue of wounds in both groups were significantly higher than those before treatment ( P < .01), and the levels in the treatment group were significantly higher than those in the control group ( P < .01). Shengji Yuhong ointment can improve the healing rate of chronic ulcer of lower limbs.

Flammacerium is a topical treatment composed of silver sulfadiazine and cerium nitrate initially used in burns. The objective was to assess the effectiveness of silver sulfadiazine and cerium nitrate on ischemic necrosis wounds of the lower limb as an alternative to amputation for a period of 12 weeks. Patients were prospectively randomized to receive silver sulfadiazine and cerium nitrate or standard care. Patients included adults with an ischemic wound of the lower limb, with necrosis covering over at least 50%. Critical ischemia limb was confirmed by an ankle-brachial index <0.7 or >1.3 with radiological confirmation. Patient demographic data, amputations procedures, wound area, Visual Analogue Scale pain rating, clinical infection, and adverse events were recorded. Fifty patients, 34 males and 16 females, were recruited between January 2010 and April 2014, 25 in each group. The mean age was 75.14 years (±11.64). Nine amputations (36%) occurred in each group. Amputation-free survival was superior in the active treatment group versus the standard group (169 393 days, 95% confidence interval = 134.926-203.861, vs 169 393 days, 95% confidence interval = 134.926-203.861). It was not statistically significant (log-rank, P = .958). Wound area reduction between both groups was not statistically different ( P = .651). Less adverse events of the lower limb occurred in the active treatment group ( P = .001). Our study showed that silver sulfadiazine and cerium nitrate is not inferior to standardized care on ischemic necrotic wounds of the lower extremity. Further studies are still needed to confirm its effectiveness.

Venous leg ulcers are the most common form of non-healing leg ulcers. They are subjected to treatments such as topical medications, dressings, and compression therapies. This can lead to exposure to a number of allergens with subsequent sensitisation and contact dermatitis of the regional skin. This may contribute to the poor ulcer healing. To detect the various contact sensitisers in patients with venous leg ulcers through patch testing, patients from 6 centres across India with venous leg ulcers of longer than 6 weeks duration were enrolled for the study. They were patch tested using a special parch test kit with 27 antigens. A total of 172 patients were included in the study; 82 (48.2%) tested positive for at least 1 antigen. Among them, polyvalent sensitisation was noted in 71% of patients. Wood tar mix (10.4%) and the framycetin (8.7%) were the most common allergens. There is a high frequency of allergic sensitisation to various ingredients of topical therapies used in the venous ulcer management, which may interfere with wound healing. Avoiding them can help obtain a better therapeutic outcome., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

In this report, we report a case study on a 50-year-old male patient with different chronic wounds, such as venous ulcer and arterial ulcer in both legs. These wounds have persisted for more than 10 years, despite the different treatments applied, including, different dressings, hyperbaric camera, as well as the used of several medicines of oral and topical application. The case is addressed with the aim to evaluate if treatment that uses combined techniques such as low level laser therapy (LLLT), photodynamic therapy and cellulose membrane is able to improve healing and reduction of time of treatment in those types of chronic wounds. The results show the clinical protocol is effective for the healing of arterial and venous ulcers and can be considered as a promising possibility., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Critical colonization or local infection is very common in chronic wounds, but clinically problematic. Because therapeutic options for these conditions are limited in number and efficacy, the study authors tested a new acid-oxidizing solution (AOS [Nexodyn]; APR Applied Pharma Research S.A., Balerna, Switzerland) to determine its ancillary antimicrobial properties and potential support for wound healing., Design and Setting: This open-label clinical case series was conducted with a prospective, single-arm design at the Federal County Hospital in Bregenz, Austria., Patients: In the study, 30 patients with critically colonized or locally infected chronic leg ulcers of any origin were included., Interventions: The AOS was applied on each leg ulcer at every dressing change for 35 days., Main Outcome Measures: The tolerability and performance of the AOS were assessed by evaluating the ulcer characteristics and comparing them with those at baseline. The clinical course of wounds was analyzed using standard measures for bioburden, local infection, pain, pH, and wound healing., Main Results: Application of the solution was well tolerated, and no adverse events were recorded. In all patients, local infection was overcome, and wound bed pH and wound area decreased significantly. In addition, patient pain levels decreased to a level where interventions were not required after study day 7. In 37% of all patients, a complete resolution of chronic ulcers was achieved by the end of the study period., Conclusion: According to these results, the AOS seems to be a valid and highly tolerable treatment to support wound healing in locally infected ulcers. Nevertheless, larger controlled cohort studies are needed to substantiate these findings.

Background: Chronic ulcers are a common problem, with chronic diabetic and venous ulcers forming a large proportion. This is the first case-control study to assess the effect of topical timolol on healing of chronic venous and chronic diabetic ulcers., Methods: The study included 60 patients with chronic leg ulcers. The ulcers in the study group (n = 30) were treated with topical 0.5% timolol maleate solution along with antibiotics and dressings; those in the control group (n = 30) received only antibiotics and dressings. The ulcers in both groups were evaluated at 4, 8, and 12 weeks, and ulcer area was calculated. Healing rate was assessed by calculating the percentage change in ulcer area., Results: The mean percentage change in area at 4, 8, and 12 weeks was 25.29, 43.77, and 61.79 in the study group and 11.92, 22.40, and 29.62 in the control group. Analysis showed that there were significant differences in percentage change in ulcer of the study and control groups at all three time points and also within the groups. The type of ulcer, history of alcohol consumption, and smoking did not affect the healing rates in the study group., Conclusions: Topical β-blockade using timolol improves the healing of chronic leg ulcers., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To report a case of refractory ulcerated necrobiosis lipoidica (NL) with significant response to treatment with topical tacrolimus., Subject: A 55-year-old woman without diabetes and with a previous history of NL presented to the Helen L. and Martin S. Kimmel Hyperbaric and Advanced Wound Healing Center of NYU Langone Medical Center, New York, with bilateral lower-leg ulcerations resistant to wound healing techniques at other institutions., Materials and Methods: Repeat biopsy performed at the author's institution confirmed the diagnosis of NL. Initial therapy was based on reports of other successful treatment methods, which included collagen wound grafts and collagen-based dressings coupled with compression. These methods initially showed promising results; however, the wounds reulcerated, and any gains in wound healing were lost. Alternative options were initiated, including topical clobetasol and narrowband ultraviolet B; however, no significant improvement was observed. The patient's lower-extremity wounds began to deteriorate. The patient also refused systemic therapy. Treatment was changed to topical 0.1% tacrolimus ointment and was applied daily for 10 months with multilayer compression wraps., Results: Both lower-extremity ulcerations began to show significant improvement, with the ulcers progressing toward closure except for 1 very small area on the left lower extremity., Conclusions: Topical tacrolimus seems to be an effective treatment option for patients with refractory chronic ulcerated NL who do not want systemic oral therapy. The authors found that successful wound closure may require a multimodal approach, which promotes wound healing, but also concurrently addresses the underlying disease process.

This study aimed to evaluate the effect of EMLA 5% cream applied to painful chronic leg ulcers (CLUs) as a primary dressing on wound healing and health-related quality of life (HRQoL). A pilot, parallel-group, nonblinded, randomized controlled trial was conducted in 6 community nursing procedure clinics in New South Wales, Australia. A total of 60 participants with painful CLUs of varied etiology were randomly assigned to the intervention (EMLA daily for 4 weeks as a primary dressing, followed by usual care) or usual care only. Wound size and HRQoL were measured at baseline, end of the intervention period (week 4), and week 12. At baseline, wound sizes were similar for both the intervention and control groups. During the intervention period, there was no significant difference in wound sizes between groups (intervention group: median (cm 2 ) = 2.4, IQR = 1.3-12.7; control group: median (cm 2 ) = 5.0, IQR = 2.5-9.9; P = .05). Mean HRQoL scores for all subscales at baseline and weeks 4 and 12 were similar between groups except for Wellbeing, which was significantly higher in the intervention group at the end of the 4-week intervention period (intervention group: mean = 52.41, SD = 24.50; control group: mean = 38.15, SD = 21.25; P = .03; d = 0.62). The trial findings suggest that daily applications of EMLA as a primary dressing do not inhibit wound healing and may improve patient well-being. Studies with larger samples are required to more comprehensively evaluate the impact of this treatment on wound healing and HRQoL.

Objective: Treatment of wounds difficult to heal concerns 50% of the elderly population in Italy and is therefore a relevant social burden. The present study shows how the treatment with autologous leuco-platelets reduces the healing time of wounds improving the functional recovery., Patients and Methods: Patients (n=100) with ulcers of the legs were divided in two groups: 1) 50 patients treated with conventional therapies; 2) 50 patients treated with autologous leuco-platelet concentrate (LPC) and hyaluronic acid (HIAFF, Hyalofill-F® ) as a scaffold., Results: After 2 months, a 49% reduction in wound area was observed in the second group and in about 65% wound reduction was achieved in 15 days (4 LPC dressings). In contrast, patients treated by conventional therapies, showed a longer healing time and a greater percentage of failures. Morphometric analysis of biopsy samples obtained from the edge as well as from the bottom of the lesions obtained from the LPC group, detected an abundant presence of neoformed capillaries, characterized by a cubic, "reactive endothelium", close to the site of LPC infiltration., Conclusion: These results suggest that healing was promoted not only by limiting bacterial infections but also by the release of chemotactic and proangiogenic factors from leukocytes and platelets, improving the neoformation of capillaries., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: The purpose of this retrospective registry data analysis was to explore the effectiveness of a novel multivalent topical ointment (Terrasil Infection Control Wound Care Ointment; Aspiera Medical, Woonsocket, Rhode Island), containing a patented mineral complex and 0.2% benzethonium chloride in the treatment of nonhealing acute and chronic wounds., Design: Aspiera Medical designed a registry to capture physician experiences and treatment results with Terrasil Infection Control Wound Care Ointment. Physicians were asked to enter deidentified patient data into an online registry., Setting: Wound clinics in the United States were asked to participate in the registry., Patients: Physicians at 4 wound clinics treated 30 patients (26 of whom completed the treatment) with various chronic wounds that had persisted for an average of 6 months and entered treatment data into the registry., Interventions: Patients applied the ointment according to physician orders. Concurrent treatments used by patients included offloading, compression wraps, and dressings, such as collagen and calcium alginate. Patients were treated until complete wound closure or lost to follow-up., Main Outcome Measures: Physicians calculated each patient's percentage wound reduction at each visit., Main Results: Thirty patients were entered into the registry. Pretreatment and posttreatment measurements were available for 26 of them. Patients achieved an average surface area reduction of 84% in a mean of 23 days' treatment., Conclusion: The antimicrobial and moisturizing ointment studied appears to be effective in promoting wound closure in a variety of acute and chronic wounds. Wounds studied included diabetic foot ulcers, venous leg ulcers, venous stasis ulcers, surgical infections, burns, and insect bites. The results of this registry data analysis will be used to inform planned clinical trials.

The aim of this study was to evaluate the results of treatment of venous lower limbs ulcers through the topical application of polynucleotides and hyaluronic acid gel (PNHA): Nucliaskin S™ (Mastelli srl, San Remo, Italy). This study was carried out in 39 consecutive patients who were randomly allocated to two groups: group I (20 patients) received treatment with PNHA (topical gel application two times a week, for a total of 6 weeks); group II (19 patients) received only hyaluronic acid (HA) topical application. All patients received a surgical debridement of the ulcerative lesions before topical treatment with PNHA or HA. Pre-treatment data indicated the area of ulceration. The number of healed ulcers and the variation in area of ulceration were considered as endpoints. The endpoints were observed after 45 days from the beginning of treatment. Complete wound healing occurred in 60% of limbs of group I and in 22% of those of group II patients. The average area reduction was 67% versus 34% in patients of group I and II, respectively. No side effects were recorded in both groups. Our experience shows that PNHA has an elevated trophic effect and speeds the healing rate of venous lower limb ulcers. This treatment may be a valid option in clinical practice., (© 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The pharmacological activities of many Punica granatum L. components suggest a wide range of clinical applications for the prevention and treatment of diseases where chronic inflammation is believed to play an essential etiologic role. The current work reports a case study analyzing the effect produced by a magistral formulation of ethanolic extracts of Punica granatum peels on a non-healing chronic ulcer. The complete closure of the chronic ulcer that was initially not responsive to standard medical care was observed. A 2% (w/w) P. granatum peels ethanolic extract hydrogel-based formulation (PGHF) was standardized and subjected to physicochemical studies to establish the quality control parameters using, among others, assessment criteria such as optimum appearance, pH range, viscosity and hydrogel disintegration. The stability and quantitative chromatographic data was assessed in storage for six months under two temperature regimes. An efficient HPLC-DAD method was established distinguishing the biomarkers punicalin and punicalagin simultaneously in a single 8 min run. PGHF presented suitable sensorial and physicochemical performance, showing that punicalagin was not significantly affected by storage (p > 0.05). Formulations containing extracts with not less than 0.49% (w/w) total punicalagin might find good use in wound healing therapy.

Background: This pilot study was aimed to assess the variations of some microscopical parameters in skin ulcers, caused by chronic venous insufficiency of the lower extremities (chronic leg ulcers), in 15 patients refractory to previous conventional treatments during photodynamic therapy (PDT)., Methods: Samples of control, wounded and PDT treated skin were taken and analyzed by immunohistochemistry., Results: The cellular infiltrate, as well as the thickness of epidermis, vascularization, mast cell and fibroblast numbers, were increased in chronic wounds as compared to healthy skin. After completion of PDT, fibroblasts appeared further increased in number. Mast cells, closely clustered with fibroblasts, also showed an increase in their numbers, degranulation index and expression of basic fibroblast growth factor., Conclusions: The present findings support a primary role of fibroblasts in the wound healing process upon PDT treatment, given their early and intense reaction to injury. Mast cells seem to play an accessory yet important role, on the basis of their number and degranulation index variations and expression of basic FGF. In addition, the clustering of mast cells with fibroblasts around blood vessels suggest that these cells may stimulate angiogenesis and, in parallel, fibroblasts to secrete extracellular matrix during PDT therapy.

Aim: The aim of this study was to determine the effect of low-dose aspirin on venous leg ulcer healing when used in addition to compression., Background: The mainstay of treatment for venous leg ulcers is compression therapy and there are few adjuvant treatments to accelerate healing., Design: Pragmatic, community-based, double-blind, randomized trial., Methods: Participants with venous leg ulcers will receive either 150 mg aspirin or placebo daily for up to 24 weeks. Participants will receive background treatment with compression therapy (system of choice guided by participant and/or clinical preference) delivered through district nursing services. The primary outcome will be time-to-healing. Secondary outcomes will include proportion healed at 24 weeks, change in ulcer area, change in health-related quality of life, adherence, efficacy of blinding and adverse events. The trial was funded in June 2014., Discussion: The trial commenced in March 2015 and is successfully recruiting. The trial is one of three trials that will contribute to an individual participant data meta-analysis to be undertaken at the York Trials Centre., Trial Registration: Registered 5 June 2014 ClinicalTrials.gov NCT02158806. Protocol version 1·1, 14 April 2015., (© 2015 John Wiley & Sons Ltd.)

Objective: Ozone therapy has a large clinical application in many therapeutic areas because of its well-known antimicrobial, immunological, and oxygenating properties. Recently, interest has grown regarding the application of ozonated oil for vascular leg ulcer treatment. The efficacy of an innovative spray formulation of ozonated oil and α-bisabolol combination in the topical treatment of chronic venous leg ulcers was evaluated compared with standard epithelialization cream., Design: A randomized controlled trial was conducted., Setting: A total of 29 patients older than 18 years with chronic venous leg ulcers for less than 2 years' duration were assessed., Patients: Patients were randomized to receive daily application of both ozonated oil and α-bisabolol or the control cream (vitamin A, vitamin E, talc, and zinc oxide) for 30 days., Main Outcome Measures: Patients were evaluated on 4 different visits: at days 0, 7, 14, and 30. At each visit, the wound surfaces were measured. Wound area ratio and the speed of ulcer healing were calculated., Main Results: At the end of treatment, the proportion of patients with complete ulcer healing was higher with ozonated oil and α-bisabolol formulation (25% vs 0%). Furthermore, the changes in ulcer surface area were significant for ozonated oil and α-bisabolol formulation only (P < .05), in particular, observing a significant and progressive reduction of the wound surface by 34%, 59%, and 73%, after 7, 14, and 30 days of treatment, respectively., Conclusion: The innovative spray formulation of ozonated oil and α-bisabolol combination shows promise as an important new therapeutic option in the adjuvant treatment of venous ulcers.

Lower leg ulcers are a serious and long-term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N = 6) or physiological saline (placebo; N = 6) in a randomised, placebo-controlled, double-blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow-up at 20 weeks. Wound area was significantly reduced to 34·8 ± 16·4% of week 0 levels at 20 weeks in APC-treated wounds (p = 0·01). At 20 weeks, three APC-treated wounds had completely healed, compared to one saline-treated wound. Full-thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p < 0·05), demonstrating improved patient quality of life as assessed by the Cardiff Wound Impact Questionnaire. This pilot trial suggests that APC is a safe topical agent for healing chronic lower leg ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Macrophages undergo a transition from pro-inflammatory to healing-associated phenotypes that is critical for efficient wound healing. However, the regulation of this transition during normal and impaired healing remains to be elucidated. In our studies, the switch in macrophage phenotypes during skin wound healing was associated with up-regulation of the peroxisome proliferator-activated receptor (PPAR)γ and its downstream targets, along with increased mitochondrial content. In the setting of diabetes, up-regulation of PPARγ activity was impaired by sustained expression of IL-1β in both mouse and human wounds. In addition, experiments with myeloid-specific PPARγ knockout mice indicated that loss of PPARγ in macrophages is sufficient to prolong wound inflammation and delay healing. Furthermore, PPARγ agonists promoted a healing-associated macrophage phenotype both in vitro and in vivo, even in the diabetic wound environment. Importantly, topical administration of PPARγ agonists improved healing in diabetic mice, suggesting an appealing strategy for down-regulating inflammation and improving the healing of chronic wounds., (Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

The purpose of this study was to compare the efficacy of dressings containing octenidine vs. dressings containing silver in the wound healing in the course of a chronic venous disease. There were two groups of 40 patients who met the inclusion criteria and who did not meet the exclusion criteria. The patients were randomly assigned into the groups (envelope method). The first, "O group" was treated with octenidine-based dressings. The second, "S group" was treated with silver dressings. The study lasted for 56 days. All patients in the research were treated with medical compression stockings with cotton understockings. Microbiological eradication was observed on the 28th day of the study among 33% of patients in the treatment group vs. 6% in control group. On the 56th day of the treatment, these percentages equalled 72% and 35%. The rate of healing was faster in the 0 group than in the S group. In the wounds <10 cm(2) it was faster by 1.35 cm(2)/week and in wounds >10 cm(2) it equalled 3.44 cm(2). The reduction of pain level was 37.5% higher in the O group, in contrast with the S group. One change of a dressing in the O group led to a 0.06 cm(2) greater wound size reduction and in the case of wounds >10 cm(2) to 0.29 cm(2) reduction compared with the S group. The presented results indicate that the efficacy of dressings containing octenidine is higher compared to silver dressings., (© 2015 by the Wound Healing Society.)

The most frequent causes of leg ulcers include venous incompetency (superficial and deep), arterial insufficiency, trauma, vasculitis, and neoplasm. Leg ulcers from injury by stingrays are quite rare. In this case report, we describe a leg ulcer caused by a stingray sting complicated by infection, which healed completely without surgery. In addition, since there few cases in the literature describing such traumas, we performed a comprehensive review of the literature. Important is the fact that the wound healing was complete without resorting to surgery, but only with a correct targeted antibiotic therapy and the use of a collagenase, which has the particularity of having hyaluronic acid as a component., (© The Author(s) 2014.)

Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways.

Non-healing wounds are associated with an inflammatory and proteolytic wound environment, and recent therapeutic strategies have been focused on reversing these changes. Connexins, as members of gap junctions, are important in intercellular signaling and wound repair. Connexin 43 (Cx43) downregulation is associated with normal wound healing, and it has been found to be upregulated in non-healing venous leg ulcers (VLUs). Ghatnekar et al. (2014) report findings of a small phase II trial performed in Indian patients with chronic VLUs, reporting that ACT1, a mimetic peptide of Cx43, accelerates healing in the treatment group. Despite standard care with compression therapy and adjuvant therapy for refractory wounds, at present in clinical practice a significant number of patients remain unhealed. The potential for ACT1 exists to help heal refractory VLUs, but it faces additional regulatory hurdles.

Background: The aryl hydrocarbon receptor has been shown to be involved in wound healing., Objective: The aim of this study was to assess the effect of tryptophan on wound healing in vitro and in a clinical trial., Methods: The ability of tryptophan and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to increase wound healing was assessed in an in vitro scratch wound model in human keratinocytes. Topical tryptophan and vehicle were assessed for 12 weeks in 51 patients with lower limb ulcers that were resistant to conventional therapies., Results: TCDD 0.1 nM and tryptophan 1 µM increased the rate of scratch recovery in a culture model. Topical tryptophan induced stronger pain relief and faster re-epithelialization than its vehicle in patients with lower limb ulcers., Conclusion: Tryptophan shows promising potential as a novel topical treatment for wound healing.

Background: The vasodilator cilostazol (Pletal(®)), a phosphodiesterase-3 inhibitor, is approved in the United States for treatment of intermittent claudication. This study was aimed at evaluating its efficacy as an adjunct in the management of arterial ulceration., Methods: The clinical records of patients treated with cilostazol from 2000 to 2010 at one institution were obtained. Of the 561 patients treated with cilostazol, we identified 82 (101 limbs) who started on therapy only after wounds were present and whose records were sufficient to assess healing. Only if all wounds in a limb completely healed without intervening arterial reconstruction, amputation, primary closure, or skin grafting, the limb was deemed healed with the assistance of cilostazol. With bilateral involvement, both limbs had to heal for the patient to be judged healed. Subjects who were lost to follow-up, died, or underwent surgical interventions other than debridement were deemed failures. Age, weight, height, body mass index (BMI), creatinine, diabetes, insulin therapy, hemodialysis, smoking history, congestive heart failure, cilostazol dose, and length of therapy were compared, as well as, the number of wounds, size of largest wound, chronicity, ankle-brachial index, the presence of exposed bone/tendon/joint, or the presence of gangrene., Results: Overall 30 of 82 patients (36.6%) and 41 of 101 (40.6%) limbs were deemed healed without surgical intervention or revascularization (open or endovascular). When 9 limbs that healed after skin grafts (n = 2) or foot-sparing amputations (n = 7) but without revascularization were considered, the overall rate of lower extremity limb salvage was 50.5%. Demographic characteristics were similar in the 2 groups except healed patients tended to be taller and weigh more but had similar BMI. The incidence of diabetes was higher in nonhealed limbs (73.3% vs. 50.0%, P = 0.0587). Gangrene was less common in healed patients (22.6% vs. 49.1%, P = 0.059) and healed limbs (22.0% vs. 48.3%, P = 0.027). Most subjects received 200 mg of cilostazol daily (healed:177 ± 53 mg vs. nonhealed: 172 ± 47 mg). Mean length of therapy in healed patients was 278 ± 302 days compared with 108 ± 129 days in nonhealed subjects before discontinuation of drug therapy or surgery, death, or loss to follow-up intervened., Conclusions: The observed limb healing rate with cilostazol compares favorably to the ~20% rate observed in subjects treated with placebo in multicenter trials of another vasodilator, iloprost. Although gangrene and diabetes correlate with lower prospects for healing, our data suggest that cilostazol helps promote healing of wounds when arterial insufficiency is present., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs)., Background: Chronic venous ulceration affects 1-3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial., Methods: A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: 'Healed ulcer', 'Healing ulcer' or 'No improvement' were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model., Results: Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings., Conclusion: The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs.

Stenotrophomonas maltophilia is a recently described organism which was mainly reported either in nosocomial setup, or in immunosuppresed individuals. This was rarely reported as cutaneous pathogenic organism causing cellulitis-like lesion, paronychia, mucocutaneous ulcers and ecthyma gangrenosum in immunocompromised individuals. Here we describe a case of leg ulcer caused by S. maltophilia in an immuno-competent patient. The infection was possibly community acquired as the patient had no exposure to hospital environment. The bacillus was sensitive to cotrimoxazole and levofloxacin, and the patient was successfully treated with cotrimoxazole. Our case is unique not only because it is probably the first ever case of leg ulcer caused by S. maltophilia, but also because of its unusual occurrence in immunocompetent patient., (© 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.)

The immunological mechanisms that are triggered by Low-Intensity Pulsed Ultrasound (LIPUS) in wound healing are unknown. In the present study, experimental groups were used to assess the treatment of chronic venous ulcers with 30mW/cm(2) SATA peripheral LIPUS three times per week compared to a daily treatment of 1% silver sulfadiazine (SDZ). The ulcers of the SDZ group (n=7) (G1) and LIPUS group (n=9) (G2) were photographed five times three months, and the images were analyzed using ImageJ software to quantify the total area (S), fibrin/sphacel area (yellow) and granulation area (red). The healing process was evaluated by the wound healing rate (WHR), granulation tissue rate (GTR) and fibrin/sphacel tissue rate (FTR). The ulcers were biopsied on days 1 and 45 and stained for collagen fiber quantification (picrosirius) and CD68(+) protein and VEGF (vascular endothelial growth factor) expression using HRP-streptavidin (horseradish peroxidase-streptavidin). On day 90, G2 had a mean 41% decrease in the ulcer area, while no decrease was observed in G1 (p<0.05). An increased tendency toward positive labeling of collagen fibers and VEGF (p>0.05) was observed in G2 compared to G1, and the number of CD68(+) cells was greater in G2 than in G1 (p<0.05). LIPUS presents superior activity compared to SDZ in stimulating the inflammatory and proliferative (angiogenesis and collagenesis, respectively) phases of chronic venous wound healing., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This product focus seeks to give an overview of the management of wound bioburden in relation to the use of antimicrobial dressings, according to recent guidelines and best practice statements. Identification of critical colonisation/localised infection and the role of biofilms is a key aspect of effective wound management. Silver antimicrobial dressings are efficient in reducing bacteria in wounds, but must be used appropriately to prevent overuse. Silver sulphadiazine has traditionally been used for the treatment of burns or Pseudomonas infection in leg ulceration, often in a cream formation. This article will be looking specifically at the effective use of Urgotul SSD in three critically colonised/non healing wounds.

Chronic wounds are characterized by prolonged inflammation, bacterial bioburden, and ischemia. These factors represent the barriers to wound healing that need to be addressed in order to achieve wound closure. The authors performed the initial clinical testing of WinVivo Wound Ointment ("WinVivo"), a novel topical ointment containing several botanicals that have been previously shown to promote favorable wound environment and advance wound healing. In this series of 13 patients with difficult-to-heal lower-extremity wounds, WinVivo was well tolerated and demonstrated the ability to simultaneously support granulation tissue formation; decrease the amount of exudate, edema, and malodor; and reduce pain. The ulcers included in this study have been present for a minimum of 3 weeks and a maximum of 5 years prior to the start of treatment with WinVivo. Eight of 13 wounds have previously been treated with at least 1 type of advanced wound healing modality, such as dermal substitutes or negative-pressure wound therapy. Treatment with WinVivo lasted for 3 to 12 weeks and resulted in a mean 88% wound closure, with 4 wounds healing completely. In addition to significant reduction in wound size, all patients have exhibited other clinical benefits, suggesting overall improvement in wound conditions. Future studies in a larger population, as well as case-control studies comparing WinVivo with a standard of care, are therefore warranted to further evaluate the efficacy of this new treatment.

Tepescohuite is an extract obtained from the bark of the Mimosa tenuiflora tree and is used as an empirical treatment in wounds for its healing and antiseptic properties. Venous leg ulcers (VLUs) are a common health care problem in most countries with a high rate of morbidity. The standard of care is moist interactive healing and compression; however, the ideal topical treatment is yet to be established. This study is designed to evaluate the effectiveness and safety of M. tenuiflora cortex extract (MTC-2G) in the treatment of VLUs in an Interdisciplinary Wound and Ostomy Care Center (IWOCC). A randomised, placebo-controlled, double blind clinical trial was conducted to compare the use of a hydrogel containing MTC-2G with the hydrogel alone in VLUs. The study included all patients with venous ulcers referred to the IWOCC. Laboratory tests and tissue biopsies were performed at the beginning and at the end of the study. The patients were instructed to daily cleansing followed by topical application of the hydrogel and compression. Forty-one patients were included, 22 patients received the MTC-2G and 19 patients received the hydrogel only. Of the 41 patients, 32 completed the study, 18 in the experimental arm and 14 in the control group, 19 were women and 13 men. The mean age of the subjects was 60 years. The mean time from presentation was 38 months. The mean surface reduction was 6·29 cm(2) [confidence interval (IC) 95%: 3·28-9·29] (P = 0·0001) in the MTC-2G group and 5·85 cm(2) (95% CI: 3·58-8·12) (P = 0·001) in the hydrogel group. There was no significant difference between the groups (P = 0·815). No changes in the laboratory parameters were noted. In the histology, there were not any differences between groups either. A hydrogel containing MTC-2G was not superior to a hydrogel alone in the treatment of VLUs., (© 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

The maintenance of an aseptic environment for chronic wounds is one of the most challenging tasks in the wound-healing process. Furthermore, the emergence of antibiotic-resistant bacterial strains is on the rise, rendering conventional treatments less effective. A new antibacterial material consisting of a polyurethane Tecophilic(™) nanofibre textile (NT) that was prepared by electrospinning and doped by a tetraphenylporphyrin (TPP) photosensitizer activated by visible light was tested for use in wound beds and bandages. In vitro experiments were performed to assess the antibacterial activity of the textile against three bacterial strains. Furthermore, the new textile was tested in 162 patients with chronic leg ulcers. A complete inhibition of in vitro growth of the three tested bacterial strains was observed on the surface of NTs that had been illuminated with visible light and was clinically demonstrated in 89 patients with leg ulcers. The application of the textiles resulted in a 35% decrease in wound size, as assessed via computer-aided wound tracing. Wound-related pain, which was estimated using a visual analogue scale, was reduced by 71%. The results of this trial reveal that the photoinactivation of bacteria through the photosensitized generation of short-lived, highly reactive singlet oxygen O(2) ((1) Δ(g) ) results in relatively superficial antibacterial effects in comparison with standard antiseptic treatment options. Thus, such treatment does not interfere with the normal healing process. This method therefore represents a suitable alternative to the use of topical antibiotics and antiseptics and demonstrates potentially broad applications in medicine., (© 2012 John Wiley & Sons A/S.)

Martorell's ulcer is a type of ischaemic ulcer of the lower leg, defined by severe pain and female-to-male predominance. The aim of this article is to assess the therapeutic effectiveness of PGE(1), both in pain control and in the healing times of Martorell's ulcers for patients already undergoing antihypertensive treatment. Between January 2004 and December 2008, we recruited 10 patients with Martorell's ulcers. These patients were organized into two groups (A and B). Group A included six patients who underwent only antihypertensive treatment with calcium channel blockers or angiotensin converting enzyme inhibitors. Group B consisted of four patients who underwent continuous administration of PGE(1) through a single-day elastomer (120 µg/24 hours) for 7 days. In both groups, we observed a progressive reduction in the surface area of Martorell's ulcers until complete recovery, but there was a significant difference with regards to healing time. We also observed a significant improvement in symptomatic pain after only 2 days of PGE(1) therapy. It has now been proved that antihypertensive treatment leads to ulcers healing but, according to our experience, intravenous infusion of prostaglandins improves peripheral perfusion and symptomatic pain and decreases healing time., (© 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

A new healing procedure has been developed on the basis of the successful treatment of therapy-resistant hypoxic (and practically anoxic) leg ulcerations located within a heavy dermatoliposclerosis. The procedure involves an initial intra-ulceral application of haemoglobin followed by the intermittent administration of normobaric oxygen via inhalation. Haemoglobin is capable of externally supplying the granulating wound bed with oxygen at low partial pressure in a physiological manner, like a micro lung, so that oxidative stress can be avoided. A long-term daily administration of oxygen from within - including the peri-ulceral skin - is achieved by intermittent normobaric oxygen inhalation (INBOI) regularly throughout the day in the form of 1-hour sessions.Using this combined healing treatment during haemoglobin applications the ulcerations healed within about 1 month, and subsequently with INBOI therapy within further approx. 4 months the peri-ulceral skin regenerated as far as the oxygenation status was concerned: The peri-ulceral transcutaneous oxygen partial pressure (tcPO(2)) of zero (measured during breathing of normal air) rose to a satisfactory value of approx. 35 mmHg. After 28 months of treatment, the completely hypoxic and degenerated skin on the leg had practically returned to normal with a PO(2) of 45 mmHg. Furthermore, the skin dermatoliposclerosis regressed. The skin regeneration was long-lasting, which was probably related to cellular tissue regeneration with an increase in the capillary density, whereby it had to be maintained by regular oxygen inhalation (INBOI maintaining treatment). By unintended intra-individual therapy variations it is evidenced that local hypoxia was the reason for skin degeneration: 3 x 1 h oxygen inhalation were sufficient for the healing treatment; 2 x 1 h sufficed for maintenance, whereas 2 x 0.5 h did not.The new procedure carries practically no risks, is simple, cheap and effective. Whereas the application of haemoglobin requires professional supervision, the oxygen inhalation can be carried out at home following initial guidance and monitoring by a physician. Using this novel method, the therapy-resistant ulceration could be closed within 5 months, during which daily outpatient care was only necessary for 1 month. The successful outcome of the treatment in terms of improvement of oxygen supply can monitored at any time using peri-ulceral tcPO(2) measurements, whereby, due to the inhomogeneity of the values, measurements at a minimum of two locations at the wound edge are strongly recommended and more measurements at more skin locations would be preferable.Besides its use in the healing of ulcers, the new procedure is also suitable for the prevention of ulceration development (prophylactic INBOI treatment) in skin rendered susceptible due to the presence of hypoxia. Here, peri-ulceral transcutaneous oxygen partial pressures of below 10 mmHg should be considered as being critical and are an indication for a prophylactic oxygen inhalation treatment. The new procedure may also be suitable even before the peri-ulceral oxygen partial pressure falls below 10 mmHg. Four measures for rehabilitation, conservation, and prevention with regard to a healed chronic wound are proposed.

Chronic leg ulcers are a debilitating, often painful, and costly condition. Leg ulcer healing may be impaired by bacterial colonization, which, unless effective intervention is instigated, can lead to infection. Although it is generally agreed that an antimicrobial dressing is clinically indicated when a wound becomes critically colonized, there is currently no agreement on what constitutes the best practice in the use of antimicrobials. This research compared the effectiveness of two commonly used antimicrobials: nanocrystalline silver and cadexomer iodine. A randomized-controlled trial was conducted in which 281 community nursing clients with leg ulcers compromised by bacterial burden were randomly assigned to have their wounds treated with either silver or iodine dressings. Sixty-four percent of ulcers healed within 12 weeks. The performance of each of the two antimicrobials was comparable in terms of overall healing rate and the number of wounds healed. However, use of silver compounds was associated with a quicker healing rate during the first 2 weeks of treatment and in wounds that were larger, older, and had more exudate. This trial provides some insights as to circumstances in which one product may be preferred over the other.

Background: The treatment of skin ulcers frequently presents a management challenge. Nonhealing wounds with poor response to conventional wound management therapy represent a significant cause of disability, affecting approximately 1% of the global population. Activated protein C is a serine protease with anticoagulant, angiogenic, and anti-inflammatory properties that has shown efficacy in patients for the treatment of severe sepsis. We report 4 cases of nonhealing lower limb skin ulcers that were treated with activated protein C., Observations: The study included 4 patients whose wounds were not improving despite standard wound treatment for 4 months or more. Activated protein C was applied topically to their wounds once weekly for 4 weeks. All 4 patients showed a rapid positive response to treatment that was maintained during a 4-month follow-up period. The treatment was well tolerated, with no remarkable adverse effects or complications., Conclusions: Activated protein C can stimulate wound healing in patients with skin ulcers that are refractory to conventional wound-healing therapies. The likely mechanism of action is its recognized ability to stimulate angiogenesis and reepithelialization and to inhibit inflammation. Activated protein C has potential as a therapeutic option for patients with chronic skin ulcers.

Background: Although a number of cytokine or growth factor therapies for wound acceleration have been reported, few mentioned the quality of the outcome. The lower extremity is important in esthetics as well as in function, because it is exposed. Recently, a growth factor, namely basic growth factor (bFGF) is widely used for difficult wound healing with a porcine-derived bilayered artificial dermis for better wound closure. Thus, their combination use was tested clinically., Methods: Sequential lower extremity reconstruction by an artificial dermis with or without bFGF administration and secondary split-thickness skin grafting was measured for hardness using a durometer, and the moisture parameters assessed such as effective contact coefficient, transepidermal water loss (TEWL), water content and thickness using a moisture meter for at least 6 months after the final procedure and compared with normal skin control., Results: There was significantly less skin hardness using a durometer in bFGF treatment compared with non-bFGF treatment (16.2 +/- 3.83 vs. 29.2 +/- 4.94, p < 0.01). Effective contact coefficient, TEWL, water content, and thickness in non-bFGF treatment were all significantly greater than those in bFGF treatment, whereas water content and thickness in bFGF treatment were comparable with those of the control., Conclusion: The use of bFGF as artificial dermis for extensive and deeper tissue loss coverage demonstrated better reconstruction quality in terms of hardness using a durometer and the function of the stratum corneum by moisture analysis.

Objective: An ulcer categorized as Fontaine's stage IV represents a chronic wound, risk factor of arteriosclerosis, and co-morbidities which disturb wound healing. Our objective was to analyze wound healing and to assess potential factors affecting the healing process., Methods: 199 patients were included in this 5-year study. The significance levels were determined by chi-squared and log-rank tests. The calculation of patency rate followed the Kaplan-Meier method., Results: Mean age and co-morbidities did not differ from those in current epidemiological studies. Of the patients with ulcer latency of more than 13 weeks (up to one year), 40% required vascular surgery. Vascular surgery was not possible for 53 patients and they were treated conservatively. The amputation rate in the conservatively treated group was 37%, whereas in the revascularizated group it was only 16%. Ulcers in patients with revascularization healed in 92% of cases after 24 weeks. In contrast, we found a healing rate of only 40% in the conservatively treated group (p<0.001). Revascularization appeared more often in diabetic patients (n=110; p<0.01) and the wound size and number of infections were elevated (p=0.03). Among those treated conservatively, wound healing was decelerated (p=0.01/0.02; chi(2) test)., Conclusions: The success of revascularization, presence of diabetes mellitus, and wound treatment proved to be prognostic factors for wound healing in arterial ulcers.

To determine the quantity and quality of current research on the effectiveness of silver-based dressings and topical agents for the treatment of leg ulcers, this paper presents a systematic review of randomized controlled trials (RCTs) looking at the effects of silver-based dressings and topical agents on leg ulcer healing. Electronic databases were searched up to May 2006 for relevant randomized controlled trials. Journals and conference proceedings were also searched. The methodological quality of selected trials was assessed and statistical pooling of the results from similar studies undertaken. Rate of healing, proportion of ulcers completely healed and change in ulcer size were observed. Nine studies were considered eligible for inclusion. These studies varied in terms of the types of leg ulcers treated, interventions used, and outcomes assessed. Studies provided inconsistent evidence regarding the effects of silver-based dressings and topical agents on leg ulcer healing. Studies generally provided poor evidence due to a lack of statistical power, poor study designs, and incomplete reporting. In conclusion, the current evidence base on the use of these silver-based products on leg ulcers is limited, both in terms of the quantity available and the quality of the evidence. This review highlights the need for further, more rigorous research to be carried out before the use of these silver-based interventions in routine leg ulcer management is supported.

Background: Topical silver treatments and silver dressings are increasingly used for the local treatment of contaminated or infected wounds, however, there is a lack of clarity regarding the evidence for their effectiveness., Objectives: To evaluate the effects on wound healing of topical silver and silver dressings in the treatment of contaminated and infected acute or chronic wounds., Search Strategy: We sought relevant trials from the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Wounds Group Specialised Register in March 2006 and in MEDLINE, EMBASE, CINAHL, and digital dissertations databases up to September 2006. In addition, we contacted companies, manufacturers and distributors for information to identify relevant trials., Selection Criteria: Randomised controlled trials (RCTs) assessing the effectiveness of topical silver in the treatment of contaminated and infected acute or chronic wounds., Data Collection and Analysis: Eligibility of trials, assessment of trial quality and data extraction were undertaken by two authors independently. Disagreements were referred to a third author., Main Results: Three RCTs were identified, comprising a total of 847 participants. One trial compared silver-containing foam (Contreet) with hydrocellular foam (Allevyn) in patients with leg ulcers. The second trial compared a silver-containing alginate (Silvercel) with an alginate alone (Algosteril). The third trial compared a silver-containing foam dressing (Contreet)) with best local practice in patients with chronic wounds.The data from these trials show that silver-containing foam dressings did not significantly increase complete ulcer healing as compared with standard foam dressings or best local practice after up to four weeks of follow-up, although a greater reduction of ulcer size was observed with the silver-containing foam. The use of antibiotics was assessed in two trials, but no significant differences were found. Data on pain, patient satisfaction, length of hospital stay, and costs were limited and showed no differences. Leakage occurred significantly less frequently in patients with leg ulcers and chronic wounds treated with a silver dressing than with a standard foam dressing or best local practice in one trial., Authors' Conclusions: Only three trials with a short follow-up duration were found. There is insufficient evidence to recommend the use of silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds.