[Compression therapy of venous leg ulcers in the decongestion phase]. / Kompressionstherapie des Ulcus cruris venosum in der Phase der Entstauung.

Compression therapy is the basis for successful treatment in most patients with venous leg ulcers. Concerning compression therapy, the initial phase of decongestion and the following phase of maintenance should be differentiated. While in the maintenance phase (ulcer) stocking systems are now frequently recommended, in the decongestion phase compression bandages are mostly still used, which however are often inappropriately applied. In German-speaking countries, compression therapy with short-stretch bandages has a long tradition. However, their correct application requires good training and monitoring, which is often lacking in daily practice. Less error-prone treatment alternatives are multicomponent systems, some of which have an optical marker for the control of the correct subbandage pressure. In another new type of compression system, which is called adaptive or wrap bandages, the compression pressure can be adjusted using a Velcro fastener. Accompanying intermittent pneumatic compression therapy can also be used in the decongestion phase. Thus, there are now several different treatment options that can be used for the decongestion phase in patients with venous leg ulcers. Often bandages with short-stretch materials are very prone to errors and should in most cases be replaced by other compression systems today. The patient's preference, need, and capability should be considered when selecting the appropriate system for the individual patient.

Evaluation of two fibrous wound dressings for the management of leg ulcers: results of a European randomised controlled trial (EARTH RCT).

OBJECTIVE: To evaluate the performance (efficacy, safety and acceptability) of a new micro-adherent absorbent dressing (UrgoClean®) compared with a hydrofiber dressing (Aquacel®) in the local management of venous leg ulcers, in the debridement stage. METHOD: A non-inferiority European randomised controlled clinical trial (RCT) was conducted in 37 centres, on patients presenting with venous or predominantly venous, mixed aetiology leg ulcers at their sloughy stage (with more than 70% of the wound bed covered with slough at baseline). Patients were followed over a 6-week period and assessed weekly. The primary judgement criteria was the relative regression of the wound surface area after the 6-week treatment period. Secondary endpoints were the relative reduction of sloughy tissue and the percentage of patients presenting with a debrided wound. RESULTS: Altogether, 159 patients were randomised to either UrgoClean (test group; n=83) or Aquacel (control group; n=76) dressings. Regarding the wound healing process predictive factors (wound area, duration, ABPI value, recurrence), at baseline, the two groups were well balanced, for both wound and patient characteristics. Compression therapy was administered to both groups and after a median 42-day treatment period, the percentage of relative reduction of the wound surface area was very similar (-36.9% vs -35.4% in the UrgoClean and control groups, respectively). When considering the secondary criteria at week 6, the relative reduction of sloughy tissue was significantly higher in the UrgoClean group than in the control group (-65.3% vs -42,6%; p=0.013). The percentage of debrided wounds was also significantly higher in the test group (52.5% vs 35.1%; p=0.033). CONCLUSION: This 'EARTH' RCT confirmed that the UrgoClean dressing has similar efficacy and safety compared to Aquacel. However, UrgoClean also showed better autolytic properties than the control group in the management of venous leg ulcers at the sloughy stage. The new UrgoClean dressing therefore represents a promising therapeutic option within the current range of autolytic dressings available. DECLARATION OF INTEREST: This study was sponsored by a grant from the pharmaceutical company Laboratoires Urgo. S. Bohbot and O. Tacca are employees of Laboratoires Urgo. S. Meaume, J. Dissemond and G. Perceau have received monetary compensation as presenters for Laboratoires Urgo. Data management and statistical analyses were conducted independently by Vertical (Paris, France).

A prospective study on the use of a non-adhesive gelling foam dressing on exuding leg ulcers.

OBJECTIVE: This non-comparative phase II study aimed to evaluate the safety and performance of a non-adhesive gelling foam dressing (GFD-N) in leg ulcer management. METHOD: Forty-six subjects with moderately to heavily exuding leg ulcers were treated with a regimen including GFD-N. Dressings were changed at least every seven days for four weeks or until healing. RESULTS: Mean GFD-N wear time was 3.2 days per subject. Mean wound area decreased from 10.1 cm2 at baseline to 5.1 cm2 at four weeks (p<0.001) and healed in five subjects (11%). The surrounding skin improved or remained stable in all but one subject. When compared with pre-study dressings, ulcer pain decreased for GFD-N, both with the dressing in place (p<0.001) and on dressing removal (p<0.001). Of final investigator ratings for 45 subjects, most were 'excellent' for ease of application (89%), ease of removal (96%), conformability (67%) and overall performance (58%). Five subjects experienced adverse events; none were serious or dressing-related. CONCLUSION: This small study demonstrates that GFD-N was safe, effective and convenient for wound healing, exudate management, pain/comfort and ease of use.

Treatment of recalcitrant venous leg ulcers with autologous keratinocytes in fibrin sealant: a multinational randomized controlled clinical trial.

In a multicenter trial, the effect of a commercially available combination of autologous keratinocytes (3-6 x 10(6)/mL) with fibrin sealant (Tissucol Duo S Immuno, Baxter Hyland Immuno) on the healing of recalcitrant venous leg ulcers (duration >3 months) was compared with standard care. The primary endpoint was time to healing, and the secondary endpoint was number of healed ulcers in both groups. Both groups received compression therapy with short-stretch bandages. Forty-four (38.3%) of the 116 patients who had BioSeed-S treatment achieved complete healing of the target ulcer compared with 24 (22.4%) of 109 patients who received standard treatment. The advantage for treatment with BioSeed-S over standard treatment was statistically significant (chi-square test: p=0.0106). Time to complete healing of ulcers: the log-rank test for equality over strata revealed a superiority of treatment with BioSeed-S+compression (median: 176 days) over compression+standard care (median >201 days) (p<0.0001). This study, to date the largest multicenter study with autologous keratinocytes, provides evidence for its efficacy in the treatment of patients with therapy-resistant chronic venous leg ulcers.

[Systematic management of chronic wounds employing the TIME concept]. / Systematisches Management chronischer Wunden nach dem TIME-prinzip.

The notion that chronic wounds are merely a variant of acute wounds is obsolete. The pathophysiology of chronic wounds differs in essence from that of acute wounds. The former is a specific pathological entity that requires both a systematic disease-specific diagnostic work-up and treatment. For the diagnosis and treatment of chronic wounds, the Wound Bed Preparation Advisory Board has proposed a new conceptthat goes bythe acronym of TIME, the letters of which refer to the structures to be diagnosed and treated: T = tissue, I = inflammation or infection, M = moisture (wound exudate), E = edge (of the wound). The present article discusses the principles and scientific background to this TIME concept.

Enzymatic versus autolytic debridement of chronic leg ulcers: a prospective randomised trial.

OBJECTIVE: A randomised clinical trial (n = 42) compared the effectiveness of two approaches to debriding chronic leg ulcers: TenderWet 24, which is designed to support the autolytic degradation process, and Iruxol N (Santyl), an enzymatic treatment claimed to enhance the degradation process. METHOD: Patients were randomly assigned to one of the two treatment groups for three weeks. Wounds were evaluated weekly for the amount of eschar/slough, the area of healthy granulation and the re-epithelialised area. RESULTS: During days 1-14 slough within the groups was reduced by almost 19% for TenderWet 24 and by 9% for Iruxol N, followed by an increase of 26% and 10% respectively in granulation tissue. These effects were less accentuated during days 7-21. There was a further 11% improvement in tissue debridement for the TenderWet 24 group and a relapse (+9.1%) in the Iruxol N group. CONCLUSION: Although TenderWet 24 appeared to be more efficient in a few cases, the general efficacy of the two products appeared to be almost the same as no statistically significant superiority of either product was found.

Treatment of therapy-refractive ulcera cruris of various origins with autologous keratinocytes in fibrin sealant.

BACKGROUND: Evaluation of the effects of cultivated, subconfluent, autologous keratinocytes in fibrin sealant (BioSeed-S) on the healing of therapy-refractive chronic wounds. PATIENTS AND METHODS: Open observational study in 60 patients with chronic leg ulcers and impaired wound healing of various origins. After whole-skin excision and cultivation of the autologous keratinocytes, the suspended cells were applied to the preconditioned wound in fibrin sealant. Wound epithelization and wound size were recorded at defined times. RESULTS: Fifty-two of the 60 participating patients could be evaluated. After 6 weeks, 29 ulcers (55.8%) were healed. The mean epithelization increased between the 8th and 42nd postoperative day from 23% to 62.5%. In 50.0% of the patients, global assessment of the wound showed a high degree of epithelization or healing after 42 days. In 32.6% of treated patients, improvement was observed, while no healing tendency was to be found in 17.4%. CONCLUSION: The present observational study indicates that the transplantation of autologous keratinocytes suspended in fibrin sealant could be of advantage in the treatment of refractive leg ulcers.

Development, validation and clinical use of the FLQA-I, a disease-specific quality of life questionnaire for patients with lymphedema.

BACKGROUND: It is known from clinical practice that lymphatic diseases can be associated with reductions of quality of life (QoL). Due to the lack of validated methods, only few studies however have systematically investigated the QoL in lymphedema. The aim of the study was 1) to develop a standardized QoL questionnaire specific for lymphedema and 2) to assess the QoL in these patients. PATIENTS AND METHODS: We developed and tested the FLQA-l, a novel QoL questionnaire developed specific for use in lymphedema on the basis of the previously validated FLQA vein questionnaire. The questionnaire consists of 92 items that refer to the following scales: Physical status, everyday life, social life, emotional well-being, treatment, satisfaction and profession/household. 392 patients with primary (n = 246) and secondary (n = 146) lymphedema were included in the validation study. RESULTS: The FLQA-l showed good internal consistency; Cronbach's alpha was higher than 0.75 in all scales. There were no floor and ceiling effects and satisfactory item selectivity. The test-retest reliability, sensitivity to change and convergent validity with other psychometric instruments were satisfactory. Clinically, patients with lymphedema showed markedly impaired QoL in all fields, compared to persons with early stage venous insufficiency, and comparable reductions of QoL, compared to patients with venous leg ulcer. CONCLUSION: These data indicate that the FLQA-l is a reliable and valid questionnaire for the assessment of QoL in lymphedema. Since the QoL is impaired in many patients with lymphedema, QoL evaluation may be helpful for clinical diagnostics as well as for outcome measurement of specific edema therapy.

Short-stretch versus multilayer compression for venous leg ulcers: a comparison of healing rates.

OBJECTIVE: To compare the performance of two compression systems, (multilayer elastic [Profore], Smith and Nephew) and (short stretch [Comprilan], Beiersdorf), in the treatment of venous leg ulcers in a randomised controlled trial. METHOD: Eighty-nine patients with venous leg ulcers were randomised to receive treatment with Profore (44 patients) or short-stretch (45 patients) compression bandages. Allevyn (Smith and Nephew) was used as the wound contact layer under both systems. RESULTS: Patients treated with Profore healed significantly faster than those treated with short stretch (p = 0.03) and were 2.9 times more likely to heal at any given time during the study period. Younger wounds healed significantly faster than older wounds (p = 0.01). CONCLUSION: Patients treated with Profore healed faster than those treated with short-stretch bandages. In addition, treatment costs are lower with Profore. In this trial the average cost per patient was [symbol: see text] 1345 (short stretch) and [symbol: see text] 587 (Profore).

Elevated expression of extracellular matrix metalloproteinase inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers.

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to matrix remodelling in venous leg ulcers. Extracellular MMP inducer (EMMPRIN; CD147) has been reported to increase MMP expression, and membrane type 1 MMP (MT1-MMP) has been implicated in the activation of MMPs. OBJECTIVES: To examine whether and to what degree EMMPRIN, MMP-2, MT1-MMP and membrane type 2 MMP (MT2-MMP) are expressed in venous leg ulcers as well as the association with MMP activity. METHODS: EMMPRIN, MMP-2, MT1-MMP and MT2-MMP were analysed by zymography and immunohistochemistry in biopsies from healthy skin and lesional tissue from venous leg ulcers. RESULTS: Zymography provided direct evidence of increased proteolytic activity of MMP-2 in lesional skin in comparison with healthy controls. Immunostaining showed intense expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP in dermal structures of venous leg ulcers, whereas only EMMPRIN and MMP-2 showed elevated expression in perivascular regions. Our findings indicate that venous leg ulcers are characterized by elevated expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP. The immunohistological findings of skin alterations reflect the dynamic process of activation of soluble and membrane-bound MMPs, which may be highly induced by EMMPRIN. CONCLUSIONS: These data suggest for the first time that membrane-bound MMPs may favour enhanced turnover of the extracellular matrix and support unrestrained MMP activity in venous leg ulcers.

The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in patients with chronic venous insufficiency: a double blind placebo-controlled randomised study.

BACKGROUND: The objective was to evaluate the oedema-protective effect of a vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines. PATIENTS AND METHODS: 231 patients were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin and 540 mg troxerutin per day) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry. RESULTS: 226 patients were evaluated. After ceasing compression stockings, an edema protective effect was detected in the SB-LOT-group but not in the controls. Recurrence of leg volume increase was by 6.5 +/- 12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p = 0.0402). The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group (p = 0.0041). Significant differences were also observed with regard to clinical global impression and therapeutic effect. No serious adverse drug reaction or clinically relevant impairment of laboratory parameters occur. CONCLUSION: This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who discontinue compression after a short time.

The role of the urokinase-type plasminogen activator (uPA) and its receptor (CD87) in lipodermatosclerosis.

BACKGROUND: Lipodermatosclerosis refers to a sclerosing panniculitis and dermopathy of the lower extremities sometimes seen in association with venous ulceration. Matrix metalloproteinases are implicated in the pathogenesis of venous leg ulcers and the in vitro activation of recombinant MMP-2 is controlled by the plasminogen activation system. To better understand the role of plasminogen activation in the pathogenesis of venous leg ulcers we investigated fibrinolytic factors and their inhibitors in tissue samples of lipodermatolsclerosis. METHODS: The expression and the functional state of the urokinase-type plasminogen activator (uPA), the tissue-type plasminogen activator (tPA), the urokinase receptor (CD87), the plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) were assayed using reverse transcription polymerase chain reaction, Western blot, fibrin zymography and immunohistochemistry analyses in tissue samples of lipodermatosclerosis. RESULTS: Our results provide direct evidence of elevated expression of uPA (p<0.01) and CD87 (p<0.01) mRNA and protein level in lipodermatosclerosis in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and CD87 could be detected. Fibrin zymography showed significantly elevated endogenous uPA activity (p<0.01) in liposclerotic lesions compared to healthy controls. CONCLUSION: Our findings indicate that elevated plasminogen activation in lipodermatosclerotic tissue may play a crucial role in the pathogenesis of venous leg ulceration.

EMLA anaesthetic cream for sharp leg ulcer debridement: a review of the clinical evidence for analgesic efficacy and tolerability.

Sharp debridement is a fast method of achieving a clean leg ulcer, which promotes healing and enables skin grafting. EMLA cream is the only topical anaesthetic for which there is clinical evidence of analgesic efficacy for debridement. Thirteen clinical investigations of EMLA are reviewed. Four double-blind studies and one open randomised controlled study show that EMLA applied to the ulcer for 30-45 min under occlusion significantly reduces the pain from sharp debridement, decreases the incidence of post-debridement pain and reduces the time needed to achieve a clean ulcer, giving potential savings in healthcare costs. Doses of up to 10 g EMLA result in plasma levels of lidocaine and prilocaine well below toxic levels. Repeated treatment does not change the bacterial flora of the ulcer and rarely causes sensitisation. The treatment of pain in leg ulcer patients is important for patient satisfaction and for patient-perceived quality of life.

Plasminogen activation in venous leg ulcers.

BACKGROUND: Venous leg ulceration results from chronic venous insufficiency of the lower extremities. We recently showed that matrix metalloproteinase (MMP) -2 plays a major part in the pathogenesis of venous leg ulcers. In vitro activation of recombinant MMP-2 is controlled by the activity of the urokinase-type plasminogen activator (uPA), which acts as a fibrin-independent plasminogen activator. The activity of MMP-2 is potentiated by binding of uPA to the uPA receptor (uPAR). OBJECTIVES: We aimed to clarify the role of plasminogen activation in venous leg ulcers. METHODS: The expression of uPA, uPAR, the tissue-type plasminogen activator, and plasminogen activator inhibitor (PAI) -1 and PAI-2 was investigated using reverse transcription followed by polymerase chain reaction and Western blotting. RESULTS: These provided direct evidence of elevated expression of uPA and uPAR at the mRNA and protein levels in venous leg ulcers, in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and uPAR was detected. Fibrin zymography showed significantly elevated endogenous uPA activity in venous leg ulcers in comparison with healthy controls. CONCLUSIONS: Our findings indicate venous leg ulcers to be characterized by elevated plasminogen activation, suggesting that this enzyme cascade plays a crucial part in maintaining proteolytic activity in venous leg ulcers.