The efficacy of low-frequency ultrasound as an added treatment for chronic wounds: A meta-analysis

We performed a meta-analysis to evaluate the effect of low-frequency ultrasound as an added treatment for chronic wounds. A systematic literature search up to May 2022 was performed and 838 subjects with chronic wounds at the baseline of the studies; 412 of them were using the low-frequency ultrasound (225 low-frequency high-intensity contact ultrasound for diabetic foot wound ulcers, and 187 low-frequency low-intensity non-contact ultrasound for a venous leg wound ulcers), and 426 were using standard care (233 sharp debridements for diabetic foot wound ulcers and 193 sham treatments for venous leg wound ulcers). Odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of low-frequency ultrasound as an added treatment for chronic wounds using the dichotomous, and contentious methods with a random or fixed-effect model. The low-frequency high-intensity contact ultrasound for diabetic foot wound ulcers had significantly lower non-healed diabetic foot wound ulcers at ≥3 months (OR, 0.37; 95% CI, 0.24-0.56, P < .001), a higher percentage of diabetic foot wound ulcers area reduction (MD, 17.18; 95% CI, 6.62-27.85, P = .002) compared with sharp debridement for diabetic foot wound ulcers. The low-frequency low-intensity non-contact ultrasound for a venous leg wound ulcers had a significantly lower non-healed venous leg wound ulcers at ≥3 months (OR, 0.31; 95% CI, 0.15-0.62, P = .001), and higher percentage venous leg wound ulcers area reduction (MD, 18.96; 95% CI, 2.36-35.57, P = .03) compared with sham treatments for a venous leg wound ulcers. The low-frequency ultrasound as an added treatment for diabetic foot wound ulcers and venous leg wound ulcers had significantly lower non-healed chronic wound ulcers at ≥3 months, a higher percentage of chronic wound ulcers area reduction compared with standard care. The analysis of outcomes should be with caution because of the low sample size of all the 17 studies in the meta-analysis and a low number of studies in certain comparisons.     

Low-frequency ultrasound (20-40 kHz) as an adjunctive therapy for chronic wound healing: a systematic review of the literature and meta-analysis of eight randomized controlled trials

Ultrasound as a therapeutic agent in chronic wound healing has been studied extensively. This systematic review and meta-analysis specifically examines low-frequency (20-30 kHz) ultrasound delivered at either low or high intensity. The objective of this review was to determine whether low-frequency ultrasound used as an adjunctive therapy improves the outcomes of complete healing and reduction of size of chronic lower limb wounds. PubMed, Cochrane/CENTRAL, technical assessment, relevant wound-related journals, and clinical guidelines were searched along with contacting manufacturers and authors of relevant randomized controlled trials were completed. Searches focused on the use of low-frequency ultrasound in randomized controlled trials. Data were collected via a data collection form and was adjudicated independently via coauthors. Meta-analyses and heterogeneity checks were performed using Mantel-Haenszel and inverse variance (fixed and random effects) statistical methods on studies with similar outcomes (complete healing and percent wound area reduction) over similar time periods. Single study results were reported via the statistical methods used in the study. Eight randomized controlled trials were identified. Results demonstrated that early healing (at ≤5 months) in patients with venous stasis and diabetic foot ulcers was favorably influenced by both high- and low-intensity ultrasound delivered at a low frequency-either via contact or noncontact techniques. However, the quality of the data may be suspect, especially for low-frequency low-intensity noncontact ultrasound because of significant biases. In patients presenting with either venous stasis or diabetic foot ulcers (Wagner classification 1-3), early healing appears to be facilitated by either low-frequency low-intensity noncontact ultrasound or low-frequency high-intensity contact ultrasound.     

Multiplexed analysis of matrix metalloproteinases in leg ulcer tissue of patients with chronic venous insufficiency before and after compression therapy

Elevated matrix metalloproteinases (MMP) levels have been implicated in the pathogenesis of chronic venous insufficiency ulcers. Quantitative measurements of a broad range of MMP proteins in human tissue treated with compression bandaging have not been reported. The goal of this study was to determine the expression of a wide range of proteases in untreated venous leg ulcer tissue and the changes in these levels after 4 weeks of high‐strength compression therapy. Twenty‐nine limbs with new or untreated chronic venous insufficiency and leg ulceration received therapy for 4 weeks with sustained high compression bandaging. Biopsies were obtained from healthy tissue and from ulcerated tissue before and after therapy. A novel multiplexed protein assay was used to measure multiple MMPs in a single sample. MMP protein activity, TIMP protein levels, and gene expression levels were also addressed. MMP1, 2, 3, 8, 9, 12, and 13 protein levels were elevated in ulcer tissue compared with healthy tissue. MMP8 and 9 were highly expressed in ulcer tissue. MMP3, 8, and 9 significantly decreased following treatment. Reduction in the levels of MMP1, 2, and 3 was associated with significantly higher rates of ulcer healing at 4 weeks. We conclude that compression therapy results in a reduction of the pro‐inflammatory environment characterizing chronic venous ulcers, and ulcer healing is associated with resolution of specific elevated levels of protease expression.     

A painless method of ultrasonically assisted debridement of chronic leg ulcers: a pilot study.

OBJECTIVES: Devitalized tissue in a recalcitrant leg ulcer is common and may impede healing. The aim of this study was to evaluate the use of a non-invasive low frequency ultrasound device to debride chronic leg ulcers as an adjunct to compression bandages therapy. METHODS: 19 patients with leg ulceration of at least 6 months were recruited. Low frequency ultrasound at 25kHz was delivered by a portable Sonaca--180 via a handheld probe, using normal saline as the irrigation/coupling medium. The ultrasound was applied for 10-20 seconds per probe head area onto the ulcer. Each leg underwent treatment at an interval of 2-3 weeks with compression bandages reapplied at the end of the treatment. Serial colour photographs were taken to evaluate the response at each visit. RESULTS: Each patient received on average 5.7 treatments each ranged from 5-20 minutes depending on the ulcer size. Symptomatic relief (pain and odour reduction) was achieved in 6 patients. 7 patients achieved complete ulcer healing (mean ulcer size=4.72+/-SD 1.872cm(2)) but no response was observed in 8 patients. There were no major complications of the treatment which was relatively painless. CONCLUSIONS: The application of low frequency ultrasound debridement may heal some recalcitrant ulcers when standard compression regimens have failed. It is cheap and does not require admission. The role of simple wound cleansing requires further investigation.     

Severe Chronic Venous Insufficiency Treated by Foamed Sclerosant

Our objective was to chronicle our experience in using sclerosant foam to treat severe chronic venous insufficiency (CVI). Forty-four patients with 60 limbs severely affected by severe CVI were entered into the study. They had lipodermatosclerosis, CEAP 4 (seven limbs); atrophie blanche or scars of healed venous ulcerations, CEAP 5 (18 limbs); and frank, open venous ulcers, CEAP 6 (35 limbs). Patients and limbs were collected into three groups. In group I, all limbs were treated with compression without intervention. Group II consisted of crossover patients who failed compression treatment. Group III consisted of patients treated promptly with sclerosant foam therapy without a waiting period of compression. A standing Doppler duplex reflux examination was done in all cases. Compression was by Unna boot or long stretch elastic bandaging. Foam was generated from Polidocanol 1%, 2%, or 3% by the two-syringe technique and administered under ultrasound guidance. Posttreatment compression was used for 14 days. In addition to clinical and ultrasound evaluation at 2, 7, 14, and 30 days, venous severity scoring was noted at entry and discharge. In group I, 12 patients were discharged from care within 6 weeks of initiating compression. All eight of the class 6 limbs had healed. Group II consisted of four CEAP class 5 limbs and eight class 6 limbs that had failed to heal with compression. Five of eight venous ulcers healed within 2 weeks, two more healed by 4 weeks, and one required 6 weeks to heal. In group III, 7 of 11 venous ulcers healed within 2 weeks and four more within 4 weeks. Venous severity scores reflected the success of treatment, with the greatest change occurring in group III and the least in group I. Limbs treated with foam had a statistically better outcome than those without (p = 0.041). One patient failed foam sclerotherapy, another had pulmonary emboli 4 months after foam treatment, and a single medial gastrocnemius thrombus was discovered 24 hr after treatment. Treatment of severe CVI with compression and foam sclerotherapy causes more rapid resolution of the venous insufficiency complications and does so without an increase in morbidity.     

Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers

OBJECTIVES: Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid. METHODS: This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment. RESULTS: Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment. CONCLUSION: Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.     

Prospective,multicenter study of managing lower extremity venous ulcers

Seventy patients with 90 venous ulcers were randomly assigned to hydrocolloid or conventional dressing and compression therapy at four study centers. The ulcers had been present for a mean of 47.8 in the control and 46.2 weeks in the treatment group and 42% of all patients had recurrent ulcers. Ulcers treated with hydrocolloid dressings reduced 71% and control treated wounds reduced 43% in area after 7.2 weeks of treatment. Thirty-four percent of all ulcers healed. Mean time to healing was 7 weeks for the hydrocolloid dressing group and 8 weeks for the control group. Most ulcers were less painful at final evaluation, but reduction in pain was more pronounced in hydrocolloid-dressed ulcers (p =0.03). At baseline as well as during follow-up, significant differences between study centers were observed. Ulcers in patients in the United Kingdom were larger and less likely to heal ( p =0.001). Size of the ulcer at baseline was associated with treatment response and time to healing ( p =0.002). Percent reduction in ulcer area after 2 weeks was also correlated with treatment outcome ( p =0.004) and time to healing ( p =0.002). When all treatment outcome predictors were analyzed together, only percent reduction in area after 2 weeks remained statistically significant ( p =0.002), with percent reduction during the first 2 weeks of treatment >30% predicting healing.     

Local therapy and treatment costs of chronic, venous leg ulcers with electrical stimulation (Dermapulse®): A prospective, placebo controlled, double blind trial

The purpose of our study was the evaluation of the therapeutic benefit and the economical profit of low-frequency pulsed current applied to therapy-resistant venous leg ulcers. We investigated 39 patients in a prospective, placebo-controlled, double blind study on the effect of low-frequency pulsed current (Dermapulse^®) on healing in chronic venous ulcers during a 4-month course of treatment. All patients had chronic venous ulcers. The following criteria were recorded: ulcer size, pain, capillary density, and transcutaneous oxygen partial pressure. In verum group 3, ulcers healed and ulcer area was reduced significantly. In placebo group two ulcers healed. Ulcer size was reduced significantly in each group (paired test), the difference of ulcer area reduction between the "verum" and the placebo group (unpaired test) was not significant. Capillary density in the ulcer increased in both groups. In verum group, electrical stimulation led to rapid and lasting reduction of pain (unpaired test, p =0.049). By means of the process calculation method for the subgroup of outpatients this treatment method was economically effective. Electrical stimulation seems to be a viable treatment option for therapy-resistant venous leg ulcers.     

The use of a portable, wearable form of pulsed radio frequency electromagnetic energy device for the healing of recalcitrant ulcers: a case report

Pulsed radio frequency energy (PRFE) has successfully been used to treat diabetic and venous stasis ulcers. In this case report, a lightweight wearable form of a PFRE device was evaluated and used to treat three diabetic foot ulcers and one venous stasis ulcer. The ulcers were present on the four patients for more than 3 months and had failed to heal after conventional treatment. A lightweight battery-powered, wearable form of PRFE device was introduced as a treatment and used 6-8 hours per day for a period of 6 weeks. All patients after 1 week of therapy showed improvement and wound size was seen to decrease. Patient 1 had a venous stasis ulcer, and reported significant pain relief after 2 weeks treatment. Patients 2 and 3 achieved complete healing after 3 weeks treatment, and patients 1 and 4 had a 95% and 88% reduction in wound size, respectively, after the 6-week study period. Both these patients continued to complete healing using the PRFE device after the 6-week study period. PRFE treatment delivered in the form of a wearable lightweight patch appears to offer promise in the treatment of recalcitrant chronic wounds.     

A prospective pilot study of ultrasound therapy effectiveness in refractory venous leg ulcers

Venous insufficiency is the most common cause of leg ulcers in the United States. Venous leg ulcers cost the health care system billions of dollars annually, and healing rates are less than 70% with standard of care; therefore, new therapies are needed to increase healing times and minimize associated costs. Non contact ultrasound therapy has been used to treat a variety of chronic wounds including venous leg ulcers, and it is thought that ultrasound has an effect on decreasing the bacterial count in wounds, although the exact mechanism of action of ultrasound is yet to be determined. We conducted an open labelled pilot study of 10 refractory venous ulcers of large size to determine the effect of non contact ultrasound on wound closure, bacterial counts, expression of inflammatory cytokines and pain reduction. We lacked a sham control group but we compared the baseline and end of treatment assessments and noted the differences. We found a significant reduction in wound area (P = 0·0039) over the 4-week treatment period. We also found a decline in individual and total bacterial counts; however, these differences were not significant. For all patients, there was also a trend toward reduced inflammatory cytokine expression compared with baseline levels; however, this reduction did not reach statistical significance. Interestingly, there was a correlation between healing and change in cytokine expression, which showed statistically significance for tumour necrosis factor (TNF)-αP = 0·0395, IL-1a P = 0·0351, IL-6 P = 0·0508, IL-8 P = 0·0990. Pain as measured by the visual analogue scale (VAS) was reduced from 4 at the baseline to 2·7 by the end of the study. In conclusion, we found that patients treated with ultrasound therapy and compression therapy show clinical improvement over the course of 4 weeks and had a decrease in inflammatory cytokines, bacterial counts and pain.     

Surgery of the superficial venous system in elderly patients

Chronic venous insufficiency, which traditionally has been attributed to failure of the deep venous system, may result from reflux in the superficial venous system. Chronic venous insufficiency is common in elderly patients, but surgical treatment is seldom offered to this patient population. We evaluated the results of superficial venous surgery for the treatment of severe chronic venous insufficiency in a cohort of elderly patients. The authors assessed patients aged 70 years or more with chronic venous insufficiency that had failed conventional conservative treatment. The superficial and deep venous systems were thoroughly investigated by duplex ultrasonography. Associated medical conditions were reevaluated and their treatment optimized. Twenty-eight patients (11 men, 17 women), aged between 70 and 89 years (mean 79), underwent superficial venous surgery. Open ulcers, active dermatitis and recurrent erysipelas were evident in 12, 9 and 7 patients, respectively. Limb swelling and severe pain were present in 25 (89%). The operations were performed under general or regional anesthesia with overnight hospitalization. Surgical treatment consisted of ligation of the points of reflux at the junctions of the superficial and deep systems, as defined by the duplex examination (21 saphenofemoral junctions, 5 saphenopopliteal junctions, 10 perforator veins), and stripping of the long saphenous vein to knee level (15 patients). Postoperative ambulatory treatment was continued until the wounds were completely closed. All ulcers healed completely within 8 weeks. No cardiac, respiratory, or renal complications were encountered. Wound infection at the groin occurred in 1 patient. Cellulitis of the calf area developed in 4 patients. Two ulcers recurred during follow-up of 1 to 5 years (mean 2.5). Surgery of the superficial venous system for treatment of severe chronic venous insufficiency is effective and can be achieved with minimal morbidity in selected elderly patients. The risk/benefit ratio for this procedure has been reduced sufficiently to ensure a major improvement in the quality of life of such patients.     

The impact of differential expression of extracellular matrix metalloproteinase inducer, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2 and PDGF-AA on the chronicity of venous leg ulcers.

INTRODUCTION: Alteration in the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-2 (MMP-2), tissue inhibitors of matrix metalloproteinases (TIMP-2) and platelet derived growth factor (PDGF-AA) may contribute to poor healing in venous leg ulcers. AIM: The aim of this study is to determine the expression of EMMPRIN, MMP-2, TIMP-2 and PDGF-AA in the ulcer exudates and perivascular tissue of healing and non-healing chronic venous ulcers. PATIENTS, MATERIALS AND METHODS: Forty patients with chronic venous ulcers were included in this study, with a mean age of 60 years. Eleven patients were males and 29 were females. All patients had normal ankle brachial index and a venous ulcer of at least 8 weeks duration. Immuno-histochemistry using monoclonal antibodies to PDGF-AA, MMP-2, TIMP-2 and EMMPRIN was carried out on paraffin embedded punch biopsy skin specimens from the ulcer edge. Enzyme linked immunosorbent assay for PDGF, MMP-2 and TIMP-2 were carried out on wound fluids collected from patients. The ulcer size and character at the initial assessment and after 8 weeks were assessed to determine the status of ulcer healing. RESULTS: No significant difference was seen in the expression of TIMP-2, MMP-2 and EMMPRIN between the two groups. However, in the non-healing group high levels of MMP-2 and low levels of TIMP-2 in the wound fluid suggest a strong correlation of these two markers in the state of healing. Analysis of wound fluid by ELISA demonstrated high PDGF-AA in the healing group (p = 0.021). Significantly increased levels of PDGF-AA (p<0001) was noted in the perivascular area on immuno-histochemistry of healing ulcers. These data suggest that PDGF-AA plays an important role in healing of venous ulcers. CONCLUSION: Non-healing venous ulcers are associated with greater activity MMP-2 activity. The ratio of MMPs to their inhibitors TIMPs, dictate the rate of healing of the ulcers. PDGF-AA activity is associated with ulcer healing, though the mechanism is unclear. EMMPRIN expression in chronic venous ulcers probably parallels the chronicity of the condition rather than propagate it. However, further studies with larger samples are needed.     

A prospective, randomized trial of Unna's boots versus hydroactive dressing in the treatment of venous stasis ulcers

In many centers the standard treatment for venous stasis ulcers consists of UB dressings. A new dressing, DuoDERM hydroactive dressing (HD), has recently been used extensively for the treatment of venous stasis ulcers. Because of this trend, a prospective, randomized trial of these two dressings was undertaken. Sixty-nine ulcers (39 HD and 30 UB) were randomized. End points were complete healing and development of complications necessitating cessation of treatment. Time to healing, cost of treatment, and patient convenience were also evaluated. Twenty-one of 30 ulcers (70%) healed with UB therapy compared with 15 of 39 ulcers (38%) treated with HD (p less than 0.01, CST). Life-table healing rates at 15 weeks were 64% for UB compared with 35% for HD (p = 0.01, log rank test). Ten of 39 patients (26%) receiving HD had complications compared with no complications in the UB group (p = 0.004, FET). For those patients whose ulcers healed, there was no significant difference (p = 0.51, STT) in the mean time required for healing or the average weekly cost of dressing materials between the HD group (7.0 weeks at +11.50 per week) and the UB group (8.4 weeks at +12.60 per week). Those patients treated with HD reported a significantly greater level of convenience than those patients with UB (p = 0.004, STT). Although treatment with HD led to better patient acceptance, those patients receiving UB therapy had a significantly greater rate of healing and a significantly lesser incidence of complications than those patients treated with HD.     

Low-power HeNe laser treatment of venous leg ulcers.

Clinical observations have suggested that low-energy lasers, mainly helium-neon (HeNe) lasers, might stimulate wound healing. A controlled study of the effects of low-power HeNe laser was performed in conjunction with a standard treatment for healing chronic venous leg ulcers on 46 patients divided randomly into two groups. All patients received standard treatment (paste-impregnated bandage and a self-adhesive elastic bandage) plus either HeNe laser (wave-length, 632.8 nm; beam power, 6 mW; continuous emission, energy density, 4 J/cm2) or placebo HeNe laser twice weekly for 12 weeks. The areas of healing were examined and compared percentage-wise after 2, 4, 6, 8, and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the HeNe group compared with the placebo group.     

Free tissue transfer provides durable treatment for large nonhealing venous ulcers

BACKGROUND: Most venous ulcers (VUs) will heal with conventional treatment, which focuses on improving regional venous hemodynamics. This treatment, however, often fails to heal large, recurrent VUs that are associated with severe lipodermatosclerosis (LDS). These complicated ulcers may require correction of local venous hemodynamics and replacement of the surrounding LDS with healthy tissue. We report our experience managing 24 especially difficult VUs with debridement and free flap coverage. PATIENTS AND METHODS: Between 1987 and 1997, 25 free flap procedures were performed in 22 patients for 24 recalcitrant VUs. Ulcers had been present for a mean of 5.24 years and had failed to heal with conservative therapy and split-thickness skin grafts (STSGs) (mean, 2.2). Eleven patients (46%) had exposed bone, tendon, or joint. At operation the area of LDS was excised, and all perforating veins were ablated. The defects after excision ranged from 100 to 600 cm(2) (mean, 237 cm(2)). The free flap was inset within the defect and covered with an STSG. RESULTS: We healed all 24 ulcers with free tissue transfer (one patient required a second flap after the first failed). There were no deaths. Local complications that required repeat STSG occurred in three (13%) of the 24 successful flap transfers. Four other flaps had minor local complications that healed with local wound care. Follow-up was available for 21 of the 24 successful flap transfers. No recurrent ulcers were identified in the territory of the flap after a mean of 58 months, but three patients had new ulcers in the same leg after 6 to 77 months. Patients with severe complications were hospitalized longer than those with minor or no complications (45.7 vs 12.8 days, P <.01), and their hospital charges were greater ($76,681 vs $30,428, P <.01). CONCLUSION: Free tissue transfer can provide rapid healing and long-term relief from severe VUs that are unable to be treated with conventional therapy. This technique improves venous hemodynamics, removes all liposclerotic tissue, provides an abundant blood supply, and resolves the tissue-related components of chronic ulceration. Although further work is needed to determine the optimal indications, this technique provides a durable treatment for especially recalcitrant ulcers.     

Effectiveness of prostaglandin E1 in patients with mixed arterial and venous ulcers of the lower limbs

Mixed arterial and venous ulcers of the lower limbs are present in around 15–30% of patients with chronic venous ulcers (CVUs) and are considered difficult‐to‐heal wounds. The aim of this study was to evaluate the results of the treatment of mixed arterial and venous ulcers of the lower limbs with prostaglandin E1 (PGE1) infusion. This study was carried out in 48 consecutive patients. Patients who showed intolerability to PGE1, and patients with peripheral neuropathy, blood or systemic diseases, malignancy and acute wound infections or necrotic tissue on the wound bed were excluded. The patients were separated at random into two main groups: group I (25 patients) received standard treatment and PGE1 infusion. Group II (23 patients) received only standard treatment. Pre‐treatment data indicated the area of ulceration. The number of healed ulcers and the variation in the area of ulceration were considered as endpoints. The endpoints were noticed after 120 days from the beginning of treatment. Healing occurred in 80% of limbs of group I and in 52·2% of limbs of group II patients. The average reduction in area was 92% versus 60% in patients of group I and II, respectively. During the whole treatment period, the incidence of adverse events was 8% in group I: there was one case of headache and one case of headache and hypotension combined. No side effects were recorded in patients of group II. In conclusion, PGE1 infusion is a determinant in the reduction of the healing time of mixed ulcers of the lower limbs.     

A placebo-controlled, double-blind study of mesoglycan in the treatment of chronic venous ulcers.

OBJECTIVES: to assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the healing of venous ulcers. Design randomised, placebo-controlled, double-blind, multicentre trial. METHODS: non-diabetic outpatients with chronic venous insufficiency confirmed by duplex ultrasound, normal ankle/arm pressure index and presence of a leg ulcer were eligible. Patients were randomised to mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally, or matching placebo, as an adjunct to compression therapy and topical wound care. Treatment and observation were continued until complete ulcer healing or for 24+/-1 weeks. Time to ulcer healing and healing rates were estimated with the Kaplan-Meier method. RESULTS: One hundred and eighty-three patients were randomised and included in the analysis (92 mesoglycan, 91 placebo). Median ulcer area upon inclusion was 3.6 cm(2)in the mesoglycan group and 3.9 cm(2)in the placebo group. The estimated time to heal 75% of the patients was 90 days on mesoglycan versus 136 days on placebo, while the cumulative rate of healing by the end of observation was 97% versus 82%, respectively. The difference in favour of mesoglycan was statistically significant (p < 0.05, centre-stratified Cox's model). The relative risk of ulcer healing with mesoglycan was 1.48. The rate of adverse events was 7/92 on mesoglycan and 6/91 on placebo. CONCLUSIONS: treatment with mesoglycan in addition to established venous ulcer therapy resulted in a significantly faster and more frequent ulcer healing, and did not raise any safety concerns.     

The treatment of venous leg ulcers: a new therapeutic use of iloprost

BACKGROUND: We conducted a study using an intravenous (i.v.) infusion of iloprost in the treatment of venous ulcers to verify whether the association of i.v. iloprost + local therapy + elastic compression has a favorable effect when compared with traditional treatment with local therapy and elastic compression. STUDY DESIGN: We evaluated the effects of iloprost in 98 consecutive patients with noncomplicated venous ulcers of lower limbs subdivided into 2 groups: the first group (48 patients) received iloprost in saline solution for 3 weeks and the second group (50 patients) received a venous infusion of a saline solution. The patients were examined at baseline time 0 (first visit) and then after 15, 30, 45, 60, 75, 90, 105, 120, 135, and 150 days. RESULTS: In the first group, after 90 days, all the ulcers had healed, whereas in the second group only 50% of ulcers had healed after 105 days. At the end of the study, in the second group only 84.09% of ulcers had healed. The statistical analysis showed a significant difference between the first (iloprost group) and the second group (placebo group). Besides, in the first group the cicatrization of the ulcer happened in a shorter period (27.90% after 60 days; 41.86% after 75 days; and 100% after 100 days) whereas in the second group, at the end of the study, in 15.91% of patients the ulcers had not recovered. CONCLUSION: Iloprost can significantly reduce healing time for venous leg ulcers through several actions.     

Effective use of negative pressure wound therapy provides quick wound-bed preparation and complete graft take in the management of chronic venous ulcers

Venous ulcers are characterised by longstanding and recurrent loss of skin integrity. Once occurred, healing is slow and recurrence is high because of inappropriate conditions of the wound bed. This study involves 20 patients with chronic venous ulcers at least 6 weeks of duration treated with negative pressure wound therapy (NPWT). Patients underwent a radical debridement of all devitalised tissues in the first operation. After adequate haemostasis, silver-impregnated polyurethane foam was applied. Once the wounds were determined to be clean and adequate granulation tissue formation was achieved, split-thickness skin grafts were applied. Black polyurethane foam was applied over them. All wounds completely healed without the need for further debridement or regrafting. The mean number of silver-impregnated foam dressing changes prior to grafting was 2·9 (one to eight changes). The mean number of NPWT foam changes was 2·6 after skin grafting (two to five changes). Two patients who did not use conservative treatments for chronic venous insufficiency (CVI) after discharge from the hospital had recurrence of venous ulcers in the follow-up period. Application of NPWT provides quick wound-bed preparation and complete graft take in venous ulcer treatment.