Effect of catalytic nanomedicine on amputation-stage chronic venous ulcers: four case studies.

BACKGROUND: Chronic ulcers represent a significant challenge for patients with compromised microcirculation. As a novel branch of research, catalytic nanomedicine has exhibited promising outcomes with the development of nanostructured composites designed to disinfect and improve the healing of chronic wounds through the incorporation of bionanocatalysts within gel matrices. PURPOSE: This study aimed to assess the impact of bionanocatalysts on 4 patients suffering from chronic venous ulcers, which had previously been indicated for lower extremity amputation. METHODS: Bionanocatalysts were synthesized and incorporated into a gel matrix. Monthly debridement was conducted with the objective of completely removing nonviable tissue. The bionanocatalyst-embedded gel was applied every other day, covering the entire wound surface and secured with a secondary dressing. RESULTS: Encouragingly, all cases exhibited complete wound closure, and patients reported no adverse side effects. CONCLUSION: These findings offer robust support for the utilization of this technology in wound healing and prompt a reevaluation of the hypothesis regarding the mechanism of action of bionanocatalysts in chronic wounds. Future research endeavors should aim to quantitatively assess the bionanocatalysts' influence on the trajectory of wound healing, as well as address the myriad challenges associated with managing chronic wounds.

Endovenous ablation for venous leg ulcers.

BACKGROUND: Venous leg ulcers (VLUs) are a serious manifestation of chronic venous disease affecting up to 3% of the adult population. This typically recalcitrant and recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The longstanding mainstay treatment for VLUs is compression therapy. Surgical removal of incompetent veins reduces the risk of ulcer recurrence. However, open surgery is an unpopular option amongst people with VLU, and many people are unsuitable for it. The efficacy of the newer, minimally-invasive endovenous techniques has been established in uncomplicated superficial venous disease, and these techniques can also be used in the management of VLU. When used with compression, endovenous ablation aims to further reduce pressure in the veins of the leg, which may impact ulcer healing. OBJECTIVES: To determine the effects of superficial endovenous ablation on the healing and recurrence of venous leg ulcers and the quality of life of people with venous ulcer disease. SEARCH METHODS: In April 2022 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scrutinised reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions on the language of publication, but there was a restriction on publication year from 1998 to April 2022 as superficial endovenous ablation is a comparatively new technology. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing endovenous ablative techniques with compression versus compression therapy alone for the treatment of VLU were eligible for inclusion. Studies needed to have assessed at least one of the following primary review outcomes related to objective measures of ulcer healing such as: proportion of ulcers healed at a given time point; time to complete healing; change in ulcer size; proportion of ulcers recurring over a given time period or at a specific point; or ulcer-free days. Secondary outcomes of interest were patient-reported quality of life, economic data and adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for eligibility, extracted data, carried out risk of bias assessment using the Cochrane RoB 1 tool, and assessed GRADE certainty of evidence. MAIN RESULTS: The previous version of this review found no RCTs meeting the inclusion criteria. In this update, we identified two eligible RCTs and included them in a meta-analysis. There was a total of 506 participants with an active VLU, with mean durations of 3.1 months ± 1.1 months in the EVRA trial and 60.5 months ± 96.4 months in the VUERT trial. Both trials randomised participants to endovenous treatment and compression or compression alone, however the compression alone group in the EVRA trial received deferred endovenous treatment (after ulcer healing or from six months). There is high-certainty evidence that combined endovenous ablation and compression compared with compression therapy alone, or compression with deferred endovenous treatment, improves time to complete ulcer healing (pooled hazard ratio (HR) 1.41, 95% CI 1.36 to 1.47; I2 = 0%; 2 studies, 466 participants). There is moderate-certainty evidence that the proportion of ulcers healed at 90 days is probably higher with combined endovenous ablation and compression compared with compression therapy alone or compression with deferred endovenous treatment (risk ratio (RR) 1.14, 95% CI 1.00 to 1.30; I2 = 0%; 2 studies, 466 participants). There is low-certainty evidence showing an unclear effect on ulcer recurrence at one year in people with healed ulcers with combined endovenous treatment and compression when compared with compression alone or compression with deferred endovenous treatment (RR 0.29, 95% CI 0.03 to 2.48; I2 = 78%; 2 studies, 460 participants). There is also low-certainty evidence that the median number of ulcer-free days at one year may not differ (306 (interquartile range (IQR) 240 to 328) days versus 278 (IQR 175 to 324) days) following combined endovenous treatment and compression when compared with compression and deferred endovenous treatment; (1 study, 450 participants). There is low-certainty evidence of an unclear effect in rates of thromboembolism between groups (RR 2.02, 95% CI 0.51 to 7.97; I2 = 78%, 2 studies, 506 participants). The addition of endovenous ablation to compression is probably cost-effective at one year (99% probability at GBP 20,000/QALY; 1 study; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Endovenous ablation of superficial venous incompetence in combination with compression improves leg ulcer healing when compared with compression alone. This conclusion is based on high-certainty evidence. There is moderate-certainty evidence to suggest that it is probably cost-effective at one year and low certainty evidence of unclear effects on recurrence and complications. Further research is needed to explore the additional benefit of endovenous ablation in ulcers of greater than six months duration and the optimal modality of endovenous ablation.

Circumferential Radical Debridement and Omental Free Flap in the Treatment of Severe Chronic Venous Ulcers.

BACKGROUND: Chronic venous leg ulcers are a significant health care burden with a difficult and unreliable treatment. Free flaps may be needed for wound coverage in severe cases. Incomplete removal of dermatoliposclerosis (DLS) area and/or not addressing the underlying venous dysfunction may contribute to the reported modest long-term results. METHODS: A series of 5 patients with severe chronic venous ulcers of the leg, resistant to conservative treatment and superficial venous surgery, were treated with radical, circumferential, subfascial resection of the DLS skin and coverage with omental free flaps. Delayed arteriovenous (AV) loops were used as recipients. All patients had previous superficial venous surgery and multiple skin grafts. Mean follow-up was 8 years (4-15 years). RESULTS: One hundred percent of flaps survived completely. No major complications occurred. One patient developed ulceration of the flap at 2 years and healed with basic wound care. At a mean follow-up of 8 years, all patients were ulcer-free. One patient died 15 years after the surgery for unrelated causes. CONCLUSIONS: Radical circumferential resection of DLS area in severe chronic venous leg ulcers and coverage with a free omental flap using staged AV loop provided durable coverage in a series of 5 patients. Complete resection of DLS area, addressing the underlying venous pathology, and draining the flap to a healthy competent vein graft (AV loop) may contribute to these favorable results.

Percutaneous mechanical thrombectomy to remove post-thrombotic obstructions and manage post-thrombotic syndrome-associated venous leg ulceration.

BACKGROUND: Up to one half of patients with a diagnosis of deep vein thrombosis will develop post-thrombotic syndrome (PTS). Patients with PTS can develop venous leg ulcers (VLUs) due to post-thrombotic obstructions (PTOs) that contribute to prolonged ambulatory venous hypertension. The current treatments for PTS, which include chronic thrombus, synechiae, trabeculations, and inflow lesions, do not target PTOs, and such obstructions can affect stenting success. The aim of the present study was to determine whether removal of chronic PTOs using percutaneous mechanical thrombectomy would promote VLU resolution and positive outcomes. METHODS: In this retrospective analysis, the characteristics and outcomes for patients with VLUs secondary to chronic PTO who were treated using the ClotTriever System (Inari Medical) between August 2021 and May 2022 were assessed. Technical success was considered the ability to cross a lesion and introduce the thrombectomy device. Clinical success was defined as a decrease of ≥1 in the severity category for the ulcer diameter using the revised venous clinical severity score (score 0, no VLU; score 1, mild VLU [size <2 cm]; score 2, moderate VLU [size 2-6 cm]; score 3, severe VLU [size >6 cm]) at the latest follow-up visit. RESULTS: A total of 11 patients with 15 VLUs on 14 limbs were identified. Their mean age was 59.7 ± 11.8 years, and four patients (36.4%) were women. The median VLU duration was 11.0 months (interquartile range [IQR], 6.0-17.0 months), and 2 patients had VLUs secondary to a deep vein thrombosis event >40 years previously. All treatments were performed in a single session, with technical success achieved in 100% of the 14 limbs. A median of five passes (IQR, four to six passes) with the ClotTriever catheter were performed per limb. Chronic PTOs were successfully extirpated, and intraprocedural intravascular ultrasound showed effective disruption of venous synechiae and trabeculations. Stents were placed in 10 limbs (71.4%). The time to VLU resolution or the latest follow-up was 12.8 ± 10.5 weeks, and clinical success was achieved for all 15 VLUs (100%), with the revised venous clinical severity score for the ulcer diameter improving from a median of 2 (IQR, 2-2) at baseline to a median score of 0 (IQR, 0-0) at last follow-up. The VLU area had decreased by 96.6% ± 8.7%. Of the 15 VLUs, 12 (80.0%) had resolved completely, and 3 had demonstrated near-complete healing. CONCLUSIONS: All patients showed complete or near-complete VLU healing within a few months after mechanical thrombectomy. Mechanical extirpation and interruption of chronic PTOs allowed for luminal gain and restoration of cephalad inflow. With additional investigation, mechanical thrombectomy with the study device could prove a vital component to the treatment of VLUs secondary to PTOs.

VIEW-VLU observational study of the effect of Varithena on wound healing in the treatment of venous leg ulcers.

OBJECTIVE: Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates. METHODS: The VIEW VLU study was a multicenter, open-label, phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein and/or anterior accessory saphenous vein systems who underwent ablation with 1% polidocanol microfoam. Primary outcomes included wound healing rate (change in wound perimeter), wound closure at 12 weeks after treatment, and time to wound closure. Secondary outcomes included VLU recurrence, numeric pain score at the ulcer location, EuroQol five-dimension five-level questionnaire quality-of-life index, and the Venous Clinical Severity Score. Patients were followed for 12 months. RESULTS: We enrolled 76 patients (80 ulcers) from 14 sites across the United States and Canada (mean age 63.6 ± 13.7 years, 39.5% female, mean body mass index 36.3). Of the enrollees, 96.3% presented with great saphenous vein incompetence. The mean baseline wound perimeter was 117.2 ± 107.4 mm and 26.3% of wounds (21/80) were circumferential. The mean ulcer age was 34.8 ± 51.8 weeks at first presentation and the mean compression therapy duration was 26.4 ± 35.9 weeks. The median wound perimeter decreased by 16.3% from baseline in the first 2 weeks after the procedure and by 27.0% at 12 weeks. By 12 weeks, 53.8% of wounds (43/80) were healed. The median time to ulcer closure by Kaplan-Meier analysis was 89 days (95% confidence interval, 62.0-117.0). In a Kaplan-Meier analysis of initially healed wounds, 88.9% (95% confidence interval, 76.9-94.8) remained closed at 12 weeks after closure. The mean numeric pain scores (ulcer site) improved by 41.0% and 64.1% at 12 weeks and 12 months after the procedure, respectively. The health-related quality-of-life index (scale of 0-1) improved from 0.65 ± 0.27 at baseline to 0.72 ± 0.28 at 12 weeks and 0.73 ± 0.30 at 12 months. By 12 weeks after treatment, the mean target leg Venous Clinical Severity Score had significantly decreased by 5.8 points, and by 12 months it had decreased by 10.0 points. CONCLUSIONS: Treatment with 1% polidocanol microfoam was associated with promising wound healing rates and low recurrence rates for VLUs, despite a challenging patient population with recalcitrant ulcers, a large percentage of which were circumferential, in patients with high body mass indexes.

A systematic review and meta-analysis of concomitant truncal and perforator surgery.

OBJECTIVE: Incompetent perforator veins are encountered frequently during ultrasound assessment of the venous system in chronic venous disease. Some studies have shown that concomitant treatment of truncal and perforator incompetence improves ulcer healing, yet a Cochrane review was unable to determine the potential benefits of perforator surgery in venous ulcer management due to poor quality evidence. This study aims to establish the exact role of concomitant treatment in patients with chronic venous disease. METHODS: A search of online databases including MEDLINE, Embase, and Cochrane was performed in March 2022. All studies comparing the outcomes of concomitant superficial venous plus perforator surgery with standard therapy were included. Variables assessed included ulcer healing, time to healing, and ulcer recurrence. Disease severity and quality of life, vein occlusion rates, number of incompetent perforator veins on duplex ultrasound post treatment, and reintervention and complication rates were also analyzed. Data were pooled using a random effects model. RESULTS: Seven studies (872 limbs) were included for analysis. Included studies were of reasonable methodological quality. Ulcer healing rates were similar in each group (relative risk [RR], 1.07; 95% confidence interval [CI] 0.96-1.19; P = .23). Two studies reported no difference in mean time (days) to ulcer healing between groups (mean difference, -14.60; 95% CI, -34.57 to 5.38; P = .15; I2 = 0%; P = .56). Ulcer recurrence was significantly lower in the concomitant group (3.7% vs 44%) (RR, 0.21; 95% CI, 0.07- 0.65; P = .007; I2 = 43%; P = .17). Overall, there was no difference in disease severity measured at 12-month follow-up, with a weighted mean difference between groups of -0.88 (95% CI, -2.05 to 0.29; P = .14; I2 = 84%; P = .002). Quality of life was reported in only one study. The total number of perforator veins identified at follow-up duplex ultrasound was significantly lower in the concomitant group (22.4% vs 89%) compared with standard therapy (RR, 0.31; 95% CI, 0.19-0.53; P < .0001; I2 = 88%; P = .0002). There was no difference between groups for occlusion rates of treated great saphenous vein or incompetent perforators (RR, 2.22; 95% CI, 0.10-49.74; P = .61). Reported minor (RR, 0.98; 95% CI, 0.63-1.52; P = .92) and thrombotic complications (RR, 2.04; 95% CI, 0.59-6.99; P = .26) were similar between groups. CONCLUSIONS: Concomitant truncal and perforator surgery is comparable to standard therapy in terms of ulcer healing, safety, and efficacy. Meta-analysis suggests that concomitant treatment could significantly reduce ulcer recurrence rates, but included studies were subject to some biases and short follow-up. Concomitant treatment may be considered to prevent recurrence rather than improve ulcer healing.

Venous leg ulcers and prevalence of surgically correctable reflux disease in a national registry.

BACKGROUND: Chronic venous disorders are common, with varicose veins occurring in ∼40% of the population. Venous leg ulcers affect 1% to 2% of the population, with the prevalence increasing ≤4% for those aged >65 years. Both conditions are expensive and together are responsible for ≤2% of the annual healthcare budget expenditure of Western societies. The ESCHAR (effect of surgery and compression on healing and recurrence) and EVRA (early venous reflux ablation) trials demonstrated that surgical correction of superficial venous reflux reduced ulcer recurrence, resulted in faster healing times (EVRA), and was proved cost-effective. Largescale data regarding patients with chronic venous leg ulcers presenting to venous centers with treatable superficial venous insufficiency has not been previously reported. Our study was designed to evaluate the percentage of patients with leg ulcers presenting to dedicated vein centers who were found to have surgically correctable superficial venous insufficiency. METHODS: The American Vein & Lymphatic Society Patient Reported Outcome Venous Registry began collecting data in 2014 and is one of two national registries focused on chronic venous disorders. The database was queried first for the presence of an ulcer using the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification (C6 status). These de-identified data were further correlated by crossing the number of ulcers for the same limb using the revised venous clinical severity score (rVCSS). The demographics, index duplex ultrasound details, and rVCSS features for ulcer duration and compression use were analyzed. Once the presence of an ulcer had been validated by CEAP and rVCSS, the population was divided into groups according to the ultrasound-reported anatomic pathology (eg, normal, reflux, obstruction, reflux plus obstruction). The query was directed toward all patients seeking a venous evaluation at participating centers from January 2018 through January 2022. RESULTS: More than 270,000 unique patient records were reviewed. Of the 270,000 records, 163,027 (60%) had had duplex ultrasound scans available, for 1794 unique patients (1879 limbs), representing 1.1% with a leg wound. Of these patients, 55.4% were men and 44.6% were women. Group S included patients with isolated superficial pathology (n = 1291; 68.7%). Group M included patients with mixed superficial and deep pathology (n = 238; 12.7%). Group D included patients with isolated deep vein pathology (n = 58; 3.1%). Finally, group N included patients with leg wounds but no venous pathology (n = 292; 15.5%). The rVCSSs for groups S and M were significantly higher than those for group N. In group S, the dominant patterns involved the great saphenous vein (GSV) above the knee (54.8%), the small saphenous vein (30.7%), and the anterior accessory GSV (14.4%). The frequency of single, double, and triple axial vein reflux identified 1.45 vessels eligible for ablation treatment per limb. In group M, the dominant patterns involved the GSV above the knee (61.7%), the small saphenous vein (26.2%), and the anterior accessory GSV (12.1%), for 1.52 axial segments per limb. Of the 84.4% of venous ulcer patients, duplex ultrasound analysis revealed that 97% of this large subset had had surgically correctable disease. CONCLUSIONS: The American Vein & Lymphatic Society Patient Reported Outcome Venous Registry demonstrated that 85% of the leg wounds in the present study were venous in origin and 97% possessed surgically correctable disease. Our findings support early referral to dedicated vein centers with appropriate venous reflux management as a part of the multidisciplinary team caring for patients with venous leg ulcers.

Cost-effectiveness of Compression Therapy With Early Endovenous Ablation in Venous Ulceration for a Medicare Population.

Importance: Venous leg ulcers (VLU) are the most common cause of lower extremity ulceration that commonly occur among older individuals and are characterized by a slow healing trajectory and frequent recurrence; in the United States, VLUs affect more than 600 000 people per year with an estimated cost of $3.5 billion. Clinical trial data show that early intervention with endovenous ablation substantially improves the healing rate and reduces recurrence among patients with VLUs, but there is a need to assess the cost-effectiveness of early endovenous ablation in the US context. Objectives: To evaluate the cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with VLU from the US Medicare perspective. Design, Setting, and Participants: This economic evaluation used a Markov model to simulate the disease progression of VLU for patients receiving compression therapy with early vs deferred ablation over 3 years. The simulated cohort included patients with VLU aged 65 years and older who had clinical characteristics similar to those in the randomized Early Venous Reflux Ablation trial in the United Kingdom. Data were analyzed from September 2021 to June 2022. Main Outcomes and Measures: Direct medical costs, quality-adjusted life years (QALYs), and the incremental monetary benefits at a willingness-to-pay threshold of $100 000/QALY. Univariate and probabilistic sensitivity analyses were performed to test uncertainty of model results. Results: This model used a simulated cohort of patients with VLU aged 65 years and older enrolled in Medicare. Early ablation dominated, with a lower per-patient cost of $12 527 and an increase of 2.011 QALYs, whereas compression therapy with deferred ablation yielded a per-patient cost of $15 208 and 1.985 QALYs gained. At a $100 000/QALY cost-effectiveness threshold, the incremental net monetary benefit was $5226 per patient in favor of early ablation. Probability of healing, followed by the probability of recurrence, was the parameter with greatest impact on model uncertainty. The probabilistic sensitivity analysis showed that early ablation was cost-effective in 59.2% of simulations at the $100 000/QALY threshold. Conclusions and Relevance: In this economic evaluation of compression therapy with early endovenous ablation, early intervention was dominant, as it was cost saving and generated greater QALYs over 3 years from the US Medicare perspective. Payers should prioritize coverage for early ablation to prevent VLU complications rather than treat a costly outcome that also reduces patient well-being.

Radiofrequency ablation of varicose veins in combination with ultrasonic-assisted wound debridement and platelet-rich plasma as well as platelet-rich fibrin technologies in treatment of lower extremity venous ulcers in office-based surgery.

Introduction: for the treatment of varicose ulcer performed clinical and laboratory reasoning of the use of ultrasonic-assisted venous ulcer debridement and Platelet-rich plasma with radiofrequency ablation in an outpatient setting, was carried out. Methods: ultrasonic-assisted debridement of trophic ulcer were performed for 50 patients with lower extremity varicose veins at decompensation stage. The effectiveness of ultrasonic-assisted debridement was evaluated by indicators of bacteriological, morphological, cytological study and assessment of trophic ulcers according to the MEASURE system. After ultrasonic-assisted debridement, the patients were divided into two groups: 30 patients, who underwent combined Platelet-rich plasma to stimulate wound regeneration and 20 patients, for whom the Granuflex hydrocolloid bandage was applied for the same purpose. Results: a comparative analysis of ulcer regeneration in two groups of patients proved that in cases of platelet rich plasma the time of transition from inflammatory-regenerative type to regenerative one is much shorter than when using a hydrocolloid dressing. In 28 patients undergoing Platelet-rich plasma (PRP) and Platelet-rich fibrin (PRF), the radiofrequency ablation of the principal superficial and perforating veins was performed. Another 22 patients performed autodermoplasty of trophic ulcers after radiofrequency ablation. Conclusion: our experience has shown that in a one-day inpatient surgical clinic such a multidisciplinary approach to treatment of venous ulcers, including ultrasonic-assisted debridement that is stimulation of wounded process by Platelet-rich plasma with further surgeries to remove the causes of decompensated chronic insufficiency, is promising regarding low costs of treatment and rehabilitation of these patients.

Efficiency of endovenous laser and glue ablation methods in comparison with conventional surgery for the treatment of venous ulcers.

INTRODUCTION: In this study, we aimed to investigate the efficiency of endovenous laser and glue ablation techniques and compared the results with conventional surgical stripping. PATIENTS AND METHODS: Between January 2005 and January 2020, among 3133 consecutive patients with superficial venous reflux disease receiving treatment at our institution, there were 112 consecutive patients with active venous ulcers. Patients were divided into 3 groups as receiving conventional open surgical treatment (Group 1, n: 70), endovenous glue ablation (Group 2, n: 20), and endovenous laser ablation (Group 3, n: 22). Comorbidity factors, duration and size of the ulcers, deep, perforating, and small saphenous vein disease detected with detailed Doppler ultrasonography, and duration for healing and recurrence were investigated. RESULTS: The age, gender, comorbidities, smoking, history of previous treatment, diameter of the small saphenous vein, number of refluxing perforating veins, size of the ulcer, and ulcer recurrence ratio were not significantly different between groups. There were 7 patients with bilateral disease and in total 119 legs were intervened. Mean durations for complete ulcer healing were significantly lower in Group 1 (53.28 ± 22.1 days) than Group 2 (73.7 ± 39.6 days); however, it did not differ significantly between Group 1 and Group 3 (62.59 ± 19.65 days), and Group 2 and Group 3 (p: 0.26). Ulcers recurred in 23 patients (33%) in stripping group at a mean follow up of 14.42 ± 4.6 months, in 7 patients (35%) in glue ablation group at a mean follow up of 11.97 ± 2.94 months, and in 5 patients (23%) in laser ablation group at a mean follow up of 12.66 ± 3.48 months (p > 0.05 for all). Increased body mass index, co-existence of chronic venous insufficiency, active cigarette smoking, non-compliance with physician advises and exercise and compression stockings, and depth of the ulcers were correlated with recurrence. CONCLUSION: The rationelle beyond treatment of the venous ulcers and prevention of recurrence relies on relief of the venous hypertension by interventional methods and/or compression therapy. None of the methods is superior over the others. Healing in short term without further recurrence may be achieved with successful intervention as well as good patient compliance.

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers.

BACKGROUND: This randomized controlled trial evaluated the safety and effectiveness of weekly and biweekly applications of dehydrated human amnion and chorion allograft (dHACA) plus standard of care compared to standard of care alone on chronic venous leg ulcers. METHODS: This open-label randomized controlled trial included patients with chronic venous leg ulcers at eight wound care centers across the United States. The primary endpoint was the proportion of healed ulcers at 12 weeks. Secondary endpoints included the proportion of ulcers achieving 40 percent closure at 4 weeks and the incidence of adverse events. RESULTS: Among 101 patients screened for eligibility, 60 were eligible and enrolled. At 12 weeks, significantly more venous leg ulcers healed in the two dHACA-treated groups (75 percent) than in the standard-of-care group (30 percent) ( p = 0.001) even after adjustment for wound area ( p = 0.002), with an odds ratio of 8.7 (95 percent CI, 2.2 to 33.6). There were no significant differences in the proportion of wounds with percentage area reduction greater than or equal to 40 percent at 4 weeks among all groups. The adverse event rate was 63.5 percent. Among the 38 adverse events, none were graft or procedure related, and all were resolved with appropriate treatment. CONCLUSIONS: dHACA and standard of care, either applied weekly or biweekly, significantly healed more venous leg ulcers than standard of care alone, suggesting that the use of aseptically processed dHACA is advantageous and a safe and effective treatment option in the healing of chronic venous leg ulcers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Factors associated with delayed venous ulcer healing after endovenous intervention for superficial venous insufficiency.

OBJECTIVE: This retrospective trial analyzed the effect of predetermined variables on venous ulcer healing after endovenous ablation of insufficient veins. METHODS: A total of 259 patients presenting 273 venous leg ulcers (VLUs) at Oulu University Hospital vascular outpatient clinic between January 2010 and December 2020 were included in the study. In addition to compression therapy, all patients received endovenous ablation (endothermal ablation and/or foam sclerotherapy) to promote venous healing. The hazard ratio (HR) for an ulcer to heal was analyzed in univariate analysis of predetermined factors, including age, sex, recurrent venous ulcer, presence of great saphenous vein or small saphenous vein reflux, persistent superficial vein reflux after ablation, recanalization in treated segments, ulcer age, body mass index >35 kg/m2, history of deep vein thrombosis, history of erysipelas, ability to move, smoking, hypertension, atrial fibrillation, coronary artery disease, diabetes mellitus, and cardiac insufficiency. Logistic regression was used in a multivariate analysis to identify independent risk factors for ulcer healing. RESULTS: In the univariate analysis, healing was negatively associated with persistent superficial vein reflux after ablation (HR, 0.117; 95% confidence interval [CI], 0.088-0.354), recanalization in treated segments (HR, 0.161; 95% CI, 0.060-0.433), nonambulatory patient (HR, 0.322; 95% CI, 0.130-0.800), history of deep vein thrombosis (HR, 0.518; 95% CI, 0.294-0.910), and presence of small saphenous vein reflux (HR, 0.565; 95% CI, 0.384-0.830). Independent risk factors included persistent superficial vein reflux after ablation (HR, 0.123; 95% CI, 0.0051-0.295). All the patients in the persistent superficial vein reflux group had their VLUs eventually healed after further endovenous treatment. CONCLUSIONS: When treating patients with VLUs, persistent superficial vein reflux after ablation was negatively associated with ulcer healing. After additional endovenous ablative treatment, ulcers with persistent reflux eventually healed.

Outcomes of Free Flap Reconstruction for Chronic Venous Ulceration in the Lower Limb: A Systematic Review.

BACKGROUND: The mainstay of treatment for venous ulceration is conservative wound management and lifelong compression therapy. For patients with recalcitrant ulcers, free flap reconstruction has been proposed as a treatment option to reconstruct the diseased soft tissues as well as the underlying insufficient venous system. This review systematically evaluates the outcomes of free flap reconstruction for chronic venous ulcers in the lower limb. METHOD: A protocol was developed a priori and registered on the PROSPERO database. A systematic search of literature was performed in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), clinical trials registries, and OpenGrey from inception to April 2020 according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies of patients undergoing free tissue transfer reconstruction for chronic venous ulcers in the lower limb were included. RESULTS: A total of 5 noncomparative cohort studies featuring 56 patients with 62 recalcitrant venous ulcers treated with 64 free flaps who had a mean age of 50 years (range, 17-76 years) were included, and a narrative analysis undertaken. Mean defect size following ulcer debridement was 153.3 cm 2 (range, 24-600 cm 2 ). Defects were reconstructed with muscle (n = 39 [60.9%]), fasciocutaneous (n = 23 [35.9%]), and visceral (n = 2 [3.1%]) free flaps, with latissimus dorsi (n = 16, 25%) and rectus abdominis flaps (n = 16, 25%) being the most frequently used. Mean follow-up ranged from 24 to 125 months. Pooled flap survival rate was 95%. No recurrence within the territory of the flap was reported, but there were 20 instances (35.7%) of new ulcers outside of the flap boundaries. CONCLUSION: There is currently an absence of evidence to support the use of free flap reconstruction for recalcitrant venous ulcers compared with conventional management. Although evidence suggests that it is technically feasible, there is no evidence to suggest it prevents ulceration outside the reconstructed region. Further studies are necessary to evaluate its effectiveness for venous ulcers in the lower limb.

[Venous ulcus cruris-Surgical treatment]. / Ulcus cruris venosum ­ chirurgische Therapie.

Venous ulcus cruris is usually a chronic disease and an extreme burden for patients and their families. An analysis based on a random statutory health insurance sample of the AOK Hessen/KV Hessen estimated the number of affected people to be 400,000 in Germany. A venous ulcus cruris is always caused by an underlying chronic venous insufficiency (CVI). A spontaneous healing of this chronic disease without treatment is not to be expected. The conservative treatment includes an adequate compression treatment and exudate management. Surgical treatment is based on three pillars: an open surgical or endovenous approach to resolve the pathological venous reflux, uIcer surgery and in rare cases the various procedures of fascia surgery as well as defect coverage by a combination of negative pressure wound therapy and skin transplantation.

Biomarkers of Skin Graft Healing in Venous Leg Ulcers.

There is a need for biomarkers that predict the success of transplantation of venous leg ulcers (with autologous split-thickness skin grafts). The primary objective of this exploratory study was to investigate the association between split-thickness skin graft healing in venous leg ulcers and candidate wound fluid biomarkers representing inflammatory cell and endogenous proteinase activities, and bioactivity. A secondary objective was to compare biomarker levels of the 17 venous leg ulcers with sterile split-thickness skin graft donor-site wounds in another 10 patients with venous leg ulcers. Wound fluids were collected for 24 h using a validated method. The concentration of preoperative matrix metalloproteinase-9 in wound fluid was higher in venous leg ulcers showing good healing (n = 10) than in venous leg ulcers showing poor healing (n = 7) 12 weeks after transplantation with meshed split-thickness skin grafts. The diagnostic value of matrix metalloproteinase-9 was good according to receiver-operating characteristic curve analysis. Matrix metalloproteinase activity in wound fluids from split-thickness skin graft donor-site wounds increased as a function of time and healing, but was still lower than matrix metalloproteinase activity in venous leg ulcer wound fluids, which showed increased levels of most biomarkers except for matrix metalloproteinase-9 and matrix metalloproteinase-2. In conclusion, wound fluid matrix metalloproteinase-9 concentration is a potential predictive biomarker of split-thickness skin graft healing in venous leg ulcers.

A Contemporary Comparison of Cyanoacrylate, Radiofrequency, and Endovenous Laser Ablation on Healing of Active Venous Ulceration.

BACKGROUND: The goal of this study is to compare the healing rates of active lower extremity venous ulcers for patients receiving one of 3 ablation methods, compare their complications, and identify factors affecting successful healing and prevention of recurrence. METHODS: For this study, data were collected retrospectively on 146 patients at a single institution, tertiary referral center, with an active venous ulcer who underwent ablation therapy via cyanoacrylate (VenaSeal), radiofrequency (RFA), or endovenous laser ablation (EVLA) from 2010 to 2020. RESULTS: The study showed a nonsignificant difference in days to ulcer healing postintervention between ablative techniques, with 80.8 days for cyanoacrylate ablation (n = 15), 70.07 for RFA (n = 44), and 67.04 days for EVLA (n = 79). A similar, nonsignificant trend was observed for ulcer recurrence, with a rate of 35.7% (5/14) for cyanoacrylate ablation, 26.7% (20/75) for EVLA, and 23.1% (9/39) for RFA. The same nonsignificant trend occurred with deep venous thrombosis following the procedure in 6.3% (1/16) of cyanoacrylate ablation, 4.8% (4/84) of EVLA, and 2.2% (1/46) of RFA cases. The rate of endovenous glue induced thrombosis was also higher (6.3%) for cyanoacrylate than endovenous heat induced thrombosis in EVLA (3.6%) and RFA (2.2%). Cox proportional hazard was significant for compliance with compression therapy (hazard ratio [HR] 2.12, confidence interval [CI] 95% = 1.10-4.20, P = 0.031) and a lack of working with a wound clinic (HR 0.50, CI 95% = 0.33-0.75, P = 0.001) were associated with the decreased time to healing of ulcer but was not influenced by the presence of other comorbidities of smoking or diabetes mellitus. CONCLUSIONS: This study indicates a trend toward cyanoacrylate ablation having longer healing times and more complications compared to other ablation methods when used in patients with active venous ulcers. Compliance with compression treatment is predictive of venous ulcer healing and working with a wound clinic had significantly longer healing times.

A strategy to enable rapid healing and prevent recurrence of venous ulcers.

INTRODUCTION: Venous ulcers are often intractable. OBJECTIVE: The aim of this study was to retrospectively analyze the effectiveness of endovenous ablation, compression therapy, moist wound healing, and skin care in the management of venous ulcers. MATERIALS AND METHODS: Twenty-eight consecutive patients (10 male, 18 female; mean age, 70.1 years) with Clinical-Etiology-Anatomy-Pathophysiology (CEAP) class C6 venous ulcer underwent endovenous ablation between December 2014 and August 2020. The main treatment strategies were radiofrequency ablation and varicectomy (including stab avulsion of incompetent perforating veins), use of compression therapy until complete healing was achieved, moist wound healing (washing the ulcer site and covering it with dressings twice daily), and skin care, taking into consideration the balance of the microbiome. RESULTS: Active venous leg ulcers (CEAP class C6) were diagnosed in 36 patients at the first visit. In 7 of these patients, compression therapy and use of strategies to promote moist wound healing resulted in ulcer healing by the day of the planned surgery. One patient was unable to quit smoking and, therefore, could not undergo surgery. After excluding these 8 patients, the authors analyzed the data from 28 patients who underwent endovenous ablation. The mean surgical time was 38.9 minutes, and the mean number of stab avulsion incision sites was 9.7. All ulcers healed within a median of 55.5 days (range, 13-365 days). Ulcer healing was achieved by 1 year in all 28 patients (100%). No ulceration recurred as of the final follow-up (median, 24.5 months [range, 3-66 months]). CONCLUSIONS: Endovenous ablation, adequate varicectomy (stab avulsion [maximum number of sites in 1 patient, 43]), compression therapy, moist wound healing, and skin care are effective in treating and preventing recurrence of venous ulcers.

Biological autologous excised varicose vein dressing compared to conservative dressing on the ulcer bed during endovenous ablation.

OBJECTIVE: To compare the use of biological autologous excised varicose vein dressing (VenoDress) compared to conservative dressing on the ulcer bed during endovenous ablation. METHODS: This retrospective non-blinded study included all consecutive patients with primary or recurrent venous leg ulcers (VLU) with superficial varices treated in one center between September 2019 and October 2020. They all underwent venous ablation, wound debridement, and when needed phlebectomy. On the study group, the excised veins were incised, formed into a sheet, and applied onto the debrided wound bed with the endothelial side facing the wound bed. Adhesion was assessed weekly for 3 weeks. The study group was compared to a control group that underwent similar procedures but with the debrided wound bed treated with low-adherent paraffin dressing. The primary outcome was complete wound healing at 1 and 3 months, and the secondary outcomes were wound-related pain and leg edema. RESULTS: Complete wound closure was documented in 17/26 study group patients at 1 month (65%) and in 25/26 (96%) at 3 months. Complete wound closure was documented in 37/82 patients in the control group (45%) and in 67/82 (82%) at 3 months. The 1-month healing rates were significantly in favor of the VenoDress group when adjusted to sex and diabetes: odds ratio = 2.81 (1.05-7.532), p = .04. The preoperative pain level of the study group (as measured by a visual analog scale VAS (0-10) decreased from 4.96 ± 2.71 to 0.73 ± 1.36 at 1 week and that of the control group from 4.8 ± 2 to 1.35 ± 1.38 at 1 week (p < .001). CONCLUSION: the use of autologous varicose veins as dressing effectively reduced pain in VLU patients compared to conventional techniques. Although its effects on wound closure appear highly promising, further validation is warranted in a randomized comparative study.