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Background: The aim of the present study was to investigate the changes in pressure over time under three different compression bandages and compare the temporal patterns of pressure changes among them., Methods: The 4-hour changes in interface pressure were investigated in 10 volunteers with no venous disease or leg swelling. In 20 patients with venous ulcers, the change in interface pressure was measured after 4 hours, 1 day, and 7 days of bandage wearing. The three bandages tested were the Smart Sleeve compression system (SSB; Carolon, Rural Hall, NC), Coban 2 (C2; 3M, St Paul, Minn), and Profore Lite (PL; Smith & Nephew, London, United Kingdom). Pressure measurements were performed using the PicoPress transducer (Microlab, Padua, Italy) and the Juzo Pressure Monitor (Juzo, Cuyahoga Falls, Ohio)., Results: In the 10 volunteers, the mean pressure loss during the first 4 hours under the SSB, C2, and PL were 4.5, 3.7, and 6.6 mm Hg, respectively. No significant differences were seen in the pressure loss among the three bandages, whether in the supine (P = .59) or standing (P = .47) position. In the 20 patients with venous ulcers, the pressure had decreased gradually over 7 days under the C2 bandages. For the SSB and PL bandages, however, the interface pressure was relatively stable during the first day but decreased significantly afterward. The mean pressure loss during the 7 days was 4.7, 7.7, and 8.6 mm Hg for the SSB, PL, and C2, respectively (P = .017). Only the SSB maintained a desirable mean pressure >30.0 mm Hg on the seventh day in the patients with venous ulcers., Conclusions: The interface pressure had decreased over time under all three studied bandages. However, the temporal pattern of the pressure changes varied among the different bandages. Therefore, monitoring the interface pressure, allowing for adjustment or changes of the bandage at an accurate point, is essential to maintain a desirable interface pressure during compression therapy., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Nonhealing leg ulcers are frequently associated with the saphenous vein reflux. Despite the success of endovascular ablations, there are patients who either fail to heal or develop recurrent ulcers. This systematic review aims to summarize the available evidence on how to treat these patients after successful elimination of superficial reflux., Methods: A systematic review was performed following the PRISMA guidelines. The MEDLINE and Embase databases were searched for full text articles in English from 1946 to July 31, 2020. All articles that did not specifically mention the treatment of persistent venous ulcers or superficial venous reflux associated with healed or active venous ulcers were eliminated. The remaining abstracts were read for mention of either recurrent or persistent venous ulcers and, if mentioned, the full article was reviewed. All study designs were included. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers., Results: Four eligible studies including a total of 161 patients (177 limbs) with C6 disease were included in the review after the screening of 546 identified articles. A total of 62 patients were treated for persistent or recurrent venous ulcers after treatment of superficial reflux. Treatments included four-layer compression dressings, repeat ablations of superficial veins, and endovenous ablation of incompetent perforator veins. Overall, successful healing was noted in 50% of patients undergoing repeat ablative procedures, 100% of patients treated solely with four-layer compression dressings, and 90% of patients treated with compression and successful ablation of incompetent perforator veins. Across all studies the presence of deep vein reflux was 31% (50 of 164 limbs), post-thrombotic (secondary) ulcers 13.7% (16 of 117), and proximal obstruction was present in a single patient. Superficial venous reflux was treated using endovenous ablation (either radiofrequency ablation or laser), foam sclerotherapy, and endovenous radiofrequency ablation with or without microphlebectomy procedures. The frequency of persistent ulcers after elimination of superficial reflux ranged from 2.3% at 2 years after the intervention to 21.1% at 1 year with follow-up ranging from 6 to 52 months., Conclusions: Although further studies are warranted to improve the quality of evidence, it seems that additional ablative procedures to address incompetent perforating veins and persistent superficial reflux in combination with ongoing compression therapy is effective in healing persistent or recurrent venous ulcers after the elimination of superficial venous reflux., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Iliocaval outflow obstruction was investigated in patients with venous ulcers caused by primary superficial disease and chronic deep vein disease METHODS: After clinical assessment, patients with healed or active venous leg ulcers underwent lower extremity duplex ultrasound examination to identify the presence of venous disease in the superficial, deep and perforating systems. Bilateral contrast venography and intravascular ultrasound examination were then performed to determine the presence and degree of iliocaval obstructive lesions., Results: This retrospective study included a total of 59 patients with 71 legs presenting active or healed ulcer. There were 16 limbs (22.5%) with superficial venous reflux associated with normal infrainguinal deep veins (group I) and 55 limbs (77.5%) with infrainguinal post-thrombotic deep venous disease (group II). Using venography and intravascular ultrasound examination, the incidence of >50% of venous obstruction in the iliocaval system in groups I and II were 75% and 83.6%, respectively. All obstructive lesions in group I were nonthrombotic. However, group II included thrombotic, nonthrombotic and combinations of the two types of obstructions. Group II had more ulcers (1.73 ± 1.3 vs 1.17 ± 0.5; P = .03), larger ulcers (>6 cm in 34.1% vs 8.3%), longer duration of ulcers (71.3 ± 110.5 months vs 37.9 ± 40.4 months; P = .03), smaller diameter of refluxing superficial veins (7.7 ± 2.6 mm vs 15.1 ± 6.6 mm; P = .001), and higher incidence of occluded iliocaval systems (18 [32.7%] vs 0; P = .003) than group I. After the exclusion of bilateral cases and thrombotic obstructions, the incidence of >50% nonthrombotic obstruction in ipsilateral and contralateral sides was 76.5% and 24.4%, respectively (P = .003)., Conclusions: The results of this study revealed that the majority of patients with venous ulcers with either infrainguinal primary superficial or post-thrombotic deep venous disease had an element of iliocaval venous obstruction., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Limb compression is a key component of protocols used to heal venous leg ulcers (VLUs). A novel ambulatory pneumatic compression device was tested in comparison with multilayered bandage (MLB) compression systems for the treatment of VLUs in a prospective randomized clinical trial., Methods: Patients with VLUs measuring 1.5 to 50 cm 2 with duration of 1 to 24 months were randomized to treatment with a pneumatic compression device, the ACTitouch adaptive compression therapy (ACT) system (Tactile Medical, Minneapolis, Minn), or MLB. The ACT group patients were seen in the clinic at weeks 1, 2, 4, 6, 9, 12, and 16 or until wounds healed; the MLB group was seen weekly for bandage and dressing changes for 16 weeks or until wounds healed. All other aspects of VLU care were standardized between the two groups. The primary study objective was to compare the VLU percentage area reduction at 16 weeks in the ACT group compared with the MLB group., Results: There were 56 patients randomized to treatment with ACT (n = 26) or MLB (n = 30). In the ACT group, five patients exited because of skin or wound problems related to the ACT device and five withdrew because of the inconvenience of using the device. Therefore, the trial was halted before full randomization so improvements to the ACT device could be made. Data collected on 42 patients who were able to tolerate treatment for the 16-week study period (per protocol group) showed that both groups experienced similar rates of wound healing. In the per protocol population, the percentage area size reduction was greater for the ACT group compared with the MLB group (83.8% vs 70.5%, respectively), whereas no significant differences were noted in the percentage of wounds that healed by 16 weeks (60.0% vs 63.0%, respectively)., Conclusions: In this truncated clinical trial, a novel dual-mode ambulatory compression device, when tolerated, achieved wound healing results similar to those with MLB for chronic VLUs. The device requires modifications to improve the patient's comfort and ease of use. However, this mode of therapy appears to have promise for improving the cost-effectiveness of treatment for chronic VLUs., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Treatment of pathologic perforator veins (PPVs) can shorten time to healing and reduce recurrence of ulcers in patients with advanced venous disease. Because of limited clinical evidence and device options, widespread adoption of PPV treatment is controversial. The objective of this study was to evaluate the safety and efficacy of endovenous laser therapy using a 400-μm optical fiber to treat PPVs., Methods: This study was a single-arm, prospective, seven-center, nonblinded clinical study examining patients with advanced skin changes or healed or active ulceration (Clinical, Etiology, Anatomy, and Pathophysiology clinical class C4b, C5, and C6). Patients received treatment with a 1470-nm laser. Procedural technical success and 10-day primary closure were evaluated. All device-related adverse events were reported. Follow-up of patients was continued for 12 months after initial ablation., Results: The primary PPV closure (at 10-day visit) rate was 76.9% (95% confidence interval, 70.3%-82.4%). Successful primary closure rates of 75.7%, 70.3%, 62.1%, 68.8%, and 71.3% of PPVs were achieved at 1 month, 3 months, 6 months, 9 months, and 12 months, respectively. Statistically significant improvements (P < .05) were seen in patients' quality of life at 1 month, 3 months, 6 months, 9 months, and 12 months compared with screening. The percentage of patients with ulcers (22.9% at screening, 14.1% at 1 month, 13.7% at 3 months, 10.1% at 6 months, 12.3% at 9 months, and 11.1% at 12 months) displayed improvement during the course of the study. Tibial deep venous thrombosis and procedural pain were the only device-related adverse events observed., Conclusions: Endovenous laser therapy for PPV using the 400-μm optical fiber with the 1470-nm laser yielded safe and effective outcomes with no major adverse sequelae., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of three treatment modalities, superficial truncal vein ablation, perforator vein ablation, and deep venous stenting on venous leg ulcer (VLU) healing, as well as their cumulative effect on ulcer healing, in an attempt to establish the best algorithm for the treatment of chronic and recalcitrant VLUs., Methods: Multicenter retrospective cohort study using a standardized database to evaluate patients with chronic venous ulcers treated between January 2013 and December 2017., Results: Eight-hundred thirty-two consecutive patients with VLU were identified at 11 centers in the United States. All patients were initially managed with wound care and compression for at least 2 months. Compression and wound care management alone, used in 187 patients, led to ulcer healing in 75% of patients by 36 months. Ulcer recurrence in patients managed without surgery at 6, 12, and 24 months was 3%, 5% and 15%, respectively. Five hundred twenty-eight patients underwent ablation of incompetent superficial veins, and 344 of those also underwent incompetent perforator ablation. Patients who underwent truncal vein ablation alone had an ulcer healing rate of 51% at 36 months. Patients who received both superficial and perforator ablation were significantly younger, and had a 17% improvement in healing at 36 months (68% vs 51%, respectively), but there was no impact of combined superficial and perforator ablations on ulcer recurrence rates. One hundred thirty-four patients had stenosis of one of more lower extremity deep veins and 95 (71%) underwent endovenous stenting. Ulcer healing and recurrence rates for those who underwent stent placement alone was 77% and 27%, respectively, at 36 months. Patients who underwent deep venous stenting and ablation of both incompetent truncal and perforator veins had an ulcer healing rate of 87% at 36 months and ulcer recurrence of 26% at 24 months., Conclusions: This study demonstrates that correction of superficial truncal vein reflux, as well as deep vein stenosis, both contribute to healing of VLU. Patients who fail to heal their VLU after superficial and perforator ablation should have the iliocaval system imaged to identify hemodynamically significant stenoses or occlusions amenable to stenting, which facilitates venous ulcer healing even in patients with large ulcers., (Copyright © 2019. Published by Elsevier Inc.)

Objective: We aimed to compare mechanochemical ablation (MOCA) and thermal ablation (radiofrequency ablation and endovenous laser therapy) for venous ulcer healing in patients with clinical class 6 chronic venous insufficiency., Methods: Electronic medical records were reviewed of patients with venous ulcers who underwent truncal or perforator ablation between February 2012 and November 2015. These records contained history of venous disease and ulcer history, procedures, complications, follow-up, method of wound care, and current status of the ulcer. The patients were grouped according to the method of ablation for comparison., Results: In 66 patients, 82 venous segments were treated, 29 with thermal methods and 53 with MOCA; 16% of patients had prior venous intervention. Before ablation, three patients in the thermal group had a history of deep venous thrombosis compared with seven in the MOCA group. On average, patients treated with MOCA were older (thermal ablation, 57.2 years; MOCA, 67.9 years; P = .0003). Ulcer duration before intervention ranged from 9.2 months for thermal ablation to 11.2 months for MOCA (P = NS). In total, 74% of patients treated with MOCA healed their ulcers compared with 35% of those treated with thermal ablation (P = .01). A healed ulcer was defined as elimination of ulcer depth and superficial skin coverage. The mean time to heal was 4.4 months in the thermal ablation group compared with 2.3 months with MOCA (P = .01). The mean length of follow-up was 12.8 months after thermal ablation and 7.9 months after MOCA (P = .02). Both age (P = .03) and treatment modality (P = .03) independently had an impact on ulcer healing on multiple logistic regression analysis. All but two patients were treated with an Unna boot after venous ablation. Complications included readmission of two patients with nonaccess-related infections, one nonocclusive deep venous thrombosis, and one late death unrelated to the procedure second to pneumonia in the setting of advanced colon cancer. There were three recurrent ulcers at 1 week, 2 months, and 7 months after MOCA that rehealed with Unna boot therapy and continued compression., Conclusions: MOCA is safe and effective in treating chronic venous ulcers and appears to provide comparable results to methods that rely on thermal ablation. Younger age and use of MOCA favored wound healing. MOCA was an independent predictor of ulcer healing. Randomized studies are necessary to further support our findings., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Venous ulcers are painful, recurrent, and difficult to heal. Electronic medical records (EMRs) are often not optimized to track wounds. Specialized wound care programs may not interface with office-based records, creating a need to standardize the process of venous ulcer measurement and dressing documentation within existing systems. This work describes the creation of an EMR protocol to track venous ulcer size, to standardize dressings, to address related health issues, and to improve education of the patient. We hypothesized that the institution of an EMR protocol to track clinical features of venous ulcer patients, including wound size and health status, would facilitate wound healing., Methods: We performed a retrospective review of a prospective database from September 2014 to May 2017. Modifications to the EMR included the formation of a venous ulcer patient list, a dressing tracker, calculation of total ulcer area, graphing of ulcer size over time, and images of the wound area. Patient education materials were created through the EMR and loaded into an automatic end-visit printout that emphasized smoking cessation, weight loss, and consultation with specialty services as necessary. Quarterly meetings with the supervising physician were established to review each patient's wound progress and to target areas of improvement., Results: During the study period, 204 patients with chronic C5 and C6 disease were observed. Before the start of the project, the healing rate was 53.3%. Wound healing rates improved from 59.5% (quarter 1) to 77.94% (quarter 8). In the quarter before the project started, there were no patients who had quit or cut down on smoking or smokeless tobacco, no patients who were referred for weight loss consultation, and nine who were already patients of bariatric surgery. During the study period, 29% of patients quit smoking, 19% decreased smoking, and 20% cut down smokeless tobacco use. There were 54 patients who underwent advanced arterial evaluation; 175 patients underwent sclerotherapy and 137 patients had endovenous thermal ablation to treat axial reflux in the affected limb. The EMR modification project took 13 months to craft and to implement, with approximately 8 hours of meeting time from the surgical team., Conclusions: A comprehensive care model for venous ulcer patients through EMR modification improved overall patient care, increased communication between providers, and facilitated ulcer healing. EMR modification can be introduced with an acceptable time investment on the part of both the provider and the institutional information technology team., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines as well as multiple RTCs support the use of intermittent pneumatic compression (IPC) for the treatment of venous leg ulcers when conservative measures fail. Unfortunately, the clinical usefulness of IPC is significantly limited by the physical limitations of pneumatic motors, which leads to bulky devices with slow inflation cycles, uncomfortable sleeves, lack of patient mobility, and ultimately poor patient compliance with therapy. A novel mechanical device for lower leg graded intermittent sequential compression was designed to address these limitations of IPC therapy for venous leg ulcer treatment by providing rapid compression cycles in a truly wearable device that offers the additional benefit of monitoring compression dose and patient compliance. The wearable intermittent compression (WIC) device was hypothesized to provide improved augmentation of venous flow compared with both baseline and standard IPC therapy., Methods: Ten patients with Clinical, Etiologic, Anatomic and Pathophysiologic class 3 to 6 venous insufficiency were recruited under institutional review board approval. The primary end point for the study was augmentation of venous blood flow as measured by peak venous velocity. Patients underwent measurement of peak venous velocity in centimeters per second at the popliteal and femoral veins for the following conditions: (1) baseline, (2) WIC device on a low setting, and (3) WIC device on a high setting. In five patients, an additional measurement of peak venous velocity in centimeters per second at the popliteal and femoral veins was completed while wearing a commercially available IPC device., Results: Both low and high settings of the WIC device resulted in higher average peak venous velocities when compared with both baseline and the IPC device (P < .05). No patients reported discomfort with either the WIC device or the IPC device during therapy., Conclusions: The WIC device significantly increases the augmentation of venous flow as measured by peak venous velocity in both the popliteal and femoral veins in patients with Clinical, Etiologic, Anatomic and Pathophysiologic class 3 to 6 venous insufficiency. In addition, the WIC device was found to be easy to use and comfortable during therapy. Future studies are planned to determine if the WIC improvements in venous flow augmentation and patient compliance will lead to higher rates of venous ulcer healing., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Despite regular treatment of venous leg ulcers (VLUs), some fail to heal. Although several risk factors have previously been identified to be associated with the failure of VLUs to heal, the majority of studies are limited to <24-week follow-up., Methods: A retrospective cohort study was performed at an academic vascular and wound center. A total of 65 patients with VLUs who were observed for a year or more were identified. These patients underwent a variety of treatments following the Society for Vascular Surgery and American Venous Forum VLU guidelines. Risk factors, which were based on previously defined elements for failure of VLUs to heal after a period of treatment, were examined. Both univariate (unadjusted) and multivariate (adjusted) logistic regression analyses were used to assess the magnitude of effect that a given risk factor had on healing., Results: Of 65 patients treated for a minimum of 52 weeks, 19 (29%) remained unhealed. By univariate analysis, deep venous disease (P = .01; odds ratio [OR], 5.82; 95% confidence interval [CI], 1.49-22.72), history of deep venous thrombosis (P < .001; OR, 14.06; 95% CI, 3.77-52.39), and depression (P = .04; OR, 3.89; 95% CI, 1.10-13.80) were all shown to be significant risk factors for nonhealing. The patient's race (ie, being nonwhite; P = .02; OR, 103.45; 95% CI, 1.94-5.53 × 10 3 ), deep venous disease (P = .05; OR, 37.0; 95% CI, 1.05-1.31 × 10 3 ), and history of deep venous thrombosis (P = .01; OR, 122.4; 95% CI, 3.09-4.84 × 10 3 ), however, were all shown to be significant for nonhealing under multivariate analysis. In addition, identification of an incompetent perforator (P = .02; OR, 0.006; 95% CI, 9.27 × 10 -5 -0.44) was conversely shown to be a good prognostic factor for healing., Conclusions: This study confirmed that risk factors known to be associated with the failure of a VLU to heal-deep venous disease and post-thrombotic etiology-were significant at 52 weeks, whereas depression and race (nonwhite) are novel risk factors. An analysis of markers of access to care showed no difference between white and nonwhite, suggesting other factors as a cause. The predominance of deep venous disease in the unhealed vs healed cohort (84% vs 48%) highlights the need for a viable treatment option for deep venous disease due to reflux. Overall, this study emphasizes the need to consider all risk factors when evaluating a patient for VLU to coordinate an effective treatment plan and to identify gaps in our treatment., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate the feasibility and safety of a polyglycolic acid (PGA) yarn implant for nonthermal ablation of saphenous vein reflux., Methods: In two consecutive cohort studies (TAHOE I and TAHOE II), the feasibility of abolition of great saphenous vein (GSV) reflux by implantation of a PGA yarn was tested under ultrasound guidance in 51 and 30 patients, respectively. The use of tumescent local anesthesia was not required. Graduated compression stockings and thrombosis prophylaxis with low-molecular-weight heparin were used for 2 weeks after intervention in the first study only., Results: Of 81 enrolled patients, 77 (95%) were available at 6-month follow-up. Complete occlusion of the treated GSV was confirmed by duplex ultrasound in all patients except one patient at day 1. In TAHOE II, closure was preserved in a higher percentage of patients at 6 weeks, with 96.4% vs 82.0% in TAHOE I. The 6-month Kaplan-Meier estimated occlusion rates for TAHOE I and TAHOE II were 68% (95% confidence interval [CI], 54%-79%) and 69% (95% CI, 49%-82%), respectively, with an estimated combined occlusion rate of 69% (95% CI, 57%-76%). Kaplan-Meier analysis yielded a combined reflux-free rate of 85% (95% CI, 75%-91%) at 3 months of follow-up and a rate of 81% (95% CI, 71%-88%) at 6 months of follow-up. Venous Clinical Severity Score (VCSS) improved from a combined mean of 4.6 ± 3.1 at baseline to 2.1 ± 2.2 and 1.6 ± 1.9 at 3 and 6 months, respectively (P < .0001 for 3- and 6-month results). In TAHOE II, four patients with venous ulcers healed at an average of 1.3 months after treatment., Conclusions: First-in-human use of an endovenous PGA yarn implant for occlusion of refluxing GSVs proved to be feasible, with no serious adverse events. However, recanalization was observed during a period of 6 months in 31% of patients., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patients with iliofemoral deep venous thrombosis are at risk for development of post-thrombotic syndrome. Iliac vein stenting has been shown to significantly improve clinical outcomes in patients with venous outflow obstruction, although many studies include a heterogeneous population with several different venous pathologic processes. Our objective was to evaluate the results of iliocaval and infrainguinal venous intervention for venous outflow obstruction due to post-thrombotic chronic venous occlusive disease., Methods: All patients treated at a single institution for symptomatic iliocaval venous occlusive lesions with and without infrainguinal extension between 2008 and 2015 were retrospectively analyzed. Nonthrombotic iliac vein lesions were excluded from analysis. All patients with symptomatic post-thrombotic occlusion of the iliac vein or inferior vena cava (IVC) and a Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) score of 3 or greater were included. Demographics of the patients, presence of IVC filters at presentation, presenting CEAP score, postintervention CEAP score, primary and secondary patency, wound healing and subjective clinical improvement outcomes, and procedural details were recorded in a database., Results: There were 105 patients with symptomatic iliocaval venous occlusive lesions identified, of which 31 patients (42 limbs) met inclusion criteria. Presenting symptoms included pain or swelling (100%); venous claudication (81%); and CEAP class 3 (76%), 4 or 5 (14%), or 6 (10%). All patients presented with either subacute (>30 days [35%]) or chronic (>90 days [65%]) iliocaval venous thrombosis. Procedural technical success with venous recanalization was achieved in 100% of cases and in 46% of IVC filter retrieval attempts. Overall clinical improvement was achieved in 84% of patients; complete clinical resolution was obtained in 42% and a decrease in CEAP score in 65%. At a mean follow-up of 14.7 months (range, 2-49 months), primary and secondary 1-year patency was 66% and 75% overall, and primary patency was equivalent between patients requiring isolated iliac venous stenting and those requiring infrainguinal stent extension (68% vs 65%, respectively; P = .74, not significant). Patients who presented with IVC filters had a higher rate of complete clinical resolution if the filter could be removed (100%) compared with those patients in whom the filter could not be removed (17%; P < .01)., Conclusions: Treatment of chronic venous occlusive disease with iliocaval and infrainguinal venous stenting is associated with acceptable 1-year patency rates, healing of venous ulcers, and a significant reduction in symptoms and CEAP score. Patients who underwent successful removal of indwelling IVC filters showed improved clinical outcomes compared with those in whom the IVC filter could not be removed., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials., Methods: Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm 2 to 12 cm 2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm 2 and ≤36 cm 2 with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure., Results: This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955-0.987])., Conclusions: Factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Our understanding of the pathophysiologic process of venous ulceration has dramatically increased during the past two decades because of dedicated, venous-specific basic science research. Currently, the mechanisms regulating venous ulceration are a combination of macroscopic and microscopic pathologic processes. Macroscopic alterations refer to pathologic processes related to varicose vein formation, vein wall architecture, and cellular abnormalities that impair venous function. These processes are primarily caused by genetic factors that lead to the destruction of normal vein wall architecture and venous hypertension. Venous hypertension causes a chronic inflammatory response that over time can cause venous ulceration. The inciting inflammatory injury is chronic extravasation of macromolecules and red blood cell degradation products and iron overload. Chronic inflammation causes white blood cell extravasation into the dermis with secretion of numerous proinflammatory cytokines. These cytokines transform the phenotype of fibroblasts to a contractile phenotype that increases tension in the dermis. In addition, iron overload keeps macrophages in an M1 phenotype, which leads to tissue destruction instead of dermal repair. Current surgical and medical therapies are primarily directed at eliminating venous hypertension and promoting venous ulcer wound healing. Despite advances in our understanding of venous ulcer formation and healing, ulcers still take an average of 6 months to heal, and ulcer recurrence rates at 5 years are >58%. To improve the care of patients with venous ulcers, we need to further our understanding of the underlying pathologic events that lead to ulcer formation, prevent healing, and decrease ulcer-free recurrence intervals., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic functions that include chemotaxis, adhesion, and proliferation, which also have a role in wound healing. The aim of this study was to determine whether suPAR and its cleaved fragments are present in venous ulcers and whether their levels are associated with healing., Methods: Ulcer exudates were collected from patients with venous leg ulcers (n = 30). Healing was defined as complete re-epithelialization within 6 months of compression therapy. Time-resolved fluorescence immunoassays were validated for quantification of suPAR and its fragments in ulcer exudates. The effect of exudates on keratinocyte migration was analyzed by an in vitro scratch assay., Results: Ulcer exudates from patients who healed (n = 9) had approximately threefold higher levels of intact suPAR (P = .005), twofold higher levels of suPARI (P = .03), and approximately threefold higher levels suPARII-III (P < .0001) compared with nonhealers (n = 21). Exudate from healing ulcers stimulated keratinocyte migration (P = .02), whereas depletion of suPAR from exudates resulted in cell apoptosis., Conclusions: We conclude that suPAR and its fragments are present in the environs of venous ulcers and may act as indicators of the propensity of venous ulcers to heal, with suPARII-III being the best discriminator. We speculate that suPAR and its fragments may have a role in the maintenance of an optimal ulcer-healing environment., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

In many countries, endovenous ablation (EVA) has replaced surgical stripping as the preferred method of eliminating saphenous reflux in symptomatic patients. Studies have examined the success of EVA at saphenous closure and improving leg pain and edema. However, less information is available on the ability of these techniques to promote venous leg ulcer healing or to prevent recurrence. The comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR) trial identified the role of saphenous stripping in reducing the rate of ulcer recurrence after healing, supporting this procedure for Clinical, Etiologic, Anatomic, and Pathologic (CEAP) clinical class 5 and 6 patients. In patients with venous ulcers, it remains controversial whether EVA procedures provide results similar to those of saphenous stripping in clinically relevant outcomes. This review examines the evidence supporting the use of thermal or nonthermal EVA in patients with healed or active venous ulcers and saphenous insufficiency., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)