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The standard treatment for patients with confirmed Venous Leg Ulcers (VLUs) is compression therapy to improve the function of the calf muscle pump. There is a significant cohort of patients who are unable to tolerate optimal compression therapy or indeed any level of compression therapy. In addition, there is a cohort of patients who can tolerate compression whose ulcers show little or no evidence of healing. There is a need for ways to further improve calf muscle pump function and to improve venous ulcer healing in these patients. Published data were reviewed on the use of Muscle Pump Activation (MPA) using common peroneal nerve neuromuscular electrical stimulation (NMES) to improve calf muscle pump function. There is physiological evidence that MPA can improve calf muscle pump function and venous return in both control subjects and in patients with venous disease. The use of MPA has also been shown to improve venous flow volume and venous flow velocity on ultrasound scanning in patients with venous disease. MPA has been shown to improve microcirculation in the skin using Laser Doppler and laser Doppler Speckle Contrast Imaging, in both normal subjects as well as in patients with venous disease and VLU. A recent randomized controlled trial of MPA plus compression therapy compared with compression therapy alone, found significantly faster rates of healing with the use of MPA in addition to compression therapy. There are indications for the use of MPA as an adjunctive treatment to enhance calf muscle pump function in patients with VLU: who cannot tolerate compression therapy who can only tolerate suboptimal, low-level compression whose ulcer healing remains slow or stalled with optimal compression., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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.)

Objectives: to analyze the evidence on the cost and effectiveness of Plaque Rich Plasma in the treatment of venous ulcers compared to other topical therapies., Methods: systematic review, with search in the databases: COCHRANE, EMBASE, MEDLINE via PubMed, LILACS, CINAHL, SCOPUS, without temporal cut and in the English, Portuguese and Spanish languages., Results: fifteen articles were included, a cost-minimization analysis showed that the cost of Plaque Rich Plasma is € 163.00 ± 65.90, slightly higher than the cost of standard dressing. Regarding effectiveness, the results of the studies associated with the meta-analysis suggest a tendency that Plaque Rich Plasma is effective in the healing of venous ulcers., Conclusions: it is concluded that there are few studies about the cost of Platelet Rich Plasma and this product tends to be effective in the healing of venous ulcers. However, more controlled and randomized clinical studies are necessary in order to establish a stronger recommendation.

Chronic wounds are those that do not progress through a normal, orderly, and timely sequence of repair. They are common and are often incorrectly treated. The morbidity and associated costs of chronic wounds highlight the need to implement wound prevention and treatment guidelines. Common lower extremity wounds include arterial, diabetic, pressure, and venous ulcers. Physical examination alone can often guide the diagnosis. All patients with a nonhealing lower extremity ulcer should have a vascular assessment, including documentation of wound location, size, depth, drainage, and tissue type; palpation of pedal pulses; and measurement of the ankle-brachial index. Atypical nonhealing wounds should be biopsied. The mainstay of treatment is the TIME principle: tissue debridement, infection control, moisture balance, and edges of the wound. After these general measures have been addressed, treatment is specific to the ulcer type. Patients with arterial ulcers should be immediately referred to a vascular surgeon for appropriate intervention. Treatment of venous ulcers involves compression and elevation of the lower extremities, plus exercise if tolerated. Diabetic foot ulcers are managed by offloading the foot and, if necessary, treating the underlying peripheral arterial disease. Pressure ulcers are managed by offloading the affected area.

The factors preventing healing in venous leg ulcers are still not fully understood. Iron-mediated tissue damage has been hypothesised, yet anecdotally anaemia is also thought to have a negative effect on wound healing. This article summarises the current evidence for these theories and their likely effects in the context of venous ulceration. A comprehensive search of the literature was conducted. Studies suggest that a number of forms of iron including haemosiderin and ferritin are implicated in progression of venous disease, ulcer formation, and impaired healing, which is thought to be primarily free radical mediated. There is a paucity of evidence for the role of iron deficiency and anaemia on ulcer healing; however, there is likely to be a highly complex interplay between the damaging effects of iron on local tissues and the negative effects of anaemia-mediated tissue hypoxia. Studies looking at options to increase local oxygen delivery such as topical haemoglobin suggest that this may have an impact on some aspects of healing, but findings are generally inconclusive. There is growing evidence that locally elevated iron levels may have a detrimental effect on ulcer healing and formation; however, more robust research is needed., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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.)

Objective: This study evaluates the effects of topical and systemic N-acetyl cysteine (NAC) treatment on wound healing in a diabetic rat model., Materials and Methods: A total of 48 male Wistar Albino rats were randomly divided into 4 groups of 12. Diabetes was induced with an intraperitoneal injection of 60 mg/kg streptozotocin. A 2-cm x 1-cm full-thickness wound was created on the back of each animal. In group 1 (control) and group 3 (systemic NAC), the wounds were closed with 0.9% sodium chloride-treated sterile gauze. In group 2 (topical NAC) and group 4 (topical + systemic NAC), the wounds were closed with sterile gauze treated with 3 mL (300 mg) of NAC. The animals in groups 3 and 4 were administered 200 mg/kg of NAC once daily through an orogastric tube. On days 1 and 14, the wounded areas were measured. Tissue and blood samples were taken on day 14 for histopathological and biochemical examination., Results: On day 14, the wounded area in groups 2, 3, and 4 was found to be smaller than in group 1 (control). Histopathologically, epithelialization and fibrosis scores were significantly lower, whereas the inflammation score was higher in group 1 than in the other groups. Tissue oxidative stress parameters (malondialdehyde, fluorescent oxidation products, total oxidative stress) were higher in the control group than in the other groups. In groups 3 and 4 (which received systemic NAC), the oxidative stress parameters in serum samples were lower than those of the control group and group 2. Serum sulphydryl levels were the lowest in group 1., Conclusions: The results of this study show that both topical and systemic administration of NAC improved wound healing in a diabetic rat model. This effect of NAC may be related to its antioxidant properties since a reduction in oxidative stress parameters in both tissue and serum were shown in the present study.

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.)

Introduction: Venous leg ulcers (VLUs) are often chronic and difficult to treat, which makes alternative options to conventional care necessary to improve ulcer healing rates. While human acellular dermal matrices (ADMs) have shown promise in treating diabetic foot ulcers, no comparative studies have been published regarding VLU treatment. Decellularized ADMs (D-ADMs) have been used successfully in the treatment of a wide variety of wound repairs and may be effective in treating VLUs., Objective: This study is a multicenter, randomized, controlled, open-label trial designed to evaluate the safety and efficacy of D-ADM compared with conventional wound care management in patients with chronic ulcers of the lower extremity., Materials and Methods: Patients were randomly assigned to receive either D-ADM or standard of care (control) in a 2:1 ratio. Treatment began at week 0 and wounds were evaluated on a weekly basis until wound closure was observed or the patient completed 24 weekly follow-up visits., Results: Eighteen patients were included in the D-ADM arm and 10 patients in the control arm. There was a strong trend of reduction in percent wound area for D-ADM patients with an average reduction of 59.6% at 24 weeks versus 8.1% at 24 weeks for control patients. In addition, healed ulcers in the D-ADM arm remained closed at a substantially higher rate after termination than healed ulcers in the control., Conclusions: In this report, the authors note the successful increase in healing rates and rate of percent wound closure as compared with conventional care options.

The calf muscles have been called the body's "second heart," improving blood circulation when exercised, usually by walking. Structured exercise training (SET) increases calf muscle pump function, lower limb circulation, and walking capacity for those with limited ambulation due to peripheral arterial disease (PAD)1 or venous insufficiency.2 This resulted in the Centers for Medicare and Medicaid Services (CMS) decision to reimburse up to thirty-six 30- to 60-minute, properly supervised hospital outpatient or office-based SET sessions over 12 weeks to treat intermittent claudication for patients with PAD. Exercise improves acute wound healing in diabetic mice3 and healthy elderly humans,4 but insufficient evidence supports its healing efficacy on ischemic ulcers,1 venous leg ulcers (VLUs),5 and diabetic foot ulcers (DFUs).6 This month's Evidence Corner examines 2 recent randomized controlled trials (RCTs) testing the effects of foot exercises that activate calf muscles on chronic VLUs7 and DFUs.8.

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.)

Background: Chronic, nonhealing wounds are a growing health care problem in the United States, affecting more than 6.5 million patients annually., Objective: This retrospective study evaluates the clinical efficacy and utility of an implantable nanomedical scaffold in the treatment of chronic, nonhealing lower extremity wounds in patients with multiple comorbidities., Materials and Methods: Data from patients with chronic wounds that had persisted for ≥ 4 weeks and were unresponsive to existing advanced wound care modalities were included in the study. Wounds received the implantable nanomedical scaffold weekly, or as deemed appropriate, for up to 12 weeks based on physician assessment of wound status., Results: A total of 82 wounds were included in this study; wound types consisted of 34 diabetic foot ulcers, 34 venous leg ulcers, and 14 other wounds. Overall, treated wounds demonstrated progressive and sustained wound area reduction over the course of treatment, with 85% achieving complete closure at 12 weeks., Conclusions: The implantable nanomedical scaffold proved to be an effective alternative to existing wound matrices capable of supporting the natural wound healing process and may provide significant benefits as part of the treatment algorithm for challenging chronic wounds.

Chronic venous disease (CVD) is a common pathology, with significant physical and psychological impacts for patients and high economic costs for national healthcare systems. Throughout the last decades, several risk factors for this condition have been identified, but only recently, have the roles of inflammation and endothelial dysfunction been properly assessed. Although still incompletely understood, current knowledge of the pathophysiological mechanisms of CVD reveals several potential targets and strategies for therapeutic intervention, some of which are addressable by currently available venoactive drugs. The roles of these drugs in the clinical improvement of venous tone and contractility, reduction of edema and inflammation, as well as in improved microcirculation and venous ulcer healing have been studied extensively, with favorable results reported in the literature. Here, we aim to review these pathophysiological mechanisms and their implications regarding currently available venoactive drug therapies., Competing Interests: The authors declare no conflict of interest. The sponsor reviewed a draft of the manuscript but had no role in the decision to publish the final version.

Increasing levels of physical activity among people with venous leg ulcers (VLUs) can potentially reduce the health cost burden, improve functional aspects of patients' lives and increase ulcer healing rates. The aim of this study was to investigate factors associated with physical activity levels in patients with VLUs. Data from 2016 to 2017 Aspirin for Venous Leg Ulcer cohort study were analysed for the present study. Ninety participants were recruited from 5 outpatient specialist wound clinics across Victoria, Australia between August 2016 and April 2017. There was a statistically significant association between diabetes and physical activity, with a higher proportion of people with type 2 diabetes in the sedentary category. Further, there was a statistically significant association between patient-reported VLU education and physical activity levels. An indirect advantage of relevant, easy-to-understand education about VLUs may increase physical activity levels, which may facilitate improved time to healing of VLUs., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The aim of this study was to validate a newly developed tool that can predict the risk of failure to heal of a venous leg ulcer in 24 weeks. The risk assessment tool was validated, and performance of the tool was assessed using Area Under the Receiver Operating Characteristic Curve (AUC) analysis. Retrospective and prospective validation was conducted through multi-site, longitudinal studies. In the retrospective study (n = 318), 30% of ulcers did not heal within 24 weeks, with the tool demonstrating an AUC of 0.80 (95% CI, 0.68-0.93, P < .001) for the total score. In the prospective study across 10 clinical sites (n = 225), 31% (n = 68) of ulcers did not heal within 24 weeks. Participants were classified with the RAT at enrolment as being at low risk (27%), moderate risk (53%) or high risk (20%) of delayed healing; the proportion of wounds unhealed at 24 weeks was 6%, 29% and 59%, respectively. Validation results of the total score indicated good discrimination and goodness of fit with an AUC of 0.78 (95% CI, 0.71-0.85, P < .001). Validation of this risk assessment tool offers assurance that realistic outcomes can be predicted for patients, and scores can guide early decisions on interventions to address specific risk factors for failing to heal, thus promoting timely healing., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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.)

Venous leg ulcer (VLU) is a huge healthcare problem with poorly understood pathophysiology. Transforming growth factor-β (TGF-β) and endoglin (Eng), are inflammatory and wound healing mediators. Eng, co-receptor for TGF-β type-II receptors, may be cleaved forming soluble Eng (sEng), antagonizing TGF-β signaling, a crucial process in vascular pathologies. We evaluated the accumulation in wound fluid (WF) of TGF-β isoforms and sEng in healing stages, showing the effects of sulodexide treatments, a glycosaminoglycan with clinical efficacy in VLU healing. Patients with inflammatory (Infl) and granulating (Gran) VLU were recruited. WFs and THP-1 monocytes exposed to Infl and Gran WF (treated/untreated with sulodexide) were analyzed for TGF-β isoforms and sEng by multiplex immunoassay. In both Infl and Gran WF, TGF-β1 and β2 were similar; TGF-β3 was significantly increased in Infl compared to Gran WFs ( p = 0.033). sEng was significantly elevated in Gran compared to Infl WFs ( p = 0.002). In THP-1 monocytes there was a significant increase in sEng after co-treatment of WF and sulodexide. The increase in TGF-β3 found in Infl WF highlights its negative effect on wound healing, while the increased levels of sEng in Gran WF affects the leukocyte adhesion/transmigration through the endothelium, reducing the inflammatory response and favoring the wound healing. Glycosaminoglycan sulodexide potentiates the effects of sEng release from monocyte, representing an important therapeutic option for wound healing., Competing Interests: The authors declare no conflict of interest.

Management of chronic wounds remains challenging in terms of prevalence and complexity. Considerable progress has been made in understanding the science of wound healing during the past decade, sparking volumes of publications and the development of hundreds of dressing and therapy options. There is a need for a simpli ed overview of evidence-based criteria to assist in the accurate diagnosis and appropriate management of chronic wounds in all care settings. An expert panel of 11 wound healing specialists experienced in various care settings convened to discuss best practices and recommended guidelines for managing major chronic wound types. Prior to the meeting, panel members reviewed 8 preselected peer-reviewed articles and 1 white paper containing treatment algorithms for all major chronic wound types. During the meeting, each panelist presented current evidence-based guidelines regarding a specific chronic wound type and case studies to illustrate concepts in the guidelines. This publication is a result of the panel discussion and presents an overview of literature- and experience- based criteria to help guide chronic wound diagnosis, assessment, treatment, and follow-up. A cycle of steps is presented as a framework to guide holistic care for all patients with chronic wounds, including de- hisced surgical wounds, diabetic foot ulcers, venous leg ulcers, arterial insu ciency ulcers, and pressure ulcers/injuries. Emphasis is placed on criteria to assist accurate diagnosis and dressing/therapy selection, holistic elements of patient and wound bed preparation, interventions to achieve patient adherence to a care plan, and follow-up to help prevent wound recurrence.

This trial compared skin blood flow, temperature and incidence of venous leg ulcers in patients with chronic venous disease using compression wraps and elevation pillows. Patients with CEAP C4 skin damage and C5 history of ulcers were randomly assigned to a cryotherapy intervention (n = 138) or placebo cuff control (n = 138) applied to the lower legs over 9 months. The time the ulcers healed prior to enrollment in the study for the cryotherapy group ranged from 1 to 2218 days (n = 8, median = 32 days); for the control group, the range was 24 to 489 days (n = 6, median = 390 days). There were no statistically significant blood flow changes measured in perfusion units with a laser Doppler flowmetre within or between the groups; mean difference between the groups was 0·62, P = 0·619. No differences were noted in skin temperature measured with an infrared thermometer within and between the groups; mean difference between the groups was -0·17°C, P = 0·540. Cryotherapy did not improve skin blood flow or temperature and did not show efficacy in preventing ulcers. However, at least 30% of intervention and 50% of control participants were anticipated to develop an ulcer during the study; only ∼7% occurred. These findings suggest that strict adherence to standard of care decreases the incidence of leg ulcers and remains a best practice for leg ulcer prevention., (© 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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.)

To retrieve the history of venous ulcers and of skin lesions in general, we must go back to the appearance of human beings on earth. It is interesting to note that cutaneous injuries evolved parallel to human society. An essential first step in the pathogenesis of ulcers was represented by the transition of the quadruped man to Homo Erectus. This condition was characterized by a greater gravitational pressure on the lower limbs, with consequences on the peripheral venous system. Furthermore, human evolution was characterized by an increased risk of traumatic injuries, secondary to his natural need to create fire and hunt (e.g. stones, iron, fire, animal fighting). Humans then began to fight one another until they came to real wars, with increased frequency of wounds and infectious complications. The situation degraded with the introduction of horse riding, introduced by the Scites, who first tamed animals in the 7th century BC. This condition exhibited iliac veins at compression phenomena, favouring the venous stasis. With time, man continued to evolve until the modern age, which is characterized by increased risk factors for venous wounds such as poor physical activity and dietary errors (1, 2).

Chronic venous disease (CVD) and its most frightening complication, chronic venous ulceration (CVU), represent an important socioeconomic burden in the western world. Metalloproteinases have been identified in the pathogenesis of several vascular diseases such as venous problems. The aim of this study was to evaluate a broad range of metalloproteinases, such as matrix metalloproteinases (MMPs), ADAMs (a disintegrin and metalloproteinases) and ADAMTSs (a disintegrin and metalloproteinases with thrombospondin motifs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) and a related protein, neutrophil gelatinase-associated lipocalin (NGAL), in patients with CVD in order to correlate their serum levels with each stage of the disease. We performed a multicenter open-label study that comprised the enrolment of 541 patients with CVD of clinical stages C1-C6, (178 males, 363 females; mean age 57·29, median age 53·72, age range 29-81); 29 subjects without CVD were included in this study (9 males and 20 females; mean age 54·44, median age 50, age range 28-84) as the control group. Enzyme-linked immunosorbent assay (ELISA) was performed for measuring serum levels of proteases and related proteins. The study found that the serum elevation of MMP-2, ADAMTS-1 and ADAMTS-7 appeared to be correlated with the initial stages of CVD, whereas the serum elevation of MMP-1, MMP-8, MMP-9, NGAL, ADAM-10, ADAM-17 and ADAMTS-4 was particularly involved in skin change complications. This study showed that each stage of CVD may be described by particular patterns of metalloproteinases, and this may have therapeutic implications in discovering new targets and new drugs for the treatment of CVD., (© 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

We investigated the associations between the self-evaluated pain status and two pain biomarker candidates, nerve growth factor and S100A8/A9, in exudate from venous leg ulcer to finally develop an objective pain evaluation method. Patients with venous leg ulcer participated in this cross-sectional observational study conducted between April and October 2014 at two medical facilities. During routine wound care, each participant self-evaluated their pain status at each examination using the 10-point numerical rating scale (present pain intensity) and the short-form McGill Pain Questionnaire 2 (continuous pain, intermittent pain, neuropathic pain, affective descriptors, and total score). Venous leg ulcer exudate sample was collected after wound cleansing. The nerve growth factor and S100A8/A9 concentrations in the venous leg ulcer exudate were measured by enzyme-linked immunosorbent assay and standardized according to the wound area. The association between each pain status and the two standardized protein concentrations was evaluated using Spearman's correlation coefficient. In 30 sample collected from 13 participants, the standardized nerve growth factor concentration was negatively correlated with continuous pain (ρ = -0.47, P = 0.01), intermittent pain (ρ = -0.48, P = 0.01), neuropathic pain (ρ = -0.51, P = 0.01), and total score (ρ = -0.46, P = 0.01). The standardized S100A8/A9 concentration was positively correlated with present pain intensity (ρ = 0.46, P = 0.03) and continuous pain (ρ = 0.48, P = 0.03). Thus, these two proteins may be useful for objective evaluation of wound pain in venous leg ulcer patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Congenital anomalies of the venous system are known but congenital absence of infrarenal inferior vena cava with absent deep venous system of the lower limbs is extremely rare., Case Presentation: We report the case of an 11-year-old Indian girl who presented with large venous collaterals on her anterior abdominal wall and recurrent non-healing venous ulcers on her left leg with complete absence of infrarenal inferior vena cava and absent deep veins of her lower limbs., Conclusions: Congenital absence of infrarenal inferior vena cava may occur with absence of the deep venous system of the lower limbs. We have reported this case because of its extreme rarity and to enhance awareness of this entity that has no treatment currently.

Objective: Axial deep venous reflux causes skin changes or ulcers in patients with chronic venous insufficiency (CVI). The study aimed to review the results of correcting axial deep venous reflux using the novel valve-free popliteal vein external banding (PVEB) technique in patients with severe CVI., Methods: We retrospectively reviewed 1252 patients (1252 limbs) who underwent PVEB for treatment of severe CVI from 2000 to 2015. The number and position of popliteal vein valves (PVVs) and gastrocnemius vein entries were analyzed. Preprocedural and postprocedural intraluminal pressure and other hemodynamic parameters were measured and compared. Synchronous skin grafting was used for large ulcers. The healing time and ulcer and symptom recurrence rate were analyzed. Long-term Venous Clinical Severity Score was compared., Results: One pair of PVV leaflets, gastrocnemius vein entries proximal to the PVV, and PVV located in the distal-third popliteal vein segment were confirmed in 87.38% of cases in the venographic study. A total of 1252 patients underwent PVEB, and 1041 patients were followed up (mean follow-up, 55.12 months; range, 9-183 months). In the short term, limb swelling and pain were relieved in 1187 patients (94.81%) without use of compression therapy. The reflux time and reflux volume were significantly reduced (P < .001). All the ulcers were healed in an average of 18 days (95% confidence interval, 16.68-19.32). In the long term, the ulcer recurrence rate was 3.63%. The Venous Clinical Severity Score was significantly reduced (P < .001)., Conclusions: PVEB, which neither opens the vein wall nor relies on the existing vein valves, can promote venous return, improve hemodynamic status, and heal venous ulcer in <2 months, with low complication and symptom recurrence rates., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: to assess the impact of protocol home visits on the functional capacity of adult and elderly patients with venous ulcers, before and after guidance received at home., Method: clinical experimental, randomized, nonblinded and controlled study, developed with 32 patients (case and control groups). Fields of research were the Wound Outpatient Care Unit of the Antônio Pedro University Hospital and households of patients treated in the outpatient unit. Data collection occurred from February to June 2014, by means of an assessment tool of the health care unit, the TINETTI index and a script for directions to be provided to study participants who received home visits., Results: participants in the case group showed significant and differentiated improvement post-intervention when compared to the control group, which remained stable., Conclusion: directions provided in the home context were beneficial to the members of the case group.

Background: Venous leg ulceration is a common and costly problem that is expected to worsen as the population ages. Current treatment is compression therapy; however, up to 50 % of ulcers remain unhealed after 2 years, and ulcer recurrence is common. New treatments are needed to address those wounds that are more challenging to heal. Targeting the inflammatory processes present in venous ulcers is a possible strategy. Limited evidence suggests that a daily dose of aspirin may be an effective adjunct to aid ulcer healing and reduce recurrence. The Aspirin in Venous Leg Ulcer study (ASPiVLU) will investigate whether 300-mg oral doses of aspirin improve time to healing., Methods/design: This randomised, double-blinded, multicentre, placebo-controlled, clinical trial will recruit participants with venous leg ulcers from community settings and hospital outpatient wound clinics across Australia. Two hundred sixty-eight participants with venous leg ulcers will be randomised to receive either aspirin or placebo, in addition to compression therapy, for 24 weeks. The primary outcome is time to healing within 12 weeks. Secondary outcomes are ulcer recurrence, wound pain, quality of life and wellbeing, adherence to study medication, adherence to compression therapy, serum inflammatory markers, hospitalisations, and adverse events at 24 weeks., Discussion: The ASPiVLU trial will investigate the efficacy and safety of aspirin as an adjunct to compression therapy to treat venous leg ulcers. Study completion is anticipated to occur in December 2018., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12614000293662.

Background: Venous leg ulcers are common, chronic wounds that are painful and reduce quality of life. Compression therapy is known to assist in the healing of venous leg ulceration. Supervised exercise training that targets an improvement in calf muscle pump function might be a useful adjunctive therapy for enhancing ulcer healing and other aspects of physical and mental health. However, the evidence of exercise for individuals with venous ulcers is sparse. Here, we describe the protocol for a study that aims to assess the feasibility of undertaking a randomised controlled trial of a supervised exercise programme in people who are receiving compression for venous ulceration., Methods/design: This is a randomised, controlled, assessor-blinded, two-centre, feasibility trial with two parallel groups. Eighty adults who are receiving lower-limb compression for a venous leg ulcer will be randomly assigned to receive usual care (compression only) or usual care plus a 12-week supervised exercise programme. Participants in the exercise group will be invited to undertake three, 60-minute sessions of supervised exercise each week, and each session will involve a combination of treadmill walking, upright cycling and strength and flexibility exercises for the lower limbs. Participants will be assessed before randomisation and 3, 6 and 12 months after randomisation. Primary outcomes include rates of recruitment, retention and adherence. Secondary outcomes include time to ulcer healing, proportion of participants healed, percentage and absolute change in ulcer size, health-related quality of life (EQ-5D-5L and VEINES-QOL/Sym), lower-limb cutaneous microvascular function (laser Doppler flowmetry coupled with iontophoresis) and physical fitness (30-second sit-to-stand test, chair sit and reach test, 6-minute walk test and ankle range of motion). The costs associated with the exercise programme and health-care utilisation will be calculated. We will also complete interviews with a sub-sample of participants to explore their experiences of having a venous ulcer and the acceptability of the exercise intervention and study procedures., Discussion: Data from this study will be used to refine the supervised exercise programme, investigate the acceptability of the intervention and study design and determine the most appropriate outcome measures, thereby providing estimates of the factors needed to design an adequately powered trial across several centres., Trial Registration: Current Controlled Trials, ISRCTN10205425 (May 2014) - http://www.controlled-trials.com/ISRCTN10205425.

Introduction: The measurement of skin and wound bed temperature in chronic wounds may be a useful way to optimize the assessment and diagnosis of chronic wound infection. The aim of this clinical research trial was to correlate the wound bed score, validated by Falanga in 2006, to wound bed and perilesional skin temperature with an easy-to-use, handheld, noninvasive thermometer., Materials and Methods: In this study, the authors recruited 18 patients affected by venous insufficiency and lower leg ulcers. A total of 24 chronic wound bed and perilesional skin ulcers were assessed using an infrared camera (FLIR T620 Thermal Imager, FLIR Systems Boston, MA). At the same visit, an operator blinded to the thermal image results made a wound bed score to make a clinical evaluation of the lesion., Results: The wound bed temperature range after dressing removal was between 31°C and 35°C, and the perilesional skin temperature range was between 31°C and 34°C. The wound bed score range was between 5-14 (14 patients > 10; 11 patients ≤ 10). The study data showed an increasing relationship between the wound bed score and the wound bed temperature according to several studies that have demonstrated 33°C is the critical temperature level required for normal cellular activity. The correlation between the wound bed score and the perilesional skin temperature is weaker compared to other measurements., Conclusion: The results obtained in this preliminary research suggest that this correlation is worth being further investigated with a larger dataset.

Introduction: Ultrasound and electric stimulation are known therapies for the treatment of chronic ulcerations. Combined modulated ultrasound and electric field stimulation (CUSEFS) have never been studied as a single modality. The authors evaluate the results of CUSEFS (BRH Medical Ltd, Jerusalem, Israel) on a variety of wound types in a number of clinics., Methods: This retrospective analysis looked at ulcers treated with CUSEFS in 4 clinics. Wounds were evaluated by an independent assessor and data was evaluated by an independent statistician. Of the 300 wounds treated with the CUSEFS device, only those classified as diabetic foot ulcers (DFUs) or venous leg ulcers (VLUs) were evaluated. A treatment was deemed successful if the wound was 50% closed within 4 weeks. Subjects were then followed to see if their wounds completely closed within 16 weeks., Results: Of the 27 DFUs treated, 59.3% (16) achieved 50% closure within 4 weeks. Of the 38 VLUs treated, 71.1% (27) achieved 50% closure within 4 weeks. It was found that variables such as gender, size of the wound at presentation, and longevity of the wound had no bearing on the outcome. The age of the patient had an effect on the outcome of the VLUs. The wound healing trajectory was supported in that there was a significant difference in the achievement of total closure between those subjects who had a successful trial and those who did not., Conclusion: Combined modulated ultrasound and electric field stimulation has a place as adjunct therapy that aids wound healing and provides an effective noninvasive treatment option.

Objective: Massive (≥100 cm(2)) venous leg ulcers (VLUs) demonstrate very low closure rates with standard compression therapy and are costly to manage. Negative-pressure wound therapy (NPWT), followed by a split-thickness skin graft (STSG), can be a cost-effective alternative to this standard care. We performed a cost analysis of these two treatments., Methods: A retrospective review was performed of 10 ulcers treated with surgical debridement, 7 days of inpatient NPWT with topical antiseptic instillation (NPWTi), and STSG, with 4 additional days of inpatient NPWT bolster over the graft. Independent medical cost estimators were used to compare the cost of this treatment protocol with standard outpatient compression therapy., Results: The average length of time ulcers were present before patients entered the study was 38 months (range, 3-120 months). Eight of 10 patients had complete VLU closure by 6 months after NPWTi with STSG. The 6-month costs of the proposed treatment protocol and standard twice-weekly compression therapy were estimated to be $27,000 and $28,000, respectively., Conclusions: NPWTi with STSG treatment is more effective for closure of massive VLUs at 6 months than that reported for standard compression therapy. Further, the cost of the proposed treatment protocol is comparable with standard compression therapy., (Copyright © 2015 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.)

Background: Exercise and adequate self-management capacity may be important strategies in the management of venous leg ulcers. However, it remains unclear if exercise improves the healing rates of venous leg ulcers and if a self-management exercise program based on self-efficacy theory is well adhered to., Method/design: This is a randomised controlled in adults with venous leg ulcers to determine the effectiveness of a self-efficacy based exercise intervention. Participants with venous leg ulcers are recruited from 3 clinical sites in Australia. After collection of baseline data, participants are randomised to either an intervention group or control group. The control group receive usual care, as recommended by evidence based guidelines. The intervention group receive an individualised program of calf muscle exercises and walking. The twelve week exercise program integrates multiple elements, including up to six telephone delivered behavioural coaching and goal setting sessions, supported by written materials, a pedometer and two follow-up booster calls if required. Participants are encouraged to seek social support among their friends, self-monitor their weekly steps and lower limb exercises. The control group are supported by a generic information sheet that the intervention group also receive encouraging lower limb exercises, a pedometer for self-management and phone calls at the same time points as the intervention group. The primary outcome is the healing rates of venous leg ulcers which are assessed at fortnightly clinic appointments. Secondary outcomes, assessed at baseline and 12 weeks: functional ability (range of ankle motion and Tinetti gait and balance score), quality of life and self-management scores., Discussion: This study seeks to address a significant gap in current wound management practice by providing evidence for the effectiveness of a home-based exercise program for adults with venous leg ulcers. Theory-driven, evidence-based strategies that can improve an individual's exercise self-efficacy and self-management capacity could have a significant impact in improving the management of people with venous leg ulcers. Information gained from this study will provide much needed information on management of this chronic disease to promote health and independence in this population., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12612000475842.

Background: Chronic venous leg ulcers are the most common wounds seen in general practice. Their management can be both challenging and time-consuming., Objective: To produce a short practical guideline incorporating the TIME concept and A2BC2D approach to help general practitioners and their practice nurses in delivering evidence-based initial care to patients with chronic venous leg ulcers., Conclusion: Most chronic venous leg ulcers can be managed effectively in the general practice setting by following the simple, evidence-based approach described in this article. Figure 1 provides a flow chart to aid in this process. Figure 2 illustrates the principles of management in general practice., Discussion: Effective management of chronic ulcers involves the assessment of both the ulcer and the patient. The essential requirements of management are to debride the ulcer with appropriate precautions, choose dressings that maintain adequate moisture balance, apply graduated compression bandage after evaluation of the arterial circulation and address the patient's concerns, such as pain and offensive wound discharge.

Results of treatment of 43 patients, suffering varicose disease, complicated by trophic disorders, were analyzed. To the patients a complex was prescribed, including sorpents, angioprotectors, locally - ointments. There were operated 14 patients.

Context: Patients with venous leg ulcers experience multiple symptoms, including pain, depression, and discomfort from lower leg inflammation and wound exudate. Some of these symptoms impair wound healing and decrease quality of life (QOL). The presence of co-occurring symptoms may have a negative effect on these outcomes. The identification of symptom clusters could potentially lead to improvements in symptom management and QOL., Objectives: To identify the prevalence and severity of common symptoms and the occurrence of symptom clusters in patients with venous leg ulcers., Methods: For this secondary analysis, data on sociodemographic characteristics, medical history, venous history, ulcer and lower limb clinical characteristics, symptoms, treatments, healing, and QOL were analyzed from a sample of 318 patients with venous leg ulcers who were recruited from hospital outpatient and community nursing clinics for leg ulcers. Exploratory factor analysis was used to identify symptom clusters., Results: Almost two-thirds (64%) of the patients experienced four or more concurrent symptoms. The most frequent symptoms were sleep disturbance (80%), pain (74%), and lower limb swelling (67%). Sixty percent of patients reported three or more symptoms at a moderate-to-severe level of intensity (e.g., 78% reported disturbed sleep frequently or always; the mean pain severity score was 49 of 100, SD 26.5). Exploratory factor analysis identified two symptom clusters: pain, depression, sleep disturbance, and fatigue; and swelling, inflammation, exudate, and fatigue., Conclusion: Two symptom clusters were identified in this sample of patients with venous leg ulcers. Further research is needed to verify these symptom clusters and to evaluate their effect on patient outcomes., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

An increasing number of compression systems available for treatment of venous leg ulcers and limited evidence on the relative effectiveness of these systems are available. The purpose of this study was to conduct a randomised controlled trial to compare the effectiveness of a four-layer compression bandage system and Class 3 compression hosiery on healing and quality of life (QL) in patients with venous leg ulcers. Data were collected from 103 participants on demographics, health, ulcer status, treatments, pain, depression and QL for 24 weeks. After 24 weeks, 86% of the four-layer bandage group and 77% of the hosiery group were healed (P = 0·24). Median time to healing for the bandage group was 10 weeks, in comparison with 14 weeks for the hosiery group (P = 0·018). The Cox proportional hazards regression found participants in the four-layer system were 2·1 times (95% CI 1·2-3·5) more likely to heal than those in hosiery, while longer ulcer duration, larger ulcer area and higher depression scores significantly delayed healing. No differences between groups were found in QL or pain measures. Findings indicate that these systems were equally effective in healing patients by 24 weeks; however, a four-layer system may produce a more rapid response., (© 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

This study aimed to assess the feasibility of a home-based exercise programme and examine the effects on the healing rates of venous leg ulcers. A 12-week randomised controlled trial was conducted investigating the effects of an exercise intervention compared to a usual care group. Participants in both groups (n = 13) had active venous ulceration and were treated in a metropolitan hospital outpatients clinic in Australia. Data were collected on recruitment from medical records, clinical assessment and questionnaires. Follow-up data on progress in healing and treatments were collected fortnightly for 12 weeks. Calf muscle pump function data were collected at baseline and 12 weeks from recruitment. Range of ankle motion data were collected at baseline, 6 and 12 weeks from recruitment. This pilot study indicated that the intervention was feasible. Clinical significance was observed in the intervention group with a 32% greater decrease in ulcer size (P = 0·34) than the usual care group, and a 10% (P = 0·74) improvement in the number of participants healed in the intervention group compared to the usual care group. Significant differences between groups over time were observed in calf muscle pump function parameters [ejection fraction (P = 0·05), residual volume fraction (P = 0·04)] and range of ankle motion (P = 0·01). This pilot study is one of the first to examine and measure clinical healing rates for participants involved in a home-based progressive resistance exercise programme. Further research is warranted with a larger multi-site study., (© 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.)

In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well-defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1·35; lower-upper quartiles 0·71-1·83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2·22; 1·12-2·33; P = 0·0024) when compared with NGTA, in combination with a significant increase in CD (1·75; 0-3; P = 0·0054). In scar, the LDP was similar to that in the NGTA (1·03; 0·77-1·83; P = 0·278), combined with the highest CD (5·75; 4·5-8) in comparison with the previous stages of the area (for both pairs, P < 0·0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low., (© 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

Background: Venous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available., Principal Findings: In wound edge biopsies from human venous leg ulcers we found a striking upregulation of dermal N-cadherin, Zonula Occludens-1 and the gap junction protein Connexin43 (Cx43) compared to intact skin, and in stark contrast to the down-regulation of Cx43 expression seen in acute, healing wounds. We targeted the expression of these proteins in 3T3 fibroblasts to evaluate their role in venous leg ulcers healing. Knockdown of Cx43 and N-cadherin, but not Zonula Occludens-1, accelerated cell migration in a scratch wound-healing assay. Reducing Cx43 increased Golgi reorientation, whilst decreasing cell adhesion and proliferation. Furthermore, Connexin43 and N-cadherin knockdown led to profound effects on fibroblast cytoskeletal dynamics after scratch-wounding. The cells exhibited longer lamelipodial protrusions lacking the F-actin belt seen at the leading edge in wounded control cells. This phenotype was accompanied by augmented activation of Rac-1 and RhoA GTPases, as revealed by Förster Resonance Energy Transfer and pull down experiments., Conclusions: Cx43 and N-cadherin are potential therapeutic targets in the promotion of healing of venous leg ulcers, by acting at least in part through distinct contributions of cell adhesion, migration, proliferation and cytoskeletal dynamics.