Chronic Venous Leg Ulcers Research Articles

New Insights on the Effects of Dietary Omega-3 Fatty Acids on Impaired Skin Healing in Diabetes and Chronic Venous Leg Ulcers.

Long-chain Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are widely recognized as powerful negative regulators of acute inflammation. However, the precise role exerted by these dietary compounds during the healing process is still largely unknown, and there is increasing interest in understanding their specific effects on the implicated cells/molecular factors. Particular attention is being focused also on their potential clinical application in chronic pathologies characterized by delayed and impaired healing, such as diabetes and vascular diseases in lower limbs. On these bases, we firstly summarized the current knowledge on wound healing (WH) in skin, both in normal conditions and in the setting of these two pathologies, with particular attention to the cellular and molecular mechanisms involved. Then, we critically reviewed the outcomes of recent research papers investigating the activity exerted by Omega-3 PUFAs and their bioactive metabolites in the regulation of WH in patients with diabetes or venous insufficiency and showing chronic recalcitrant ulcers. We especially focused on recent studies investigating the mechanisms through which these compounds may act. Considerations on the optimal dietary doses are also reported, and, finally, possible future perspectives in this area are suggested.

Improving Adherence to Wearing Compression Stockings for Chronic Venous Insufficiency and Venous Leg Ulcers: A Scoping Review

PurposePatient adherence to wearing compression stockings in the management of chronic venous insufficiency (CVI) and venous leg ulcers (VLUs) is low. Poor adherence with compression stockings contributes to recurrence and impaired healing of VLUs. As such, the purpose of this review was to report on the scientific evidence related to adherence and explore modifiable factors which impact adherence with compression stockings.MethodsA systematic search was conducted from inception to 31 October 2019. Following the PRISMA-ScR Checklist, PubMed, Medline, CINAHL, Cochrane, Embase, OT Seeker and Web of Science were explored using search terms: compression/compression stocking/compression garment/compression sock/stockings/garments and adherence/compliance/concordance.ResultsWe identified 2613 papers of which 125 full text papers were assessed for eligibility and 69 met inclusion criteria. Papers were grouped and charted by concepts relevant to the research questions and narratively synthesized. Several dominant themes emerged, and a conceptual framework was developed incorporating modifiable variables, adherence itself, and outcomes related to adherence. Specifically considering interventions to improve adherence, only five of 14 randomized controlled trials were able to demonstrate improvements in adherence through unidimensional approaches. All nine of the case studies/series demonstrated a positive impact on adherence, eight of which described a personalized multidimensional approach. A lack of consensus around defining, measuring, and quantifying adherence with compression stockings was identified, resulting in wide variation in reported adherence rates.ConclusionInconsistency in the definition and measurement of adherence limits meaningful interpretation of the literature. No individual intervention has consistently demonstrated improved adherence. Multidimensional interventions show promise but require further investigation with high-quality trials. Improving adherence appears to improve health outcomes in VLU /CVI populations but there is a lack of information directly linking improved adherence with cost outcomes.Trial RegistrationOpen Science Framework: ACTRN12620000544976p.

Efficacy of Oxidized Regenerated Cellulose/Collagen Dressing for Management of Skin Wounds: A Systematic Review and Meta-Analysis.

Objective The purpose of this study was to evaluate the wound healing efficacy of oxidized regenerated cellulose (ORC)/collagen dressing and ORC/collagen/silver-ORC dressings compared to standard of care or control in treatment of chronic skin wounds such as diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), and pressure injuries sore ulcers (PISUs). Methods An electronic search was carried out in four popular databases PubMed, Scopus, Embase, and CENTRAL to identify thirteen included studies, comparing the clinical efficacy of ORC/collagen dressings when compared to control in management of chronic skin wounds, especially DFUs, VLUs, and PISUs, and skin graft donor site wounds. Results Consolidated data from thirteen comparative clinical studies undertaken for management of DFUs, VLUs, and PISUs showed favorable outcomes towards use of ORC/collagen compared to other traditional and hydrocolloid foam dressings in terms of wound healing rate (P=0.02) and percentage wound relative reduction (P=0.003). The time taken to achieve complete wound healing in the included studies did not show any statistical significant difference (P=0.24). There was no significant difference in adverse events between ORC/collagen-treated group and comparative group (P=0.19). Conclusion ORC/collagen wound dressings are beneficial in terms of improved wound healing rate and percentage wound relative reduction compared to already existing traditional standard of care with non-MMP, inhibiting biomaterials such as moistened gauze, autologous growth factors, hydrocolloid foam dressings, or ovine extracellular matrix.

Once daily 300 mg aspirin with compression versus compression alone in patients with chronic venous leg ulcers (ASPiVLU): A randomised, double-blinded, multicentre, placebo-controlled, clinical trial

AimVenous leg ulcers are lower limb skin ulcers characterised by a cycle of healing and recurrence due to underlying chronic venous insufficiency. While compression improves healing outcomes, many ulcers do not heal. As a daily 300 mg oral dose of aspirin in conjunction with compression may improve healing outcomes, we investigated the effect of adjuvant aspirin on venous leg ulcer healing in participants already receiving compression. Materials and methodsWe conducted a prospective, randomised, double-blinded, placebo-controlled, clinical trial (known as ASPiVLU). Participants were recruited from six wound clinics in Australia. We screened 844 participants. Community-dwelling adult participants identified at six hospital outpatient clinics and clinically diagnosed with a venous leg ulcer present for 6+ weeks were eligible between April 13, 2015 to June 30, 2018. We randomised 40 participants (n = 19 aspirin, n = 21 placebo) and evaluated against the primary outcome. There were no dropouts. Ten serious adverse events in six participants were recorded. None were study related. The primary outcome measure was healing at 12 weeks based on blinded assessment. ResultsWe found no difference in the number of ulcers healed at 12 weeks between the intervention and control groups. ConclusionThis study could not detect whether or not aspirin affected VLU healing speed. This is likely because we recruited fewer participants than expected due to the high number of people with venous leg ulcers in Australia who were already taking Aspirin; future research should investigate other adjuvant therapies or different study designs.

Physical Activity as an Adjunct to Compression Therapy on Healing Outcomes and Recurrence in Patients With Venous Leg Ulcers: A Scoping Review Protocol.

Background: Chronic venous leg ulceration is a common and costly clinical issue across the world, affecting up to 3 in 1,000 people. Compression therapy is recommended as the gold standard treatment in clinical practice, although a large number of venous leg ulcers remain unhealed after several years. Physical activity may improve healing although there is limited evidence on the effects of physical activity as an adjuvant treatment to compression to improve venous leg ulcers healing and prevent recurrence.Objectives: This scoping review protocol aims to systematically search, appraise, and synthesize quantitative research evidence to assess the effect of physical activity interventions applied in conjunction with compression therapy on venous leg ulcer healing and recurrence.Methods and Analysis: We will use the methodology framework suggested by Arksey and O'Malley, Levac et al., the JBI as a guide. We will also follow the three-step search strategy recommended by the JBI to systematic search for relevant published research, ongoing clinical trials, and grey literature. Two review authors will independently screen titles and abstracts followed by full-text review to determine final eligibility for inclusion. The search process will be reported using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart. Characteristics of physical activity interventions, primary outcomes related to ulcer healing and recurrence, and secondary outcomes of interest included quality of life, pain level, adverse effects, and economic costs will be extracted and summarized. The review will provide a descriptive account of the findings from included studies. Where appropriate, data will be pooled for a meta-analysis using a random effects model.Discussion: Physical activity interventions represent a low-cost, potentially useful adjuvant treatment to compression therapy for the management of venous leg ulcers. Several gaps in knowledge remain that are answerable via a targeted scoping review. This protocol outlines the rationale, objectives, and the planned methodology for conducting the study.Ethics and Dissemination: The scoping review will use data from publicly available sources and ethical approval is not required. Findings from this review will be submitted to a peer-reviewed journal, presented at relevant conferences and disseminated via social media.

Efficacy and Safety of a Hyaluronic Acid-Containing Gauze Pad in the Treatment of Chronic Venous or Mixed-Origin Leg Ulcers: A Prospective, Multicenter, Randomized Controlled Trial

Introduction. Hyaluronic acid (HA)-containing formulations routinely are utilized along with standard therapy to promote faster healing of chronic wounds; evidence to guide clinical decisions on the use of topical HA in the healing of vascular leg ulcers is limited. Objective. This study compared the efficacy and safety of an HA-impregnated gauze pad with an identical gauze pad without HA in the treatment of chronic leg ulcers of vascular origin. Materials and Methods. A prospective, multicenter, multinational, parallel-group, randomized, double-blind, clinical study was conducted between June 13, 2017, and December 31, 2018. Adults with 1 or more chronic leg ulcers of venous or mixed origin between 2 months and 4 years’ duration were eligible to participate. Participants were randomized to treatment consisting of standard care (ie, ulcer cleansing, debridement/anesthesia as necessary, and optimized compression) and either application of a gauze pad containing 0.05% HA or a neutral comparator once daily for a maximum of 20 weeks. The primary efficacy endpoint was complete ulcer healing (100% reepithelialization of the wound area centrally assessed by 1 independent and experienced assessor blinded with respect to the treatment applied, as shown on digital photographs taken under standardized conditions at or before 20 weeks and confirmed 3 weeks later). Secondary efficacy endpoints included the percentage of completely healed target ulcers, residual area of target ulcer relative to baseline, the condition of the periulcerous skin, the total amount of analgesics used, the incidence of infection at the ulcer site of the target ulcer, patient adherence to treatment, time to achieve complete healing as centrally assessed, and pain intensity as measured by a visual analog scale. Results. Among the 168 participants (82 in the HA gauze pad group and 86 in the neutral gauze pad group), 33 (39.8%) in the HA group experienced complete healing of the target ulcer, which was significantly higher than the neutral comparator group (15, 18.5%; P = .002). Results in the full analysis and per-protocol sets were consistent with the primary results; no significant difference was noted in outcomes when participants’ wounds were stratified according to baseline ulcer size. Conclusions. HA delivered in a gauze pad formulation could be a beneficial treatment for chronic leg ulcers of venous or mixed origin.

Recurrent venous leg ulcers: management in general practice

Venous leg ulcers commonly recur. Annemarie Brown highlights some self-care strategies that patients can use to reduce their risk Chronic venous leg ulcers are commonly seen in general practice and although healing rates for leg ulcers have improved, recurrence rates are high with around 60–70% reported to recur after healing. The primary prevention strategy is the life-long wearing of compression hosiery; however, compliance is low for several reasons including lack of understanding of the need to wear compression hosiery and difficulties applying and removing it. Self-care strategies such as physical exercise and mobility, leg elevation and appropriate skin care, can help to prevent recurrence of venous leg ulcers. Practice nurses are ideally placed to provide this advice, which can help improve patient's quality of life while reducing the financial burden of treating open ulceration for the NHS.

A COMPARATIVE STUDY BETWEEN THE EFFECTIVENESS OF AUTOLOGOUS PLATELET-RICH FIBRIN VERSUS SALINE DRESSING IN THE MANAGEMENT OF CHRONIC VENOUS LEG ULCERS

Background: Venous disease is responsible for around 85% of all chronic lower limb ulcers in resource-rich countries. Venous leg ulcer is a chronic condition, and various treatment modalities are available. Various adjunctive wound care therapies and procedures are available that can be utilized as part of a comprehensive approach to healing venous stasis ulcers. Platelet-rich brin (PRF) is one of the newer modalities and it contains broblast growth factor (FGF), VEGF, angiopoietin and platelet-derived GF which enhances the wound healing. We conducted a randomized controlled trial to compare the efcacy of PRF versus saline dressing in chronic venous leg ulcers. Aim: To compare the efcacy of autologous PRF with saline dressing in patients with chronic venous leg ulcer in terms of mean reduction in ulcer area, presence of infection and cosmetic outcome at the end of 4 weeks. Materials and Methods: Thirty patients with chronic venous leg ulcers of >6 months duration having an ulcer area of 1 cm × 1 cm to 5 cm × 5 cm were taken into the study and were randomly divided into two groups. Group 1: Patients received PRF dressing. 10 mL of patient's blood was taken and centrifuged at 3000 rpm for 15 min. A brin clot obtained in the middle of the tube was removed and used for dressing over the wound surface. It was repeated every week for 4 weeks. Group 2: Patients received saline dressings once a week for 4 weeks. The assessment of the ulcer size was done with the help of photographs, and ulcer area was measured. Results: The mean reduction in the area of the ulcer size in PRF group was 81.84%, and the mean reduction in the area of the ulcer size in Saline group was 59.84%. Conclusion: Platelet rich brin matrix is a novel modality and an ideal, safe, affordable therapeutic option for chronic venous leg ulcers.

Multidimensional Pain Characteristics in Older Adults with Chronic Venous Leg Ulcers.

Objective: Pain affects wound healing, treatment, and quality of life because it has significant impacts on physical, psychological, and social well-being. Despite the fact that more than half of chronic venous leg ulcer (CVLU) patients experience mild-to-moderate pain, the multidimensional characteristics of CVLU pain are not well documented. The objective of this study was to describe the multidimensional pain characteristics, including the sensory, affective, cognitive, and behavioral dimensions, of CVLU before debridement. Approach: Participants (N = 40) were recruited from a wound clinic. We conducted a descriptive analysis of clinical data, including pain, wound, and demographic characteristics, collected at the first visit. Results: The mean age of participants was 70.8 ± 9.1 years, 22 (55%) participants were female, and 35 (87.5%) were white. Participants reported mean current pain intensity (2.9 ± 2.7), least (1.2 ± 2.2) and worst (4.8 ± 3.4) pain intensity in 24 h, and tolerable pain level (4.9 ± 2.64) on a 0-10 scale. They described pain as periodic (66.7%, n = 26) with multiple pain quality descriptors (5.4 ± 2.9). Their past pain treatments provided some pain relief (65%, n = 25). For 68% (n = 27), their pain was the same as they expected. Nearly all had a tendency not to tell others about their pain (95%, n = 38). Innovation: This study is the first to describe the multidimensional pain characteristics of patients with CVLU as measured with PAINReportIt. Conclusion: Patients with CVLU reported willingness to tolerate a relatively high level of pain and experience the level of pain they anticipate. Multidimensional pain assessment will assist clinicians to select individualized therapies to manage pain and improve quality of life for these patients.

A prospective clinical trial evaluating changes in the wound microenvironment in patients with chronic venous leg ulcers treated with a hypothermically stored amniotic membrane.

Amniotic tissues have been long utilised to treat chronic wounds; however, there are few studies evaluating how the wound microenvironment responds to these therapies. The goal of this study was to evaluate the changes in wounds treated with a hypothermically stored amniotic membrane (HSAM). In this prospective single‐arm study, 15 female patients with venous leg ulcers were treated with HSAM from male donors and standard of care for 12 weeks. Over the course of the study, wound exudate was collected and evaluated using proteomic microarrays. Biopsies were collected during the course of treatment to detect the presence of HSAM tissue. By 4 weeks, 60% of subjects achieved 50% or greater reduction in wound size, and by 12 weeks, 53% of subjects achieved 100% re‐epithelialization. HSAM DNA was detected in 20% of biopsies as determined by the detection TSPY4, indicating HSAM was no longer present within the wound bed approximately 7 days from the last treatment for the majority of wounds. Proteomic analysis of wound exudate found that wounds on a healing trajectory had significantly higher levels of MMP‐10, MMP‐7, and TIMP‐4 and significantly lower levels of CX3CL1, FLT‐3 L, IL‐1ra, IL‐1a, IL‐9, IL‐2, IL‐3, MCP‐1, and TNF‐b compared with other wounds.

Objective assessment of Platelet-Rich Plasma (PRP) potentiality in the treatment of Chronic leg Ulcer: RCT on 80 patients with Venous ulcer.

Chronic venous leg ulcer reduces the patients' activities and their overall quality of life. Platelet-rich plasma (PRP) was previously investigated as promising less invasive management for leg ulcers. To re-assess the efficacy and safety of PRP in the management of chronic leg ulcers due to venous factors. RCT enrolled 80 patients who clinically presented with chronic venous leg ulcers. Forty patients were allocated randomly for the treatment with autologous platelet-rich plasma (PRP). Intradermal and subdermal injection of PRP by 27guage syringe weekly, in all edges and in the granular floor of the ulcer for 4-6 sessions. Another 40 patients managed by conventional treatment by compression and dressing for the same period were allocated as Group B. Objective assessment achieved by the percentage of reduction of the size of the ulcer area, rate of healing, incidence of recurrence, and if side effects have been reported. PRP therapy showed better results and high p value significance when compared to conventional therapy. This study shows that PRP is effective and significant in promoting the wound healing process in chronic leg venous ulcers. PRP is simple, safe, and has a short learning curve technique.

An observational study protocol to explore loneliness and systemic inflammation in an older adult population with chronic venous leg ulcers

BackgroundChronic venous leg ulcers (CVLUs) are the most common type of lower extremity wound. Even when treated with evidenced-based care, 30–50% of CVLUs fail to heal. A specific gap exists about the association between psychosocial stressors, particularly loneliness, and biomarkers of inflammation and immunity. Loneliness is highly prevalent in persons with CVLUs, has damaging effects on health, and contributes to the development of multiple chronic conditions, promotes aberrant inflammation, and diminishes healing. However, the confluence of loneliness, inflammation and the wound healing trajectory has not been elucidated; specifically whether loneliness substantially mediates systemic inflammation and alters healing over time. This study seeks to address whether there is a specific biomarker profile associated with loneliness, CVLUs, and wound healing that is different from non-lonely persons with CVLUs.MethodsAn observational prospective study will identify, characterize and explore associations among psychosocial stressors, symptoms and biomarkers between 2 CVLU groups, with loneliness+ (n = 28) and without loneliness- (n = 28) during 4 weeks of wound treatment, measured at 3 time points. We will examine psychosocial stressors and symptoms using psychometrically-sound measures include PROMIS® and other questionnaires for loneliness, social isolation, depression, anxiety, stigma, sleep, fatigue, pain, quality of life, cognition, and function. Demographics data including health history, sex, age, wound type and size, wound age, and treatment will be recorded from the electronic health record. We will characterize a biomarker panel of inflammatory genes including chemotaxic and growth factors, vascular damage, and immune regulators that express in response to loneliness to loneliness and CVLUs using well-established RNA sequence and PCR methods for whole blood samples. In an exploratory aim we will explore whether age and sex/psychological stressors and symptoms indicate potential moderation/mediation of the effect of loneliness on the biomarker profile over the study period.DiscussionThis study will provide insight into the influence of psychosocial stressors, symptoms, and biological mechanisms on wound healing, towards advancing a future healing prediction model and interventions to address these stressors and symptoms experienced by persons with CVLUs.

Evaluation of timolol maleate gel for management of hard-to-heal chronic venous leg ulcers. Phase II randomised-controlled study

BackgroundVenous leg ulcers (VLUs) often take a very long time to heal. Timolol maleate has been reported as displaying efficacy in healing of VLUs. ObjectivesTo evaluate the efficacy of timolol maleate gel in the management of hard-to-heal VLUs and to assess its safety as a topical agent during 12 weeks of use in combination with conventional treatment. MethodsA prospective, phase-II randomised-controlled trial with a sample size based on Fleming's one-stage design (P0=0.25, P1=0.45, alpha=0.1, beta=0.2) was planned. Patients with VLUs present for ≥24 weeks and with ≥50% granulation tissue were included. One drop of sustained-release timolol gel (Timoptol® LP 0.5%, Santen, Tampere, Finland) per 6 cm2 VLU area was applied every 2 days for 12 weeks in timolol-treated patients, as adjuvant therapy to the standard care protocol (interface dressing and multilayer venous compression). Controls received standard care alone. The primary endpoint was to obtain ≥40% reduction in ulcer area at week 12 (W12). ResultsForty-three patients were randomised to the study, with 40 receiving at least one treatment and included in the analysis: 21 timolol-treated patients and 19 controls (females: 70%; median age: 72.5 [range 35–93] years). At W12, ≥40% ulcer-area reduction was achieved in 14/21 (67%) timolol-treated patients vs. 6/19 (32%) controls. No serious adverse events occurred. Local wound infections not requiring systemic antibiotics occurred in 5 cases in the timolol group and in one case in the controls. ConclusionsThese results support the benefit and safety of using timolol maleate to manage hard-to-heal VLUs, but confirmation is required in a larger multicentre randomised phase-III study.

Contact allergy in patients with chronic venous leg ulcers.

Contact allergy in patients with chronic venous leg ulcers.

The Influence of Combined Physical Therapy Procedures on Oxygen Partial Pressure in Tissues Surrounding Ulcer in Patients With Venous Leg Ulcers.

Venous ulcers in lower legs remain a profound treatment problem in contemporary medicine. Proper healing requires, among other things, sufficient blood supply and provision of suitable amount of oxygen to the treated tissues. The aim of the study was to assess the influence of combined physical therapy applied in patients with chronic venous leg ulcers on the oxygen partial pressure values. Fifty-four patients (25 females and 29 males), in the age range of 38 to 89 years with chronic venous leg ulcers, underwent a cycle of 15 procedures with the use of Laserobaria-S device. During a procedure, the patient's lower limb was simultaneously exposed to oxygen having the pressure of 1.5 ATA, low-frequency magnetic field, and low-energy light radiation. Before procedures, directly after the first procedure, as well as on completion of the entire therapeutic cycle, the patients underwent oxygen partial pressure measurements in the tissues surrounding the ulceration area, by means of transcutaneous oximetry, with the use of Medicap Précise 8008s device. The combined physical therapy shows a statistically significant increase of oxygen partial pressure values in tissues surrounding the ulceration, from the average of 68.63 ± 17.04 mm Hg before commencing the therapeutic cycle, to the average of 74.20 ± 18.92 mm Hg after the first procedure (P < .001) and to the average value of 83.79 ± 20.74 mm Hg (P < .001) after completion of therapeutic cycle. Combined physical therapy procedures cause a statistically significant increase of oxygen partial pressure values in tissues surrounding the ulceration, assessed using the objective method of transcutaneous oximetry, both in women and men.

Challenges in the reflux ablation in a patient with chronic venous leg ulcer – case report

Challenges in the reflux ablation in a patient with chronic venous leg ulcer – case report

The Effect of Bacterial Colonization and Maggot Debridement Treatment on Wound Healing in Chronic Venous Leg Ulcers.

The debridement of necrotic and infected tissues, which prolong the wound healing process, is important for the preparation of the wound bed. Therefore, wound-bed preparation and debridement are vital components of venous leg ulcer management. We aimed to present a perspective to evaluate the clinical and microbiological efficacy of Maggot Debridement Therapy (MDT) in the treatment of chronic leg ulcers caused by venous insufficiency. Thirty-eight patients with chronic venous leg ulcers who were referred to our unit with an MDT request were included in the study. Lucilia sericata larvae were applied to the wounds two days a week until the necrotic tissue was cleared. Swab samples were regularly taken before and immediately after each larval application for wound culture. Changes in the percentage of wound surface area and growing pathogenic microorganisms were recorded during the follow-up period. The sample consisted of 38 patients with 55 venous leg ulcers. The mean initial ulcer surface area was 99.1 cm2 (range 3 - 500). Complete debridement was achieved in all ulcers in the 2nd week, on average. Twenty-five ulcers (45.5%) were completely debrided with two one-week MDT sessions. Complete wound healing occurred in 42 ulcers (76.4%) after an average of seven MDT sessions. Microorganisms isolated from the wounds significantly decreased immediately after the first MDT session. Although many methods are used in the treatment of venous leg ulcers, they are often not effective. MDT, which is coming into widespread use today, is a simple and effective method in the treatment of these ulcers. Its effects such as biodebridement, disinfection, and growth stimulation can encourage the rapid healing of chronic venous leg ulcers.

An audience survey of practice relating to pain in the management of chronic venous leg ulcers.

Venous leg ulcers (VLU) respond well to compression, yet many ulcers remain unhealed after 1 year. Practitioners could be reluctant to apply compression to patients with significant ulcer pain. This study aimed to capture the views of practitioners on compression therapy for patients with painful VLU. A survey was conducted at a UK meeting in 2019 using handheld voting pads to capture the anonymous responses to four questions to which a mean of 90 practitioners responded. Nearly 40% of practitioners treat six or more patients a day with painful lower-limb ulcers. Some 80% felt confident in managing patients with painful ulcers; yet, most practitioners suggested they would refer onward for pain management. Some 40% would omit or reduce compression therapy as a pain management strategy. This survey supports the need for technological solutions that reduce VLU pain so that patients receive effective compression therapy.

Neuromuscular stimulation of the common peroneal nerve increases arterial and venous velocity in patients with venous leg ulcers.

Activation of the venous muscle pumps by neuromuscular stimulation of the common peroneal nerve has been previously shown to increase venous and arterial flow in the legs of healthy subjects. The aim of this study is to determine whether a similar effect is observed in patients with chronic venous leg ulcers. 1 Hz intermittent electrostimulation of the common peroneal nerve was applied to 14 patients with ulcers between 1 and 10 cm in diameter, eliciting a small, painless, regular, muscular twitch of the leg. Flow was measured using Duplex ultrasound in the popliteal vein and the popliteal artery. Peak arterial velocity increased from 57 to 78 cm/s (P = .001) in sitting position, and from 79 to 98 cm/s in recumbent position (P = .001). Peak venous velocity increased from 10 to 33 cm/s (P = .001) sitting, and from 14 to 47 cm/s (P = .001) recumbent. Significant increases were observed in both venous and arterial blood flow in the lower limb. This suggestsed that activation of the venous muscle pump and improvement of arterial flow assisted oxygen delivery at the wound site. Moreover this may be a worthwhile intervention to assist in the healing of venous leg ulcers, and may provide a mechanistic explanation for the increased healing rates previously reported with neuromuscular stimulation of the common peroneal nerve.

Intracellular escape strategies of Staphylococcus aureus in persistent cutaneous infections.

Pathogenic invasion of Staphylococcus aureus is a major concern in patients with chronic skin diseases like atopic dermatitis (AD), epidermolysis bullosa (EB), or chronic diabetic foot and venous leg ulcers, and can result in persistent and life-threatening chronic non-healing wounds. Staphylococcus aureus is generally recognized as extracellular pathogens. However, S.aureus can also invade, hide and persist in skin cells to contribute to wound chronicity. The intracellular life cycle of S.aureus is currently incompletely understood, although published studies indicate that its intracellular escape strategies play an important role in persistent cutaneous infections. This review provides current scientific knowledge about the intracellular life cycle of S.aureus in skin cells, which can be classified into professional and non-professional antigen-presenting cells, and its strategies to escape adaptive defense mechanisms. First, we discuss phenotypic switch of S.aureus, which affects intracellular routing and degradation. This review also evaluates potential intracellular escape mechanism of S.aureus to avoid intracellular degradation and antigen presentation, preventing an immune response. Furthermore, we discuss potential drug targets that can interfere with the intracellular life cycle of S.aureus. Taken together, this review aimed to increase scientific understanding about the intracellular life cycle of S.aureus into skin cells and its strategies to evade the host immune response, information that is crucial to reduce pathogenic invasion and life-threatening persistence of S.aureus in chronic cutaneous infections.