Healing Of Chronic Venous Ulcers Research Articles

Dynamic optical coherence tomography of chronic venous ulcers.

Chronic ulcers, especially venous leg ulcers, are a major burden on the healthcare system. To date there are only few non-invasive established procedures for evaluation of blood perfusion in wounds. Dynamic optical coherence tomography (D-OCT) provides images of the skin's superficial vascularisation. This study aims to investigate if and how the D-OCT measurement of chronic wounds can provide new information about the vascularisation during the healing process. We examined 16 venous ulcers over 16 weeks and evaluated the vessel morphology and density using D-OCT at the wound bed, borders, two centimetres adjacent to the wound und at non-ulcerated skin on the contralateral leg. In D-OCT scans clumps were unique and the most common vessel type in the wound area of venous ulcers, whereas lines and serpiginous vessels were the most common in non-ulcerated skin. At the wound border mottle and cluster patterns occurred more frequently. Healthy skin showed a significant increase of mesh pattern. Vessel density significantly increased at the wound area compared to non-ulcerated skin. During the healing process the wound border showed the most vascular changes while only an increase in curves was observed in the wound centre. Non-healing wounds had fewer dots and blobs at the borders, fewer dots, coils, clumps, lines and serpiginous vessels at the centre and fewer dots in adjacent skin. Temperature analysis showed higher temperatures in non-ulcerated skin, followed by the wound margin and centre. Non-healing wounds showed the lowest temperatures in the wound centre. These results highlight the non-invasive use of D-OCT for the examination and monitoring of wound healing in chronic venous ulcers. D-OCT imaging of blood vessels may offer the potential to detect disorders of wound healing at an early stage, differentiate ulcers of different genesis and to tailor more individualized, patient-oriented therapy.

Effect of Hyaluronic Acid Iontophoresis on Healing of Chronic Venous Ulcer

Purpose: The purpose of the study is to evaluate the effect of hyaluronic acid iontophoresis on healing of chronic venous ulcer. Methods: Forty patients of both genders suffering from chronic venous ulcer in area below the knee and above the ankle with area (5-20 cm2) with less than 50% necrotic tissue participated in this study. Their ages ranged from (45 to 60) years. They were selected from Vascular Surgery Department, Al Ahrar Teaching Hospital between June 2022 and January 2023. Patients were divided randomly into 2 equal groups; each one had 20 patients. Group (A) received Hyaluronic acid iontophoresis 1 session per day, 3 sessions per week, for 4 weeks, and follow up 4 weeks after the end of the treatment. In addition to conventional, medical treatment and traditional care. Group (B) received conventional medical treatment and traditional care (ulcer cleansing, debridement, dressing, compression, medication, exercise). Measurements were done by photographic digital camera for wound Surface area (WSA) and wound volume using saline injection into a wound cavity before treatment and after 4 weeks of treatment. Results: The findings of this study indicated significant decrease in WSA and wound volume after treatment in all groups A, B (p<0.001) at day 60 post treatment. There was significant decrease in ulcer surface area and ulcer volume at day 60 post treatment of study group (group A) compared with that of control group (group B) (p = 0.001).Conclusion: Hyaluronic acid iontophoresis for 6 weeks is an effective and safe adjuvant therapy in treatment of unhealed venous ulcers through accelerating wound healing, reducing Wound Surface Area (WSA) and wound volume. Keywords: Hyaluronic Acid, iontophoresis, Chronic Venous leg ulcers, Wound Healing

Active legs: Impact of physical activity as an adjuvant treatment in the healing of venous ulcers in primary care: a RCT protocol study

BackgroundVenous ulcers usually present a torpid evolution with a negative impact on patients’ quality of life. In primary care, they account for 2.5% of nursing consultations and their treatment represents high costs for national health systems. These patients usually have a low level of physical activity, with muscle pump dysfunction of the lower limbs, which may improve with increased physical activity. The purpose of this study is to analyse the effectiveness of a structured intervention involving physical activity and exercise (Active Legs) as an adjuvant treatment in improving healing of chronic venous ulcers at 3 months follow-up.MethodsA randomized, multicentre clinical trial. A total of 224 individuals receiving primary nursing care with a diagnosis of venous ulcer, with a diameter of 1 cm or greater and an ankle-brachial index between 0.8 and 1.3, able to comply with the study requirements and consenting to participate, will be sequentially included (112 per group).Both groups will receive the standard treatment in primary care, with cleansing, debridement and healing in a moist environment together with multilayer compression therapy. The intervention group will also receive a structured educational intervention involving lower limb physical exercise and daily ambulation guidelines.The primary response variables will be complete healing –understood as complete and sustained epithelialisation for at least 2 weeks– and time to healing. The secondary variables will be degree of healing, ulcer area, quality of life, pain and variables related to the healing process, prognosis, and recurrences. Sociodemographic variables, adherence to treatment and satisfaction variables will also be recorded. Data will be collected at baseline, at 3 months and at 6 months follow-up. Survival analysis (Kaplan-Meier and Cox) will be performed to measure primary effectiveness. Intention-to-treat analysis.DiscussionIf the intervention is effective, a cost-effectiveness analysis could be conducted and implemented as an additional intervention in the usual venous ulcer treatment in primary care.Trial registrationNCT04039789. [https://ClinicalTrials.gov]. 07/11/2019.

Effect of Endovenous Laser Ablation Along With Compression Therapy on Chronic Venous Ulcer Healing.

Introduction Chronic venous insufficiency is a major cause of morbidity, and there is a paucity of data regarding its epidemiology due to the lack of a central wound registry. In this study, we aimed to study the time for healing of the ulcer and compliance with compression therapy (CT) following endovenous laser ablation (EVLA) ± ultrasound-guided foam sclerotherapy (UGFS) along with CT in patients with chronic venous ulcers. Methods This prospective observational study was conducted from January 2020 to June 2021 after obtaining institutional ethical committee clearance. Patients with chronic venous ulcers (>six weeks to <six months duration) were included in this study. Demographic details, venous duplex findings, and duration of ulceration were noted. All patients underwent EVLA (Biolitec® 1470 nm) ± UGFS and CT. The patients were followed up weekly till the healing of the ulcer, followed up at one month, three months, and then at six monthly intervals to look for recurrence. Venous clinical severity score (VCSS) at presentation and follow-up, compliance with CT, rate of ulcer healing at six months, and recurrence rates at two years of follow-up were observed prospectively. Results The mean age of the study participants was 45.7±14.2 years, of which 42 (84%) were males. Ulcer size of <2 cm was present in 38%, 2-4 cmin 52%, and >4 cmin 10% of patients. A total of 38% of patients underwent only EVLA, and EVLA+UGFS were done in 62% of participants. The healing rate at six months follow-up was 92%, with the average time taken being 2.55±1.38 months. Those who remained with an unhealed ulcer at six months follow-up had anulcer size of >5 cmand an age of >50 years. Ninety-six percent of the patients were compliant with CT after an endovenous intervention. The recurrence rate at two years post-ablation was 6%. VCSS was 19.66±3.23 at presentation and 5.5±2.82 at six months of follow-up. Conclusion Endovenous ablation of superficial venous reflux along with CT is associated with a shorter healing time of venous ulcerations and reduced chances of recurrence.There is an improvement in VCSS score over the period of six months follow-up.

Efficacy of Ultrasound Guided Foam Sclerotherapy of Incompetent Ankle Perforators on Healing of Chronic Venous Ulcers with Deep Venous Reflux. (A Comparative Study)

Abstract Background Compression therapy is the standard of care for venous ulcers and chronic venous insufficiency, but the treatment of underlying venous disease to relieve venous hypertension appears to improve wound healing and to decrease recurrence. Benefits of saphenous ablation have been well demonstrated; however, evidence for the treatment of incompetent perforating veins is less clear. Objective To assess the benefit of ultrasound-guided sclerotherapy (USGS) of incompetent perforator on healing of chronic venous ulcers. Patients and Methods This is a prospective cohort study which is a double arm clinical study to assess the healing rate for patients after USGFS vs standard compression therapy of patients with incompetent perforators veins within 6 month. Results Our preliminary data add further weight to the suggestion that eradication of SVR by means of UGFS improves CVU outcomes when compared to compression alone. In this regard, UGFS appears to be more effective more than compression therapy does, therefore, appear the more attractive option in this elderly patient population. Furthermore, the follow-up data presented here does suggest long-term healing following UGFS probably requires careful follow-up and, if required. Encouraged by these promising early results the authors have embarked upon a larger study to look at the role of UGFS in the treatment of CVU in greater depth. Conclusion Ultrasound guided foam sclerotherapy of perforator incompetent veins is a welltolerated and effective outpatient procedure. This study presents a patient cohort with limited exclusion criteria, allowing a representative cross section of VLU in general. Because of its higher healing rate and lower RR compared to other therapeutic options, and the improvement in quality of life that it brings, this minimally invasive, easily repeatable procedure may become the treatment of choice for VLU. Foam sclerotherapy is a simple procedure, compared to surgical intervention, no hospitalization, no anesthesia, can be done in outpatient clinic and the patient can return home after 45 min and no work off period. The relative freedom from serious complications and its evident success, makes this modality as a possible candidate for being the first line treatment for venous ulcers.

Matrix metalloproteinase (MMP)-1 and MMP-2, but not COX-2 serve as additional predictors for chronic venous ulcer healing.

Chronic venous ulcers affect 1% of the adult population and are associated with a marked reduction in quality of life, especially if healing is prolonged. Several matrix metalloproteinases (MMPs) appear to be involved in the pathophysiology of chronic venous ulcer healing, but their exact role is still unclear. Cyclooxygenase-2 (COX-2) is an important enzyme in prostanoid synthesis, induced during inflammation in chronic venous ulcer. The first aim of our study was to compare the expression of MMP-1, MMP-2, and COX-2 in wound tissue to that in normal skin. The second aim was to observe the expression of the above factors in 29 chronic venous ulcers in 22 patients at the beginning and 4 weeks later in relation to healing rates and final healing outcome after 24 weeks. The enrolled population was divided into two groups, healed and non-healed wounds after 24 weeks. The intensity of expression of MMP-1, MMP-2 and COX-2 was assessed for each ulcer in paired wound biopsy samples and wound size measurements using laser triangulation at the beginning and after 4 weeks of observation. Initial healing rates in the first 4 weeks were calculated and proved to be an important predictive factor of healing in 24 weeks. Decreases in MMP-1 and MMP-2 after 4 weeks of observation were distinct, positive predictors for ulcer healing. Healing odds were 3.7 times higher for a decrease in MMP-1 and 2.1 times higher for a decrease in MMP-2 compared to the healing odds for a non-decrease in MMP-1 and MMP-2. In conclusion, a decrease in MMP-1 and MMP-2, but not COX-2, in wound biopsy samples after 4 weeks of observation can predict better healing of chronic venous ulcer.

Single ALA-PDT irradiation induces increase in mast cells degranulation and neuropeptide acute response in chronic venous ulcers: A pilot study.

The behavior of mast cells, their interaction with neuronal cells or nerve fibers, the expression of neuropeptides and the distribution of skin neuronal cells or nerve fibers after ALA-PDT treated vs untreated chronic wounds were investigated. Nineteen patients suffering from chronic venous ulcers (CVU) were enrolled in this study. Skin samples from wound bed before and after irradiation with ALA-PDT were taken. All specimens were anonymized and analyzed by immunohistochemistry. After completion of ALA-PDT, mast cells showed an increase of degranulation index and expression of NGF and VIP. Amongst all the neuronal mediators tested, all except for SP showed an increase of cellular expression after ALA-PDT therapy. Our study shows preliminary evidences that ALA-PDT induces rapid recruitment of mast cells around dermal fibers in chronic venous ulcers. This finding is also associated with increase in expression of multiple peripheral neuropeptides except SP by skin neuronal cells. ALA-PDT may promote healing of chronic venous ulcers via stimulation of quiescent peripheral nerves, possibly after release of inflammatory molecules by degranulating mast cells.

Role of topical phenytoin in treatment of chronic venous ulcers

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Venous leg ulcers are a common cause of significant morbidity leading to compromised quality of life and a huge financial burden on patients. Apart from the systemic therapy, many topical agents are available to accelerate healing in these ulcers. Topical phenytoin is one such agent which has been studied for promotion of wound healing. The aim of the study was to study the efficacy of topical phenytoin in healing of chronic venous ulcers.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; 56 patients of chronic venous ulcer were randomly divided in two groups of 28 each. First group was given daily dressing of phenytoin in normal saline (group A) and second group was given only normal saline dressing (group B) for a period of 8 weeks. After 8 weeks the reduction in size of ulcer was measured, on the basis of which results were calculated.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The mean age of the patients was 50.29±13.37 years. The mean duration of ulcer was 10.13±4.66 weeks. Compared to the conventional normal saline dressing, patients given phenytoin and normal saline dressing showed far greater tendency to heal (p=0.02). 35.7% patients in phenytoin group showed excellent response out of which 21.42% achieved complete healing, while in normal saline group only 14.28% patients showed excellent response and none of patient showed complete healing. No significant adverse effects were observed in either of the group.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Topical phenytoin appears to be a safe, easy, effective and inexpensive option to promote wound healing and can be used as an adjuvant for treatment of chronic venous ulcers. Further studies with larger population are merited.&lt;/p&gt;

LEV 3. Intravenous Sulodexide Promotes Wound Healing in Chronic Venous Ulcers: A New Perspective in Treatment

LEV 3. Intravenous Sulodexide Promotes Wound Healing in Chronic Venous Ulcers: A New Perspective in Treatment

Value of combined exercise and ultrasound as an adjunct to compression therapy in chronic venous leg ulcers

IntroductionChronic venous leg ulcers are very difficult to treat and take very long time to heal. Compression therapy remains the mainstay of venous ulcer conservative treatment.AimThe aim of this study was to evaluate the effectiveness of combined therapeutic exercises and ultrasound as an adjunct to compression therapy for the treatment of chronic venous leg ulcers.Settings and designThis study is a prospective randomized case-controlled one.Patients and methodsSeventy-two patients with chronic venous leg ulcers were recruited from outpatient clinics. Weallocated patients to four groups of 15 patients each. Group I was treated with therapeutic exercise program in addition to compression therapy. Group II was treated with underwater ultrasound and compression therapy. Group III was treated with therapeutic exercises as in group I and underwater ultrasound as in group II, in addition to compression therapy. Group IV was treated with compression therapy. The duration of follow-up was 12 weeks. Treatment outcome was assessed using the visual analogue scale for pain, ulcer size, the pressure ulcer scale for healing, maximum ankle dorsiflexion and plantar flexion using a plastic goniometer.ResultsVenous ulcer healing was greatest in patients receiving combined exercise and ultrasound in addition to compression therapy. Combined therapeutic exercises and ultrasound were well tolerated and no adverse reactions were noted. Patients receiving therapeutic exercises alone or ultrasound alone showed lesser degrees of improvements. No significant improvements were observed in any variable in patients who received compression therapy alone.ConclusionCombined prescription of exercises and ultrasound as an adjunct to compression therapy would be a more effective means of promoting chronic venous ulcer healing, when standard compression therapy have failed. It is safe, easy and well tolerated and should be considered as adjunctive therapy in patients with venous leg ulcers.

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only four healed the ulcers with an mean of 72 months (range: 2-204) (p=0.94). There seems to be an association between an optimal anticoagulation therapy with Warfarin monitored by INR and wound healing rates in thrombophilic patients with chronic venous ulcers. Further research is warranted. The authors have no conflict of interest.

Interventions for helping people adhere to compression treatments for venous leg ulceration.

Chronic venous ulcer healing is a complex clinical problem that requires intervention from skilled, costly, multidisciplinary wound-care teams. Compression therapy has been shown to help heal venous ulcers and to reduce recurrence. It is not known which interventions help people adhere to compression treatments. This review is an update of a previous Cochrane review. To assess the benefits and harms of interventions designed to help people adhere to venous leg ulcer compression therapy, to improve healing and prevent recurrence after healing. In June 2015, for this first update, we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched trial registries, and reference lists of relevant publications for published and ongoing trials. There were no language or publication date restrictions. We included randomised controlled trials (RCTs) of interventions that aim to help people with venous leg ulcers adhere to compression treatments compared with usual care, or no intervention, or another active intervention. Our main outcomes were ulcer healing, ulcer recurrence, quality of life, pain, adherence to compression therapy and number of people with adverse events. Two review authors independently selected studies for inclusion, extracted data, assessed the risk of bias of each included trial, and assessed overall quality of evidence for the main outcomes in 'Summary of findings' tables. One randomised controlled trial was added to this update making a total of three. One ongoing study was also identified.One trial (67 participants) compared a community-based Leg Club® that provided mechanisms for peer-support, assistance with goal setting and social interaction with home-based care. There was no clear difference in healing rates at three months (12/28 people healed in Leg Club group versus 7/28 in home-based care group; risk ratio (RR) 1.71, 95% confidence interval (CI) 0.79 to 3.71); or six months (15/33 healed in Leg Club group versus 10/34 in home-based care group; RR 1.55, 95% CI 0.81 to 2.93); or in quality of life outcomes at six months (MD 0.85 points, 95% CI -0.13 to 1.83; 0 to 10 point scale). The Leg Club may lead to a small reduction in pain at six months, that may not be clinically significant (MD -12.75 points, 95% CI -24.79, -0.71; 0 to 100 point scale, 15 point reduction is usually considered the minimal clinically important difference) (low quality evidence downgraded for risk of selection bias and imprecision).Another trial (184 participants) compared a community-based, nurse-led self-management programme of six months' duration promoting physical activity (walking and leg exercises) and adherence to compression therapy via counselling and behaviour modification (Lively Legs®) with usual care in a wound clinic. At 18 months follow-up, there were no clear differences in healing rates (51/92 healed in Lively Legs group versus 41/92 in usual care group; RR 1.24 (95% CI 0.93 to 1.67)); rates of recurrence of venous leg ulcers (32/69 with recurrence in Lively Legs group versus 38/67 in usual care group; RR 0.82 (95% CI 0.59 to 1.14)); or adherence to compression therapy (42/92 people fully adherent in Lively Legs group versus 41/92 in usual care group; RR 1.02 (95% CI 0.74 to 1.41)). The evidence from this trial was also downgraded to low quality due to risk of selection bias and imprecision.A single study compared patient education delivered via video with education delivered by text (pamphlet). However, no outcomes relevant to this review were reported.We found no studies that investigated other interventions to promote adherence to compression therapy. It is unclear whether interventions designed to help people adhere to compression therapy improve venous ulcer healing and reduce recurrence. There is a lack of trials of interventions that promote adherence to compression therapy for venous ulcers.

Pharmacological adjuncts for chronic venous ulcer healing: a systematic review.

The aim of this study was to systematically review the current evidence and determine whether there is a clinical benefit for using pharmacological agents as adjunctive treatment for chronic venous ulcers. A systematic review of the MEDLINE and EMBASE (from 1 January 1947 through 15 August 2013) and Cochrane databases (from inception through 15 August 2013) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were all randomised controlled trials investigating pharmacological adjuncts for the treatment of venous ulcers with a minimum sample size of 20 patients for each treatment arm. Ten relevant articles were identified; one pilot randomised controlled trial and four Cochrane reviews were included. Pentoxifylline, aspirin, sulodexide, mesoglycan, flavonoids, thromboxane A2 antagonist (ifetroban), zinc, prostaglandin and prostacyclin analogues were the drugs reviewed. Pentoxifylline was found to be more effective than placebo in terms of complete ulcer healing or in causing a significant improvement (greater than 60% reduction in ulcer size) (RR 1.70, 95% CI 1.30 to 2.24). Aspirin and flavonoids show potential to be effective adjuncts but methodological shortcomings and issues with bias limit the validity of results from trials involving each of these drugs, respectively. There was no significant difference between placebo and Ifetroban and likewise pooled results from trials investigating sulodexide and zinc showed no benefit in comparison to placebo. Many systemic pharmacological agents have been investigated as adjuncts to venous ulcer healing; however, pentoxifylline (400 mg, three times a day) is currently the only drug that has promising evidence to support its use. Other compounds are in early stage research.

The Effect of a Connexin43-Based Peptide on the Healing of Chronic Venous Leg Ulcers: A Multicenter, Randomized Trial

The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways.

Iliac vein stenting as an adjunct to four layer dressing in the healing of chronic venous ulcers

Abstract Venous ulcers are a major source of morbidity to the patient and result in significantly poorer quality of life [1] . Faster healing of these ulcer results in relief of significant financial burden to the patient and the society. Compression therapy continues to be the mainstay in the treatment of venous ulcers. However a group of patients have non-healing or recurrent ulcer inspite of the above treatment. We present two cases of refractory non-healing venous ulcers which were successfully treated with a combination of four layer dressing and iliac vein stenting.

Medical significance of endothelial glycocalyx. Part 2: Its role in vascular diseases and in diabetic complications

Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans and glycoproteins attached to the vascular endothelial luminal surface. Shredding of glycocalyx appears as an essential initial step in the pathophysiology of atherosclerosis and microangiopathic complications of diabetes mellitus, as well as in chronic venous disease. Atherosclerosis risk factors, as hypercholesterolemia (LDL), hyperglycemia, inflammation, salt excess and altered shear stress can damage glycocalyx. This lead to endothelial dysfunction and allows LDL and leukocytes to filtrate to the subendothelial space initiating atheroma plaque formation. Degradation of glycocalyx in diabetes mellitus is mainly due to oxidative stress and enables protein filtration (albuminuria) and endothelial disorder of microangiopathy. Chronic venous hypertension brings to altered shears stress which results in shredded glycocalyx, this allows leukocytes to migrate into venous wall and initiate inflammation leading to morphologic and functional venous changes of the chronic venous disease. Treatment with glycosaminoglycans (sulodexide) prevents or recovers the damaged glycocalyx and several of its consequences. This drug improves chronic venous disease and promotes healing of chronic venous ulcers. It has also been useful in peripheral arterial obstructive disease and in diabetic nephropathy with albuminuria.

Comparative effectiveness of surgical interventions aimed at treating underlying venous pathology in patients with chronic venous ulcer.

Chronic venous ulcers (CVUs) remain the leading causes for nonhealing wounds in the lower extremities. Although multilayer compression dressing remains the treatment gold standard, there are various surgical procedures aimed at healing CVUs with little or no evidence on the efficacy of these treatment methods. We conducted a systematic review of the effects of various surgical treatments for CVUs, in terms of ulcer healing rates, complete time to heal, recurrence rates, mortality, pain, and quality of life. We searched MEDLINE, EMBASE, the Cochrane Central Register for Controlled Trials, and the Cumulative Index for Nursing and Allied Health Literature databases from January 1980 through July 2012. We included studies that compared a surgical procedure with multilayer compression therapy or another surgical procedure among patients with CVUs. We also included studies without a comparison group if they were of sufficient quality. Two independent reviewers screened titles, abstracts, and articles for eligibility. Two reviewers extracted data on study design, applicability, results, and quality. We identified 10,676 citations, of which 22 studies (23 publications) were included. Eight studies (six randomized controlled trials, two cohorts) compared a surgical procedure with compression. Fourteen studies evaluated different surgical interventions. Adding superficial vein ligation and stripping to compression did not improve wound-healing rate. However, the recurrence rate was 50% reduced when surgery corrected the underlying superficial venous pathology (moderate to high strength of evidence [SOE]). Adding subfascial endoscopic perforator surgery with superficial vein surgery tocompression does not improve the healing rate of venous ulcers or reduce the recurrence rate except for medial and large ulcers (high SOE). The SOE was insufficient to support a conclusion about the effects of sclerotherapy when added to compression in healing CVUs. There was insufficient evidence on the surgical treatment of CVUs secondary to deep venous reflux and venous obstruction. We are unable to draw conclusions about the effects of surgical procedures on mortality, pain, and quality of life. Our ability to draw conclusions on most surgical techniques is limited due to poorly designed and executed studies, with no uniformity of treatment methods, follow-up or reporting, and lack of randomization. We found some evidence to suggest superficial vein ligation and stripping mayreduce the risk of wound recurrence, but these surgical techniques are infrequently performed. The newer minimally invasive techniques lack evidence. Randomized controlled trials for the endovenous procedures used today for treating CVUs are needed.

Doxycycline speeds up healing of chronic venous ulcers

Venous ulcers are common, with an overall prevalence of up to 2% in the general population of western countries, and have significant socioeconomic impact. Matrix metalloproteinases (MMPs) are involved in the alteration of extracellular matrix that could lead to venous ulceration. Sixty-four patients with venous ulcers were recruited in a 22-month period. All patients were subjected to the most appropriate treatment considering also the patient's wishes (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 32 persons in each (groups A and B). Patients of group A in addition to the basic treatment, described above, received the administration of oral low doses of doxycycline 20 mg b.i.d. for 3 months, whereas patients of group B received basic treatment only. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a higher healing rate compared with group B. In group B, the lower healing rate was related to higher levels of MMP-9; neutrophil gelatinase-associated lipocalin and vascular endothelial growth factor, documented in plasma; wound fluid and biopsies executed and compared between both groups. Pharmacological treatments, as doxycycline administration, which by means of its immunomodulatory and anti-inflammatory actions, through the inhibition of MMP, could improve extracellular matrix functioning and represent a possible solution to support wound healing.

Low molecular weight heparin improves healing of chronic venous ulcers especially in the elderly

Venous ulcers are common, especially in the elderly, accounting for more than 50% of all lower extremity ulcers with important socioeconomic problems. Improving extracellular matrix functioning, by heparin administration, seems to be a way to support wound healing. A total of 284 patients with venous ulcers were recruited in a 4-year period. All patients were subjected to the most appropriate treatment after considering their preference (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 142 persons in each (group A and group B as cases and controls, respectively). Patients of group A, in addition to the basic treatment as described earlier, received administration of nadroparin 2850 IU/0.3 ml through subcutaneous injection once a day for 12 months, whereas group B patients received basic treatment alone. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a healing rate of 83·80% at 12 months, whereas that of group B was 60·56%. Results by age group surprisingly showed that the group of older patients took the most advantage from long-term treatment with low molecular weight heparin; this group also had lowest recurrence rate.

A Comparative Study of Cell Therapy and Fibrin Glue Applied to Chronic Venous Ulcers

The hypothesis is that cell therapy with autologous keratinocytes promotes healing of chronic venous ulcers that failed to respond to other forms of treatment. This is a randomized study in which 31 patients with chronic venous ulcers participated, totaling 38 venous ulcers. Thirty one ulcers were included in Group 1 (G1) treated with autologous keratinocytes applied at the ulcers’ base with autologous fibrin scaffold. Group 2 (G2) included 7 ulcers treated with autologous fibrin glue only. The ulcers were evaluated with digital photography and computer image analysis [area and wound healing rate (WHR)] over 90 days. The duration of ulcers from the G1 was 118 months on average and in G2 the average was 114 months without any difference. In relation to the initial size of ulcers, both groups were similar considering the mean, SD and median respectively: G1 (18; 27; 5.6 cm2) and G2 (19.5; 0.11; 0.29 cm2). The medians of WHR in G1 and G2 have got significant differences between groups. Considering only the wounds that reached WHR larger than 0.4 (40% rate of healing), in the G1, 29% of ulcers reached it at the 30th day, 58% at the 45th, 77% at the 60th, 84% at the 75th and 90% at the 90th day while in the G2 only 14% (one ulcer) reached it at the 30th day remaining steady until the 90th day when only one more ulcer reached this rate (28.6%). The median of procedures was 2 for G1 and 3 for G2. These findings showed the relevant efficacy of cell therapy with autologous keratinocytes applied with autologous fibrin glue scaffold achieving high rates of healing from the thirtieth day of follow-up and becoming larger by the ninetieth day. In contrast, the autologous fibrin glue applied lonely in G2 did not improve the wound healing significantly. The cell therapy with autologous keratinocytes applied with autologous fibrin scaffold promotes greater healing of chronic venous ulcers than autologous fibrin glue only, particularly large recalcitrant ulcers that do not respond to conventional treatment.