BIOBOARD

Chronic venous leg ulcers are common and cause considerable burden of disease for affected patients with significant costs for health care systems worldwide. The complex pathophysiology of chronic venous leg ulcers is still not entirely understood. In addition, reliable pathogenic and/or prognostic parameters are not known. Published data suggest that patients with chronic venous leg ulcers reveal congenital or acquired thrombophilia. We examined the serum Lipoprotein (a) [Lp(a)] level, a proatherogenic and prothrombotic risk factor, in patients with chronic venous leg ulcers (n=210, stratified into patients with postthrombotic syndrome or without) and in a healthy control group (n=341). Forty-two percent of all patients, compared with 20% of healthy controls, revealed significantly increased Lp(a) serum concentrations above 0.3 g/L. Furthermore, 49% without postthrombotic syndrome but only 35% with postthrombotic syndrome showed increased Lp(a) levels. The increase of Lp(a) level was significantly different between all three groups (p<0.001). There was no correlation of Lp(a) levels and CRP values in all groups. Based on these data, it is conceivable that Lp(a) plasma level is a novel pathogenic parameter for chronic venous leg ulcers. Elevated concentrations may contribute to the pathogenesis through induction of thrombogenic microcirculatory dysregulations, impaired extravascular fibrinolysis, or other mechanisms like proinflammatory effects.

Low Factor XIII (FXIII) activity has been reported in the blood of patients with chronic venous leg ulcer (CVU). In vivo studies have described increased wound healing in CVU patients treated with FXIII concentrate, and in vitro studies have shown increased regenerative capacity in FXIII-treated fibroblasts. In addition, a common G-to-T polymorphism in the FXIIIA-subunit gene (V34L) significantly increases the activity and modifies the cross-linking properties of the FXIII molecule and this variant has been investigated as a protective factor against thrombosis, a recognized risk factor for CVU establishment. Therefore, the role of FXIII levels, FXIII V34L, FVR506Q, and FIIG20210A, common gene polymorphisms in the pathogenesis of CVU was investigated. Ninety-one patients with CVU and 195 healthy controls (91 of them sex- and age-matched) were PCR-genotyped for the FXIIIV34L, FVR506Q, and FIIG20210A substitutions and FXIIIA-subunit levels were determined by immuno-electrophoresis. The extent of the venous ulcer surface in patients was measured by computer software. The allele frequency and the genotype distribution of the FXIII polymorphism did not show significant differences between the whole group of cases and controls as well as prothrombin variants did. On the contrary, the FVR506Q variant (FV Leiden) allele was more frequent in patients, yielding a significant OR value of 5.93 (95 percent CI, 1.83-19.17; p= 0.003). Considering only CVU cases secondary to a post-thrombotic syndrome (n= 24), FV Leiden yielded a greater OR value of 16.08 (95 percent CI, 4.33-59.6; p < 0.0001). When the CVU cases were stratified by the three possible FXIII genotypes, a significant trend toward a lower mean value of the ulcerated area was clearly evident as the number of the polymorphic alleles (L34) increased in the genotype of patients (VV = 11.9 cm(2,)+/- 23.6; VL = 6.1 cm(2,)+/- 6.9; LL = 4.1 cm(2,)+/- 2.8; p= 0.01). On the other hand, FXIIIA antigen levels were similar between CVU cases and matched controls, but 11 percent of cases had FXIII deficiency (FXIIIA </= 0.65 U/ml; p= 0.003) and they showed a greater mean extension of the lesion if compared with the remaining cases without FXIIIA deficiency (14.5 cm(2), +/- 20.2 vs. 9.0 cm(2), +/- 6.3; p= 0.08). We conclude that FXIII antigen levels and FXIII V34L polymorphism may play a crucial role in the complex cascade of CVU pathophysiology, being significantly related to the CVU progression and extension because of the direct effects they have on the FXIII molecular activity.

Chronic venous leg ulcer (CVLU) arises as a chronic venous insuficiency complication and is a major cause of morbidity throughout the world. Our hypothesis is that the CVLU exudate composition is a biochemical representation of the wound clinical state. Then, Fourier Transform Infrared (FTIR) spectroscopy could be a useful and less-invasive technique to study the clinical state of the ulcer. For this, the aim of this work was to perform a spectral characterization of the exudate from CVLU using FTIR spectroscopy to identify potential healing markers. 45 exudate samples from CVLU, 95% of the strains isolated from CVLU in planktonic and biofilm phenotypes and other related biological samples such as human plasma, serum, urine, blood cells, urea, creatinine, glucose and albumin were studied by FTIR spectroscopy. According to the vibration frequency of biomolecules’ (lipids, proteins, nucleic acids and carbohydrates) characteristic bonds in the infrared region, different spectral windows were selected and spectral areas of each window were measured. Besides, Savitzky–Golay second derivatives were obtained for all spectra and peaks from each standardized window were detected. FTIR spectroscopy allowed identification of sample types (exudate, plasma, serum, urine) as each one presents a unique relative composition and ratios range. Also, this technique could be useful to identify bacteria in the phenotypic-ulcer state and allows differentiation of whether bacteria are in the bio?lm or planktonic form which is unlikely by conventional methods. In this work we found some spectral markers (areas, peaks) that allow identification of several parameters in the exudate such as (a) total cellularity, (b) inflammatory cell load, (c) bacterial load, (d) fibrin amount, and (e) inflammatory proteins. Because the measured areas or founded peaks are concentration-dependent this method could also serve to measure them. Therefore, FTIR spectroscopy could be useful to evaluate patient evolution as all these exudate parameters represent critical negative markers for wound healing.

Healing of Chronic Arterial and Venous Leg Ulcers With Systemic Electromagnetic Fields

The definition of the venous ulcer

Chronic Venous Leg Ulcers (CVLUs) are vascular diseases and require complex wound care from a patient, wound, health personnel and dressing factors. Cadexomer Iodine (CI) and Polyhexamethylene Biguanide (PHMB) are antimicrobial and broad-spectrum wound washing fluids. The uncontrolled infection will complicate wound healing due to bacteria or plankton from the biofilm stage to infection, which causes a long healing time. Purpose: to determine the effectiveness of the combination of Polyhexamethylene biguanide and Cadexomer Iodine on venous leg ulcer wound healing. Methods: This study is a case study using CVLUs as a sample, with pre-test and post-test designs, patients with CVLUs received topical antimicrobial CI and PHMB interventions on wounds for 7 weeks. The sample in this study used one sample with a pre-post treatment design for seven days.. The instrument uses the Bates Jensen Wound Assessment Tool. Results: The combination of CI and PHMB was shown to improve the healing of CVLUs by controlling bacterial infection in wounds. In the 2nd week, the wound was 26cm x 15cm, the slough was reduced, and the red base wound increased. In the 3rd week, the wound was stage 4, and the granulation increase was 75%. In the 7th treatment, the wound size scale increased 7cmx4cm, the wound became stage 2, and a significant increase in epithelialization was 75%. Conclusion: The combination of PHMB and CI has been shown to control infection at the biofilm stage to critical colonization, reduce odour and significantly control infection, and increase granulation and epithelialization in CVLUs

The purpose of this study was to systematically review the literature on the benefits and harms of advanced wound dressings on wound healing, mortality, quality of life, pain, condition of the wound bed, and adverse events for patients with chronic venous leg ulcers as compared with treatment with compression alone. We searched for primary studies in the databases of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature(®) from January 1980 through July 2012. Each study title, abstract, and full article was evaluated by two independent reviewers. Thirty-seven studies met our specific search criteria, although most evidence was of low or insufficient quality. Cellular dressings, collagen, and some antimicrobial dressings may improve healing rates of chronic venous leg ulcers vs. compression alone or other dressings. Limited data were available on other outcomes. The poor quality of the literature limits conclusions and necessitates future, well-conducted studies to evaluate the effectiveness of advanced wound dressings on chronic venous ulcers.

Chronic venous insufficiency has been recognized as one of the most common health problems experienced by the older adult. Unfortunately, an all too frequent complication of this circulatory disorder is the development of a venous leg ulcer. Chronic venous leg ulcers can have a negative impact on the general well-being of the older adult and costs to the health care system associated with the treatment of chronic venous leg ulcers are substantial. A review of the literature revealed that no qualitative research studies have been conducted in relation to the older adult's experience of living with a chronic venous leg ulcer. Rather, there are a few anecdotes in relation to the venous leg ulcer experience that have been written from a health care professional's perspective. Thus, in the context of chronic venous leg ulcers, the explanatory model of the client has not yet been documented. The purpose of this study was to gain an understanding of the chronic venous leg ulcer experience from the perspective of community-dwelling older adults. The phenomenological approach to qualitative methodology was used for this study. This approach seeks to describe human experience as it is lived. Six individuals, over sixty-five years of age, agreed to participate in this study; they were currently being seen or had been seen on a regular basis by a home care nurse for treatment of their chronic venous leg ulcers. Participants were each interviewed twice and these interviews were guided by open-ended questions. Analysis of the data revealed that participants moved through three sequential phases of a "living with a chronic venous leg ulcer continuum” as they lived with chronic venous insufficiency and chronic venous leg ulcers. In the first phase of the continuum, participants experienced the effects of living with their chronic circulatory disorder. They encountered losses in relation to physical endurance, gratifying activities, companionship, and predictability in their lives. In addition to experiencing loss, the participants encountered a gain as a result of having a chronic venous leg ulcer: the emotional support afforded them by home care nurses and homemakers involved in their care. In the second phase of the continuum, participants evaluated how significantly their chronic venous leg ulcers had affected their lives. In so doing, the participants either appraised their leg ulcer as having been detrimental to their quality of life, or inconsequential with regard to living a satisfying life. The key factor that influenced the appraisal that participants made of their leg ulcers was whether or not their circulatory disorder had impacted on a primary source of satisfaction in their life. In the third and final phase of the continuum, the participants coped with their circulatory disorder in one of two ways. Each participant either "put their life on hold" if they had appraised their leg ulcer as being detrimental to them, or they "got on with life" if they had appraised their leg ulcer as being inconsequential. The implications for nursing practice, education, and research were identified in light of the research findings.

Frequency rhythmic electrical modulation system (FREMS) is an innovative type of transcutaneous electrotherapy used in a rehabilitation setting for the treatment of pain, especially in diabetic patients. In a randomized clinical trial, we tested the hypothesis that FREMS is effective in the treatment of chronic and painful venous leg ulcers in 20 older patients. Group A (10 patients) received FREMS and topical treatment, whereas group B (10 patients) received topical treatment alone. Over a period of 3 consecutive weeks, 15 treatment sessions were done for each group. Wound healing and tissue repair were evaluated with the Visitrack digital planimetry system and photos. Pain was evaluated using the Visual Analogic Scale (VAS). The measurements were done at baseline and after 5, 10, and 15 days of treatment, with follow-up measurements after 15 and 30 days from the last treatment session. Group A showed a statistically significant decrease in ulcer area during the treatment and follow-up. The VAS score showed a statistically significant decrease after 5 and 10 days of treatment. Group B showed a statistically decrease in ulcer area after 5, 10, and 15 days of treatment with a reduction of VAS score only at 15 days of follow-up. At the end of the treatment, the comparison of the change in ulcer area and the change in VAS score of each group showed a statistically significant difference between groups, suggesting the therapeutic and analgesic efficacy of FREMS in reducing pain and area of chronic venous leg ulcers in older adults. Further investigation is needed to determine its reproducibility in larger case series or randomized clinical trials with longer follow-up periods.

To investigate the clinical performance and safety of a new silver-containing wound-contact layer, Physiotulle -Ag (Coloplast), in the treatment of chronic venous leg ulcers with delayed healing and signs of critical colonisation. This was an open prospective non-comparative multicentre clinical study. Patients were treated for four weeks with Physiotulle -Ag, which was covered by Alione Hydrocapillary Dressing (Coloplast). Thirty patients were recruited into the study. One ulcer healed after three weeks of treatment. The mean relative ulcer area reduced by 55% after four weeks. Over the study period the mean amount of healthy granulation tissue increased from 26% to 62%, and the mean amount of fibrin decreased from 63% to 32%. The ratio of malodorous wounds was 50% at inclusion, 20% after one week and 3% after four weeks. The dressing was considered easy or very easy to apply in 100% and easy to remove in 89% of dressing evaluations. The dressing combination showed good exudate-management properties. Incidence and severity of maceration, erythema and eczema decreased during the study and no device-related adverse events were recorded. Physiotulle -Ag is safe and easy to use in chronic venous leg ulcers in which healing is delayed and with signs of critical colonisation.

Within chronic wounds, the relationship between the clinical diagnosis of infection and bacterial/immuno-inflammatory responses is imprecise. This study prospectively examined the interrelationship between clinical, microbiological, and proinflammatory biomarker levels between chronic venous leg ulcers (CVLUs) and diabetic foot ulcers (DFUs). Wound swabs and fluids were collected from CVLUs (n = 18) and DFUs (n = 15) and diagnosed clinically as noninfected or infected; and qualitative/quantitative microbiology was performed. CVLU and DFU fluids were also analyzed for cytokine, growth factor, receptor, proteinase/proteinase inhibitor; and oxidative stress biomarker (protein carbonyl, malondialdehyde, and antioxidant capacity) levels. While no correlations existed between clinical diagnosis, microbiology, or biomarker profiles, increasing bacterial bioburden (≥10(7) colony-forming unit/mL) was associated with significant alterations in cytokine, growth factor, and receptor levels. These responses contrasted between ulcer type, with elevated and decreased cytokine, growth factor, and receptor levels in CVLUs and DFUs with increasing bioburden, respectively. Despite proteinase biomarkers exhibiting few differences between CVLUs and DFUs, significant elevations in antioxidant capacities correlated with increased bioburden in CVLU fluids, but not in DFUs. Furthermore, oxidative stress biomarker levels were significantly elevated in all DFU fluids compared with CVLUs. This study provides further insight into the contrasting disease-specific host responses to bacterial challenge within infected CVLUs and DFUs.

Background Surgical correction of isolated superficial venous reflux in ulcerated legs reduces short-term recurrence rates but little is known about long-term recurrence. This study aimed to assess the influence of venous reflux pattern and appropriate surgical correction on ulcer healing and long-term recurrence. Methods Patients with chronic leg ulcers were assessed prospectively at a one-stop clinic over 4 years to July 1999. Patients with an ankle: brachial pressure index (ABPI) greater than 0·85, including those with diabetes mellitus and rheumatoid arthritis, were treated with weekly four-layer bandaging in community leg ulcer clinics. Venous duplex studies in all ulcerated legs assessed venous reflux pattern and patients with isolated superficial reflux were offered surgery. Patients were advised to wear class 2 elastic compression stockings after healing and were reviewed at 1, 3, 6 and 9 months, and at 1, 2 and 3 years. Ipsilateral ulceration following healing was designated as recurrence. Results Some 766 ulcerated legs in 689 patients were assessed; 633 legs had an ABPI greater than 0·85. Venous duplex assessment revealed 8 per cent of these legs to have pure deep, 38 per cent pure superficial and 43 per cent a mixed reflux pattern. Ten per cent of legs had no demonstrable reflux. Some 131 of 241 limbs with pure superficial reflux underwent surgery. Healing rates at 12 and 24 weeks for all legs with an ABPI greater than 0·85 were 48 and 68 per cent respectively. Neither venous pattern nor surgery affected ulcer healing rates. Overall 1-, 2- and 3-year recurrence rates for venous ulcers were 25, 31 and 38 per cent respectively. The influence of venous reflux pattern and surgery on ulcer recurrence is summarized in Table. Conclusion Ulcer healing rates are not influenced by venous reflux pattern or surgery. Surgical correction of superficial venous reflux in the presence of chronic leg ulceration reduces long-term ulcer recurrence rates.

Pain medicine practices vary across different regions within a country and between countries. The objective of the survey was to study the variation in interventional pain medicine practices in the United Kingdom (UK) and the United States (US). A survey was designed in 2019 on Survey Monkey®. Pain physicians from the UK and the US were invited to respond. A total of 120 responses were received from pain physicians in the UK and 122 from the US. Twenty-six percent and 90% of pain physicians in the UK and US, respectively, are in full-time pain medicine practice. There was marked variation in the utilization of diagnostic medial branch blocks before performing radiofrequency denervation (RFD) between the UK and the US. In the UK, 42% of pain physicians, and 50% in the US, use a 20-gauge or a 22-gauge radiofrequency needle for lumbar RFD. Around 30% to 50% of pain physicians, both in the UK and the US, discontinued antithrombotic agents before medial branch blocks at all the spinal levels. Around 50% of pain physicians in the UK and US are stopping anticoagulants before lumbar and cervical RFD. Over 95% of UK and US respondents stopped antithrombotic agents for interlaminar and transforaminal epidural injections along the spine. At the lumbar level, 51% of pain physicians in the UK and 47% in the US use a particulate steroid for the initial lumbar transforaminal epidural injection (TFESI); and 4% and 14% in the UK and US, respectively, use a particulate steroid for initial cervical TFESI. Eight percent of pain physicians in the UK and 20% from the US would switch to a particulate steroid if the initial TFESI with a nonparticulate steroid did not provide satisfactory pain relief. Ten percent of pain physicians from the United Kingdom and 20% from the US believed that this switch provides better pain relief. Interventional pain physicians from the UK and the US were invited to respond. This may not reflect global practice. Our survey has highlighted the wide variation in interventional pain medicine practices both in the UK and the US. The relevant governing bodies in the UK and in the US should encourage clinicians to use at least an 18-gauge radiofrequency needle for RFD at the lumbar level. Discontinuing antithrombotic agents for the lumbar medial branch block is not justifiable. Pain physicians must discuss the advantages and disadvantages of using a nonparticulate over a particulate steroid preparation with the patient before performing TFESI as a standard procedure during the consenting process. Antithrombotic agents, epidural steroid, medial branch blocks, pain practice variations, particulate and nonparticulate steroids, radiofrequency denervation, spinal interventions.

Background: The treatment of chronic venous leg ulcer (CVLU) is a major challenge. Much scientific advancement was made. Chitosan, derived from N-deacetylation of chitin, has been successfully used to promote wound healing. Silver nanoparticles (AgNPs) are used as bactericides. The aim of this work is to evaluate the efficacy and safety of chitosan alone or that impregnated with AgNPs compared to traditional compression bandage dressing in the treatment of CVLU. Materials and Methods: Thirty-eight CVLU patients completed the treatment for 3 months. They were treated with compression bandage and categorized into three groups: Group A included 12 patients used chitosan impregnated with the AgNPs, Group B included 11 patients used chitosan alone, and Group C included 15 patients used compression bandage alone. For all patients, routine investigations, lower limbs Duplex ultrasound and bacterial culture and sensitivity from the ulcers before and after treatment were done. Results: The healing of ulcers in the treated groups was mostly apparent in Groups A and C. Conclusions: Chitosan impregnated with AgNPs can be a hopeful treatment for CVLU. However, compression bandage alone is also effective for the treatment of CVLU.

The prevalence and incidence of chronic venous leg ulcers (CVLUs) are increasing worldwide, as are the associated financial costs. Although it has long been known that their underlying etiology is venous insufficiency, the molecular aspects of healing versus nonhealing, as well as the psychoneurologic symptoms (PNS; pain, cognitive dysfunction, fatigue, depression, and anxiety) associated with CVLUs remain understudied. In this biobehaviorally focused review, we aim to elucidate the complex mechanisms that link the biological and molecular aspects of CLVUs with their PNS. Innovations in "omics" research have increased our understanding of important wound microenvironmental factors (e.g., inflammation, microbial pathogenic biofilm, epigenetic processes) that may adversely alter the wound bed's molecular milieu so that microbes evade immune detection. Although these molecular factors are not singularly responsible for wound healing, they are major components of wound development, nonhealing, and PNS that, until now, have not been amenable to systematic study, especially over time. Further, this review explores our current understanding of the molecular mechanisms by which the immune activation that contributes to the development and persistence of CVLUs also leads to the development, persistence, and severity of wound-related PNS. We also make recommendations for future research that will expand the field of biobehavioral wound science. Biobehavioral research that focuses on the interrelated mechanisms of PNS will lead to symptom-management interventions that improve quality of life for the population burdened by CVLUs.