Bacterial protease activity as a biomarker to assess the risk of non-healing in chronic wounds: Results from a multicentre randomised controlled clinical trial.

Millions worldwide suffer from chronic wounds challenging clinicians and burdening healthcare systems. Bacteria impede wound healing; however, the diagnosis of excessive bacterial burden or infection is elusive. Clinical signs and symptoms of infection are inaccurate and unreliable. This trial evaluated a novel, point-of-care, lateral flow diagnostic designed to detect virulence factors released by the most common bacteria found in chronic wounds. A multicentre prospective cohort clinical trial examined the efficacy of a diagnostic test in detecting bacterial proteases taken from swab samples of chronic venous, arterial, pressure and mixed aetiology chronic wounds. Two hundred and sixty six wounds were included in the analysis of the study. The wounds were tested at the start of the study after which investigators were permitted to use whatever dressings they desired for the next 12 weeks. Healing status at 12 weeks was assessed. The presence of elevated bacterial protease activity decreased the probability of wound healing at 12 weeks. In contrast, a greater proportion of wounds were healed at 12 weeks if they had little or no bacterial protease activity at study start. In addition, the presence of elevated bacterial protease activity increased the time it takes for a wound to heal and increased the risk that a wound would not heal, when compared to the absence of bacterial protease activity. The results of this clinical trial indicate that bacterial protease activity, as detected by this novel diagnostic test, is a valid clinical marker for chronicity in wounds. The diagnostic test offers a tool for clinicians to detect clinically significant bacteria in real time and manage bacteria load before the clinical signs and symptoms of infection are evident.

Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled clinical trial.

OBJECTIVES: Perfusion and blood oxygen levels are frequently insufficient in patients with hard-to-heal wounds due to poor circulation, vascular disruption and vasoconstriction, reducing the wound's capacity to heal. This study aimed to investigate the effect of topical oxygen on healing rates in patients with hard-to-heal diabetic foot ulcers (DFUs) (i.e., non-responsive over four weeks). METHOD: This multicentre, open-label, community-based randomised clinical trial compared standard care (SOC) with or without continuous topical oxygen therapy (TOT) for 12 weeks in patients with DFUs or minor amputation wounds. SOC included debridement, offloading with total contact casting (TCC) and appropriate moisture balance. Primary endpoints were the number of patients to achieve complete wound closure and percentage change in ulcer size. Secondary endpoints were pain levels and adverse events. RESULTS: For the study, 145 patients were randomised with index ulcers graded Infectious Diseases Society of America (IDSA) 1 or 2, or Wagner 1 or 2. In the intention-to-treat analysis, 18/64 (28.1%) patients healed in the SOC group at 12 weeks compared with 36/81 (44.4%) in the SOC plus TOT group (p=0.044). There was a statistically significant reduction in wound area between the groups: SOC group mean reduction: 40% (standard deviation (SD) 72.1); SOC plus TOT group mean reduction: 70% (SD 45.5); per protocol p=0.005). There were no significant differences in changes to pain levels or adverse events. CONCLUSION: This study suggests that the addition of TOT to SOC facilitates wound closure in patients with hard-to-heal DFUs.

Efficacy and safety of a porcine peritoneum-derived matrix in diabetic foot ulcer treatment: a pilot study.

OBJECTIVE: A third of people with diabetes will develop a foot ulcer during their lifetime. The absence of pain secondary to neuropathy often leads to a delay in diagnosis and treatment. Diabetic foot ulcer (DFU) complications, such as infection and amputation, increase mortality and strain the financial resources of health systems across the world. Cellular and/or tissue products (CTPs) have played an important role in the closure of DFUs. Investigators continue to search for new CTPs that facilitate healing. The aim of this study was to assess the efficacy and safety of a porcine peritoneum-derived matrix in DFU treatment. METHOD: Patients with longstanding DFUs participated in this institutional review board-approved, multicentre, prospective pilot study evaluating the time to healing over 12 weeks. In addition to weekly assessments for wound size, investigators analysed bacterial burden using the MolecuLight procedure (MLiX) and bacterial protease (BPA) testing. Participants received a weekly application of Meso Wound Matrix Scaffold (MWM), a lyophilised porcine peritoneum-derived matrix (DSM Biomedical Inc., Exton, PA, US) for up to eight weeks. Descriptive statistics were chosen for this analysis. RESULTS: A total of 12 male patients and three female patients with an average age of 57 years were enrolled over a two-month period. The average wound duration was 30 weeks. Due to unrelated health issues, four participants were withdrawn. For the study endpoint of complete wound closure at 12 weeks, six (55%) of the remaining 11 patients achieved complete closure, and four (36%) patients healed during the 8-week treatment period. The average number of CTP applications was six. Patients who healed all had negative BPA by nine weeks and no fluorescence on MLiX, indicating low bacterial load. CONCLUSION: This small pilot study indicates that patients with longstanding DFUs may respond to a porcine peritoneal-derived CTP. In this study, the CTP appears to have inhibited bacterial growth in the wound; however, further research is needed.

Diagnostic Accuracy of Point-of-Care Fluorescence Imaging for the Detection of Bacterial Burden in Wounds: Results from the 350-Patient Fluorescence Imaging Assessment and Guidance Trial.

Objective: High bacterial load contributes to chronicity of wounds and is diagnosed based on assessment of clinical signs and symptoms (CSS) of infection, but these characteristics are poor predictors of bacterial burden. Point-of-care fluorescence imaging (FL) MolecuLight i:X can improve identification of wounds with high bacterial burden (>104 colony-forming unit [CFU]/g). FL detects bacteria, whether planktonic or in biofilm, but does not distinguish between the two. In this study, diagnostic accuracy of FL was compared to CSS during routine wound assessment. Postassessment, clinicians were surveyed to assess impact of FL on treatment plan. Approach: A prospective multicenter controlled study was conducted by 20 study clinicians from 14 outpatient advanced wound care centers across the United States. Wounds underwent assessment for CSS followed by FL. Biopsies were collected to confirm total bacterial load. Three hundred fifty patients completed the study (138 diabetic foot ulcers, 106 venous leg ulcers, 60 surgical sites, 22 pressure ulcers, and 24 others). Results: Around 287/350 wounds (82%) had bacterial loads >104 CFU/g, and CSS missed detection of 85% of these wounds. FL significantly increased detection of bacteria (>104 CFU/g) by fourfold, and this was consistent across wound types (p < 0.001). Specificity of CSS+FL remained comparably high to CSS (p = 1.0). FL information modified treatment plans (69% of wounds), influenced wound bed preparation (85%), and improved overall patient care (90%) as reported by study clinicians. Innovation: This novel noncontact, handheld FL device provides immediate, objective information on presence, location, and load of bacteria at point of care. Conclusion: Use of FL facilitates adherence to clinical guidelines recommending prompt detection and removal of bacterial burden to reduce wound infection and facilitate healing.

A Post-marketing Surveillance Study of Chronic Wounds Treated With a Native Collagen Calcium Alginate Dressing.

Chronic wounds (ie, wounds that fail to progress through a normal, orderly, timely sequence of repair) continue to pose significant clinical and economic burdens. A prospective, descriptive, 3-week post-marketing surveillance study was conducted across 3 wound care centers in the United States to evaluate the effectiveness of a collagen calcium alginate dressing on chronic wounds in conjunction with standard care (SC) practices (eg, offloading, debridement, compression) to support healing. Eligible participants had to be >18 years of age, have at least 1 chronic wound, and no known sensitivity to collagen. Demographic characteristics were recorded at the screening visit on case report forms. At each visit, wound-related pain was assessed using the Visual Analog Scale along with wound characteristics including size (using digital planimetry), wound exudate (minimal, moderate, heavy), and odor (none, mild). Participants were monitored for adverse events as well as infection based on signs and symptoms in and around the local wound bed, the deeper structures, and the surrounding skin. An intention-to-treat approach was used for all analyses. If an observation was missing, the last observation carried forward principle was used. For wounds that healed, pain and exudate were set to 0 (no pain/exudate) at visit 4. Descriptive, paired t tests and the Wilcoxon signed rank test were used to analyze the data. Of the 31 participants (15 men, 16 women, mean age 66.6 years), most (13, 42%) had a diabetic foot ulcer or venous leg ulcer (10, 32%); median duration of all wounds was 148 days. Thirty (30) patients completed the study. The mean number of comorbidities was 10.6 ± 6.3, and patients used a mean of 9.3 ± 5.64 prescription or over-the-counter medications. For all wounds combined, mean wound area was 4.8 ± 8.38 cm2 at baseline. At week 3, a decrease in wound area of 38.1% was noted (median: 45% ± 42.54; P = .006); 3 wounds healed completely. The change in wound exudate level from visit 1 to visit 4 was statistically significant (P = .006). No adverse events or infections occurred. In this population, the use of etiology-appropriate SC and a collagen calcium alginate dressing resulted in a decrease in wound area after 3 weeks of care. Longer-term studies to confirm these observations and controlled clinical studies to compare the effects of this dressing to other nongauze dressing treatments are needed.

Novel Multivalent Wound-Healing Ointment Provides Bioburden Control and Moisture Management: A Retrospective Registry Data Analysis.

OBJECTIVE: The purpose of this retrospective registry data analysis was to explore the effectiveness of a novel multivalent topical ointment (Terrasil Infection Control Wound Care Ointment; Aspiera Medical, Woonsocket, Rhode Island), containing a patented mineral complex and 0.2% benzethonium chloride in the treatment of nonhealing acute and chronic wounds. DESIGN: Aspiera Medical designed a registry to capture physician experiences and treatment results with Terrasil Infection Control Wound Care Ointment. Physicians were asked to enter deidentified patient data into an online registry. SETTING: Wound clinics in the United States were asked to participate in the registry. PATIENTS: Physicians at 4 wound clinics treated 30 patients (26 of whom completed the treatment) with various chronic wounds that had persisted for an average of 6 months and entered treatment data into the registry. INTERVENTIONS: Patients applied the ointment according to physician orders. Concurrent treatments used by patients included offloading, compression wraps, and dressings, such as collagen and calcium alginate. Patients were treated until complete wound closure or lost to follow-up. MAIN OUTCOME MEASURES: Physicians calculated each patient's percentage wound reduction at each visit. MAIN RESULTS: Thirty patients were entered into the registry. Pretreatment and posttreatment measurements were available for 26 of them. Patients achieved an average surface area reduction of 84% in a mean of 23 days' treatment. CONCLUSION: The antimicrobial and moisturizing ointment studied appears to be effective in promoting wound closure in a variety of acute and chronic wounds. Wounds studied included diabetic foot ulcers, venous leg ulcers, venous stasis ulcers, surgical infections, burns, and insect bites. The results of this registry data analysis will be used to inform planned clinical trials.

Defining a new diagnostic assessment parameter for wound care: Elevated protease activity, an indicator of nonhealing, for targeted protease-modulating treatment.

It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil-derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2-4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies.

A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers.

Venous leg ulcers produce significant clinical and economic burdens on society and often require advanced wound therapy. The purpose of this multicenter, randomized, controlled study is to evaluate the safety and efficacy of one or two applications of dehydrated human amnion/chorion membrane allograft and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. The primary study outcome was the proportion of patients achieving 40% wound closure at 4 weeks. Of the 84 participants enrolled, 53 were randomized to receive allograft and 31 were randomized to the control group of multilayer compression therapy alone. At 4 weeks, 62% in the allograft group and 32% in the control group showed a greater than 40% wound closure (p = 0.005), thus showing a significant difference between the allograft-treated groups and the multilayer compression therapy alone group at the 4-week surrogate endpoint. After 4 weeks, wounds treated with allograft had reduced in size a mean of 48.1% compared with 19.0% for controls. Venous leg ulcers treated with allograft had a significant improvement in healing at 4 weeks compared with multilayer compression therapy alone.

Macrodystrophia lipomatosa of a fifth digit: a case report.

UNLABELLED: Macrodystrophia lipomatosa (MDL) is a rare, nonhereditary, congenital malformation that primarily affects the proliferation of mesenchymal structures. It presents with localized macrodactyly of one or more digits. The characteristic pathology is associated with hypertrophic fibroadipose tissues, more so to the plantar aspect of the foot. This condition can pose a threat to vascular supply, innervation, and even joint function. We present a single case of a 4-year-old male patient who presented with progressive enlargement of a unilateral left fifth digit since birth. The patient became increasingly symptomatic. Amputation was the selected treatment, and on pathological review of the specimen, the diagnosis of MDL was confirmed. The patient is approximately 1 year postoperative and has recovered uneventfully with an improved quality of life. The purpose of this article is to raise awareness of this condition with an emphasis on diagnosis through ancillary imaging results. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case report.