Multidisciplinary expert consensus statements and recommendations for use of hypochlorous acid as a solution for negative pressure wound therapy with instillation.

BACKGROUND: HOCl (eg, pHAp) preserved solutions have antimicrobial properties and are considered safe and effective for wound management. NPWTi-d (or NPWTi) is an established adjunctive wound modality for a variety of wound etiologies in various anatomic locations in which an instillate solution dwells on the surface of the wound to assist in wound bed preparation. A variety of solutions have been used, including 0.9% normal saline wound cleansers and antiseptics. pHAp is growing in popularity as the solution of choice for NPWTi-d. OBJECTIVE: To evaluate consensus statements on the use of NPWTi-d with pHAp. METHODS: A 15-member multidisciplinary panel of expert clinicians in the United States, Canada, and France convened in person in April 2023 in Washington, D.C. and/or corresponded later to discuss 10 statements on the use of pHAp with NPWTi-d. The panelists then replied "agree" or "disagree" to each statement and had the option to provide comments. RESULTS: Ten consensus statements are presented, along with the proportion of agreement or disagreement and summary comments. Although agreement with the statements on NPWTi-d with pHAp varied, the statements appear to reflect individual preferences for use rather than concerns about safety or efficacy. CONCLUSION: The consensus indicates that NPWTi-d with pHAp can have a beneficial effect in wound care.

Scars.

Wound healing occurs as a response to disruption of the epidermis and dermis. It is an intricate and well-orchestrated response with the goal to restore skin integrity and function. However, in hundreds of millions of patients, skin wound healing results in abnormal scarring, including keloid lesions or hypertrophic scarring. Although the underlying mechanisms of hypertrophic scars and keloid lesions are not well defined, evidence suggests that the changes in the extracellular matrix are perpetuated by ongoing inflammation in susceptible individuals, resulting in a fibrotic phenotype. The lesions then become established, with ongoing deposition of excess disordered collagen. Not only can abnormal scarring be debilitating and painful, it can also cause functional impairment and profound changes in appearance, thereby substantially affecting patients' lives. Despite the vast demand on patient health and the medical society, very little progress has been made in the care of patients with abnormal scarring. To improve the outcome of pathological scarring, standardized and innovative approaches are required.

A Retrospective Self-Controlled Study Evaluating the Prophylactic Effects of CACIPLIQ20 on Postsurgical Scars.

Background: CACIPLIQ20 (OTR3, Paris, France) is a medical device used for the treatment of chronic skin ulcers. It contains a heparan sulfate mimetic that accelerates tissue healing by stabilizing matrix proteins and protecting heparin-binding growth factors. In humans, an open self-controlled study suggested that the topical application of CACIPLIQ20 optimizes skin healing following surgery. Objectives: To expand previous findings using a different CACIPLIQ20 administration regimen. Methods: Twenty-four females were referred for breast-reduction surgery. Each patient had their own control with 1 CACIPLIQ20-treated and 1 saline-treated control breast. The treated side (right or left) was randomly assigned by the operating surgeon. Scar appearance was assessed by 6 independent raters using a global visual scar comparison scale based on scar photographs. All raters were blinded toward the CACIPLIQ20-treated side. Results: The follow-up period following surgery ranged from 1 to 12 months with a median follow-up of 6 months. Overall, there was a mean improvement of 15.2% (SD = 26.7) in favor of CACIPLIQ20 (P = .016). On the CACIPLIQ20-treated side, the mean score per patient was above 20% in 11 patients and above 30% improvement in 8 cases. In contrast, only 3 patients were considered improved by at least 20% on the control side and only 1 above 30%. A comparison of different application regimens suggested that the best trend was obtained with a single administration of CACIPLIQ20 at Day 0. Conclusions: In conclusion, CACIPLIQ20 could represent an interesting scar prophylactic therapy, based on a single administration at the time of surgery, and without any known adverse effects.

Topical Erythropoietin Accelerates Wound Closure in Patients with Diabetic Foot Ulcers: A Prospective, Multicenter, Single-Blind, Randomized, Controlled Trial.

The diabetic foot ulcer (DFU) is a major disabling complication of diabetes mellitus. Growing evidence suggests that topical erythropoietin (EPO) can promote wound healing. The aim of this study is to clinically assess the efficacy of a proprietary topical EPO-containing hydrogel for treating DFUs. We conducted a randomized, controlled trial in 20 patients with DFUs. After a 14-day screening period, the DFUs of 20 eligible participants who fulfilled the inclusion criteria were randomly assigned (1:1) to either a 12-week of daily treatment with topical EPO and standard-of-care (SOC) or SOC treatment alone. The DFUs were assessed weekly until week 12. The primary outcome was 75% ulcer closure or higher. After 12 weeks of treatment, 75% ulcer closure was achieved in 6 of the 10 patients whose DFUs were treated with topical EPO and in one of the 8 patients whose DFUs were treated with SOC alone. The mean area of the DFUs that were treated with topical EPO and SOC was significantly smaller than those treated with SOC alone (1.2 ± 1.4 cm2 vs. 4.2 ± 3.4 cm2; p = 0.023). Re-epithelialization was faster in the topically EPO-treated DFUs than in the SOC-treated DFUs. There were no treatment-related adverse events. We conclude that topical EPO is a promising treatment for promoting the healing of DFUs. Clinical Trial Registration number: NCT02361931.

Evaluation of Fluorescent Light Energy for the Treatment of Acute Second-degree Burns.

INTRODUCTION: The use of photobiomodulation has been proposed to improve wound healing for the last two decades. Recent development in photobiomodulation has led to the development of a novel biophotonic platform that utilizes fluorescent light energy (FLE) within the visible spectrum of light for healing of skin inflammation and wounds. MATERIALS AND METHODS: In this article, FLE was used in preliminary analysis on 18 case studies of acute second-degree burns and in a pilot study using an ex vivo human skin model. Efficacy of FLE on wound healing and tissue remodeling was evaluated by monitoring improvements in the treated tissues, assessing pain for the patients, and by performing human genome microarray analysis of FLE-treated human skin samples. RESULTS: Healing was reported for all 18 patients treated with FLE for acute second-degree burns without reported adverse effects or development of infections. Furthermore, preliminary ex vivo skin model data suggest that FLE impacts different cellular pathways including essential immune-modulatory mechanisms. CONCLUSIONS: The results presented in this article are encouraging and suggest that FLE balances different stages of wound healing, which opens the door to initiating randomized controlled clinical trials for establishing the efficacy of FLE treatment in different phases of wound healing of second-degree burns.

Challenges and Management in Wound Care.

SUMMARY: Wounds have been one of the most prominent pathologies since the beginning of humanity. For the last 5 decades, a drastic improvement of healing has been observed, thanks to new medical devices based on fluid aspiration capacities and the development of negative pressure wound therapy. Negative-pressure wound therapy was initially designed for a double action, fluid aspiration and mechanical stimulation of wound edges by a foam. Successive technical evolutions of negative pressure wound therapy were declined since 1997 when Argenta and Morykwas first presented their solution. The adjunct of instillation in 2009 was considered as the first interactive dressing, allowing topical wound solutions to sequentially reach the wound, in alternance with negative pressure. Other devices based on the same principle were designed to prevent postoperative infections when placed over a suture after surgery. This long evolution could enhance the armamentarium of possible solutions, considerably reducing the wound healing time.

A pilot multi-centre prospective randomised controlled trial of RECELL for the treatment of venous leg ulcers.

Venous leg ulcers (VLUs) have a significant impact on approximately 3% of the adult population worldwide, with a mean NHS wound care cost of £7600 per VLU over 12 months. The standard care for VLUs is compression therapy, with a significant number of ulcers failing to heal with this treatment, especially with wound size being a risk factor for non-healing. This multicentre, prospective, randomised trial evaluated the safety and effectiveness of autologous skin cell suspension (ASCS) combined with compression therapy compared with standard compression alone (Control) for the treatment of VLUs. Incidence of complete wound closure at 14 weeks, donor site closure, pain, Health-Related Quality of Life (HRQoL), satisfaction, and safety were assessed in 52 patients. At Week 14, VLUs treated with ASCS + compression had a statistically greater decrease in ulcer area compared with the Control (8.94 cm2 versus 1.23 cm2 , P = .0143). This finding was largely driven by ulcers >10 to 80 cm2 in size, as these ulcers had a higher mean percentage of reepithelialization at 14 weeks (ASCS + compression: 69.97% and Control: 11.07%, P = .0480). Additionally, subjects treated with ASCS + compression experienced a decrease in pain and an increase in HRQoL compared with the Control. This study indicates that application of ASCS + compression accelerates healing in large venous ulcers.

A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study.

OBJECTIVE: Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone. RESEARCH DESIGN AND METHODS: Patients with diabetes and chronic DFUs were randomized (double-blind) to either active TWO2 therapy or sham control therapy-both in addition to optimal SOC. The primary outcome was the percentage of ulcers in each group achieving 100% healing at 12 weeks. A group sequential design was used for the study with three predetermined analyses and hard stopping rules once 73, 146, and ultimately 220 patients completed the 12-week treatment phase. RESULTS: At the first analysis point, the active TWO2 arm was found to be superior to the sham arm, with a closure rate of 41.7% compared with 13.5%. This difference in outcome produced an odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P = 0.010. After adjustment for University of Texas Classification (UTC) ulcer grade, the OR increased to 6.00 (97.8% CI 1.44, 24.93), P = 0.004. Cox proportional hazards modeling, also after adjustment for UTC grade, demonstrated >4.5 times the likelihood to heal DFUs over 12 weeks compared with the sham arm with a hazard ratio of 4.66 (97.8% CI 1.36, 15.98), P = 0.004. At 12 months postenrollment, 56% of active arm ulcers were closed compared with 27% of the sham arm ulcers (P = 0.013). CONCLUSIONS: This sham-controlled, double-blind randomized controlled trial demonstrates that, at both 12 weeks and 12 months, adjunctive cyclical pressurized TWO2 therapy was superior in healing chronic DFUs compared with optimal SOC alone.

Negative pressure wound therapy with instillation: International consensus guidelines update.

The use of negative pressure wound therapy with instillation and dwell time (NPWTi-d) has gained wider adoption and interest due in part to the increasing complexity of wounds and patient conditions. Best practices for the use of NPWTi-d have shifted in recent years based on a growing body of evidence and expanded worldwide experience with the technology. To better guide the use of NPWTi-d with all dressing and setting configurations, as well as solutions, there is a need to publish updated international consensus guidelines, which were last produced over 6 years ago. An international, multidisciplinary expert panel of clinicians was convened on 22 to 23 February 2019, to assist in developing current recommendations for best practices of the use of NPWTi-d. Principal aims of the meeting were to update recommendations based on panel members' experience and published results regarding topics such as appropriate application settings, topical wound solution selection, and wound and patient characteristics for the use of NPWTi-d with various dressing types. The final consensus recommendations were derived based on greater than 80% agreement among the panellists. The guidelines in this publication represent further refinement of the recommended parameters originally established for the use of NPWTi-d. The authors thank Karen Beach and Ricardo Martinez for their assistance with manuscript preparation.

Complex Wound Healing Outcomes for Outpatients Receiving Care via Telemedicine, Home Health, or Wound Clinic: A Randomized Controlled Trial.

Use of telemedicine has expanded rapidly in recent years, yet there are few comparative studies to determine its effectiveness in wound care. To provide experimental data in the field of telemedicine with regard to wound care, a pilot project named "Domoplaies" was publicly funded in France in 2011. A randomized, controlled trial was performed to measure the outcomes of patients with complex wounds who received home wound care from a local clinician guided by an off-site wound care expert via telemedicine, versus patients who received in-home or wound clinic visits with wound care professionals. The publicly funded network of nurses and physicians highly experienced in wound healing was used to provide wound care recommendations via telemedicine for the study. The healing rate at 6 months was slightly better for patients who received wound care via telemedicine (61/89; 68.5%) versus wound care professional at home (38/59; 64.4%) versus wound care clinic (22/35; 62.9%), but the difference was not significant (P = .860833). The average time to healing for the 121/183 wounds that healed within 6 months was 66.8 ± 32.8 days for the telemedicine group, 69.3 ± 26.7 for the wound care professional at home group, and 55.8 ± 25.0 days for the wound care clinic group. Transportation costs for the telemedicine and home health care groups were significantly lower than the wound clinic group, and death rate was similar between all the 3 groups (P < .01). Telemedicine performed by wound healing clinicians working in a network setting offered a safe option to remotely manage comorbid, complex wound care patients with reduced mobility.

Interim Results of the Remede d'Or Study: A Multicenter, Single-Blind, Randomized, Controlled Trial to Assess the Safety and Efficacy of an Innovative Topical Formulation of Erythropoietin for Treating Diabetic Foot Ulcers.

Objective: To inform on the interim results of the Remede d'Or study, which is a prospective, multicenter, single-blind, randomized, controlled clinical study on the safety and efficacy of RMD-G1, a topical carbopol-based hydrogel with a fibronectin matrix whose active pharmaceutical ingredient is erythropoietin (EPO), for treating diabetic foot ulcers (DFU). Approach: The trial will comprise 20 patients with type 2 diabetes mellitus with neuroischemic DFUs who will be randomized into two groups: (1) a control group in which standard-of-care (SOC) will be used to treat the DFUs, and (2) a test group in which SOC and RMD-G1 will be used to treat the DFUs. On day 0, all participants will be randomized to receive either RMD-G1 and SOC treatment or SOC alone. The primary endpoint of the study is complete closure of the DFU within the 12-week study period following daily treatments and dressing changes. Results: Interim results reveal that those DFUs which were treated with RMD-G1 responded positively: there was a significant reduction in the wound areas. In contrast, the condition of those DFUs which were treated with only SOC deteriorated. Innovation: To date, no topical therapies with proven efficacy for treating DFUs exist. Topical application of EPO-based RMD-G1 in conjunction with SOC to a DFU accelerates their healing and closure. Conclusions: The interim results of this trial indicate that topical RMD-G1 is a safe adjunctive therapy to SOC, which accelerates the closure of a DFU. RMD-G1 is safe pharmaceutical because EPO has a proven safety profile.

Collagen regeneration template in the management of full-thickness wounds: a prospective multicentre study.

OBJECTIVE: To evaluate the tolerance and healing rate of a collagen regeneration template in covering full-thickness wounds, including rate of adverse events. METHOD: In this prospective, multicentre study, patients with a full-thickness wound underwent two-stage surgery consisting of implantation of a collagen regeneration template followed by a split-thickness skin graft (STSG). Patients were followed-up for 12 months. Adverse events arising from either the implantation or STSG were evaluated. RESULTS: Of the 33 patients included in the study, 29 completed the full follow-up period. During the study, 13 adverse events occurred at the treated wound site, as reported by 11 patients during follow-up. These included local infection (n=5), a diffuse infection (n=1) and non-infectious seroma under the silicon layer (n=1). The mean percentage of take of the collagen template at 21±7 days after implantation was 81.2% of the treated surface. The mean percentage of take of STSG at 28 days after grafting was 84.4% of grafted surface. STSG was successful in 28 patients, but was completely rejected at 12 months for one patient. Mean functional score at 12 months, as evaluated by the treating surgeons, was 76.8/100 and mean aesthetic score was 62.7/100. CONCLUSION: This study found use of a collagen regeneration template to be a safe procedure for the coverage of full thickness-wounds.

Hidradenitis Suppurativa: A Systematic Review and Meta-analysis of Therapeutic Interventions.

Hidradenitis suppurativa is a chronic inflammatory condition that affects skin regions bearing apocrine glands. Although hidradenitis suppurativa is difficult to treat and cure, the currently available treatments are directed toward managing the lesions and associated symptoms. This review presents an evidence-based outline of the available treatment options. We searched four electronic databases and extracted data from retrieved studies for qualitative or quantitative analysis. Meta-analysis was conducted using the comprehensive meta-analysis software to generate pooled standardized mean differences or risk ratios. Numerous medical treatments are available for hidradenitis suppurativa such as antibiotics, retinoids, antiandrogens, immunosuppressive and anti-inflammatory agents and radiotherapy for early lesions. Adalimumab, an anti-tumor necrosis factor antibody, was superior to placebo in reducing Sartorius score (standardized mean difference = -0.32, confidence interval [-0.46, -0.18], P < 0.0001) and pain (risk ratio = 1.42, confidence interval [1.07, 1.9], P = 0.02), when given weekly (not every other week). Combination therapies (such as antibiotics and hyperbaric oxygen therapy) have been tested, which have shown promising results that are yet to be confirmed. Based on the quality of evidence, the most recommended treatments for hidradenitis suppurativa include adalimumab and laser therapy. Surgery (either by simple excision or complete local excision followed by skin graft) is the first choice for intractable disease presenting in the late stages. However, the evidence on most of these treatments is deficient and further randomized trials are needed to establish the most efficient therapies for hidradenitis suppurativa management.

Impregnated acetate gauze compared with lipido-colloid contact layer at dressing removal pain: a single-blind cross-over randomised control trial.

OBJECTIVE: To evaluate the performance of Jelonet Plus (JP) and UrgoTul (UT), assessing pain at dressing removal when managing acute or chronic wounds at granulation and epithelialisation stages. METHODS: This was a randomised, multicentre, controlled single-blinded study using a cross-over design. Hospitalised and ambulatory patients presenting with non-infected acute or chronic wounds (at least 40% of wound area of ≤100cm2 covered with granulation tissue) were randomly allocated to be treated with either JP or UT dressings applied according to a standardised local care procedure for two days. At the following visit, patients received the other dressing for a second 2-day period. Pain was evaluated after two days of dressing application and immediately after its removal using a 100mm Visual Analog Scale (VAS). A pain level >30mm was considered as clinically relevant. A lower limit of -12% was determined as the threshold necessary to demonstrate the non-inferiority of JP compared to UT. RESULTS: For the 99 patients completing the study, a difference of 7.9% was observed in favour of JP (83.8% JP versus 75.9% UT) for pain immediately after dressing removal (VAS score < 30mm) with a confidence interval (CI) lower limit of -2.6%, demonstrating non-inferiority (pre-defined limit of -12%). Concerning pain at dressing removal, a difference of 19.6% was observed in favour of JP (81.6% versus 62.0%; p=0.029 for superiority analysis), with a CI lower limit ranging from 2.4% to 38.9%. Therefore, superiority could be concluded. A statistically significant period effect was detected (p=0.003) with fewer patients experiencing pain after the second period day 2 (D2) to day 4 (D4) than the first day 0 (D0) to D2. A statistically significant cross-over effect was also detected (p=0.047), with fewer patients experiencing pain when JP was applied first followed by UT. This suggests a carry-over effect thus preventing a full cross-over design analysis. Adherence of the dressing was less frequent with the JP than the UT dressing (2.0% JP versus 6.9% with UT). CONCLUSION: Non-inferiority of pain at dressing removal was demonstrated with JP. Superiority on this criteria was non-significant but we found adherence of the dressing to the wound bed to be more rare.

Management of infected diabetic wound: a scoping review of guidelines.

Background: Various international guidelines and recommendations are available for management of diabetic foot infections. We present a review of the guidelines and recommendations for management of these infections. Methods: A systematic literature search was conducted through MEDLINE, CENTRAL, EMBASE, LILACS, DARE, and national health bodies. Based on the review of fifteen documents, we present details on the importance of suspecting and diagnosing skin, superficial infections, and bone infections in diabetics. Results: The guidelines recommend classifying the infections based on severity to guide the treatment. While antibiotics have shown the best results, other treatments like hyperbaric oxygen therapy and negative wound pressure have been debated. It is suggested that a team of specialists should be in-charge of managing the infected wounds. Infectious Diseases Society of America (IDSA) 2012 guidelines are widely followed world-over. All guidelines and reviews have consistent suggestions on the assessment of the severity of infection, diagnosis, start, selection, and duration of antibiotic therapy. Conclusions: It is reasonable to conclude that the IDSA 2012 guidelines are commonly followed across the world. There is a consensus among the Australian guidelines, Canadian guidelines, IDSA 2012, National Institute for Health and Care Excellence (NICE) 2015, and International Working Group on the Diabetic Foot (IWGDF) 2016 guidelines on the management of infected wounds for patients with diabetes mellitus.

REAL-WORLD CLINICAL EVALUATION AND COSTS OF TELEMEDICINE FOR CHRONIC WOUND MANAGEMENT.

BACKGROUND: Chronic wounds are frequent, affect quality of life, and increase care costs. Telemedicine provides potential for effective wound care management, especially for the monitoring of complex wounds at home. OBJECTIVES: The objective of the present study was to determine the clinical effects and costs of telemedicine for the follow-up of complex chronic wounds from the perspective of the public health insurance. The study ran over a period of 9 months. METHODS: We conducted a prospective, pragmatic, open-label, observational study and carried out a cost-effectiveness analysis. A total of 116 patients with chronic wounds were assigned to their choice of two groups: telemedicine (N = 77) and traditional follow-up (control; N = 39). The primary outcome was the time to healing. Secondary outcomes included percentage of wounds reaching target objective, percentage of wounds healed completely, outpatient care costs, travel costs, and hospitalizations. RESULTS: Time to healing was shorter in the telemedicine group than in the control group (137 versus 174 days; p .05). Outpatient care and hospitalization costs were not significantly different. The main results in terms of economic savings were medical transport costs reimbursed by the French public health insurance, which were significantly lower in the telemedicine group. Telemedicine costs were found to be €4,583 less per patient compared with standard practice over 9 months. CONCLUSIONS: This trial suggests that telemedicine saves travel costs and results in a shorter healing time than traditional follow-up.