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.

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.

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.

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.

Antibiotic therapy of diabetic foot infections: A systematic review of randomized controlled trials.

Diabetic foot infection is a common diabetic complication that may end in lower limb amputation if not treated properly. We performed this systematic review to assess the clinical efficacy of different antibiotic regimens, whether systemic or topical, in the treatment of moderate to severe diabetic foot infections. We searched Medline, Web of Science, SCOPUS, Cochrane CENTRAL, and ScienceDirect for randomized controlled trials that evaluated the efficacy of antibiotic regimens in moderate to severe diabetic foot infections. The primary outcome of interest was the clinical efficacy (cure/improvement rates) of the regimens. We included 16 trials (4,158 patients) in this review, from which we extracted 10 comparisons: some trials compared systemic antibiotics to each other, others compared systemic to topical agents, while one study compared the combined topical and systemic agents to systemic antibiotics alone. Qualitative analysis of the findings of these studies showed that: (1) pipracillin/tazobactam was superior to ertapenem in severe infections (clinical resolution rate: 91.5% compared with PIP/TAZ 97.2%, p ≤ 0.04), but had similar efficacy in moderate infections, (2) ertapenem was more effective than tigecycline in moderate to severe infections (absolute difference -5.5, [95% CI -11.0, 0.1]), (3) the adjuvant use of topical agents with systemic antibiotics improved the outcomes, compared with systemic antibiotics alone (p = 0.024), (4) the rates of recurrence and re-ulceration were significantly lower in patients using the amino-penicillin regimen, compared with those using oral/intravenous ofloxacin, and (5) lower rates of complications accompanied the imipenem/cilastatin regimen, compared with the pipracillin/tazobactam regimen (p = 0.13). In conclusion, data from the included studies showed better results for ertapenem when compared with tigecycline; however, it was inferior to pipracillin/tazobactam in severe infections. The adjuvant use of topical agents improves the efficacy of systemic antibiotics in diabetic foot infection.

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.

Failure rates of artificial dermis products in treatment of diabetic foot ulcer: A systematic review and network meta-analysis.

Diabetic foot ulcer (DFU) is a frequent complication in diabetic patients, occurring in up to 25% of those affected. Among the treatments available to clinicians, the use of bioengineered skin substitutes is an attractive alternative. Artificial dermis functions as a matrix, covering the wound and supporting healing and reconstruction of the lost tissue. This study was aimed at reviewing the use of five regeneration matrices (namely, Integra, Nevelia, Matriderm, Pelnac, and Renoskin) as reported by clinical trials. We searched Medline, Embase, ISI Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases for relevant studies. Risk of failure rates was analysed by relative risk ratio method and complete ulcer healing was studied using network meta-analysis. Thirteen studies (12 randomized clinical trials and one cohort study) were eligible for analysis. The network meta-analysis based on a single study for Matriderm and 12 studies for other products showed that Matriderm was statistically inferior in achieving complete ulcer healing, as compared to all other products combined. In the second phase analysis, which was limited to three studies using artificial dermis products, there was a 57% reduction in the risk of reepithelialization failure for DFU patients who used Matriderm or Pelnac, compared to those who used Pelnac with basic fibroblast growth factor spray or skin grafting. The data showed an overall low failure rate suggesting that these bioengineered skin products provide a suitable support and microenvironment for healing of DFUs with low ulcer recurrence rates. This systematic review with meta-analysis highlights the pressing need for more studies investigating the safety, efficacy and failure rates of regeneration matrices in the treatment of DFUs.

Novel foam dressing using negative pressure wound therapy with instillation to remove thick exudate.

We describe our experience with a novel foam dressing architecture in tandem with negative pressure wound therapy and instillation (NPWTi-d) for removing viscous wound exudate and infectious materials. A retrospective review was conducted of the outcomes of 21 patients who received NPWTi-d using a reticulated open cell foam instillation dressing with through holes (ROCF-CC) designed to facilitate the removal of thick wound exudate and infectious materials. NPWTi-d with ROCF-CC was used to treat large complex chronic wounds with viscous wound exudate that contained substantial areas of devitalised tissue. Debridement was performed as appropriate or available. NPWTi-d with ROCF-CC assisted in loosening, solubilising and detaching viscous exudate, dry fibrin, wet slough and other infectious materials. Percent surface area of black non-viable tissue and yellow fibrinous slough was reduced to ≤ 10% in 18/21 (85·7%) and 12/21 (57·1%) wounds, respectively, after an average of 1-3 applications (3-9 days) of NPWTi-d with ROCF-CC. Preliminary evidence suggests that adjunctive use of NPWTi-d with ROCF-CC may help clean large, complex wounds when complete surgical debridement is not possible or appropriate and/or when areas of slough and non-viable tissue remain present on the wound surface.

Clinical recommendations and practical guide for negative pressure wound therapy with instillation.

Effective wound management involves a comprehensive assessment of the patient and the wound to determine an optimal wound treatment plan. It is critical to identify and address factors that may impair wound healing, prior to selecting the most appropriate therapy for each patient. Negative pressure wound therapy (NPWT) is a well-established advanced therapy that has been successful in adjunctive management of acute and chronic wounds. In recent years, the introduction of topical wound solution delivery in combination with NPWT has provided further benefits to wound healing. A commercially available system now offers automated, volumetric control of instilled topical wound solutions with a dwell time in combination with NPWT (NPWTi-d; V.A.C. VeraFlo Therapy, KCI, an Acelity company, San Antonio, TX). This NPWTi-d system differs from other instillation systems in that a timed, predetermined volume of topical wound solution is intermittently delivered (versus continuously fed) and allowed to dwell in the wound bed (without NPWT), for a user-selected period of time before NPWT is resumed. This added accuracy and process simplification of solution delivery in tandem with NPWT have prompted use of NPWTi-d as first-line therapy in a wider subset of complex wounds. However, considerably more research is required to validate efficacy of NPWTi-d in various wound types. The purpose of this review is to provide a relevant overview of wound healing, describe current literature supporting the adjunctive use of NPWTi-d, propose a clinical approach for appropriate application of NPWTi-d and conclude with case studies demonstrating successful use of NPWTi-d. Based on this review, we conclude that either a large case series examining effects of NPWTi-d on different wound types or possibly a large prospective registry evaluating NPWTi-d with real-world topical wound solutions versus immediate debridement and closure would be valuable to the medical community in evaluating the efficacy of this promising therapy.

Erythropoietin, a novel repurposed drug: an innovative treatment for wound healing in patients with diabetes mellitus.

Developing a new drug is expensive: the cost of going from bench to bedside is about $US1 billion. Therefore, the repurposing of an approved drug is potentially rewarding because it expands the drug's existing therapeutic profile and preempts additional development costs. As the safety profile of a repurposed drug is already well known, any new investigations could then focus on its efficacy and other therapeutic benefits. Recombinant erythropoietin (EPO) is a potential candidate for repurposing because the results of numerous studies have shown that systemic and topical EPO is therapeutically beneficial when it is administered to healthy and diabetic animals with acute and chronic skin wounds and burns. Moreover, the molecular mechanisms of EPO's actions have been elucidated: EPO acts on those nonhematopoietic cells which are involved in the innate immune response where it promotes cellular proliferation and differentiation, exerts its cytoprotective actions, and inhibits apoptosis. In this review, the mechanism of EPO's action in skin wound healing is reviewed, and its potential for treating acute and chronic skin wounds and stimulating tissue regeneration in diabetic patients is discussed.

Clinical impact of negative-pressure wound therapy: a 1,126-patient observational prospective study.

Negative-pressure wound therapy (NPWT) was developed in the early 1990s and reported in 1997 by Argenta and Morykwas. Ignored at first, this technique progressively came to be considered as an outstanding advancement in reconstructive surgery. Several randomized controlled studies produced evidence for the effect of NPWT on promotion of granulation tissue formation and prevention of tissue damage and amputation. However, no important longitudinal study has yet produced clinical and economic data on the consequences of integrating NPWT into practice in multiple institutions. This prospective, comparative longitudinal study of NPWT as a clinical-practice innovation was conducted in 1,126 patients between March 2006 and June 2009 in 30 university and nonuniversity public and private hospitals in France. NPWT was proposed in a nonrandomized fashion for various clinical indications, and the patients were divided into two groups, one using NPWT, the second using standard care. Efficacy criteria were spontaneous closure, closure after surgical coverage using skin grafts or flaps, or achievement of 40% wound area regression. The results, observed in a pragmatic but not randomized study, are suggestive of a favorable impact of NPWT in multiple clinical situations. The significance of differences between surgical patients who underwent NPWT and those who did not was unclear, as NPWT had already been adopted by most of the surgical wards.

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.

Neoplastic wounds and degenerescence.

Between 5% and 10% of cancer patients develop malignant wounds. Cancer wounds can occur as a clinical entity, especially over the breast, with the development of painful, spreading cancer invasions of the skin. Marjolin's ulcers develop in open wounds after a long period, and form rare malignancies arising from previously traumatised, chronically inflamed, or scarred skin. Marjolin's ulcer is associated with malignant transformation of chronic ulcers, sinus tracts, and burn scars. Squamous cell carcinoma may be linked to a wide variety of medical and surgical clinical situations, such as chronic ulcers, sinuses, chronic osteomyelitis, radiotherapy, burn scars, chronic pressure ulcers, as well as cystostomy sites, and Fournier's gangrene scars. Melanomas, lymphomas, and other cancers can also be observed. Basal cell carcinoma is more frequently observed in ulcers associated with venous insufficiency. According to some reports, the ulcer should have existed for at least 3 years to evoke a diagnosis of degenerescence as opposed ulcerated tumour. Epidermoid carcinomas represent between 0.21% and 0.34% of cancers that develop over leg ulcers, but large series are still lacking. The current lack of epidemiological data could be rectified by more frequent evocation of the diagnosis and a policy of systematic biopsy of chronically open wounds.

Negative pressure wound therapy with saline instillation: 131 patient case series.

Negative pressure wound therapy combined with timed, cyclical instillation (NPWTi) of topical wound solutions has been recently presented as a new adjunctive modality for treating wounds with signs of infection. Normal saline, antiseptics and antimicrobials all have been proposed in scientific and clinical studies as potentially effective when used with NPWTi for treating heavily infected wounds. This is a prospective clinical study of 131 patients with 131 wounds treated with NPWTi using saline between January 2012 and December 2012 in two orthopaedic centres and one surgical wound healing centre in France. Saline was exclusively used. Results were favourable: in 98% of the cases, the wounds could be closed after debridement and following the use of NPWTi. Mean duration of NPWTi was 12·19 days. This does not preclude the need for treating the biofilm appropriately with more active antibacterial products when biofilm has been documented.

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.

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.

Extracorporeal shock wave therapy (ESWT) for wound healing: technology, mechanisms, and clinical efficacy.

For almost 30 years, extracorporeal shock wave therapy has been clinically implemented as an effective treatment to disintegrate urinary stones. This technology has also emerged as an effective noninvasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life. Intensive wound care is required, and this places an enormous burden on society in terms of lost productivity and healthcare costs. Therefore, cost-effective, noninvasive, and efficacious treatments are imperative to achieve both (accelerated and complete) healing of problematic wounds and reduce treatment-related costs. Several experimental and clinical studies show efficacy for extracorporeal shock wave therapy as means to accelerate tissue repair and regeneration in various wounds. However, the biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains unclear. Potential mechanisms, which are discussed herein, include initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves. This review aims to provide an overview of shock wave therapy, its history and development as well as its current place in clinical practice. Recent research advances are discussed emphasizing the role of extracorporeal shock wave therapy in soft tissue wound healing.