Multi-drug resistant Staphylococcus epidermidis from chronic wounds impair healing in human wound model.

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm-forming bacteria. As one of the most abundant skin-commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S. epidermidis distribution in VLUs and associated resistome were analysed in ulcer tissue from patients. Virulence of S. epidermidis isolates from VLUs were evaluated by whole genome sequencing, antimicrobial susceptibility testing, in vitro biofilm and binding assays, and assessment of biofilm-forming capability and pro-inflammatory potential using human ex vivo wound model. We demonstrated that S. epidermidis isolates from VLUs inhibit re-epithelialization through biofilm-dependent induction of IL-1ß, IL-8, and IL-6 which was in accordance with impaired healing outcomes observed in patients. High extracellular matrix binding ability of VLU isolates was associated with antimicrobial resistance and expression levels of the embp and sdrG, responsible for bacterial binding to fibrinogen and fibrin, respectively. Finally, we showed that S. epidermidis from VLUs demonstrate pathogenic features with ability to impair healing which underscores the emergence of treatment-resistant virulent lineages in patients with chronic ulcers.

Hydration response technology dressings for low to excessively exuding wounds: a systematic review.

OBJECTIVE: The aim of this systematic review was to identify and qualify the current available evidence of the wound exudate handling capabilities and the cost-effectiveness of hydration response technology (HRT). HRT combines physically modified cellulose fibres and gelling agents resulting in wound dressings that absorb and retain larger quantities of wound exudate. METHOD: A systematic search was conducted in MEDLINE (via PubMed and PubMed Central) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search was conducted using an unlimited search period. Studies or reviews that evaluated effect on wound exudate and cost-effectiveness, as well as the impact on wound healing were considered. Records focusing on wound management using HRT devices were included. RESULTS: The literature search identified four studies and one comparative analysis, ranging from low to moderate quality, that compared HRT dressings to other interventions (carboxymethyl cellulose dressing, other superabsorbent dressings, negative pressure wound therapy). CONCLUSION: The analysed data supported the beneficial use of dressings with HRT for exuding wounds which was characterised by fewer dressing changes, improved periwound skin conditions and reduced costs.

First clinical evaluation of the safety and efficacy of tarumase for the debridement of venous leg ulcers.

We report the first clinical evaluation of a new enzymatic wound debridement product containing tarumase in venous leg ulcer patients. As a first-in-human study, this was a prospective, open-label, multi-centre, dose escalation study across five dose cohorts and involving a total of 43 patients treated three times weekly for up to 4 weeks (12 applications). The primary and secondary endpoints of the study were to assess the systemic safety, local tolerability, and early proof of concept both for wound debridement and healing. Results indicated that the tarumase enzyme was well tolerated when applied topically to wounds, with no indications of systemic absorption, no evidence of antibody generation, and no systemic effects on coagulation pathways. Locally, there was no evidence of pain on application, no local itching, no increases in erythema, oedema, exudate or bleeding and only a few treatment emergent adverse events were reported. As the concentration of tarumase was escalated, trends towards faster and improved effectiveness of wound debridement were observed, especially in patients with significant slough at baseline. Trends towards faster rates of healing were also noted based on observations of increased granulation tissue, increased linear healing and reduction in surface area over the 4-week treatment period.

Fluid handling by foam wound dressings: From engineering theory to advanced laboratory performance evaluations.

This article describes the contemporary bioengineering theory and practice of evaluating the fluid handling performance of foam-based dressings, with focus on the important and clinically relevant engineering structure-function relationships and on advanced laboratory testing methods for pre-clinical quantitative assessments of this common type of wound dressings. The effects of key wound dressing material-related and treatment-related physical factors on the absorbency and overall fluid handling of foam-based dressings are thoroughly and quantitively analysed. Discussions include exudate viscosity and temperature, action of mechanical forces and the dressing microstructure and associated interactions. Based on this comprehensive review, we propose a newly developed testing method, experimental metrics and clinical benchmarks that are clinically relevant and can set the standard for robust fluid handling performance evaluations. The purpose of this evaluative framework is to translate the physical characteristics and performance determinants of a foam dressing into achievable best clinical outcomes. These guiding principles are key to distinguishing desirable properties of a dressing that contribute to optimal performance in clinical settings.

Circulating endothelial precursor cells are associated with a healed diabetic foot ulcer evaluated in a prospective cohort study.

The goal of this multicentre study was to evaluate whether circulating endothelial precursor cells and microparticles can predict diabetic foot ulcer healing by the 16th week of care. We enrolled 207 subjects, and 40.0% (28.4, 41.5) healed by the 16th week of care. Using flow cytometry analysis, several circulating endothelial precursor cells measured at the first week of care were associated with healing after adjustment for wound area and wound duration. For example, CD34+ CD45dim , the univariate odds ratio was 1.19 (95% confidence interval: 0.88, 1.61) and after adjustment for wound area and wound duration, the odds ratio was (1.67 (1.16, 2.42) p = 0.006). A prognostic model using CD34+ CD45dim , wound area, and wound duration had an area under the curve of 0.75 (0.67, 0.82) and CD34+ CD45dim per initial wound area, an area under the curve of 0.72 (0.64, 0.79). Microparticles were not associated with a healed wound. Previous studies have indicated that circulating endothelial precursor cells measured at the first office visit are associated with a healed diabetic foot ulcer. In this multicentred prospective study, we confirm this finding, show the importance of adjusting circulating endothelial precursor cells measurements by wound area, and show circulating endothelial precursor cells per wound area is highly predictive of a healed diabetic foot ulcer by 16th week of care.

Anti-Tumor Necrosis Factor Alpha Therapeutic Drug Monitoring in Inflammatory Disease: A Systematic Review.

BACKGROUND: Monoclonal antibodies encompass an increasingly important treatment for a variety of dermatologic conditions including hidradenitis suppurativa (HS). The high failure rate and cost of anti-tumor necrosis alpha (TNF-α) agents and emergence of biologic treatments critically warrant treatment strategies that identify treatment failures early and optimize therapy. This review’s primary objective is to understand the current literature on biologic therapeutic drug monitoring (TDM) used in chronic inflammatory diseases and apply this knowledge to future dermatologic studies and treatment. METHODS: Randomized controlled trials (RCTs) or high-quality retrospective analyses of RCTs investigating the outcomes of biologic TDM were identified between January 1979 and January 2020 within the PubMed/MEDLINE database using keywords: "biologic," "therapeutic drug monitoring," and "randomized controlled trial," combined with common medical conditions for which biologics are prescribed: "rheumatoid arthritis," "inflammatory bowel disease," "psoriasis," "Crohn’s," "ulcerative colitis," "vasculitis," and "hidradenitis suppurativa." The methods and findings of each study were compared. RESULTS: Three RCTs were included all examining TDM of TNF-α inhibitors in inflammatory bowel disease (IBD). Two studied TDM of infliximab, and one adalimumab. An additional high-quality retrospective analysis of an infliximab RCT captured in our search was also included. Two of the three RCTs (TAXIT and PAILOT) found proactive TDM superior to clinically based dosing and reactive TDM, respectively. The third RCT (TAILORX) found no significant difference between proactive and reactive TDM. CONCLUSION: TDM of anti-TNF-α biologics in IBD has demonstrated success through RCTs. Knowledge gained from these studies applies to dermatologic treatment. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6671.

Hidradenitis Suppurativa: Surgery, Lasers, and Emerging Techniques.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that is characterized by painful nodules, abscesses and tunnels in skin folds. Current management of HS often requires a multidisciplinary approach, including medical, procedural, surgical, and psychosocial intervention. Here we review surgical techniques for the treatment of HS. While many surgical options are available for patients with HS, it is imperative that surgical planning focuses on medical optimization, patient risk factors, disease severity, and patient preferences to achieve the best outcomes.

The development of a core outcome set for clinical effectiveness studies of bordered foam dressings in the treatment of complex wounds.

AIM: The aim of this project was to develop a core outcome set (COS) for clinical effectiveness studies of bordered foam dressings in the treatment of complex wounds. METHODS: The research project followed the Core Outcome Measures in Effectiveness Trials (COMET) initiative and consisted of two phases. The first phase prepared the background and process, while the second phase had three steps: outcome list generation via systematic review and qualitative study, Delphi consensus study, and consensus meeting. The study has been registered in the Core Outcome Measures in Effectiveness Trials database. RESULTS: The systematic review resulted in 82 outcomes and 20 additional outcomes were obtained during the interviews. After refinement, 111 panellists from 23 countries rated a list of 51 outcomes. In the following consensus meeting, six outcomes were prioritized to be included in the core outcome set. After the consensus meeting, a patient-reported outcome was added to the core outcome set. CONCLUSION: The COS for evaluating the effectiveness of bordered foam dressings in treating complex wounds includes 7 outcomes: "ability to stay in place", "leakage", "pain", "dressing related periwound skin changes", "change in wound size over time", and "overall satisfaction". These identified outcomes are correlated with contemporary bioengineering testing and evaluation methods for dressing performance, which underpins the need for a close multidisciplinary collaboration to advance the field of wound dressings. The outcome 'overall satisfaction' reflects the impact of complex wounds and their treatment on a patient's daily life. The use of these outcomes is recommended to improve data synthesis and promote evidence-based practice. Future developments in COS development involve creating measurement instruments and relevant endpoints for these outcomes.

Mechanical and contact characteristics of foam materials within wound dressings: Theoretical and practical considerations in treatment.

In the treatment of acute and chronic wounds, the clinical performance of a given foam-based dressing, and, ultimately, the wound healing and cost of care outcomes are strongly influenced by the mechanical performance of the foam material/s within that dressing. Most aspects of the mechanical performance of foam materials, for example, their stiffness, frictional properties, conformability, swelling characteristics and durability, and the overall mechanical protection provided by a foam-based dressing to a wound strongly depend on the microstructure of the foam components, particularly on their microtopography, density and porosity. This article, therefore, provides, for the first time, a comprehensive, self-inclusive compilation of clinically relevant theoretical and practical considerations, based on published analytical and experimental research as well as clinical experience related to the mechanical performance of foams in foam-based wound dressings. The current bioengineering information is useful for establishing understanding of the importance of mechanical properties of foams in foam-based dressings among clinicians and researchers in industry and academia, and other potential stakeholders in the wound care field, for example, regulators and buyers. This information is also particularly important for the development of standardised test methods for the evaluation of foam-based wound dressings and resulting standard mechanical performance metrics for these dressings.

Clinical performance characteristics for bordered foam dressings in the treatment of complex wounds: An international wound dressing technology expert panel review.

The aim of this article is to identify and describe clinical practice performance characteristics for bordered foam dressings in the treatment of complex wounds. Our recently published systematic review of outcomes and applied measurement instruments for the use of bordered foam dressings in complex wounds has led to us identifying a range of important clinical and patient-centred issues related to this dressing class. Specifically, here, we focus on an overview of performance criteria in the areas of application, adhesion, exudate management and debridement functions of bordered foam dressings. Our hope is that by highlighting the clinical performance criteria, future testing standards for wound dressings will more closely match our clinical expectations and, thereby, assist clinicians to make better wound treatment choices based on meaningful and clinically relevant dressing product performance standards. complex wounds, complex wound care, treatment, bordered foam dressings, dressing performance.

Further evidence that wound size and duration are strong prognostic markers of diabetic foot ulcer healing.

Diabetic foot ulcers (DFU) are a critical problem for those with diabetes mellitus. Predicting the healing likelihood of a DFU is important to implementing appropriate care, allocating resources, having access to advanced therapies, having successful clinical trials, calibrating clinical trial results, and providing information to administrative entities on patient and provider outcomes. Prognostic modelling can also be important when attempting to compare results across trials or care centres. In a prospective cohort study, we demonstrate and replicate that simple wound characteristics like wound area and wound duration can be used to predict wound healing by the 16th week of care. The models were based on previous literature and replicated using a machine learning algorithm. The use of wound duration and wound area in a prognostic model continues to be important when comparing study results, centre-based outcomes, as well as designing clinical trials.

Comorbidity screening in hidradenitis suppurativa: Evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk. OBJECTIVE: To provide evidence-based screening recommendations for comorbidities linked to HS. METHODS: Systematic reviews were performed to summarize evidence on the prevalence and incidence of 30 comorbidities in patients with HS relative to the general population. The screening recommendation for each comorbidity was informed by the consistency and quality of existing studies, disease prevalence, and magnitude of association, as well as benefits, harms, and feasibility of screening. The level of evidence and strength of corresponding screening recommendation were graded by using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: Screening is recommended for the following comorbidities: acne, dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. It is also recommended to screen patients with Down syndrome for HS. The decision to screen for specific comorbidities may vary with patient risk factors. The role of the dermatologist in screening varies according to comorbidity. LIMITATIONS: Screening recommendations represent one component of a comprehensive care strategy. CONCLUSIONS: Dermatologists should support screening efforts to identify comorbid conditions in HS.

Fish Skin Grafts with Omega-3 for Treatment of Chronic Wounds: Exploring the Role of Omega-3 Fatty Acids in Wound Healing and A Review of Clinical Healing Outcomes.

Chronic, non-healing wounds, such as diabetic foot ulcers and venous leg ulcers, have a significant economic impact on healthcare and are associated with elevated patient morbidity. Among the toolset of treatment options available to clinicians, skin grafts from other species (xenografts) are often used to promote wound closure. While porcine xenografts have been the most used skin xenograft over the years, acellular fish skin grafts from Atlantic cod (Gadus morhua) have steadily gained traction in usage. Unlike other skin grafts, acellular fish skin grafts have a substantial lipid profile primarily composed of omega-3 fatty acids, notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish oil supplementation has been shown to result in faster rates of wound epithelialization, and omega 3 fatty acids provide barrier protection against bacteria and alter the inflammatory profile of wounds. EPA and DHA have been shown to have modulatory effects on the progression of wound healing. These characteristic omega-3 fatty acids and their metabolites alter skin physiology at a cellular and molecular level. Clinically, fish skin grafts continually demonstrate increased efficacy in treatment of wounds. When applied to non-responsive diabetic foot ulcers, acellular fish skin grafts have resulted in accelerated healing rates and significantly more fully healed wounds when compared to standard options. Here, we explore the role of omega-3 fatty acids in wound regeneration and repair, with particular focus on EPA and DHA. Then, we review clinical research outcomes to address notable clinical research studies and highlight the therapeutic potential of fish skin grafts with omega-3 as a treatment for chronic, non-healing wounds.

Clinical research on the use of bordered foam dressings in the treatment of complex wounds: A systematic review of reported outcomes and applied measurement instruments.

OBJECTIVE: The aim of this review article was to identify reported outcomes and measurement instruments used in clinical research on bordered foam dressings in the treatment of complex wounds. METHODS: MEDLINE (PubMed interface), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, and The Cochrane Library were systematically searched using a combination of key terms including; wounds, bordered foam dressing, and treatment. Studies were included if they (1) targeted an adult population, (2) addressed the treatment of complex wounds with a bordered foam dressing as the primary wound dressing, (3) were retrieved from original research, and (4) were published between 2000 and 2022. There were no restrictions on language or study design. Studies that focused primarily on the prevention of complex wounds were excluded. Data extraction included outcome domains, outcomes, instruments, time points, and outcome measures. The OMERACT Filter 2.0 was used as a conceptual framework for the extraction of outcomes. RESULTS: A total of 24 outcome domains and 82 outcomes were identified. The outcomes were categorised into five core areas: (1) impact on life, (2) dressing performance, (3) pathophysiological manifestations, (4) resource use, and (5) adverse events. Thirtynine outcomes (47.0%) were measured at more than one time point. The most frequently reported time point was 'at the end of treatment' (62.7%). Outcomes were measured using self-report instruments, clinical observations, and bio-physiological instruments. CONCLUSION: This systematic review identified reported outcomes and measurement instruments in research on bordered foam dressings in the treatment of complex wounds. The variety and lack of consistency in terms of instruments, time points and outcome measurements made it difficult to compare data directly across different reported studies. A solution to the variety in outcome reporting across studies in complex wound care, and moreover for the treatment with bordered foam dressings, is the development of a Core Outcome Set (COS). The outcomes in this review article will inform the next steps of developing a COS, where patients, clinicians and researchers will be involved to decide on the final outcomes included in a COS for the treatment of complex wounds with bordered foam dressings.

The therapeutic potential of cannabinoids for integumentary wound management.

The increasing legalization of Cannabis for recreational and medicinal purposes in the United States has spurred renewed interest in the therapeutic potential of cannabinoids (CBs) for human disease. The skin has its own endocannabinoid system (eCS) which is a key regulator of various homeostatic processes, including those necessary for normal physiologic wound healing. Data on the use of CBs for wound healing are scarce. Compelling pre-clinical evidence supporting the therapeutic potential of CBs to improve wound healing by modulating key molecular pathways is herein reviewed. These findings merit further exploration in basic science, translational and clinical studies.

Examining risk factors and preventive treatments for first venous leg ulceration: A cohort study.

BACKGROUND: Large studies that examine risk factors for first occurrence of venous leg ulcerations are needed to guide management. OBJECTIVE: To investigate factors associated with development of first occurrence of venous leg ulcerations. METHODS: A retrospective cohort study using a validated national commercial claims database of patients with venous insufficiency. Subjects were followed to determine whether they developed first occurrence of venous leg ulcerations, and risk and protective factors were analyzed. RESULTS: Adjusted hazard ratio (AHR) for comorbidities demonstrated an increased risk in men (AHR 1.838; 95% confidence interval [CI] 1.798-1.880), older age (45-54 years: AHR 1.316, 95% CI 1.276-1.358; 55-64 years, AHR 1.596, 95% CI 1.546-1.648), history of nonvenous leg ulceration (AHR 3.923; 95% CI 3.699-4.161), anticoagulant use (AHR 1.199; 95% CI 1.152-1.249), antihypertensive use (AHR 1.067; 95% CI 1.040-1.093), and preexisting venous insufficiency including chronic venous insufficiency (AHR 1.244; 95% CI 1.193-1.298), edema (AHR 1.224; 95% CI 1.193-1.256), and chronic venous hypertension (AHR 1.671; 95% CI 1.440-1.939). Possible protective factors were having venous surgery (AHR 0.454; 95% CI 0.442-0.467), using compression stockings (AHR 0.728; 95% CI 0.705-0.753), using prescribed statin medications (AHR 0.721; 95% CI 0.700-0.743), and using pain medications (AHR 0.779; 95% CI 0.757-0.777). LIMITATIONS: Risk of misclassification, given the use of International Classification of Diseases, Ninth Revision codes. Possible confounding factors such as body mass index could not be adequately controlled with these codes. CONCLUSION: The new evidence presented supports a paradigm shift toward venous leg ulceration prevention.

Sonographic Evaluation of Hidradenitis Suppurativa with Smartphone-Linked Portable Ultrasound.

BACKGROUND: Clinical staging systems for hidradenitis suppurativa (HS) have poor interrater reliability and may underestimate disease activity. Sonographic staging systems may overcome these challenges, but conventional ultrasound (US) machines are expensive and bulky. Portable (p)US may facilitate the integration of sonography into routine practice. OBJECTIVES: To assess the ability of a novel smartphone-linked pUS device to identify key sonographic lesions of HS. METHODS: The charts of 16 patients with HS who were assessed with pUS at the outpatient Dermatology and Wound Care Clinics of a university hospital center were retrospectively reviewed. Clinical and sonographic images of the affected areas were examined. The main outcome measures were the number of patients with identifiable sonographic lesions and the number of patients with subclinical lesions detected by pUS. RESULTS: All 3 key sonographic lesions of HS were identifiable with pUS. Sonographic lesions were identified in 10 patients (62.5%). Subclinical lesions were identified in 2 patients (12.5%); in both cases, this affected management decisions. CONCLUSIONS: We demonstrate the ability of pUS to identify the key sonographic lesions of HS. pUS is a simple and affordable way to integrate HSUS into clinical and research settings, with clear potential benefits to patients.

Functional Imaging in Wounds: Imaging Modalities of Today and Tomorrow.

Wound care is a multidisciplinary field with significant economic burden to our healthcare system. Not only does wound care cost the US healthcare system $20 billion annually, but wounds also remarkably impact the quality of life of patients; wounds pose significant risk of mortality, as the five-year mortality rate for diabetic foot ulcers (DFUs) and ischemic ulcers is notably higher compared to commonly encountered cancers such as breast and prostate. Although it is important to measure how wounds may or may not be improving over time, the only relative "marker" for this is wound area measurement-area measurements can help providers determine if a wound is on a healing or non-healing trajectory. Because wound area measurements are currently the only readily available "gold standard" for predicting healing outcomes, there is a pressing need to understand how other relative biomarkers may play a role in wound healing. Currently, wound care centers across the nation employ various techniques to obtain wound area measurements; length and width of a wound can be measured with a ruler, but this carries a high amount of inter- and intrapersonal error as well as uncertainty. Acetate tracings could be used to limit the amount of error but do not account for depth, thereby making them inaccurate. Here, we discuss current imaging modalities and how they can serve to accurately measure wound size and serve as useful adjuncts in wound assessment. Moreover, new imaging modalities are also discussed and how up-and-coming technologies can provide important information on "biomarkers" for wound healing.

Correlates of injection-related wounds and skin infections amongst persons who inject drugs and use a syringe service programme: A single center study.

Risk factors associated with wounds and skin infections amongst persons who inject drugs may have changed in the era of fentanyl and now stimulant coinjection. We assessed the number of injection site wounds and skin infections and associated factors amongst 675 persons who inject drugs in a syringe services programme. Of this sample, 173 participants reported a total of 307 wounds and skin infections. Significant factors associated with increased number of wounds and skin infections were age 30 or older, female gender, ever experiencing homelessness, cocaine injection, and injecting between 5 and 10 years. Wounds and skin infections were common amongst syringe services programme clients and are associated with certain risk factors that may help to design effective interventions. Given the high prevalence of wounds in syringe services programme clients, wound care clinicians can make a significant difference and improve outcomes. We also shed light on correlates of wounds and skin infections in persons who inject drugs in order to spur further research to devise efficacious interventions for this underserved group.

Use of Topical Timolol Maleate as Re-Epithelialization Agent for Treatment of Recalcitrant Wounds of Varying Etiologies.

Background: Chronic wounds remain a challenge for the clinician and healthcare system. It is therefore vital for additional therapies that target steps involved in wound recalcitrance. Recently, topical timolol has shown promising results for use in wound healing. Objective: The goal of this study was to assess timolol's effectiveness in healing wounds of varying etiologies. Methods: This multi-center series took place from 2016¬­2019 at the wound healing centers at the University of Miami Health System and the Veterans Affairs Northern California Healthcare. We identified all wound patients who received treatment with topical timolol maleate 0.5% for at least 4 weeks after failing previous treatments. Timolol drops at a dose of 1 drop per cm2 of wound area were instilled with dressing changes twice a day, once a day, every other day, or continuous application. Once they began the study, they stopped all concurrent therapies aside from standard of care. Healing outcomes were classified into 3 categories: healed, defined as complete re-epithelialization of the wound and closure, improved, defined as decreasing wound size area (WSA), and worsening, defined as increasing WSA. Results: We identified 39 patients, 32 males and 7 females that had a total of 55 chronic wounds of varying etiologies. Thirty-four of the wounds had completely healed, 15 wounds improved in WSA, 4 wounds were unchanged in WSA, and 2 wounds worsened in WSA. Conclusions: In line with our previous experience, we found topical timolol to be a safe, cost-effective, and efficacious treatment for recalcitrant wounds of varying etiologies.