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.

Autologous Blood-Derived Products (ABDPs) for the Treatment of Chronic Wounds.

Autologous blood-derived therapies have emerged as a unique and promising treatment option for chronic wounds. From whole blood clots to spun-down clot constituents, these therapies are highly versatile and tend to have a lower cost profile, allow for point-of-service preparation, and inherently carry minimal to no risk of rejection or allergic reaction when compared to many alternative cellular and matrix-like products. Subsequently, a diversity of processing systems, devices, and kits have surfaced on the market for preparing autologous blood-derived products (ABDPs) and many have demonstrated preclinical and clinical efficacy in facilitating chronic wound healing. However, not all ABDPs are created equal, and the lack of standardization among product formulations and cell concentrations as well as varying complexities in preparation protocols has led to unreliable substrate viabilities and overall inconsistent conclusions on efficacy. Additionally, external factors, such as the ease of drawing blood, the health of a patient's blood, and the reimbursement landscape have dissuaded some practitioners from incorporating ABDPs into an algorithm of care for recalcitrant wounds. Here, we attempt to categorize ABDPs into "classes" and examine their efficacy, advantages, and limitations when used as both a primary therapy and an adjunct for treating chronic wounds as well as comment on some potential considerations that may help gear future product development and application.

PACE: randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial.

BACKGROUND: Revascularization is the primary treatment modality for chronic limb-threatening ischaemia (CLTI), but is not feasible in all patients. PLX-PAD is an off-the-shelf, placental-derived, mesenchymal stromal cell-like cell therapy. This study aimed to evaluate whether PLX-PAD would increase amputation-free survival in people with CLTI who were not candidates for revascularization. METHODS: People with CLTI and minor tissue loss (Rutherford 5) who were unsuitable for revascularization were entered into a randomized, parallel-group, placebo-controlled, multinational, blinded, trial, in which PLX-PAD was compared with placebo (2 : 1 randomization), with 30 intramuscular injections (0.5 ml each) into the index leg on days 0 and 60. Planned follow-up was 12-36 months, and included vital status, amputations, lesion size, pain and quality-of-life assessments, haemodynamic parameters, and adverse events. RESULTS: Of 213 patients enrolled, 143 were randomized to PLX-PAD and 70 to placebo. Demographics and baseline characteristics were balanced. Most patients were Caucasian (96.2%), male (76.1%), and ambulatory (85.9%). Most patients (76.6%) reported at least one adverse event, which were mostly expected events in CLTI, such as skin ulcer or gangrene. The probability of major amputation or death was similar for placebo and PLX-PAD (33 and 28.6% respectively; HR 0.93, 95% c.i. 0.53 to 1.63; P = 0.788). Revascularization and complete wound healing rates were similar in the two groups. A post hoc analysis of a subpopulation of 121 patients with a baseline haemoglobin A1c level below 6.5% showed improved 12-month amputation-free survival (HR 0.46, 0.21 to 0.99; P = 0.048). CONCLUSION: Although there was no evidence that PLX-PAD reduced amputation-free survival in the entire study population, benefit was observed in patients without diabetes mellitus or whose diabetes was well controlled; this requires confirmation in further studies. Trial registration: NCT03006770 (http://www.clinicaltrials.gov); 2015-005532-18 (EudraCT Clinical Trials register - Search for 2015-005532-18).

The Shift to Synthetics: A Review of Novel Synthetic Matrices for Wound Closure.

Since the late 1990s, a growing number of "skin substitutes" have become available to practitioners seeking to heal large surface wounds. These extracellular matrices were originally from xenograft sources, and then from very highly engineered living human cellular tissues. More recently, they consist of biosynthetic materials that are combinations of silicone, collagen and chondroitin. The list of xenograft materials as well as minimally manipulated human tissues, such as human skin-, amniotic- and placental-based products, has grown exponentially. Over the last 5 years, truly synthetic materials have become part of the armamentarium available for closing large wounds. The first notable product in this category was made of polyurethane. These purely synthetic products do not have any components made of naturally occurring structures, such as collagen. In this review, we seek to create a rudimentary framework in which to understand these synthetic products and to review the current literature that supports the use of these novel yet intriguing therapies.

Acellular Fish Skin for Tissue Replacement.

In modern practice, xenografts play a crucial role in wound management due to their regenerative properties. Of the various xenografts currently available on the market, acellular fish skin (AFS) grafts have emerged as a more effective alternative to existing xenografts and other standard of care (SOC) treatments for wound healing. Since AFS grafts require minimal processing, they maintain their structural integrity and natural properties, including an abundance of Omega-3 fatty acids, which is a distinctive, pro-regenerative feature. AFS grafts are also unique in that they are not derived from mammalian tissue, so there is no risk of viral transmission and no cultural or religious barriers to use. AFS grafts have been shown to be more cost-effective in the treatment of diabetic foot ulcers (DFUs) and result in a higher percentage of healed wounds, fewer amputations, and better patient quality of life. Several studies and case reports have highlighted the versatility of AFS in not only acute and chronic wound healing, but also for burn wound skin regeneration. Additionally, AFS may have promise as an implantable biologic matrix for suture line reinforcement in hernia repairs or breast and dura reconstruction.

Implantable Biologics for Soft Tissue Surgery Reinforcement.

Soft tissue reinforcement focuses on medical grafts that are designed to support and regenerate soft tissue under or near suture lines. Soft tissue is defined as areas of similarly specialized cells that function to connect, support, and surround other structures and organs of the body. These tissues include skin, subcutaneous tissue, fascia, ligaments, tendons, fibrous tissues, fat, synovial membranes, and muscle. Most of the implantable devices used for this purpose are made of collagen, the most abundant protein in mammals and a key component of the extracellular matrix of soft tissues that allows for tissue repair. For suture line reinforcement, exogenous collagen from various sources is implanted under or in continuity with the suture line to allow for increased strength and better healing. First introduced in the field of breast reconstruction, this practice is now also used in hernia repair, dural repair, vaginal slings, amputation reinforcement, tendon repair reinforcement, and even dental soft tissue regeneration.

Best practice for wound repair and regeneration use of cellular, acellular and matrix-like products (CAMPs).

There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.

Blood-Borne Microparticles Are an Inflammatory Stimulus in Type 2 Diabetes Mellitus.

The proinflammatory state associated with diabetes mellitus (DM) remains poorly understood. We found patients with DM have 3- to 14-fold elevations of blood-borne microparticles (MPs) that bind phalloidin (Ph; Ph positive [+] MPs), indicating the presence of F-actin on their surface. We hypothesized that F-actin-coated MPs were an unrecognized cause for DM-associated proinflammatory status. Ph+MPs, but not Ph-negative MPs, activate human and murine (Mus musculus) neutrophils through biophysical attributes of F-actin and membrane expression of phosphatidylserine (PS). Neutrophils respond to Ph+MPs via a linked membrane array, including the receptor for advanced glycation end products and CD36, PS-binding membrane receptors. These proteins in conjunction with TLR4 are coupled to NO synthase 1 adaptor protein (NOS1AP). Neutrophil activation occurs because of Ph+MPs causing elevations of NF-κB and Src kinase (SrcK) via a concurrent increased association of NO synthase 2 and SrcK with NOS1AP, resulting in SrcK S-nitrosylation. We conclude that NOS1AP links PS-binding receptors with intracellular regulatory proteins. Ph+MPs are alarmins present in normal human plasma and are increased in those with DM and especially those with DM and a lower-extremity ulcer.

Median nerve somatosensory evoked potential alarm related to head and neck positioning for carotid surgery.

Head positioning in carotid surgery represents an often overlooked but sensitive period in the surgical plan. A 53-year-old male presented a significant decrement in median nerve somatosensory evoked potential (mSEP) following head and neck positioning for carotid pseudoaneurysm repair before skin incision.Neurophysiological monitoring was performed with mSEP and electroencephalography early during the patient's preparation and surgery. Within five minutes after rotation and extension of the head to properly expose the surgical field, the contralateral m-SEP significantly decreased in both cortical (N20/P25) and subcortical (P14/N18) components. Partial neck correction led to m-SEP improvement, allowing to proceed with the carotid repair. We discuss possible underlying pathophysiological mechanisms responsible for these changes and highlight the relevance of an early start on monitoring to avoid neurological deficits.

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.

Novel Reconstructive Ladder for Reestablishing Functional Skin Graft Coverage in Chronic Lower Extremity Wounds.

Background: Chronic lower extremity (LE) wounds frequently require significant interventions to close. The success of any method depends on an adequately prepared wound bed, while factors including wound size, perfusion, contamination, or exposed tissue structures can thwart efforts. We propose a standardized algorithm of care utilizing an acellular dermal matrix, split-thickness skin graft (STSG), and negative pressure wound therapy (NPWT) for the treatment of LE wounds. Methods: This was a single-center, retrospective cohort study examining patients who underwent LE wound debridement, placement of fetal bovine dermis (FBD), and STSG between 2016 and 2022. The primary outcome was wound closure, while secondary outcomes were wound infection and amputation-free survival. Results: Twenty patients (mean age 59 years, M:F 12:8)-including 24 LE venous ulcers (29.4%), amputation sites (29.4%), diabetic foot ulcers (25.0%), and atypical wounds (16.7%) with an average area of 39.15 cm2-underwent debridement and FBD placement followed by STSG a median of 61 days thereafter. Of these patients, 83.3% received NPWT after FBD and STSG with 86% closure. There was successful engraftment in 92% of wounds whose FBD placement was within 2 months of STSG. Of wounds that had <50% engraftment, 75% had a STSG placed over 2 months after FBD placement. Of those patients with post-STSG infection, 75% had the graft placed >2 months after FBD placement, one of which required proximal amputation. Conclusions: By following a treatment plan including debridement with treatment of infection, application of FBD with placement of STSG within 2 months thereafter, and reinforcing NPWT, chronic wounds will have an increased rate of successful reepithelialization. Many cases experienced delays from FBD engraftment until STSG application due to schedule and insurance impediments, which led to less favorable outcomes. Therefore, a protocol that involves scheduling the placement of STSG 4 weeks after successful engraftment of FBD has been adopted.

Skin Expansion Technology in Acute Burns and Chronic Wounds.

The ability to grow skin has long been a topic of study and therapeutic interest. Currently, the main ways of doing this are 1) by placing tissue-expansion devices in the subcutaneous space and expanding skin over time, which can then be moved to cover contiguous structures, and 2) via processes that require relatively long (30 days) incubation periods to grow the patient's autogenous skin into laminar sheets. Over the past five years, there have been significant developments in the ability to expand skin cells, either at the bedside or in the laboratory, but much more rapidly than with previous methods. We explore and discuss the current skin cell-expansion techniques, focusing on point-of-care therapeutic interventions that can be used in the burn population as well as the chronic wound population, hair follicle stem-cell incubation techniques and studies supporting this therapy, as well as micro bullae grafting, and morcellated skin cell therapy. The current data supporting these therapeutic interventions and their current direction are outlined in detail.

How to Decide Upon an Appropriate Post-Operative Dressing: 2022.

In the current era, there are numerous advanced postoperative dressings. The ideal postoperative dressing is one that is thought to improve patient comfort, manage postoperative drainage, potentially allow for visualization of the wound, improve postoperative healing, and possibly reduce bacterial invasion. However, many advanced surgical dressings have shown increased ease of handling and increased patient comfort, but have not shown true superiority with regard to objective criteria. To ease the overall evaluation of such products, we have categorized them as standard of care dressings, engineered dressings, antimicrobial engineered dressings, skin glues and adhesives, and closed incisional negative pressure wound therapy. Among these categories, closed incisional negative pressure wound therapy has repeatedly shown superior subjective and objective outcomes. However, due to cost constraints, this therapy is not ideal for everyone. In many cases, the postoperative dressing should be dictated by the type of surgery, the location of the surgery, and the comorbidities of the patient. The authors will review the appropriate indications for the use of all categories of postoperative dressing and identify specific items that have shown great promise. The current guidelines will also be reviewed.

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.

The impact of the SARS-CoV-2 pandemic on the management of chronic limb-threatening ischemia and wound care.

In the wake of the coronavirus pandemic, the critical limb ischemia (CLI) Global Society aims to develop improved clinical guidance that will inform better care standards to reduce tissue loss and amputations during and following the new SARS-CoV-2 era. This will include developing standards of practice, improve gaps in care, and design improved research protocols to study new chronic limb-threatening ischemia treatment and diagnostic options. Following a round table discussion that identified hypotheses and suppositions the wound care community had during the SARS-CoV-2 pandemic, the CLI Global Society undertook a critical review of literature using PubMed to confirm or rebut these hypotheses, identify knowledge gaps, and analyse the findings in terms of what in wound care has changed due to the pandemic and what wound care providers need to do differently as a result of these changes. Evidence was graded using the Oxford Centre for Evidence-Based Medicine scheme. The majority of hypotheses and related suppositions were confirmed, but there is noticeable heterogeneity, so the experiences reported herein are not universal for wound care providers and centres. Moreover, the effects of the dynamic pandemic vary over time in geographic areas. Wound care will unlikely return to prepandemic practices. Importantly, Levels 2-5 evidence reveals a paradigm shift in wound care towards a hybrid telemedicine and home healthcare model to keep patients at home to minimize the number of in-person visits at clinics and hospitalizations, with the exception of severe cases such as chronic limb-threatening ischemia. The use of telemedicine and home care will likely continue and improve in the postpandemic era.

A dual pressure indicator, two-layer compression system for treatment of venous leg ulcers: a review.

OBJECTIVE: Venous leg ulcers (VLUs) are considered the most frequent category of hard-to-heal limb ulcers. Although evidence-based care of VLUs suggests that compression therapy plays a pivotal role in the standard of care, patient adherence is considered low, with at least 33% non-compliance, either due to perceived problems from clinicians regarding their own competency in applying the bandages, or from the patient finding the wrapping bothersome. For many years, four-layer bandaging has been considered the 'gold standard', but application can be difficult and may also prove uncomfortable for patients. Accurate application may be facilitated by a stretch indicator which has been engineered to act as a surrogate for appropriate pressure application that can address the skill concern, while fewer layers can save clinicians' time and improve the quality of life of patients. Here, we review the literature supporting a two-layer system which combines elastic (long stretch) and inelastic (short stretch) components as well as both layers having graphic markers to define that the dressing has been applied at the proper tension. METHOD: An initial search was conducted on PubMed and then followed up by a manual search of Google Scholar to retrieve evidence of different levels, in order to evaluate the outcomes of use of the specific two-layer compression system with pressure indicators in the management of patients presenting with VLUs. RESULTS: A total of four papers discussing the specific compression system in question were identified from 32 publications retrieved from PubMed, while a further six were retrieved from Google Scholar. These 10 publications were considered relevant to the two-layer system and were analysed for the outcomes of care, including wound healing, appropriate application, time-saving and better patient acceptance and adherence. CONCLUSION: Previous authors have demonstrated that two-layer systems are equivalent to four-layer systems. However, the ability to reproducibly apply appropriate compression has remained a question. The papers reviewed demonstrate that evidence suggests that the two-layer compression bandage system with indicators provides continuous, consistent and comfortable treatment that may be easier to apply with accurate pressure levels due to their indicator systems, and therefore, is a procedure that may increase patient adherence and acceptability to the wound therapy.