Arterial Leg Ulcers in the Octogenarian.

Arterial leg ulcers are a debilitating sequela of chronic ischemia, and their management, particularly in the octogenarian, is an immense challenge. ALUs are frequently a manifestation of end-stage peripheral arterial disease, and their presence portends a high morbidity and mortality. Management primarily relies on restoration of flow, but in the geriatric population, interventions may carry undue risk and pathologies may not be amenable. Adjunctive therapies that improve quality of life and decrease morbidity and mortality are therefore essential, and understanding their benefits and limitations is crucial in developing a multimodal treatment algorithm of care for the uniquely challenging octogenarian population.

The Clinical Utility of Powdered and Flowable Matrices in Wound Repair and Tissue Regeneration.

Cellular and matrix-like products come in many forms. Among them, powdered and micronized formulations have become increasingly available and popular owing to their unique properties and advantages. Powders have increased tissue contact which many believe can enhance granulation tissue formation, they fill irregular and deep cavities, and they can be used in concert with sheet-like products and skin grafts for improved healing. Despite their advantages, powdered products do have certain limitations that hinder their use, including poor insurance coverage and a lack of CPT coding for adequate reimbursement in an outpatient setting, making their use primarily limited to the operating room. Also, most published data on powdered products consists of smaller case studies and case series, with few reports evaluating the efficacy and utility of powdered formulations compared to their sheet-like progenitors. In this manuscript, we organize available powdered matrix products by type of substrate: xenograft, allograft, placental-based, and synthetic, and review the data in support of various products in specific wound types. This review of the supporting literature provides the current body of evidence on the utility of powdered matrices in wounds.

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.

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.

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.

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.