Wound Fluid Extracellular Microvesicles: A Potential Innovative Biomarker for Wound Healing.

Background: Extracellular vesicles, or microvesicles, are a large family of membrane-bound fluid-filled sacs that cells release into the extracellular environment. Extracellular microvesicles (EMVs) are essential for cell-to-cell communications that promote wound healing. We hypothesize a correlation between the concentration of EMVs in wound fluid and the percentage of wound healing in treated chronic, nonhealing, wounds. A prospective, multicenter, randomized, single-blind clinical trial was conducted to evaluate EMV concentration in relation to wound healing percentages. Methods: Wound fluid samples were obtained from 16 patients with stage IV trunk pressure ulcers. Patients were divided equally into two groups: (1) control group on negative pressure wound therapy (NPWT) alone and (2) study group with NPWT plus porcine extracellular matrix dressing. NPWT was replaced two times a week, and porcine extracellular matrix applied once weekly for all subjects. An NPWT canister device, called a wound vacuum-assisted closure, containing wound fluid was collected from each patient every 4 weeks. EMVs were isolated and the concentration measured by nanoparticle tracking analysis. Results: The study group's total healing percentage was around 89% after 12 weeks compared with the control group's percentage of about 52% (P ≤ 0.05). Using R programming software, simple linear regression was carried out to investigate the hypothesis. Data demonstrated significant positive correlation (R2 = 0.70; P = 0.05) between EMV concentrations and the healing percentage. Conclusions: There is a positive correlation between EMV concentration and wound healing percentages. Results propose that the EMVs in wound fluid could serve as a biomarker for healing.

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.

A rare presentation of Rosai-Dorfman-Destombes disease with central nervous system involvement and cutaneous wounds.

OBJECTIVE: The aim of this case report is to investigate an uncommon presentation of Rosai-Dorfman-Destombes (RDD) disease, and discuss possible differential diagnoses and treatment options for this pathology. RDD is a rare disorder of histiocytes that typically presents in patients as painless cervical lymphadenopathy. However, this case involves a patient with the central nervous system (CNS) type of RDD who later developed cutaneous lesions. METHOD: Several differential diagnoses were examined, including hidradenitis suppurativa, pilonidal cyst and pressure ulcers. It is important to be able to exclude these diagnoses based on the presentation, patient demographic and wound location. RESULTS: Biopsies verified the presence of RDD in the patient's suprasellar hypothalamic mass and skin lesions, confirming the patient had both CNS-RDD and cutaneous-RDD in the absence of lymphadenopathy. CONCLUSION: Recognising the unique manifestations of rare diseases such as RDD prevents delay of proper intervention and treatment.

Dystrophic Calcinosis Cutis Leading to a Nonhealing Wound in a Patient with Chronic Venous Insufficiency.

The presence of bony-appearing fragments and calcifications appearing superficially in a chronic, nonhealing wound raises suspicion for osteomyelitis. When radiological imaging and tissue biopsy of the lesion return negative for osteomyelitis, however, the differentials must be widened to successfully manage and heal a chronic wound. In this report, we discuss a case of an 80-year-old morbidly obese woman with a history of chronic venous insufficiency, hereditary hemochromatosis, and squamous cell carcinoma who presented to the wound clinic with a 5-month history of a nonhealing wound with bony-appearing fragments and calcifications on her left anterior leg status postbiopsy during routine skin examination. Upon clinical correlation with laboratories and imaging, it was determined that the cause of her nonhealing wound was due to dystrophic calcinosis cutis.

Malignant wound aetiology, diagnosis and management: a case series and literature review.

OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy. METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles. RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC. CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.

How to Select an Extracellular Matrix for Wound Repair: A Comprehensive Review.

Background: An extracellular matrix (ECM) is a network of proteins and other molecules that provide support and structure to cells and tissues in the body. Since its discovery in 1930, researchers have reproduced the ECM through an array of evolving technologies, developing products that accelerate healing times, minimize scarring, and reduce pain. When selecting which ECM product to use, physicians rely on personal experience while considering wound location, type of tissue lost, exposed structures, chronicity, and even the patient's religious preferences. While comparison trials between a few different types of ECMs exist, there lacks a thorough investigation that assesses a majority of ECMs against each other. Methods: Herein, we conducted a literature review using the PubMed database and utilized 71 articles to identify the best ECM for wound healing and positive patient outcomes. The primary search terms included extracellular matrix, xenograft, porcine, bovine, allograft, bioengineered matrix, acellularized fish skin, wounds, wound healing, and wound care. We did not exclude any specific type of research, but predominantly reviewed clinical trials, case series, and other review articles. We focused on the most popular and commonly used ECMs and constructed our results into the Table. Results: We compared the indications, advantages, and disadvantages of each ECM and concisely illustrated these findings to provide a guide on how to select an ECM (Table). Allografts, whether they are glycerol or cryopreserved, suffice as a treatment choice and are superior to exposure healing. However, they do not produce healing at the same rate or quality as bioengineered matrices, porcine and bovine xenografts, or acellularized fish skin (AFS). Bioengineered matrices and porcine and bovine xenografts offer antimicrobial properties, low immunogenicity, cost effectiveness, and availability. The compromise with these ECMs is with healing times and cosmesis. Acellularized fish skin (AFS) provides diverse utility, antimicrobial activity, low immunogenicity, faster healing times, and cosmetic superiority. However, AFS yields a potential cost burden and is not plentiful or easily accessible in some parts of the world. Conclusions: Our findings assist in removing the subjectivity component of selecting an ECM and suggest further comparison or head-to-head trials would yield a more algorithmic approach to wound healing. We suggest to consider implementing the Disabilities of the Arm, Shoulder, and Hand (DASH) score as an additional objective comparison method in these future trials.

Proceedings of the Leaders in Wound Healing conference.

SerenaGroup Research Foundation, New Orleans, 17-19 April 2023.

Differential diagnosis of stage 2, 3 and 4 pressure injuries of the pelvis and lower extremity: a case series.

Constant, unrelieved pressure of local tissue, particularly over bony prominences, may provoke damage that progresses to necrosis and pressure injury (PI). Differentiating PIs from conditions of similar appearance is imperative to minimising complications and implementing prompt treatment. This case series describes several conditions that may be mistaken for a PI. Outlined are the key differences in patient history, presentation and clinical cues that assist in correctly identifying the true pathology behind these conditions. Conditions reviewed included: pyoderma gangrenosum; necrotising fasciitis; genital herpes; Marjolin ulcer, Rosai-Dorfman disease; vascular disease; coagulopathies; calciphylaxis; trauma and surgical wounds; pilonidal cysts; graft-versus-host disease; hidradenitis suppurativa; Stevens-Johnson syndrome; epidermolysis bullosa; radiation wounds; spider bites; and end-of-life skin failure pressure ulcers (also known as Kennedy ulcers). Although commonly recognised and diagnosed, stage 2, 3 and 4 PIs occasionally prove to be difficult to pinpoint, with undefined characteristics and similarities in presentation to several other conditions. Therefore, it is clinically vital to be aware of their appearance, risk factors and aetiology in order to make an appropriate patient assessment and avoid misdiagnosis.

Management of Radiation-induced Tissue Injuries: A Review of Current Treatment Strategies.

Although radiation therapy remains an integral component in cancer treatment, the sequela of tissue damage can result in long-term morbidity and mortality for patients. This article aimed to perform a comprehensive review of the current literature for both nonsurgical and surgical management strategies for radiation-induced injuries. Methods: A literature search was performed on PubMed to review the current described management and treatment options for radiation-induced injuries. Patient demographics, medical diagnoses, complications, strategies of management care, and outcomes were reviewed. Results: The most commonly described management options and reconstructive techniques of radiation wounds were analyzed and reported. Conclusions: Consideration of current techniques and outcomes in the management of radiation-induced wounds demonstrates that impaired wound healing remains a major problem. This literature review provides a detailed overview of the most frequently used therapies with recommendations for surgeons.

Wounds resulting from non-malignant haematological disease: a case series.

A proactive and systemic approach is imperative to preventing wounds due to disorders of non-malignant haematologic disease. Here, the authors provide several examples of patients with either a known history or acute diagnosis of a coagulation disorder with the aim of reviewing potential cutaneous injuries as well as diagnosis and treatment. A description of the wound and treatment course along with recommendations where appropriate are presented. The article serves as a general review for health professionals who may encounter patients with this disorder and who are involved in treatment decisions. After reviewing the article, the practitioner will be able to identify cutaneous injuries that may be secondary to an underlying haematological disorder, review the diagnosis and treatment recommended, and understand the need for a multidisciplinary approach to patient care.

Use of Multimodal Long-Wave Infrared Thermography Devices in Clinical Practice.

Background: The current practice of assessing wounds is highly dependent on visual examination and clinical judgment; these methods are highly subjective and leave great room for error. Objective measures of wound severity and healing are necessary tools that have been lacking in clinical practice. Long-wave infrared thermography (LWIT) has diverse applications that can be optimized to help detect and monitor wounds. Methods: This work is a retrospective case series of pertinent patients encountered by the authors in clinical practice. Results: Nine cases were ultimately selected to best represent the multitude of benefits that can be seen with the utilization of LWIT devices. Conclusions: Through this case series, we show the many advantages of LWIT devices. This technology is safe, noninvasive, and user friendly and, most importantly, gives objective, instant, and repeatable measurements.

Clinical Indications of Cultured Epithelial Autografts.

ABSTRACT: Cultured epithelial autografts (CEAs) have been used for decades as a treatment for massive burn injuries. Cultured epithelial autografts allow for wounds to heal by taking a small sample and growing a patient's own epithelium in culture to create large, graftable sheets. This technique is especially useful in large wounds where donor sites are limited compared with conventional skin grafting. However, CEAs have a variety of uses in wound healing and reconstruction and have the potential to aid in the closure of several types of defects. Cultured epithelial autografts have shown applicability in large burns, chronic nonhealing wounds, ulcerating wounds of various etiologies, congenital defects, wounds requiring specialized epithelium to replace like by like, and wounds in critically ill patients. Several factors must be considered when using CEAs, such as time, cost, and outcomes. In this article, we detail the various clinical applications of CEAs and how they can be situationally advantageous outside of their original purpose.

Pancreatic panniculitis secondary to pancreatic cyst with lower extremity wounds as a primary presenting feature: a case report and literature review.

INTRODUCTION: Pancreatic panniculitis is a rare skin manifestation of pancreatic disease. It is characterized by inflammation and liquefactive necrosis of subcutaneous fat. Treatment involves addressing the underlying cause and providing supportive wound care. CASE REPORT: The authors present a case of a 68-year-old man who developed painful, erythematous wounds on his lower extremities that progressed to purple, edematous lesions with purulent drainage. During the progression of his wounds, he developed epigastric pain and acute pancreatitis. Subsequent CT scan showed a pancreatic cyst that had extended into the portal vein. Deep, excisional biopsy of the wounds helped further narrow the differential. Histology indicated "ghost cells," which are adipocytes with a central clearing and dark basophilic calcium deposits in the cytoplasm. CONCLUSION: The presence of ghost adipocytes is a rather unique histopathological feature consistent with pancreatic panniculitis and should be considered in combination with the overall clinical picture to determine the underlying etiology. Pancreatic panniculitis can be a primary presenting feature and possible complication of pancreatic disease.

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.

Successful use of amoxicillin-clavulanate acid in a patient with severe wound infection with wound communication secondary to Actinomyces.

INTRODUCTION: Actinomyces is a common genus of bacteria that is typically found in the oral cavity, gastrointestinal tract, and genitourinary tract, as well as on the skin. Gleimia europaea (formerly A europaeus) is a facultative anaerobic gram-positive rod that has been well associated with abscesses of the groin, axilla, and breast, as well as with decubitus ulcer. Infection with this species usually involves multiple abscesses communicating through sinus tracts. Treatment typically requires a prolonged course of penicillin or amoxicillin (up to 12 months). CASE REPORT: A 62-year-old male patient presented with a PI with fistulous tract and tunneling infected with Actinomyces, which was successfully treated with amoxicillin-clavulanic acid. CONCLUSIONS: The outcomes in this case support the use of surgical debridement, meticulous wound care, and appropriate antibiotic coverage to achieve accelerated wound healing of sacral PI with actinomycotic involvement.

The role of the plastic surgeon in wound care.

Wound healing is multifactorial and requires careful management. Plastic surgeons have an important role in optimizing healing of various wound types, including large wounds; wounds in sensitive areas (eg, face, hands, feet); wounds with exposed vessels, nerves, and bone; and wounds for which SOC is unsuccessful; as well as in the use of advanced biologics. It is important for the primary care physician and ancillary health care team to understand timing and basic wound healing principles to know when to consult a plastic surgeon to optimize wound healing for possible flap or skin graft closure. This literature review discusses principles of wound management as they relate to referral from primary care providers to specialists in plastic surgery and transitions of care, along with indications that warrant plastic surgery consultation and underscore the importance of interdisciplinary communication, understanding, and cooperation in wound management. Careful attention to fundamentals, including nutritional status, wound debridement, and comorbidities, combined with a strong understanding of the aforementioned indications that warrant the involvement of a plastic and reconstructive surgeon, can result in efficient, rapid wound healing at relatively minimal cost.

Redesigning Sentinel Lymph Node Biopsy Guidelines in Melanoma Cases.

Background: Accurately staging and prognosticating melanoma classically depends on a sentinel lymph node biopsy (SLNB). The mainstay predictors of SLNB positivity according to the American Joint Committee on Cancer (AJCC) are Breslow depth and ulceration. Nevertheless, even with these predictors, negative SLNBs, even in deep melanomas, are a common occurrence and may result in unnecessary invasive procedures for patients. This suggests that the parameters for determining SLNB candidates are a potential area for improvement in surgical dermatology (surgical oncology and plastic surgery). Methods: The authors conducted a systemic review to assess current AJCC guidelines on when a SLNB in melanoma is indicated. We also investigated how age, mitotic rate, lymphovascular invasion, satellitosis, melanoma subtype, anatomical location, and an immunocompromised state affected positivity rates in sentinel lymph node biopsies in melanoma. Results: These variables significantly impacted SLNB positivity rates and serve as evidence to support the proposal of redesigning SLNB guidelines in melanoma. Conclusions: Integrating the current AJCC guidelines with the newly examined variables will create patient-specific recommendations centered on the aim of reducing the number of invasive procedures while increasing SLNB positivity rates and prognostication.