An 86-year-old man presented with a slowly enlarging, subject to chronic mechanical irritation, pedunculated keratotic papule on the plantar tip of the right hallux in the setting of severe peripheral arterial disease. Excision was deferred until after endovascular revascularization to reduce the risk of nonhealing and limb complications, after which the lesion was removed without wound sequelae. Histopathology demonstrated a conical papule with a central collagenous core and an overlying cap of compact hyperkeratosis. This case highlights key clinicopathologic features that distinguish acral keratotic tumors and underscores the importance of perfusion optimization when planning elective excision on an ischemic limb.

Secondary intention healing after Mohs micrographic surgery (MMS) is often chosen for complex or concave sites, preserving tissue and enabling recurrence surveillance. However, secondary intention healing is associated with prolonged healing, visible scarring, and psychosocial distress. Psychological stress impairs repair through neuroendocrine activation, elevating cortisol and catecholamines that disrupt immune function and delay inflammatory resolution. Inflammation, in turn, hinders fibroblast activity, extracellular matrix remodelling and collagen organization, further slowing closure. Emerging evidence supports a 'psychosocial-inflammatory feedback loop' in which visible wounds heighten distress, distress amplifies inflammation and inflammation delays healing. This review integrates in vitro, animal, and clinical findings demonstrating the biological plausibility and clinical relevance of this loop in Mohs micrographic surgery. We propose a framework combining psychoneuroimmunology and wound biology to explain prolonged recoveries in some secondary intention healing patients. Recognising this interplay can inform closure selection, patient counselling and postoperative care-especially for wounds in highly visible areas. Multidisciplinary strategies combining optimal closure techniques, targeted anti-inflammatory therapies and psychological support may disrupt the cycle, accelerate healing and improve quality of life.

Bacterial biofilms represent a formidable challenge in the treatment of chronic wounds, largely because of their resistance to conventional antibiotics. The emergence of multidrug-resistant (MDR) bacterial strains exacerbates this issue, necessitating a shift towards exploring alternative therapeutic approaches. In response to this urgent need, there has been a surge in research efforts aimed at identifying effective non-antibiotic treatments. Recently noted among the non-antibiotic options are selective serotonin reuptake inhibitors (SSRIs) and beta-adrenergic (β-AR) antagonists. Both have demonstrated antimicrobial activities and wound-healing properties, which makes them particularly promising potential therapeutics for chronic wounds. This review seeks to comprehensively evaluate the landscape of non-antibiotic strategies for managing wound infections. By analysing the latest research findings and clinical developments, it aims to shed light on emerging therapeutic alternatives. Additionally, the review delves into the potential of repurposing systemic therapeutics for topical application, offering insights into the feasibility and challenges associated with current approaches. We also address the necessity of translating promising preclinical results into tangible clinical benefits.

INTRODUCTION:Diabetic foot ulcers (DFUs) are a common complication in diabetes, leading to high amputation risk and significant healthcare costs. Given topical timolol's emergence as a potential wound-healing agent, our study explored its impact on epidermal integrity. METHODS:This study was a post hoc analysis conducted as part of a randomized controlled trial at the Veterans Affairs Northern California Health Care System. Twenty patients, who had DFUs healed in the original trial, 10 in the timolol arm, and 10 in the placebo arm, were enrolled in the study. The primary outcome was transepidermal water loss, measured monthly for 3 months of post-healing using a closed-chamber device. The secondary outcome was re-ulceration rates over 1 year. RESULTS:Transepidermal water loss at 1, 2, and 3 months of post-healing was significantly lower in the timolol group than in the placebo group (p < 0.01). Linear mixed models identified contralateral foot transepidermal water loss as a significant predictor of healed diabetic foot ulcer site transepidermal water loss (estimate = 0.76, p < 0.001). The interaction between timolol treatment and months since healing significantly reduced transepidermal water loss over time (estimate = -2.2, p = 0.002). The use of a wheelchair was also associated with a significant decrease in transepidermal water loss (estimate = -7.7, p = 0.01). Initial transepidermal water loss values were higher in patients who re-ulcerated, but the difference was not statistically significant (p = 0.42). There was no difference in re-ulceration rates in this small pilot study. CONCLUSION:Topical timolol significantly improved skin barrier function in healed DFUs, reducing transepidermal water loss. Although re-ulceration rates were not significantly different, the trend suggests potential benefits. Further studies with larger sample sizes and longer follow-up are needed to confirm these findings and explore transepidermal water loss's predictive value for re-ulceration.

Purpose of Review In recent years, drug repurposing has gained traction as a method to accelerate the availability of effective treatments. This review focuses on timolol, originally a topical non-selective β-adrenergic antagonist used for increased intraocular pressure and glaucoma, and its emerging role in the wound healing landscape—a field that has been lacking in effective treatments for decades. Recent Findings Preclinical and clinical studies have highlighted timolol’s promise as a therapeutic option in wound healing. Its benefits are attributed to various mechanisms including improved re-epithelialization, modulation of inflammation, and wound maturation, in addition to its impacts microbial quorum sensing and virulence. However, existing research also points to the need for larger, more comprehensive clinical trials to determine optimal dosing, efficacy, and safety. Some such trials are presently underway. Summary Timolol presents a new avenue for wound healing therapies, overcoming limitations seen in current treatment options. This review outlines timolol’s historical context in wound care, elaborates on its pharmacological mechanisms, and assesses ongoing research to validate its therapeutic potential. Future studies are needed for more conclusive data on its efficacy and safety in wound management.

Vagus nerve stimulation (VNS) has been approved as a treatment for various conditions, including drug-resistant epilepsy, migraines, chronic cluster headaches and treatment-resistant depression. It is known to have anti-inflammatory, anti-nociceptive and anti-adrenergic effects, and its therapeutic potential for diverse pathologies is being investigated. VNS can be achieved through invasive (iVNS) or non-invasive (niVNS) means, targeting different branches of the vagus nerve. iVNS devices require surgical implantation and have associated risks, while niVNS devices are generally better tolerated and have a better safety profile. Studies have shown that both iVNS and niVNS can reduce inflammation and pain perception in patients with acute and chronic conditions. VNS devices, such as the VNS Therapy System and MicroTransponder Vivistim, have received Food and Drug Administration approval for specific indications. Other niVNS devices, like NEMOS and gammaCore, have shown effectiveness in managing epilepsy, pain and migraines. VNS has also demonstrated potential in autoimmune disorders, such as rheumatoid arthritis and Crohn's disease, as well as neurological disorders like epilepsy and migraines. In addition, VNS has been explored in cardiovascular disorders, including post-operative atrial fibrillation and myocardial ischemia-reperfusion injury, and has shown positive outcomes. The mechanisms behind VNS's effects include the cholinergic anti-inflammatory pathway, modulation of cytokines and activation of specialised pro-resolving mediators. The modulation of inflammation by VNS presents a promising avenue for investigating its potential to improve the healing of chronic wounds. However, more research is needed to understand the specific mechanisms and optimise the use of VNS in wound healing. Ongoing clinical trials may support the use of this modality as an adjunct to improve healing.

Chronic wounds are a common and costly health issue affecting millions of individuals in the United States, particularly those with underlying conditions such as diabetes, venous insufficiency, and peripheral artery disease. When standard treatments fail, advanced wound care therapies, such as skin substitutes, are often applied. However, the clinical effectiveness, indications, and comparative benefits of these therapies have not been well established. In this study, we report on the usage of both acellular and cellular, single and bilayer, natural and synthetic, dermal, and epidermal skin substitutes in a VA hospital system. We performed a retrospective chart review to understand the ordering and usage patterns of advanced wound therapies for patients with chronic wounds at the VA Northern California Health Care System. We examined types of products being recommended, categories of users recommending the products, indications for orders, and rate of repeated orders. Neuropathic, venous, or pressure ulcers were the main indications for using advanced wound matrices. Only 15.6% of patients for whom the matrices were ordered had supporting laboratory tests. Exactly 34.3% of the ordered matrices were not applied. And the use of wound matrices resulted in increased costs per patient visit of $1018-$3450. Our study sheds light on the usage patterns of these therapies in a VA healthcare facility and highlights the need for more robust evidence-based studies to determine the true benefits, efficacy, and cost-effectiveness of these innovative treatment options.

Spindle cell lipomas are a rare type of lipoma usually presenting in middle-aged to older men, often located on the posterior neck or shoulder; presentation on the foot is exceptionally uncommon. We report a 24-year-old man with spindle cell lipomas on the hallux of his left foot. He experienced an uneventful recovery after excision of the mass. We discuss clinical, radiologic, and histopathologic features of spindle cell lipomas and we review the differential diagnosis at this anatomic site.

Venous leg ulcers, the most common leg ulcer, occur in patients with chronic venous insufficiency due to venous hypertension. Evidence supports the conservative treatment with lower extremity compression, ideally between 30-40 mm Hg. Pressures in this range provide enough force to partially collapse lower extremity veins without restricting arterial flow in patients without peripheral arterial disease. There are many options for applying such compression, and those who apply these devices have varying levels of training and backgrounds. In this quality improvement project, a single observer utilised a reusable pressure monitor to compare pressures applied using different devices by individuals in wound clinics with diverse training from specialties of dermatology, podiatry, and general surgery. Average compression was higher in the dermatology wound clinic (n = 153) compared to the general surgery clinic (n = 53) (35.7 ± 13.3 and 27.2 ± 8.0 mm Hg, respectively, p < 0.0001), and wraps applied by clinic staff (n = 194) were nearly twice as likely as a self-applied wrap (n = 71) to have pressures greater than 40 mm Hg (relative risk: 2.2, 95% confidence interval: 1.136-4.423, p = 0.02). Pressures were also dependent upon the specific compression device used, with CircAid®s (35.5 mm Hg, SD: 12.0 mm Hg, n = 159) providing higher average pressures than Sigvaris Compreflex (29.5 mm Hg, SD: 7.7 mm Hg, n = 53, p = 0.009) and Sigvaris Coolflex (25.2 mm Hg, SD: 8.0 mm Hg, n = 32, p < 0.0001). These results indicate that the device-provided pressure may be dependent on both the compression device and the background and training of the applicator. We propose that standardisation in the training of compression application and increased use of a point-of-care pressure monitor may improve the consistency of applied compression, thus improving adherence to treatment and outcomes in patients with chronic venous insufficiency.

Early detection of whether a wound is a "healer" or a "non-healer" using image analysis enables healthcare professionals to administer appropriate interventions. We propose a few-shot wound healing assessment framework, WoundNet, to classify temporal wound image sequences as "healer" or "non-healer." The contributions of this work are twofold: 1) Meta-learning: We study transfer learning approaches to train an image encoder for enhanced feature learning using domain adaption and contrastive learning, and 2) Few-shot classification: We classify image embeddings based on latent space similarity. We analyze the performance of the WoundNet framework in various settings, and experimental results show that temporal wound image sequences can be classified with an accuracy of up to 92%.

BACKGROUND:Patients with chronic wounds have an increased risk of developing allergic contact dermatitis (ACD). Reports of ACD to wound care products are not uncommon. To minimize contact sensitization in patients with chronic wounds, allergenic ingredients should be avoided when possible.OBJECTIVE:With more than 5000 wound care products available in the United States, it is essential to understand which products can be chosen to minimize allergen exposures.METHODS:Ingredients in wound care products in 5 wound care clinics across 2 institutions were cross-referenced with the American Contact Dermatitis Society core allergen series 2020.RESULTS:Of the 267 wound care products included, 97 (36.3%) contained at least one allergen, including 31 dressings/wraps (22.3%), 25 medications (69.4%), 12 cleaning supplies (36.3%), 16 tapes/glues (80%), 2 instruments (14.3%), 8 emollients and vehicles (61.5%), 1 ostomy product (11.1%), and 2 odor-eliminating products (66.7%). Thirty-four different allergens were identified across all products. The most common allergens present in the included items were acrylates and propylene glycol, followed by parabens, cetyl stearyl alcohol, tocopherol, fragrance, and phenoxyethanol.CONCLUSIONS:Many wound care products contain at least one contact allergen, highlighting the importance of clinician education on ACD in the context of wound care product selection.

Background: Poor diabetic foot ulcer (DFU) outcomes have sparked the development of bioengineered cellular and acellular matrix products. Trials using these substitutes have demonstrated varying improvements over standard of care (SOC). However, few directly compare these products to one another, outcomes of which could inform cost-of-care decisions.Methods: This randomized, single-blinded, three-arm, controlled non-inferiority trial carried out at the VA Northern California Health Care System utilized two intervention arms: acellular matrix (ACM) and cellular matrix (CM), and a SOC arm to directly compare effectiveness between up to eight weekly matrix applications for DFU treatment. Patients with a nonhealing DFU who met inclusion/exclusion criteria were block-randomized into one of the three arms by sex, race, and age. The primary outcome was complete re-epithelialization of the ulcer at 12 weeks following treatment onset. All participants who completed the two-week phase-in period were included in primary and safety analyses, per protocol. The margin used to establish non-inferiority was 0. This trial is registered with ClinicalTrials.gov, NCT01450943, and is completed.Findings: 117 patients were included from October 1, 2011, through March 31, 2018, including 35 patients (41 male) in the CM group, 42 (47 male, one female) in the ACM group, 26 (26 male, two female) in the SOC group, including 14 patients who were lost to follow up. Complete re-epithelialization of the ulcer by 12 weeks occurred in 67·3% (N=103) of the total patients; 57·1% (20/35) in the cellular matrix (CM) group, 78·6% (33/42) in the acellular matrix (ACM) group, and 61·5% (16/26) in the SOC group (p>0·05). No differences were found in wound recidivism or adverse event occurrence. Two CM subjects, three ACM subjects, and one SOC subject experienced adverse events.Interpretation: No difference in effectiveness was found between SOC, ACM, and CM, suggesting that rigorous SOC can significantly reduce the economic burden associated with DFU treatment.Trial Registration: This trial is registered with ClinicalTrials.gov, NCT01450943.Funding: This work was supported by VA Merit Award CX000369, MPI SED and RRI.Declaration of Interest: We declare no competing interests.Ethical Approval: The research protocol was approved by relevant institutional review boards at the VA Northern California Health Care System. The trial was performed according to the principles of the Declaration of Helsinki .

Penetrating and blunt trauma to the plantar aspect of the foot are common. Both penetrating and blunt trauma may be associated with an injury to the blood vessels, which may go undetected clinically. A minor puncture, blunt trauma and repeated blunt trauma can injure small arteries leading to an arteriovenous fistula (AVF). The arterial rupture leads to a system of veins creating a small AVF and appearing clinically as a blue colored, painful lesion. A case of such an injury is presented where the clinical examination, magnetic resonance arteriogram and point of service ultrasound with duplex imaging was used to diagnose the AVF. The AVF was treated in the clinic with a percutaneous ultrasound-guided laser procedure. The laser procedure was effective and there was minimal post procedural morbidity.

Dermatology Division, VA Northern California Health Care System, Mather, CA. Correspondence: Harrison Shawa, BS, Dermatology Division, VA Northern California Health Care System, 10535 Hospital Way, Mather, CA 95655 (e-mail: [email protected]). The authors declare no conflicts of interest.