Corrigendum: Spindle cell lipoma: a rare case report on the hallux.

The original article was published on February 15, 2024 and corrected on April 15, 2024.The revised version of the article corrects Figure 2. The changes appear in the revised online PDF copy of this article.

Spindle cell lipoma: a rare case report on the hallux.

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.

Vagus nerve stimulation: Potential for treating chronic wounds.

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.

Patterns of use of advanced wound matrices in the Veterans Administration clinics.

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.

Consistent application of compression: An under-considered variable in the prevention of venous leg ulcers.

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.

Potential Allergens in Wound Care Products.

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.

Potential Allergens in Wound Care Products.

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.

Acral Amelanotic Melanoma Mimicking a Foot Ulcer.

Acral amelanotic melanoma can be difficult to diagnose and is often clinically aggressive. The present report describes a case of an acral amelanotic melanoma presenting as a non-healing wound after mimicking a plantar wart for two years. The decision to biopsy a borderline-suspicious lesion on the lower extremity in an elderly individual must be weighed carefully, as lower extremity biopsy carries a risk of poor wound healing and other complications. We discuss clinical and epidemiologic features that can assist in deciding when to perform a biopsy in this setting and can improve the early detection of acral amelanotic melanoma.

Application of Intralesion Ultrasound-Guided Laser Ablation for Plantar Foot Mass Involving Arteriovenous Fistula: A Case Report.

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.

Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.

Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.

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.

Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study.

BACKGROUND: Diabetic foot ulcers (DFUs) are the most common cause of leg amputations and their management is extremely challenging. Despite many advances and expensive therapies, there has been little success in improving outcomes of DFUs. In prior work our laboratory has examined the effects of beta-adrenergic antagonists (ßAAs) on skin and skin-derived cells. We have shown that ßAAs enhance the rate of keratinocyte migration, promote angiogenesis, and hasten wound healing in scratch wounds in vitro, in animal wound models, and in anecdotally reported cases of chronic wounds that healed successfully after topical application of the ßAA timolol. Thus, we propose to test timolol directly on DFUs to determine if it improves healing above the current standard of care (SOC). This study will examine the efficacy and safety of topically applied beta-antagonist Timoptic-XE® (timolol maleate ophthalmic gel forming solution) in subjects with DFUs. METHODS/DESIGN: This is a phase two, randomized, double-blinded, controlled, and parallel-group clinical trial with two treatment arms, SOC plus topical Timoptic-XE® and SOC plus a non-biologically active gel (hydrogel, as placebo drug). Study subjects with a DFU will be selected from the Veterans Affairs Northern California Health Care System (VANCHCS). Study duration is up to 31 weeks, with three phases (screening phase for two weeks, active phase for up to 12 weeks, with an additional second consecutive confirmatory visit after 2 weeks, and follow-up phase comprising monthly visits for 4 months). Subjects will apply daily either the topical study drug or the placebo on the foot ulcer for 12 weeks or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a monthly follow-up period. DISCUSSION: This is a clinical translation study, moving the investigators' pre-clinical laboratory research into a translational study in which we will analyze clinical outcomes to assess for safety and estimate the efficacy of a topical beta-antagonist in healing of DFUs. The results from this trial may establish new treatment paradigms and safety profile for DFU treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03282981. Registered on June 14th, 2018.

Microbiome-skin-brain axis: A novel paradigm for cutaneous wounds.

Chronic wounds cause a significant burden on society financially, medically, and psychologically. Unfortunately, patients with nonhealing wounds often suffer from comorbidities that further compound their disability. Given the high rate of depressive symptoms experienced by patients with chronic wounds, further studies are needed to investigate the potentially linked pathophysiological changes in wounds and depression in order to improve patient care. The English literature on wound healing, inflammatory and microbial changes in chronic wounds and depression, and antiinflammatory and probiotic therapy was reviewed on PubMed. Chronic wound conditions and depression were demonstrated to share common pathologic features of dysregulated inflammation and altered microbiome, indicating a possible relationship. Furthermore, alternative treatment strategies such as immune-targeted and probiotic therapy showed promising potential by addressing both pathophysiological pathways. However, many existing studies are limited to a small study population, a cross-sectional design that does not establish temporality, or a wide range of confounding variables in the context of a highly complex and multifactorial disease process. Therefore, additional preclinical studies in suitable wound models, as well as larger clinical cohort studies and trials are necessary to elucidate the relationship between wound microbiome, healing, and depression, and ultimately guide the most effective therapeutic and management plan for chronic wound patients.

Ultrasound as a diagnostic and interventional aid at point-of-care in dermatology clinic: a case report.

Ultrasound is currently underutilized in dermatology practice. However, ultrasound provides clinicians with precise and unique information on cutaneous and subcutaneous lesions, while minimizing costs and complications related to more common and invasive diagnostic methods. We report a patient who presented with a tender subcutaneous mass that was diagnosed and treated using point-of-care ultrasound-guidance at the dermatology clinic. Ultrasound revealed features consistent with a ganglion cyst, which was subsequently injected with triamcinolone acetonide under ultrasound-guidance with the resolution of symptoms upon follow-up one month later. Our study demonstrates the utility of ultrasound as an effective, time-efficient diagnostic and interventional aid that can modify dermatology practice.

Interleukin-17: Potential Target for Chronic Wounds.

Chronic wounds exhibit persistent inflammation with markedly delayed healing. The significant burden of chronic wounds, which are often resistant to standard therapy, prompts further research on novel therapies. Since the interleukin-17 family has been implicated as a group of proinflammatory cytokines in immune-mediated diseases in the gut and connective tissue, as well as inflammatory skin conditions, we consider here if it may contribute to the pathogenesis of chronic wounds. In this review, we discuss the interleukin-17 family's signaling pathways and role in tissue repair. A PubMed review of the English literature on interleukin-17, wound healing, chronic wounds, and inflammatory skin conditions was conducted. Interleukin-17 family signaling is reviewed in the context of tissue repair, and preclinical and clinical studies examining its role in the skin and other organ systems are critically reviewed. The published work supports a pathologic role for interleukin-17 family members in chronic wounds, though this needs to be more conclusively proven. Clinical studies using monoclonal interleukin-17 antibodies to improve healing of chronic skin wounds have not yet been performed, and only a few studies have examined interleukin-17 family expression in chronic skin wounds. Furthermore, different interleukin-17 family members could be playing selective roles in the repair process. These studies suggest a therapeutic role for targeting interleukin-17A to promote wound healing; therefore, interleukin-17A may be a target worthy of pursuing in the near future.

Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds.

Objective: There are no safety or absorption studies to guide topical timolol therapy for treatment of chronic wounds. This study was undertaken to address this gap. Approach: A prospective, observational, cross-sectional comparative study of timolol plasma levels in patients after topical administration to a chronic wound, compared with levels in patients after timolol ocular administration for the indication of glaucoma. Results: There was no statistically significant difference in the average plasma level of timolol in wound as compared with glaucoma patients. No bradycardia or wheezing was observed after administration. Innovation: We determined the single time point concentration of timolol in plasma 1 h after application of timolol 0.5% gel-forming solution to debrided chronic wounds, providing insight as to the safety of this emerging off-label treatment. Conclusion: The topical application of timolol for chronic wounds shares the same safety profile as the widely used application of ocular administration for glaucoma.

Limb salvage of the foot with Lisfranc amputation following squamous cell carcinoma.

The indolent character of squamous cell carcinoma of the foot can be misleading and might result in unwarranted excisions or delayed treatment.