The Management of Chronic Graft-Versus-Host Disease Skin Ulcers after Hematopoietic Stem Cell Transplantation: A Case Report.

ABSTRACT: The comprehensive management of a patient with chronic graft-versus-host disease skin ulcers after hematopoietic stem cell transplantation is challenging. This report describes the case of a 53-year-old woman who presented with ulcers on her right leg 140 weeks after a bone marrow transplant. The patient received wound assessment and management based on the Triangle of Wound Assessment and Wound Bed Preparation 2021, respectively. Hydrogel and antibacterial protease dressings were applied along with systemic oral administration of moxifloxacin hydrochloride (two capsules, two times daily) and JiXueGanPian tablets (classic Chinese herbal formula; two capsules, two times daily), hospital-community-home continuous care, and patient-centered education. Finally, after 133 days of nursing, the patient's wound was completely healed without complications or other skin issues. The use of hydrogel combined with the antibacterial protease dressing was a promising technique for handling this type of wound, enhanced by multidisciplinary collaboration. Of course, providing patients with education that focuses on prevention is necessary.

Healing refractory livedoid vasculopathy-related skin ulcers by ozone therapy: a case-based review.

Chronic skin wounds represent a prominent etiological factor in the occurrence of non-traumatic foot amputations on a global scale and pose a substantial threat to the patient's well-being and mortality in the absence of effective treatment strategies. There exists a subset of patients that exhibit an insufficient response to different treatment options, comprising antibiotics, dressings, gauze bandages, debridement, rehabilitation, collagen patch, and vacuum-assisted closure. In this patient group, distinct treatment strategies emerge before surgery and amputation. Ozone therapy is one of them. Ozone exhibits a wide variety of effects such as antimicrobial, anti-inflammatory, antioxidant, and trophic. Its trophic effect is mediated by disinfection, stimulation of granulation tissue, acceleration of the angiogenesis process, and detoxification mechanisms. In this article, we presented the beneficial effect of ozone therapy in a case of chronic skin ulcer associated with livedoid vasculopathy. In this context, we aimed to discuss the role of ozone therapy in the management of chronic skin ulcers. Finally, we focused on ozone therapy as a promising method in inflammatory rheumatic diseases.

Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review.

INTRODUCTION: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs. METHODS: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data. RESULTS: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity. CONCLUSIONS: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

Immersion Ultrasound Therapy in Combination with Manual Therapy in the Treatment of Ischemic Digital Ulcers in Systemic Sclerosis.

Background and Objectives: Digital ulcers (DUs) are the most common complication in patients with Systemic Sclerosis (SSc). They cause pain with hand dysfunction and negatively impact activities of daily and working life. Our study aims to evaluate the efficacy of a combined treatment of manual therapy and ultrasound therapy in SSc patients with ischemic DU (IDU) compared to manual therapy alone. Materials and Methods: We conducted a before-and-after study (non-randomized study). We enrolled a consecutive series of IDU patients undergoing rehabilitation treatment and divided them into two groups: a treatment group consisting of patients undergoing a combination of manual therapy and US water immersion and a standard care group consisting of patients subjected to manual therapy alone. At the time of the first visit (T0) and at the end of the 4-week rehabilitation period (T1), we evaluated functional capacity, pain intensity, ulcer evolution, and quality of life. Results: In the treatment group, we observed a statistically significant improvement in the functional capacity of the hand (DHI: 28.15 ± 11.0 vs. 19.05 ± 8.83; p < 0.05), pain (NRS: 5.55 ± 1.2 vs. 2.9 ± 1.09; p < 0.05), and PSST score (24.4 ± 4.0 vs. 16.2 ± 2.36; p < 0.05). In the standard care group, we observed a statistically significant improvement only for the functional capacity of the hand (DHI: 28.85 ± 9.72 vs. 22.7 ± 7.68; p < 0.05). Finally, from the comparison between the treatment group and the standard care group, we observed statistically significant improvements in pain (2.9 ± 1.09 vs. 4.5 ± 1.07; p < 0.05) and in the PSST scale (16.2 ± 2.36 vs. 20.4 ± 4.02; p < 0.05). Furthermore, at the end of treatment in the treatment group, 15 ulcers (62.5%) were completely healed, while in the standard care group, only 3 ulcers were completely healed (14.3%). Conclusions: Combined treatment with manual therapy and ultrasound therapy appears to be useful in the management of IDU in patients with scleroderma.

Case report and literature review on a large MBC with ulceration.

RATIONALE: Metaplastic breast cancer (MBC) is a rare tumor of the breast, and skin ulceration of breast tumors is a difficult clinical problem that reduces the patient's quality of life. PATIENT CONCERNS: There are currently no Standard Treatment Guidelines for MBC at present, and the treatment for the skin ulceration of breast tumors is limited in clinics. DIAGNOSIS: Here, we report the case of a patient with a large MBC and skin ulceration, accompanied by exudation and odor. INTERVENTION: The combined treatment of albumin paclitaxel and carrelizumab (anti-PD-1 immunotherapy) was effective in reducing the tumor, but it increased the severity of the skin ulceration. After taking traditional Chinese medicine, the skin ulceration healed completely. Then the patient underwent a mastectomy and radiotherapy. OUTCOMES: The patient has a high quality of life and was in good condition after the comprehensive treatment. LESSONS: This suggests that traditional Chinese medicine may have a good auxiliary therapeutic effect on the skin ulceration of MBC.

Combination of Full-Field and Fractional Erbium: YAG Laser for Nonhealing Wounds.

BACKGROUND: To evaluate the outcomes of a heterogeneous group of patients with chronic ulcer receiving a combination regimen of full-field and fractional erbium-doped yttrium aluminum garnet (erbium: YAG) laser applications. METHODS: Enrolled in this study were patients with chronic ulcer who had received at least 2 erbium: YAG laser sessions. Fractional applications followed the initial full-field application for debridement. The therapeutic outcomes were evaluated by serial photographs. The primary outcome measure was the proportion of patients achieving complete re-epithelialization at the first year. RESULTS: Forty-three treatment regions from 23 patients between 40 and 90 years (F: M = 11:12; age: 60.3 ± 15.5 years, mean ± SD) were eligible. The ulcers' median duration was 24 months (min-max: 2-240 months). The median number of laser sessions was 5 (min-max: 2-12). Of arterial (n = 13), immunologic (n = 9), venous (n = 8), diabetic (n = 8), and mechanical ulcers (n = 5), the primary outcome measure was achieved in 69%, 77.7%, 75%, 88.8%, and 100% of the groups, respectively. CONCLUSION: Full-field erbium: YAG laser applications preserve the vascular architecture and enable delicate debridement. Ongoing maintenance fractional laser sessions promote wound healing. Similar to the previous reports of erbium: YAG laser in venous and diabetic ulcers, arterial ulcers, and ulcers of immunologic origin demonstrated an objective treatment response along with different adjuvant approaches.

Evidence-Based Nutritional Interventions in Wound Care.

BACKGROUND: The role of nutritional intervention in wound care has been a topic of controversy. Although the efficacy of macronutrient supplementation has been well described, there is a paucity of evidence and no official recommendation regarding the use of vitamins and minerals to optimize wound healing. This is the first review of vitamin and mineral wound intervention that systematically summarizes the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and distills the evidence by wound type. METHODS: In this comprehensive review, the authors outline the nutrients and delivery methods used in the identified studies, analyze reported treatment outcomes, summarize nutrient effectiveness, and propose evidence-based conclusions to improve wound healing outcomes and enhance the consistency of nutritional intervention in wound care. RESULTS: Thirty-six studies with a combined total of 2339 patients investigated the use of oral, topical, or intravenous vitamin and/or mineral supplementation for treatment of the following wound types: burn wounds (n = 3), pressure ulcers (n = 7), diabetic ulcers (n = 4), venous ulcers (n = 7), digital ulcers (n = 1), skin incisions (n = 9), hypertrophic scars (n = 4), and sinonasal wounds (n = 1). Improved outcomes were reported in patients with burn wounds receiving vitamins A, B1, B6, B12, D, and E and zinc, calcium, copper, magnesium, selenium, and zinc; patients with pressure ulcers receiving vitamin C and zinc; patients with diabetic ulcers receiving vitamin A, B9, D, and E; patients with venous ulcers receiving zinc; and patients with hypertrophic scars receiving vitamin E. CONCLUSIONS: Based on the high-level data provided in this review, the use of specific nutritional interventions may improve the outcome of certain wound types. Further investigation is warranted to draw definitive conclusions.

Locoregional Treatments for Digital Ulcers in Systemic Sclerosis: A Systematic Review.

The management of digital ulcers in systemic sclerosis is difficult. While the 2017 European League Against Rheumatism (EULAR) guidelines clearly defined the use of systemic therapies for digital ulcers, little is known about the efficacy of locoregional treatments. The aim of this review is to systematically assess the spectrum of published locoregional therapies for digital ulcers. A total of 58 studies were included. Among the different locoregional treatment strategies described, injections of fat-derived cells and botulinum toxin showed promising results in the reduction of pain and the number of digital ulcers. By contrast, this review found that sympathectomy yielded disappointing results, with low rates of effectiveness and frequent recurrence. For other treatments, such as hyperbaric oxygen therapy, phototherapy (ultraviolet A), low-level light therapy, intermittent compression, Waon therapy, extracorporeal shockwave, vitamin E gel, and topical dimethyl sulphoxide, the conflicting results or limited published data reflected the low level of evidence. Larger randomized clinical trials are required to confirm the validity of promising techniques.

Clinical Features, Prognostic Factors, and Treatment Interventions for Ulceration in Patients With Infantile Hemangioma.

Importance: Ulceration is a common complication of infantile hemangioma (IH), which leads to substantial morbidity. Ulceration in IH has not been systematically studied since the advent of ß-blocker therapy for IH. Objectives: To examine treatment interventions used for ulceration in IH and identify clinical prognostic indicators of healing time. Design, Setting, and Participants: A retrospective, multicenter cohort study was conducted on 436 consecutive patients with a clinical diagnosis of ulcerated IH and available clinical photographs. Patients receiving care at tertiary referral centers evaluated between 2012 and 2016 were included; statistical and data analysis were performed from February 7 to April 27, 2020. Exposures: Clinical characteristics, treatment interventions, course, complications, and resource use were analyzed. Treatment interventions for ulceration in IH included local (wound care, topical), systemic (ß-blocker, corticosteroids), and procedural (pulsed-dye laser). Main Outcomes and Measures: The primary end point was time to complete or nearly complete ulceration healing. Clinical characteristics were analyzed to determine the responses to most common interventions and prognostic factors for healing of ulceration. Results: Of the 436 patients included in the study, 327 were girls (75.0%); median age at ulceration was 13.7 weeks (interquartile range, 8.86-21.30 weeks). The median heal time was 4.79 weeks (95% CI, 3.71-5.86 weeks) with wound care alone, 5.14 weeks (95% CI, 4.57-6.00 weeks) with timolol, 6.36 weeks (95% CI, 5.57-8.00 weeks) with a systemic ß-blocker, and 7.71 weeks (95% CI, 6.71-10.14 weeks) with multimodal therapy. After adjusting for IH size, a dose of propranolol less than or equal to 1 mg/kg/d was associated with shorter healing time compared with higher propranolol doses (hazard ratio, 2.04; 95% CI, 1.11 to 3.73; P = .02). Size of the IH was identified as a significant prognostic factor for healing time in multivariable analysis. Increasing size of IH portends a proportionately longer time to heal of the ulceration. Conclusions and Relevance: Despite the use of ß-blockers, this cohort study found that a subset of patients with IH ulceration continued to experience prolonged IH healing times. Larger IH size appears to be a poor prognostic factor for time to heal. For patients requiring systemic therapy, initiation of propranolol at lower doses (≤1 mg/kg/d) should be considered.

Influence of hyperbaric oxygen therapy on thrombus formation ability in humans.

Background: Hyperbaric oxygen (HBO2) therapy was introduced nearly 300 years ago. However, its effect on thrombus formation is unclear. This may be because platelet and coagulation functions are unstable, yielding variable results; hence, accurate measurement is difficult. Our study aimed to analyze changes in thrombus formation before and after HBO2 therapy by using a total thrombus formation analysis system (TTAS). Methods: Six patients were prescribed HBO2 therapy for skin and soft tissue ulcers, and necrotic fasciitis. Blood samples were collected immediately before and after treatment. Then samples were put into a reservoir that connected to AR-chip to assess changes in the thrombus formation ability of both platelets and coagulation factors. We examined the differences in the thrombus formation ability using T-TAS. Time until the onset of white thrombus formation (T10) and complete occlusion of the capillary (T80) were analyzed by a two-way repeated measure analysis of variance (ANOVA). Results: The duration to pressure increase of samples after HBO2 therapy was longer than the duration before HBO2 therapy (p<0.05). This suggests decreased clot adhesiveness to the inner surface of the simulated blood vessel and reduced clot formation ability. Conclusions: The results for T10 and T80 suggest that HBO2 therapy reduced thrombus formation ability in the enrolled patients. We believe that T-TAS is a promising method to predict the efficacy of HBO2 therapy.

ARTERIAL INSUFFICIENCIES: Hyperbaric Oxygen Therapy for Selected Problem Wounds.

The use of hyperbaric oxygen (HBO2) for the treatment of selected problem wounds has focused almost entirely on the diabetic foot ulcer (DFU) in recent years. The prevalence of DFUs in today's patient population and the reimbursement available for the treatment of DFUs have given it priority status in discussions about problem wounds, but there are sound fundamental reasons why additional oxygen may have benefits in the treatment of non-DFU wounds.

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound.

In recent years, several studies suggested that the ability of hyperbaric oxygen therapy (HBOT) to promote healing in patients with diabetic ulcers and chronic wounds is due to the reduction of inflammatory cytokines and to a significant decrease in neutrophils recruitment to the damaged area. α4 and ß2 integrins are receptors mediating the neutrophil adhesion to the endothelium and the comprehension of the effects of hyperbaric oxygenation on their expression and functions in neutrophils could be of great importance for the design of novel therapeutic protocols focused on anti-inflammatory agents. In this study, the α4 and ß2 integrins' expression and functions have been evaluated in human primary neutrophils obtained from patients with chronic non-healing wounds and undergoing a prolonged HBOT (150 kPa per 90 minutes). The effect of a peptidomimetic α4ß1 integrin antagonist has been also analyzed under these conditions. A statistically significant decrease (68%) in ß2 integrin expression on neutrophils was observed during the treatment with HBO and maintained one month after the last treatment, while α4 integrin levels remained unchanged. However, cell adhesion function of both neutrophilic integrins α4ß1 and ß2 was significantly reduced 70 and 67%, respectively), but α4ß1 integrin was still sensitive to antagonist inhibition in the presence of fibronectin, suggesting that a combined therapy between HBOT and integrin antagonists could have greater antinflammatory efficacy.

Frontiers in translational systemic sclerosis research: A focus on the unmet 'cutaneous' clinical needs (Viewpoint).

This viewpoint considers four cutaneous unmet clinical needs of patients with systemic sclerosis (SSc), namely the rapidly progressive skin thickening (scleroderma) which occurs early on in diffuse cutaneous disease; digital (finger and toe) ulcers; calcinosis; and cutaneous telangiectases. All four problems cause pain, disability and/or disfigurement, all impact on quality of life, and for each, we require effective treatments. For each unmet need, we give a brief description of the clinical problem (including clinical burden), pathophysiology and current treatment, followed by a personal viewpoint of the key questions which research must address. For the painful, debilitating skin thickening of early diffuse cutaneous SSc, studies are required to decide whether corticosteroids are effective and safe (current opinion is divided) and whether phototherapy approaches have a role. Also, we need to develop and validate reliable outcome measures for clinical trials of promising new therapies: these could be composite indices, novel non-invasive imaging methods and patient-reported outcome measures, possibly in combination as they provide complementary information. For digital ulcers, again we require validated outcome measures for clinical trials. We also need to explore local (including topical) treatments, which are free from systemic adverse effects, and preventative strategies for high-risk patients. For calcinosis, we need to better understand pathophysiology, to validate outcome measures and to develop topical treatments. For telangiectases, we need to "use" these highly accessible lesions to help unravel the vascular pathophysiology of SSc and explore their different properties as potential biomarkers.

Traditional and advanced therapeutic modalities for wounds in the paediatric population: an evidence-based review.

OBJECTIVE: Children can have non-healing wounds due to a wide range of pathologies, including epidermolysis bullosa (EB), pilonidal disease and Stevens-Johnson syndrome, with some causes being iatrogenic, including extravasation injuries and medical device-related hospital-acquired pressure ulcers. Furthermore, paediatric wounds are vastly different from adult wounds and therefore require a different treatment approach. While there are numerous types of dressings, topical remedies, and matrices with high-tier evidence to support their use in adults, evidence is scarce in the neonatal and paediatric age groups. The purpose of this review is to discuss the basic principles in paediatric wound management, as well as to present new treatment findings published in the literature to date. The benefits and risks of using different types of debridement are discussed in this review. Various topical formulations are also described, including the need to use antibiotics judiciously. METHOD: Databases were searched for relevant sources including Pubmed, Embase, Web of Science and DynaMed. Search terms used included 'wound care', 'wound management', 'paediatrics', 'children', 'skin substitutes', and 'grafts'. Additionally, each treatment and disease entity was searched for relevant sources, including, for example: 'Apligraf', 'dermagraft', 'Manuka honey', 'antibiotic', 'timolol', and 'negative pressure wound therapy' (NPWT). RESULTS: Amniotic membrane living skin equivalent is a cellular matrix that has been reportedly successful in treating paediatrics wounds and is currently under investigation in randomised clinical trials. Helicoll is an acellular matrix, which shows promise in children with recessive dystrophic EB. NPWT may be used as a tool to accelerate wound closure in children; however, caution must be taken due to limited evidence to support its safety and efficacy in the paediatric patient population. Integra has been reported as a useful adjunctive treatment to NPWT as both may act synergistically. Hospitalised children and neonates frequently have pressure ulcers, which is why prevention in this type of wound is paramount. CONCLUSION: Advancements in wound care are rapidly expanding. Various treatments for non-healing wounds in paediatric and neonatal patients have been reported, but high tier evidence in these populations is scarce. We hope to shed light on existing evidence regarding the different therapeutic modalities, from debridement techniques and dressing types to tissue substitutes and topical remedies. There have been promising results in many studies to date, but RCTs involving larger sample sizes are necessary, in order to determine the specific role these innovative agents play in paediatric wounds and to identify true safety and efficacy.

NMR-based metabolomic analysis for the effects of Huiyang Shengji extract on rat diabetic skin ulcers.

ETHNOPHARMACOLOGICAL RELEVANCE: Huiyang Shengji formula (HSF) is a compound Chinese herbal medicine prescription, and has long been used for treating chronic non-healing wounds. AIM OF THE STUDY: The purpose of this study was to provide new insight into molecular mechanisms of healing effects of the HSF treatments. MATERIALS AND METHODS: We established a rat diabetic skin ulcer (DSU) model, and assessed healing effects of four HSF treatments on DSUs by calculating wound healing rates and immunohistochemical detection of the expressions of angiogenesis-related factors in the model rats (Mod) relative to normal rats (Nor), including Huiyang extract (HE), Shengji extract (SE), Huiyang Shengji extract (HSE) and HSE associated with acupuncture (Ac-HSE). We then performed NMR-based metabolomic analyses on skin tissues of the Nor, Mod, HSE-treated, Ac-HSE-treated rats to address metabolic mechanisms underlying these effects. RESULTS: These treatments up-regulated expressions of two angiogenesis-related factors VEGF and CD31, and improved efficacy of healing DSUs, in which HSE and Ac-HSE exhibited the most significant effects. Compared with Mod, HSE and Ac-HSE groups shared four characteristic metabolites (lactate, histidine, succinate and acetate) and four significantly altered metabolic pathways with Nor. Both HSE and Ac-HSE treatments could partly reverse the metabolically disordered pathological state of DSUs to the normal state. They might improve wound healing through promoting glucose metabolism, BCAAs metabolism, and enhancing antioxidant capacity and angiogenesis in DSU tissues. Ac-HSE significantly enhanced wound healing rates compared to HSE, potentially owing to significant capacities of enhancing anti-oxidation and angiogenesis and interfering three more metabolic pathways. CONCLUSIONS: This work provides a mechanistic understanding of the healing effects of the HSE and Ac-HSE treatments on DSUs, is of benefit to improvements of the HSF treatments for clinically healing chronic non-healing wounds.

Elevated Arsenic and Lead Concentrations in Natural Healing Clay Applied Topically as a Treatment for Ulcerative Dermatitis in Mice.

Ulcerative dermatitis in laboratory mice remains an ongoing clinical problem and animal welfare issue. Many products have been used to treat dermatitis in mice, with varying success. Recently, the topical administration of healing clays, such as bentonite and green clays, has been explored as a viable, natural treatment. We found high concentrations of arsenic and lead in experimental samples of therapeutic clay. Given the known toxic effects of these environmental heavy metals, we sought to determine whether the topical administration of a clay product containing bioavailable arsenic and lead exerted a biologic effect in mice that potentially could introduce unwanted research variability. Two cohorts of 20 singly housed, shaved, dermatitis free, adult male CD1 mice were dosed daily for 2 wk by topical application of saline or green clay paste. Samples of liver, kidney and whole blood were collected and analyzed for total arsenic and lead concentrations. Hepatic and renal concentrations of arsenic were not different between treated and control mice in either cohort; however, hepatic and renal concentrations of lead were elevated in clay treated mice compared to controls in both cohorts. In addition, in both cohorts, the activity of δ-aminolevulinate acid dehydratase, an enzyme involved with heme biosynthesis and a marker of lead toxicity, did not differ significantly between the clay-treated mice and controls. We have demonstrated that these clay products contain high concentrations of arsenic and lead and that topical application can result in the accumulation of lead in the liver and kidneys; however, these concentrations did not result in measurable biologic effects. These products should be used with caution, especially in studies of lead toxicity, heme biosynthesis, and renal α2 microglobulin function.

Asiaticoside nitric oxide gel accelerates diabetic cutaneous ulcers healing by activating Wnt/ß-catenin signaling pathway.

Diabetic ulcers, gangrene, local infections and other traumatic symptoms of wound healing are all directly related. Promoting the early healing of diabetic cutaneous ulcers (DCU) and reducing the disability and treatment costs is an important research project integrating traditional Chinese and Western medicine. Nitric oxide (NO) is a key component of wound healing, and endogenous NO secretion is insufficient during the development of DCU. It has been reported that exogenous NO can promote wound healing, but exogenous NO has a short half-life and is difficult to adhere to the skin. Asiaticoside (AC) is extracted from the traditional Chinese medicine Centella asiatica, and has angiogenic, anticancer, antioxidant, anti-inflammatory, and wound-healing effects. Therefore, our study is based on the hypothesis that the combination of AC and NO to treat DCU is possible. In this study we considered gels of AC and NO, and evaluated the effects of the gel on DCU healing. Based on our study, it was found that the combined effect of asiaticoside and NO could accelerate the healing rate of DCU wounds. The asiaticoside NO gel can inhibit the growth of bacteria in the wound surface, alleviate the inflammatory reaction of wound, and increase the expression of VEGF, iNOS, eNOS and CD34. Our research shows that asiaticoside NO gel may promote DCU wound healing by regulating Wnt/ß-Catenin signaling pathway. It will provide new targets and strategies for the diagnosis and treatment of DCU.

Electrical Stimulation in the Treatment of Lymphedema and Associated Skin Ulcers.

Background: Lymphedema is a disorder in which lymph accumulates in the interstitial spaces due to poor lymphatic flow resulting from hypoplasia or aplasia of the lymphatic vessels, or to morpho-functional alterations that impair lymphatic flow. Lymphedema is a debilitating condition associated initially with inflammation that then degenerates into hardening of affected tissues and the formation of ulcers on the skin of affected limbs. No definitive treatment is available. The only therapy for lymphedema consists of physiotherapy, surgery, and compression to reduce impairment, which only treats the symptoms, not the causes. A possible new therapy that could reinforce the treatment of lymphedema progression and complications is electrical stimulation (ES). Many studies underline the effects of electric currents on the different cell mechanisms associated with disease. Methods and Results: In this review, we summarize the effects of ES on the molecular and cellular processes involved in the pathophysiology of lymphedema, highlighting their therapeutic potential for edema reduction, ulcer repair, and restoration of lymphatic flow in vitro and in vivo. Conclusions: ES exerts its effect on the main stages that characterize lymphedema, from its onset to ulcer formation. There are few evidences on lymphatic models and more molecular studies are needed to understand the mechanism of action of this application in the treatment of lymphedema.

Beneficial Effect of Intense Pulsed Light on the Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVE: Wound healing in diabetes mellitus (DM) patients is one of the major health concerns globally. Intense pulsed light (IPL) has been widely used in cosmetic dermatology via mechanisms involving fibroblast stimulation, collagen synthesis, and dermal remodeling, which are events that also occur during the process of wound healing. This present study was aimed to evaluate the possible beneficial effect of IPL on the wound healing in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in Sprague-Dawley rats using streptozotocin. The rats were randomly divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL exposure and wounding (DM + IPL-Con group). The wounds were created on the dorsal skin of rats. Wound closure rate, collagen deposition, and angiogenesis were assessed. RESULTS: There were no significant differences in the wound closure rate and mean time to wound closure between IPL-treated diabetic rats and normal rats. By contrast, delayed wound closure and prolonged mean time to wound closure were both noticed in DM only group. Enhanced collagen deposition and angiogenesis were observed in IPL-Pre, but not IPL-Con diabetic rats, as compared with untreated DM rats. CONCLUSION: Results of this study may provide novel insight into future preventive strategies using IPL for the management of wounds in diabetic patients. Lasers Surg Med. © 2019 Wiley Periodicals, Inc.