Effect of a Topical Gel Based on Adelmidrol + Trans-Traumatic Acid in the Treatment of Diabetic Foot Ulcers: An Open-Label Study.

BACKGROUND: Diabetic foot ulceration is a severe complication of diabetes characterized by chronic inflammation and impaired wound healing. This study aimed to evaluate the effect of a medical device gel based on adelmidrol + trans-traumatic acid in the healing process of diabetic foot ulcers. METHODS: Thirty-seven diabetic patients with foot ulcers of mild/moderate grade were treated with the gel daily for 4 weeks on the affected area. The following parameters were evaluated at baseline and weekly: 1) wound area, measured by drawing a map of the ulcer and then calculated with photo editing software tools, and 2) clinical appearance of the ulcer, assessed by recording the presence/absence of dry/wet necrosis, infection, fibrin, neoepithelium, exudate, redness, and granulation tissue. RESULTS: Topical treatment led to progressive healing of diabetic foot ulcers with a significant reduction of the wound area and an improvement in the clinical appearance of the ulcers. No treatment-related adverse events were observed. CONCLUSIONS: The results of this open-label study show the potential benefits of adelmidrol + trans-traumatic acid topical administration to promote reepithelialization of diabetic foot ulcers. Further studies are needed to confirm the observed results.

Efficacy of topical epigallocatechin gallate (EGCG) 1% on the healing of chronic plantar ulcers in leprosy.

BACKGROUND: Chronic plantar ulcers in leprosy (CPUL) occur in areas that have a sensory and an autonomic nerve impairment where the wound healing takes longer. Framycetin gauze dressing (FGD) is best used in the wound healing process during the inflammatory phase because it contains antibiotics. Epigallocatechin gallate (EGCG) is the highest component in the extract of green tea that can accelerate blood vessel formation, has an anti-inflammatory effect, and reepithelialization. OBJECTIVE: To investigate the effect of topical EGCG 1% on the healing of CPUL. MATERIALS AND METHODS: An analytical experimental approach comparing the topical EGCG 1% and FGD applied every 3 days up to 8 weeks on the healing of CPUL. Size of the ulcers, side effects and possible complications from both approaches were monitored weekly. RESULTS: Ulcer healing in the EGCG group was significantly better than the FGD group with significant clinical and statistical differences (p < .032). There were no side effects in both the study groups. Complications, such as an increase in the size of the ulcer, were noted in one subject in the control group. This may have been caused by FGD and claw foot condition. CONCLUSIONS: EGCG 1% is more effective than FGD in accelerating the healing process of CPUL.

Utilización del sevoflurano de forma tópica en úlceras de la extremidad inferior: revisión sistematizada / Use of sevoflurane topically on leg ulcers: systematized review

Las úlceras de la extremidad inferior siguen siendo en la actualidad un problema global. Las opciones analgésicas para el control del dolor se basan generalmente en medidas farmacológicas con acción local y/o sistémica. El sevoflurano es un anestésico general inhalatorio, asociado a sus efectos sobre el sistema nervioso central, y tradicionalmente no se emplea por otras vías que no sea inhalado. Sin embargo, hoy en día se le conoce una acción analgésica a nivel central y también periférico. Actualmente, su uso clínico ha llevado a algunos autores a considerar la posibilidad de nuevos efectos del sevoflurano a través de la vía tópica. OBJETIVO: Sintetizar las evidencias científicas disponibles sobre el uso del sevoflurano aplicado de forma tópica en úlceras de la extremidad inferior. METODOLOGÍA: Revisión sistematizada de la literatura científica, siguiendo la guía PRISMA. La búsqueda de estudios se realizó en las principales bases de datos bibliográficas, sin límite de fechas ni de idiomas. También se realizó una búsqueda incluyendo resúmenes de congresos. RESULTADOS: Se obtuvieron un total de 120 referencias. Finalmente, ocho de ellas correspondían a los estudios incluidos para la síntesis cualitativa. En la mayoría de los estudios se encontró una disminución del dolor de 8 a 2 puntos en las escalas empleadas. CONCLUSIONES: Los escasos estudios parecen sugerir un importante efecto analgésico aplicado de forma tópica, un probable efecto antibacteriano y un posible efecto promotor de la cicatrización. Sin embargo, son necesarios más estudios comparativos con un tamaño de muestra mayor, con mejor calidad en sus diseños

Leg ulcers are a global problem daily. The analgesic options for pain control are generally based on pharmacological measures with local and / or systemic action. Sevoflurane is a general inhalation anesthetic, associated with its effects on the central nervous system, its use not being traditional by other routes that are not inhaled. However, today it is known an analgesic action at the central level and at the peripheral level. Actually, the clinical use of this product has led some authors to consider the possibility of new effects of Sevoflurane topically. OBJECTIVE: To synthesize the available scientific evidences about the use of Sevoflurane topically on leg ulcers. METHODOLOGY: Systematized review of the scientific literature, following the PRISMA guide. The main bibliographic databases were searched without date or language limits. Also references lists and congress abstracts were searched. RESULTS: 120 references were identified. Finally, 8 of them were selected for qualitative synthesis. In most studies, was found a decrease in pain of 8 to 2 points in the scales used. CONCLUSIONS: The few studies suggest an analgesic effect applied topically, a probable antibacterial effect and a possible healing promoting effect. However, comparative studies of large sample are needed, with a better quality designs

Efficacy of Topical Insulin Therapy for Chronic Trophic Ulcers in Patients with Leprosy: A Randomized Interventional Pilot Study.

BACKGROUND: Chronic trophic ulcers (CTUs), especially those located over the plantar region, are a leading cause of deformity and disability in patients with leprosy. Despite the various treatment modalities available, CTUs can be chronic and refractory to treatment. The successful use of topical insulin in various types of wounds led researchers to evaluate its safety and efficacy in the treatment of plantar CTUs. METHODS: Forty-two patients who had completed a multidrug treatment for leprosy were recruited and randomized into two groups. In the test group, 23 patients received 10 units (0.1 mL) of topical insulin (Actrapid) in 1 mL of normal saline twice daily over treated areas. The placebo group (n = 19) received topical normal saline only. The primary end point was the proportion of patients with complete wound closure by 12 weeks. Secondary end points included time to healing, wound area reduction, Physician Global Assessment of Efficacy scores, and Dermatology Life Quality Index scores at the end of 12 weeks. RESULTS: The majority of CTUs (80%) were situated over the forefoot; the metatarsal head of the hallux was the most common site (86%). Wound healing was faster (0.61 ± 0.31 vs 0.14 ± 0.42 cm per week, P < .0001), and the number of days to complete healing was significantly shorter in the test group compared with the placebo group (31.5 ± 17.6 vs 44.3 ± 16.2 days, P = .02). The only observed adverse effect in the test group was white granular deposits over the CTU (n = 10). CONCLUSIONS: Topical insulin therapy may be a safe, efficacious, cheap, and easily available treatment option in CTUs among patients with leprosy.

A new waterborne chitosan-based polyurethane hydrogel as a vehicle to transplant bone marrow mesenchymal cells improved wound healing of ulcers in a diabetic rat model.

Foot ulcers, a common complication of diabetes, can cause physical incapacity and are derived from several factors, including poor wound healing. New therapeutic strategies are needed to minimize this complication for the sake of patients' health. We therefore developed a new chitosan- polyurethane hydrogel membrane (HPUC) and the test results confirmed that HPUC present low cytotoxicity and improved wound healing when used with mononuclear bone marrow fraction cells in the diabetic rat model. The biodegradable hydrogels were produced in block copolymer networks with a combination of chitosan blocks and biodegradable polyurethane. The membranes were characterized by FTIR, 13C-NMR and thermogravimetry. Swelling and hydrolytic degradation were also evaluated. The non-solubility of the membranes in good solvents and the chemical characterization confirmed that the network structure was formed between the PU and the chitosan through urea/urethane bonds. The findings confirm that the HPUC have interesting properties that make them suitable for wound healing applications.

The bacteriostatic effect of controlled-flux electrolyzed acidic solution on healthy hallucal skin.

BACKGROUND: There are various treatment protocols to manage the increased bacterial load in plantar ulcers. Recently, Controlled-Flux Electrolyzed Acidic Solution (CFEAS), with a pH less than 3, has appeared to be an effective option since its antimicrobial effect could help in the healing of those ulcers. In order to evaluate its potential in this sense, the aim of the present study was to compare bacterial growth on healthy hallucal skin using two types of bandaging (control and Controlled-Flux Electrolysed Acidic Solution). MATERIAL AND METHODS: In a sample of 19 healthy subjects, two experiments were performed. In the first, for each subject, two identical hallux bandages were applied in the early morning. At random between left and right foot, either physiological saline (wetting every 2 h) was applied or nothing (control). In the second, two days later, new bandages were applied as before, but now either wetting with Controlled-Flux Electrolysed Acidic Solution (experimental, again wetting every 2 h) or nothing (control). In each experiment, the bacterial load in the nail fold was assessed at the first moment and after 10 h from standard counts of bacterial colony forming units (CFU). RESULTS: In the first experiment, the CFU counts had increased significantly (p < 0.05) in both toes after the 10-h period. In the second experiment, while the bacterial load increased significantly (p = 0.001) from 0.68 ±â€¯0.8 × 104 CFU/cm2 (the "pre" sample) to 1.3 ±â€¯0.9 × 104 CFU/cm2 (the "post" sample) in the control toe, in the experimental CFEAS toe, the pre sample bacterial load was 0.61 ±â€¯0.6 × 104 CFU/cm2, and the post sample 0.9 ±â€¯0.8 × 104 CFU/cm2, with no significant difference between them (p = 0.221). Negative cultures were obtained in 3 cases (15.78%) of the experimental toe post sample, and equal post and pre counts in 2 cases (10.5%). CONCLUSION: Controlled-Flux Electrolyzed Acidic Solution has an effect on healthy hallucal skin that is bacteriostatic, and in some cases bactericidal. This effect could be very helpful in treating plantar ulcers when there is a greatly increased bacterial load in the wound, thus potentially favoring the normal formation of granulation tissue in the skin and normal healing and closure of the ulcer.

The beneficial effect of traditional Japanese herbal (Kampo) medicine, Hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang), for patients with chronic wounds refractory to conventional therapies: A prospective, randomized trial.

Hochu-ekki-to (HET) is a traditional Japanese herbal (Kampo) medicine for the treatment of severe weakness, loss of appetite, and indigestion in elderly patients and for the prevention of opportunistic infections. The impact of HET on patients with chronic wounds refractory to conventional therapies was investigated in a prospective, randomized trial, including 18 patients divided into medication (7.5 g oral HET per day, n = 9) and control (n = 9) groups. Wound healing during the 12-week study period was scored based on depth, exudate, size, inflammation/infection, granulation tissue, necrotic tissue, and pocket size. At 12 weeks, wound healing progressed in all nine patients in the medication group, whereas wound healing progressed in only three patients in the control group (significant difference, p < 0.01; relative risk: 3.00). In the medication group, the total score decreased significantly at 8 weeks and later. To the best of our knowledge, this study was the first to show that HET promoted the healing of chronic wounds resistant to conventional treatments. HET may be a choice as an adjunctive therapy for chronic wounds, particularly for patients with malnutrition. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031620).

Plantar ulcerative lichen planus: rapid improvement with a novel triple-therapy approach.

Ulcerative lichen planus (ULP) is a rare variant of lichen planus that is characterized by chronic, painful, and disabling ulcerations. Ulcerative lichen planus has been known to be resistant to many treatments, and therapeutic interventions often involve use of aggressive immunosuppressive medications without satisfactory remission of symptoms. We present the case of a 56-year-old man with an 8-year history of painful ulcerations on the right plantar foot as well as a large ulceration of the left lateral tongue. Biopsy confirmed a suspected diagnosis of plantar ULP. The patient developed marked clinical improvement of the cutaneous and oral mucosal lesions with oral and topical steroids, topical tacrolimus, and oral doxycycline after only 4 weeks of treatment. It is important for dermatologists to be aware of the potential diagnosis of plantar ULP, especially in the evaluation of chronic treatment-resistant ulcers that often have been previously misdiagnosed. We introduce this novel therapeutic regimen as a rapidly effective and relatively safe alternative to conventional immunosuppressive agents for long-term management of plantar ULP.

[Research progress of dipeptidyl peptidase 4 inhibitors on healing of chronic diabetic foot ulcers].

Objective: To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers. Methods: The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly. Results: DPP-4 inhibitors can accelerated the ulcer healing. The mechanisms probably include inhibiting the expression of the matrix metalloproteinase (MMP) and restoring the balance of the wound MMP and the tissue inhibitors of MMP; promoting recruitment of endothelial progenitor cells and augmenting angiogenesis; optimizing extracellular matrix construction and the immune response to persistent hypoxia in chronic diabetes wounds, and so on. At present, clinical researches show that DPP-4 inhibitors may be considered as an adjuvant treatment for chronic diabetic foot ulcers. Conclusion: DPP-4 inhibitors show promise in the local wound healing of chronic diabetic foot ulcers. However, more strictly designed, adequately powered, long-term follow-up, and high-quality randomized control trials are needed to further verify their efficacy and safety for chronic diabetic foot ulcers.

The management of livedoid vasculopathy focused on direct oral anticoagulants (DOACs): four case reports successfully treated with rivaroxaban.

Livedoid vasculopathy (LV) is a thrombotic skin disease characterized by episodic painful ulcerations of the distal aspects of the legs. Its healing process typically leaves small porcelain-white scars called atrophie blanche as a result of the occlusion of cutaneous microcirculation. The main goals of the treatment are pain management and the prevention of ulceration and of progressive scarring in the malleolar area. The therapeutic management is still a challenge, however, and most treatments were based on anecdotal off-label protocols. Over such context, direct oral anticoagulants (DOACS) arise as a potential treatment for this disease. This class of medications became an alternative from initial large studies applied on different pathologic scenarios regarding thromboembolic events. In that line, recent case series using DOACS, including rivaroxaban, started to emerge in the literature related to LV and reported successful prevention of cutaneous infarctions and ulcerations, providing physicians with a new promising alternative. The current report describes four cases of long-term recalcitrant LV, in which rivaroxaban monotherapy effectively reduced pain and cutaneous ulcerations in a few weeks of treatment without relevant side effects. The authors also review therapy management of the disease, focused on DOACS, and suggest a step-by-step approach to treat these patients, taking into consideration different resource profiles of each level of local health centers, the gravity of the cases, and risks/benefits for patients.

The efficacy of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) and a mixture of topical hAMMSC-CM + vitamin C and hAMMSC-CM + vitamin E on chronic plantar ulcers in leprosy:a randomized control trial.

BACKGROUND: Healing of chronic plantar ulcers in leprosy (CPUL) typically takes a long time due to impaired neurological function, thereby reducing the levels of growth factors and cytokines. Cytokines can be found in metabolite products from amniotic membrane stem cells. Chronic ulcers are frequently characterized by high levels of reactive oxygen species. Vitamin E (α-tocopherol) is widely used in skin lesions, owing to its antioxidant and anti-inflammatory properties. Vitamin C also has antioxidant, anti-inflammatory, and collagen synthesis properties which are useful in wound healing. Herein, we compared the effects of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) alone and with vitamins C and E on healing of CPUL. METHODS: In this randomized controlled trial, topical agents were applied every 3 days for up to 8 weeks. Ulcer size, side-effects, and possible complications were monitored weekly. RESULTS: Healing percentage increased each week in all groups. Mean difference in ulcer size was highest in the hAMMSC-CM + vitamin E group, implying better progress of wound healing. There were no side-effects or complications. CONCLUSIONS: hAMMSC-CM + vitamin E is best for healing of CPUL.

Polyhexanide 0.2% in treatment of trophic foot ulcers in leprosy - preliminary study.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects peripheral nerves, skin and mucous membranes. The impairment of neural function as well as sensory or sensory-motor disabilities in leprosy continue to be a problem that requires careful attention in the management of patients with the aim to avoid or minimize their progression to prevent sequelae. One of the most common characteristics of these ulcers is the tendency to chronicity, with variable therapeutic response. In this article, we shall discuss the therapeutic management of thirteen trophic leprosy ulcers in eight patients using polyhexanide 0.2% products.

Fifty-Patient Study Evaluating the Efficacy of Modified Collagen With Glycerin in Periwound Skin Management.

The management of chronic nonhealing ulcers pose a great challenge because they are associated with morbidity and increased costs. This report presents the observations of standard management along with application of modified collagen with glycerin (MCG) in the periwound area for management of nonhealing wounds. This observational report included 50 patients (33 male, 17 female) aged 24 to 94 years having nonhealing wounds. All wounds were treated using standard treatment protocols (TIME concept), whereas the periwound severity was assessed using the Harikrishna Periwound Skin Classification (HPSC). All patients received once-daily application of MCG lotion directly in the periwound areas and compression bandaging until there was complete wound healing. Patient compliance was ensured by regular follow-up and counseling. All diabetic patients were counseled to ensure glycemic control during the entire follow-up period. The criteria used for wound healing were based on clinical observation, and proper epithelialization of the wound was the end point. The median age of the wounds was 12.0 weeks (95% CI = 8.00 - 58.08). Majority of the non-healing wounds were diabetic foot ulcers with age of wound between 4 weeks to 15 years. The median time to complete wound healing was 12.71 (95% CI = 10.00-16.67) weeks. Standard treatment protocol of TIME principle with periwound area assessment based on HPSC 2015 and treatment accordingly with topical application of MCG along with additional measures has shown complete healing of nonhealing wounds. However, further large-scale comparative studies are needed to substantiate these effects on a larger population.

The Management of Critically Colonized and Locally Infected Leg Ulcers with an Acid-Oxidizing Solution: A Pilot Study.

OBJECTIVE: Critical colonization or local infection is very common in chronic wounds, but clinically problematic. Because therapeutic options for these conditions are limited in number and efficacy, the study authors tested a new acid-oxidizing solution (AOS [Nexodyn]; APR Applied Pharma Research S.A., Balerna, Switzerland) to determine its ancillary antimicrobial properties and potential support for wound healing. DESIGN AND SETTING: This open-label clinical case series was conducted with a prospective, single-arm design at the Federal County Hospital in Bregenz, Austria. PATIENTS: In the study, 30 patients with critically colonized or locally infected chronic leg ulcers of any origin were included. INTERVENTIONS: The AOS was applied on each leg ulcer at every dressing change for 35 days. MAIN OUTCOME MEASURES: The tolerability and performance of the AOS were assessed by evaluating the ulcer characteristics and comparing them with those at baseline. The clinical course of wounds was analyzed using standard measures for bioburden, local infection, pain, pH, and wound healing. MAIN RESULTS: Application of the solution was well tolerated, and no adverse events were recorded. In all patients, local infection was overcome, and wound bed pH and wound area decreased significantly. In addition, patient pain levels decreased to a level where interventions were not required after study day 7. In 37% of all patients, a complete resolution of chronic ulcers was achieved by the end of the study period. CONCLUSION: According to these results, the AOS seems to be a valid and highly tolerable treatment to support wound healing in locally infected ulcers. Nevertheless, larger controlled cohort studies are needed to substantiate these findings.

Polyhexanide 0 2% in treatment of trophic foot ulcers in leprosy - preliminary study

Abstract: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects peripheral nerves, skin and mucous membranes. The impairment of neural function as well as sensory or sensory-motor disabilities in leprosy continue to be a problem that requires careful attention in the management of patients with the aim to avoid or minimize their progression to prevent sequelae. One of the most common characteristics of these ulcers is the tendency to chronicity, with variable therapeutic response. In this article, we shall discuss the therapeutic management of thirteen trophic leprosy ulcers in eight patients using polyhexanide 0.2% products.

[A Papua New Guinean with three foot ulcers]. / Een Papoea met drie ulcera op zijn voet.

A 25-year-old Papuan presented with three painless foot ulcers with undermined edges, induration and oedema. The appearance was typical for Buruli ulcer, which is caused by Mycobacterium ulcerans. A smear was positive for acid fast bacilli. Buruli ulcers are found in patients from humid and tropical regions and are treated with rifampicin and streptomycin during eight weeks.