Network Pharmacology Study on Herb Pair Bletilla striata-Galla chinensis in the Treatment of Chronic Skin Ulcers.

BACKGROUND: Herb pair Bletilla striata-Galla chinensis (BS-GC) is a classic combination of topical traditional Chinese medicine formulae in the treatment of chronic skin ulcers (CSUs). OBJECTIVE: The aim of this study is to explore the effective active ingredients of BS-GC, as well as the core targets and signal transduction pathways of its action on CSUs. METHODS: The ingredients of BS-GC were obtained from TCMSP and HERB databases. The targets of all active ingredients were retrieved from the SwissTargetPrediction database. The targets of CSUs were obtained from OMIM, GeneCards, Drugbank, and DisGeNET databases. A drug-disease target protein-protein interaction (PPI) network was constructed to select the most core targets, and an herb-ingredient-target network was built by utilizing Cytoscape 3.7.2. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG) analysis and verified the results of network pharmacology through molecular docking. RESULTS: A total of 40 active ingredients from the herb pair BS-GC were initially screened, and a total of 528 targets were retrieved. Meanwhile, the total number of CSU targets was 1032. Then, the number of common targets between BS-GC and CSUs was 107. The 13 core targets of herb pair BS-GC with CSUs were filtered out according to the PPI network, including AKT1, TNF, EGFR, BCL2, HIF1A, MMP-9, etc. The 5 main core active ingredients were 1-(4-Hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene-4,7-diol, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol, physcion, dihydromyricetin, and myricetin. The main biological processes were inflammation, oxidative stress, and immune response, involving the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, NF-κB signaling pathway, and calcium signaling pathway. Molecular docking results showed good binding activity between the 5 main core active ingredients and 13 core targets. CONCLUSION: This study predicted the core targets and signal transduction pathways in the treatment of CSUs to provide a reference for further molecular mechanism research.

Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat. OBJECTIVE: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs. RESULTS: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines. CONCLUSION: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections.

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.

Effectiveness of a kinesio-taping-based treatment in stage IV sacral pressure ulcers in older patients: a pilot study.

OBJECTIVE: As reduced tissue vascularity is one of the mechanisms that prevent skin ulcers from healing, treatments that can improve local circulation could accelerate their clinical resolution. Given that kinesio-taping (KT) can improve tissue blood circulation and lymphatic drainage, we aimed to determine whether applying KT close to stage IV pressure ulcers (PUs) could improve their healing. METHOD: Older patients with stage IV sacral PUs, and impaired mobility and functional dependency who were consecutively admitted in a six-month period to the Home Care service of Galliera Hospital (Genoa, Italy) were screened for participation in this pilot clinical trial. Patients' PUs were divided into two treatment areas-in the experimental intervention, KT was applied close to a portion of the PU, while the contralateral portion of the same lesion was treated according to the standard protocol ('control'). The surface reduction of both portions was measured every four days, for a total of five examinations (timepoints (T2-T6) after the baseline evaluation (T1). RESULTS: A total of 12 patients (male=5, female=7; mean age 78.83±8.94 years) fulfilled the inclusion criteria and were enrolled in the study. At all timepoints (T2-T6), the mean percentage reduction was significantly greater in KT-treated areas than in control areas: T2=20.66% versus 6.17%, respectively; p<0.001; T3=37.33% versus 17.31%, respectively; p<0.001; T4=57.01% versus 30.06%, respectively; p<0.001; T5=69.04% versus 40.55%, respectively; p<0.001; and T6=80.34% versus 51.91%, respectively; p<0.001. Furthermore, from T3 onwards, a significantly higher number of KT-treated areas than control areas had halved in size, the maximum difference being recorded at T5 (10 versus two, respectively; p=0.002). CONCLUSION: From the findings of this pilot study, KT would seem to be an effective, rapid, low-cost therapy for advanced sacral PUs in older patients with impaired mobility and functional dependency. Declaration of interest: The authors have no conflicts of interest to declare.

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.

Limb Salvage with Multiple Modalities: A Case Report of a Diabetic Heel Ulcer Associated with Peripheral Arterial Disease.

ABSTRACT: A large diabetic heel ulcer with peripheral arterial disease is an independent predictor of limb loss; below-knee amputation is not uncommon in such cases. One treatment is multimodal therapy, which includes partial calcanectomy. Because there is a limit to the ulcer surface area that can be sutured after partial calcanectomy, the remaining raw surface is treated with another method. In this case report, the authors describe a patient with peripheral arterial disease who had a 7 × 9-cm diabetic heel ulcer. The patient was treated with partial calcanectomy after catheter-based endovascular therapy revascularization and then maggot therapy after residual-wound dimensions were reduced by negative-pressure wound therapy.

Methotrexate Cutaneous Ulceration: A Systematic Review of Cases.

BACKGROUND: Methotrexate cutaneous ulceration is a rare methotrexate complication, and has only been described in case reports and case series. OBJECTIVE: To document patient characteristics, morphologic features, and mortality risk factors for methotrexate cutaneous ulceration. METHODS: A systematic literature review of PubMed and Embase (last date 1 November 2021) was performed with data collected from case reports and case series. This study was limited to cases of cutaneous ulceration; presence of oral ulceration was collected from within these cases. RESULTS: 114 cases (men = 57.9%, mean age = 61 years) of methotrexate cutaneous ulceration met inclusion criteria. Psoriasis (69.3%), rheumatoid arthritis (18.4%), and mycosis fungoides (6.1%) were the most common indications for methotrexate use. Morphologies included erosions localized to psoriatic plaques (33.3%), epidermal necrosis/necrolysis (35.1%), localized ulceration (16.7%), and skin-fold erosions (5.3%). Methotrexate dose preceding toxicity varied greatly; median 20 mg/week, interquartile range 15-40 mg/week, range 5-150 mg/week. Most patients had risk factors for serum toxicity (baseline renal dysfunction = 37.8%, concurrent NSAID use = 28.1%, inadequate folic acid use = 89.1%). Thirty percent of cases involved mistakenly high methotrexate doses. Fourteen patients (12%) died. Absence of folic acid use (69% vs. 100%, p value < 0.001), pancytopenia (33% vs. 86%, p value < 0.001), and renal dysfunction at presentation (47% vs. 92%, p value < 0.001) were associated with increased mortality. LIMITATIONS: Selection bias present due to abstraction from case reports and case series. CONCLUSION: Methotrexate cutaneous ulceration is commonly preceded by dosage mistakes, absence of folic acid supplementation, and concurrent use of nephrotoxic medications. Renal impairment, pancytopenia, and absence of folic acid supplementation are key risk factors for mortality from this adverse medication reaction. Providers should regularly monitor methotrexate dosing adherence, drug-drug interactions, and perform routine laboratory evaluation. Index of suspicion for this toxicity should remain high given the varied clinical presentation and high mortality.

Efficacy of local oxygen-ozone therapy for the treatment of digital ulcer refractory to medical therapy in systemic sclerosis: A randomized controlled study.

BACKGROUND: This study aimed to investigate the efficacy of local oxygen-ozone therapy in systemic sclerosis (SSc) patients with digital ulcers (DUs) who were resistant to medical therapy and had impairment in activities of daily living. METHODS: Participants' demographic data, and clinical parameters were recorded. Twenty-five SSc patients with DUs were randomized to the ozone group (I) (n = 13) to receive medical treatment plus local oxygen-ozone therapy and the control group (II) (n = 12) to receive medical treatment only. Hand functions were assessed using the Health Assessment Questionnaire (HAQ) and the Modified Hand Mobility in Scleroderma (HAMISm) test. Clinical parameters, HAQ, and mHAMIS scores were re-evaluated in participants 4 weeks after the initiation of treatment. RESULTS: Demographic and clinical characteristics of the two groups showed no significant differences. At 4 weeks after the initial treatment, the efficacy rate was significantly higher in the ozone group than that in the control group (92% versus 42% P = 0.010). Clinical parameters, HAQ, and HAMISm scores were significantly improved in the treatment group compared to those in the control group (P < 0.05). CONCLUSION: Local oxygen-ozone therapy was effective in the treatment of SSc patients with resistant DUs and improved clinical parameters and functional disability.

Gene set enrichment analysis and ingenuity pathway analysis to identify biomarkers in Sheng-ji Hua-yu formula treated diabetic ulcers.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-ji Hua-yu (SJHY) formula is a Chinese herbal prescription for diabetic ulcers (DUs) treatment, which can accelerate wound reconstruction and shorten the healing time. However, its mechanism role maintains unclear. AIM OF THE STUDY: To elucidate the molecular mechanisms of SJHY application on DUs. MATERIALS AND METHODS: To begin with, transcriptome sequencing was adopted to identified differentially expression mRNAs among normal ulcers, DUs, and DUs + SJHY treatment in vivo. Liquid chromatography-tandem mass spectrometry was applied for the quality control of SJHY formula. GO and KEGG enrichment analysis were used to identify the mechanisms underlying the therapeutic effect of SJHY formula, and then gene set enrichment analysis and ingenuity pathway analysis were conducted for functional analysis. Further, qPCR detection was performed in vivo for validation. RESULTS: SJHY administration could regulate the glucose metabolic process, AMPK and HIF-1 pathway to accelerate healing processes of DUs. Besides, CRHR1, SHH, and GAL were identified as the critical targets, and SLC6A3, GRP, FGF23, and CYP27B1 were considered as the upstream genes of SJHY treatment. Combined with animal experiments, the prediction results were validated in DUs mice model. CONCLUSIONS: This study used modular pharmacology analysis to identify the biomarkers of SJHY formula and provide the potential therapeutic targets for DUs treatment as well.

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.

Open study of photodynamic therapy for skin ulcers infected with MRSA and Pseudomonas aeruginosa.

BACKGROUND: Drug-resistant bacterial infections are a global problem. Novel treatment methods that simultaneously control infection and promote wound healing without leading to new resistant bacteria are needed. Photodynamic therapy (PDT) is a useful antibiotic-free treatment approach. Our previous studies have shown that PDT for skin ulcers infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) can achieve infection control and promoting wound healing in vitro and in vivo murine model. Here, we investigated the safety and effectiveness of PDT with 5-aminolevulinic acid (ALA-PDT) for human skin ulcers infected with MRSA and PA. METHODS: ALA-PDT with macrogol ointment containing 0.5% ALA-HCl and 0.005% EDTA-2Na (wavelength 410 nm, 10 J/cm2) was performed on consecutive days in patients aged ≥20 years who had skin ulcers infected with MRSA and PA. RESULTS: Six of our seven patients showed a clear tendency for ulcer area reduction to ≤60% of that measured at baseline. ALA-PDT was judged to be completely safe in all patients; only one patient had an increase in bacterial count. CONCLUSIONS: ALA-PDT is safe and effective for MRSA and PA infected skin ulcers to control and heal wound.

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.

[Analysis of animal models of chronic skin ulcers based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

Based on the characteristics of clinical symptoms of chronic skin ulcers in traditional Chinese and Western medicine, the current animal models of skin ulcers are summarized. This article analyzes the advantages and disadvantages of animal models according to the etiology and pathogenesis of chronic skin ulcers, traditional Chinese and Western medicine diagnostic criteria and observation indicators, and eva-luates the agreement between the existing animal models and the characteristics of clinical syndromes of traditional Chinese and Western medicine for chronic skin ulcers. Through analysis and comparison, it is found that most of the existing modeling methods are single-factor animal models, and there are certain gaps in the physiological and pathological characteristics of chronic skin ulcers caused by clinical multi-factors and interactions. Most of the modeling methods are guided by Western medicine. The lack of pathogenic factors of traditional Chinese medicine(TCM) in the process of modeling. Therefore, this article proposes to establish a reasonable quantification standard for chronic skin ulcer animal models, and to establish a combination model of chronic skin ulcer disease with traditional Chinese and Western medicine as the focus of future animal model research.

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.

Outcomes of older adults aged 90 and over with cutaneous malignancies after electrochemotherapy with bleomycin: A matched cohort analysis from the InspECT registry.

BACKGROUND: With extending life expectancy, more people are diagnosed with cutaneous malignancies at advanced ages and are offered nonsurgical treatment. We assessed outcomes of the oldest-old adults after electrochemotherapy (ECT). METHODS: The International Network for Sharing Practices of ECT (InspECT) registry was queried for adults aged ≥90 years (ys) with skin cancers/cutaneous metastases of any histotype who underwent bleomycin-ECT (2006-2019). These were subanalysed with patients aged <90 ys after matching 1:2 for tumor location, number, size, histotype, and previous treatments. We assessed ECT modalities, toxicity (CTCAE), response (RECIST), and patient perception (EQ-5D). RESULTS: Sixty-one patients represented the study cohort (median 92 ys, range 92-104), 122 the control group (median 77 ys, range 23-89). Among the oldest-old, 44 patients (72%) had primary/recurrent skin cancers, 17 (28%) cutaneous metastases. Median tumour size was 15 mm (range, 5-450). The oldest-old adults underwent ECT mainly under local/regional anaesthesia (59% vs 39% p = .012). We observed no differences regarding dose and route of chemotherapy (intravenous vs intratumoral, p = .308), electrode geometry (linear vs hexagonal, p = .172) and procedural duration (18 vs 21 min, p = .378). Complete response (57.4 [95%-CI 44.1%-70.0%] vs 64.7% [95%-CI 55.6%-73.2%], p = .222) and 1-year local control (76.7% vs 81.7, p = .092) rates were comparable. Pain and skin hyperpigmentation were mild in both groups. Skin ulceration persisted longer in the oldest-old patients (4.4 vs 2.4 months, p = .008). CONCLUSIONS: The oldest-old adults with cutaneous malignancies undergo ECT most commonly under local/regional anaesthesia with safety profiles and clinical effectiveness similar to their younger counterparts, except in case of ulcerated tumors.

Analysis of animal models of chronic skin ulcers based on characteristics of clinical symptoms of traditional Chinese and Western medicine / 中国中药杂志

Based on the characteristics of clinical symptoms of chronic skin ulcers in traditional Chinese and Western medicine, the current animal models of skin ulcers are summarized. This article analyzes the advantages and disadvantages of animal models according to the etiology and pathogenesis of chronic skin ulcers, traditional Chinese and Western medicine diagnostic criteria and observation indicators, and eva-luates the agreement between the existing animal models and the characteristics of clinical syndromes of traditional Chinese and Western medicine for chronic skin ulcers. Through analysis and comparison, it is found that most of the existing modeling methods are single-factor animal models, and there are certain gaps in the physiological and pathological characteristics of chronic skin ulcers caused by clinical multi-factors and interactions. Most of the modeling methods are guided by Western medicine. The lack of pathogenic factors of traditional Chinese medicine(TCM) in the process of modeling. Therefore, this article proposes to establish a reasonable quantification standard for chronic skin ulcer animal models, and to establish a combination model of chronic skin ulcer disease with traditional Chinese and Western medicine as the focus of future animal model research.