Refractory Skin Ulcers Research Articles

Human Periodontal Ligament Stem Cells (hPDLSCs) Spontaneously Differentiate into Myofibroblasts to Repair Diabetic Wounds.

Advanced glycation end product (AGE) accumulation due to diabetes causes vascular and neurological lesions, delaying healing. The use of stem cells could overcome these problems. Although many studies have shown the potential beneficial effects of stem cell therapies in the treatment of chronic and refractory skin ulcers, their delivery methods are still under investigation. Human periodontal ligament stem cells (hPDLSCs) can spontaneously differentiate into myofibroblasts in specific cultures; therefore, they have the potential to effectively treat diabetic wounds and may also have applications in the field of medical cosmetics. The myofibroblastic differentiation ability of hPDLSCs in the presence of AGEs was evaluated by the expression of α-SMA and COL1A1 using RT-qPCR and WB technology. Wound healing in diabetic mice, induced by streptozotocin (STZ) and assessed using H&E staining, Masson staining, and immunohistochemical (IHC) and immunofluorescence (IF) staining, was used to validate the effects of hPDLSCs. In the wound tissues, the expression of α-SMA, COL1A1, CD31, CD206, iNOS, and vimentin was detected. The findings indicated that in H-DMEM, the expression of COL1A1 exhibited a significant decrease, while α-SMA demonstrated an increase in P7 cells, ignoring the damage from AGEs (p < 0.05). In an STZ-induced diabetic C57BL/6J mice whole-skin defect model, the healing rate of the hPDLSCs treatment group was significantly higher than that in the models (on the 7th day, the rate was 65.247% vs. 48.938%, p < 0.05). hPDLSCs have been shown to spontaneously differentiate into myofibroblasts in H-DMEM and resist damage from AGEs in both in vivo and in vitro models, suggesting their potential in the field of cosmetic dermatology.

Epithelioid sarcoma: a rare cause of refractory chronic skin ulcers.

We report two cases of chronic skin ulcers that were misdiagnosed as skin and soft tissue infections and as an inflammatory myofibroblastic tumour before the final diagnosis of epithelioid sarcoma at our institution. Our coverage of this rare but fatal tumour that can cause chronic skin ulcers is critical because early diagnosis and treatment can reduce morbidity and mortality.

Recombinantly expressed rhFEB remodeled the skin defect of db/db mice

Fibronectin (FN) and collagen are vital components of the extracellular matrix (ECM). These proteins are essential for tissue formation and cell alignment during the wound healing stage. In particular, FN interacts with collagens to activate various intracellular signaling pathways to maintain ECM stability. A novel recombinant extra domain-B fibronectin (EDB-FN)-COL3A1 fusion protein (rhFEB) was designed to mimic the ECM to promote chronic and refractory skin ulcer wound healing. rhFEB significantly enhanced cell adhesion and migration, vascular ring formation, and the production of new collagen I (COL1A1) in vitro. rhFEB decreased M1 macrophages and further modulated the wound microenvironment, which was confirmed by the treatment of db/db mice with rhFEB. Accelerated wound healing was shown during the initial stages in rhFEB-treated db/db mice, as was enhanced follicle regeneration, re-epithelialization, collagen deposition, granulation, inflammation, and angiogenesis. The wound chronicity of diabetic foot ulcers (DFUs) remains the main challenge in current and future treatment. rhFEB may be a candidate molecule for regulating M1 macrophages during DFU healing.Key points• A recombinant protein EDB-FN-collagen III (rhFEB) was highly expressed in Escherichia coli• rhFEB protein induces COL1A1 secretion in human skin fibroblasts• rhFEB protein accelerates diabetic wound healing

Treatment of dermal ulcer with autologous fibrin glue: Two case reports of an exploratory prospective pilot study.

The healing of recurrent and refractory skin ulcers requires a long time, during which there is risk of infection, and hospital admission is occasionally required for surgical or daily conservative treatment. Therefore, the development of promising treatments that promote faster, uneventful healing is a must. Composed of cryoprecipitate and thrombin, fibrin glue has a history of surgical use for preventing bleeding and spinal fluid leakage. Moreover, in-house cryoprecipitates contain higher concentrations of coagulation factors and cytokines that may enhance wound healing than commercially available products. However, the efficacy of completely autologous fibrin glue (AFG) in tissue repair has not yet been fully demonstrated. This study aimed to evaluate the efficacy of AFG in the treatment of refractory skin ulcers in comparison with the conventional treatment. Two patients with skin ulcer on their lower extremities due to trauma or scleroderma who showed resistance to conventional treatment were included in the study. Both study participants were diagnosed with refractory skin ulcer and were ineligible for autologous skin transplantation. AFG was prepared following autologous blood donation using a Cryoseal® system. Subsequently, AFG was administered to 50% of the area of each ulcer and observed for 4 weeks in comparison with recombinant basic fibroblast growth factor with bucladesine sodium treatment that was administered to the rest of the ulcer. The skin ulcer after trauma in participant 1 showed better improvement in the AFG-treated area. Although AFG did not show superiority regarding the ulcer area of a patient with scleroderma, it guarded the continuous exudation from the edge of the swollen skin surrounding the ulcer. AFG showed effective and beneficial results for wound healing of refractory skin ulcer and prevented exudation without any severe adverse events.

Interpretation of 2020 edition of Japanese "Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers"

Patients with connective tissue diseases and vasculitis often develop refractory skin ulcers in various parts of the body due to abnormal autoimmune reactions, and the skin ulcers caused by different types of diseases have strong heterogeneity. In 2020, The Journal of Dermatology published the Japanese "Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers", which is an updated version of its 2016 edition, to guide clinical management of related diseases in a more scientific and standard way. By interpreting the guidelines, this paper aims to help domestic clinicians clarify the diagnosis and treatment objectives of connective tissue disease and vasculitis-associated skin ulcers, accelerate skin wound healing, and improve healing quality.

Current State and Issues of Regenerative Medicine for Rheumatic Diseases.

The prognosis of rheumatic diseases is generally better than that of malignant diseases. However, some cases with poor prognoses resist conventional therapies and cause irreversible functional and organ damage. In recent years, there has been much research on regenerative medicine, which uses stem cells to restore the function of missing or dysfunctional tissues and organs. The development of regenerative medicine is also being attempted in rheumatic diseases. In diseases such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and rheumatoid arthritis, hematopoietic stem cell transplantation has been attempted to correct and reconstruct abnormalities in the immune system. Mesenchymal stem cells (MSCs) have also been tried for the treatment of refractory skin ulcers in SSc using the ability of MSCs to differentiate into vascular endothelial cells and for the treatment of systemic lupus erythematosus SLE using the immunosuppressive effect of MSCs. CD34-positive endothelial progenitor cells (EPCs), which are found in the mononuclear cell fraction of bone marrow and peripheral blood, can differentiate into vascular endothelial cells at the site of ischemia. Therefore, EPCs have been used in research on vascular regeneration therapy for patients with severe lower limb ischemia caused by rheumatic diseases such as SSc. Since the first report of induced pluripotent stem cells (iPSCs) in 2007, research on regenerative medicine using iPSCs has been actively conducted, and their application to rheumatic diseases is expected. However, there are many safety issues and bioethical issues involved in regenerative medicine research, and it is essential to resolve these issues for practical application and spread of regenerative medicine in the future. The environment surrounding regenerative medicine research is changing drastically, and the required expertise is becoming higher. This paper outlines the current status and challenges of regenerative medicine in rheumatic diseases.

Reconstruction for refractory skin ulcer with distal tibial fracture by distal tibial nail and skin graft

Reconstruction for refractory skin ulcer with distal tibial fracture by distal tibial nail and skin graft

Calcification in Werner syndrome associated with lymphatic vessels aging.

In addition to the symptoms of aging, the main symptoms in Werner syndrome (WS), a hereditary premature aging disease, include calcification of subcutaneous tissue with solid pain and refractory skin ulcers. However, the mechanism of calcification in WS remains unclear. In this study, the histological analysis of the skin around the ulcer with calcification revealed an accumulation of calcium phosphate in the lymphatic vessels. Moreover, the morphological comparison with the lymphatic vessels in PAD patients with chronic skin ulcers demonstrated the ongoing lymphatic remodeling in WS patients because of the narrow luminal cross-sectional area (LA) of the lymphatic vessels but the increment of lymphatic microvessels density (MLVD). Additionally, fluorescence immunohistochemical analysis presented the cytoplasmic distribution and the accumulation of WRN proteins in endothelial cells on remodeling lymphatic vessels. In summary, these results point out a relationship between calcification in lymphatic vessels and the remodeling of lymphatic vessels and suggest the significance of the accumulation of WRN mutant proteins as an age-related change in WS patients. Thus, cytoplasmic accumulation of WRN protein can be an indicator of the decreasing drainage function of the lymphatic vessels and the increased risk of skin ulcers and calcification in the lymphatic vessels.

A Royal Jelly Mixture with Berberine for Dressing Change on a Refractory Skin Ulcer: A Case Report

It has been reported that a 92-year-old female had got a bruise superficialwound on her right leg one and a half years ago, developing into refractoryskin ulcer due to improper management before. A prepared cream, mixedroyal jelly with berberine for dressing change, was made on the scenethrough the crush of berberine tablets, working with fresh royal jelly.Topical dressing change with the cream was done every 3 days, and twomonths later, such the ulcer became clean and was covered fully with freshgranulation tissue. This kind of cream consists of the ingredients of TCMpurely, free of antibiotic, and being quite effective clinically, also helpfulfor proper use of antibiotic.

Application of “One Syndrome and One Produce” model in the management of chronic and refractory skin ulcer in the “Yanjing Ulcer Healing” workshop

Application of “One Syndrome and One Produce” model in the management of chronic and refractory skin ulcer in the “Yanjing Ulcer Healing” workshop

Frailty, Complexity, and Priorities in the Use of Advanced Palliative Care Resources in Nursing Homes.

Background and objectives: This study aimed to determine the frailty, prognosis, complexity, and palliative care complexity of nursing home residents with palliative care needs and define the characteristics of the cases eligible for receiving advanced palliative care according to the resources available at each nursing home. Materials and Methods: In this multi-centre, descriptive, and cross-sectional study, trained nurses from eight nursing homes in southern Spain selected 149 residents with palliative care needs. The following instruments were used: the Frail-VIG index, the case complexity index (CCI), the Diagnostic Instrument of Complexity in Palliative Care (IDC-Pal), the palliative prognosis index, the Barthel index (dependency), Pfeiffer’s test (cognitive impairment), and the Charlson comorbidity index. A consensus was reached on the complexity criteria of the Diagnostic Instrument of Complexity in Palliative Care that could be addressed in the nursing home (no priority) and those that required a one-off (priority 2) or full (priority 1) intervention of advanced palliative care resources. Non-parametric tests were used to compare non-priority patients and patients with some kind of priority. Results: A high percentage of residents presented frailty (80.6%), clinical complexity (80.5%), and palliative care complexity (65.8%). A lower percentage of residents had a poor prognosis (10.1%) and an extremely poor prognosis (2%). Twelve priority 1 and 14 priority 2 elements were identified as not matching the palliative care complexity elements that had been previously identified. Of the studied cases, 20.1% had priority 1 status and 38.3% had priority 2 status. Residents with some kind of priority had greater levels of dependency (p < 0.001), cognitive impairment (p < 0.001), and poorer prognoses (p < 0.001). Priority 1 patients exhibited higher rates of refractory delirium (p = 0.003), skin ulcers (p = 0.041), and dyspnoea (p = 0.020). Conclusions: The results indicate that there are high levels of frailty, clinical complexity, and palliative care complexity in nursing homes. The resources available at each nursing home must be considered to determine when advanced palliative care resources are required.

Hyperbaric oxygen improves the effectiveness of wet healing in the treatment of refractory skin ulcers

Objective To explore the effect of combining hyperbaric oxygen inhalation with wet healing in the treatment of chronic refractory ulcers of the skin. Methods Sixty male Sprague-Dawley rats were randomly formed into a general treatment group (group A), a wet healing group (group B), and a hyperbaric oxygen + wet healing group (group C), each of 20. Chronic and refractory skin ulcers were induced on all of the rats after one week of routine feeding and 6 hours of fasting. Six courses (once daily for 10 days/course)of the three treatments were then administered. After 2, 4 and 6 courses of treatment the wound healing rate and recovery were analyzed using histopathological methods. Results After 2, 4 and 6 courses of treatment, the average wound healing rates of groups B and C were significantly higher than group A′s average, and that of group C was significantly better than that of group B. After 6 courses of treatment, group C′s average histopathology score was significantly higher than that of group B, and those of groups B and C were both significantly higher than group A′s average. Conclusion Single wet healing is better than common treatment for chronic skin ulcers, but hyperbaric oxygen inhalation can further improve its effectiveness. Key words: Hyperbaric oxygen; Wet healing; Skin ulcers

Image Gallery: Cutaneous ulcers in anti-MDA5 dermatomyositis successfully treated with sildenafil.

E‐mail: cris.collantes.rguez@gmail.com Funding sources: no external funding. Conflicts of interest: none to declare. Dear Editor, A man in his 30s with a history of anti‐MDA5 dermatomyositis (DM) with refractory skin ulcers (Fig. 1a) was successfully treated with sildenafil (Fig. 1b). Figure 2 shows a timeline of the clinical course of his disease. Nowadays, there is no treatment approved for skin ulcers in DM. These ulcers reflect a severe underlying vasculopathy. We hypothesize that sildenafil, which has vasodilator properties, may have helped with pain relief and ulcer healing. On the other hand, it did not show any effect on pulmonary clinical improvement, probably given the advanced fibrosis of the lung parenchyma in our patient. ...

Two Cases of Squamous Cell Carcinoma Arising on Refractory Skin Ulcers in Patients with a History of Hansen's Disease

Two Cases of Squamous Cell Carcinoma Arising on Refractory Skin Ulcers in Patients with a History of Hansen's Disease

A Case of Dermatomyositis Complicated with Refractory Multiple Skin Ulcer

A Case of Dermatomyositis Complicated with Refractory Multiple Skin Ulcer

Ethanol Embolotherapy for the Management of Refractory Chronic Skin Ulcers Caused by Arteriovenous Malformations

PurposeTo describe the clinical features and treatment outcomes of ethanol embolotherapy in refractory chronic skin ulcers caused by arteriovenous malformations (AVMs). Materials and MethodsFrom October 2011 to October 2015, 12 patients (5 male; mean age, 26.2 y) with refractory chronic skin ulcers caused by AVMs were treated at a single institution. Ethanol embolotherapy was performed by direct puncture techniques. Needles were directly inserted toward the nidus of the lesion based on imaging analysis. When fast blood reflux was noted, angiography was performed to ensure only the nidus and draining vein were opacified. Symptoms before and after treatment, previous treatment of AVMs and ulcers, embolotherapy sessions, follow-up time, complications, and degree of devascularization were recorded. Treatment outcomes were established by evaluating symptom outcomes and the degree of devascularization on follow-up angiography. ResultsFifty embolotherapy procedures were performed in 12 patients: 6 underwent procedures on the head and neck, 4 on the feet, and 2 on the hands. Four patients (33.3%) experienced complete resolution of abnormal angioarchitecture according to follow-up angiography. Complete control of ulcers was achieved in all 12 patients. Two procedures (4%) in 2 patients (16.7%) caused superficial skin necrosis that healed spontaneously within 4 weeks. Thirteen procedures (26%) in 9 patients (75%) caused blistering immediately after treatment. There were no major complications. ConclusionsIn a limited series, ethanol embolotherapy was effective and safe in the treatment of refractory chronic skin ulcers caused by AVMs.

Leucocyte- and platelet-rich fibrin (L-PRF) as a regenerative medicine strategy for the treatment of refractory leg ulcers: a prospective cohort study

Chronic wounds (VLU: venous leg ulcer, DFU: diabetic foot ulcer, PU: pressure ulcer, or complex wounds) affect a significant proportion of the population. Despite appropriate standard wound care, such ulcers unfortunately may remain open for months or even years. The use of leukocyte- and platelet-rich fibrin (L-PRF) to cure skin ulcers is a simple and inexpensive method, widely used in some countries but unknown or neglected in most others. This auto-controlled prospective cohort study explored and quantified accurately for the first time the adjunctive benefits of topical applications of L-PRF in the management of such refractory ulcers in a diverse group of patients. Forty-four consecutive patients with VLUs (n = 28, 32 wounds: 17 ≤ 10 cm2 and 15 > 10 cm2), DPUs (n = 9, 10 wounds), PUs (n = 5), or complex wounds (n = 2), all refractory to standard treatment for ≥3 months, received a weekly application of L-PRF membranes. L-PRF was prepared following the original L-PRF method developed more than 15 years ago (400g, 12 minutes) using the Intra-Spin L-PRF centrifuge/system and the XPression box kit (Intra-Lock, Boca Raton, FL, USA; the only CE/FDA cleared system for the preparation of L-PRF). Changes in wound area were recorded longitudinally via digital planimetry. Adverse events and pain levels were also registered. All wounds showed significant improvements after the L-PRF therapy. All VLUs ≤ 10 cm2, all DFUs, as well as the two complex wounds showed full closure within a 3-month period. All wounds of patients with VLUs > 10 cm2 who continued therapy (10 wounds) could be closed, whereas in the five patients who discontinued therapy improvement of wound size was observed. Two out of the five PUs were closed, with improvement in the remaining three patients who again interrupted therapy (surface evolution from 7.35 ± 4.31 cm2 to 5.78 ± 3.81 cm2). No adverse events were observed. A topical application of L-PRF on chronic ulcers, recalcitrant to standard wound care, promotes healing and wound closure in all patients following the treatment. This new therapy is simple, safe and inexpensive, and should be considered a relevant therapeutic option for all refractory skin ulcers.

Hyperbaric oxygen therapy for a refractory skin ulcer after radical mastectomy and radiation therapy: a case report

BackgroundRadiation therapy is performed as an adjuvant therapy when indicated following surgical resection of malignant tumors. However, radiation exposure induces acute or chronic dermatitis, depending on the radiation dose, interval, tissue volume, or irradiated area of the body. Radiation-induced skin ulcers and osteomyelitis of the underlying bone are intractable late-stage complications of radiation therapy, and often require reconstructive surgery to cover exposed tissue. Hyperbaric oxygen therapy has been suggested as a treatment for delayed radiation injury with soft tissue and bony necrosis.Case presentationA 74-year-old Japanese female underwent left radical mastectomy for breast cancer (T3N3M0, stage IIIB) in 1987. Radiation therapy was initiated 6 weeks after the surgery. She received telecobalt-60 in a total dose of 50 Gy with 25 fractions to the left supraclavicular, parasternal and left axillary regions, and electron treatment (9 MeV) in a total dose of 50 Gy in 25 fractions to the left chest wall. After irradiation, her skin became thinner and more fragile on the left chest wall, but no severe infections were observed. She noticed a small ulcer that repeatedly healed and recurred in 2000. She visited the hospital where she received radiation therapy and was treated for a skin ulcer on the left chest wall in December 2012. A fistula developed and then pus was discharged in January 2013. She was referred to the hyperbaric medical center in February 2013, and the fistula (1.5 × 3 cm) with pus discharge was observed. She was diagnosed with a late-onset radiation-induced skin ulcer that developed 25 years after radical mastectomy. HBO2 (2.5 atmospheres absolute with 100% oxygen for 60 minutes) was indicated for the refractory ulcer and osteomyelitis of the ribs. The patient was treated with HBO2 a total of 101 times over the course of 1 year and completely recovered.ConclusionsHyperbaric oxygen therapy can be performed safely for even more than 100 sessions in patients with radiation-induced skin ulcers and osteomyelitis. Hyperbaric oxygen therapy can be considered as an alternative, conservative treatment when surgical resection for late-onset, radiation-induced skin ulcers is not indicated because of fragile skin in the irradiated areas.

Refractory Skin Ulcer Caused by Achlorophyllic Algae

Refractory Skin Ulcer Caused by Achlorophyllic Algae

A case of rheumatoid arthritis with refractory skin ulcers treated successfully with abatacept

A case of rheumatoid arthritis with refractory skin ulcers treated successfully with abatacept