A randomised Trial of Autologous Blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in LEprosy: The TABLE trial.

INTRODUCTION: Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established. METHODS: We evaluated the 'second generation' autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images. RESULTS: The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment. CONCLUSION: Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy. TRIAL REGISTRATION: ISRCTN14933421. Date of trial registration: 16 June 2020.

Cutaneous Crohn disease presenting as "knife-edged" ulcers: a case report.

BACKGROUND: CCD presents as non-caseating granulomas within the skin at a site distant from the GI tract. CCD is a debilitating extraintestinal sequela of CD that can sometimes precede its GI manifestations. In the absence of GI symptoms, the histopathologic and clinical features of CCD can present as a variety of inflammatory skin conditions that can range from ruptured follicle-associated granulomas to cutaneous ulcerations. While a variety of therapeutic options for patients with CCD and concurrent luminal CD have been described in the literature, there is no standard treatment algorithm for the management of refractory CCD with limited or covert GI involvement. CASE REPORT: The authors discuss the case of a 33-year-old female who presented to the wound care clinic with multiple "knife-edged" cutaneous ulcerations involving the intertriginous spaces, found to be consistent with CCD. Her original cutaneous symptoms and diagnosis manifested with minimal GI involvement and responded to IVIG treatment. CONCLUSIONS: This case supports the inclusion of CCD in the differential diagnosis in patients with knife-edged granulomatous skin lesions in intertriginous locations. This clinical condition may present in the setting of no or limited GI symptoms. The management of CCD and a proposed treatment algorithm are also presented.

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.

Autologous blood products: Leucocyte and Platelets Rich Fibrin (L-PRF) and Platelets Rich Plasma (PRP) gel to promote cutaneous ulcer healing - a systematic review.

OBJECTIVE: To summarise evidence on the effectiveness of Platelet-Rich Plasma (PRP) gel and Leucocyte and Platelet Rich Fibrin (L-PRF) gel as agents promoting ulcer healing compared with the standard wound dressing techniques alone. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Individual patient randomised controlled trials on skin ulcers of all types excluding traumatic lesions.Intervention group: treatment with topical application of L-PRF gel or PRP gel to the wound surface. CONTROL GROUP: treatment with standard skin ulcer care using normal saline, normgel or hydrogel dressings. INFORMATION SOURCES: Medline (Ovid), Excerpta Medica Database (EMBASE), Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science and manual search of studies from previous systematic reviews and meta-analyses. The papers published from 1946 to 2022 with no restriction on geography and language were included. The last date of the search was performed on 29 August 2022. DATA EXTRACTION AND SYNTHESIS: Independent reviewers identified eligible studies, extracted data, assessed risk of bias using V.2 of the Cochrane risk-of-bias tool for randomised trials tool and assessed certainty of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN OUTCOME MEASURES: Time to complete healing, proportion healed at a given time and rate of healing. RESULTS: Seven studies met the inclusion criteria, five using PRP gel and two using L-PRF gel. One study showed a better proportion of complete healing, three reported reduced meantime to complete healing and five showed improved rate of healing per unit of time in the intervention group. The risk of bias was high across all studies with one exception and the GRADE showed very low certainty of evidence. CONCLUSION: The findings show potential for better outcomes in the intervention; however, the evidence remains inconclusive highlighting a large research gap in ulcer treatment and warrant better-designed clinical trials. PROSPERO REGISTRATION NUMBER: CRD42022352418.

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

INTRODUCTION: 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. PATIENT CONCERNS: This study aimed to evaluate the efficacy of AFG in the treatment of refractory skin ulcers in comparison with the conventional treatment. DIAGNOSIS: 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. INTERVENTIONS: 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. OUTCOMES: 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. CONCLUSION: AFG showed effective and beneficial results for wound healing of refractory skin ulcer and prevented exudation without any severe adverse events.

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.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

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.

Endothelial progenitor cell derived exosomes mediated miR-182-5p delivery accelerate diabetic wound healing via down-regulating PPARG.

Diabetic wound is one of the most common and serious complications of diabetes, which is characterized by abnormal number and quality of wound repair related cells. Previous studies have shown that human endothelial progenitor cells derived exosomes (EPCs-EXO) can promote diabetic wound healing through modulating vascular endothelial cell function. The purpose of this study was to investigate the biological effects and molecular mechanisms of EPCs-EXO on diabetic wound healing. The regulation of EPCs-EXO on human immortalized epidermal cell line HaCaT in high glucose (HG) environment was evaluated. Our data showed that EPCs-EXO promoted the proliferation, migration, while inhibited apoptosis of HaCaTs challenged by HG via elevating miR-182-5p expression level in vitro. Skin wound healing was significantly enhanced by EPCs-EXO in diabetic mice. Moreover, bioinformatics analyses and luciferase reporter assay indicated that exosomal miR-182-5p was bound to PPARG 3' UTR sequence and inhibited the expression of PPARG. Collectively, our findings provided a new role of EPCs-EXO in the clinical treatment of diabetic skin wounds. Diabetic wound is one of the most common and serious complications of diabetes, which is characterized by abnormal number and quality of wound repair related cells. Previous studies have shown that human endothelial progenitor cells derived exosomes (EPCs-EXO) can promote diabetic wound healing through modulating vascular endothelial cell function. The purpose of this study was to investigate the biological effects and molecular mechanisms of EPCs-EXO on diabetic wound healing. The regulation of EPCs-EXO on human immortalized epidermal cell line HaCaT in high glucose (HG) environment was evaluated. Our data showed that EPCs-EXO promoted the proliferation, migration, while inhibited apoptosis of HaCaTs challenged by HG via elevating miR-182-5p expression level in vitro. Skin wound healing was significantly enhanced by EPCs-EXO in diabetic mice. Moreover, bioinformatics analyses and luciferase reporter assay indicated that exosomal miR-182-5p was bound to PPARG 3' UTR sequence and inhibited the expression of PPARG. Collectively, our findings provided a new role of EPCs-EXO in the clinical treatment of diabetic skin wounds.

Treatment of Vascular Complications in Systemic Sclerosis: What Is the Best Approach to Diagnosis and Management of Renal Crisis and Digital Ulcers?

Vasculopathy as exemplified by scleroderma renal crisis (SRC) and digital ulcers (DUs) is a cardinal feature of systemic sclerosis (SSc) and is associated with significant morbidity, including in patients with early disease. Prompt recognition and management is required to alleviate potentially irreversible damage from SSc-associated vasculopathy. Both SRC and DUs share many etiopathogenic drivers which inform the therapeutic strategy. The aim of our review was to describe the diagnosis and management of SRC and DUs in SSc, and to discuss unmet needs for future research.

Calciphylaxis and skin ulcers: a diagnostic and therapeutic challenge.

INTRODUCTION: Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare and severe disorder that presents with skin ischemia and necrosis. Diagnosis is challenging, and even if the condition is diagnosed in the early stages, the mortality rate is exceptionally high, ranging from 45% to 80%. CASE REPORT: A 55-year-old male with chronic kidney disease secondary to diabetic nephropathy presented with painful, severe, necrotic ulcers in the lower legs and underwent treatment with sodium thiosulfate, debridement of necrotic tissue, and topical oxygen therapy. Complete healing of the ulcers was achieved within 3 months. CONCLUSION: This case report raises awareness of this rare condition and details successful treatment in 1 patient.

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.

Trigeminal trophic syndrome, a rare and often overlooked cause of facial ulceration: a case report and literature review.

Trigeminal trophic syndrome (TTS) is an uncommon and relatively unknown cause of facial ulceration that occurs after damage to the trigeminal nerve. It characteristically involves non-healing facial ulceration(s) with accompanying anesthesia, paresthesia, and dysesthesia along the distribution of a trigeminal dermatome. The ulcerations are believed to be self-induced in response to paresthesia. The disease is most common in middle-aged women, manifesting as a unilateral crescent-shaped ulceration on the ala nasi, with sparing of the nasal tip. The diagnosis is clinical and mostly based on exclusion of other possible causes of facial ulcerations, with emphasis on neoplasms, infection-associated vasculitis, and factitial disorders. There are no specific histological or laboratory signs. There is no standard treatment protocol; however, a number of different successful strategies have been reported, including pharmaceutical and surgical interventions, transcutaneous nerve stimulation, and simple occlusion dressings. Due to the self-inflicted nature of this disorder, the cornerstone of management is patient education with behavioral modification. Here, we report a case of TTS following herpes zoster ophthalmicus and review the current literature on this subject.

Avaliação in vitro do potencial reparador de matriz de Quitosana associada a Madecassoside: aplicações no tratamento de lesões cutâneas / In vitro evaluation of the matrix repairing potential of Chitosan associated with Madecassoside: applications in the treatment of skin lesions

A cicatrização de úlceras cutâneas depende de fatores-chave que incluem a interação adequada dos diferentes constituintes celulares da epiderme, derme e tecido subcutâneo. A restauração da barreira epidérmica é altamente eficiente durante o período embrionário, com um relativo decréscimo na vida adulta. Distúrbios sistêmicos, como diabetes e hanseníase, podem comprometer a capacidade de reparação da pele, gerando ulceras crônicas, que são consideradas como relevantes problemas de saúde pública. O presente estudo se propôs a estabelecer parâmetros de eficiência de membranas bioativas, preparadas com o biopolímero quitosana (QT), em associação ao extrato vegetal, madecassoside (MA). Nas preparações obtidas, foram avaliadas características físico-químicas e propriedades antimicrobianas. A biocompatibilidade das preparações, e sua capacidade de promover migração celular, foi testada in vitro em fibroblastos da linhagem NIH/3T3. As membranas foram divididas em grupos: QT 2%; QT/MA 0,10% (QTMA010); QT/MA 0,25% (QTMA025); QT/MA 0,50% (QTMA050). Os grupos foram avaliados em diferentes intervalos de tempo, de 0 a 96 horas (T0, T24, T48, T72, T96). Nossos dados indicam que membranas bioativas, preparadas com quitosana (QT 2%) e madecassoside (MA 0,10%, 0,25%, 0,50%), são biocompatíveis e possuem propriedades físico-químicas adequadas. As preparações contendo associação de ambos os compostos se mostraram superiores à QT. A capacidade de promover migração de fibroblastos, in vitro, foi estatisticamente superior em todos os grupos acrescidos de MA, indicando um papel relevante desse composto em preparações de utilização tópica para cicatrização úlceras cutâneas.

Get It Off Your Chest: A Narrative Review of Breast Ulcers.

GENERAL PURPOSE: To provide comprehensive information about breast ulcers to facilitate accurate diagnosis and treatment of these lesions. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Differentiate common wound complications after mastectomy.2. Identify the clinical manifestations of various types of breast ulcers.3. Explain appropriate pharmacologic and nonpharmacologic treatment options for various types of breast ulcers.

Cutaneous breast ulcers are uncommon but important encounters in clinical practice. Myriad causes may introduce ulcers in the breast tissue. Women are more prone to breast ulcers than men because of having heavier breast fatty tissue. Thorough medical history may easily reveal the underlying etiology; however, a tissue biopsy is often required to rule out other potential causes. The clinical presentation varies based on the underlying etiology, but some clues include surgical scars for postoperative wound dehiscence or well-defined violaceous borders with undermined ulcer base in pyoderma gangrenosum. In this article, the authors divide breast cancers into two major groups: with and without underlying mass. Depending on the underlying etiology, treatment may involve topical medications; optimal wound care; systemic medications such as antibiotics, immunosuppressive medications, or biologics; surgery; or a combination of all of the above. This article aims to shed light on a less frequent anatomic location of ulcers and provide advice to clinicians to facilitate accurate diagnosis and treatment.

[Emphasis on multidisciplinary collaboration in clinical diagnosis and treatment of autoimmune disease-related ulcers].

The global prevalence and incidence of autoimmune diseases are increasing year by year, and the autoimmune diseases have become a major threat to public health. In the progression of the diseases, persistent and complex abnormal immune responses often lead to long-term unhealed skin ulcers, which not only affect the life quality of patients, but also lead to the aggravation of primary diseases. Therefore, doctors in burn surgery and other wound repair surgeries should pay attention to the understanding of autoimmune diseases. In the treatment of autoimmune disease-related ulcers, it is recommended to formulate a unified treatment plan according to the law of occurrence and development of the diseases, and multidisciplinary cooperation is needed to accelerate wound healing and improve the quality of wound healing.