Non-healing Ulcers Research Articles

A comparative study of efficacy of platelet rich fibrin and conventional saline dressing in chronic non-healing ulcers: A randomized controlled trial in a tertiary care centre, Chengalpattu, Tamil Nadu

Non-healing ulcers pose a significant risk for deformities and platelet-rich fibrin (PRF) emerges as a promising treatment modality with feasible, easy, cost-effective day care therapy for chronic non-healing ulcers, exhibiting notable improvement in these chronic conditions. This study aims at demonstrating the efficacy of PRF (platelet rich fibrin) dressing in chronic non- healing ulcers.A prospective study with Forty patients of chronic non-healing ulcer aged more than 18 years are recruited, treated with PRF dressing and normal saline dressing. PRF dressing is repeated every week for 4 weeks and for normal saline dressing it is done every alternate days for the same period. Photographs were taken before treatment and at every subsequent session and sizes are measured in baseline (1) and 2,3,4 weeks. Each patient was followed up after four weeks from the last visit.In this study, excellent improvement was seen in 57% of total ulcers, 15% have showed moderate improvement. PRF dressing have shown significant improvement with >75% improvement in the size of the ulcer in visit 3 where as normal saline have shown only 34% improvement in 3 visit. Depth of the ulcer improved to 100% and 35% in visit 3 for PRF and normal saline dressing respectively.This study have found that PRF dressing has shown significant reduction in the overall size of the ulcer and quality of life with minimal visits and without any adverse events.

Hidden Diagnosis - Chronic Non-Healing Leg Ulcer

Chronic ulcers present a significant clinical challenge, often necessitating tailored, multi-faceted interventions and strict adherence to treatment protocols. Accurate diagnosis and management require a thorough understanding of the ulcer's etiology and associated systemic conditions. This case report highlights a 35-year-old male with a chronic non-healing leg ulcer, compounded by a history of deep vein thrombosis (DVT) and pulmonary thromboembolism. Despite negative findings for common vasculitic and procoagulant profiles, a biopsy revealed leukocytoclastic vasculitis, and subsequent HLA-B51 testing confirmed the diagnosis of Behçet’s disease. The patient was treated with a combination of prednisolone, mycophenolate mofetil, and rivaroxaban, resulting in notable regression of the ulcer. This case underscores the importance of considering Behçet’s disease in young male patients presenting with chronic non-healing ulcers and thromboembolic events. Early diagnosis and vigilant, multidisciplinary management are essential to mitigate complications such as pulmonary artery hemorrhage and neuro-Behçet’s disease. This report emphasizes the need for comprehensive diagnostic approaches and long-term follow-up to prevent irreversible organ damage and improve patient outcomes.

Mixed Connective Tissue Disease Presenting as Diabetic Ulcer in a 52 Year Old Female Patient: A Case Report

Mixed connective tissue disease (MCTD) is a rare and complex autoimmune condition characterized by overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis. Due to the varied clinical presentation and the absence of validated classification criteria, early diagnosis can be challenging, often leading to misclassification or delayed recognition. Here, we report a case of a 52-year-old female with MCTD and vasculitis, underscoring the importance of considering uncommon autoimmune etiologies in patients with non-healing ulcers. The patient presented with skin tightening, Raynaud’s phenomenon, and chronic non-healing ulcers, initially attributed to diabetic complications. Diagnostic evaluation revealed high-titre anti-U1-RNP antibodies, confirming MCTD. Treatment with oral steroids, cyclophosphamide, and sildenafil led to significant clinical improvement, particularly in ulcer resolution. This case emphasizes the critical need for early intervention and a multidisciplinary approach in managing autoimmune vasculitis associated with MCTD to prevent progression and optimize patient outcomes.

Umbilical cord mesenchymal stem cells combined with autologous platelet-rich plasma for lower extremity venous ulcers: A case report and literature review.

Nonhealing ulcers are difficult to manage because they deviate from the normal wound healing process. Conventional therapy cannot achieve satisfactory therapeutic effects. To verify the effectiveness of combined treatment with human umbilical cord mesenchymal stem cells (hUMSCs) and platelet-rich plasma (PRP) for nonhealing ulcers, we studied a patient with left lower limb venous ulcer (LEVU) treated with combined injection therapy. We present the case of a LEVU patient who has not healed for a long period of time (up to 1 year). LEVU was diagnosed with clinical symptoms. The hUMSCs plus PRP were injected into the wound edge and base (1 µL of cells/cm2 of wound surface), 0.5 mL at each point, with a distance of approximately 1 to 3 cm between points. The injection point was determined according to the extent of wound involvement. Seven days after hUMSC + PRP application, the wound area decreased by nearly 50%. The ulcers had almost completely healed by day 62, and no serious treatment-related toxic side effects were observed. hUMSCs can improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. PRP has also been suggested to promote wound healing through the secretion of various nutritional factors. The combination of hUMSCs and PRP has a mutually reinforcing effect, which may achieve a 1 + 1 > 2 effect. Therefore, the combination of hUMSCs and PRP may be a safe and effective treatment option for LEVU.

Transcriptomics Revealed Differentially Expressed Transcription Factors and MicroRNAs in Human Diabetic Foot Ulcers

Non-healing diabetic foot ulcers (DFUs) not only significantly increase morbidity and mortality but also cost a lot and drain healthcare resources. Persistent inflammation, decreased angiogenesis, and altered extracellular matrix remodeling contribute to delayed healing or non-healing. Recent studies suggest an increasing trend of DFUs in diabetes patients, and non-healing DFYs increase the incidence of amputation. Despite the current treatment with offloading, dressing, antibiotics use, and oxygen therapy, the risk of amputation persists. Thus, there is a need to understand the molecular and cellular factors regulating healing in DFUs. The ongoing research based on proteomics and transcriptomics has predicted multiple potential targets, but there is no definitive therapy to enhance healing in chronic DFUs. Increased or decreased expression of various proteins encoded by genes, whose expression transcriptionally and post-transcriptionally is regulated by transcription factors (TFs) and microRNAs (miRs), regulates DFU healing. For this study, RNA sequencing was conducted on 20 DFU samples of ulcer tissue and non-ulcerated nearby healthy tissues. The IPA analysis revealed various activated and inhibited transcription factors and microRNAs. Further network analysis revealed interactions between the TFs and miRs and the molecular targets of these TFs and miRs. The analysis revealed 30 differentially expressed transcription factors (21 activated and 9 inhibited), two translational regulators (RPSA and EIF4G2), and seven miRs, including mir-486, mir-324, mir-23, mir-186, mir-210, mir-199, and mir-338 in upstream regulators (p < 0.05), while causal network analysis (p < 0.05) revealed 28 differentially expressed TFs (19 activated and 9 inhibited), two translational regulators (RPSA and EIF4G2), and five miRs including mir-155, mir-486, mir-324, mir-210, and mir-1225. The protein–protein interaction analysis revealed the interaction of various novel proteins with the proteins involved in regulating DFU pathogenesis and healing. The results of this study highlight many activated and inhibited novel TFs and miRs not reported in the literature so far, as well as the targeted molecules. Since proteins are the functional units during biological processes, alteration of gene expression may result in different proteoforms and protein species, making the wound microenvironment a complex protein interaction (proteome complexity). Thus, investigating the effects of these TFs and miRs on protein expression using proteomics and combining these results with transcriptomics will help advance research on DFU healing and delineate potential therapeutic strategies.

SDC4 protein action and related key genes in nonhealing diabetic foot ulcers based on bioinformatics analysis and machine learning

SDC4 protein action and related key genes in nonhealing diabetic foot ulcers based on bioinformatics analysis and machine learning

COVID-19 and COVID-19 Vaccine-Related Skin Ulcerations in the Lower Extremities: A Case Report and Literature Review

Several associations have been made between COVID-19 and vasculitis. Recent data also shows the prevalence and association of de novo vasculitis with either COVID-19 infection or COVID-19 post vaccination. In this article, we present the case of new-onset leukocytoclastic vasculitis, secondary to COVID-19 vaccination, that was complicated by severe infected and nonhealing ulcers in the lower extremities. Case A 53-year-old male patient presented to the dermatology clinics with a three-week history of painful necrotic patches coalescent of the lateral malleolus of the right and left ankles. History goes back to when the patient reported developing pruritic papules two weeks after receiving his second shot of the Pfizer BioNTech COVID-19 vaccine (BNT162b2). Punch biopsy was consistent with leukocytoclastic vasculitis. He was prescribed a four-week course of systemic corticosteroids and antibiotics as per cultures. Vascular assessment confirmed normal peripheral arterial and venous system. Two months later, the patient re-presented with fever and worsening of his lower extremity ulcers. He underwent debridement of his wounds. Intra-operative cultures revealed multidrug resistant bacteria. He required an additional debridement session a few days later and a 14-day course of Piperacillin-Tazobactam. The patient was subsequently discharged on corticosteroids and Azathioprine and followed up in the vascular surgery and rheumatology clinics. At four months follow-up, the patient's wounds were almost completely healed. Conclusion This article highlights a case of severe new-onset COVID-19 vaccine-associated leukocytoclastic vasculitis complicated with infected ulcers that required debridement twice in addition to a prolonged course of antibiotics and immunosuppression therapy. To our knowledge, none of the cases reported in the literature were this severe in nature. In this post-pandemic era, it must remain high on the differential list, and healthcare specialists should maintain a high index of suspicion when evaluating sudden new-onset skin lesions that do not have an immediately apparent etiology.

Modelling the cost-effectiveness of a chloramine gel in treating infected, non-healing diabetic foot ulcers.

Organic chloramines have been developed as a topical wound bed preparation gel. This study aimed to estimate whether the addition of chloramine gel (Chlorasolv, RLS Global AB, Sweden) to standard care compared with standard care alone would afford a cost‑effective technology to the UK's health services for treating infected, non-healing diabetic foot ulcers (DFUs). A Markov model was developed to simulate the management of infected, non-healing DFUs. The model utilised data from a randomised controlled trial and was used to estimate the cost-effectiveness of chloramine plus standard care compared with standard care alone over a period of 24 weeks, expressed as the incremental cost per quality-adjusted life year (QALY) gained at 2021/22 prices. Using adjunctive chloramine to treat infected, non-healing DFUs was found to shorten the time to healing by 36% (from a mean of 17.1 weeks per ulcer to a mean of 11.0 weeks per ulcer). This translated into a 6% improvement in the probability of being healed by 24 weeks and a corresponding 3% improvement in health-related quality of life (HRQoL). Also, use of adjunctive chloramine was found to reduce the total cost of ulcer management by 13%. Sensitivity analysis found that adjunctive chloramine remained a cost-effective treatment, even when the value of the model inputs was varied by ±20%. Within the limitations of the study, treatment with adjunctive chloramine instead of standard care alone could potentially afford the UK's health services a cost-effective debridement strategy for infected, non-healing DFUs, due to its ability to accelerate the time to healing.

Mitochondrial Bioenergetics of Functional Wound Closure is Dependent on Macrophage-Keratinocyte Exosomal Crosstalk.

Tissue nanotransfection (TNT)-based fluorescent labeling of cell-specific exosomes has shown that exosomes play a central role in physiological keratinocyte-macrophage (mϕ) crosstalk at the wound-site. Here, we report that during the early phase of wound reepithelialization, macrophage-derived exosomes (Exomϕ), enriched with the outer mitochondrial membrane protein TOMM70, are localized in leading-edge keratinocytes. TOMM70 is a 70 kDa adaptor protein anchored in the mitochondrial outer membrane and plays a critical role in maintaining mitochondrial function and quality. TOMM70 selectively recognizes cytosolic chaperones by its tetratricopeptide repeat (TPR) domain and facilitates the import of preproteins lacking a positively charged mitochondrial targeted sequence. Exosomal packaging of TOMM70 in mϕ was independent of mitochondrial fission. TOMM70-enriched Exomϕ compensated for the hypoxia-induced depletion of epidermal TOMM70, thereby rescuing mitochondrial metabolism in leading-edge keratinocytes. Thus, macrophage-derived TOMM70 is responsible for the glycolytic ATP supply to power keratinocyte migration. Blockade of exosomal uptake from keratinocytes impaired wound closure with the persistence of proinflammatory mϕ in the wound microenvironment, pointing toward a bidirectional crosstalk between these two cell types. The significance of such bidirectional crosstalk was established by the observation that in patients with nonhealing diabetic foot ulcers, TOMM70 is deficient in keratinocytes of wound-edge tissues.

Ayurveda heals - Virechana for wound healing with special reference to Shareerika (Pittaja) Vrana: A case report

Shareerika Vrana also called as Nija Vrana are said to be result of Doshopaplava (Dosha dushti) and are Kashta Sadhya as compared to Sadyo Vrana. A 43 years old female patient approached outpatient department with chief complaints of a non-healing wound in the both of her feet at the dorsal aspect associated with pain, discharge & burning sensation. On examination it was analyzed as Shareerika (Pittaja) Vrana (non-healing ulcer). Patient was treated with classical Ayurveda therapeutic measures, Shodhana Karma (Virechana Karma), & Ropana Karma (Bahya and Abhyantara), which included daily dressing with Jatyadi Taila along with Triphala guggulu & Gandhaka rasayana internally. A remarkable improvement in the condition of the wound is observed with significant healing during treatment period with complete healing in 7 days post Virechana Karma. In this study, an attempt is made to prove the role of Virechana in Wound Healing with special reference to Shareerika Vrana. Keywords: Shareerika Vrana, Virechana Karma, Shashthi Upakrama, Ropana karma

A comparative analysis of vacuum assisted closure therapy and conventional dressings: outcomes in chronic diabetic foot ulcers among Indian patients

Background: India faces a growing diabetes epidemic, with approximately 77 million individuals affected. Chronic non-healing diabetic foot ulcers (DFUs) are a common complication of diabetes and a major healthcare challenge in Conventional wound care methods often result in prolonged healing times, increasing the risk of infection, hospitalization, and amputations. Vacuum-assisted closure (VAC) therapy, a modern treatment modality, offers a potentially more effective approach to managing these ulcers. Methods: This prospective, observational study was conducted at a tertiary care hospital in India from March 2022 to March 2024. One hundred patients with chronic non-healing DFUs were randomized into VAC therapy or conventional dressing groups. The primary outcomes included wound size reduction and healing time, while secondary outcomes involved patient satisfaction and cost-effectiveness. Results: VAC therapy significantly reduced wound size (65.2% vs. 40.5%) and shortened healing time (6.2 vs. 10.9 weeks) compared to conventional dressings. Additionally, VAC therapy led to higher patient satisfaction and proved more cost-effective due to fewer dressing changes and shorter hospital stays. Conclusions: VAC therapy outperforms conventional dressings in managing DFUs, offering faster healing, better patient satisfaction, and cost-effectiveness. Expanding its use in India could greatly improve diabetic foot care outcomes.

Problems when diagnosing cutaneous leishmaniasis: a retrospective study analyzing clinical, histopathological and immunohistochemical features.

Cutaneous leishmaniasis (CL) incidence in Switzerland is rising due to factors like migration and globalization. The aim of this work was to investigate CL frequency in Switzerland and identify clinical and histopathological difficulties in diagnosing CL in a non-endemic country. This retrospective study evaluated the clinical and histopathological characteristics of all CL cases from two dermatopathology laboratories between 2000 and 2022. Skin biopsies were histopathologically reviewed using HE, Giemsa, and immunohistochemical stain for CD1a and a specific Leishmania antibody (LA). PCR to detect Leishmania DNA was performed if sufficient tissue was available. 42 cases (27m, 15f) were included. The correct clinical diagnosis of CL was only made in 15 (35.7%) cases. In seven (16.6%) cases, CL was missed in the initial histopathologic evaluation. Two main histopathological patterns were observed: granulomatous and pseudolymphomatous. Immunohistochemical staining with CD1a and Leishmania-specific antibody was positive in 91% and 80% of cases, respectively. Leishmania PCR was positive in 25 of 26 cases, mainly detecting Old World species. CL is rare in Switzerland and often misdiagnosed clinically and histopathologically. CD1a and specific Leishmania antibody stainings are useful. CL should be considered in non-healing ulcers, even without a history of travel to endemic areas.

Nonhealing vulvar ulcer associated with hyperkeratotic depigmented plaques.

Nonhealing vulvar ulcer associated with hyperkeratotic depigmented plaques.

Diagnostic dilemma in a non-healing ulcer of the tongue

Diagnostic dilemma in a non-healing ulcer of the tongue

Fillet Flap For Non-Healing Ulcer Of Foot Revisited

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Mucor mycosis of tibia: A case report of An unsolved entity

Mucormycosis of tibia is a highly aggressive fungal infection. It is an uncommon affection especially in immunocompromised host who have more propensity for such affections.The nonhealing ulcer of the left leg in an immunocompromised host status of a 45-year-old male presented with a radiological lytic lesion of the distal lower fourth of tibia. The initial biopsy confirmed tubercular affection which responded to antitubercular medications to allow radiological healing. However, the repeat biopsy showed Mucormycosis which remained recalcitrant to antifungal medications with unresponsive wound healing and persisting suppuration. The case presented unique scenario of superadded fungal infection in a healing tubercular osteomyelitis tibia with alcoholic liver disease compromised host immunity.The fungal infection of tibia remains an unsolved entity with poor clinical and functional outcomes. An early detection, high degree of suspicion with an adequate dosage of antifungal medications may allow resolution of the dreaded infection though an effective treatment remains an unsolved entity.

Comparative efficacy of autologous platelet rich plasma and conventional dressing in the management of chronic ulcers

Background: Chronic ulcers pose a major global healthcare challenge. The use of platelet-rich plasma (PRP) for treating these wounds has garnered interest because of its potential healing benefits. Objective were to determine the effect of autologous PRP therapy on the percentage of surface area reduction/healing in chronic ulcers. Methods: This randomized controlled trial was conducted at the department of general surgery of M.M. institute of medical sciences and research (M.M.I.M.S.R.) Mullana, Ambala from May 1, 2023, to April 30, 2024. Patients aged 18-80 years of either gender with chronic ulcers were enrolled. Patients were randomly allocated to the PRP group and control group. PRP group was administered autologous PRP once in two weeks for 6 weeks after debridement, while for the control group conventional saline dressings were done after debridement. Final assessment was done at 8 weeks. Results: Of the 60 patients, the mean age was 53.90±11.23 years. There were 49 (82%) males and 11 (18%) females. At 8 weeks, the PRP group achieved 83.78% (SD=2.99) reduction in surface area of ulcers, whereas the control group had a 57.78% (SD=1.32) reduction in surface area of ulcers, with a p=0.0000 indicating a significant difference. The small sample size and 56-day follow-up period are insufficient to assess long-term treatment effects. Conclusions: A better outcome of PRP was observed compared to conventional dressing in patients with chronic non-healing ulcers.

A Study of Cadaveric Skin Graft Harvest and Usage: An Observational Prospective Pilot Study.

Background Burn injuries pose a significant global public health challenge, causing substantial morbidity and mortality, particularly in low- and middle-income countries. Timely and effective wound coverage is critical in treating severe burns to prevent infection, reduce pain, and promote healing. Cadaveric skin grafts (allografts) have become essential in treating extensive burn wounds, serving as temporary biological dressings to prepare the wound bed for autografting. This study aims to comprehensively analyze the process of cadaveric skin graft harvest and usage in a tertiary care setting. It seeks to evaluate the procedures, challenges, and outcomes associated with cadaveric skin grafts, contributing to optimizing burn care practices and improving patient outcomes. Methods This observational study was conducted at a tertiary care hospital and burns center with a skin bank, involving 44 cadaveric skin graft harvests and 27 applications between July 1, 2011, and June 30, 2013. The study focused on prospective donors and recipients needing cadaveric skin grafts. Inclusion criteria for donors included consent from the next of kin and the absence of infections or septicemia, while exclusion criteria included prolonged post-mortem intervals and medico-legal cases. The procedures adhered to the Euro Skin Bank protocols, encompassing retrieval, processing, storage, and usage. Data were analyzed using Epi-Info version 7.2.1 software, employing descriptive statistics for categorical variables. Ethical clearance was obtained from the university ethical committee, with mandatory written informed consent for skin donation. Results Out of 519 deaths in the tertiary care hospital, significant barriers to skin donation included septicemia, skin changes, late reporting, young age, medico-legal issues, and positive viral markers. Notably, 114 (21.97%) of next of kin refused consent. Cadaveric skin was harvested in five (11.36%) cases, with potential donors identified in 78 (15.02%) of deaths. Donors were predominantly older males, with efficient procurement processes ensuring timely harvests. The tertiary burns center facilitated 39 (88.63%) cases of cadaveric skin harvests with a skin bank, either at the donor's home or other hospitals notified to the burns center. Cadaveric skin grafts were applied in 27 cases, primarily for burns, with high graft uptake observed over 10 days. Non-healing ulcers showed 100% graft uptake. The survival rate among burn patients was 20 (74%), with deaths mainly due to sepsis and multi-organ failure. Significant barriers to obtaining consent included a lack of awareness, superstitions, social stigmas, and religious objections. Conclusion The study highlights the critical role of cadaveric skin in managing extensive wounds, particularly burns. Despite challenges in obtaining consent and limited donor availability, cadaveric skin grafts effectively prepared wound beds for autografting, contributing to improved patient outcomes. Increasing community awareness and addressing superstitions and social stigmas are essential for improving donation rates.

Modulatory Effects of 830 nm on Diabetic Wounded Fibroblast Cells: An In Vitro Study on Inflammatory Cytokines.

Background:After skin damage, a complicated set of processes occur for epidermal and dermal wound healing. This process is hindered under diabetic conditions, resulting in nonhealing diabetic ulcers. In diabetes there is an increase in inflammation and proinflammatory cytokines. Modulating cells using photobiomodulation (PBM) may have an effect on inflammation and cell viability, which are crucial for the healing of wounds. Objective: This study explored the impact of PBM in the near-infrared spectrum (830 nm; 5 J/cm2) on inflammation in diabetic wound healing. Materials and Methods: Five cell models, namely normal, wounded, diabetic, diabetic wounded, and wounded with d-galactose were used. Cell morphology and migration rate were assessed, while cellular response measures included viability (Trypan blue and adenosine triphosphate), apoptosis (annexin-V/PI), proinflammatory cytokines interleukin-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2, nuclear translocation of nuclear factor kappa B (NF-κB), and gene expression of advanced glycation end product receptor (AGER). Results: PBM resulted in increased levels of TNF-α, supported by activation of NF-κB. PBM stimulated translocation of NF-κB and upregulation of AGER. Conclusions: PBM modulates diabetic wound healing in vitro at 830 nm through stimulated NF-κB signaling activated by TNF-α.

Amniotic membrane graft (AMG) for persistent epithelial defects following infective corneal ulcers and keratitis - A systematic review.

Management of nonhealing corneal ulcers is challenging as it can lead to complications such as melting, descemetocele, and perforation, which can be prevented by amniotic membrane graft (AMG). The absence of any review (English language) on AMG for corneal ulcers prompted us to conduct this review. We looked for clinical trials (randomized and controlled) on the effect of AMG combined with other treatments, through various search engines utilizing the terms amniotic membrane and corneal ulcer. All patients who received AMG and/or conventional medication were included. Risk of bias tools derived from Cochrane collaboration were used to ascertain the standard and quality of the trials. Visual acuity and epithelial healing time were the main outcome measures studied. Three trials were finally selected for analysis. AMG was noted to be associated with better uncorrected visual acuity and reduction in neovascularization. There was no difference in best corrected visual acuity, epithelial healing time, and corneal opacity. There is evidence that the use of AMG is associated with improved uncorrected visual acuity as well as reduction in neovascularization of the cornea among patients with corneal ulcers, but there was no improvement in epithelial healing time or corneal opacity. Further multicenter randomized controlled trials are needed to elicit the beneficial effects of the intervention and augment the validity of this review.