Scars, burns & healing最新文献

Introduction: Complex diabetes-related foot wounds are at high risk of infection and subsequent major amputation unless healed expediently. Biodegradable Temporising Matrix (BTM) is a synthetic matrix that facilitates the organisation of the extracellular matrix, resulting in a neodermis layer over these difficult-to-heal areas. The aim of this study was to evaluate the efficacy of using BTM in the reconstruction of challenging diabetic foot wounds.

Methods: Eighteen patients with complex diabetic foot wounds (exposed tendon, fascia, joint, bone), or chronic ulcers at high shear stress locations had BTM applied. Indications for BTM application were high shear stress location (66.6%), exposed bone (16.6%), exposed fascia (5.6%), exposed tendon (5.6%) and chronic non-healing wound (5.6%). The time to complete healing, infection rate and incidence of subsequent wound breakdown was analysed.

Discussion: Thirteen of 18 patients completed the BTM treatment regime with all these patients achieving complete wound healing at a median time of 13 weeks. One patient had partial treatment with BTM and four patients were withdrawn from the study following BTM application. The rate of infection and re-ulceration were both 15.4%.

Conclusion: This is the first prospective cohort pilot study evaluating the use of BTM for complex diabetic foot wounds. BTM demonstrates potential in healing uninfected, non-ischaemic diabetic foot wounds with exposed deep structures and chronic wounds subject to high shear stress. The re-ulceration and infection rates were relatively low for this high-risk population. BTM may also offer promise as an alternative to free flaps.

Lay summary: The prevalence of diabetes and its complications, including foot ulcers and wounds, have significantly increased worldwide over the last 40 years. Increasingly patients are admitted to hospital for antibiotics, debridements and subsequent amputations from these wounds. Complex diabetes-associated wounds are those at highest risk of these complications or necessitating more extensive, complex operations such as free flaps. These wounds may have exposed deep structures, be at risk of high shear stress or be chronic non-healing wounds.Temporisers are a type of material which integrates into the wound and promotes in-growth of tissue, ideal for healing over these difficult to heal areas. Biodegradable Temporising Matrix (BTM) is a synthetic temporising matrix which has demonstrated positive outcomes in facilitating healing in burns and plastics wounds, but its effectiveness in diabetic foot wounds has not yet been proven. This is the first prospective cohort pilot study evaluating the use of BTM for complex diabetic foot wounds. BTM demonstrates potential in healing uninfected, non-ischaemic complex diabetic foot wounds and potentially avoiding more complex operations.

Introduction: Black salve ointments are variable in their composition with no standard formula. Patient's may turn to unregulated products to self-treat their conditions. Products that are accessible without a prescription are not necessarily safe and may pose risk to those who use them, as in this case with the use of black salve ointment.

Methods: This case report discusses the use of black salve ointment on a nodular neck cyst in a 55-year-old Hispanic male patient. The patient applied the black salve ointment (Two Feathers Healing Ointment®) to the cyst, where the ointment remained in contact with his skin for seven days. He required oral antibiotics and was referred to wound care for follow up.

Discussion: After close follow up and treatment with antibiotics, the eschar healed and left a concave scar on his neck with no other observed complications.

Conclusion: Healthcare providers are encouraged to discuss complementary and alternative medicine options with patients as some may lead to dangerous effects.

Lay summary: This is a case report about a 55 year old male patient who used an over the counter product called Black Salve to treat a cyst on his neck. He came to his primary care doctor's office for a usual checkup. Just before leaving his appointment, he mentioned a dark discolored area on his neck appeared after applying the black salve ointment. The black salve caused his skin to break down, get infected, and turn black. He was treated with antibiotics and close follow up care. After the wound healed, he was left with a scar on his neck from where the ointment broke down the skin. Since this product is available without a prescription, it is important that consumers know that it is not safe for use and may cause complications. If in doubt, ask a healthcare provider about a products risks before use.

Introduction: Toxic epidermal necrolysis (TEN) is one of the most severe cutaneous adverse reactions with a mortality rate of 30%. Due to a lack of consensus regarding the treatment and management of TEN, therapy is individualized on a case-to-case basis.

Purpose: The scientific literature about Stevens-Johnson Syndrome (SJS) and TEN is summarized and assessed to aid and assist in determining the optimal course of treatment.

Methods: PubMed and Google Scholar, among others, were searched with the keywords: "Toxic Epidermal Necrolysis", "corticosteroids", "cyclosporine", "etanercept", "intravenous immunoglobulin", "Stevens-Johnson syndrome" and filtered by year. The research articles generated by the search, and their references, were reviewed.

Results: TEN is a severe dermatological condition that is mainly caused by medicines. World-wide guidelines differ in care plans. As there is no consensus on the management of TEN, this article aims to summarize the efficacy and feasibility of the management aspect of TEN from previous studies. Supportive care is highly accepted, along with early discontinuation of all medicines (hydration & electrolytes). Corticosteroids and cyclosporine have been used in therapy. Intravenous immunoglobulin (IVIG) is currently being administered; however, their efficacy by themselves and in combination remains uncertain.

Conclusion: Current evidence predominantly from retrospective studies suggests no individual treatment has sufficient efficacy and a multi-faceted regimen stands to be favored. Therapeutic regimens from corticosteroids to IVIG are under constant evaluation. The life-threatening nature of TEN warrants further confirmation with more extensive, robust randomized, controlled trials.

Lay summary: Toxic epidermal necrolysis (TEN) is a serious skin reaction with a 30% chance of mortality. Commonly TEN is caused by medicines and results in a burn like appearance and sensation in patients. Usually administered medicine is cleared effectively by the human body but when the clearance of few metabolites from medicine is disrupted due to few genes, it leads to an ominous response by the body. This response involves several intermediate chemicals that primarily attack skin cells. Treatment guidelines differ globally. Supportive care is highly accepted, along with early discontinuation of all medicine. Currently, a multi-faceted treatment regimen is favored. Treatments like corticosteroids to immunoglobulins are under constant evaluation. Identification of the perfect combination of treatment needs confirmation from robust randomized controlled trials.

Introduction: Scarless healing is the ideal outcome of wound healing and is exhibited in some species. This narrative review assembles the current understanding of fibroblast heterogenicity along with the latest fibroblast-related targets for scar reduction therapies. Human regenerative wound healing is deemed possible due to the wound regeneration already seen in the early gestation foetus. Methods: This literature narrative review was undertaken by searching PubMed and Web of Science databases and Google Scholar to find articles concerning the fibroblast involvement in wound healing. We evaluated and collated these articles to form a consensus of the current understanding of the field. Discussion: This article describes current understanding of fibroblast heterogenicity and involvement in wound healing, focusing on the role of fibroblasts during physiological scarring. We also present the current most promising targets involving fibroblasts in the reduction of scarring and how we can manipulate the behaviour of fibroblasts to mimic the wound regeneration models in the human foetus. These targets include the pro-fibrotic EN1 positive fibroblast lineage, TGFβ1 inhibition, and genetic therapies utilising miRNAs and siRNAs. Conclusion: No therapies are currently available to eradicate scarring; however, treatment options are available to reduce the appearance of scarring. Further research into the heterogenicity and interactions of fibroblasts in both the foetus and adult is needed, and this may lead to the development of novel treatments against scarring.

Lay summary: Scarless healing refers to the repair of a wound with minimal residual scarring. The main cell responsible for the repair process is the fibroblast. It is now understood that there are different types of fibroblasts. Simply, some of these fibroblasts lead to scarring and some lead to regeneration. The early human foetus has mainly regenerative fibroblasts, but during aging the number of scarring fibroblasts increase to become the majority in the adult . Understanding how we can modify this process may ultimately result in the reduction in scarring. Currently, scar reduction therapies are aimed at optimal wound healing, surgical removal of abnormal scars, and using steroids and other drugs to encourage better wound repair by limiting the effect of scarring fibroblasts. Future therapies aim to target specific groups of fibroblasts to encourage regenerative wound healing. This narrative review aims to cover the current understanding of the different groups of fibroblasts and their effect on wound healing. We also cover the current and potential therapies that can be used to reduce scarring and suggest further areas for research in this field.

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Background: Burn injuries affect more than 60,000 children every year in the UK, with many experiencing scarring as a result. Scarring can be highly variable, and research is required to explore the factors that may influence variability, as well as the psychosocial impact of these injuries on children and their caregivers. A multicentre burns cohort study is being planned to investigate genetic determinants of scarring and long-term psychosocial outcomes. Public involvement (PI) is an essential element of the design and feasibility stages of this planning. As part of this work, this study aimed to gain an in-depth understanding of parents' attitudes towards participation in burns research, specifically a longitudinal cohort study of children with small burns (<10% total body surface area [TBSA]).

Methods: In total, 16 parents of children with burns took part in semi-structured interviews regarding their experiences of taking part in research and their attitudes towards the potential future cohort study. Interviews were audio-recorded, transcribed verbatim and analysed using Reflexive Thematic Analysis.

Results: Four themes were identified: 'Acknowledging trauma'; 'Aligning research with experience'; 'Research as a reciprocal relationship'; and 'Contributing to change'.

Discussion: These four themes represent factors that parents suggested were important for acceptability, relevance, recruitment and retention of participants into a longitudinal multicentre cohort study of children with a burn injury and their caregivers.

Conclusion: The findings of this study will be incorporated into the design of such a study, as well as having wide reaching relevance for research in the field of paediatric burn injuries.

Lay summary: Background to this subject More than 60,000 children experience a burn injury every year in the UK and many of these injuries lead to scarring. We know that the extent of this scarring can vary, and we know that some children and their parents/caregivers manage well but others struggle with the challenges they face after having a burn. Researchers would like to carry out research on these topics, including asking participants to take part in research over several years to find out how genetics might influence scarring, as well as their psychological experiences over this time. Before they conduct this study, it is very important that researchers understand parents' attitudes towards this kind of research. The current study aimed to find out parents' opinions and ask what issues were important to them when taking part in burns research. Details of how the work was conducted Parents of children who had experienced a scald (a type of burn injury) were asked to take part in a research interview. In total, 16 parents took part in this study. We recorded these interviews and analysed them,

Background: Stem cell therapy holds promise to improve healing and stimulate tissue regeneration after burn injury. Preclinical evidence has supported this; however, clinical studies are lacking. We examined the application of bone marrow-derived mesenchymal stem cells (BM-MSC) to deep second-degree burn injuries using a two-dose escalation protocol.

Methods: Ten individuals aged 18 years or older with deep second-degree burn wounds were enrolled. The first five patients were administered 2.5 × 10³ BM-MSC/cm² to their wounds. After safety of the initial dose level was assessed, a second group of five patients was treated with a higher concentration of 5 × 10³ allogeneic BM-MSC/cm². Safety was assessed clinically and by evaluating cytokine levels in mixed recipient lymphocyte/donor BM-MSC reactions (INFγ, IL-10 and TNFα). At each visit, we performed wound measurements and assessed wounds using a Patient and Observer Scar Assessment Scale (POSAS).

Results: All patients responded well to treatment, with 100% closure of wounds and minimal clinical evidence of fibrosis. No adverse reactions or evidence of rejection were observed for both dose levels. Patients receiving the first dose concentration had a wound closure rate of 3.64 cm²/day. Patients receiving the second dose concentration demonstrated a wound closure rate of 10.47 cm²/day. The difference in healing rates between the two groups was not found to be statistically significant (P = 0.17).

Conclusion: BM-MSC appear beneficial in optimising wound healing in patients with deep second-degree burn wounds. Adverse outcomes were not observed when administering multiple doses of allogeneic BM-MSC.

Lay summary: Thermal injuries are a significant source of morbidity and mortality, constituting 5%-20% of all injuries and 4% of all deaths. Despite overall improvements in the management of acutely burned patients, morbidities associated with deeper burn injuries remain commonplace. Burn patients are too often left with significant tissue loss, scarring and contractions leading to physical loss of function and long-lasting psychological and emotional impacts.In previous studies, we have demonstrated the safety and efficacy of administering bone marrow-derived mesenchymal stem cells (BM-MSC) to chronic wounds with substantial improvement in healing and evidence of tissue regeneration. In this report, we have examined the application of BM-MSC to deep second-degree burn injuries in patients.The aim of the present phase I/II clinical trial was to examine the safety and efficacy of administering allogeneic BM-MSC to deep second-degree burns. We utilised two different dose levels at concentrations 2.5 × 10³ and 5 × 10³ cells/cm². Patients with deep second-degree burn wounds up to 20% of the total body surface area wer

Background: Diabetic foot ulcers (DFU) are characterised by high levels of inflammatory mediators, resulting from sustained hyperglycaemic insult and the local microbial biofilm. The intralesional administration of epidermal growth factor (EGF) has emerged as an effective treatment that stimulates granulation and closure of DFU, reducing the risk of amputation. Within the wound, fibroblasts play key roles during the healing process, promoting granulation and contraction. The aim of the present study was to examine the anti-inflammatory effect of EGF in DFU-derived fibroblasts, challenged with lipopolysaccharide (LPS), under hyperglycaemic conditions, recreating in vitro what happens in a clinical scenario.

Methods: Healthy skin (HS) and DFU granulation tissue biopsies were used to isolate primary fibroblasts. The effect of LPS on cell proliferation was analysed. Transcriptional expression of toll-like receptor (TLR) pathway mediators (TLR4, TLR2, CD14, MYD88 and NFKB) and pro-inflammatory cytokines (TNF, IL-6 and IL-1B) were measured by semi-quantitative polymerase chain reaction (qPCR), in cells treated with appropriate concentrations of LPS, EGF and their combination. IL-6 protein concentration was quantified by ELISA.

Results: LPS stimulated proliferation of HS-derived fibroblasts, while inhibiting the proliferation of cells derived from DFU at the highest assayed concentration of 1 µg/mL. Regarding the TLR signalling pathway, LPS increased messenger RNA levels of mediators and pro-inflammatory genes, while EGF, alone or in the presence of LPS, downregulated them, except for IL-1B.

Conclusion: The results suggest that EGF might elicit an anti-inflammatory response in LPS-challenged fibroblasts, even in a hyperglycaemic milieu. Collectively, our findings contribute to explain newly observed effects of EGF in the clinical arena.

Lay summary: In this research article, we analyse the putative anti-inflammatory effect of epidermal growth factor (EGF) on fibroblast isolated from diabetic foot ulcer (DFU) granulation tissue. To induce the inflammatory response, the cells were treated with lipopolysaccharide (LPS), simulating the gram-negative bacterial infection that takes place in the wounds of diabetic patients. We studied the expression of genes involved in bacterial recognition receptors signalling pathway and those that code for different pro-inflammatory cytokines.We obtained primary fibroblasts from biopsies of a neuropathic diabetic ulcer and from healthy skin, the former was used as the control. Cells were isolated and grown in high glucose Dulbecco's Modified Eagle Medium (DMEM) culture medium, to simulate the hyperglycaemic insult. The effect of increasing concentrations of LPS on cell proliferation was analysed. Relative transcriptional expression of genes in the study was quantified by quantitative polymerase chain react

Introduction: Burn injuries are a common traumatic injury. Large burns have high mortality requiring intensive care and accurate mortality predictions. To assess if machine learning (ML) could improve predictions, ML algorithms were tested and compared with the original and revised Baux score.

Methods: Admission data and mortality outcomes were collected from patients at Uppsala University Hospital Burn Centre from 2002 to 2019. Prognostic variables were selected, ML algorithms trained and predictions assessed by analysis of the area under the receiver operating characteristic curve (AUC). Comparison was made with Baux scores using DeLong test.

Results: A total of 17 prognostic variables were selected from 92 patients. AUCs in leave-one-out cross-validation for a decision tree model, an extreme boosting model, a random forest model, a support-vector machine (SVM) model and a generalised linear regression model (GLM) were 0.83 (95% confidence interval [CI] = 0.72-0.94), 0.92 (95% CI = 0.84-1), 0.92 (95% CI = 0.84-1), 0.92 (95% CI = 0.84-1) and 0.84 (95% CI = 0.74-0.94), respectively. AUCs for the Baux score and revised Baux score were 0.85 (95% CI = 0.75-0.95) and 0.84 (95% CI = 0.74-0.94). No significant differences were observed when comparing ML algorithms with Baux score and revised Baux score. Secondary variable selection was made to analyse model performance.

Conclusion: This proof-of-concept study showed initial credibility in using ML algorithms to predict mortality in burn patients. The sample size was small and future studies are needed with larger sample sizes, further variable selections and prospective testing of the algorithms.

Lay summary: Burn injuries are one of the most common traumatic injuries especially in countries with limited prevention and healthcare resources. To treat a patient with large burns who has been admitted to an intensive care unit, it is often necessary to assess the risk of a fatal outcome. Physicians traditionally use simplified scores to calculate risks. One commonly used score, the Baux score, uses age of the patient and the size of the burn to predict the risk of death. Adding the factor of inhalation injury, the score is then called the revised Baux score. However, there are a number of additional causes that can influence the risk of fatal outcomes that Baux scores do not take into account. Machine learning is a method of data modelling where the system learns to predict outcomes based on previous cases and is a branch of artificial intelligence. In this study we evaluated several machine learning methods for outcome prediction in patients admitted for burn injury. We gathered data on 93 patients at admission to the intensive care unit and our experiments show that machine learning methods can reach an accuracy comparable with Baux scores in calculating the risk of fatal outcomes. This study r

Introduction: The extracellular matrix (ECM) plays an integral role in wound healing. It provides both structure and growth factors that allow for the organised cell proliferation. Large or complex tissue defects may compromise host ECM, creating an environment that is unfavourable for the recovery of anatomical function and appearance. Acellular dermal matrices (ADMs) have been developed from a variety of sources, including human (HADM), porcine (PADM) and bovine (BADM), with multiple different processing protocols. The objective of this report is to provide an overview of current literature assessing the clinical utility of ADMs across a broad spectrum of applications.

Methods: PubMed, MEDLINE, EMBASE, Scopus, Cochrane and Web of Science were searched using keywords 'acellular dermal matrix', 'acellular dermal matrices' and brand names for commercially available ADMs. Our search was limited to English language articles published from 1999 to 2020 and focused on clinical data.

Results: A total of 2443 records underwent screening. After removing non-clinical studies and correspondence, 222 were assessed for eligibility. Of these, 170 were included in our synthesis of the literature. While the earliest ADMs were used in severe burn injuries, usage has expanded to a number of surgical subspecialties and procedures, including orthopaedic surgery (e.g. tendon and ligament reconstructions), otolaryngology, oral surgery (e.g. treating gingival recession), abdominal wall surgery (e.g. hernia repair), plastic surgery (e.g. breast reconstruction and penile augmentation), and chronic wounds (e.g. diabetic ulcers).

Conclusion: Our understanding of ADM's clinical utility continues to evolve. More research is needed to determine which ADM has the best outcomes for each clinical scenario.

Lay summary: Large or complex wounds present unique reconstructive and healing challenges. In normal healing, the extracellular matrix (ECM) provides both structural and growth factors that allow tissue to regenerate in an organised fashion to close the wound. In difficult or large soft-tissue defects, however, the ECM is often compromised. Acellular dermal matrix (ADM) products have been developed to mimic the benefits of host ECM, allowing for improved outcomes in a variety of clinical scenarios. This review summarises the current clinical evidence regarding commercially available ADMs in a wide variety of clinical contexts.