Surgical release of the chest wall skin and fascia for sclerodermatous graft versus host disease causing restrictive lung disease: A case report.

INTRODUCTION: Graft versus host disease (GVHD) remains a significant source of morbidity and mortality in the setting of allogeneic stem cell transplantation. Skin involvement is reported to be as high as 70-95 % in this group with GVHD and the severity of the involvement varies widely. Surgical management of complications of severe cutaneous GVHD is uncommon and is rarely mentioned as a treatment option. CASE PRESENTATION: We present a case of severe sclerodermatous skin changes restricting chest expansion and exercise tolerance to the point of limiting basic activities of daily life. A 54-year-old male presents with severe restrictive lung disease from sclerodermatous graft versus host disease (GVHD) after stem cell transplant for Chronic Myeloid Leukaemia (CML). He experienced limited symptomatic relief from maximal medical therapy and photochemotherapy, and subsequently underwent a skin release and split skin grafting of his chest and abdomen in an effort to improve exercise tolerance and quality of life. CLINICAL DISCUSSION: Despite an initial improvement in functioning, the patient's spirometry and lung function continued to decline with time, possibly suggesting that he did not gain a sustained benefit from surgical release of his cutaneous GVHD. CONCLUSION: While delineating between disease progression and surgical outcome is difficult in this case, the patient would argue that by delaying or reducing further decline in function, the surgical release procedures led to improved quality of life in subsequent years. However further research is required to establish a clear role for surgery in the treatment of refractory cutaneous GVHD.

The seven-fold rise in incidence of Stevens-Johnson syndrome & toxic epidermal necrolysis: Associations with COVID-19 and the vaccine.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare, potentially life threatening mucocutaneous hypersensitivity reaction resulting in desquamation of the skin and mucosa. These patients are managed on burns units due to the widespread desquamation. We report the largest case series of participants developing SJS/TEN in the setting of recent COVID infection or vaccination. We found a seven-fold increase in SJS/TEN since the COVID pandemic. This increase correlates with an increase in COVID infections and vaccination rates. We explore the immunopathological relationships between COVID and SJS/TEN and propose theories for possible associations.

The impact of COVID-19 on adult burns: A statewide review of epidemiology and clinical outcomes.

INTRODUCTION: The COVID-19 pandemic has significantly impacted the clinical presentations of burns and the provision of services. This study aims to describe and analyse patterns and trends in adult burns across New South Wales (NSW) and the Australian Capital Territory. METHODS: A NSW statewide retrospective review was conducted from 2017 to 2022 for adult patients with burns. A comparative analysis was performed for the COVID-19 group (2020-2022) and control group between 2017 and 2019. RESULTS: We found a total of 11,433 patients (7102 non-COVID vs 4331 COVID-19). The average age in the COVID-19 group was 1.4 years older than counterparts (40.6 vs 42.0, p < 0.001). The 18 - 25 and 36 - 45 age groups experienced significantly lower proportions of presentations, whereas, the 76-85 years experienced significantly higher proportions. There was a significantly higher proportion of pressure injuries (0.1% vs 0.4%, p < 0.001) and contact burns (17.2% vs 18.7%), but lower explosions (1.3% vs 0.2%) for the COVID-19 group compared to their counterparts. The mean TBSA% was 0.4% greater in the COVID-19 group compared to their counterparts (2.4 vs 2.8, p < 0.001). There were significantly more operating sessions (0.2 vs 0.3, p < 0.001). The mean length of stay was significantly greater by 0.8 days for the COVID-19 group compared to their counterparts (1.5 vs 2.3, p < 0.001). CONCLUSIONS: Epidemiological changes were not greatly different to previous years from the impact of COVID-19. The shift in elderly presentations and operative interventions reflects the holistic care of burns units working in a new landscape with an invigorated focus on telehealth and outpatient care.

Skin 11ß-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics.

Background: Excessive scarring and fibrosis are the most severe and common complications of burn injury. Prolonged exposure to high levels of glucocorticoids detrimentally impacts on skin, leading to skin thinning and impaired wound healing. Skin can generate active glucocorticoids locally through expression and activity of the 11ß-hydroxysteroid dehydrogenase type 1 enzyme (11ß-HSD1). We hypothesised that burn injury would induce 11ß-HSD1 expression and local glucocorticoid metabolism, which would have important impacts on wound healing, fibrosis and scarring. We additionally proposed that pharmacological manipulation of this system could improve aspects of post-burn scarring. Methods: Skin 11ß-HSD1 expression in burns patients and mice was examined. The impacts of 11ß-HSD1 mediating glucocorticoid metabolism on burn wound healing, scar formation and scar elasticity and quality were additionally examined using a murine 11ß-HSD1 genetic knockout model. Slow-release scaffolds containing therapeutic agents, including active and inactive glucocorticoids, were developed and pre-clinically tested in mice with burn injury. Results: We demonstrate that 11ß-HSD1 expression levels increased substantially in both human and mouse skin after burn injury. 11ß-HSD1 knockout mice experienced faster wound healing than wild type mice but the healed wounds manifested significantly more collagen deposition, tensile strength and stiffness, features characteristic of excessive scarring. Application of slow-release prednisone, an inactive glucocorticoid, slowed the initial rate of wound closure but significantly reduced post-burn scarring via reductions in inflammation, myofibroblast generation, collagen production and scar stiffness. Conclusions: Skin 11ß-HSD1 expression is a key regulator of wound healing and scarring after burn injury. Application of an inactive glucocorticoid capable of activation by local 11ß-HSD1 in skin slows the initial rate of wound closure but significantlyimproves scar characteristics post burn injury.

Intravenous iron therapy to treat burn anaemia: A retrospective cohort study.

PURPOSE: Intravenous iron is an effective treatment for anaemia in many populations but has not been evaluated in those with burn anaemia. This study aimed to evaluate the efficacy and safety of intravenous iron to manage burn anaemia. METHODOLOGY: This was a retrospective cohort study of patients admitted to the Royal Brisbane and Women's Hospital with burns to at least 15% total body surface area (TBSA). Data collected from patient records included demographics, treatment details, and outcomes including length of stay, blood transfusions, and serum haemoglobin concentrations. Linear mixed effects regression models were used to assess the effect of treatment with intravenous iron on haemoglobin over time. RESULTS: Sixty patients met inclusion criteria, with 11 (18%) treated using intravenous iron. Those treated with intravenous iron had higher TBSA burns (median 39% vs 18%, P = 0.0005), more operations (3 vs 1, P = 0.0012), and more blood transfusions (median 8 units vs 0 units, P = 0.0002). One patient (9%) experienced a minor adverse drug reaction from intravenous iron. When examining the change in modelled haemoglobin levels over the first 14 days following the last major operation, the change in the intravenous iron group (11.22 g/L) was 14.56 g/L greater than the change in the group not receiving intravenous iron (-3.34 g/L, P = 0.0282). CONCLUSION: This exploratory study provides preliminary evidence of benefit and safety of intravenous iron treatment on burn anaemia recovery.

Iron status in patients with burn anaemia.

PURPOSE: The iron status of burn patients is poorly understood, limited by difficulty interpreting conventional iron studies in the context of the acute phase response triggered by critical illness. The aim of this study was to evaluate the iron status of patients with burn anaemia using recent post-operative guidelines. METHODOLOGY: This retrospective cohort study utilised data collected from records for adult patients admitted to the Royal Brisbane and Women's Hospital with burns to at least 15% TBSA. Rates of iron deficiency, defined as ferritin< 100 µg/L or ferritin 100-300 µg/L with transferrin saturation< 20%, and low iron availability, defined as transferrin saturation< 20%, were calculated. RESULTS: Of 60 included patients (90% male), 16 (27%) underwent iron studies. 11 (18%) were treated with intravenous iron. Iron studies showed that five (31%) patients had evidence of iron deficiency, and ten out of 12 (83%) had evidence of reduced iron availability. Two patients (40%) with evidence of iron deficiency were not treated with intravenous iron. CONCLUSION: Application of recent guidelines for interpretation of conventional iron studies in patients with inflammatory states may improve the identification of iron deficiency in burn patients. Iron deficiency may be an under-recognised and under-treated contributor to burn anaemia.

Cold burns as a result of cosmetic cryolipolysis: An emerging concern from the NSW Statewide Burn Injury Service.

Cold burns are an uncommon mechanism of burn injury in Australia, where environmental exposure to freezing temperatures is rare. Aetiological research shows that most likely causes are related to intentional injury or industrial accidents1 Cryolipolysis, a cosmetic technique advertised as 'fat freezing', has recently emerged as a method of fat reduction and body contouring. Whilst perceived as safe4,5, this study presents the world's first case series on cold burns sustained from cryolipolysis. A retrospective review was undertaken of the New South Wales Statewide Burn Injury Service (SBIS) Registry, a prospectively collected database of all patients treated by NSW burns units. Ten patients from 2012 to 2020 were identified who sustained cold burns as a direct complication of cosmetic cryolipolysis. Mean total body surface area (TBSA) injured was 1% (range 0.5-3%). Burn depth ranged from superficial to full thickness. Two patients required excision and split-thickness skin grafts. Mean time to complete healing was 10 days (range 7-13) for those patients with partial thickness injuries, and 38 days (range 32-45) for those who required skin grafts. This case series provides strong evidence that cyrolipolysis can cause cold burns leading to varying degrees of skin injury, even requiring skin grafts. These injuries should be classified as burns and referred to specialist burn centres for treatment. Further research is needed to determine the specific aspects of cryolipolysis cold burn risk, and practitioners trained to reduce this risk and include it in consent processes. The authors advocate for education and regulation to prevent such injuries, and challenge perceptions of the technique as a minor, risk-free cosmetic treatment.

Alginate Dressings Continuously for 14 Days on Uncontaminated, Superficial, Partial Thickness Burns.

Calcium alginate dressings are commonly used on split-thickness skin donor sites, where they are typically removed after 14 days. Alginates have been used previously on superficial, partial thickness burns, but changed every 3 to 5 days. In this study, alginates were applied to superficial, partial thickness burns on adults within 36 hours of injury, then left intact for up to 14 days. Wound healing (≥95% wound epithelialization) and pain were measured. Twenty-one burns were reviewed on ten patients. Per the initial protocol, six patients were reviewed every 3 to 5 days, with removal of only secondary dressings, until days 13 to 14, when the alginate dressings were removed. One patient was reviewed every 3 to 5 days until day 10, when a clinic nurse removed the alginate dressing. Restrictions on movement during the COVID pandemic necessitated a protocol change, with only one review at approximately day 14 for removal of alginate and secondary dressings; three patients were reviewed in this manner. Burns on all patients were 100% epithelialized at the time of final review and there were no complications, such as scarring, infection, or need for grafting. Following initial debridement and dressings, patients reported minimal pain. Dressing costs appeared to be significantly decreased. This protocol may be particularly useful for patients managed in rural and remote locations, with telemedicine support if required.

Thermoresponsive and Injectable Hydrogel for Tissue Agnostic Regeneration.

Injectable hydrogels can support the body's innate healing capability by providing a temporary matrix for host cell ingrowth and neovascularization. The clinical adoption of current injectable systems remains low due to their cumbersome preparation requirements, device malfunction, product dislodgment during administration, and uncontrolled biological responses at the treatment site. To address these challenges, a fully synthetic and ready-to-use injectable biomaterial is engineered that forms an adhesive hydrogel that remains at the administration site regardless of defect anatomy. The product elicits a negligible local inflammatory response and fully resorbs into nontoxic components with minimal impact on internal organs. Preclinical animal studies confirm that the engineered hydrogel upregulates the regeneration of both soft and hard tissues by providing a temporary matrix to support host cell ingrowth and neovascularization. In a pilot clinical trial, the engineered hydrogel is successfully administered to a socket site post tooth extraction and forms adhesive hydrogel that stabilizes blood clot and supports soft and hard tissue regeneration. Accordingly, this injectable hydrogel exhibits high therapeutic potential and can be adopted to address multiple unmet needs in different clinical settings.

Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice.

Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality. The underlying mechanism of infections has been widely investigated by scientist, while standard wound management is routinely been used in general practice. However, strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization, delayed healing and drug resistance. In the present review, we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis, non-surgical methods and surgical methods. Moreover, we highlight emerging innovations in the development of antimicrobial peptides, phages, controlled drug delivery, wound dressing materials and herbal medicine, and find that sensitive diagnostics, combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.

Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing.

Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti-androgen drug, flutamide accelerates cutaneous wound healing, whereas paradoxically systemic dihydrotestosterone (DHT) improves burn wound healing. We developed and characterized a PCL scaffold that is capable of controlled release of androgen (DHT) and anti-androgen (F) individually or together. This study aims to investigate whether local modification of androgen actions has an impact on burn injury wound healing. In a full-thickness burn wound healing, mouse model, DHT/F-scaffold showed a significantly faster wound healing compared with F-scaffold or DHT-scaffold. Histology analysis confirmed that DHT/F-scaffold exhibited higher re-epithelization, cell proliferation, angiogenesis, and collagen deposition. Dual release of DHT and F from PCL scaffolds promoted cell proliferation of human keratinocytes and alters the keratinocyte cell cycle. Lastly, no adverse effects on androgen-dependent organs, spleen and liver were observed. In conclusion, we demonstrated DHT plus F load PCL scaffolds accelerated burn wound healing when loading alone did not. These findings point to a complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.

Ventilatory support in Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are blistering cutaneous disorders that often manifest with epidermal and mucosal necrosis. In extreme cases, the upper or bronchial airways are threatened, necessitating intubation and mechanical ventilation. This systematic review and meta-analysis examines the prevalence of mechanical ventilation (MV) in patients with SJS or TENS, despite maximal medical therapy, and additionally aims to identify the risk factors associated with this requirement. MATERIALS AND METHODS: A systematic review of the literature was performed using the PRISMA guidelines and meta-analysis of proportions. RESULTS: Six articles were included, with pooled total of 18648 cases. The weighted prevalence of MV was 27.5% (95%CI 17.8-39.9%). The need for MV was more closely associated with TEN, compared to SJS (OR 4.40, 95%CI 2.73-7.10, I2=48%, p<.00001.) Risk factors associated with the need for MV included bacteremia (OR 5.02, 95%CI 2.87-8.79, I2=0%, p<.00001), shock/organ failure on admission (OR 261.99, 95%CI 21.88-3137, I2=71, p<.0001), total body surface area (TBSA) >30% (OR 4.47, 95%CI 1.41-14.20, I2=71, p=.01.). CONCLUSION: Limited published evidence with significant heterogeneity exists within the literature regarding the need for MV in SJS and TEN. Greater cutaneous involvement, and more critically unwell patients appear more likely to require MV.

Wound healing and dermal regeneration in severe burn patients treated with NovoSorb® Biodegradable Temporising Matrix: A prospective clinical study.

INTRODUCTION: For extensive burns, autologous donor skin may be insufficient for early debridement and grafting in a single stage. A novel, synthetic polyurethane dermal template (NovoSorb® Biodegradable Temporising Matrix, BTM) was developed to address this need. The aim of this study was to evaluate use of BTM for primary dermal repair after deep burn injury. METHODS: A multicentre, prospective, clinical study was conducted from September 2015 to May 2018. The primary endpoint was % split skin graft take over applied BTM at 7-10 days after grafting. Secondary endpoints included % BTM take, incidence of infection and adverse events, and scar quality to 12 months after BTM application. RESULTS: Thirty patients were treated with BTM and delayed split skin grafting. The % graft take had a mean of 81.9% and % BTM take had a mean of 88.6%, demonstrating effective integration of BTM. When managed appropriately, it was possible for BTM to integrate successfully despite findings suggestive of infection. Scar quality improved over time. DISCUSSION: These results provide additional clinical evidence on the safety and performance of BTM as an effective dermal substitute in the treatment of patients with deep burn injuries.

Management of foot burns with an emphasis on high-risk groups.

BACKGROUND: Burns injuries are dynamic and evolve over time. Burn injuries to the feet present with seasonal variation, affecting clinical outcomes for certain high-risk groups. Although they affect a very small percentage of the body, burn injuries to the feet can affect mobility, morbidity and rehabilitation, particularly in patients with diabetes. OBJECTIVE: The aim of this article is to provide an understanding of seasonal variation in foot burns for high-risk groups and how to manage them appropriately. This article provides a comprehensive analysis on epidemiology, pathology and management, with the aim of providing guidance for general practitioners (GPs). DISCUSSION: The management of foot burns is multidisciplinary, involving GPs, allied health specialists, nurses, medical and surgical specialties. The epidemiological variations of these injuries have shown differences in clinical outcomes among high-risk groups such as the elderly and people with diabetes. Education and prevention are crucial in reducing the rate of injury in the rising number of patients in high-risk groups.

Low-protein diet accelerates wound healing in mice post-acute injury.

BACKGROUND: Wound healing processes are influenced by macronutrient intake (protein, carbohydrate and fat). The most favourable diet for cutaneous wound healing is not known, although high-protein diets are currently favoured clinically. This experimental study investigates the optimal macronutrient balance for cutaneous wound healing using a mouse model and the Geometric Framework, a nutrient modelling method, capable of analyzing the individual and interactive effects of a wide spectrum of macronutrient intake. METHODS: Two adjacent and identical full-thickness skin excisions (1 cm2) were surgically created on the dorsal area of male C57BL/6 mice. Mice were then allocated to one of 12 high-energy diets that varied in protein, carbohydrate and fat content. In select diets, wound healing processes, cytokine expression, energy expenditure, body composition, muscle and fat reserves were assessed. RESULTS: Using the Geometric Framework, we show that a low-protein intake, coupled with a balanced intake of carbohydrate and fat is optimal for wound healing. Mice fed a low-protein diet progressed quickly through wound healing stages with favourable wound inflammatory cytokine expression and significantly accelerated collagen production. These local processes were associated with an increased early systemic inflammatory response and a higher overall energy expenditure, related to metabolic changes occurring in key macronutrient reserves in lean body mass and fat depots. CONCLUSIONS: The results suggest that a low-protein diet may have a greater potential to accelerate wound healing than the current clinically used high-protein diets.

The contradictory role of androgens in cutaneous and major burn wound healing.

Wound healing is a complex process involving four overlapping phases: haemostasis, inflammation, cell recruitment and matrix remodeling. In mouse models, surgical, pharmacological and genetic approaches targeting androgen actions in skin have shown that androgens increase interleukin-6 and tumor necrosis factor-α production and reduce wound re-epithelization and matrix deposition, retarding cutaneous wound healing. Similarly, clinical studies have shown that cutaneous wound healing is slower in men compared to women. However, in major burn injury, which triggers not only local wound-healing processes but also systemic hypermetabolism, the role of androgens is poorly understood. Recent studies have claimed that a synthetic androgen, oxandrolone, increases protein synthesis, improves lean body mass and shortens length of hospital stay. However, the possible mechanisms by which oxandrolone regulates major burn injury have not been reported. In this review, we summarize the current findings on the roles of androgens in cutaneous and major burn wound healing, as well as androgens as a potential therapeutic treatment option for patients with major burn injuries.

Treatment of Partial Thickness Burns: A Prospective, Randomized Controlled Trial Comparing Four Routinely Used Burns Dressings in an Ambulatory Care Setting.

This prospective, randomized controlled trial study compared the effects of four dressings for adult partial thickness burns, focusing on re-epithelialization time and cost effectiveness. Adults with partial thickness burns meeting inclusion criteria were randomized to either Biobrane™, Acticoat™, Mepilex® Ag, or Aquacel® Ag. Primary endpoint for analysis was >95% re-epithelialization. Incremental cost-effectiveness ratios were calculated based on dressing costs. Dominance probabilities between treatment arms were calculated from bootstrap resampling trial data. One hunderd thirty-one partial thickness burn wounds in 119 patients were randomized. Adjusting for sex, age, smoking status, burn mechanism, TBSA, and first aid adequacy, Mepilex® Ag had a reduced time to re-epithelialization compared to Biobrane™ (IRR: 1.26; 95% CI: 1.07-1.48, P < .01). Economic analysis showed that there was a 99%, 71%, and 53% probability that Mepilex® Ag dominated (cheaper and more effective) Biobrane™, Acticoat™, and Aquacel® Ag, respectively. Mepilex® Ag achieved faster re-epithelialization and better cost effectiveness. Patient satisfaction and comfort seems better with Biobrane™ although not reflected within the end outcome of the healed wound. It is the patients' (after extensive education) and clinicians' choice, level of experience, and availability of products in praxis that will guide the decision as to which the product is used individually on which patient.