Graft-Host Interaction and Its Effect on Wound Repair Using Mouse Models.

Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was to better understand the molecular changes in the wound triggered by autologous and synthetic grafting. Defining the wound changes at the molecular level during grafting sets the basis to test other engineered skin grafts by design. In this study, a full-thickness skin graft (SKH-1 hairless) mouse model was established. An autologous full-thickness skin graft (FTSG) or an acellular fully synthetic Biodegradable Temporising Matrix (BTM) was grafted. The wound bed/grafts were analysed at histological, RNA, and protein levels during the inflammation (day 1), proliferation (day 5), and remodelling (day 21) phases of wound repair. The results showed that in this mouse model, similar to others, inflammatory marker levels, including Il-6, Cxcl-1, and Cxcl-5/6, were raised within a day post-wounding. Autologous grafting reduced the expression of these inflammatory markers. This was different from the wounds grafted with synthetic dermal grafts, in which Cxcl-1 and Cxcl-5/6 remained significantly high up to 21 days post-grafting. Autologous skin grafting reduced wound contraction compared to wounds that were left to spontaneously repair. Synthetic grafts contracted significantly more than FTSG by day 21. The observed wound contraction in synthetic grafts was most likely mediated at least partly by myofibroblasts. It is possible that high TGF-ß1 levels in days 1-21 were the driving force behind myofibroblast abundance in synthetic grafts, although no evidence of TGF-ß1-mediated Connective Tissue Growth Factor (CTGF) upregulation was observed.

In-hospital outcomes of paediatric burn injuries managed in children's hospitals compared to general hospitals.

INTRODUCTION: In Australia and New Zealand, children with burn injuries are cared for in either general hospitals which cater to both adult and paediatric burn injuries or in children's hospitals. Few publications have attempted to analyse modern burn care and outcomes as a function of treating facilities. AIM: The aim of this study was to compare in-hospital outcomes of paediatric burn injuries managed in children's hospitals to those treated in general hospitals that regularly treated both adult and paediatric burn patients. METHODS: A retrospective cohort study of cases was undertaken using data from the Burns Registry of Australia and New Zealand (BRANZ). All paediatric patients with data for an acute or transfer admission to a BRANZ hospital and registered with BRANZ with a date of admission between 1 July 2016 and 30 June 2020 were included in the study. The primary outcome of interest was the acute admission length of stay. Secondary outcome measures of interest included admission to the intensive care unit and readmission to a specialist burn service within 28 days. The Alfred Hospital Ethics Committee granted ethical approval for this study (project 629/21). RESULTS: A total of 4630 paediatric burn patients were included in the analysis. Approximately three quarters of this cohort (n = 3510, 75.8%) were admitted to a paediatric only hospital, while the remaining quarter (n = 1120, 24.2%) were admitted to a general hospital. A greater proportion of patients admitted to general hospitals underwent burn wound management procedures in the operating theatre (general hospitals 83.9%, children's hospitals 71.4%, p < 0.001). Patients admitted to children's hospitals had a longer median time to their first episode of grafting (children's hospitals 12.4 days, general hospitals 8.3 days, p < 0.001). The adjusted regression model for hospital LOS indicate that patients admitted to general hospitals had a 23% shorter hospital LOS, compared to patients admitted to children's hospitals. Neither the unadjusted or adjusted model for intensive care unit admission was significant. After accounting for relevant confounding factors, there was no association between service type and hospital readmission rates. CONCLUSIONS: Comparing children's hospitals and general hospitals, different models of care seem to exist. Burn services in children's hospitals adopted a more conservative approach and were more inclined to facilitate healing by secondary intention rather than surgical debridement and grafting. General hospitals are more "aggressive" in managing burn wounds in theatre early, and debriding and grafting the burn wounds whenever considered necessary.

Understanding the mechanisms of spontaneous and skin-grafted wound repair: the path to engineered skin grafts.

Spontaneous wound repair is a complex process that involves overlapping phases of inflammation, proliferation and remodelling, co-ordinated by growth factors and proteases. In extensive wounds such as burns, the repair process would not be achieved in a timely fashion unless grafted. Although spontaneous wound repair has been extensively described, the processes by which wound repair mechanisms mediate graft take are yet to be fully explored. This review describes engraftment stages and summarises current understanding of molecular mechanisms which regulate autologous skin graft healing, with the goal of directing innovation in permanent wound closure with skin substitutes. Graftability and vascularisation of various skin substitutes that are either in the market or in development phase are discussed. In doing so, we cast a spotlight on the paucity of scientific information available as to how skin grafts (both autologous and engineered) heal a wound bed. Better understanding of these processes may assist in developing novel methods of wound management and treatments.

Biomarkers for the Early Diagnosis of Sepsis in Burns: Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of all biomarkers studied to date for the early diagnosis of sepsis in hospitalized patients with burns. BACKGROUND: Early clinical diagnosis of sepsis in burns patients is notoriously difficult due to the hypermetabolic nature of thermal injury. A considerable variety of biomarkers have been proposed as potentially useful adjuncts to assist with making a timely and accurate diagnosis. METHODS: We searched Medline, Embase, Cochrane CENTRAL, Biosis Previews, Web of Science, and Medline In-Process to February 2020. We included diagnostic studies involving burns patients that assessed biomarkers against a reference sepsis definition of positive blood cultures or a combination of microbiologically proven infection with systemic inflammation and/or organ dysfunction. Pooled measures of diagnostic accuracy were derived for each biomarker using bivariate random-effects meta-analysis. RESULTS: We included 28 studies evaluating 57 different biomarkers and incorporating 1517 participants. Procalcitonin was moderately sensitive (73%) and specific (75%) for sepsis in patients with burns. C-reactive protein was highly sensitive (86%) but poorly specific (54%). White blood cell count had poor sensitivity (47%) and moderate specificity (65%). All other biomarkers had insufficient studies to include in a meta-analysis, however brain natriuretic peptide, stroke volume index, tumor necrosis factor (TNF)-alpha, and cell-free DNA (on day 14 post-injury) showed the most promise in single studies. There was moderate to significant heterogeneity reflecting different study populations, sepsis definitions and test thresholds. CONCLUSIONS: The most widely studied biomarkers are poorly predictive for sepsis in burns patients. Brain natriuretic peptide, stroke volume index, TNF-alpha, and cell-free DNA showed promise in single studies and should be further evaluated. A standardized approach to the evaluation of diagnostic markers (including time of sampling, cut-offs, and outcomes) would be useful.

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.

Use of peritoneum in neovagina construction in gender-affirming surgery: A systematic review.

BACKGROUND: Gender dysphoria is defined as discomfort or distress that is caused by a discrepancy between a person's gender identity and that person's sex assigned at birth. The main objective of this study was to review the application, efficacy and outcomes of a novel surgical technique, peritoneal pull-through technique vaginoplasty, in gender-affirming surgery. Specific outcome parameters include (1) healing time (2) depth of cavity achieved (3) alleviation of dysphoria (4) morbidity of the surgery. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and PROSPERO registration obtained prior to commencement (PROSPERO CRD42020206736). A search was performed in OVID MEDLINE, EMBASE, Willey Online Library and PubMed. Specialty-related journals, grey literature and reference lists of relevant articles were manually searched. RESULTS: From 476 potentially relevant articles, 12 articles were analysed. The publications were all level 4 or level 5 evidence. Healing times were poorly reported or often not mentioned. Eight authors reported neovagina cavity depth of at least 13 cm and good patient satisfaction. Alleviation of dysphoria was not discussed by any of the publications and only six reported complications. Average follow up reported ranged from 6 weeks to 14.8 months. CONCLUSION: The application of peritoneal pull-through vaginoplasty in gender-affirming surgery is promising and novel. However, there is a paucity of data. Further research and longer-term data are required to assess the efficacy and safety of this technique. Patients seeking this surgery overseas should be informed of the potential difficulties they may face.

Burn wound excision within 24 h: A 9-year review.

BACKGROUND: Severe burns are accompanied by an acute and prolonged hypermetabolic response typified by elevated levels of proinflammatory cytokines and acute phase proteins. When persistent, this inflammatory response can result in multi-organ dysfunction and death. Regarded as the standard of care, early removal of devitalised tissue and eschar mitigates this hypermetabolic response. Ascertaining the optimal time point for early excision, which remains controversial, has several clinical implications. METHODS: This retrospective observational study included 836 adult thermal burns patients with total burned surface area ≥20% from all Burns Registry of Australia and New Zealand (BRANZ) Hospital sites, including the Victorian Adult Burns Service (VABS), from July 1 2009 to June 30 2018. Patients were divided into two groups, "early" and "delayed", based on a 24-hour excision cut-off from when the injury occurred. Outcome measurements included mortality, hospital length of stay, intensive care unit length of stay, ventilation requirements and the incidence of positive blood cultures. RESULTS: Among all patients at BRANZ sites, excision within 24 h was associated with reduced mean length of ICU stay (6.6 ± 8.1 vs. 9.2 ± 10.6 days; p = 0.008) and lower mean mechanical ventilator hourly use (94.9 ± 160.8 vs. 159.2 ± 219.1 h; p = 0.001) in the 20-29% TBSA sub-group. Beyond this, no significant differences were observed in outcome measurements. CONCLUSIONS: While it is physiologically important to perform early burn wound excision to mitigate the inflammatory response, delaying excision beyond 24 h for surgical planning, possibly up to 72 h after injury, may be a reasonable approach for certain patient groups.

Wound healing after cultured epithelial autografting in patients with massive burn injury: A cohort study.

BACKGROUND/AIM: Last century, our laboratory produced Cultured Epithelial Autograft (CEA) for clinical use by the affiliated adult burn service and other burn units across the country. Production of CEA for clinical use was discontinued after several years because of a low success rate and subsequent low demand. Recently, at our burns unit, a cell culture program was reintroduced as a direct response to the need for improvement in ongoing deficiencies and clinical requirements in burn wound closure. The aim of this study was to validate the laboratory processes and clinical algorithms established and share our recent clinical experiences involving CEA. METHODS: This observational cohort study recruited patients with burns exceeding 35% TBSA admitted to the Victorian Adult Burns Service at The Alfred (December 2013-December 2016). Autologous keratinocytes were expanded and delivered through sheets of fibrin carrier. RESULTS: Twelve patients were recruited to participate in the study. Thirty-two sites were treated with CEA. CEA applied in combination with widely meshed SSG led to the highest take rate (90.1%) at 7-10 days. Further, debridement and grafting were necessary in sixteen of thirty-two sites treated, all involving wound beds prepared with Cuono method or sites treated with CEA only. CONCLUSION: It is important to address the problem of wound bed contamination, either through increased resistance on the part of the construct or wound bed sterilization. Improved understanding of the relative importance of vascularization, control of cell behavior, the extracellular matrix, immune function, and intrinsic antimicrobial capacity for graft take would then inform a more targeted approach to skin tissue engineering for wound closure in severe burns.

Distraction ligamentotaxis for complex proximal interphalangeal joint fracture dislocations: a clinical study and the modified pins rubber band traction system revisited.

BACKGROUND: The purpose of this study is to present our experience with the modified pins and rubber band traction system, discuss problems encountered, and make recommendations to optimize outcomes. METHODS: Data was collected prospectively from November 2013 to March 2017 at a tertiary referral hospital in Melbourne, Australia. Patients with closed complex proximal interphalangeal joint fracture dislocations that were considered unsuitable for other surgical options were included in the study. Patients underwent dynamic skeletal distraction using the modified (Deshmukh) pins rubber band traction system. Outcomes were measured using the Nominal Rating Scale for pain; Disabilities of the Arm, Shoulder, and Hand (DASH) score; active and passive range of motion; patient rating scale; and complications. RESULTS: Twenty patients underwent the procedure, and 19 were included in analyses. At the final follow-up assessment, an average of 62° and 77° was achieved for proximal interphalangeal joint active and passive range of motion, respectively. Pain levels were low (median score of 0 at rest and 1 ranging, out of 10). Four patients suffered minor pin site infections. CONCLUSION: Distraction ligamentotaxis is a useful part of the armamentarium, especially in the absence of more suitable procedures. It is important to select appropriate patients, educate, and ensure adherence to postoperative therapy. Employing the Deshmukh frame modification streamlines the theatre processes, and removal of wires at approximately 4 weeks minimizes risk of pin site infection.

Retrospective review of a tertiary adult burn centre's experience with modified Meek grafting.

BACKGROUND: Autologous split skin grafting is the gold standard in treating patients with massive burns. However, the limited availability of donor sites remains a problem. The aim of this study is to present our experience with the modified Meek technique of grafting, outcomes achieved and recommendations for optimized outcomes. METHODS: We retrospectively reviewed patient records from our tertiary referral burn centre and the Bi-National Burns Registry to identify all patients who had modified Meek grafting between 2010 and 2013. Patient records were reviewed individually and information regarding patient demographics, mechanism of injury and surgical management was recorded. Outcome measures including graft take rate, requirement for further surgery and complications were also recorded. RESULTS: Eleven patients had modified Meek grafting procedures. The average age of patients was 46 years old (range 23 - 64). The average total body surface area (TBSA) burnt was 56.75 % (range 20-80 %). On average, 87 % of the grafted areas healed well and did not require regrafting. In the regrafted areas, infection was the leading cause of graft failure. CONCLUSIONS: Modified Meek grafting is a useful method of skin expansion. Similar to any other grafting technique, infection needs to be sought and treated promptly. It is recommended for larger burns where donor sites are not adequate or where it is desirable to limit their extent.

Keystone Island Flap: Effects of Islanding on Vascularity.

UNLABELLED: Based on his clinical observations the "red dot sign" and hyperemic flare, Behan has advocated the superior vascularity of the island flap design for at least 2 decades. The aim of this study was to determine whether (1) surgical islanding of a flap alters the vascularity or blood supply of the flap and (2) these changes in blood supply explain Behan's clinical observations of "red dot sign" and hyperemic flare. METHODS: Patients undergoing local island fasciocutaneous flaps or anterolateral thigh fasciocutaneous free flaps were recruited for this trial from a single institution over a 10-month period (September 2013 to July 2014). Three adjacent specimens of skin and subcutaneous fat (control, non-island, and island) were harvested from each patient at various stages of their surgery for histological assessment. A pathologist reviewed randomized specimens for microvascular variables, including arteriole wall thickness, arteriole diameter, venule wall thickness, and venule diameter. RESULTS: Thirteen patients (with 14 sets of specimen) were recruited for this study. When compared with the control state, both arteriole diameter and venule diameter in island flaps were significantly increased. CONCLUSIONS: These results validate Behan's clinical observations of "red dot sign" and hyperemic flare. Further studies are required to directly compare island and non-island flap designs.

Use of the keystone island flap for advanced head and neck cancer in the elderly--a principle of amelioration.

Traditional management strategies of advanced head and neck cancer in the elderly include palliation and radical resection with microsurgical reconstruction. The keystone flap approach is an alternate reconstructive technique with a range of benefits for the aging population. This publication presents a series of elderly patients with head and neck cancer who underwent resection and reconstruction using the keystone flap principles. The aim is to demonstrate the value of this reconstructive technique in the various anatomical regions of the head and neck. Various operative sequences are accompanied by illustrations and discussions of the underlying principles.

A devastating complication: duodenal perforation due to biliary stent migration.

Endoscopic retrograde cholangiopancreatography (ERCP) plays an important diagnostic and potentially therapeutic role in the management of a broad range of biliary and pancreatic disorders. However, it is an invasive procedure with an associated complication rate in the vicinity of 5% to 15% and mortality rate of 1%. We present an unusual case of a patient who sustained a stent-related duodenal perforation after undergoing ERCP. We reviewed the current literature in regard to risk factors, etiology, diagnosis, management, and prognosis of ERCP-related perforations, aiming to provide a brief, updated overview of this devastating complication.