An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury.

BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.

SMOOTH protocol: A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring.

BACKGROUND: Burn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells. METHODS: We will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan® Cortex, Cutometer® and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy. DISCUSSION: This study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04736251.

Rapid redesign and effect on clinical workload of a supra-regional burns and plastic surgery service during the COVID-19 pandemic.

INTRODUCTION: In March 2020, South Wales experienced the most significant COVID-19 outbreak in the UK outside of London. We share our experience of the rapid redesign and subsequent change in activity in one of the busiest supra-regional burns and plastic surgery services in the UK. METHODS: A time-matched retrospective service evaluation was completed for a 7-week "COVID-19" study period and the equivalent weeks in 2018 and 2019. The primary aim of this study was to evaluate plastic surgery theatre use and the impact of service redesign. Comparison between study periods was tested for statistical significance using two-tailed t-tests. RESULTS: Operation numbers reduced by 64% and total operating time by 70%. General anaesthetic cases reduced from 41% to 7% (p<0.0001), and surgery was mainly carried out in ringfenced daycase theatres. Emergency surgery decreased by 84% and elective surgery by 46%. Cancer surgery as a proportion of total elective operating increased from 51% to 96% (p<0.0001). The absolute number of cancer-related surgeries undertaken was maintained despite the pandemic. CONCLUSION: Rapid development of COVID-19 SOPs minimised inpatient admissions. There was a significant decrease in operating while maintaining emergency and cancer surgery. Our ringfenced local anaesthetic Plastic Surgery Treatment Centre was essential in delivering a service. COVID-19 acted as a catalyst for service innovations and the uptake of activities such as telemedicine, virtual MDTs, and online webinars. Our experiences support the need for a core burns and plastic service during a pandemic, and show that the service can be effectively redesigned at speed.

An Unusual Presentation to the Burns Unit-A Cautionary Tale.

The authors report a case of a 34-year-old female with systemic lupus erythematosus (SLE) and lupus nephritis who was referred to the regional burns service with a suspected contact burn to the left flank and hypogastrium from a hot water bottle. The patient had been applying a hot water bottle to the area at night for pain relief and after 3 days she noticed a localized area of erythema which became larger and began to blister over a period of 5 days. The blistered areas were erythematous and wet; however, the capillary refill time was sluggish. The lesion was initially diagnosed and treated as a superficial partial thickness burn that had developed secondary to prolonged contact with a hot water bottle. However, due to the history of immunosuppression as well as elements of the lesion being unusual for a burn, we consequently diagnosed this as herpes zoster infection. This case highlights the importance of always thinking of alternative diagnoses. There are several cases in the literature where shingles has been dangerously misdiagnosed, furthermore leading to patients being mistakenly treated and even operated on. In the early stages, abdominal shingles may present very similarly to superficial partial thickness burns, both with neuropathic pain, erythema, and blistering. It is important for the burns surgeon to be aware of this diagnosis as a differential in atypical presentations, and to pay particular attention to the timeline of events is the key to diagnosis.

Development and Initial Validation of Calculated Tumor Area as a Prognostic Tool in Cutaneous Malignant Melanoma.

IMPORTANCE: Breslow thickness is a 1-dimensional surrogate prognostic feature for tumor size, yet tissue sections have 2 dimensions. Therefore, a 2-dimensional feature, calculated tumor area (CTA), was devised. OBJECTIVE: To determine CTA precision and prognostic value. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort of patients with cutaneous melanoma presented to the Leicester and Nottingham National Health Service hospital trusts in the United Kingdom. Eligible patients in the Leicester development sample had available primary tumor tissue; a diagnosis from January 1, 2004, through December 31, 2011; invasive disease; and Leicestershire residency. Patients in the Nottingham validation sample had an anonymized spreadsheet with primary melanoma diagnosed from January 1, 2003, through December 31, 2005, or from January 1, 2008, through December 31, 2010. From a starting population of 1463 patients in both data sets, a total of 224 (15.3%) were excluded to yield a study population of 1239. Data were analyzed from April 30, 2018, through January 10, 2019. INTERVENTION: An observational analysis of the prognostic value of CTA in patients with cutaneous melanoma. MAIN OUTCOMES AND MEASURES: Independent association of CTA with melanoma-specific survival and confounding effect of CTA on Breslow thickness in survival analysis. RESULTS: A total of 1239 patients with melanoma were assessed, including 649 (52.4%) women, with a median age of 60 years (interquartile range, 47-71 years). An intraclass correlation coefficient for CTA on 13 cases was 0.99. In 918 patients in the Leicester cohort, CTA was an independent prognostic factor in Cox proportional hazards regression models after adjusting for Breslow thickness, age, sex, ulcer, mitotic rate, and microsatellites (hazard ratio [HR], 1.87; 95% CI, 1.49-2.34; P < .001). Validation in 321 patients in the Nottingham cohort showed an HR of 1.55 (95% CI, 1.15-2.09; P = .005) and in the combined 1239 cases, an HR of 1.70 (95% CI, 1.43-2.03; P < .001). Breslow thickness was significant in multivariable analysis only when CTA was not in the model. The relative importance of CTA was shown by its retention in all 100 bootstrap multivariable models with backward selection, whereas Breslow thickness was retained in only 53. Melanomas stratified by CTA showed wider separation of survival curves than those stratified by Breslow thickness using the American Joint Committee on Cancer Staging Manual, 8th Edition (HRs, 1.00 to 41.46 vs 1.00 to 36.95, respectively), and the model with CTA categories had a Bayesian information criterion difference of 13.9 compared with T category, indicating substantially better fit. This model had a Harrell C index of 83.7%, and bootstrap analysis showed little evidence of model optimism, with a corrected calibration slope of 0.99. CONCLUSIONS AND RELEVANCE: This study provides a novel microscopic feature, CTA, with evidence of its independent prognostic value. This evidence suggests that CTA should be a priority for further study.

Identifying patient concerns during consultations in tertiary burns services: development of the Adult Burns Patient Concerns Inventory.

OBJECTIVES: Identifying the issues and concerns that matter most to burns survivors can be challenging. For a number of reasons, but mainly relating to patient empowerment, some of the most pressing concerns patients may have during a clinical encounter may not naturally be the focal point of that encounter. The Patient Concerns Inventory (PCI) is a tried and tested concept initially developed in the field of head and neck cancer that empowers patients during a clinical encounter through provision of a list of prompts that allows patients to self-report concerns prior to consultation. The aim of this study was to develop a PCI for adult burns patients. DESIGN: Content for the PCI was generated from three sources: burns health-related quality of life tools, thematic analysis of one-to-one interviews with 12 adult burns patients and 17 multidisciplinary team (MDT) members. Content was refined using a Delphi consensus technique, with patients and staff members, using SurveyMonkey. SETTING: Within outpatient secondary care. PARTICIPANTS: Twelve adult burns patients and MDT members from two regional burns centres. RESULTS: A total of 111 individual items were generated from the three sources. The Delphi process refined the total number of items to 58. The main emergent domains were physical and functional well-being (18 items), psychological, emotional and spiritual well-being (22 items), social care and social well-being (7 items) and treatment-related concerns (11 items). CONCLUSIONS: The Adult Burns Patient Concerns Inventory is a 58-item, holistic prompt list, designed to be used in the outpatient clinic. It offers a new tool in burn care to improve communication between healthcare professionals and patients, empowering them to identify their most pressing concerns and hence deliver a more focused and targeted patient-centred clinical encounter.

Breslow Density Is a Novel Prognostic Feature That Adds Value to Melanoma Staging.

Histomorphologic prognostic biomarkers that can be measured using only an hematoxylin and eosin stain are very attractive because they are simple and cheap. We conceived an entirely novel biomarker of this type, the Breslow density (BD), which measures invasive melanoma cell density at the site where Breslow thickness (BT) is measured. This study assessed BD's prognostic value. In this study, BD was measured in 1329 melanoma patients. Measurement accuracy and precision was assessed using intraclass correlation coefficient (ICC). Survival was assessed with a primary end-point of melanoma-specific survival (MSS) and also overall survival and metastasis-free survival. We found that BD measurement was accurate compared with gold standard image analysis (ICC, 0.84). Precision was excellent for 3 observers with different experience (ICC, 0.93) and for an observer using only written instructions (ICC, 0.93). BD was a highly significant predictor in multivariable analysis for overall survival, MSS, and metastasis-free survival (each, P<0.001) and it explained MSS better than BT, but BT and BD together had best explanatory capability. A BD cut point of ≥65% was trained in 970 melanomas and validated in 359. This cut point showed promise as a novel way to upstage melanoma from T stage "a" to "b." BD was combined with BT to create a targeted burden score. This was a validated as an adjunct to American Joint Committee on Cancer stage. In summary, BD can be measured accurately and precisely. It demonstrated independent prognostic value and explained MSS better than BT alone. Notably, we demonstrated ways that BD could be used with American Joint Committee on Cancer version 8 staging.

Long-term clinical and histological analysis of Integra dermal regeneration template.

BACKGROUND: This study looked at clinical and histological outcomes of patients treated with Integra more than 2 years earlier. Although previous studies have investigated the short-term clinical and histological results, there have been no studies to investigate longer-term changes. METHODS: Fourteen patients (23 sites) were assessed. Patients used a visual analogue scale to score characteristics of their scars. Objective evaluation of the reconstructions was carried out using the Cutometer MPA580. Punch biopsy specimens of the sites were stained and labeled immunohistochemically with S100, CD31, and CD34 antisera. RESULTS: The highest scoring category by patients was softness (median, +45 percent). The lowest score was sweating, which all patients scored 0. The median Cutometer readings ranged from 39 to 52 percent of the control values. Histological examination showed three patterns of collagen arrangement; parallel arrangement was found in over 60 percent of specimens. Elastic fibers were identified in all specimens; however, all were of abnormal morphology. The majority of specimens showed evidence of nerve fiber regeneration although confined to the mid- or lower reticular dermis. There was no regeneration of skin adnexa. CONCLUSIONS: This study showed significant improvements in patient-assessed mobility, softness, and appearance. Collagen and elastic fibrin were present in all specimens, nerve fiber regeneration was limited to the mid- or lower reticular dermis, and adnexal structures were absent. The typical wrinkled appearance of mature Integra reconstruction cannot be said to be entirely due to a lack of elastic fibers.

Topical negative pressure therapy: does it accelerate neovascularisation within the dermal regeneration template, Integra? A prospective histological in vivo study.

BACKGROUND: The use of topical negative pressure (TNP) dressings with dermal regeneration template (DRT), Integra, has improved outcomes and simplified aftercare. Previous clinical studies have suggested accelerated vascularisation; with a reduction in the duration of the 1st stage after the application of Integra, from 2 to 4 weeks to as little as 4 days, but with no histological evidence. However, histological studies, without TNP, have shown that vascularisation occurs between the second and the fourth week. This study set out to examine histologically the rate of DRT neovascularisation when combined with TNP. METHODS: Eight patients with nine reconstruction sites were enlisted. Unmeshed Integra and fibrin sealant to promote adherence were used. TNP was applied for the duration between the 1st and the 2nd stages. Patients underwent serial biopsies on days 7, 14, 21 and 28 post-application. The biopsies were stained with H&E and endothelial markers CD31 and CD34. Template vascularisation was assessed as a percentage of the template depth in which patent, canalised vascular channels could be demonstrated. RESULTS: The median percentage of the template depth which demonstrated canalised channels was 0%, 20%, 61% and 80% for days, 7, 14, 21 and 28, respectively. CONCLUSION: The application of TNP dressings to dermal templates can reduce shearing forces, restrict seroma and haematoma formation, simplify wound care and improve patient tolerance. However, this study could not demonstrate that TNP accelerates neovascularisation as verified by the presence of histologically patent vascular channels.