Living in Western Australia induces some physiological adaptations of seasonal acclimatisation in the surgical burns team.

Seasonal acclimatization is known to result in adaptations that can improve heat tolerance. Staff who operate on burn injuries are exposed to thermally stressful conditions and seasonal acclimatization may improve their thermoeffector responses during surgery. Therefore, the aim of this study was to assess the physiological and perceptual responses of staff who operate on burn injuries during summer and winter, to determine whether they become acclimatized to the heated operating theater. Eight staff members had physiological and perceptual responses compared during burn surgeries conducted in thermoneutral (CON: 24.1 ± 1.2°C, 45 ± 7% relative humidity [RH]) and heated (HOT: 31.3 ± 1.6°C, 44 ± 7% RH) operating theaters, in summer and winter. Physiological parameters that were assessed included core temperature, heart rate, total sweat loss, sweat rate, and urinary specific gravity. Perceptual responses included ratings of thermal sensation and comfort. In summer, CON compared to winter CON, baseline (85 ± 15 bpm VS 94 ± 18 bpm), mean (84 ± 16 bpm VS 93 ± 18 bpm), and peak HR (94 ± 17 bpm VS 105 ± 19 bpm) were lower (p < 0.05), whereas core temperature was not different between seasons in either condition (p > 0.05). In HOT, ratings of discomfort were higher in summer (15 ± 3) than winter (13 ± 3; p > 0.05), but ratings of thermal sensation and sweat rate were similar between seasons (p > 0.05). The surgical team in burns in Western Australia can obtain some of the physiological adaptations that result from seasonal acclimatization, but not all. That is most likely due to a lower than required amount of outdoor heat exposure in summer, to induce all physiological and perceptual adaptations.

Postoperative hypothermia is associated with reduced length of stay in adult acute burn survivors.

BACKGROUND: The hypermetabolic response after a burn predisposes patients to hypothermia due to dysfunction of thermoregulation. Traditionally, hypothermia is avoided actively in burn care due to reported complications associated with low body temperature. The likelihood of hypothermia with acute burn surgery is compounded by general anesthesia, exposure of wound areas and prolonged operation times. However, we find limited studies exploring the effects of perioperative hypothermia on length of stay in the adult burn population. OBJECTIVE: To determine associations between postoperative hypothermia and hospital length of stay in adult burns patients. METHOD: This retrospective cohort study involved patients admitted to the State Adult Burn Unit in Western Australia between 1st January 2015 to 28th February 2021. All adults who underwent surgery for acute burn, and had postoperative recovery room body temperature recorded, were included in the study. In this study, we defined normothermia as >36.5C and hypothermia as < 36.0 °C with mild, moderate, and severe hypothermia being 35.0-35.9 °C, 34.0-34.9 °C and < 34.0 °C, respectively. Patients with hyperthermia were excluded. Multivariable general linear models explored if hypothermia was independently associated with length of stay. RESULTS: Among 1486 adult patients, 1338 (90%) were normothermic postoperatively, with temperatures >36.0C. We included 148 (10%) patients with hypothermia (temperature <36.0 °C) postoperatively. Most burns in the study population were minor: 96% had burns < 15% TBSA. Data modelling demonstrated that hypothermia was associated with a shorter length of hospital stay (coefficient = -0.129, p = 0.041). CONCLUSION: In adult acute burn patients, postoperative hypothermia was associated with reduced length of stay after surgery. The positive results of this study indicate that a review of the core temperature targets with acute burn surgery, and timing of burn patient cooling practices in general is warranted.

Early ambulation impacts on quality-of-life outcomes positively after lower limb burn injury: A group trajectory analysis.

INTRODUCTION: Despite the challenges of providing burn care throughout the 2.5MKm2 jurisdiction of Western Australia, early intervention after injury remains a key premise of the multidisciplinary model of care applied by the State Adult Burn Unit (SABU) team. In particular, contemporary guidelines support the facilitation of early ambulation after lower limb burn and skin grafting. Thus, this study aimed to evaluate the association between the timing of ambulation after burn and surgery on quality of life (QoL) outcomes. METHODS: Data from 1707 lower limb burn patients aged ≥ 18, admitted to the SABU between February 2011- December 2019, were included. Self-reported QoL longitudinal outcomes were assessed using the Short Form 36 and Burn Specific Health Scale Brief. Three recovery trajectories were defined according to their QoL outcome responses, mapped out to one year. Early ambulation was defined as occurring within 48 h of acute burn or surgery, as per SABU routine practice. RESULTS: Early ambulation was shown to have a positive association to the higher QoL trajectory group (>75% of cohort), though not statistically significant for the Physical Component (PCS) and Mental health Component (MCS) summary scores of the SF36; however, ambulation pathway was associated with adjusted long-term BSHS-B QoL outcomes. The least favorable trajectory of long-term recovery of the physical aspects of QoL was seen in those with higher TBSA and complications and increasing age and comorbidities. In contrast, the mental health components of QoL were robust to all those factors, apart from pre-existing comorbidities. CONCLUSION: Early ambulation after lower limb burn, and surgery, was positively associated with early and long-term QoL outcomes. Recovery trajectory is strongly indicated by where the patient journey begins after early acute care. The optimal physical QoL recovery trajectory was shared by those who were younger with reduced TBSA; complications; and, comorbidities whereas the mental health QoL trajectories were only impacted by comorbidities.

Trauma patient heterotopic ossification diagnosis is associated with increased hospital length of stay.

BACKGROUND: Traumatic heterotopic ossification (tHO) refers to the development of extra-skeletal bone in muscle and soft tissues following tissue insult secondary to surgery or trauma. This presents a persistent clinical concern associated with significant patient morbidity and expense to diagnose and treat. Traumatic HO is a substantial barrier to rehabilitation for trauma-injured patients. As such, the development of tHO after burn and other trauma is hypothesised to prolong inpatient length of stay (LOS) and thus increase health care costs. OBJECTIVE: To investigate the association between an inpatient tHO diagnosis and hospital LOS in trauma patients. METHODS: A retrospective audit of trauma patients over a 14-year period was completed using data from four WA hospitals. Burn and neurological trauma patients diagnosed with tHO as an inpatient (tHO+) and control subjects (tHO-), matched (1:3) by age, gender, and injury severity factors, were identified using medical diagnostic codes. Data relating to patient and injury-related determinants of LOS from tHO+ and tHO- subjects were analysed to model the association of tHO on total hospital length of stay. RESULTS: 188 identified patients were hospitalised due to traumatic injury; 47 patients with tHO following burn injury (n = 17), spinal cord injury (n = 13) and traumatic brain injury (n = 17), and 141 control patients. Those who developed tHO during hospitalisation had a significantly higher median LOS than matched trauma patients who did not develop tHO (142 days vs. 61 days). Multivariate regression analyses identified the following independent predictive factors of a prolonged hospital LOS: tHO diagnosis, mechanical ventilation hours, injury to the hip region and thigh area, other ossification disorder, pressure injury, admission to intensive care unit and deep vein thrombosis. Trauma patients diagnosed with tHO during their hospital admission stayed 1.6 times longer than trauma patients matched for injury severity without a tHO diagnosis (IRR 1.56, 95% CI 1.35-1.79, p<0.001). CONCLUSION: Traumatic heterotopic ossification is an independent explanatory factor for increased hospital LOS in patients following burns, spinal cord, and traumatic brain injury. Early diagnosis may assist in reducing the impact of tHO on acute hospital stay after trauma.

Non-severe thermal burn injuries induce long-lasting downregulation of gene expression in cortical excitatory neurons and microglia.

Burn injuries are devastating traumas, often leading to life-long consequences that extend beyond the observable burn scar. In the context of the nervous system, burn injury patients commonly develop chronic neurological disorders and have been suggested to have impaired motor cortex function, but the long-lasting impact on neurons and glia in the brain is unknown. Using a mouse model of non-severe burn injury, excitatory and inhibitory neurons in the primary motor cortex were labelled with fluorescent proteins using adeno-associated viruses (AAVs). A total of 5 weeks following the burn injury, virus labelled excitatory and inhibitory neurons were isolated using fluorescence-activated cell sorting (FACS). In addition, microglia and astrocytes from the remaining cortical tissue caudal to the motor cortex were immunolabelled and isolated with FACS. Whole transcriptome RNA-sequencing was used to identify any long-lasting changes to gene expression in the different cell types. RNA-seq analysis showed changes to the expression of a small number of genes with known functions in excitatory neurons and microglia, but not in inhibitory neurons or astrocytes. Specifically, genes related to GABA-A receptors in excitatory neurons and several cellular functions in microglia were found to be downregulated in burn injured mice. These findings suggest that non-severe burn injuries lead to long lasting transcriptomic changes in the brain, but only in specific cell types. Our findings provide a broad overview of the long-lasting impact of burn injuries on the central nervous system which may help identify potential therapeutic targets to prevent neurological dysfunction in burn patients.

Timing of surgery in acute deep partial-thickness burns: A study protocol.

For deep partial-thickness burns no consensus on the optimal treatment has been reached due to conflicting study outcomes with low quality evidence. Treatment options in high- and middle-income countries include conservative treatment with delayed excision and grafting if needed; and early excision and grafting. The majority of timing of surgery studies focus on survival rather than on quality of life. This study protocol describes a study that aims to compare long-term scar quality, clinical outcomes, and patient-reported outcomes between the treatment options. A multicentre prospective study will be conducted in the three Dutch burn centres (Rotterdam, Beverwijk, and Groningen). All adult patients with acute deep-partial thickness burns, based on healing potential with Laser Doppler Imaging, are eligible for inclusion. During a nine-month baseline period, standard practice will be monitored. This includes conservative treatment with dressings and topical agents, and excision and grafting of residual defects if needed 14-21 days post-burn. The subsequent nine months, early surgery is advocated, involving excision and grafting in the first week to ten days post-burn. The primary outcome compared between the two groups is long-term scar quality assessed by the Patient and Observer Scar Assessment Scale 3.0 twelve months after discharge. Secondary outcomes include clinical outcomes and patient-reported outcomes like quality of life and return to work. The aim of the study is to assess long-term scar quality in deep partial-thickness burns after conservative treatment with delayed excision and grafting if needed, compared to early excision and grafting. Adding to the ongoing debate on the optimal treatment of these burns. The broad range of studied outcomes will be used for the development of a decision aid for deep partial-thickness burns, to fully inform patients at the point of consent to surgery and support optimal person-centred care.

First do no harm: A patient-reported survey of split skin graft donor site morbidities following thin and super-thin graft harvest.

The split-thickness skin graft (STSG) donor site is the commonest used during burn surgery which has its own complications and as such the focus should be on minimizing it. Modifications to practice in our unit which we believe aid this include limiting the amount of STSG taken and the harvest of super-thin STSGs, with 0.003-0.005 in. (0.08-0.13 mm) being the commonest dermatome settings used. A patient-reported survey via a mobile phone link to a questionnaire was sent to 250 patients who had a STSG for an acute burn between 1st August 2020 and 31st July 2021. Patient demographics were collected from electronic records including the thickness of the FTSG taken when recorded. Patient responses were statistically analyzed and logistic regression with backwards elimination was performed to explore which contributing factors led to an improved experience of the donor site. Questionnaire responses were obtained from 107 patients (43%). These were between one and two and a half years after the injury. Concerning early donor site issues, itch was a problem for 52% of patients, pain was a problem for 48% of patients. Less common problems (fewer than 25% of patients) were leaking donor sites, wound breakdown, and over-granulation. Regarding long-term outcomes, increased, decreased or mixed pigmentation at the donor site was reported by 32% patients at the time of the survey. Hyper-vascular donor sites were reported by 24% patients. Raised or uneven feeling donor sites were reported by 19% patients, firm or stiff donor sites by 13% patients, and altered sensation by 10% patients. At the time of the survey, 70% responders reported their donor site looked "the same or about the same as my normal skin". Of these, 62 reported how long it took for this to happen, and it equates to a third looking normal at 6 months and half looking normal at a year. For the 32 patients who reported their donor site looking abnormal, 72% were "not bothered" by it. Patients with super-thin grafts (0.003-0.005 in.) were significantly more likely to have normal sensation, normal stiffness, and be less raised at their donor sites than those who had thin grafts (0.006-0.008 in.). This survey gives important information on patients' experiences of donor site morbidity that may form part of an informed consent process and allow tailored advice. Furthermore, it suggests that super-thin grafts may provide a superior donor site experience for patients.

Perioperative hypothermia prevention: development of simple principles and practice recommendations using a multidisciplinary consensus-based approach.

OBJECTIVES: To develop a consensus on evidence-based principles and recommendations for perioperative hypothermia prevention in the Australian context. DESIGN: This study was informed by CAN-IMPLEMENT using the ADAPTE process: (1) formation of a multidisciplinary development team; (2) systematic search process identifying existing guidance for perioperative hypothermia prevention; (3) appraisal using the AGREE II Rigor of Development domain; (4) extraction of recommendations from guidelines meeting a quality threshold using the AGREE-REX tool; (5) review of draft principles and recommendations by multidisciplinary clinicians nationally and (6) subsequent round of discussion, drafting, reflection and revision by the original panel member team. SETTING: Australian perioperative departments. PARTICIPANTS: Registered nurses, anaesthetists, surgeons and anaesthetic allied health practitioners. RESULTS: A total of 23 papers (12 guidelines, 6 evidence summaries, 3 standards, 1 best practice sheet and 1 evidence-based bundle) formed the evidence base. After evidence synthesis and development of draft recommendations, 219 perioperative clinicians provided feedback. Following refinement, three simple principles for perioperative hypothermia prevention were developed with supporting practice recommendations: (1) actively monitor core temperature for all patients at all times; (2) warm actively to keep body temperature above 36°C and patients comfortable and (3) minimise exposure to cold at all stages of perioperative care. CONCLUSION: This consensus process has generated principles and practice recommendations for hypothermia prevention that are ready for implementation with local adaptation. Further evaluation will be undertaken in a large-scale implementation trial across Australian hospitals.

Carbon dioxide laser treatment of burn-related scarring: Results of the ELIPSE (Early Laser Intervention Promotes Scar Evolution) prospective randomized controlled trial.

AIM: To investigate the impact of ablative fractional carbon dioxide laser (AFCO2L) on patient-reported outcomes measures, subjective scar appearance, dermal architecture, and gene transcription in early burn scars. METHODS: Fifteen adult patients with a burn-related scar were recruited. Inclusion criteria were two non-contiguous scar areas of 1% total body surface area, similar baseline Vancouver scar scale (VSS) score and 3months since the time of injury. All participants acted as their own control. Scars were randomized to treatment or control. Treatment scars received three AFCO2L treatments at 6-week intervals. Outcome measures were recorded at baseline, 3, 6, and 12-months post-treatment. Measures included blinded VSS, Patient Observer Scar Assessment Scale (POSAS), Brisbane Burn Scar Impact Profile (BBSIP), blinded scar photo assessment, histological tissue analysis, and RNA sequencing analysis. RESULTS: No significant difference was found in VSS, scar erythema, or pigmentation. Patient POSAS improved in scar thickness and texture following AFCO2L. All elements of BBSIP improved in control and laser groups. AFCO2L-treated scars were scored better than control scars by blinded raters. RNA sequencing illustrated that AFCO2L induced sustained changes in fibroblast gene expression. CONCLUSIONS: AFCO2L treated scars had significantly altered scar thickness and texture 6 months post-laser and were rated better than controls on blinded photo analysis after 3 treatments. RNASeq results suggest laser treatment alters the transcriptome of treated fibroblasts for at least 3 months after treatment. Expansion of this research to study in more depth fibroblast changes in response to laser, as well as assessing the impact on daily activity and quality of life, will be beneficial.

Higher operating theatre temperature during burn surgery increases physiological heat strain, subjective workload, and fatigue of surgical staff.

Raising the ambient temperature of the operating theatre is common practice during burn surgeries to maintain the patient's core body temperature; however, the effects of operating in the heat on cognitive performance, manual dexterity, and perceived workload of surgical staff have not been assessed in a real-world context. Therefore, the aim was to assess the real-time impact of heat during burn surgeries on staff's cognitive function, manual dexterity, and perceptual measures (workload, thermal sensation, thermal comfort, perceived exertion, and fatigue) and physiological parameters (core temperature, heart-rate, fluid loss, and dehydration). Ten burn surgery staff members were assessed in CON (24.0±1.1°C, 45±6% relative humidity [RH]) and HOT (30.8±1.6°C, 39±7% RH) burn surgeries (average 150 min duration). Cognitive performance, manual dexterity, and perceptual measures were recorded pre- and post-surgery, while physiological parameters were recorded throughout surgery. HOT conditions did not significantly affect manual dexterity or cognitive function (p > .05), however HOT resulted in heat strain (increased heart-rate, core temperature, and fluid loss: p < .05), and increased subjective workload, discomfort, perceived exertion, and fatigue compared to CON conditions (p < .05). Cognitive function and manual dexterity were maintained in hot conditions, suggesting that operating in approximately 31°C heat is a safe approach for patient treatment. However, job burnout, which is positively correlated with perceived workload, and the impact of cumulative fatigue on the mental health of surgery staff, must be considered in the context of supporting an effective health workforce.

Examining the patient profile and variance of management and in-hospital outcomes for Australian adult burns patients.

BACKGROUND: Burn injuries are a common subtype of trauma. Variation in models of care impacts clinical measures of interest, but a nation-wide examination of these measures has not been undertaken. Using data from the Burns Registry of Australia and New Zealand (BRANZ), we explored variation between Australian adult burn services with respect to treatment and clinical measures of interest. METHODS: Data for admissions July 2016 to June 2020 were extracted. Clinical measures of interest included intensive care admission, skin grafting, in-hospital death, unplanned readmissions, and length of stay (LOS). Estimated probabilities, means, and corresponding 95% confidence intervals (CI) were calculated for each service. RESULTS: The BRANZ recorded 8365 admissions during the study period. Variation between specialist burn services in admissions, demographics, management, and clinical measures of interest were observed. This variation remained after accounting for covariates. Specifically, the adjusted proportion (95% CI) of in-hospital mortality ranged from 0.15% (0.10-0.21%) to 1.22% (0.9-1.5%). The adjusted mean LOS ranged from 3.8 (3.3-4.3) to 8.2 (6.7-9.7) days. CONCLUSIONS: A decade after its launch, BRANZ data displays variation between Australian specialist burn services. We suspect differences in models of care between services contributes to this variation. Ongoing research has begun to explore reasons underlying how this variation influences clinical measures of interest. Further engagement with services about models of care will enhance understanding of this variation and develop evidence-based guidelines for burn care in Australia.

Enhancing the accuracy of surgical wound excision following burns trauma via application of Rapid Evaporative IonisationMass Spectrometry (REIMS).

BACKGROUND: Surgical wound excision is a necessary procedure for burn patients that require the removal of eschar. The extent of excision is currently guided by clinical judgement, with excessinto healthy tissue potentially leading to excessive scar, or inadequate debridement increasing risk of infection. Thus, an objective real-time measure to facilitate accurate excision could support clinical judgement and improve this surgical procedure. This study was designed to investigate the potential use of Rapid evaporative ionisation mass spectrometry (REIMS) as a tool to support data-driven objective tissue excision. METHODS: Data were acquired using a multi-platform approach that consisted of both Rapid Evaporative Ionisation Mass Spectrometry (REIMS) performed on intact skin, and comprehensive liquid chromatography-mass spectrometry (LC-MS/MS) lipidomics performed on homogenised skin tissue extracts. Data were analysed using principal components analysis (PCA) and multivariate orthogonal projections to latent squares discriminant analysis (OPLS-DA) and logistic regression to determine the predictability of the models. RESULTS: PCA and OPLS-DA models of the REIMS and LC-MS/MS lipidomics data reported separation of excised and healthy tissue. Molecular fingerprints generated from REIMS analysis of healthy skin tissue revealed a high degree of heterogeneity, however, intra-individual variance was smaller than inter-individual variance. Both platforms indicated high levels of skin classification accuracy. In addition, OPLS-DA of the LC-MS/MS lipidomic data revealed significant differences in specific lipid classes between healthy control and excised skin samples; including lower free fatty acids (FFA), monoacylglycerols (MAG), lysophosphatidylglycerol (LPG) and lysophosphatidylethanolamines (LPE) in excised tissue and higher lactosylceramides (LCER) and cholesterol esters (CE) compared to healthy control tissue. CONCLUSIONS: Having established the heterogeneity in the biochemical composition of healthy skin using REIMS and LC-MS/MS, our data show that REIMS has the potential to distinguish between excied and healthy skin tissue samples. This pilot study suggests that REIMS may be an effective tool to support accurate tissue excision during burn surgery.

Delirium in hospitalised adults with acute burns - A systematic review.

INTRODUCTION: Delirium is a potentially modifiable, acutely altered mental state, commonly characterised as a hospital-acquired complication. Studies of adult inpatients with acute burns with and without delirium identify causative risks related to the injury or treatment and outcomes related to the patient and healthcare system. We compare patients with and without delirium, providing a high-level quantitative synthesis of delirium risks and outcomes to inform guidelines and future research. METHODS: A systematic review, meta-analysis and GRADE evaluation of risks and outcomes associated with delirium in adults with acute burns was conducted using PRISMA guidelines and PROSPERO protocol CRD42021283055. The Newcastle-Ottawa Scale was used to assess quality. RESULTS: Investigators reviewed ten studies. ASA score ≥ 3, Total Body Surface Area Percentage (TBSA)> 10%, surgery done, ICU admission, hospital and also Intensive Care Unit (ICU) lengths of stay all had statistically significant associations with delirium, with low-very low certainty on GRADE evaluation. Limitations were heterogeneous studies, review methodology and study bias. CONCLUSION: Delirium represents a significant risk to comorbid patients with burns that are hospitalised, receive ICU care, and surgery. Further research is indicated to precisely categorise delirium along the clinical journey to identify modifiable factors, prevention, and proactive therapy.

Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells.

Background: Recent evidence suggests that burn patients are at increased risk of hospital admission for infection, mental health conditions, cardiovascular disease and cancer for many years after discharge for the burn injury itself. Burn injury has also been shown to induce sustained immune system dysfunction. This change to immune function may contribute to the increased risk of chronic disease observed. However, the mechanisms that disrupt long-term immune function in response to burn trauma, and their link to long-term morbidity, remain unknown. In this study we investigated changes to immune function after burn injury using a murine model of non-severe injury. Methods: An established mouse model of non-severe burn injury (full thickness burn equivalent to 8% total body surface area) was used in combination with an orthotopic model of B16 melanoma to investigate the link between burns and cancer. Considering that CD8+ T cells are important drivers of effective tumour suppression in this model, we also investigated potential dysregulation of this immune population using mouse models of burn injury in combination with herpes simplex virus infection. Flow cytometry was used to detect and quantify cell populations of interest and changes in immune function. Results: We demonstrate that 4 weeks after a non-severe burn injury, mice were significantly more susceptible to tumour development than controls using an orthotopic model of B16 melanoma. In addition, our results reveal that CD8+ T cell expansion, differentiation and memory potential is significantly impaired at 1 month post-burn. Conclusions: Our data suggests that CD8+ T cell-mediated immunity may be dysfunctional for a sustained period after even non-severe burn injury. Further studies in patients to validate these findings may support clinical intervention to restore or protect immunity in patients after burn injury and reduce the increased risk of secondary morbidities observed.

Quantification of the negative impact of sedation and inotropic support on achieving early mobility in burn patients in ICU: A single center observational study.

INTRODUCTION: Early rehabilitation for burns survivors in the intensive care unit (ICU) is arguably more challenging than the general population. Early achievement of functional verticality milestones (FVMs) has the potential to ameliorate the detrimental effects of bed rest and immobility observed in ICU patients and reduce healthcare costs. However, the time to achieving FVMs after burn injury is influenced by factors such as sedation practices, cardiovascular stability, mechanical ventilation, acute skin reconstruction and length of stay (LOS) during the acute intensive care period. OBJECTIVES/AIMS: The aims of this study were to identify the association between early achievement of FVMs and factors influencing cessation of bedrest in adult patients with burns receiving ICU care, and to explore barriers to achievement of FVMs as recorded by clinicians. METHODS: A 5-year retrospective observational cohort study was conducted. The digital medical records were reviewed for each case to explore episodes of FVMs and patient factors which may contribute to persistent bed rest, such as use of infused sedative and/or inotropic medication, mechanical ventilation, burn surgery, total body surface area (TBSA), ICU length of stay and pre-ICU practices. Logistic regression was used to examine the association between FVM achievement and treatment and injury factors in ICU survivors. RESULTS: The total sample available for analysis included 64 patients. When sedation/agitation score was within recommended limits, odds of achieving FVMs was 21 times greater than periods outside those limits. When deep sedatives were infused, the odds of achieving FVMs decreased by 87% compared to periods when there was no infusion of these medications. In addition, the odds of achieving FVMs was reduced by 13% for each increase of 1 mL/h in the daily maximum noradrenaline dose. DISCUSSION AND CONCLUSION: Maintaining sedation and agitation scores within the optimal range, and minimising sedative infusion and inotropic support enhances the likelihood of early and frequent mobilization in patients with burns admitted to ICU. Additional barriers identified were mechanical ventilation, burns surgery, pre-ICU practices and ICU length of stay. The challenge for clinicians moving forward is to determine how these factors may be modified to increase early mobilization of burn patients in ICU.

The epigenetics of keloids.

Keloid scarring is a fibroproliferative disorder of the skin with unknown pathophysiology, characterised by fibrotic tissue that extends beyond the boundaries of the original wound. Therapeutic options are few and commonly ineffective, with keloids very commonly recurring even after surgery and adjunct treatments. Epigenetics, defined as alterations to the DNA not involving the base-pair sequence, is a key regulator of cell functions, and aberrant epigenetic modifications have been found to contribute to many pathologies. Multiple studies have examined many different epigenetic modifications in keloids, including DNA methylation, histone modification, microRNAs and long non-coding RNAs. These studies have established that epigenetic dysregulation exists in keloid scars, and successful future treatment of keloids may involve reverting these aberrant modifications back to those found in normal skin. Here we summarise the clinical and experimental studies available on the epigenetics of keloids, discuss the major open questions and future perspectives on the treatment of this disease.

An Experimental Simulation of Heat Effects on Cognition and Workload of Surgical Team Members.

OBJECTIVE: To isolate heat exposure as a cause of cognitive impairment and increased subjective workload in burns surgical teams. SUMMARY OF BACKGROUND DATA: Raising ambient temperature of the operating room can improve burns patient outcomes, but risks increased cognitive impairment and workload of surgical team members. Prior research indicates ambient heat exposure depletes physiological and cognitive resources, but these findings have not been studied in the context of burns surgical teams. METHODS: Seventeen surgical team members completed 2 surgery simulations of similar complexities in a hot and in a normothermic operating room. During each simulation, participants completed multiple cognitive tests to assess cognitive functioning and the SURG-TLX to self-assess workload. Order effects, core body temperature changes due to menstruation, and circadian rhythms were controlled for in the experimental design. Descriptive statistics, correlations, and mixed ANOVAs were performed to assess relationships between ambient heat exposure with cognitive functioning and perceived workload. RESULTS: Heat had a main effect on executive functioning and verbal reasoning. Duration of heat exposure (heat ∗ time) increased response times and negatively impacted executive functioning, spatial planning, and mental rotation. Perceived workload was higher in the hot condition. CONCLUSIONS: We provide causal evidence that over time, heat exposure impairs cognitive speed and accuracy, and increases subjective workload. We recommend building on this study to drive best-practices for acute burns surgery and design work to enable burns teams to maintain their cognitive stamina, lower their workload, and improve outcomes for patients and surgeons.

Effectiveness of negative pressure wound therapy in the prevention of surgical wound complications in the cesarean section at-risk population: a parallel group randomised multicentre trial-the CYGNUS protocol.

INTRODUCTION: Caesarean delivery is steadily becoming one of the more common surgical procedures in Australia with over 100 000 caesarean sections performed each year. Over the last 10 years in Australia, the caesarean section rate has increased from 28% in 2003 to 33% in 2013. On the international stage, the Australian caesarean delivery rates are higher than the average for the Organisation for Economic Co-operation and Development, Australia ranked as 8 out of 33 and is second to the USA. Postoperative surgical site infections (SSIs) and wound complications are the most common and costly event following a caesarean section. Globally, complication rates following a caesarean delivery vary from 4.9% to 9.8%. Complications such as infection and wound breakdown affect the postpartum mother's health and well-being, and contribute to healthcare costs for clinical management that often spans the acute, community and primary healthcare settings. Published level one studies using advanced wound dressings in the identified 'at-risk' population prior to surgery for prophylactic intervention are yet to be forthcoming. METHODS AND ANALYSIS: A parallel group randomised control trial of 448 patients will be conducted across two metropolitan hospitals in Perth, Western Australia, which provide obstetric and midwifery services. We will recruit pregnant women in the last trimester, prior to their admission into the healthcare facility for delivery of their child. We will use a computer-generated block sequence to randomise the 448 participants to either the interventional (negative pressure wound therapy (NPWT) dressing, n=224) or comparator arm (non-NPWT dressing, n=224). The primary outcome measure is the occurrence of surgical wound dehiscence (SSWD) or SSI. The Centres for Disease Control reporting definition of either superficial or deep infection at 30 days will be used as the outcome measure definition. SWD will be classified as per the World Union of Wound Healing Societies grading system (grade I-IV). We will assess recruitment rate, and adherence to intervention and follow-up. We will assess the potential effectiveness of NPWT in the prevention of postpartum surgical wound complications at three time points during the study; postoperative days 5, 14 and 30, after which the participant will be closed out of the trial. We will use statistical methods to determine efficacy, and risk stratification will be conducted to determine the SWD risk profile of the participant. Follow-up at day 30 will assess superficial and deep infection, and wound dehiscence (grade I-IV) and the core outcome data set for wound complications. This study will collect health-related quality of life (European Quality of Life 5-Dimensions 5-Level Scale), mortality and late complications such as further surgery with a cost analysis conducted. The primary analysis will be by intention-to-treat. This clinical trial protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and the Consolidated Standards of Reporting Trials guidelines. ETHICS AND DISSEMINATION: Ethics approval was obtained through St John of God Health Care (HREC1409), Western Australia Department of Health King Edward Memorial Hospital (HREC3111). Study findings will be published in peer-reviewed journals and presented at international conferences. We used the SPIRIT checklist when writing our study protocol. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ACTRN12618002006224p).

Secreted Factors from Keloid Keratinocytes Modulate Collagen Deposition by Fibroblasts from Normal and Fibrotic Tissue: A Pilot Study.

Interactions between keratinocytes and fibroblasts in the skin layers are crucial in normal tissue development, wound healing, and scarring. This study has investigated the role of keloid keratinocytes in regulating collagen production by primary fibroblasts in vitro. Keloid cells were obtained from removed patients' tissue whereas normal skin cells were discarded tissue obtained from elective surgery procedures. Fibroblasts and keratinocytes were isolated, cultured, and a transwell co-culture system were used to investigate the effect of keratinocytes on collagen production using a 'scar-in-a-jar' model. Keloid fibroblasts produced significantly more collagen than normal skin fibroblasts in monoculture at the RNA, secreted protein, and stable fibrillar protein level. When keloid keratinocytes were added to normal skin fibroblasts, expression of collagen was significantly upregulated in most samples, but when added to keloid fibroblasts, collagen I production was significantly reduced. Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. This suggests that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology.