Platelets after burn injury - hemostasis and beyond.

Burn injuries are common and often life-threatening trauma. With this trauma comes an interruption of normal hemostasis, with distinct impacts on platelets. Our interest in the relationships between burn injury and platelet function stems from two key perspectives: platelet function is a vital component of acute responses to injury, and furthermore the incidence of cardiovascular disease (CVD) is higher in burn survivors compared to the general population. This review explores the impact of burn injury on coagulation, platelet function, and the participation of platelets in immunopathology. Potential avenues of further research are explored, and consideration is given to what therapies may be appropriate for mediating post-burn thrombopathology.

Development of a value-based healthcare burns core set for adult burn care.

BACKGROUND: Value-based healthcare (VBHC) is increasingly implemented in healthcare worldwide. Transparent measurement of the outcomes most important and relevant to patients is essential in VBHC, which is supported by a core set of most important quality indicators and outcomes. Therefore, the aim of this study was to develop a VBHC-burns core set for adult burn patients. METHODS: A three-round modified national Delphi study, including 44 outcomes and 24 quality indicators, was conducted to reach consensus among Dutch patients, burn care professionals and researchers. Items were rated on a nine-point Likert scale and selected if ≥ 70% in each group considered an item 'important'. Subsequently, instruments quantifying selected outcomes were identified based on a literature review and were chosen in a consensus meeting using recommendations from the Dutch consensus-based standard set and the Dutch Centre of Expertise on Health Disparities. Time assessment points were chosen to reflect the burn care and patient recovery process. Finally, the initial core set was evaluated in practice, leading to the adapted VBHC-burns core set. RESULTS: Twenty-seven patients, 63 burn care professionals and 23 researchers participated. Ten outcomes and four quality indicators were selected in the Delphi study, including the outcomes pain, wound healing, physical activity, self-care, independence, return to work, depression, itching, scar flexibility and return to school. Quality indicators included shared decision-making (SDM), the number of patients receiving aftercare, determination of burn depth, and assessment of active range of motion. After evaluation of its use in clinical practice, the core set included all items except SDM, which are assessed by 9 patient-reported outcome instruments or measured in clinical care. Assessment time points included are at discharge, 2 weeks, 3 months, 12 months after discharge and annually afterwards. CONCLUSION: A VBHC-burns core set was developed, consisting of outcomes and quality indicators that are important to burn patients and burn care professionals. The VBHC-burns core set is now systemically monitored and analysed in Dutch burn care to improve care and patient relevant outcomes. As improving burn care and patient relevant outcomes is important worldwide, the developed VBHC-burns core set could be inspiring for other countries.

Coherency image analysis to quantify collagen architecture: implications in scar assessment.

An important histological difference between normal, uninjured dermis and scar tissue such as that found in keloid scars is the pattern (morphological architecture) in which the collagen is deposited and arranged. In the uninjured dermis, collagen bundle architecture appears randomly organized (or in a basket weave formation), whereas in pathological conditions such as keloid scar tissue, collagen bundles are often found in whorls or in a hypotrophic scar collagen is more densely packed in a parallel configuration. In the case of skin, a scar disables the dermis, leaving it weaker, stiff and with a loss of optimal functionality. The absence of objective and quantifiable assessments of collagen orientation is a major bottleneck in monitoring progression of scar therapeutics. In this article, a novel quantitative approach for analyzing collagen orientation is reported. The methodology is demonstrated using collagen produced by cells in a model scar environment and examines collagen remodeling post-TGFß stimulation in vitro. The method is shown to be reliable and effective in identifying significant coherency differences in the collagen deposited by human keloid scar cells. The technique is also compared for analysing collagen architecture in rat sections of normal, scarred skin and tendon tissue. Results demonstrate that the proposed computational method provides a fast and robust way of analyzing collagen orientation in a manner surpassing existing methods. This study establishes this methodology as a preliminary means of monitoring in vitro and in tissue treatment modalities which are expected to alter collagen morphology.

The QuickDASH is an appropriate tool for measuring the quality of recovery after upper limb burn injury.

BACKGROUND: Upper limb (UL) burns commonly result in significant dysfunction. The measurement of disability is vital to assess recovery after burn injury. The QuickDASH questionnaire was developed to evaluate UL disorders. The aim of this study was to evaluate its validity, repeatability and responsiveness for burn patients. METHODS: In 2006, 85 patients with UL burns were recruited at Royal Perth Hospital. Each completed both QuickDASH and Burns Specific Health Scale-Brief (BSHS-B) at regular intervals after their burn. Further, 67 patients repeated the questionnaire 1 day after completing it at discharge. RESULTS: Validity-Criterion validity was demonstrated between QuickDASH and BSHS-B through good correlations (r(2)=-0.79 to -0.89). Construct validity was demonstrated using burn severity markers. QuickDASH scores significantly differed when grouped according to major burn, full thickness burn, surgery and need for hospital admission. Repeatability-QuickDASH showed excellent repeatability (ICC=0.93). Responsiveness-Effect size of QuickDASH was demonstrated to be greater than BSHS-B at all measurement points. CONCLUSIONS: This longitudinal study confirms the validity, repeatability and responsiveness of the QuickDASH outcome measure in patients with upper limb burns. It supports the use of the QuickDASH in this population to help assess change in functional level.

The use of cultured epithelial autograft in the treatment of major burn wounds: eleven years of clinical experience.

INTRODUCTION: In patients with burns involving over 50% total body surface area (TBSA), donor skin is limited. Tissue engineering, particularly cultured epithelial autograft (CEA), offers a potential solution to assist in expedient wound closure. MATERIALS AND METHODS: Prior to 1994, the application of CEA was restricted to confluent cell sheets. The introduction of an autologous cell suspension (CellSpray) in 1994 enabled cells to be delivered to the wound via aerosol onto debrided burn and donor skin graft wound areas. This retrospective clinical audit of major burn injured patients (n=84) describes the use of CEA in those with over 50%TBSA in Western Australia (WA) between 1992 and 2002. RESULTS: The initial introduction of CEA was as confluent sheets, as this evolved to the use of CEA in suspension there was a reduction in the required surgical intervention and total length of stay (TLOS) divided by %TBSA. DISCUSSION: With the audit covering an 11-year period, many facets of clinical burn care have evolved. The WA experience has demonstrated CEA has been positively integrated into clinical practice in association with traditional wound care techniques of skin grafting to augment wound healing.

The use of cultured epithelial autograft in the treatment of major burn injuries: a critical review of the literature.

INTRODUCTION: The need to achieve rapid wound closure in patients with massive burns and limited skin donor sites led to the investigation of in vitro cellular expansion of keratinocytes. The use of cultured epithelial autografts (CEA) was first reported in the treatment of major burns in 1981. Since that time, support for the use of CEA has varied, ranging from 'a useful agent' to having 'no demonstrable effect on the outcome of extensively burned patients'. METHODS: This critical review of the literature examines issues associated with the use of CEA and the introduction of the technology into clinical practice. The factors potentially limiting the use of cultured CEA are the time necessary to culture CEA sheets, the reliability of 'take', vulnerability of grafts on the newly healed surface, long-term durability and the cost implications of such treatment. The available literature was located and critically evaluated using the Australian National Health and Medical Research Council Guidelines. FINDINGS: In the identified literature, the level of evidence to support the use of CEA in major burn injures is limited and often restricted to case studies and case series with no Level 1 evidence currently available. CONCLUSION: The main question arising 'Does CEA have a role in the treatment of major burns?' has proven difficult to answer due to the wide variation in both the quality of study design and the findings. At best, the literature review has highlighted areas of concern that have hindered the successful use of CEA. Our review critically evaluates the use of CEA and explores the advances in techniques towards attempting to improve reliable clinical implementation of CEA. The need for higher level research into the use of CEA is emphasised by this review.

Alternate electrode placement for whole body and segmental bioimpedance spectroscopy.

Bioimpedance spectroscopy (BIS) is frequently used to monitor body fluid and body composition in healthy and clinical populations. BIS guidelines state that there should be no skin lesions at the site of electrodes, and if lesions are present, electrode positions should be changed. However, alternate electrode positions are yet to be reported. This study aimed to determine if ventral electrode placements were suitable alternatives for whole body and segmental BIS measurements. Three alternate electrode placements were assessed for whole body BIS using a combination of ventral hand and foot electrode placements. An alternate position was assessed for upper and lower body segmental BIS. The results demonstrated that for whole body BIS, if drive and sense electrodes on the hand are moved to ventral positions, but foot electrodes remain in standard positions, then whole body BIS variables were comparable to standard electrode positioning (percentage difference range = 0.01 to 1.65%, p = 0.211-0.937). The alternate electrode placement for upper limb segmental BIS, results in BIS variables that are comparable to that of the standard positioning (percentage difference range = 0.24-3.51%, p = 0.393-0.604). The alternate lower limb electrode position significantly altered all resistance and predicted BIS variables for whole body and lower limb segmental BIS (percentage difference range = 1.06-12.09%, p < 0.001). If wounds are present on the hands and/or wrist, then the alternate electrode position described in this study is valid, for whole body and upper limb segmental BIS.

Interpretation of the DermaLab Combo® pigmentation and vascularity measurements in burn scar assessment: an exploratory analysis.

BACKGROUND: The DermaLab Combo® measures pigmentation and vascularity of a burn scar more reliably than the modified Vancouver Scar Scale (mVSS). This study aims to examine how the DermaLab Combo® continuous measurements of pigmentation and vascularity of burns scars relate to the mVSS, a standard clinical scar assessment method; and secondly, to obtain evidence to support the concurrent validity of DermaLab Combo® measurements for pigmentation and vascularity. METHOD: Scar assessments were performed on an index burn scar of 100 subjects using two methods: the mVSS (two raters) and the DermaLab Combo® device (one rater). Using the DermaLab Combo®, measurements of pigmentation and vascularity for the index scar and an adjacent normal skin site were obtained. Indices were generated to represent the scar pigmentation (melanin index, MI%) and scar vascularity (erythema index, EI%) relative to the patient's matched normal skin. Exploratory univariate and bivariate analyses were conducted and the concordance of classification by mVSS score using DermaLab® cut-off values was assessed. RESULTS: For pigmentation, the results suggest a 80% classification concordance for the DermaLab Combo® MI% values into mVSS pigmentation categories (hypopigmentation, normal pigmentation and hyperpigmentation) using two predictors (MI% and EI%) and visually fitted discriminant axis cut-offs. Due to the high degree of overlap of EI% values between the vascularity categories, meaningful classification of EI% values using the mVSS was not possible. CONCLUSION: Quantifying percentage changes in melanin and erythema relative to matched normal skin improved understanding of the DermaLab Combo® pigmentation and vascularity measurements. The DermaLab Combo® pigmentation MI% values were able to be classified into pigmentation categories of the mVSS, and pigmentation classification concordance was further improved with consideration of the scar's DermaLab Combo® vascularity EI% values. The DermaLab Combo® is an objective tool; however, while the measurement provides continuous numerical data that may be useful for identifying change over time in clinical scar monitoring of pigmentation and vascularity, further work will be useful to understand the DermaLab Combo® measurements to optimise the interpretation of these data.

Towards more efficient burn care: Identifying factors associated with good quality of life post-burn.

BACKGROUND: As minor burn patients constitute the vast majority of a developed nation case-mix, streamlining care for this group can promote efficiency from a service-wide perspective. This study tested the hypothesis that a predictive nomogram model that estimates likelihood of good long-term quality of life (QoL) post-burn is a valid way to optimise patient selection and risk management when applying a streamlined model of care. METHOD: A sample of 224 burn patients managed by the Burn Service of Western Australia who provided both short and long-term outcomes was used to estimate the probability of achieving a good QoL defined as 150 out of a possible 160 points on the Burn Specific Health Scale-Brief (BSHS-B) at least six months from injury. A multivariate logistic regression analysis produced a predictive model provisioned as a nomogram for clinical application. A second, independent cohort of consecutive patients (n=106) was used to validate the predictive merit of the nomogram. RESULTS AND DISCUSSION: Male gender (p=0.02), conservative management (p=0.03), upper limb burn (p=0.04) and high BSHS-B score within one month of burn (p<0.001) were significant predictors of good outcome at six months and beyond. A Receiver Operating Curve (ROC) analysis demonstrated excellent (90%) accuracy overall. At 80% probability of good outcome, the false positive risk was 14%. The nomogram was validated by running a second ROC analysis of the model in an independent cohort. The analysis confirmed high (86%) overall accuracy of the model, the risk of false positive was reduced to 10% at a lower (70%) probability. This affirms the stability of the nomogram model in different patient groups over time. An investigation of the effect of missing data on sample selection determined that a greater proportion of younger patients with smaller TBSA burns were excluded due to loss to follow up. CONCLUSION: For clinicians managing comparable burn populations, the BSWA burns nomogram is an effective tool to assist the selection of patients to a streamlined care pathway with the aim of improving efficiency of service delivery.

The aggregation of early-onset melanoma in young Western Australian families.

BACKGROUND: Few studies have examined the familial aggregation of melanoma or its co-aggregation with other cancers using whole-population based designs. This study aimed to investigate aggregation patterns in young Western Australian families, using population-based linked health data to identify individuals born in Western Australia between 1974 and 2007, their known relatives, and all incident cancer diagnoses within the resulting 1,506,961 individuals. METHODS: Cox proportional hazards regression models were used to compare the risk of melanoma for first-degree relatives of melanoma cases to that for first-degree relatives of controls, with bootstrapping used to account for correlations within families. The risk of (i) developing melanoma based on the number of first-degree relatives with other cancers, and (ii) developing non-melanoma cancers based on the number of first-degree relatives diagnosed with melanoma was also investigated. RESULTS: First-degree relatives of melanoma cases had a significantly greater incidence of melanoma than first-degree relatives of individuals not affected with melanoma (Hazard Ratio (HR)=3.58, 95% bootstrap confidence interval (CI): 2.43-5.43). Sensitivity analyses produced a higher hazard ratio estimate when restricted to melanoma cases diagnosed before 40 years of age (HR=3.77, bootstrap 95% CI: 2.49-6.39) and a lower estimate when only later-onset cases (>40 years) were considered (HR=2.45, bootstrap 95% CI: 1.23-4.82). No significant evidence was found for co-aggregation between melanoma and any other cancers. CONCLUSIONS: Results indicated a strong familial basis of melanoma, with the higher than expected hazard ratio observed likely to reflect early-age at onset cases in this young cohort, supported by the results of the sensitivity analyses. Exploratory analyses suggested that the determinants of melanoma causing the observed aggregation within families may be independent of other malignancies, although these analyses were limited by the young age of the sample. Determining familial aggregation patterns will provide valuable knowledge regarding improved clinical risk prediction and the underlying biological mechanisms of melanoma and other cancers.

Systemic factors influencing the growth of cultured epithelial autograft.

This is a retrospective study of 23 consecutive patients who had biopsies taken for cultured epidermal autograft between February 1993 and September 1994. Keratinocyte cultures were initiated on all of these biopsies. Of these 23 biopsies, it was noted that the cells obtained from three patients grew particularly slowly or failed to grow at all. Taking into account that the biopsy and culture conditions were standard for all patients, we investigated whether the patient's previous medical history may have had any effect on the ability of the cells to be cultured in vitro. Our results indicated that the keratinocyte cultures of patients with a significant past medical history, and particularly those with underlying pathology affecting their general physical condition, have a decreased growth rate. This raises the question that general patient condition can possibly influence the clinical use of the technique.

Implication of basement membrane development on the underlying scar in partial-thickness burn injury.

There is increasing evidence from the scientific literature that the developing epithelial basement membrane has the potential to influence the underlying dermis. The most rapidly dividing and active cell within the skin complex is the basal cell of the epidermis. The basal cell is well known to produce numerous protein factors which influence cellular growth and differentiation. The underlying dermal fibroblasts, by comparison, are relatively static. The concept that basal cells have an influence on the dermal and overall skin environment via the extracellular expression of proteins in the extracellular matrix, is gaining increased interest. A hypertrophic scar is a dermal phenomenon resulting from an imbalance in collagen production and maturation. Although the collagen is produced by the fibroblast, the extracellular matrix is an area where the epidermal cells have a potential influence. It is therefore the purpose of this paper to explore the idea that the cultured epithelial autograft may have an influence on the quality of scarring.

Direct measurement of cutaneous pressures generated by pressure garments.

Pressure garments are the mainstay of burn scar management despite limited scientific evidence. This study demonstrates a simple method of directly measuring the cutaneous pressures generated by a pressure garment. The results show pressure garments generate an increase in subdermal pressures in the range 9-90 mmHg depending on the anatomical site. Garments over soft sites generate pressures ranging from 9 to 33 mmHg. Over bony prominences the pressures range from 47 to 90 mmHg. This method is believed to be more representative of the pressures generated than the interpositional techniques that measure garment-skin interface pressure, as it avoids garment distortion, the interference effect of the measurement device (size, conformation, area) and directly measures subdermal pressures. The method should be useful for larger research projects on pressure therapy and also for clinical management of pressure garments in the treatment of hypertrophic scar.

Current difficulties and the possible future directions in scar assessment.

The quantitative assessment of the results of burn management is notoriously difficult. With the focus changing from survival to cosmetic and functional outcome, the scar assessments are increasingly important. The scar is a sum of the injury and all subsequent interventions on the way to healing. As such it is a complex structure, abnormal in its colour, depth, contour and pliability. To develop a quantitative system we believe it is vital to be able to track accurately an area of injury through time. Further, that physiological data acquired by a number of measurement tools be fused accurately to the morphologically correct information.

The treatment of hypopigmented lesions with cultured epithelial autograft.

Hypopigmentation may be a significant problem after burn injury. It is often difficult to predictably repair with conventional surgical techniques. It has been our experience that epidermal cells cultured from patients with dark skin produce pigment within the epidermal cell sheets, which indicates the presence of melanocytes. The presence of melanocytes and melanin in these cell sheets was demonstrated with the use of histochemical techniques. The results indicate that repigmentation with cultured epithelial autograft is possible. We describe a novel technique of dermabrasion and a co-culture of epidermal cells and melanocytes.

Early use of pressure masks to avoid facial contracture during the pregrafting phase.

This article introduces the concept of early application of pressure therapy as a form of splinting in the pregrafting phase. It is based on the principles of (1) the use of pressure therapy to reduce contraction and hypertrophic scar formation and (2) the knowledge that most wound contraction occurs within the initial few weeks of healing. This idea has most application in facial burns, where wound contraction can be disfiguring and functionally disabling, and in situations where unavoidable delay in debridement and grafting may be present. The idea is illustrated with a case report.

Sprayed keratinocyte suspensions accelerate epidermal coverage in a porcine microwound model.

Keratinocyte suspensions can potentially treat a variety of epidermal defects, but the mechanism of action has not been fully determined. We developed a porcine model to study the effect of sprayed cell suspensions delivered on small wounds within a meshed autograft. Paired full-thickness surgically excised wounds were covered with a fully expanded 3:1 meshed split-thickness autograft. A keratinocyte cell suspension was sprayed onto half of the wounds at a seeding density of 2.8 x 10(3) cells/cm2; the remaining wounds were sprayed with cell culture medium alone. Histologic analysis at days 5 and 8 showed an increase in average epidermal thickness, confluence, keratin cysts, and blood vessels in the keratinocyte cell suspension group compared with the cell culture medium control group. Wounds sprayed with the cell suspension showed faster and better quality of epithelialization than wounds sprayed with cell culture medium alone.

Melanocyte repopulation in full-thickness wounds using a cell spray apparatus.

Melanocyte restoration is critical in reconstituting skin color. We developed a spotted (piebald) pig wound model to study methods of restoring melanocytes to the epidermis. Paired, full-thickness, porcine wounds were covered with nonpigmented, fully expanded, 3:1 meshed, split-thickness skin grafts and were sprayed with an epidermal cell suspension. The suspensions were highly pigmented skin (HPS) cell isolates for half of the wounds (n = 16) and nonpigmented skin (NPS) cell isolates for the remaining wounds (n = 16). Histologic sections showed 6.0 +/- 3.0 and 15 +/- 4.0 pigmented melanocytes per high-power field on days 8 and 20 in HPS-treated wounds and no pigmented melanocytes in NPS-treated wounds. Melanin pigment was dispersed in all layers of the epithelium for the HPS group on day 20 compared with a lack of melanin pigment observed in the NPS group. Cell spraying may provide a clinical method to restore color to skin; further work is needed to control the expression of melanin.

Sexuality, body image and relationships following burns: analysis of BSHS-B outcome measures.

BACKGROUND: The Burns Specific Health Scale - Brief (BSHS-B) was analyzed to investigate the longitudinal impact of burns on sexuality and body image. Four sub-domains of the BSHS-B domains were of particular interest: sexuality, body image, affect and relationships, and as such were investigated for correlation between all of the sub-scales of the BSHS-B. METHODS: A total of 1846 observations from 865 Western Australian burn patient BSHS-B questionnaires were analyzed. Descriptive statistical methods included dichotomous and ordinal scale variables and medians, as well at the range for continuous variables. Inferential statistical methods used longitudinal linear mixed-effects models and random effects models with the BSHS-B total and its sub-scales as dependent variables. RESULTS: The four BSHS-B domains of interest all showed no significant change over time, indicating that the psychological and psychosocial impact of burns does not significantly improve for burn survivors, regardless of good physical and functional recovery. CONCLUSIONS: Burn survivors experience sexuality, body image and relationship changes following a burn, which may affect their quality of life (QoL) over time. Rehabilitation services need to be aware of these issues and create rehabilitation programs that specifically and meaningfully address these issues for burn survivors.