Verapamil is Less Effective than Triamcinolone for Prevention of Keloid Scar Recurrence After Excision in a Randomized Controlled Trial.

A double-blind randomized controlled trial with a paired split-scar design compared verapamil, an L-type Ca2+ channel antagonist, and triamcinolone for prevention of keloid recurrence after excision. Ca2+ channel blocking activity of verapamil in keloid cells was explored. One keloid was excised per subject and each wound half randomized to receive intralesional injections of triamcinolone (10 mg/ml) or verapamil (2.5 mg/ml) at monthly intervals (4 doses). Interim analysis was performed after 14 subjects were completed. Survival analysis demonstrated significantly higher keloid recurrence with verapamil compared to triamcinolone 12 months post-surgery (log-rank test, p = 0.01) and higher overall risk of recurrence with verapamil (hazard ratio 8.44, 95% CI 1.62-44.05). The study was terminated early according to the stopping guideline (p < 0.05). Verapamil is safe but not as effective as triamcinolone in preventing keloid recurrence after excision. Further study is necessary to determine if clinical response to verapamil is linked to modulation of intracellular Ca2+.

Long-term mortality among older adults with burn injury: a population-based study in Australia.

OBJECTIVE: To assess if burn injury in older adults is associated with changes in long-term all-cause mortality and to estimate the increased risk of death attributable to burn injury. METHODS: We conducted a population-based matched longitudinal study - based on administrative data from Western Australia's hospital morbidity data system and death register. A cohort of 6014 individuals who were aged at least 45 years when hospitalized for a first burn injury in 1980-2012 was identified. A non-injury comparison cohort, randomly selected from Western Australia's electoral roll (n = 25 759), was matched to the patients. We used Kaplan-Meier plots and Cox proportional hazards regression to analyse the data and generated mortality rate ratios and attributable risk percentages. FINDINGS: For those hospitalized with burns, 180 (3%) died in hospital and 2498 (42%) died after discharge. Individuals with burn injury had a 1.4-fold greater mortality rate than those with no injury (95% confidence interval, CI: 1.3-1.5). In this cohort, the long-term mortality attributable to burn injury was 29%. Mortality risk was increased by both severe and minor burns, with adjusted mortality rate ratios of 1.3 (95% CI: 1.1-1.9) and 2.1 (95% CI: 1.9-2.3), respectively. CONCLUSION: Burn injury is associated with increased long-term mortality. In our study population, sole reliance on data on in-hospital deaths would lead to an underestimate of the true mortality burden associated with burn injury.

Preparedness and training in staff responding to a burns disaster.

Effective disaster response is preceded by effective disaster planning, and insufficient staff training has been identified as a problem in the preparation of hospitals for major incidents. Despite this, little is known about the exact levels of training doctors and nurses responding to a disaster receive. The authors conducted a six-question survey delivered to staff involved in the hospital response to a burns mass disaster in Western Australia. The occupation, and also the clinical area in which the respondent worked, influenced the level of training they received. Training in formal disaster courses and practical exercises in mock disaster situations needs to be ongoing for all staff members for correct implantation of disaster plans. Findings may be useful in informing current and future efforts to improve hospital preparedness.

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.

Motivating patients towards better recovery after burn: The development of a booklet to reframe perspectives.

INTRODUCTION: Posttraumatic growth after burn results from integrated changes in worldview. It incorporates acceptance, belief in the self, compassion, determination and planning, emotional management and family/friend support. METHOD: The booklet was developed in two phases. In the first phase burn survivors were invited to tell their stories pertaining to their burn recovery experiences. These stories were categorised into the above framework, and presented alongside supporting information from the burn clinical psychologist in an initial draft of the booklet. In the second phase of the study, a combination of one-to-one interviews and a focus group of burn survivors discussed, suggested improvements to the final booklet and evaluated for usefulness and acceptability. RESULTS: A booklet was developed with a blend of patient stories and professional advice to positively reframe, integrate changed perspectives and motivate patients towards better psychological recovery after burn. It was evaluated to be useful and acceptable to new burn patients. CONCLUSION: This booklet, designed to positively reframe perspectives for better psychosocial burn recovery, was developed with patients and evaluated by patients. It was found to be useful and acceptable to new burn patients.

Long-Term Laryngotracheal Complications After Inhalation Injury: A Scoping Review.

Long-term laryngotracheal complications (LTLC) after inhalation injury (II) are an under-recognized condition in patients with burns. The purpose of this study was to systematically review all available evidence on LTLC after II and identify gaps in knowledge to guide the direction of future research. A scoping review was performed to synthesize all available evidence on LTLC after II, as guided by the question, "What are the LTLC after II, in patients with or without a history of translaryngeal intubation and/or tracheostomy?". MEDLINE, Web of Science, Ovid Embase, Cochrane Library, and Google Scholar were searched for publications on this topic. Of the 3567 citations screened, a total of 153 full-text articles were assessed for eligibility and 49 were included in the scoping review. The overall level of evidence was low, with case reports constituting 46.7% of all included human studies. The lesions were most frequently in the trachea (36.9%), followed by the glottis (34.7%) and subglottis (19.0%). LTLC occur in 4.8 to 6.5% of patients after II and these complications are under-recognized in burns patients. The risk factors for LTLC include high-grade II, elevated initial inflammatory responses, prolonged translaryngeal intubation, and a history of tracheostomy. The goal of management is to restore airway patency, preserve voice quality, and restore normal diet and swallow function. There is limited high-level evidence on LTLC, particularly with regards to long-term functional morbidity in voice and swallow. Large, prospective studies are required to address this gap in knowledge.

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.

Burn injury has a systemic effect on reinnervation of skin and restoration of nociceptive function.

Burn injury can lead to abnormal sensory function at both the injury and at distant uninjured sites. Here, we used a mouse model to investigate return of nociceptive function and reinnervation of the skin at the wound and uninjured distant sites following a 3% total burn surface area full-thickness burn injury. We have previously shown that topical application of zinc-metallothionein-IIA (Zn(7) -MT-IIA) accelerates healing following burn injury, and here, we investigated the potential of Zn(7) -MT-IIA to enhance reinnervation and sensory recovery. In all burn-injured animals, there was a significant reduction in nociceptive responses (Semmes-Weinstein filaments) at locations near and distant to the wound up to 8 weeks following injury. Cutaneous nerve reinnervation (assessed using protein gene product 9.5 immunohistochemistry) of the wound center was slow in the epidermis but rapid in the dermis. In the dermis, nerves subsequently degenerated both at the wound center and in distant uninjured areas. In contrast, epidermal nerve densities in the distant uninjured areas returned to normal, uninjured levels. Zn(7) -MT-IIA did not influence return of nociceptive function nor reinnervation. We conclude that burn injury compromises nociceptive function and nerve regeneration both at the injury site and systemically; thus, therapies in addition to Zn(7) -MT-IIA should be explored to return normal sensory function.

A Methylome and Transcriptome Analysis of Normal Human Scar Cells Reveals a Role for FOXF2 in Scar Maintenance.

Scars are maintained for life and increase in size during periods of growth such as puberty. Epigenetic changes in fibroblasts after injury may underpin the maintenance and growth of scars. In this study, we combined methylome and transcriptome data from normotrophic mature scar and contralateral uninjured normal skin fibroblasts to identify potential regulators of scar maintenance. In total, 219 significantly differentially expressed and 1,199 significantly differentially methylated promoters were identified, of which there were 12 genes both significantly differentially methylated and expressed. Of these, the two transcription factors, FOXF2 and MKX, were selected for further analysis. Immunocytochemistry and qPCR suggested that FOXF2 but not MKX had elevated expression in scar fibroblasts. Using RNA sequencing, FOXF2 knockdown was shown to significantly reduce the expression of extracellular matrix‒related genes, whereas MKX did not appear to affect similar pathways. Finally, FOXF2 knockdown was also shown to significantly decrease collagen I production in scar and keloid fibroblasts. This study provides insights into the maintenance of normotrophic scar, suggesting that FOXF2 is an important regulator of this process. Targeting genes responsible for maintenance of scar phenotype may ameliorate scar appearance and improve patient outcomes in the future.

Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis.

Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases.

A quantitative analysis of the relationship between posttraumatic growth, depression and coping styles after burn.

INTRODUCTION: Posttraumatic growth (PTG) is "the subjective experience of positive psychological change reported by an individual as a result of the struggle with trauma" (Zoellner and Maercker, 2006 [1]). PTG after burn is similar to PTG after other types of trauma (Martin et al., 2016 [2]). The aim was to assess the relationship between coping styles, via the BriefCOPE (Carver et al., 1989 [9]), and posttraumatic growth via the Posttraumatic Growth Inventory (Cann et al., 2010 [4]), in an adult burn population. METHOD: 36 burn patients who required surgery for wound closure were recruited within 2 years of their burn. They completed the PTGI, DASS-D, and BriefCOPE, and again one month later. Regression analysis with backwards elimination assessed the relationships between coping styles, depression and posttraumatic growth. RESULTS: Of the 14 coping types identified in the BriefCOPE, three were associated with PTG after burn: positive reframing, religion and acceptance. Three coping strategies were associated with greater levels of depression: behavioural disengagement, venting and self-blame. CONCLUSION: Behavioural disengagement, venting and self-blame behaviours can be used as 'red flags' to trigger early screening for depression and to enable timely treatment of depression. To maximise posttraumatic growth interventions that promote positive reframing, use of religion, and acceptance are necessary.

Burn disasters--an audit of the literature.

All events that result in disasters are unique, and it is impossible to become fully prepared. However, through thorough planning and preparedness, it is possible to gain a better understanding of the typical injury patterns and problems that arise from a variety of hazards. Such events have the potential to claim many lives and overwhelm local medical resources. Burn disasters vary in scope of injury and procedures required, and are much more labor and resource intensive than non-burn disasters. This review of the literature should help determine whether, despite each event having its own unique features, there still are common problems disaster responders face in the prehospital and hospital phases, what recommendations were made from these disasters, and whether these recommendations have been implemented into practice and the current disaster planning processes. The objective of this review was to assess: (1) prehospital and hospital responses used during past burn disasters; (2) problems faced during those disaster responses; (3) recommendations made following those disasters; (4) whether these recommendations were integrated into practice; and (5) the key characteristics of burn disasters and how they differ from other disasters. This review is important to determine why, despite having disaster plans, things still go wrong.

An Australian study of long-term hospital admissions and costs comparing patients with unintentional burns and uninjured people.

BACKGROUND: The objective of this study was to describe and quantify the long-term hospital service use (HSU) after burn injury and associated costs in a population-based cohort of patients with unintentional burns and compare with uninjured people. METHODS: This retrospective population-based cohort study analysed de-identified linked health administrative data of all unintentional burns patients (n = 10,460) between 2000 and 2012 in Western Australia and a matched uninjured comparison cohort (n = 42,856). HSU after burn injury (annual admission counts and cumulative length of stay) was examined. HSU costs were based on the Australian Refined Diagnosis Related Groups (AR-DRGs) code on each record. Generalised linear models were used to examine and quantify associations between burn injury and long-term HSU and associated costs. RESULTS: There were 48,728 hospitalisations after burn occurring within the study period in the burn cohort; in the uninjured comparison cohort, there were 53,244 post-study index hospitalisations. Of those in the burn cohort, 63.9% (n = 6828) had a further hospitalisation after burn injury; this compared with 40.4% (n = 17,297) in the uninjured cohort. After adjustment for socio-demographic and pre-existing health conditions the burn cohort had 2.48 times the hospitalisation rate compared to the uninjured cohort (95% CI: 2.33-2.65). The cost of post-index hospitalisations in the burn cohort totalled to $AUS248.3 million vs $AUS240.8 million in the uninjured cohort. After adjustment, the burn cohort had hospital costs 2.77 times higher than the uninjured controls (95% CI: 2.58-2.98). CONCLUSIONS: After adjustment for covariates, burn patients experienced greater hospital use for a prolonged period after the initial injury compared with uninjured people. The mean cost per episode of care was generally higher for members of the burn cohort compared to the uninjured cohort indicating either more complicated admissions or admissions for more expensive conditions.

Retrospective cohort study of health service use for cardiovascular disease among adults with and without a record of injury hospital admission.

OBJECTIVE: To quantify postinjury cardiovascular-related health service use experienced by mid to older aged adults hospitalised for injury, compared with uninjured adults. Additionally, to explore the effect of beta-blocker medications on postinjury cardiovascular hospitalisations among injury patients, given the potential cardioprotective effects of beta blockers. DESIGN: A retrospective cohort study using linked administrative and survey data. PARTICIPANTS: Records of 35 026 injured and 60 823 uninjured matched adults aged over 45 from New South Wales, Australia, who completed the 45 and up survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Admission rates and cumulative lengths of stay for cardiovascular hospitalisations, and prescription rates for cardiovascular medications. Negative binomial and Cox proportional hazards regression modelling were used to generate incident rate ratios (IRRs) and HR. RESULTS: Compared with the uninjured, those with injury had a 19% higher adjusted rate of postinjury cardiovascular admissions (IRR 1.19, 95% CI 1.14 to 1.25), spent 40% longer in hospital for ardiovascular disease (IRR 1.40, 95% CI 1.26 to 1.57) and had slightly higher cardiovascular prescription rates (IRR 1.04, 95% CI 1.02 to 1.06), during study follow-up. Those in the injury cohort that used beta blockers both prior to and after injury (continuous) appeared to have reduced need for post-injury cardiovascular hospitalisation (IRR 1.09, 95% CI 1.17 to 1.42) compared with those commencing on beta blockers after injury (after 30 days: IRR 1.69, 95% CI 1.37 to 2.08). CONCLUSIONS: Apparent increased postinjury hospitalisation rates and prolonged length of stay related to cardiovascular disease suggest that injury patients may require clinical support for an extended period after injury. Additionally, injury patients who were on continuous beta blocker treatment appeared to have lower need for post-injury cardiovascular hospitalisations. However, the data do not allow us to draw clear conclusions and further clinical research is required.

Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars.

As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission.

A vaccine against rumen methanogens can alter the composition of archaeal populations.

The objectives of this study were to formulate a vaccine based upon the different species/strains of methanogens present in sheep intended to be immunized and to determine if a targeted vaccine could be used to decrease the methane output of the sheep. Two 16S rRNA gene libraries were used to survey the methanogenic archaea in sheep prior to vaccination, and methanogens representing five phylotypes were found to account for >52% of the different species/strains of methanogens detected. A vaccine based on a mixture of these five methanogens was then formulated, and 32 sheep were vaccinated on days 0, 28, and 103 with either a control or the anti-methanogen vaccine. Enzyme-linked immunosorbent assay analysis revealed that each vaccination with the anti-methanogen formulation resulted in higher specific immunoglobulin G titers in plasma, saliva, and rumen fluid. Methane output levels corrected for dry-matter intake for the control and treatment groups were not significantly different, and real-time PCR data also indicated that methanogen numbers were not significantly different for the two groups after the second vaccination. However, clone library data indicated that methanogen diversity was significantly greater in sheep receiving the anti-methanogen vaccine and that the vaccine may have altered the composition of the methanogen population. A correlation between 16S rRNA gene sequence relatedness and cross-reactivity for the methanogens (R(2) = 0.90) also exists, which suggests that a highly specific vaccine can be made to target specific strains of methanogens and that a more broad-spectrum approach is needed for success in the rumen. Our data also suggest that methanogens take longer than 4 weeks to adapt to dietary changes and call into question the validity of experimental results based upon a 2- to 4-week acclimatization period normally observed for bacteria.

Burn induced nervous system morbidity among burn and non-burn trauma patients compared with non-injured people.

OBJECTIVE: Burns cause acute damage to the peripheral nervous system with published reports identifying that neurological changes after injury remain for a prolonged period. To shed some light on potential mechanisms, we assessed injury etiology and patterns of nervous system morbidity after injury by comparing long-term hospital admissions data of burns patients and other non-burn trauma patients with uninjured people. METHODS: Linked hospital and death data of a burn patient cohort (n=30,997) in Western Australia during the period 1980-2012 were analysed along with two age and gender frequency matched comparison cohorts: non-burn trauma patients (n=28,647) and; non-injured people (n=123,399). The number of annual NS disease admissions and length of stay (LOS) were used as outcome measures. Multivariable negative binomial regression modelling was used to derive adjusted incidence rate ratios and 95% confidence intervals (IRR, 95% CI) and adjusted Cox regression models and hazard ratios (HR) were used to examine time to first nervous system admission after burn and incident admission rates. RESULTS: The most common peripheral nervous system condition identified in each cohort (burn, non-burn trauma, uninjured) were episodic and paroxysmal disorders followed by nerve root and plexus disorders and polyneuropathies/peripheral NS conditions. Significantly elevated admission rates for NS conditions (IRR, 95% CI) were found for the burn (2.20, 1.86-2.61) and non-burn trauma (1.85, 1.51-2.27), compared to uninjured. Peripheral nervous system admission rates after injury (IRR, 95% CI) were significantly higher regardless of age at time of injury for the burn (<15years: 1.97, 1.49-2.61; 15-45: 2.70, 2.016-3.55; ≥45year: 1.62, 1.33-1.97) and non-burn trauma cohorts (<15years: 1.91, 1.55-2.35; 15-45: 1.94, 1.51-2.49; ≥45year: 1.42, 1.18-1.72), when compared to the uninjured. Significantly higher rates of incident NS hospitalisations were found for the burn cohort vs. uninjured cohort for a period of 15-years after discharge (0-5 years: HR, 95% CI: 1.97, 1.75-2.22; 5-15 years; HR, 95% CI: 1.44, 1.28-1.63). The non-burn trauma cohort had significantly higher incident nervous system admissions for 10 years after discharge (0-30 days: HR, 95% CI: 4.75, 2.44-9.23; 30days to 1-year HR, 95% CI: 2.95, 2.34-3.74; 1-5 years; HR, 95% CI: 1.47, 1.26-1.70; 5-10 years; HR, 95% CI: 1.34, 1.13-1.58). CONCLUSIONS: Results suggest that injury patients are at increased risk of peripheral nervous system morbidity after discharge for a prolonged period of time. The time patterns associated with incident nervous system conditions suggest possible differences in underlying pathology and long-term patient care needs. Further research is needed to elucidate the underlying neuropathology.

Carbon dioxide laser treatment in burn-related scarring: A prospective randomised controlled trial.

AIM: To investigate the effect of ablative fractional CO2 laser (AFCO2L) on burns scar appearance and dermal architecture at 6 weeks and up to 3-years post-treatment. METHODS: Twenty adult patients with a burn-related scar were recruited. Inclusion criteria were a minimum scar area of 10 × 10 cm and Vancouver scar scale (VSS) score of >5 and ≥6 months since the time of injury. The region of scar was randomised to treatment/control zones. Treatment zones received 3 standardised laser treatments at 4- to 6-week intervals. All areas of scar received standard scar care. Outcome measures were recorded at baseline, 6-weeks post final treatment and up to 3 years post-treatment. Measures included blinded assessor VSS, Patient Scar Assessment Scale and histological tissue analysis. RESULTS: Nineteen and nine patients completed the short- and long-term studies, respectively. Clinical results revealed improvement in all scar areas over time. There was a statistically significant improvement in pain and itch in the treatment zone compared to the control zone at 6 weeks. Histological data revealed a significant increase in medium-sized collagen fibres at 6 weeks relative to the control site. Sub-group analysis according to scar age revealed greater histological improvement following laser treatment in immature scars relative to more mature scar. CONCLUSIONS: Results demonstrate that 3 treatments of AFCO2L significantly improve scar pain, itch and dermal architecture at 6 weeks post-treatment. Histological results suggest greater potential in treating immature scar. Further investigation into the timing of laser treatment could help assist treatment protocols.

A peptide inhibitor of c-Jun promotes wound healing in a mouse full-thickness burn model.

Significant damage to tissue surrounding burn injuries occurs after the removal of the thermal source. This damage is caused by a combination of both necrotic and apoptotic cell death in the zone of stasis. Preserving the zone of stasis can reduce the wound size and thereby improve wound healing. We tested whether a peptide previously identified to inhibit necrotic and apoptotic cell death in neurons through c-Jun inhibition could enhance wound healing. We first tested the effects of this peptide on a keratinocyte and fibroblast cell line in culture. The peptide promoted proliferation of keratinocytes but had no effect on fibroblast proliferation, while the peptide also inhibited ultraviolet-induced apoptosis of keratinocytes. We finally tested the peptide in vivo, using a mouse model of burn injury. Wounds that were treated with the peptide reepithelialized faster than controls, while cell death surrounding the wound site was markedly reduced 24 hours postinjury, suggesting that the prevention of apoptosis as well as the proliferative effects of this peptide contribute to the wound healing process. Our data implicate c-Jun in multiple processes during wound repair and demonstrate that treatment of burn injuries using inhibitors of c-Jun dimerization at the time of injury can promote wound healing.

Exogenous metallothionein-IIA promotes accelerated healing after a burn wound.

Severe injury to the epidermal barrier often results in scarring and life-long functional deficits, the outcome worsening with a number of factors including time taken to heal. We have investigated the potential of exogenous metallothionein IIA (Zn(7)-MT-IIA), a naturally occurring small cysteine-rich protein, to accelerate healing of burn wounds in a mouse model. Endogenous MT-I/II expression increased in basal keratinocytes concurrent with reepithelialization after a burn injury, indicating a role for MT-I/II in wound healing. In vitro assays of a human keratinocyte cell line indicated that, compared with saline controls, exogenous Zn(7)-MT-IIA significantly increased cell viability by up to 30% (p<0.05), decreased apoptosis by 13% (p<0.05) and promoted keratinocyte migration by up to 14% (p<0.05), all properties that may be desirable to promote rapid wound repair. Further in vitro assays using immortalized and primary fibroblasts indicated that Zn7-MT-IIA did not affect fibroblast motility or contraction (p>0.05). Topical administration of exogenous Zn(7)-MT-IIA (2 microg/mL) in vivo, immediately postburn accelerated healing, promoted faster reepithelialization (3 days: phosphate-buffered saline (PBS), 8.9+/-0.3 mm diameter vs. MT-I/II, 7.1+/-0.7 mm; 7 days: PBS 5.8+/-0.98 mm vs. MT-I/II, 3.6+/-1.0 mm, p<0.05) and reduced epidermal thickness (MT-I/II: 45+/-4 microm vs. PBS: 101+/-19 microm, p<0.05) compared with controls. Our data suggest that exogenous Zn(7)-MT-IIA may prove a valuable therapeutic for patients with burns and other skin injuries.