Short- and Long-term Outcomes of an Acellular Dermal Substitute versus Standard of Care in Burns and Reconstructions: A Phase I/II Intrapatient Randomized Controlled Trial.

OBJECTIVE: Dermal substitutes promote dermal regeneration and improve scar quality, but knowledge gaps remain regarding their efficacy and indications for use. The authors investigated the safety and short- and long-term efficacy of an acellular dermal substitute in patients with full-thickness wounds. METHODS: This intrapatient randomized controlled, open-label, phase I (safety) and phase II (efficacy) study compared treatment with Novomaix (Matricel GmbH), a dermal collagen/elastin-based scaffold, with split-thickness skin graft (STSG) only. The primary safety outcome was graft take at 5 to 7 days postsurgery. Postsurgical scar quality was assessed by measuring elasticity, color, and scores on the Patient and Observer Scar Assessment Scale at 3 months, 12 months, and 6 years. RESULTS: Twenty-five patients were included, of which 24 received treatment allocation. Graft take and wound healing were statistically significantly lower/delayed in the dermal matrix group compared with STSG alone (P < .004). Serious adverse events were delayed epithelialization in four dermal matrix and three STSG study areas. At 12 months postsurgery, skin extension (P = .034) and elasticity (P = .036) were better for the dermal matrix group compared with the group receiving STSG alone. Other scar quality parameters at 12 months and 6 years did not differ between treatment arms. CONCLUSIONS: The dermal substitute was a safe treatment modality for full-thickness wounds. Compared with STSG alone, time to wound healing was slightly increased. Nevertheless, scar quality at 12 months seemed somewhat improved in the wounds treated with the dermal substitute, indicative of enhanced scar maturation. In the long term, final scar quality was similar for both treatment modalities.

Hydrosurgical and conventional debridement of burns: randomized clinical trial.

BACKGROUND: Tangential excision of burned tissue followed by skin grafting is the cornerstone of burn surgery. Hydrosurgery has become popular for tangential excision, with the hypothesis that enhanced preservation of vital dermal tissue reduces scarring. The aim of this trial was to compare scar quality after hydrosurgical versus conventional debridement before split-skin grafting. METHODS: A double-blind randomized within-patient multicentre controlled trial was conducted in patients with burns that required split-skin grafting. One wound area was randomized to hydrosurgical debridement and the other to Weck knife debridement. The primary outcome was scar quality at 12 months, assessed with the observer part of the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes included complications, scar quality, colour, pliability, and histological dermal preservation. RESULTS: Some 137 patients were randomized. At 12 months, scars of the hydrosurgical debrided wounds had a lower POSAS observer total item score (mean 2.42 (95 per cent c.i. 2.26 to 2.59) versus 2.54 (95 per cent c.i. 2.36 to 2.72; P = 0.023)) and overall opinion score (mean 3.08 (95 per cent c.i. 2.88 to 3.28) versus 3.30 (95 per cent c.i. 3.09-3.51); P = 0.006). Patient-reported scar quality and pliability measurements were significantly better for the hydrosurgically debrided wounds. Complication rates did not differ between both treatments. Histologically, significantly more dermis was preserved with hydrosurgery (P < 0.001). CONCLUSION: One year after surgery scar quality and pliability was better for hydrosurgically debrided burns, probably owing to enhanced histological preservation of dermis. REGISTRATION NUMBER: Trial NL6085 (NTR6232 (http://www.trialregister.nl)).

The impact of incisional negative pressure wound therapy on scar quality and patient-reported outcomes: A within-patient-controlled, randomised trial.

Literature provides a moderate level of evidence for the beneficial effects of incisional negative pressure wound therapy (iNPWT) on scar quality. The purpose of this study was to establish if iNPWT results in improved scar outcomes in comparison to the standard of care. Therefore, a within-patient randomised controlled, open-label trial was conducted in transgender men undergoing gender-affirming mastectomies. A unilateral side was randomised to receive iNPWT (PICO™, Smith&Nephew) without suction drains and contrastingly the standard dressing (Steri-Strips™) with suction drain. Scar quality and questionnaires were bilaterally measured by means of objective assessments and patient-reported outcome measures (PROM) at 1, 3 and 12 months. Objective scar outcomes were scar pliability (Cutometer®), colouration (DSM-II) and scar width (3-D imaging). PROM outcomes were related to scars (POSAS and SCAR-Q) and body satisfaction (BODY-Q). From 85 included patients, 80 were included for analyses. No significant difference between treatments was seen in the quantitative outcomes of scar pliability, colour, and width. For qualitative scar outcomes, several significant findings for iNPWT were found for several subscales of the POSAS, SCAR-Q, and BODY-Q. These effects could not be substantiated with linear mixed-model regression, signifying no statically more favourable outcome for either treatment option. In conclusion, this study demonstrated that some PROM outcomes were more favourable for the iNPWT compared to standard treatment. In contrast, the quantitative outcomes showed no beneficial effects of iNPWT on scar outcomes. This suggests that iNPWT is of little benefit as a scar-improving therapy.

Scar formation from the perspective of complexity science: a new look at the biological system as a whole.

A burn wound is a complex systemic disease at multiple levels. Current knowledge of scar formation after burn injury has come from traditional biological and clinical studies. These are normally focused on just a small part of the entire process, which has limited our ability to sufficiently understand the underlying mechanisms and to predict systems behaviour. Scar formation after burn injury is a result of a complex biological system-wound healing. It is a part of a larger whole. In this self-organising system, many components form networks of interactions with each other. These networks of interactions are typically non-linear and change their states dynamically, responding to the environment and showing emergent long-term behaviour. How molecular and cellular data relate to clinical phenomena, especially regarding effective therapies of burn wounds to achieve minimal scarring, is difficult to unravel and comprehend. Complexity science can help bridge this gap by integrating small parts into a larger whole, such that relevant biological mechanisms and data are combined in a computational model to better understand the complexity of the entire biological system. A better understanding of the complex biological system of post-burn scar formation could bring research and treatment regimens to the next level. The aim of this review/position paper is to create more awareness of complexity in scar formation after burn injury by describing the basic principles of complexity science and its potential for burn care professionals.

Variation in platelet-rich plasma compositions used for wound healing indications.

At present, the role of platelet-rich plasma (PRP) in burn and wound management is undefined. We present some of the evidence for PRP in wound healing and other medical fields. Currently, the high variation in product composition, mode and timing of application prevent a clear definition of the position of PRP in wound healing. Perspectives on solving these issues are described.

A systematic review evaluating the influence of incisional Negative Pressure Wound Therapy on scarring.

Pathological scars can result in functional impairment, disfigurement, a psychological burden, itch, and even chronic pain. We conducted a systematic review to investigate the influence of incisional Negative Pressure Wound Therapy (iNPWT) on scarring. PubMed, EMBASE and CINAHL were searched for preclinical and clinical comparative studies that investigated the influence of iNPWT on scarring-related outcomes. Individual studies were assessed using the OHAT Risk of Bias Rating Tool for Human and Animal studies. The body of evidence was rated using OHAT methodology. Six preclinical studies and nine clinical studies (377 patients) were identified. Preclinical studies suggested that iNPWT reduced lateral tension on incisions, increased wound strength, and reduced scar width upon histological assessment. Two clinical studies reported improved patient-reported scar satisfaction as measured with the PSAS (1 year after surgery), POSAS, and a VAS (both 42, 90, and 180 days after surgery). Five clinical studies reported improved observer-reported scar satisfaction as measured with the VSS, SBSES, OSAS, MSS, VAS, and POSAS (7, 15, 30, 42, 90, 180, and 365 days after surgery). Three clinical studies did not detect significant differences at any point in time (POSAS, VAS, and NRS). Because of imprecision concerns, a moderate level of evidence was identified using OHAT methodology. Preclinical as well as clinical evidence indicates a beneficial influence of iNPWT on scarring. Moderate level evidence indicates that iNPWT decreases scar width and improves patient and observer-reported scar satisfaction.

Antibacterial and safety tests of a flexible cold atmospheric plasma device for the stimulation of wound healing.

Cold atmospheric plasma (CAP) devices generate an ionized gas with highly reactive species and electric fields at ambient air pressure and temperature. A flexible dielectric barrier discharge (DBD) was developed as an alternative antimicrobial treatment for chronic wounds. Treatment of Staphylococcus aureus in collagen-elastin matrices with CAP for 2 min resulted in a 4 log reduction. CAP treatment was less effective on S. aureus on dermal samples. CAP did not affect cellular activity or DNA integrity of human dermal samples when used for up to 2 min. Repeated daily CAP treatments for 2 min lowered cellular activity of dermal samples to 80% after 2 to 4 days, but this was not significant. Repeated treatment of ex vivo human burn wound models with CAP for 2 min did not affect re-epithelialization. Intact skin of 25 healthy volunteers was treated with CAP for 3× 20" to determine safety. Although participants reported moderate pain scores (numerical rating scale 3.3), all volunteers considered the procedure to be acceptable. Severe adverse events did not occur. CAP treatment resulted in a temporarily increased local skin temperature (≈3.4°C) and increased erythema. Lowering the plasma power resulted in a significantly lower erythema increase. Good log reduction (2.9) of bacterial load was reached in 14/15 volunteers artificially contaminated with Pseudomonas aeruginosa. This study demonstrated the in vitro and in vivo safety and efficacy in bacterial reduction of a flexible cold plasma device. Trial registration number NCT03007264, January 2, 2017 KEY POINTS: • CAP strongly reduced bacterial numbers both in vitro and in vivo. • Re-epithelialization of burn wound models was not affected by repeated CAP. • CAP treatment of intact skin was well tolerated in volunteers.

Course of scar quality of donor sites following split skin graft harvesting: Comparison between patients and observers.

There exists little to no data on the development of donor-site scars that remain after split skin graft harvesting. The objectives of this study were to (a) examine changes in characteristics of donor-site scar quality over time and (b) assess the agreement between patient-reported and observer-reported donor-site scar quality in a burn population. A prospective cohort study was conducted including patients who underwent split skin grafting for their burn injury. Patients and observers completed the Patient and Observer Scar Assessment Scale (POSAS) for the first harvested donor site at 3 and 12 months post-surgery. This study included 80 patients with a median age of 34 years. At 3 months post-surgery, the patients scored the POSAS items itch and color as most deviant from normal skin, both improved between 3 and 12 months (3.1 vs 1.5 and 5.0 vs 3.5, respectively [P < .001]). Other scar characteristics did not show significant change over time. The patients' overall opinion score improved from 3.9 to 3.2 (P < .001). Observers rated the items vascularization and pigmentation most severe, only vascularization improved significantly between both time points. Their overall opinion score decreased from 2.7 to 2.3 (P < .001). The inter-observer agreement between patients and observers was considered poor (ICC < 0.4) at both time points. Results of current study indicate that observers underestimate the impact of donor-site scars. This has to be kept in mind while guiding therapy and expectations. LEVEL OF EVIDENCE: II, prospective cohort study.

Safety and bactericidal efficacy of cold atmospheric plasma generated by a flexible surface Dielectric Barrier Discharge device against Pseudomonas aeruginosa in vitro and in vivo.

BACKGROUND: Cold atmospheric plasma (CAP), which is ionized gas produced at atmospheric pressure, could be a novel and potent antimicrobial therapy for the treatment of infected wounds. Previously we have shown that CAP generated with a flexible surface Dielectric Barrier Discharge (sDBD) is highly effective against bacteria in vitro and in ex vivo burn wound models. In the current paper, we determined the in vitro and in vivo safety and efficacy of CAP generated by this sDBD device. METHODS: The effect of CAP on DNA mutations of V79 fibroblasts was measured using a hypoxanthine-guanine-phosphoribosyltransferase (HPRT) assay. Furthermore, effects on cell proliferation, apoptosis and DNA damage in ex vivo burn wound models (BWMs) were assessed using immunohistochemistry. Next, 105 colony forming units (CFU) P. aeruginosa strain PAO1 were exposed to CAP in a 3D collagen-elastin matrix environment to determine the number of surviving bacteria in vitro. Finally, rat excision wounds were inoculated with 107 CFU PAO1 for 24 h. The wounds received a single CAP treatment, repeated treatments on 4 consecutive days with CAP, 100 µL of 1% (wt/wt) silver sulfadiazine or no treatment. Wound swabs and punch biopsies were taken to determine the number of surviving bacteria. RESULTS: Exposure of V79 fibroblasts to CAP did not increase the numbers of mutated colonies. Additionally, the number of proliferative, apoptotic and DNA damaged cells in the BWMs was comparable to that of the unexposed control. Exposure of PAO1 to CAP for 2 min resulted in the complete elimination of bacteria in vitro. Contrarily, CAP treatment for 6 min of rat wounds colonized with PAO1 did not effectively reduce the in vivo bacterial count. CONCLUSIONS: CAP treatment was safe but showed limited efficacy against PAO1 in our rat wound infection model.

Topical treatment for facial burns.

BACKGROUND: Burn injuries are an important health problem. They occur frequently in the head and neck region. The face is the area central to a person's identity that provides our most expressive means of communication. Topical interventions are currently the cornerstone of treatment of burns to the face. OBJECTIVES: To assess the effects of topical interventions on wound healing in people with facial burns of any depth. SEARCH METHODS: In December 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the effects of topical treatment for facial burns were eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment of the certainty of the evidence. MAIN RESULTS: In this first update, we included 12 RCTs, comprising 507 participants. Most trials included adults admitted to specialised burn centres after recent burn injuries. Topical agents included antimicrobial agents (silver sulphadiazine (SSD), Aquacel-Ag, cerium-sulphadiazine, gentamicin cream, mafenide acetate cream, bacitracin), non-antimicrobial agents (Moist Exposed Burn Ointment (MEBO), saline-soaked dressings, skin substitutes (including bioengineered skin substitute (TransCyte), allograft, and xenograft (porcine Xenoderm), and miscellaneous treatments (growth hormone therapy, recombinant human granulocyte-macrophage colony-stimulating factor hydrogel (rhGMCS)), enzymatic debridement, and cream with Helix Aspersa extract). Almost all the evidence included in this review was assessed as low or very low-certainty, often because of high risk of bias due to unclear randomisation procedures (i.e. sequence generation and allocation concealment); lack of blinding of participants, providers and sometimes outcome assessors; and imprecision resulting from few participants, low event rates or both, often in single studies. Topical antimicrobial agents versus topical non-antimicrobial agents There is moderate-certainty evidence that there is probably little or no difference between antimicrobial agents and non-antimicrobial agents (SSD and MEBO) in time to complete wound healing (hazard ratio (HR) 0.84 (95% confidence interval (CI) 0.78 to 1.85, 1 study, 39 participants). Topical antimicrobial agents may make little or no difference to the proportion of wounds completely healed compared with topical non-antimicrobial agents (comparison SSD and MEBO, risk ratio (RR) 0.94, 95% CI 0.68 to 1.29; 1 study, 39 participants; low-certainty evidence). We are uncertain whether there is a difference in wound infection (comparison topical antimicrobial agent (Aquacel-Ag) and MEBO; RR 0.38, 95% CI 0.12 to 1.21; 1 study, 40 participants; very low-certainty evidence). No trials reported change in wound surface area over time or partial wound healing. There is low-certainty evidence for the secondary outcomes scar quality and patient satisfaction. Two studies assessed pain but it was incompletely reported. Topical antimicrobial agents versus other topical antimicrobial agents It is uncertain whether topical antimicrobial agents make any difference in effects as the evidence is low to very low-certainty. For primary outcomes, there is low-certainty evidence for time to partial (i.e. greater than 90%) wound healing (comparison SSD versus cerium SSD: mean difference (MD) -7.10 days, 95% CI -16.43 to 2.23; 1 study, 142 participants). There is very low-certainty evidence regarding whether topical antimicrobial agents make a difference to wound infection (RR 0.73, 95% CI 0.46 to 1.17; 1 study, 15 participants). There is low to very low-certainty evidence for the proportion of facial burns requiring surgery, pain, scar quality, adverse effects and length of hospital stay. Skin substitutes versus topical antimicrobial agents There is low-certainty evidence that a skin substitute may slightly reduce time to partial (i.e. greater than 90%) wound healing, compared with a non-specified antibacterial agent (MD -6.00 days, 95% CI -8.69 to -3.31; 1 study, 34 participants). We are uncertain whether skin substitutes in general make any other difference in effects as the evidence is very low certainty. Outcomes included wound infection, pain, scar quality, adverse effects of treatment and length of hospital stay. Single studies showed contrasting low-certainty evidence. A bioengineered skin substitute may slightly reduce procedural pain (MD -4.00, 95% CI -5.05 to -2.95; 34 participants) and background pain (MD -2.00, 95% CI -3.05 to -0.95; 34 participants) compared with an unspecified antimicrobial agent. In contrast, a biological dressing (porcine Xenoderm) might slightly increase pain in superficial burns (MD 1.20, 95% CI 0.65 to 1.75; 15 participants (30 wounds)) as well as deep partial thickness burns (MD 3.00, 95% CI 2.34 to 3.66; 10 participants (20 wounds)), compared with antimicrobial agents (Physiotulle Ag (Coloplast)). Miscellaneous treatments versus miscellaneous treatments Single studies show low to very low-certainty effects of interventions. Low-certainty evidence shows that MEBO may slightly reduce time to complete wound healing compared with saline soaked dressing (MD -1.7 days, 95% CI -3.32 to -0.08; 40 participants). In addition, a cream containing Helix Aspersa may slightly increase the proportion of wounds completely healed at 14 days compared with MEBO (RR 4.77, 95% CI 1.87 to 12.15; 43 participants). We are uncertain whether any miscellaneous treatment in the included studies makes a difference in effects for the outcomes wound infection, scar quality, pain and patient satisfaction as the evidence is low to very low-certainty. AUTHORS' CONCLUSIONS: There is mainly low to very low-certainty evidence on the effects of any topical intervention on wound healing in people with facial burns. The number of RCTs in burn care is growing, but the body of evidence is still hampered due to an insufficient number of studies that follow appropriate evidence-based standards of conducting and reporting RCTs.

Improved and standardized method for assessing years lived with disability after burns and its application to estimate the non-fatal burden of disease of burn injuries in Australia, New Zealand and the Netherlands.

BACKGROUND: Burden of disease estimates are an important resource in public health. Currently, robust estimates are not available for the burn population. Our objectives are to adapt a refined methodology (INTEGRIS method) to burns and to apply this new INTEGRIS-burns method to estimate, and compare, the burden of disease of burn injuries in Australia, New Zealand and the Netherlands. METHODS: Existing European and Western-Australian health-related quality of life (HRQL) datasets were combined to derive disability weights for three homogenous burn injury groups based on percentage total body surface area (%TBSA) burned. Subsequently, incidence data from Australia, New Zealand, and the Netherlands from 2010 to 2017 were used to compute annual non-fatal burden of disease estimates for each of these three countries. Non-fatal burden of disease was measured by years lived with disability (YLD). RESULTS: The combined dataset included 7159 HRQL (EQ-5D-3 L) outcomes from 3401 patients. Disability weights ranged from 0.046 (subgroup < 5% TBSA burned > 24 months post-burn) to 0.497 (subgroup > 20% TBSA burned 0-1 months post-burn). In 2017 the non-fatal burden of disease of burns for the three countries (YLDs/100,000 inhabitants) was 281 for Australia, 279 for New Zealand and 133 for the Netherlands. CONCLUSIONS: This project established a method for more precise estimates of the YLDs of burns, as it is the only method adapted to the nature of burn injuries and their recovery. Compared to previous used methods, the INTEGRIS-burns method includes improved disability weights based on severity categorization of burn patients; a better substantiated proportion of patients with lifelong disability based; and, the application of burn specific recovery timeframes. Information derived from the adapted method can be used as input for health decision making at both the national and international level. Future studies should investigate whether the application is valid in low- and middle- income countries.

Allogeneic platelet-rich plasma (PRP) is superior to platelets or plasma alone in stimulating fibroblast proliferation and migration, angiogenesis, and chemotaxis as relevant processes for wound healing.

BACKGROUND: Platelet-rich plasma (PRP) is frequently used in the treatment of acute and chronic wounds. One of the major problems concerning the use of PRP is the absence of a well-characterized and standardized product, which leads to a high variety in study outcomes. Therefore, more studies on the composition and standardization of PRP in wound healing are needed. STUDY DESIGN AND METHODS: Platelet concentrates derived from healthy blood donors were made in plasma (PC-plasma) or platelet additive solution (PC-PAS). The effects of PC-plasma, PC-PAS, and plasma were then tested on proliferation, differentiation, and migration of fibroblasts, as well as sprouting of endothelial cells in fibrin gels and chemotaxis of white blood cells (WBCs). RESULTS: PC-plasma stimulates the migration and proliferation of human dermal fibroblasts more than plasma or platelets alone. Furthermore, platelet factors decrease the expression of α-smooth muscle actin in dermal fibroblast cultures. PC-plasma also stimulates sprouting of endothelial cells. Finally, PC-plasma also acts as a strong chemoattractant for WBCs. CONCLUSIONS: Allogeneic PC-plasma has beneficial effects on various aspects of wound healing in vitro and is superior to plasma or platelets alone. PC-plasma is an attractive candidate for further in vivo evaluation.

Patient-reported scar quality of adults after burn injuries: A five-year multicenter follow-up study.

Scar formation is an important adverse consequence of burns. How patients appraise their scar quality is often studied shortly after sustaining the injury, but information in the long-term is scarce. Our aim was, therefore, to evaluate long-term patient-reported quality of burn scars. Adults with a burn center admission of ≥1 day between August 2011 and September 2012 were invited to complete a questionnaire on long-term consequences of burns. We enriched this sample with patients with severe burns (>20% total body surface area [TBSA] burned or TBSA full thickness >5%) treated between January 2010 and March 2013. Self-reported scar quality was assessed with the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS). Patients completed this scale for their-in their opinion-most severe scar ≥5 years after burns. This study included 251 patients with a mean %TBSA burned of 10%. The vast majority (91.4%) reported at least minor differences with normal skin (POSAS item score ≥2) on one or more scar characteristics and 78.9% of the patients' overall opinion was that their scar deviated from normal skin. Patients with severe burns had higher POSAS scores, representing worse scar quality, than patients with mild/intermediate burns, except for color, which was high in both groups. A longer hospital stay predicted reduced scar quality (both mean POSAS and mean overall opinion of the scar) in multivariate analyses. In addition, female gender was also associated with a poorer overall opinion of the scar. In conclusion, this study provides new insights in long-term scar quality. Scars differed from normal skin in a large part of the burn population more than 5 years after burns, especially in those with severe burns. Female gender is associated with a poorer patients' overall opinion of their scar, which may be an indication of gender differences in perception of scar quality after burns.

SPS-neutralization in tissue samples for efficacy testing of antimicrobial peptides.

BACKGROUND: Accurate determination of the efficacy of antimicrobial agents requires neutralization of residual antimicrobial activity in the samples before microbiological assessment of the number of surviving bacteria. Sodium polyanethol sulfonate (SPS) is a known neutralizer for the antimicrobial activity of aminoglycosides and polymyxins. In this study, we evaluated the ability of SPS to neutralize residual antimicrobial activity of antimicrobial peptides [SAAP-148 and pexiganan; 1% (wt/v) in PBS], antibiotics [mupirocin (Bactroban) and fusidic acid (Fucidin) in ointments; 2% (wt/wt))] and disinfectants [2% (wt/wt) silver sulfadiazine cream (SSD) and 0.5% (v/v) chlorhexidine in 70% alcohol]. METHODS: Homogenates of human skin models that had been exposed to various antimicrobial agents for 1 h were pipetted on top of Methicillin-resistant Staphylococcus aureus (MRSA) on agar plates to determine whether the antimicrobial agents display residual activity. To determine the optimal concentration of SPS for neutralization, antimicrobial agents were mixed with PBS or increasing doses of SPS in PBS (0.05-1% wt/v) and then 105 colony forming units (CFU)/mL MRSA were added. After 30 min incubation, the number of viable bacteria was assessed. Next, the in vitro efficacy of SAAP-148 against various gram-positive and gram-negative bacteria was determined using PBS or 0.05% (wt/v) SPS immediately after 30 min incubation of the mixture. Additionally, ex vivo excision wound models were inoculated with 105 CFU MRSA for 1 h and exposed to SAAP-148, pexiganan, chlorhexidine or PBS for 1 h. Subsequently, samples were homogenized in PBS or 0.05% (wt/v) SPS and the number of viable bacteria was assessed. RESULTS: All tested antimicrobials displayed residual activity in tissue samples, resulting in a lower recovery of surviving bacteria on agar. SPS concentrations at ≥0.05% (wt/v) were able to neutralize the antimicrobial activity of SAAP-148, pexiganan and chlorhexidine, but not of SSD, Bactroban and Fucidin. Finally, SPS-neutralization in in vitro and ex vivo efficacy tests of SAAP-148, pexiganan and chlorhexidine against gram-positive and gram-negative bacteria resulted in significantly higher numbers of CFU compared to control samples without SPS-neutralization. CONCLUSIONS: SPS was successfully used to neutralize residual activity of SAAP-148, pexiganan and chlorhexidine and this prevented an overestimation of their efficacy.

Potential factors contributing to the poor antimicrobial efficacy of SAAP-148 in a rat wound infection model.

BACKGROUND: We investigated the efficacy of a synthetic antimicrobial peptide SAAP-148, which was shown to be effective against Methicillin-resistant Staphylococcus aureus (MRSA) on tape-stripped mice skin. Unexpectedly, SAAP-148 was not effective against MRSA in our pilot study using rats with excision wounds. Therefore, we investigated factors that might have contributed to the poor efficacy of SAAP-148. Subsequently, we optimised the protocol and assessed the efficacy of SAAP-148 in an adapted rat study. METHODS: We incubated 100 µL of SAAP-148 with 1 cm2 of a wound dressing for 1 h and determined the unabsorbed volume of peptide solution. Furthermore, 105 colony forming units (CFU)/mL MRSA were exposed to increasing dosages of SAAP-148 in 50% (v/v) human plasma, eschar- or skin extract or PBS. After 30 min incubation, the number of viable bacteria was determined. Next, ex vivo skin models were inoculated with MRSA for 1 h and exposed to SAAP-148. Finally, excision wounds on the back of rats were inoculated with 107 CFU MRSA overnight and treated with SAAP-148 for 4 h or 24 h. Subsequently, the number of viable bacteria was determined. RESULTS: Contrary to Cuticell, Parafilm and Tegaderm film, < 20% of peptide solution was recovered after incubation with gauze, Mepilex border and Opsite Post-op. Furthermore, in plasma, eschar- or skin extract > 20-fold higher dosages of SAAP-148 were required to achieve a 2-log reduction (LR) of MRSA versus SAAP-148 in PBS. Exposure of ex vivo models to SAAP-148 for 24 h resulted in a 4-fold lower LR than a 1 h or 4 h exposure period. Additionally, SAAP-148 caused a 1.3-fold lower mean LR at a load of 107 CFU compared to 105 CFU MRSA. Moreover, exposure of ex vivo excision wound models to SAAP-148 resulted in a 1.5-fold lower LR than for tape-stripped skin. Finally, SAAP-148 failed to reduce the bacterial counts in an adapted rat study. CONCLUSIONS: Several factors, such as absorption of SAAP-148 by wound dressings, components within wound exudates, re-colonisation during the exposure of SAAP-148, and a high bacterial load may contribute to the poor antimicrobial effect of SAAP-148 against MRSA in the rat model.

Activation, function and content of platelets in burn patients.

Burn injury has severe impact on the physiologic homeostasis. Platelet counts show a distinct course post-burn injury, with a nadir at day 3 followed by a thrombocytotic period with at peak at day 15, with a gradual return to normal. So far, it is unknown how the functionality and activational status of platelets develop post burn. In this study, we investigated if the function, activation and growth factor content of platelets of burn patients are affected and how this evolves in time. Six burn patients with over 15% total burned surface area were followed during 1 month. Standard hematological and coagulation analyses, thromboelastography (TEG), platelet-function analyzer-100 (PFA), several platelet activation parameters (CD62P-CD63, AnnexinV) and growth factors (TGFb1, VEGF, PDGF-AB/BB, EGF, TGFb2, FGF-2, PDGF-AA) analyses were performed. TEG analyses showed procoagulant changes. PFA-100 analyses were nearly all within normal range. CD62P and CD63 and Annexin-V indicated no clear activation of platelets. Growth factor content followed the same course as the platelet count, reflecting a constant growth factor per platelet ratio. Concluding, platelets post burn-injury appears to be functional and not overly activated. However, burn patients seem to remain in a procoagulant state for an extensive period, which may impact their pathology.

Preexpansion in Phalloplasty Patients: Is It Effective?

BACKGROUND: Phalloplasty is performed as genital gender-affirming surgery in transmasculine persons. It requires the harvest of sizeable autologous fasciocutaneous flaps, which is associated with donor-site morbidity and extensive scarring. Flap preexpansion has been used to facilitate wound closure and reduce scarring, but the efficacy of flap preexpansion in phalloplasty is unclear. The objective of this study was to assess the safety and effectiveness of preexpansion before phalloplasty. METHODS: Transmasculine persons who underwent phalloplasty between December 2006 and July 2014 at our institution were identified and invited to participate. A chart review was performed to obtain patient demographics and expander-related complications. Outcomes regarding the donor-site scar (Patient Observer Scar Assessment Scale, scar size, patient satisfaction) were measured at the outpatient clinic and compared between transmasculine persons treated with and transmasculine persons treated without preexpansion. RESULTS: Of 33 transmasculine persons who underwent phalloplasty, 17 underwent preexpansion. Phalloplasty techniques included the use of the radial forearm free flap, the anterolateral thigh flap, or a combination of both. In total, 34 tissue expanders were placed in the forearm (n = 12) and/or thigh (n = 22). Complications occurred in 18 (52.9%) of 34 tissue expanders and in 13 (76.5%) of 17 transmasculine persons. Seven reoperations were performed because of extrusion (n = 2), infection (n = 2), port failure (n = 2), or leakage (n = 1). Sixteen transmasculine persons visited our clinic for scar assessment (8 with and 8 without preexpansion). Primary closure was achieved in 4 (31%) of 13 expanded donor sites. Relative scar size was reduced when the wound could be closed primarily, but overall scar size, quality, and satisfaction did not differ significantly between groups. CONCLUSION: Donor-site expansion before phalloplasty was associated with high rates of expander-related complications and expander failure. Primary closure of the donor site was achieved in less than a third of the cases. Primary closure may potentially lead to smaller scars and greater satisfaction; however, we concluded that the potential advantages of preexpansion do not outweigh the high risk of complications and lack of success.

Detection of bacteria in burn wounds with a novel handheld autofluorescence wound imaging device: a pilot study.

OBJECTIVE: To compare the detection of bacteria in burn wounds between an bacterial fluorescence imaging device MolecuLight i:X, (Canada), and standard microbiological swabs. METHODS: Wounds were swabbed three times on one occasion; once with a standard swab, once with a high-fluorescent area swab, indicating a bacterial load >104 colony-forming units (CFU)/gram and a finally with a non-fluorescent (nF) area swab. Proportion agreement of the microbiological results was calculated and the accuracy of the device to detect relevant bacteria was assessed. RESULTS: A total of 14 patients with 20 wounds participated in the study. Median post-burn day at sampling time was 21 days. Of the 20 wounds, nine had a positive swab result in either of the three swabs, and 11 showed a highfluorescent area. Overall, positive and negative proportion agreement between standard swab and high-fluorescent swab sample results were 100%. Sensitivity, specificity, positive and negative predictive values of presence of high-fluorescence were 78%, 64%, 64%, and 78%, respectively. For Pseudomonas aeruginosa detection, these results were 100%, 70%, 44% and 100%, respectively. CONCLUSION: The diagnostic accuracy of the bacterial fluorescence imaging device to detect relevant bacteria in burn wounds was moderate and the reliability was equal to standard swabbing. Further research in larger sample sizes and on the relevance of minimal bacterial load and its potential to help with Pseudomonas aeruginosa management is needed.

Growth Factor Quantification of Platelet-Rich Plasma in Burn Patients Compared to Matched Healthy Volunteers.

Platelet rich plasma (PRP) is blood plasma with a platelet concentration above baseline. When activated, PRP releases growth factors involved in all stages of wound healing, potentially boosting the healing process. To expand our knowledge of the effectiveness of PRP, it is crucial to know the content and composition of PRP products. In this study, growth factor quantification measurements of PRP from burn patients and gender- and age-matched controls were performed. The PRP of burn patients showed levels of growth factors comparable to those of the PRP of healthy volunteers. Considerable intra-individual variation in growth factor content was found. However, a correlation was found between the platelet count of the PRP and most of the growth factors measured.

Sustainable effectiveness of single-treatment autologous fat grafting in adherent scars.

Following severe injury, not just the skin but also the subcutis may be destroyed. Consequently, the developing scar can become adherent to underlying structures. Reconstruction of the subcutis can be achieved by autologous fat grafting. Our aim was to evaluate the long-term scar outcome after single-treatment autologous fat grafting using a comprehensive scar evaluation protocol. Scar assessment was performed preoperatively in 40 patients. A 12-month follow-up assessment was performed in 36 patients, using the Cutometer, the Patient and Observer Scar Assessment Scale, and DSM II ColorMeter. The Cutometer parameters elasticity and maximal extension improved with 28 and 22% (both p < 0.001), respectively. Nearly all scores of the scar assessment scale decreased significantly, which corresponds to improved scar quality. In addition, the mean melanin score was ameliorated over time. Thus, we demonstrated the sustainable effectiveness of single-treatment autologous fat grafting in adherent scars, indicated by improved pliability, and overall scar quality.