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.

[Iatrogenic burns in neonates]. / Iatrogene brandwonden bij pasgeborenen.

BACKGROUND: Despite the availability of different medical tools to simplify blood withdrawal, an old-fashioned method is still frequently being used in neonatal infants: the use of warm elements such as a warm washcloth or a glove filled with warm water, wrapped around an extremity. Use of these warm elements may easily cause contact burns in neonates. Unfortunately, not seldom we see and treat neonates with these burn injuries. CASE DESCRIPTION: We present the case of a neonate, who was referred to our outpatient clinic with an iatrogenic contact burn. The patient received topical treatment and wound dressings for over a month time. Scars remained. CONCLUSION: We would like to raise awareness among care givers on this type of injuries. To prevent these iatrogenic burns injuries, we advise to use alternative methods to simplify blood withdrawal.

[Frostbite due to recreational nitrous oxide use]. / Bevriezingswonden door recreatief lachgasgebruik.

BACKGROUND: There is a new type of injury that is observed increasingly often: frostbite of the thighs that has occurred as result of holding a cylinder containing nitrous oxide in position between the legs during recreational use of said substance. Because skin symptoms are often mild in the first few days after the event, the severity of the injury is often not recognized. However, patients can suffer serious scarring from this type of injury. CASE DESCRIPTION: We present two cases involving young patients who were referred to the burns unit with lesions sustained through nitrous oxide use. Upon inspection we observed deep frostbite wounds, which necessitated operative treatment. The patients had to undergo multiple operations and remained under our care for management of their scars. CONCLUSION: It is important to recognize this injury and to consult one of the burns units to treat these patients in a timeline and appropriate manner.

Validity of thermography for measuring burn wound healing potential.

Accurate assessment of burn wound depth and the associated healing potential is vital in determining the need for surgical treatment in burns. Infrared thermography measures the temperature of the burn wound noninvasively, thereby providing indirect information on its blood flow. Previous research demonstrated that a small, low-priced, handheld thermal imager has an excellent reliability, but a moderate validity for measuring burn wound healing potential. A new and more sensitive version of this convenient device has become available. The aim of this study was to evaluate the validity of thermography for measuring burn wound healing potential, compared to Laser Doppler Imaging (LDI) as a reference standard. Thermal images and LDI scans were obtained from burn wounds between 2 and 5 days postburn. Temperature differences between burned and nonburned skin (ΔT) were calculated. To evaluate validity, ΔT values were compared to the healing potential categories assessed by LDI. Two receiver operating characteristic curves were created and two ΔT cutoff values were calculated to illustrate the ability to discriminate between burn wounds that heal in a time period of less than 14 days, between 14 and 21 days, and more than 21 days. Between June and October 2018, 43 burn wounds in 32 patients were measured. ΔT cutoff values of 0.6°C (sensitivity 68%, specificity 95%) and -2.3°C (sensitivity 30%, specificity 95%) were calculated to discriminate between burn wounds that heal in <14 and ≥14 days, and burn wound that heal in ≤21 and >21 days, respectively. This study shows a good validity of the feasible thermal imager for the assessment of burn wound healing potential. Therefore, we consider it a promising technique to be used for triage in local hospitals and general practices, and as a valuable addition to clinical evaluation in burn centers.

The Use of Integra in Extensive Full-Thickness Scalp Burn Involving the Skull in a Child.

Extensive full-thickness burn injury of the scalp involving the skull is a challenge to reconstruct. Here, the authors report a case of a 6-year old girl who suffered extensive flame burn injury involving a scalp defect of 1,5% total body surface area. After necrosectomy, full table damage of the skull was observed with a partially exposed dura mater. Neurosurgical consultation was necessary to accomplish a vital wound bed. Subsequently, in the absence of enough adequate tissue available for flap surgery reconstruction, reconstruction was performed by using a bilayer Integra Dermal Regeneration Template (IDRT) resulting in a lasting and stable coverage of the defect. This is the first case-report describing application of IDRT on a full-thickness scalp and skull defect with exposed dura mater in a child. Our results are encouraging and demonstrate that Integra can be used in a child to successfully cover exposed dura when no viable skull remains.

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.

Perforator-Based Interposition Flaps Perform Better Than Full-Thickness Grafts for the Release of Burn Scar Contractures: A Multicenter Randomized Controlled Trial.

BACKGROUND: Burn scar contractures remain a significant problem for the severely burned patient. Reconstructive surgery is often indicated to improve function and quality of life. Skin grafts (preferably full-thickness grafts) are frequently used to cover the defect that remains after scar release. Local flaps are also used for this purpose and provide healthy skin subcutaneous tissue. The vascularization and versatility of local flaps can be further improved by enclosing a perforator at the base of the flap. Until now, no randomized controlled trial has been performed to determine which technique has the best effectiveness in burn scar contracture releasing procedures. METHODS: A multicenter randomized controlled trial was performed to compare the effectiveness of perforator-based interposition flaps to full-thickness skin grafts for the treatment of burn scar contractures. The primary outcome parameter was change in the surface area of the flap or full-thickness skin graft. Secondary outcome parameters were width, elasticity, color, Patient and Observer Scar Assessment Scale score, and range of motion. Measurements were performed after 3 and 12 months. RESULTS: The mean surface area between flaps (n = 16) and full-thickness skin grafts (n = 14) differed statistically significantly at 3 months (123 percent versus 87 percent; p < 0.001) and 12 months (142 percent versus 92 percent; p < 0.001). In terms of the secondary outcome parameters (specifically, the Patient and Observer Scar Assessment Scale observer score and color), interposition flaps showed superior results compared with full-thickness skin grafts. CONCLUSION: Perforator-based interposition flaps result in a more effective scar contracture release than full-thickness skin grafts and should therefore be preferred over full-thickness skin grafts when possible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Transepidermal water loss measured with the Tewameter TM300 in burn scars.

Transepidermal water loss (TEWL) is a physiological characteristic to measure the efficiency of the skin barrier. The aim was to investigate the reliability of the Tewameter TM300 for the assessment of TEWL (g/m2/h) in burn scars. Also the relation between TEWL scar values and scar quality parameters was investigated. Three different study areas (scar, healthy adjacent and contralateral skin) were assessed in 55 adult patients. The intra- and inter-observer reliability were tested using the intra-class correlation coefficient (ICC) and the standard error of measurement (SEM). The inter-observer reliability for the three areas was excellent with ICC values between 0.85 and 0.94. SEM values were between 1.76 and 3.97g/m2/h. Bland-Altman plots showed relatively wide LoA values for scar and healthy skin. Mean TEWL scar values were significantly higher than healthy skin (p<0.001). Significant correlations were found between TEWL hypertrophic scar values and erythema (r=0.60, p=0.001) and a negative correlation for weeks after burn (r=-0.61, p=0.001). TEWL values were significantly different between 3 and 6 months and 3 and 12 months old scars (respectively p=0.021 and p=0.002). To evaluate the skin barrier function over time as a measure for scar maturation, Tewameter TM300 measurements have to be performed according to strict and standardized protocols.

The application of platelet-rich plasma in the treatment of deep dermal burns: A randomized, double-blind, intra-patient controlled study.

Platelet-rich plasma (PRP) is a fraction of blood with a platelet concentration above baseline. When platelets get activated, growth factors involved in wound healing are released. The application of PRP has shown good results in wound care, however, up to date no substantial research has been performed on the effect of PRP in burn treatment. This randomized double blind intra-patient controlled study investigates the effect of autologous PRP on wound healing in burns that require surgery with a meshed split skin graft (SSG). Fifty-two patients with various areas of deep dermal to full thickness burns, receiving surgery with a SSG were included after informed consent. Comparable study areas A and B (intra-patient) were appointed, randomized and either treated with a SSG and PRP or with a SSG alone. At day 5 to 7 postoperative, the epithelialization and graft take rate were assessed. Three, six, and twelve months postoperative, follow-up measurements were performed in the form of POSAS-questionnaires, DermoSpectroMeter, and Cutometer measurements. There was no statistically significant difference between the mean take rate nor the mean epithelialization rate at day 5-7 between the PRP-treated and control areas. However, PRP-treated wound areas showed more often better or equal epithelialization and take rates at day 5-7 than the standard treated areas. Minor effects were also seen in the reoperated and early operated subgroups. At 3, 6, and 12 months postoperative, POSAS scores from the patients and the observers, Dermaspectro-, and Cutometer measurements did not depict a significant difference between the PRP and standard treated areas. Concluding, the addition of PRP in the treatment of burn wounds did not result in improved graft take and epithelialization, nor could we demonstrate better scar quality. There was, however, a considerable variation in our clinical population.

Outcome of Burns Treated With Autologous Cultured Proliferating Epidermal Cells: A Prospective Randomized Multicenter Intrapatient Comparative Trial.

Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative, since this may enhance wound closure and improve scar quality. A prospective, multicenter randomized clinical trial was performed in 40 adult patients with acute full thickness burns. On two comparable wound areas, conventional treatment with SSGs was compared to an experimental treatment consisting of SSGs in combination with cultured autologous epidermal cells (ECs) seeded in a collagen carrier. The primary outcome measure was wound closure after 5-7 days. Secondary outcomes were safety aspects and scar quality measured by graft take, scar score (POSAS), skin colorimeter (DermaSpectrometer) and elasticity (Cutometer). Wound epithelialization after 5-7 days was significantly better for the experimental treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon), whereas the take rates of the grafts were similar. No related adverse events were recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The POSAS of the observer after 3 and 12 months and of the patient after 12 months were significantly better for the experimental area. Improvements between 12% and 23% (p ≤ 0.010, Wilcoxon) were detected for redness, pigmentation, thickness, relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12 months were closer to normal skin for the experimental treatment than for conventional treatment (p ≤ 0.025 paired samples t-test). Skin elasticity showed significantly higher elasticity (p = 0.030) in the experimental area at 3 months follow-up. We showed a safe application and significant improvements of wound healing and scar quality in burn patients after treatment with ECs versus SSGs only. The relevance of cultured autologous cells in treatment of extensive burns is supported by our current findings.

Progress towards cell-based burn wound treatments.

Cell therapy as part of the concept of regenerative medicine represents an upcoming platform technology. Although cultured epidermal cells have been used in burn treatment for decades, new developments have renewed the interest in this type of treatment. Whereas early results were hampered by long culture times in order to produce confluent sheets of keratinocytes, undifferentiated proliferating cells can nowadays be applied on burns with different application techniques. The application of cells on carriers has improved early as well as long-term results in experimental settings. The results of several commercially available epidermal substitutes for burn wound treatment are reviewed in this article. These data clearly demonstrate a lack of randomized comparative trials and application of measurable outcome parameters. Experimental research in culture systems and animal models has demonstrated new developments and proof of concepts of further improvements in epidermal coverage. These include combinations of epidermal cells and mesenchymal stem cells, and the guidance of both material and cell interactions towards regeneration of skin appendages as well as vascular and nerve structures.