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Management of procedural pain in burn care is challenging. Lidocaine-prilocaine cream 5%, eutectic mixture of local anesthetics (EMLA®), is a widely used, effective local anesthetic cream approved for normal intact skin, genital mucosa for superficial surgical procedures, and debridement of chronic leg ulcers. This comprehensive review aimed to determine the safety, analgesic efficacy, and effects of EMLA on burn pathophysiology to provide evidence-based clinical recommendations for introducing the topical anesthetic into burn care. The PRISMA guidelines were followed for conducting a systematic PubMed search to include all relevant preclinical and clinical studies, according to pre-specified eligibility criteria. Fifteen studies were included in a qualitative synthesis, among which nine were human and six were animal studies. To date, safety and pharmacokinetic data on EMLA application in burns have been limited. Nevertheless, human studies indicated that EMLA is safe and provides adequate procedural-pain relief in adults when applied to smaller burns. Caution should be exercised when using EMLA in younger children, as systemic toxicity, pertaining to prilocaine-induced methemoglobinemia, has been reported owing to overdosing (high doses applied over large burn areas). Furthermore, animal studies demonstrate the potential beneficial effects of EMLA on burn pathophysiology such as anti-inflammatory, decreased capillary permeability to plasma proteins and edema formation, and improved tissue perfusion, which are factors that may impact burn wound progression. Current data on EMLA use in the management of procedural pain in small burns are sparse but suggest that EMLA is safe and effective in adults. Further clinical pharmacokinetic studies are warranted, especially for application on larger burn areas. [ABSTRACT FROM AUTHOR]

Introduction Spider bites as the cause of necrotic skin and soft tissue lesions occur very rarely in Central and Northern Europe. Recluse spiders, distributed almost worldwide, are one of two genera of spiders with confirmed capability of causing necrotic lesions. In the facial region, the resulting defects represent a potential reconstructive challenge, especially in younger patients. Methods This case report has been reported in line with the SCARE criteria. Presentation of case We describe a case of a 19-year-old female with a suspected bite from a recluse spider sustained during a recreational trip to Guatemala. She was bitten on the right upper aspect of the nose, and within a week developed a large necrotic lesion extending to the medial canthus. Following her return to Denmark the defect was reconstructed with a trimmed full-thickness skin graft. An initially planned second-stage reconstructive procedure was cancelled, as the patient was satisfied with the primary result. Discussion Most aspects of the extended reconstructive ladder were evaluated before selecting the optimal reconstruction for this patient. In younger patients, reconstructive surgery requires special considerations, primarily due to age-related limitations combined with generally high expectations to the aesthetic outcome. Conclusion In the few reported cases of necrotic spider bites in the facial region, active reconstructive measures have resulted in the best outcomes. Tissue expansion of local or regional skin may have a potential role, but in certain patients, simple reconstructive solutions will provide an aesthetically satisfactory result without requiring extensive or multi-stage surgeries, as demonstrated in this case. [ABSTRACT FROM AUTHOR]

Summary Indoleamine 2,3-dioxygenase (IDO) has been described as a major mechanism of immunosuppression in tumors, though the mechanisms of this are poorly understood. Here, we find that expression of IDO by tumor cells results in aggressive tumor growth and resistance to T-cell-targeting immunotherapies. We demonstrate that IDO orchestrates local and systemic immunosuppressive effects through recruitment and activation of myeloid-derived suppressor cells (MDSCs), through a mechanism dependent on regulatory T cells (Tregs). Supporting these findings, we find that IDO expression in human melanoma tumors is strongly associated with MDSC infiltration. Treatment with a selective IDO inhibitor in vivo reversed tumor-associated immunosuppression by decreasing numbers of tumor-infiltrating MDSCs and Tregs and abolishing their suppressive function. These findings establish an important link between IDO and multiple immunosuppressive mechanisms active in the tumor microenvironment, providing a strong rationale for therapeutic targeting of IDO as one of the central regulators of immune suppression. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC)-therapy is increasingly being evaluated in clinical trials. Dermal delivery is not only time consuming but also unreliable, potentially hampering the therapeutic result. Therefore, qualification of cell delivery protocols is essential. This study evaluated a clinically relevant automated multi-needle injection method for cutaneous MSC-therapy, allowing the skin to be readily and timely treated, by assessing both the cellular health post-ejection and dermal delivery. Following dispensation through the injector (31 G needles: 9- or 5-pin) the cellular health and potency (perceived- and long-term (12 h) viability, recovery, metabolism, adherence, proliferation and IDO1-expression) of adipose-derived stem cells (10–20–50 ×106 cells/ml) were assessed in vitro in addition to dermal delivery of solution in human skin. No significant detrimental effect on the perceived cell viability, recovery, metabolism, adherence or IDO1-expression of either cell concentration was observed. However, the overall long-term viability and proliferation decreased significantly regardless of cell concentration, nonetheless marginally. An injection depth above 1.0 mm resulted in all needles piercing the skin with dermal delivery from up to 89% needles and minimal reflux to the skin surface, and the results were confirmed by ultrasound and histology. The automated injector is capable of delivering dermal cell-doses with an acceptable cell quality. • Qualification of cell delivery protocols is crucial to ensure reproducible therapies. • The study validates a clinically relevant injection method for cutaneous MSC-therapy. • The method reliably delivers dermal doses with an acceptable cell viability. • The method allows for the skin to be readily treated with MSC in a timely manner. [ABSTRACT FROM AUTHOR]

Aim: Mesenchymal stem cell (MSC) therapies are emerging as a promising strategy to promote tissue repair, and may extend their utility to burn care. This comprehensive review of the extant literature, evaluated all in vivo studies, to elucidate the potential protective and therapeutic effect of MSCs in acute thermal skin burns.Methods: PubMed was systematically searched, according to PRISMA guidelines, and all relevant preclinical and clinical studies were included according to pre-specified eligibility criteria.Results: Forty-two studies were included in a qualitative synthesis, of which three were human and 39 were animal studies. The preclinical studies showed that MSCs can significantly reduce inflammation, burn wound progression and accelerate healing rate of acute burns. The underlying mechanisms are complex and not fully understood but paracrine modulators, such as immunomodulatory, antioxidative and trophic factors, seem to play important roles. Allogeneic MSC therapy has proved feasible in humans, and could allow for prompt treatment of acute burns in a clinical setting.Conclusion: MSC therapy show positive results, regarding improved burn wound healing and immunologic response. However, most findings are based on small animal studies. Randomized clinical trials are warranted to investigate the regenerative effects in human burns before translating the findings into clinical practice. [ABSTRACT FROM AUTHOR]