Mucorales-disseminated infection in burn wound.

A previously fit and well man in his 50s was rescued from a burning apartment with Glasgow Coma Scale 3 and admitted to the burn intensive care unit with 18% mixed dermal and full thickness burns and inhalation injury. He received standardised acute burn treatment according to the Emergency Management of Severe Burn guidelines and was found to have acute kidney injury requiring dialysis and cerebral watershed infarcts. The burns were deep especially on the left leg that was deemed unsalvageable and on day 8, he underwent a mid-femoral amputation.A wound swab on day 8 grew mould and with progression of skin necrosis, Mucorales infection was clinically suspected. Microbiological assessment of the swab confirmed Mucorales infection-an invasive fungus with the ability to invade blood vessels leading to vessel thrombosis and tissue necrosis and associated with high mortality. Recommended radical debridement with free cutaneous margins was not possible due to the widespread disease, and the patient was treated conservatively with antifungal therapy and survived.

High Self-Reported Satisfaction After Top Surgery in Gender-Affirming Surgery: A Single-Center Study.

Purpose: Top surgery, or masculinization of the chest, is often the first and sometimes only procedure in gender-affirming surgery for transgender- and gender-diverse persons assigned female at birth. In recent years, there has been improved access to care for transgender individuals and increased demand for top surgery. Our aim was to investigate the degree of satisfaction with the postoperative outcome after top surgery in transgender men. Methods: Ninety transgender men who underwent top surgery between September 1, 2013 and August 31, 2018 were included. Patients were surveyed from 5 to 62 months after surgery. Participants' files were evaluated for complications, and 84 (response rate 93.3%) participants answered a questionnaire evaluating patient satisfaction postoperatively. Results: Patients were either satisfied or partially satisfied with the overall experience of undergoing surgery and the postoperative result in 90.5% of responses. Patients were very satisfied with their clothed appearance in 89.3% of responses, whereas only 44.1% were very satisfied with their nonclothed appearance and 46.4% partially satisfied. Patients were also very satisfied with postoperative scars in 47.6% of responses and nipple reconstruction in 48.8%. Only two patients expressed their regret. Conclusion: Satisfaction outcomes after top surgery are generally positive, especially in respect of clothed appearance, self-confidence, and self-acceptance.

Efficacy of mesenchymal stem cell-delivery using perpendicular multi-needle injections to the skin: Evaluation of post-ejection cellular health and dermal delivery.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The automated injector is capable of delivering dermal cell-doses with an acceptable cell quality.

[Corrosions and frostbites].

Thermal burns are by far the most frequent and account for approx. 90% of all burns, while frostbites, chemical and electrical burns (CB) cover the remaining approx. 10%. This review gives an overview of the treatment of corrosions and frostbites. CB and frostbites are relatively rare and prompt initiation of proper treatment is essential for both. CB should be diluted as soon as possible, preferably with a neutralizing solution. Treatment of systemic hypothermia comes before management of peripheral frostbite. Frostbites involve thawing in warm water, followed by vasodilation, thrombolysis and amputation if indicated.

Low Risk of Persistent Pain, Sensory Disturbances, and Complications Following Mastectomy After Gender-Affirming Surgery.

Purpose: In recent years, there has been a significant increase in referrals for gender-affirming surgery to departments of plastic surgery in Denmark. There is currently no literature on postsurgical pain in trans men after mastectomy. We aimed at investigating the prevalence and severity of postsurgical persistent pain, sensory disturbances, and complications in trans men after mastectomy. Methods: The 90 trans men who underwent bilateral mastectomy between September 1, 2013 and August 31, 2018 were included. Patients' files were evaluated for complications, and 84 (response rate 93.3%) patients answered a questionnaire (validated for women undergoing oncologic mastectomy) regarding persistent pain and sensory disturbances. Results: Twenty-three patients (27.4%) reported either unilateral or bilateral persistent pain after mastectomy. Of these, 14 (60.9%) patients categorized the pain as mild. However, 77 (95.2%) of the patients did not use analgesics and nonopioid pain medication was sufficient for the remainder. Sensory disturbances were found in 44 (47.5%) of the patients, and 4 (4.8%) patients reported clear signs of neuropathic pain. Seven (7.8%) patients developed hematomas, and areola necrosis was seen in four (4.4%) patients. Due to infection, seven (7.8%) patients received antibiotics. Conclusion: Mastectomy as a part of gender-affirming surgery is a safe procedure with a few, nonsevere, complications. Although a quarter of the patients experienced persistent pain, the majority of that pain is mild, intermittent and can be treated with nonopioid pain medication.

Mesenchymal stem cell therapy of acute thermal burns: A systematic review of the effect on inflammation and wound healing.

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.

[Keraunoparalysis after lightning injury with transient ischaemia and paralysis of an extremity].

Keraunoparalysis is a transient paralysis of the extremities, which results from close contact with lightning. In this case report, a 58-year-old man came in close contact with a bolt of lightning. His left foot was pulseless, pale, cold and with absence of capillary refill. His symptoms were initially interpreted as arterial occlusion, and therefore bypass surgery and even amputation were considered. However, his symptoms resolved within hours. Therefore, clinicians must consider keranoparalysis as a differential diagnosis in patients struck by lightning.

[New Nordic guidelines on management of burn injuries].

Denmark has recently entered a collaboration with other Nordic countries to ensure a common strategy in the management of burn mass casualties. The collaboration is based upon the guideline Emergency Management of Severe Burns originating from the Australian and New Zealand Burn Association. The desire to establish a common Nordic strategy has led to a number of changes in the national guidelines for the treatment of burn injuries. The new guidelines recently implemented at the national university hospital of Denmark, Rigshospitalet, are presented in this review.

[Sex reassignment surgery in Denmark].

This review summarises the knowledge of sex reassignment surgery in Denmark. Sex reassignment surgery aims at confirming a transgender person's gender identity and can consist of surgery on breasts, genitals, thyroid cartilage, vocal cords as well as facial and body contours. In Denmark, most procedures are performed at a highly specialised level after referral to Center for Gender Identity. Some choose to get procedures performed abroad. Depending on the surgical procedure additional surgery can be necessary, however, patient satisfaction is generally high. Surgery has been shown to increase patients' quality of life and decrease gender dysphoria.

Cell-Enriched Fat Grafting Improves Graft Retention in a Porcine Model: A Dose-Response Study of Adipose-Derived Stem Cells versus Stromal Vascular Fraction.

BACKGROUND: Cell-enrichment of fat grafts has produced encouraging results, but the optimal concentrations and types of added cells are unknown. The authors investigated the effects of enrichment with various concentrations of ex vivo-expanded adipose-derived stem/stromal cells and stromal vascular fraction on graft retention in a porcine model. METHODS: Adipose-derived stem/stromal cells were culture-expanded, and six fat grafts (30 ml) were prepared for each minipig (n = 13). The authors investigated grafts enriched with 2.5 × 10 to 20 × 10 adipose-derived stem cells/ml and stromal vascular fraction and nonenriched control grafts. Each pig served as its own control. Magnetic resonance imaging was performed immediately after grafting and 120 days postoperatively before the pigs were euthanized, and histologic samples were collected. RESULTS: The authors recorded an enhanced relative graft retention rate of 41 percent in a pool of all cell-enriched grafts compared to the nonenriched control (13.0 percent versus 9.2 percent; p = 0.0045). A comparison of all individual groups showed significantly higher graft retention in the 10 × 10-adipose-derived stem/stromal cells per milliliter group compared with the control group (p = 0.022). No significant differences were observed between the cell-enriched groups (p = 0.66). All fat grafts showed a significantly better resemblance to normal fat tissue in the periphery than in the center (p < 0.009), but no differences in overall graft morphology were observed between groups (p > 0.17). CONCLUSIONS: Cell-enriched fat grafting improved graft retention and was feasible in this porcine model. No significant differences in graft retention were observed among the various adipose-derived stem/stromal cell concentrations or between adipose-derived stem/stromal cell and stromal vascular fraction enrichment. Future studies using this model can help improve understanding of the role of adipose-derived stem/stromal cells in cell-enriched fat grafting.

[Treating scars with lipofilling].

Hypertrophic, keloidal and contracted scars can be cosmetically and functionally debilitating, and by patients this is often perceived as traumatising. Psychological and social impairments are common in these types of scars. Currently, autologous lipofilling, with or without enrichment with stem cells, is performed to improve scar quality. In this review, we evaluate the evidence on lipofilling as a treatment of scars. The literature mainly consists of studies of low-level evidence, i.e. they lack controls and randomisation. Nevertheless, all studies indicate, that lipofilling may improve the quality of scars.

FcγRIIIa-dependent IFN-γ release in whole blood assay is predictive of therapeutic IgG1 antibodies safety.

Immunomodulatory monoclonal IgG1 antibodies developed for cancer and autoimmune disease have an inherent risk of systemic release of pro-inflammatory cytokines. In vitro cytokine release assays are currently used to predict cytokine release syndrome (CRS) risk, but the validation of these preclinical tools suffers from the limited number of characterized CRS-inducing IgG1 antibodies and the poor understanding of the mechanisms regulating cytokine release. Here, we incubated human whole blood from naïve healthy volunteers with four monoclonal IgG1 antibodies with different proven or predicted capacity to elicit CRS in clinic and measured cytokine release using a multiplex assay. We found that, in contrast to anti-CD52 antibodies (Campath-1H homolog) that elicited high level of multiple inflammatory cytokines from human blood cells in vitro, other IgG1 antibodies with CRS-inducing potential consistently induced release of a single tested cytokine, interferon (IFN)-γ, with a smaller magnitude than Campath. IFN-γ expression was observed as early as 2-4 h after incubation, mediated by natural killer cells, and dependent upon tumor necrosis factor and FcγRIII. Importantly, the magnitude of the IFN-γ response elicited by IgG1 antibodies with CRS-inducing potential was determined by donor FcγRIIIa-V158F polymorphism. Overall, our results highlight the importance of FcγRIIIa-dependent IFN-γ release in preclinical cytokine release assay for the prediction of CRS risk associated with therapeutic IgG1 antibodies.

Targeting the TGFß pathway with galunisertib, a TGFßRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade.

BACKGROUND: TGFß signaling plays a pleotropic role in tumor biology, promoting tumor proliferation, invasion and metastasis, and escape from immune surveillance. Inhibiting TGFß's immune suppressive effects has become of particular interest as a way to increase the benefit of cancer immunotherapy. Here we utilized preclinical models to explore the impact of the clinical stage TGFß pathway inhibitor, galunisertib, on anti-tumor immunity at clinically relevant doses. RESULTS: In vitro treatment with galunisertib reversed TGFß and regulatory T cell mediated suppression of human T cell proliferation. In vivo treatment of mice with established 4T1-LP tumors resulted in strong dose-dependent anti-tumor activity with close to 100% inhibition of tumor growth and complete regressions upon cessation of treatment in 50% of animals. This effect was CD8+ T cell dependent, and led to increased T cell numbers in treated tumors. Mice with durable regressions rejected tumor rechallenge, demonstrating the establishment of immunological memory. Consequently, mice that rejected immunogenic 4T1-LP tumors were able to resist rechallenge with poorly immunogenic 4 T1 parental cells, suggesting the development of a secondary immune response via antigen spreading as a consequence of effective tumor targeting. Combination of galunisertib with PD-L1 blockade resulted in improved tumor growth inhibition and complete regressions in colon carcinoma models, demonstrating the potential synergy when cotargeting TGFß and PD-1/PD-L1 pathways. Combination therapy was associated with enhanced anti-tumor immune related gene expression profile that was accelerated compared to anti-PD-L1 monotherapy. CONCLUSIONS: Together these data highlight the ability of galunisertib to modulate T cell immunity and the therapeutic potential of combining galunisertib with current PD-1/L1 immunotherapy.

[Handling of hypermetabolism in major burn injuries].

Multitrauma, critical illness and major burn injuries give rise to a stress response with a consequential increase in resting energy expenditure. Especially for burn trauma patients, this stress response is severe and prolonged and may cause a reduced lean muscle mass, loss of peripheral fatty tissue, hyperglycaemia and stress-induced diabetes. This review provides an overview of current strategies to attenuate the hypermetabolic stress response in order to improve the clinical outcome for these patients.

Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-ß receptor type I inhibitor.

Transforming growth factor-ß (TGFß) is an important driver of tumor growth via intrinsic and extrinsic mechanisms, and is therefore an attractive target for developing cancer therapeutics. Using preclinical models, we characterized the anti-tumor activity of a small molecule inhibitor of TGFß receptor I (TGFßRI), galunisertib (LY2157299 monohydrate). Galunisertib demonstrated potent and selective inhibition of TGFßRI with corresponding inhibition of downstream signaling via inhibition of SMAD phosphorylation (pSMAD). Galunisertib also inhibited TGFß-induced pSMAD in vivo, which enabled a pharmacokinetic/pharmacodynamic profile in Calu6 and EMT6-LM2 tumors. Galunisertib demonstrated anti-tumor activity including inhibition of tumor cell migration and mesenchymal phenotype, reversal of TGFß-mediated immune-suppression, and tumor growth delay. A concentration-effect relationship was established with a dosing schedule to achieve the optimal level of target modulation. Finally, a rat model demonstrated a correlation between galunisertib-dependent inhibition of pSMAD in tumor tissues and in PBMCs, supporting the use of PBMCs for assessing pharmacodynamic effects. Galunisertib has been tested in several clinical studies with evidence of anti-tumor activity observed in subsets of patients. Here, we demonstrate that galunisertib inhibits a number of TGFß-dependent functions leading to anti-tumor activity. The enhanced understanding of galunisertib provides rationale for further informed clinical development of TGFß pathway inhibitors.

Assessment of burn size in obese adults; a literature review.

PURPOSE: Obesity causes changes in the total body surface area as well as the distribution of skin surfaces. In burn management, three methods are commonly used to determine the surface area burned: the patient's palm, the rule of nines, and the Lund-Browder chart. These methods rely on the distribution of skin surface, although none of these methods consider differences in body mass. This study investigates the relationship between body surfaces and body mass in the assessment of burn size to determine the validity of the conventional methods when applied to obese individuals. METHODS: The current literature was reviewed using relevant electronic databases. The initial search yielded 247 results. Relevant articles were then reviewed. A total of seven publications fulfilled the inclusion criteria. RESULTS: The palmar surface area ranged between 0.59%-1.22%, depending on BMI, gender, and ethnicity, compared to 1% according to conventional methods. The palmar surface area of obese individuals approximated 0.7% of the total body surface area in Caucasians. The surface areas comprised 5%-7.5% of the total body surface area for each arm, 15%-20% for each leg, and 40%-52% for the trunk in obese or morbidly obese individuals, compared to 9%, 18%, and 36%, respectively, for normal-weight adults. CONCLUSIONS: The commonly used methods for assessment of burns should be used with caution when applied to obese burn patients, and the clinical parameters observed even more systematically.

Reconstructive considerations following a necrotic spider bite on the face: A case report.

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.

Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity.

Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL). In the bilateral flank tumour models, intratumoral administration of NDV-ICOSL results in enhanced infiltration with activated T cells in both virus-injected and distant tumours, and leads to effective rejection of both tumours when used in combination with systemic CTLA-4 blockade. These findings highlight that intratumoral immunomodulation with an oncolytic virus expressing a rationally selected ligand can be an effective strategy to drive systemic efficacy of immune checkpoint blockade.

[Chemoprevention of photocarcinogenesis using antioxidants].

The skin is constantly exposed to reactive oxygen species (ROS) from both endogenous and exogenous sources. Ultraviolet irradiation is a well-known contributor of photocarcinogenesis and photoaging, as it - among other things - promotes the production of ROS which damage nucleic acids, proteins and lipids. Topical or oral administration of antioxidants is presumed to counteract the damaging effects of ROS to the skin, thus potentially lowering the risk of skin cancers and skin aging. We review the current literature on chemoprevention of photocarcinogenesis using antioxidants.

[A free musculocutaneous flap and an intramedullary nail made the use of a prosthesis possible in a high traumatic femoral amputation].

The length of the stump and the quality of the soft tissue coverage are important for prosthesis fitting and mobility. In a high traumatic femoral amputation soft tissue reconstruction with a free musculocutaneous latissimus dorsi (LD) flap was performed to preserve bone length and provide proper tissue coverage. The extremely short stump was later on lengthened using a motorized intramedullary nail (Fitbone), and the achieved bone-lengthening was 14 cm. With the combined modalities of an LD-flap and Fitbone lengthening of the stump, the patient now has a useful limb function.