Objectives: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19).

METHODS:Mice with a lineage-specific deletion of DDR2 (Pdgfra-CreER +/-;Ddr2 fl/fl ) and CreER -/controls as well as a congenital deletion of DDR2 (Ddr2 slie/slie ) and littermate controls (LC) received a 30% total body surface area dorsal burn with concurrent unilateral Achilles' tenotomy (burn/tenotomy, BT). C57B6 mice received BT and were treated with DDR2 inhibitor imatinib for 16 days post-injury to assess the role of DDR2 inhibition on HO. HO volume and collagen alignment were assessed by micro-CT and second-harmonic generation of collagen fibers, respectively. Confocal microscopy was performed to visualize expression of pFAK in MLin cells in vivo. Ddr2 slie/ slie and LC MLin cells were plated onto 3D collagen matrices or 2D collagen-coated plates to determine the effect of DDR2 on focal adhesion (FA) orientation and TAZ activation in vitro, respectively. Tamoxifen (TMX)-induced Pdgfra-CreER +/-;Ddr2 fl/fl and CreER -/control MLin cells were subjected to traction force microscopy (TFM) to determine strain forces on collagen-coated gels in vitro. TMX-treated Pdgfra-CreER +/-;Ddr2 fl/fl and WT MLin cells were treated with TRULI, an inhibitor of LATS, which phosphorylates and inhibits YAP and TAZ nuclear translocation, to define the role of DDR2 deletion in YAP/TAZ signaling in vitro. RESULTS:Previous analyses from our group identified Ddr2 as highly expressed and activated specifically in MLin cells following injury (omitted). Inhibition of DDR2 with imatinib decreased HO (A). Pdgfra-CreER +/-;Ddr2 fl/fl mice also showed reduced HO (B). Ddr2 slie/slie showed greater disorganization in collagen compared to LC following BT (C). FA analysis of vinculin showed altered FA orientation in Ddr2 slie/slie MLin cells which may explain the altered collagen alignment seen in vivo (D). TFM demonstrated the ability of MLin cells to provide strain on the ECM, though strain energy was similar between both groups (E). We hypothesized that DDR2 alters HO formation through a FAK and YAP/TAZ dependent process. Ddr2 slie/slie mice showed reduced activated pFAK in vivo at the HO site (F) and reduced nuclear (transcriptionally active) TAZ in vitro (G). TRULI-treated MLin cells with a DDR2 deletion showed reduced nuclear TAZ localization compared to WT MLin cells (H).CONCLUSION: These findings suggest that MLin-cell DDR2 signaling following injury promotes HO due to altered FA orientation and signaling through a FAK/YAP/ TAZ pathway to activate osteogenic differentiation. Collagen alignment alternations may be due to changes in FA orientation. Having identified the role of MLin DDR2 on HO and ECM alignment following injury, these results suggest that DDR2 may be an effective target in preventing aberrant MLin cell osteogenesis following injury.

Introduction Complex burns are a challenge, often requiring prolonged reconstruction. Management requires consideration not only to the skin but to underlying structures and often requires staged-reconstruction and revision for increasingly unsatisfactory results. This standard is expensive, limited by donor-site availability, and often impacts quality of life. Here we demonstrate the efficacy of single-staged minced skin grafting in an incubator-like microenvironment with a negative-pressure moist wound chamber device to achieve rapid epithelialization after burns. Methods Full-thickness burns were induced to female Yorkshire swine. Escharectomies were performed to the level of fascia after seventy-two hours. One group received standard of care skin grafting with a bolster dressing. In another group, split-thickness skin was cut into pixel size (0.3x0.3 mm) grafts, followed by application of either bolster or negative-pressure moist wound chamber dressing. Wounds were followed for 4-weeks with serial photography, ultrasound, and biopsies for histology. Results As early as one week, epithelialization started in the group with pixel grafts with negative-pressure moist wound chamber dressings with visible epithelioid islands on the wound bed granulation tissue. This progressed with a similar trend throughout the 4-week period eventually leading to near-complete epithelization and keratinization. There was reconstruction of trilaminar cutaneous architecture demonstrated by the presence of distinct, viable epidermal, dermal and hypodermal elements as well as viability of adipose on histology. Distinct differences in contour were noted between the bolster and negative-pressure moist wound chamber groups. Conclusions Minced grafting minimized donor burden and alleviated the need for graft orientation. In both the bolstered and negative-pressure moist wound chambers, pixel-grafts viably survived to form a viable basal layer. Use of positive-pressure (bolster) vs. negative-pressure moist wound chamber dressings demonstrated distinct differences in the convexity/concavity and topography of the singe-stage skin graft with critical implications for aesthetic reconstruction. Applicability of Research to Practice This study introduces the efficacy of a single-staged trilaminar reconstruction with the use of a negative-pressure moist wound chamber for complex burns. These findings support the potential for a new paradigm in the treatment of complex burns which allows for single-stage reconstruction with minimal donor site morbidity.

No abstract