K-wire Versus Screw Fixation in Displaced Lateral Condyle Fractures of the Humerus in Children: A Multicenter Study of 762 Fractures.

INTRODUCTION: Lateral humeral condyle fractures account for 12% to 20% of all distal humerus fractures in the pediatric population. When surgery is indicated, fixation may be achieved with either Kirschner-wires or screws. The literature comparing the outcomes of these 2 different fixation methods is currently limited. The purpose of this study is to compare both the complication and union rates of these 2 forms of operative treatment in a multicenter cohort of children with lateral humeral condyle fractures. METHODS: This retrospective study was performed across 6 different institutions. Data were retrospectively collected preoperatively and 6 weeks, 3, 6, and 12 months postoperatively. Patients were divided into 2 cohorts based on the type of initial treatment: K-wire fixation and screw fixation. Statistical comparisons between these 2 cohorts were performed with an alpha of 0.05. RESULTS: There were 762 patients included in this study, 72.6% (n=553) of which were treated with K-wire fixation. The mean duration of immobilization was 5 weeks in both cohorts, and most patients in this study demonstrated radiographic healing by 11 weeks postoperatively, regardless of treatment method. Similar reoperation rates were seen among those treated with K-wires and screws (5.6% vs. 4.3%, P =0.473). Elbow stiffness requiring further intervention with physical therapy was significantly more common in those treated with K-wires compared with children treated with screws (21.2% vs. 13.9%, P =0.023) as was superficial skin infection (3.8% vs. 0%, P =0.002), but there was no significant difference in nonunion rates between the two groups (2.4% vs. 1.3%, P =1.000). CONCLUSION: We found similar success rates between K-wire and screw fixation in this patient population. Contrary to previous studies, we did not find evidence that treatment with screw fixation decreases the likelihood of experiencing nonunion. However, given the unique complications associated with K-wire fixation, such as elbow stiffness and superficial skin infection, the treatment with screw fixation remains a reasonable alternative to K-wire fixation in these patients. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Mineral coated microparticles doped with fluoride and complexed with mRNA prolong transfection in fracture healing.

Introduction: Impaired fracture healing, specifically non-union, has been found to occur up to 14% in tibial shaft fractures. The current standard of care to treat non-union often requires additional surgeries which can result in long recovery times. Injectable-based therapies to accelerate fracture healing have the potential to mitigate the need for additional surgeries. Gene therapies have recently undergone significant advancements due to developments in nanotechnology, which improve mRNA stability while reducing immunogenicity. Methods: In this study, we tested the efficacy of mineral coated microparticles (MCM) and fluoride-doped MCM (FMCM) to effectively deliver firefly luciferase (FLuc) mRNA lipoplexes (LPX) to the fracture site. Here, adult mice underwent a tibia fracture and stabilization method and all treatments were locally injected into the fracture. Level of osteogenesis and amount of bone formation were assessed using gene expression and histomorphometry respectively. Localized and systemic inflammation were measured through gene expression, histopathology scoring and measuring C-reactive protein (CRP) in the serum. Lastly, daily IVIS images were taken to track and measure transfection over time. Results: MCM-LPX-FLuc and FMCM-LPX-FLuc were not found to cause any cytotoxic effects when tested in vitro. When measuring the osteogenic potential of each mineral composition, FMCM-LPX-FLuc trended higher in osteogenic markers through qRT-PCR than the other groups tested in a murine fracture and stabilization model. Despite FMCM-LPX-FLuc showing slightly elevated il-1ß and il-4 levels in the fracture callus, inflammation scoring of the fracture callus did not result in any differences. Additionally, an acute systemic inflammatory response was not observed in any of the samples tested. The concentration of MCM-LPX-FLuc and FMCM-LPX-FLuc that was used in the murine fracture model did not stimulate bone when analyzed through stereological principles. Transfection efficacy and kinetics of delivery platforms revealed that FMCM-LPX-FLuc prolongs the luciferase signal both in vitro and in vivo. Discussion: These data together reveal that FMCM-LPX-FLuc could serve as a promising mRNA delivery platform for fracture healing applications.

Forward genetics screens using macrophages to identify Toxoplasma gondii genes important for resistance to IFN-γ-dependent cell autonomous immunity.

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan pathogen. The parasite invades and replicates within virtually any warm blooded vertebrate cell type. During parasite invasion of a host cell, the parasite creates a parasitophorous vacuole (PV) that originates from the host cell membrane independent of phagocytosis within which the parasite replicates. While IFN-dependent-innate and cell mediated immunity is important for eventual control of infection, innate immune cells, including neutrophils, monocytes and dendritic cells, can also serve as vehicles for systemic dissemination of the parasite early in infection. An approach is described that utilizes the host innate immune response, in this case macrophages, in a forward genetic screen to identify parasite mutants with a fitness defect in infected macrophages following activation but normal invasion and replication in naïve macrophages. Thus, the screen isolates parasite mutants that have a specific defect in their ability to resist the effects of macrophage activation. The paper describes two broad phenotypes of mutant parasites following activation of infected macrophages: parasite stasis versus parasite degradation, often in amorphous vacuoles. The parasite mutants are then analyzed to identify the responsible parasite genes specifically important for resistance to induced mediators of cell autonomous immunity. The paper presents a general approach for the forward genetics screen that, in theory, can be modified to target parasite genes important for resistance to specific antimicrobial mediators. It also describes an approach to evaluate the specific macrophage antimicrobial mediators to which the parasite mutant is susceptible. Activation of infected macrophages can also promote parasite differentiation from the tachyzoite to bradyzoite stage that maintains chronic infection. Therefore, methodology is presented to evaluate the importance of the identified parasite gene to establishment of chronic infection.