Metabolomics of Mouse Embryonic CSF Following Maternal Immune Activation.

The cerebrospinal fluid (CSF) serves various roles in the developing central nervous system (CNS), from neurogenesis to lifelong cognitive functions. Changes in CSF composition due to inflammation can impact brain function. We recently identified an abnormal cytokine signature in embryonic CSF (eCSF) following maternal immune activation (MIA), a mouse model of autism spectrum disorder (ASD). We hypothesized that MIA leads to other alterations in eCSF composition and employed untargeted metabolomics to profile changes in the eCSF metabolome in mice after inducing MIA with polyI:C. We report these data here as a resource, include a comprehensive MS1 and MS2 reference dataset, and present additional datasets comparing two mouse strains (CD-1 and C57Bl/6) and two developmental time points (E12.5 and E14.5). Targeted metabolomics further validated changes upon MIA. We show a significant elevation of glucocorticoids and kynurenine pathway related metabolites. Both pathways are relevant for suppressing inflammation or could be informative as disease biomarkers. Our resource should inform future mechanistic studies regarding the etiology of MIA neuropathology and roles and contributions of eCSF metabolites to brain development.

Current State of Pediatric Cardio-Oncology: A Review.

The landscape of pediatric oncology has dramatically changed over the course of the past several decades with five-year survival rates surpassing 80%. Anthracycline therapy has been the cornerstone of many chemotherapy regimens for pediatric patients since its introduction in the 1960s, and recent improved survival has been in large part due to advancements in chemotherapy, refinement of supportive care treatments, and development of novel therapeutics such as small molecule inhibitors, chimeric antigen receptor T-cell therapy, and immune checkpoint inhibitors. Unfortunately, many cancer-targeted therapies can lead to acute and chronic cardiovascular pathologies. The range of cardiotoxicity can vary but includes symptomatic or asymptotic heart failure, arrhythmias, coronary artery disease, valvar disease, pericardial disease, hypertension, and peripheral vascular disease. There is lack of data guiding primary prevention and treatment strategies in the pediatric population, which leads to substantial practice variability. Several important future research directions have been identified, including as they relate to cardiac disease, prevention strategies, management of cardiovascular risk factors, risk prediction, early detection, and the role of genetic susceptibility in development of cardiotoxicity. Continued collaborative research will be key in advancing the field. The ideal model for pediatric cardio-oncology is a proactive partnership between pediatric cardiologists and oncologists in order to better understand, treat, and ideally prevent cardiac disease in pediatric oncology patients.

Role of the Egami Score in Predicting Intravenous Immunoglobulin Resistance in Kawasaki Disease Among Different Ethnicities.

Early treatment with intravenous immunoglobulin (IVIG) is necessary to help reduce the risk of coronary artery abnormalities, such as coronary artery aneurysms and to help alleviate symptoms, in Kawasaki disease. Some patients, however, do not respond to an initial dose of IVIG and require additional doses. Prediction of these IVIG nonresponders may be of assistance in altering initial therapy to make it more effective. The Egami score has been validated in the Japanese population to predict IVIG nonresponders but has shown to be ineffective in US populations. This study evaluates the Egami score in a Midwest US population, subdividing patients by race and the diagnosis of typical or atypical type of Kawasaki disease. Patients were included in the study if they met criteria for Kawasaki disease and received IVIG in the inpatient setting. A total of 182 patients were studied, and in all studied groups, the Egami score had poor sensitivity at predicting IVIG nonresponders. Sensitivity of the score differed between races and differed between typical and atypical Kawasaki disease. The Egami score, as well as other systems, have been validated to predict IVIG nonresponders. These, however, lack sensitivity in the US population. Other scores developed in the United States have also lacked sensitivity, likely due to the absence of race or Kawasaki disease classification as variables. The development of a sensitive scoring system to predict IVIG nonresponders in US populations will require the incorporation of race and Kawasaki disease classification, factors that seem to alter IVIG response.

Wound complications from idiopathic clubfoot surgery: a comparison of the modified Turco and the Cincinnati treatment methods.

PURPOSE: Treatment protocols using the Turco and the Cincinnati incisions are widely used for the surgical correction of clubfoot deformity. However, it is unclear which surgical approach leads to fewer wound problems. We therefore sought to determine which treatment method led to a lower incidence of wound complications. STUDY DESIGN: A retrospective chart review of 217 consecutive patients (308 feet) who underwent a primary posteromedial release for the treatment of idiopathic clubfoot under the age of 24 months via either the modified Turco or Cincinnati treatment methods was used to document the incidence of postoperative wound complications. The modified Turco protocol involved immediate postoperative casting in neutral, whereas the Cincinnati method involved staged casting with the foot initially in equinus, then to neutral with a cast change 7 days later. RESULTS: A significantly lower incidence of wound complications was seen in the Cincinnati treatment group when compared with the modified Turco treatment method (6.9% vs 19.6%, respectively, P < 0.003). When patients were stratified based on immediate versus staged postoperative casting methods, there was a significantly lower incidence of wound complications (P < 0.05) in feet in the Cincinnati treatment group versus the modified Turco treatment method; however, the statistical populations were markedly unequal. Among all feet treated with the Cincinnati method, patients who underwent a staged cast change had significantly fewer wound problems when compared with those who underwent immediate casting with the foot in neutral (5.1% vs 16.7%, respectively, P < 0.04). CONCLUSIONS: In the surgical correction of idiopathic clubfoot, the incidence of wound complications is significantly decreased with the use of the Cincinnati treatment method rather than the modified Turco treatment protocol. Whether this effect is a result of the incision or the postoperative casting protocol is unclear.