Background Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (COVID-19). We aimed to describe the typical presentation and outcomes of children diagnosed with this hyperinflammatory condition. Methods We conducted a systematic review to communicate the clinical signs and symptoms, laboratory findings, imaging results, and outcomes of individuals with MIS-C. We searched four medical databases to encompass studies characterizing MIS-C from January 1st, 2020 to July 25th, 2020. Two independent authors screened articles, extracted data, and assessed risk of bias. This review was registered with PROSPERO CRD42020191515. Findings Our search yielded 39 observational studies ( n = 662 patients). While 71·0% of children ( n = 470) were admitted to the intensive care unit, only 11 deaths (1·7%) were reported. Average length of hospital stay was 7·9 ± 0·6 days. Fever (100%, n = 662), abdominal pain or diarrhea (73·7%, n = 488), and vomiting (68·3%, n = 452) were the most common clinical presentation. Serum inflammatory, coagulative, and cardiac markers were considerably abnormal. Mechanical ventilation and extracorporeal membrane oxygenation were necessary in 22·2% ( n = 147) and 4·4% ( n = 29) of patients, respectively. An abnormal echocardiograph was observed in 314 of 581 individuals (54·0%) with depressed ejection fraction (45·1%, n = 262 of 581) comprising the most common aberrancy. Interpretation Multisystem inflammatory syndrome is a new pediatric disease associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is dangerous and potentially lethal. With prompt recognition and medical attention, most children will survive but the long-term outcomes from this condition are presently unknown. Funding Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study

Background: Studies summarizing the clinical picture of COVID-19 in children are lacking. This review characterizes clinical symptoms, laboratory, and imaging findings, as well as therapies provided to confirmed pediatric cases of COVID-19. Methods: Adhering to PRISMA guidelines, we searched four medical databases (PubMed, LitCovid, Scopus, WHO COVID-19 database) between December 1, 2019 to May 14, 2020 using the keywords "novel coronavirus", "COVID-19" or "SARS-CoV-2". We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Risk of bias was appraised through the quality assessment tool published by the National Institutes of Health. PROSPERO registration # CRD42020182261. Findings: We identified 131 studies across 26 countries comprising 7780 pediatric patients. Although fever (59¢1%) and cough (55¢9%) were the most frequent symptoms 19¢3% of children were asymptomatic. Patchy lesions (21¢0%) and ground-glass opacities (32¢9%) depicted lung radiograph and computed tomography findings, respectively. Immunocompromised children or those with respiratory/cardiac disease comprised the largest subset of COVID-19 children with underlying medical conditions (152 of 233 individuals). Coinfections were observed in 5.6% of children and abnormal laboratory markers included serum D-dimer, procalcitonin, creatine kinase, and interleukin-6. Seven deaths were reported (0¢09%) and 11 children (0¢14%) met inclusion for multisystem inflammatory syndrome in children. Interpretation: This review provides evidence that children diagnosed with COVID-19 have an overall excellent prognosis. Future longitudinal studies are needed to confirm our findings and better understand which patients are at increased risk for developing severe inflammation and multiorgan failure. Funding: Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study.

Understanding which children are at increased risk for poor outcome with COVID-19 is critical. In this study, we link pediatric population-based data from the US Center for Disease Control and Prevention to COVID-19 hospitalization and in-hospital death. In 27,045 US children with confirmed COVID-19, we demonstrate that African American [OR 2.28 (95% CI: 1.93, 2.70)] or mixed race [OR 2.95 (95% CI: 2.28, 3.82)] and an underlying medical condition [OR 3.55 (95% CI: 3.14, 4.01)] are strong predictors for hospitalization. Death occurred in 39 (0.19%) of 20,096 hospitalized children; children with a prior medical condition had an increased odd for death [OR 8.8 (95% CI: 3.7, 21.1)].Conclusion: Hospitalization and in-hospital death are rare in children diagnosed with COVID-19. However, children at higher risk for these outcomes include those with an underlying medical condition, as well as those of African American descent.

<b><i>Introduction:</i></b> Approximately 7,000 newborns die every day, accounting for almost half of child deaths under 5 years of age. Deciphering which neonates are at increased risk for mortality can have an important global impact. As such, integrating high computational technology (e.g., artificial intelligence [AI]) may help identify the early and potentially modifiable predictors of neonatal mortality. Therefore, the objective of this study was to collate, critically appraise, and analyze neonatal prediction studies that included AI. <b><i>Methods:</i></b> A literature search was performed in PubMed, Cochrane, OVID, and Google Scholar. We included studies that used AI (e.g., machine learning (ML) and deep learning) to formulate prediction models for neonatal death. We excluded small studies (<i>n</i> &#x3c; 500 individuals) and studies using only antenatal factors to predict mortality. Two independent investigators screened all articles for inclusion. The data collection consisted of study design, number of models, features used per model, feature importance, internal and/or external validation, and calibration analysis. Our primary outcome was the average area under the receiving characteristic curve (AUC) or sensitivity and specificity for all models included in each study. <b><i>Results:</i></b> Of 434 articles, 11 studies were included. The total number of participants was 1.26 M with gestational ages ranging from 22 weeks to term. Number of features ranged from 3 to 66 with timing of prediction as early as 5 min of life to a maximum of 7 days of age. The average number of models per study was 4, with neural network, random forest, and logistic regression comprising the most used models (58.3%). Five studies (45.5%) reported calibration plots and 2 (18.2%) conducted external validation. Eight studies reported results by AUC and 5 studies reported the sensitivity and specificity. The AUC varied from 58.3% to 97.0%. The mean sensitivities ranged from 63% to 80% and specificities from 78% to 99%. The best overall model was linear discriminant analysis, but it also had a high number of features (<i>n</i> = 17). <b><i>Discussion/Conclusion:</i></b> ML models can accurately predict death in neonates. This analysis demonstrates the most commonly used predictors and metrics for AI prediction models for neonatal mortality. Future studies should focus on external validation, calibration, as well as deployment of applications that can be readily accessible to health-care providers.

Objectives:To characterise the mortality and neurological outcomes of paediatric cardiac patients requiring cardiopulmonary resuscitation for more than 30 minutes prior to extracorporeal membrane oxygenation cannulation and to identify risk factors associated with adverse outcomes in this population.Materials and methods:Observational retrospective cohort study in paediatric cardiac patients undergoing cardiopulmonary resuscitation for greater than 30 minutes prior to cannulation in a tertiary children’s hospital, from July 2000 to July 2013.Results:Seventy-three paediatric cardiac patients requiring cardiopulmonary resuscitation for more than 30 minutes prior to cannulation were included in the study. Survival to hospital discharge was 43.8%, with 75% of survivors having either normal neurologic function or only mild disability. Multivariable logistic regression analysis demonstrated that increased use of calcium during resuscitation (odds ratio 14.5, p 0.01), cardiopulmonary resuscitation duration >50 minutes (odds ratio 4.12, p 0.03), >6 interruptions of chest compressions during cannulation (odds ratio 6.40, p 0.03), the need for continuous renal replacement therapy (odds ratio 11.1, p 0.001), and abnormal pupillary response during extracorporeal membrane oxygenation (odds ratio 33.9, p 0.006) were independent predictors for hospital mortality.Conclusion:Survival after cardiopulmonary resuscitation for more than 30 minutes prior to extracorporeal membrane oxygenation cannulation in our paediatric cardiac cohort was 43.8%. Factors associated with mortality included calcium use during resuscitation, longer cardiopulmonary resuscitation, increased chest compression pauses during cannulation, the use of continuous renal replacement therapy, and abnormal pupils during extracorporeal membrane oxygenation support. A prospective assessment of these factors in paediatric cardiac patients may be beneficial in improving outcomes.

BackgroundInflammation plays an important role in the pathogenesis of many lung diseases. Preclinical studies suggest that mesenchymal stromal cell (MSC) conditioned media (CdM) can attenuate inflammation. Our aim was threefold: (1) summarize the existing animal literature evaluating CdM as a therapeutic agent for pediatric/adult lung disease, (2) quantify the effects of CdM on inflammation, and (3) compare inflammatory effects of CdM to MSCs.MethodsAdhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed in five databases. Meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD).ResultsA total of 10 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, and acute respiratory distress syndrome. CdM decreased inflammatory cells (1.02 SMD, 95% CI 0.86, 1.18) and cytokines (0.71 SMD, 95% CI 0.59, 0.84). The strongest effect for inflammatory cells was in bronchopulmonary dysplasia (3.74 SMD, 95% CI 3.13, 4.36) while pulmonary hypertension had the greatest reduction in inflammatory cytokine expression (1.44 SMD, 95% CI 1.18, 1.71). Overall, CdM and MSCs had similar anti-inflammatory effects.ConclusionsIn this meta-analysis of animal models recapitulating lung disease, CdM improved inflammation and had an effect size comparable to MSCs. While these findings are encouraging, the risk of bias and heterogeneity limited the strength of our findings.

Social constructs are known risk factors for multisystem inflammatory syndrome in children. A review of 206 patients demonstrated that children who were non-Hispanic Black, over the age of 12 years or living in a disadvantaged neighborhood associated with severe multisystem inflammatory syndrome in children (intensive care unit admission, intubation and/or vasopressor use).

Background Lung disease is a leading cause of morbidity and mortality. A breach in the lung alveolar-epithelial barrier and impairment in lung function are hallmarks of acute and chronic pulmonary illness. This review is part two of our previous work. In part 1, we demonstrated that CdM is as effective as MSCs in modulating inflammation. Herein, we investigated the effects of mesenchymal stromal cell (MSC)-conditioned media (CdM) on (i) lung architecture/function in animal models mimicking human lung disease, and (ii) performed a head-to-head comparison of CdM to MSCs. Methods Adhering to the animal Systematic Review Centre for Laboratory animal Experimentation protocol, we conducted a search of English articles in five medical databases. Two independent investigators collected information regarding lung: alveolarization, vasculogenesis, permeability, histologic injury, compliance, and measures of right ventricular hypertrophy and right pulmonary pressure. Meta-analysis was performed to generate random effect size using standardized mean difference with 95% confidence interval. Results A total of 29 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. CdM improved all measures of lung structure and function. Moreover, no statistical difference was observed in any of the lung measures between MSCs and CdM. Conclusions In this meta-analysis of animal models recapitulating human lung disease, CdM improved lung structure and function and had an effect size comparable to MSCs.