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Severe pediatric sepsis continues to be associated with high mortality rates in children. Thus, an important area of biomedical research is to identify biomarkers that can classify sepsis severity and outcomes. The complex and heterogeneous nature of sepsis makes the prospect of the classification of sepsis severity using a single biomarker less likely. Instead, we employ machine learning techniques to validate the use of a multiple biomarkers scoring system to determine the severity of sepsis in critically ill children. The study was based on clinical data and plasma samples provided by a tertiary care center's Pediatric Intensive Care Unit (PICU) from a group of 45 patients with varying sepsis severity at the time of admission. Canonical Correlation Analysis with the Forward Selection and Random Forests methods identified a particular set of biomarkers that included Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), and Bicarbonate (HCO[Formula: see text]) as having the strongest correlations with sepsis severity. The robustness and effectiveness of these biomarkers for classifying sepsis severity were validated by constructing a linear Support Vector Machine diagnostic classifier. We also show that the concentrations of Ang-1, Ang-2, and HCO[Formula: see text] enable predictions of the time dependence of sepsis severity in children.

PERSEVERE is a risk model for estimating mortality probability in pediatric septic shock, using five biomarkers measured within 24 hours of clinical presentation. Here, we derive and test a temporal version of PERSEVERE (tPERSEVERE) that considers biomarker values at the first and third day following presentation to estimate the probability of a \"complicated course\", defined as persistence of ≥2 organ failures at seven days after meeting criteria for septic shock, or death within 28 days. Biomarkers were measured in the derivation cohort (n = 225) using serum samples obtained during days 1 and 3 of septic shock. Classification and Regression Tree (CART) analysis was used to derive a model to estimate the risk of a complicated course. The derived model was validated in the test cohort (n = 74), and subsequently updated using the combined derivation and test cohorts. A complicated course occurred in 23% of the derivation cohort subjects. The derived model had a sensitivity for a complicated course of 90% (95% CI 78-96), specificity was 70% (62-77), positive predictive value was 47% (37-58), and negative predictive value was 96% (91-99). The area under the receiver operating characteristic curve was 0.85 (0.79-0.90). Similar test characteristics were observed in the test cohort. The updated model had a sensitivity of 91% (81-96), a specificity of 70% (64-76), a positive predictive value of 47% (39-56), and a negative predictive value of 96% (92-99). tPERSEVERE reasonably estimates the probability of a complicated course in children with septic shock. tPERSEVERE could potentially serve as an adjunct to physiological assessments for monitoring how risk for poor outcomes changes during early interventions in pediatric septic shock.

Background: Pediatric severe sepsis is a public health problem with significant morbidities in those who survive. In this article, we aim to present an overview of the important studies highlighting the limited data available pertaining to long-term outcomes of survivors of pediatric severe sepsis. Materials and Methods: A review of literature available was conducted using PUBMED/Medline on pediatric severe sepsis outcomes. Long-term outcomes and health-related quality of life (HRQL) following severe sepsis was defined as any outcome occurring after discharge from the hospital following an episode of severe sepsis which affected either the survivor or the survivor’s family members. Results: Many children are discharged with worse clinical and functional outcomes, depending on their diagnosis, treatments received, psychological effects, and the impact of their illness on their parents. Additionally, they utilize healthcare services more than their peers and are often readmitted soon after discharge. However, pediatric HRQL studies with worthwhile outcome measures are limited and the current data on pediatric sepsis is mainly retrospective. Conclusions: There is significant and longstanding morbidity seen in children and their families following a severe sepsis illness. Further prospective data are required to study the long-term outcomes of sepsis in the pediatric population.

Background. Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus α-toxin directly injures pneumocytes and increases mortality, whereas α-toxin blockade mitigates disease. The role of α-toxin in pediatric staphylococcal-viral coinfection is unclear. Methods. We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza virus infection. Serial serum anti-α-toxin antibody titers and functional α-toxin neutralization capacity were compared across children coinfected with MRSA or methicillin-susceptible S. aureus (MSSA) and control children infected with influenza virus only. MRSA isolates were tested for α-toxin production and lethality in a murine pneumonia model. Results. Influenza virus was identified in 22 of 25 children with MRSA coinfection (9 died) and 22 patients with MSSA coinfection (all survived). Initial α-toxin-specific antibody titers were similar, compared with those in the 13 controls. In patients with serial samples, only MRSA-coinfected patients showed time-dependent increases in anti-α-toxin titer and functional neutralization capacity. MRSA α-toxin production from patient isolates correlated with initial serologic titers and with mortality in murine pneumonia. Conclusions. These data implicate α-toxin as a relevant antigen in severe pediatric MRSA pneumonia associated with respiratory viral infection, supporting a potential role for toxin-neutralizing therapy.

Objective The aim was to investigate the effects of cardiopulmonary bypass (CPB) on plasma levels of the vascular growth factors, angiopoietin (angpt)-1, angpt-2, and vascular endothelial growth factor (VEGF). Design The design was a prospective, clinical investigation. Setting The setting was a 12-bed pediatric cardiac intensive care unit of a tertiary children’s medical center. Patients The patients were 48 children (median age, 5 months) undergoing surgical correction or palliation of congenital heart disease who were prospectively enrolled following informed consent. Interventions There were no interventions in this study. Measurements and results Plasma samples were obtained at baseline and at 0, 6, and 24 h following CPB. Angpt-1, angpt-2, and VEGF levels were measured via commercial ELISA. Angpt-2 levels increased by 6 h (0.95, IQR 0.43–2.08 ng mL −1 vs. 4.62, IQR 1.16–6.93 ng mL −1 , P  < 0.05) and remained significantly elevated at 24 h after CPB (1.85, IQR 0.70–2.76 ng mL −1 ; P  < 0.05). Angpt-1 levels remained unchanged immediately after CPB, but were significantly decreased at 24 h after CPB (0.64, IQR 0.40–1.62 ng mL −1 vs. 1.99, IQR 1.23–2.63 ng mL −1 , P  < 0.05). Angpt-2 levels correlated significantly with cardiac intensive care unit (CICU) length of stay (LOS) and were an independent predictor for CICU LOS on subsequent multivariate analysis. Conclusions Angpt-2 appears to be an important biomarker of adverse outcome following CPB in children.

Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort. To test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort. Study subjects were recruited from multiple pediatric intensive care units in the United States. Biomarkers were measured in 182 pediatric subjects with septic shock using serum samples obtained during the first 24 hours of presentation. The accuracy of PERSEVERE 28-day mortality risk estimate was tested using diagnostic test statistics, and the net reclassification improvement (NRI) was used to test whether PERSEVERE adds information to a physiology-based scoring system. Mortality in the test cohort was 13.2%. Using a risk cut-off of 2.5%, the sensitivity of PERSEVERE for mortality was 83% (95% CI 62-95), specificity was 75% (68-82), positive predictive value was 34% (22-47), and negative predictive value was 97% (91-99). The area under the receiver operating characteristic curve was 0.81 (0.70-0.92). The false positive subjects had a greater degree of organ failure burden and longer intensive care unit length of stay, compared to the true negative subjects. When adding PERSEVERE to a physiology-based scoring system, the net reclassification improvement was 0.91 (0.47-1.35; p<0.001). The updated version of PERSEVERE estimates mortality probability reliably in a heterogeneous test cohort of children with septic shock and provides information over and above a physiology-based scoring system.

Initially developed by the military through wartime experiences, aeromedical transport has become the cornerstone of many pediatric and neonatal transport programs. Expedited transport of critically ill pediatric patients via rotor- or fixed-wing aircraft may improve outcomes when clinical conditions warrant the rapid delivery of patients to qualified medical centers. However, air transport provides many unique problems for practitioners. Confined space, vibration, noise, and physiologic derangements from high altitude and low cabin pressure are all unique variables encountered during air transport. A sound understanding of these effects with their potential consequences is of paramount importance. Anticipating complications from these physiologic changes is necessary for management and appropriate equipment utilization during transfer. This review explores the history of air transport, associated physiologic changes, and specific equipment needs for transporting this unique patient population.

Abstract Background Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce. Methods We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes. Results Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01–1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05–1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36–2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15–4.62]) was associated with bacterial coinfection. Conclusions Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely. The majority of US children admitted to intensive care for COVID-19 received empiric antibiotics. Community-onset bacterial coinfection was infrequent but increased with the degree of organ dysfunction, and was more common in patients with underlying nonasthma lung disease.

IntroductionChildren with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.Materials and methodsWe sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation. A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease. The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.