Severity of illness is an important consideration in making the decision to transfuse as it is the sicker patient that often needs a red cell transfusion. Red blood cell (RBC) transfusions could potentially have direct effects and interact with presenting illness by contributing to pathologies such as multi-organ dysfunction and acute lung injury thus exerting a considerable impact on overall morbidity and mortality. In this study, we examine if transfusion is an independent predictor of mortality, or if outcomes are merely a result of the initial severity as predicted by Pediatric Risk of Mortality (PRISM) III, Pediatric Index of Mortality (PIM2), and day 1 Pediatric Logistic Organ Dysfunction (PELOD) scores. A single center retrospective study was conducted using data from a prospectively maintained transfusion database and center-specific data at our pediatric ICU between January 2009 and December 2012. Multivariate regression was used to control for the effects of clinical findings, therapy, and severity scores, with mortality as the dependent variable. Likelihood ratios and area under the curve were used to test the fidelity of severity scores by comparing transfused vs. non-transfused patients. There were 4975 admissions that met entry criteria. In multivariate analysis, PRISM III scores and serum hemoglobin were significant predictors of transfusion (p < 0.05). Transfused and non-transfused subjects were distinctly disparate, so multivariate regression was used to control for differences. Severity scores, age, volume transfused, and vasoactive agents were significantly associated with mortality whereas hemoglobin was not. A substantial number of transfusions (45 %) occurred in the first 24 h, and patients transfused later (24–48 h) were more likely to die compared to this earlier time point. Likelihood ratio testing revealed statistically significant differences in severity scoring systems to predict mortality in transfused vs. non-transfused patients. This study suggests that RBC transfusion is an important risk factor that is statistically independent of severity. The timing of transfusions that related strongest to mortality remained outside the purview of severity scoring, as these happened beyond the timing of data collection for most scoring systems.

Metabolites are generated from exogenous sources such as diet. This scoping review will summarize nascent metabolite literature and discriminating metabolites for formula vs. human- milk-fed infants. Using the PICOS framework (P—Patient, Problem or Population; I—Intervention; C—Comparison; O—Outcome; S—Study Design) and PRISMA item-reporting protocols, infants less than 12 months old, full-term, and previously healthy were included. Protocol was registered with Open Science Framework (OSF). Publications from 1 January 2009–2019 were selected, for various biofluids, study designs, and techniques (such as high-performance liquid chromatography (HPLC)). From 711 articles, blinded screening of 214 articles using Abstrackr^® software, resulted in 24 for final review. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines were adopted, which included a 24-point checklist. Articles were stratified according to biofluid. Of articles reporting discriminating metabolites between formula- and human milk-fed infants, 62.5% (5/8) of plasma/serum/dried blood spot, 88% (7/8) of urine and 100% (6/6) of feces related articles reported such discriminating metabolites. Overall, no differences were found between analytical approach used (targeted (n = 9) vs. un-targeted (n = 10)). Current articles are limited by small sample sizes and differing methodological approaches. Of the metabolites reviewed herein, fecal metabolites provided the greatest distinction between diets, which may be indicative of usefulness for future diet metabolite-focused work.

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.

Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting the criteria for MODS were screened, consented (n = 24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n = 4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. Sixty-one patient samples over three time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63–3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (p-value ≤ 0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.

Metabolites are generated from critical biological functions and metabolism. This pediatric study reviewed plasma metabolites in patients suffering from multi-organ dysfunction syndrome (MODS) in the pediatric intensive care unit (PICU) using an untargeted metabolomics approach. Patients meeting the criteria for MODS were screened for eligibility and consented (n = 24), and blood samples were collected at baseline, 72 h, and 8 days; control patients (n = 4) presented for routine sedation in an outpatient setting. A subset of MODS patients (n = 8) required additional support with veno-atrial extracorporeal membrane oxygenation (VA-ECMO) therapy. Metabolites from thawed blood plasma were determined from ion pairing reversed-phase liquid chromatography–mass spectrometry (LC-MS) analysis. Chromatographic peak alignment, identification, relative quantitation, and statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the partial least squares-discriminant analysis (PLS-DA) with variance of importance (VIP) scores above ≥2.0, 7 dynamic metabolites emerged over the three time points: tauro-chenodeoxycholic acid (TCDCA), hexose, p-hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferroni adjustment for repeated measures, hexose and p-hydroxybenzoate were significant at one time point or more. Kendall’s tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patient’s pathophysiology and require operator interpretation.

Metabolites are generated from critical biological functions and metabolism. This pediatric study reviewed plasma metabolites in patients suffering from multi-organ dysfunction syndrome (MODS) in the pediatric intensive care unit (PICU) using an untargeted metabolomics approach. Patients meeting criteria for MODS were screened for eligibility and consented (n=24), and blood samples were collected at baseline, 72 hours, and 8 days; control patients (n=4), were presenting for routine sedation in an outpatient setting. A sub-set of MODS patients (n=8) required additional support with veno-atrial extracorporeal membrane oxygenation (VA-ECMO) therapy. Metabolites from thawed blood plasma were determined from ion pairing reversed-phase LC-MS analysis. Chromatographic peak alignment, identification, relative quantitation, statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the PLS-DA with VIP scores above ≥2.0, 7 dynamic metabolites emerged over the 3 time points: tauro-chenodeoxycholic acid (TCDCA), hexose, p -hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferonni adjustment for repeated measures hexose and p -hydroxybenzoate were significant at one time point, or more. Kendall’s tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patient’s pathophysiology and require operator interpretation.