Background:Polyamine levels are intricately controlled by biosynthetic, catabolic enzymes and antizymes. The complexity suggests that minute alterations in levels lead to profound abnormalities. We described the therapeutic course for a rare syndrome diagnosed by whole exome sequencing caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC), characterized by neurological deficits and alopecia.Methods:N-acetylputrescine levels with other metabolites were measured using ultra-performance liquid chromatography paired with mass spectrometry and Z-scores established against a reference cohort of 866 children.Results:From previous studies and metabolic profiles, eflornithine was identified as potentially beneficial with therapy initiated on FDA approval. Eflornithine normalized polyamine levels without disrupting other pathways. She demonstrated remarkable improvement in both neurological symptoms and cortical architecture. She gained fine motor skills with the capacity to feed herself and sit with support.Conclusions:This work highlights the strategy of repurposing drugs to treat a rare disease.Funding:No external funding was received for this work.

Lipids are stable molecules involved in metabolism and inflammation. We investigated the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n=24) were 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 were 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. PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provided stratification between sedation controls and all MODS patients for lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (PE) (p-value = 0.03). Phospholipids in patients needing ECMO were observably closer to sedation controls than other MODS patients. Nutrition intake revealed changes in lipid profiles that corresponded to calorie and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day PICU course, suggesting novel indicators for defining critically ill children.

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.

Objective: We investigated whether differences in survival exist between children of various racial/ethnic groups with cancer admitted to the PICU. Design: A retrospective multicenter analysis was conducted using Virtual Pediatric Systems data from reporting centers. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were analyzed using mixed-effects logistic regression modeling to assess for differences in mortality. Setting: One hundred thirty-five PICUs in the United States. Patients: Pediatric patients with cancer admitted to PICUs in the United States. Interventions: None. Measurements and Main Results: This study details the analysis of 23,128 PICU admissions of 12,232 unique oncology patients representing 3% of all PICU admissions with 1,610 deaths (7.0% case fatality). African American (8.5%) and Hispanic children (8.1%) had significantly higher mortality (p < 0.05) compared with Caucasian children (6.3%). Regional analysis showed Hispanic patients to have higher mortality in the West in the United States, whereas African American patients in the South in the United States had higher mortality. A pulmonary disease diagnosis in Hispanics increased odds of mortality (odds ratio, 1.39; 95% CI, 1.13–1.70), whereas a diagnosis of shock/sepsis increased risk for mortality in African Americans (odds ratio, 1.56; 95% CI, 1.11–2.20) compared with Caucasians. There were no differences between races/ethnic groups in the rates of limitations of care. After controlling for Pediatric Risk of Mortality III, PICU length of stay, stem cell transplant status, readmissions, cancer type (solid, brain, hematologic), mechanical ventilation days, and sex, Hispanic (odds ratio, 1.24; 95% CI, 1.05–1.47) and African Americans (odds ratio, 1.37; 95% CI, 1.14–1.66) had significantly higher odds of mortality compared with Caucasians. Conclusions: The results show that after controlling for severity and cancer type, a child’s race, ethnicity, and region of presentation influence mortality in the PICU. This suggests that additional investigation is warranted along with a need to rethink our approach to the evaluation and treatment of critically ill African American and Hispanic children with cancer.

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.

BackgroundThe majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.ObjectiveTo determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.Data Sources and Search StrategyWe will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages &gt;28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded.Study SelectionWe will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located.Data ExtractionData extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes.Data SynthesisWe will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow.ConclusionsBy understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs.

We examined preadmission diet and zip code in infants with severe respiratory illness in the pediatric critical care unit. Patients aged 0 to 5 months admitted to the Helen DeVos Children's Hospital from January 2011 to May 2017 (N = 187), as exclusively formula, exclusively breastfed or mixed diet were included. Formula-fed infants (n = 88; 47%) clustered to zip codes with lower median incomes (<0.005), used public insurance as their payer type (p < 0.005), and were prescribed more ranitidine (p < 0.05) on admission.

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.