Association Between Transfusion of RBCs and Subsequent Development of Delirium in Critically Ill Children.

OBJECTIVES: To determine the temporal relationship between the transfusion of RBCs and the subsequent development of delirium in a cohort of critically ill children. DESIGN: Nested retrospective cohort study within prospective cohort study. SETTING: Urban academic tertiary care PICU. PATIENTS: All consecutive admissions from September 2014 through August 2015. INTERVENTIONS: Children were screened twice daily for delirium during their PICU admission. MEASUREMENTS AND MAIN RESULTS: Among 1,547 independent admissions screened for delirium, 166 (10.7%) were transfused RBCs. Children who were transfused RBCs were more than twice as likely to be delirious during their admission compared with children who were never transfused, after controlling for known predictors of delirium development (adjusted odds ratio, 2.16; 95% CI, 1.38-3.37; p = 0.001). Among transfused children, a temporal relationship was observed between receipt of RBCs and the subsequent development of delirium. For each additional 10 mL/kg of RBCs transfused, the recipients were 90% more likely to develop delirium or coma in the 72 hours following the transfusion, after controlling for confounders (adjusted odds ratio, 1.90; 95% CI, 1.14-3.17; p = 0.01). Anemia (represented by nadir hemoglobin prior to transfusion) was not associated with delirium development. CONCLUSIONS: In this cohort of critically ill children, there is an independent association between the receipt of an RBC transfusion and the subsequent development of delirium. Further prospective studies are warranted to replicate this finding and investigate possible pathophysiologic mechanisms for this association.

Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E-/- mice.

OBJECTIVE: Exposure to dioxins has been shown to contribute to the development of inflammatory diseases, such as atherosclerosis. Macrophage-mediated inflammation is a critical event in the initiation of atherosclerosis. Previously, we showed that treatment of macrophages with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to aryl hydrocarbon receptor (AhR)-dependent activation of inflammatory mediators and the formation of cholesterol-laden foam cells. However, the mechanisms responsible for the formation of atherosclerotic lesions mediated through AhR have not been identified. METHODS AND RESULTS: An in vitro macrophage and an apolipoprotein E (ApoE)-/- mouse model were used to determine whether chemokines and their receptors are responsible for the AhR-mediated atherogenesis. Exposure of ApoE-/- mice to TCDD caused a time-dependent progression of atherosclerosis, which was associated with induction of inflammatory genes, including interleukin-8, as well as F4/80 and matrix metalloproteinase-12. A high-fat diet enhanced the TCDD-mediated inflammatory response and aggravated the formation of complex atheromas. Treatment with a CXCR2 inhibitor and an AhR antagonist reduced the TCDD-induced progression of early atherosclerotic lesions in ApoE-/- mice. CONCLUSION: The results suggest that CXCR2 mediates the atherogenic activity of environmental pollutants, such as dioxins, and contributes to the development of atherosclerosis through the induction of a vascular inflammatory response by activating the AhR-signaling pathway.

Effect of Contact Precautions on Staphylococcus aureus and Clinical Outcomes of Colonized Patients in the Neonatal Intensive Care Unit.

BACKGROUND: Staphylococcus aureus is a common pathogen in neonatal intensive care units (NICUs), yet little is known about the effect of contact precautions and clinical outcomes of colonized patients. METHODS: Retrospective cohort study of all neonates from August 2014 to November 2018 colonized with either methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) and select noncolonized patients at two neonatal intensive care units at the University of California, Los Angeles. Outcomes during two time periods (during and after the use of contact precautions) were assessed. RESULTS: A total of 234 patients were included in the study: 83 colonized and 151 noncolonized patients. There was a fourfold higher incidence of MSSA colonization versus MRSA (P < 0.001). There was a higher incidence of positive surveillance cultures after contact precautions were discontinued (P = 0.01), but this did not correlate with a higher incidence of invasive cultures (P = 0.475). There were twice as many MSSA invasive cultures than MRSA, but a higher rate of invasion with MRSA (P < 0.05). Colonized patients were more likely to develop an invasive infection than noncolonized (P = 0.003 MRSA; P = 0.004 MSSA). When controlling for gestational age and surgical interventions, colonization was more likely to be associated with skin and soft tissue infections (P < 0.001) and a longer length of stay by a mean of 27.8 days (P < 0.0001). CONCLUSIONS: Contact precautions resulted in a lower incidence of colonization without a difference in invasive cultures in our NICUs. Those colonized with S. aureus had a higher incidence of skin and soft tissue infections and a longer NICU length of stay.

FiehnLib: mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry.

At least two independent parameters are necessary for compound identification in metabolomics. We have compiled 2 212 electron impact mass spectra and retention indices for quadrupole and time-of-flight gas chromatography/mass spectrometry (GC/MS) for over 1000 primary metabolites below 550 Da, covering lipids, amino acids, fatty acids, amines, alcohols, sugars, amino-sugars, sugar alcohols, sugar acids, organic phosphates, hydroxyl acids, aromatics, purines, and sterols as methoximated and trimethylsilylated mass spectra under electron impact ionization. Compounds were selected from different metabolic pathway databases. The structural diversity of the libraries was found to be highly overlapping with metabolites represented in the BioMeta/KEGG pathway database using chemical fingerprints and calculations using Instant-JChem. In total, the FiehnLib libraries comprised 68% more compounds and twice as many spectra with higher spectral diversity than the public Golm Metabolite Database. A range of unique compounds are present in the FiehnLib libraries that are not comprised in the 4345 trimethylsilylated spectra of the commercial NIST05 mass spectral database. The libraries can be used in conjunction with GC/MS software but also support compound identification in the public BinBase metabolomic database that currently comprises 5598 unique mass spectra generated from 19,032 samples covering 279 studies of 47 species (plants, animals, and microorganisms).

Comparative metabolomics in primates reveals the effects of diet and gene regulatory variation on metabolic divergence.

Human diets differ from those of non-human primates. Among few obvious differences, humans consume more meat than most non-human primates and regularly cook their food. It is hypothesized that a dietary shift during human evolution has been accompanied by molecular adaptations in metabolic pathways. Consistent with this notion, comparative studies of gene expression levels in primates have found that the regulation of genes with metabolic functions tend to evolve rapidly in the human lineage. The metabolic consequences of these regulatory differences, however, remained unknown. To address this gap, we performed a comparative study using a combination of gene expression and metabolomic profiling in livers from humans, chimpanzees, and rhesus macaques. We show that dietary differences between species have a strong effect on metabolic concentrations. In addition, we found that differences in metabolic concentration across species are correlated with inter-species differences in the expression of the corresponding enzymes, which control the same metabolic reaction. We identified a number of metabolic compounds with lineage-specific profiles, including examples of human-species metabolic differences that may be directly related to dietary differences.