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Immunoparalysis in children with septic shock is associated with increased risk of nosocomial infections and death. Myeloid-derived suppressor cells (MDSCs) potently suppress T cell function and may perpetuate immunoparalysis. Our goal was to test the hypothesis that children with septic shock would demonstrate increased proportions of MDSCs and impaired immune function compared with healthy controls.Prospective observational study.Fifty-four bed PICU in a quaternary-care children's hospital.Eighteen children with septic shock and thirty age-matched healthy children.None.Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stained for cell surface markers to identify MDSCs by flow cytometric analysis, including granulocytic and monocytic subsets. Adaptive and innate immune function was measured by ex vivo stimulation of whole blood with phytohemagglutinin-induced interferon (IFN) γ production and lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production, respectively. Prolonged organ dysfunction (OD) was defined as greater than 7 days. Children with septic shock had a higher percentage of circulating MDSCs, along with lower LPS-induced TNFα and phytohemagglutinin-induced IFNγ production capacities, compared with healthy controls. A cut-off of 25.2% MDSCs of total PBMCs in initial samples was optimal to discriminate children with septic shock who went on to have prolonged OD, area under the curve equal to 0.86. Children with prolonged OD also had decreased TNFα production capacity over time compared with those who recovered more quickly ( p = 0.02).This article is the first to describe increased MDSCs in children with septic shock, along with an association between early increase in MDSCs and adverse OD outcomes in this population. It remains unclear if MDSCs play a causative role in sepsis-induced immune suppression in children. Additional studies are warranted to establish MDSC as a potential therapeutic target.

Objective To determine pharmacist impact on vaccination errors and missed opportunities in the pediatric primary care setting with the presence of clinical decision support (CDS) by comparing a clinic with a pharmacist and CDS to a clinic with CDS alone. Design A retrospective chart review of patients' electronic medical records compared vaccination errors and missed opportunities between 2 pediatric primary care clinics. Setting Two urban, pediatric primary care clinics were selected for the study. Participants Encounters were included in the analysis for children presenting for any visit over a 3-month period. Intervention The intervention clinic had a full-time clinical pharmacist and CDS. The comparison clinic had CDS alone. Main outcome measures Vaccination errors were defined as follows: doses administered before minimum recommended age, doses administered before minimum recommended dosing interval, unnecessary doses, and invalid doses for a combination of these reasons. Missed opportunities were defined as vaccine doses due at the date of encounter but not administered, without documented reason for vaccination delay or refusal by provider or patient. The likelihood of missing an opportunity was also assessed for patient age, visit type, and provider type. Results One thousand and twenty patient encounters were randomly selected and reviewed. The vaccination error rate was 0.4% in the comparison group and 0% in the intervention group ( P = 0.4995). The number of encounters with a missed opportunity was significantly higher in the comparison group compared with the intervention group (51 vs. 30 encounters with missed opportunities; P = 0.015; adjusted odds ratio, 2.14 [95% CI 1.3-35]). Conclusion Although the use of CDS results in a low rate of vaccination errors, technology cannot be solely relied on for vaccination recommendations in the pediatric population because of the rigidity of CDS configuration. Pharmacists continue to play a vital role to ensure that children are appropriately vaccinated in the primary care setting.

Background: A major effect of low-dose ethanol is impairment of hippocampus-dependent cognitive function. α4/δ -containing GABAARs are highly expressed within the dentate gyrus region of the hippocampus where they mediate a tonic inhibitory current that is sensitive to the enhancement by low ethanol concentrations. These receptors are also powerful modulators of learning and memory, suggesting that they could play an important role in ethanol’s cognitive impairing effects. The goal of this study was to develop a high-throughput cognitive ethanol assay, amenable to use in genetically modified mice that could be used to test this hypothesis. Methods: We developed a procedure where preexposure to a conditioning chamber is used to rescue the “immediate shock deficit.” Using this task, ethanol can be specifically targeted at the hippocampus-dependent process of contextual learning without interfering with pain sensitivity or behavioral performance. Results: Validation of this task in C57BL/6 mice indicated that 1.0 g/kg ethanol and 10 mg/kg allopregnanolone disrupt contextual learning. Ro15-4513 reversed the effects of ethanol but not allopregnanolone, whereas it produced an impairment when given alone. The high-throughput nature of this task allowed for its application in a large cohort of α4 GABAAR KO mice. Loss of the α4 GABAAR subunit produced an enhanced sensitivity to the cognitive impairing effects of ethanol. This is consistent with the enhanced ethanol sensitivity of synaptic GABAARs that has been previously observed in the dentate gyrus in these mice, but inconsistent with the reduced ethanol sensitivity of extrasynaptic GABAARs observed in the same cells. Conclusions: Overall, these findings are consistent with our hypothesis that ethanol acts directly at GABAA receptors to impair hippocampus-dependent cognitive function. Furthermore, validation of this high-throughput assay will allow for future studies to use anatomically and temporally restricted genetic manipulations to probe more deeply into the neural mechanisms of ethanol action on learning and memory circuits.