Novel Identification of Myeloid-Derived Suppressor Cells in Children With Septic Shock.

OBJECTIVES: 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. DESIGN: Prospective observational study. SETTING: Fifty-four bed PICU in a quaternary-care children's hospital. PATIENTS: Eighteen children with septic shock and thirty age-matched healthy children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

Relationship of Viral Detection with Duration of Ventilation in Critically Ill Infants with Lower Respiratory Tract Infection.

Rationale: Although respiratory virus testing is frequently done for critically ill infants with bronchiolitis, the prognostic value of this testing is unknown for those requiring positive-pressure ventilation (PPV). Objectives: To determine the differences in PPV use according to viral detection and to explore the association between viral detection and duration of PPV in critically ill children with presumed respiratory infection. Methods: This is a retrospective cohort study in a quaternary pediatric intensive care unit from February 2014 until February 2017. We evaluated 984 children less than 1 year of age who received PPV for presumed respiratory infection without significant congenital heart disease, care limitations, baseline PPV usage, or tracheostomy. Respiratory viruses were identified using a PCR panel. Analyses of duration of PPV according to viral etiology were performed using univariate and multivariable logistic regression and truncated negative binomial regression with calculated mean marginal effects (MME). Results: Overall, 85 (9%) infants had no viruses identified, 629 (64%) had a single virus detected, most commonly respiratory syncytial virus (417, 42%) followed by rhinovirus/enterovirus (145, 15%), 230 (23%) had two viruses detected, and 40 (4%) had three viruses detected. Compared with those with one or no virus detected, infants with ⩾2 viruses received longer total PPV duration in adjusted analysis (relative risk [RR], 1.4; 95% confidence interval [CI], 1.2-1.6; P < 0.001; MME = 29 h). Detection of rhinovirus/enterovirus alone, compared with respiratory syncytial virus alone, was associated with significantly shorter duration of total PPV (RR, 0.7; 95% CI, 0.62-0.87; P = <0.001; MME = -23 h), noninvasive PPV (RR, 0.7; 95% CI, 0.60-0.85; P < 0.001; MME = -15 h), and invasive PPV (RR, 0.7; 95% CI, 0.54-0.83; P < 0.001; MME = -54 h) when adjusted for weight, prematurity, and administration of early antibiotic therapy. Conclusions: Identification of viral type and number in severe bronchiolitis is an important predictor of duration of PPV.

Validity and Reliability of a New Tool to Evaluate Impaired Airway Clearance in Hospitalized Pediatric Subjects With Respiratory Distress.

BACKGROUND: Chest physiotherapy has been reported to be beneficial in specific clinical contexts, yet it carries a risk of potential serious adverse events with little benefit in other patients. Therefore, identifying and limiting airway clearance therapies to patients with the greatest potential benefit and least risk is clinically relevant and important. This study aims to validate the Airway Clearance and Expansion Index (ACE-I) for the serial assessment of hospitalized pediatric patients with impaired airway clearance and to establish reliability in score acquisition across a range of pediatric respiratory disease states. METHODS: Content validity of the category importance and category choices was assessed via a survey of well-established pediatric pulmonary and critical care physicians, as well as respiratory therapists (RTs). Inter-rater reliability testing was performed on hospitalized children from October 2016 through April 2017 and analyzed using a one-way random effects intraclass correlation. RESULTS: 51 providers (24 of 37 physicians and 27 of 92 RTs) responded to the survey. Agreement was defined as any score of 6 or greater out of 10 on a scale of 1-10. The total ACE-I scale content validity index (S-CVI) scores for category importance and category choices for physicians were 1 and 0.75, respectively, and for RTs the scores were 0.75 and 0.75, respectively. 172 subjects were scored by multiple raters, resulting in an excellent overall intraclass correlation coefficient of 0.77 (95% CI 0.71-0.83) and the following component scores: cough, 0.72 (95% CI 0.64-0.79); breath sounds, 0.54 (95% CI 0.43-0.64); chest radiograph findings, 0.84 (95% CI 0.79-0.88); and secretions 0.85, (95% CI 0.81-0.89). CONCLUSIONS: The ACE-I score addresses and quantifies 4 components of the respiratory assessment that RTs and pediatric physicians deem important in identifying patients who have impaired airway clearance and might benefit from airway clearance and expansion therapies. In addition, the ACE-I score had excellent inter-rater reliability and clinical feasibility within our single institution.

Pharmacist impact on pediatric vaccination errors and missed opportunities in the setting of clinical decision support.

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.