Combined Plasma and Urinary Metabolomics Uncover Metabolic Perturbations Associated with Severe Respiratory Syncytial Viral Infection and Future Development of Asthma in Infant Patients.

A large percentage of infants develop viral bronchiolitis needing medical intervention and often develop further airway disease such as asthma. To characterize metabolic perturbations in acute respiratory syncytial viral (RSV) bronchiolitis, we compared metabolomic profiles of moderate and severe RSV patients versus sedation controls. RSV patients were classified as moderate or severe based on the need for invasive mechanical ventilation. Whole blood and urine samples were collected at two time points (baseline and 72 h). Plasma and urinary metabolites were extracted in cold methanol and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), and data from the two biofluids were combined for multivariate data analysis. Metabolite profiles were clustered according to severity, characterized by unique metabolic changes in both plasma and urine. Plasma metabolites that correlated with severity included intermediates in the sialic acid biosynthesis, while urinary metabolites included citrate as well as multiple nucleotides. Furthermore, metabolomic profiles were predictive of future development of asthma, with urinary metabolites exhibiting higher predictive power than plasma. These metabolites may offer unique insights into the pathology of RSV bronchiolitis and may be useful in identifying patients at risk for developing asthma.

Loss of Health Promoting Bacteria in the Gastrointestinal Microbiome of PICU Infants with Bronchiolitis: A Single-Center Feasibility Study.

The feasibility of gastrointestinal (GI) microbiome work in a pediatric intensive care unit (PICU) to determine the GI microbiota composition of infants as compared to control infants from the same hospital was investigated. In a single-site observational study at an urban quaternary care children's hospital in Western Michigan, subjects less than 6 months of age, admitted to the PICU with severe respiratory syncytial virus (RSV) bronchiolitis, were compared to similarly aged control subjects undergoing procedural sedation in the outpatient department. GI microbiome samples were collected at admission (n = 20) and 72 h (n = 19) or at time of sedation (n = 10). GI bacteria were analyzed by sequencing the V4 region of the 16S rRNA gene. Alpha and beta diversity were calculated. Mechanical ventilation was required for the majority (n = 14) of study patients, and antibiotics were given at baseline (n = 8) and 72 h (n = 9). Control subjects' bacterial communities contained more Porphyromonas, and Prevotella (p = 0.004) than those of PICU infants. The ratio of Prevotella to Bacteroides was greater in the control than the RSV infants (mean ± SD-1.27 ± 0.85 vs. 0.61 ± 0.75: p = 0.03). Bacterial communities of PICU infants were less diverse than those of controls with a loss of potentially protective populations.

Evaluation of the genotoxicity of cell phone radiofrequency radiation in male and female rats and mice following subchronic exposure.

The National Toxicology Program tested two common radiofrequency radiation (RFR) modulations emitted by cellular telephones in a 2-year rodent cancer bioassay that included interim assessments of additional animals for genotoxicity endpoints. Male and female Hsd:Sprague Dawley SD rats and B6C3F1/N mice were exposed from Gestation day 5 or Postnatal day 35, respectively, to code division multiple access (CDMA) or global system for mobile modulations over 18 hr/day, at 10-min intervals, in reverberation chambers at specific absorption rates of 1.5, 3, or 6 W/kg (rats, 900 MHz) or 2.5, 5, or 10 W/kg (mice, 1,900 MHz). After 19 (rats) or 14 (mice) weeks of exposure, animals were examined for evidence of RFR-associated genotoxicity using two different measures. Using the alkaline (pH > 13) comet assay, DNA damage was assessed in cells from three brain regions, liver cells, and peripheral blood leukocytes; using the micronucleus assay, chromosomal damage was assessed in immature and mature peripheral blood erythrocytes. Results of the comet assay showed significant increases in DNA damage in the frontal cortex of male mice (both modulations), leukocytes of female mice (CDMA only), and hippocampus of male rats (CDMA only). Increases in DNA damage judged to be equivocal were observed in several other tissues of rats and mice. No significant increases in micronucleated red blood cells were observed in rats or mice. In conclusion, these results suggest that exposure to RFR is associated with an increase in DNA damage. Environ. Mol. Mutagen. 61:276-290, 2020. © 2019 Wiley Periodicals, Inc.

Ocular Surface Disease in a PICU: Incidence and Outcomes With a Dynamic Eye Care Protocol.

OBJECTIVES: Sedated intensive care patients have impaired ocular protective mechanisms putting them at risk for ocular surface disease with potential vision loss. Historically, routine eye care has been limited to critically ill patients receiving neuromuscular blockade. The aim of this project was to determine the occurrence rate of ocular surface disease in sedated and ventilated children, identify risk factors, and determine the progression of injury with routine eye care. DESIGN: Prospective cohort study. SETTING: A tertiary care medical-surgical PICU. PATIENTS: All intubated patients admitted from May 2015 to December 2016. INTERVENTIONS: Staff education regarding corneal examination with fluorescein, and routine eye care as per a PICU eye care protocol. MEASUREMENTS AND MAIN RESULTS: We evaluated 479 patients (1,242 corneal exams) and found that 15% had ocular surface disease at admission to the PICU: keratopathy 62, abrasion 16. The highest incidence was in trauma patients (39.0%) and those intubated in the emergency department (22.2%) or prehospital setting (42.9%). Of the 245 patients with multiple ocular assessments, 32.2% displayed ocular surface disease at some point during their hospitalization: keratopathy 73, abrasion 24. Ourprotocol dictated increased frequency of eye care if ocular surface disease worsened. As a result, the overall incidence of ocular surface disease decreased to 8.6% by the last examination (keratopathy 19, mild abrasion 2), but more severe ocular abnormalities such as corneal infiltrates, ulcers, or scarring were not observed. Based on multivariate analysis, clinical factors associated with increased risk of ocular surface disease included primary diagnosis, and lagophthalmos (incomplete eyelid closure). CONCLUSIONS: Ocular surface disease is an under-recognized process in critically ill pediatric patients. A standardized and dynamic protocol may improve corneal health, which in turn may reduce injury, pain, infection, and long-term vision loss.

Comparative Effectiveness of Intranasal Dexmedetomidine-Midazolam versus Oral Chloral Hydrate Targeting Moderate Sedation during Pediatric Transthoracic Echocardiograms.

Objective To compare efficacy and safety of two moderate sedation regimens for transthoracic echocardiography (TTE): intranasal dexmedetomidine-midazolam (DM) versus oral chloral hydrate (CH) syrup. Method This was a retrospective cohort of 93 children under 4 years of age receiving moderate sedation with either DM or CH for TTE from January 2011 through December 2014. Measurements and Main Results Forty-nine patients received oral CH and 44 received the intranasal combination of DM. The demographics between groups were similar except the DM patients were slightly older and heavier (each p < 0.05). Failure rate between groups did not reach statistical significance (CH 14.3% vs. DM 6.8%; p = 0.324). Total sedation to discharge time was similar between groups (CH 89.4 minutes vs. DM 89.6 minute; p = 0.97). Cardiopulmonary data did reveal a significantly lower heart rate (101.9 vs. 91.7; p < 0.001) and respiratory rate (23.4 vs. 21.0, p = 0.03) in the DM group, but no difference in blood pressure measurements or echo determined shortening fraction. Conclusion These data support the use of intranasal DM as a safe and efficacious method of moderate sedation for children undergoing TTE.

Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration.

An infant with a suspected inborn metabolism error was treated with a metabolic cocktail of intravenous sodium phenylacetate (NaPh) and sodium benzoate (NaBz) for hyperammonemia. Sequential hemodialysis (HD) then hemofiltration (HF) was performed due to hyperammonemia. Dialytic and convective clearance (K; ml/min) of ammonia, NaPh, and NaBz was measured. The K of ammonia was 57 and 37 for HD and HF, respectively. The K of NaBz was 37 and 12 for HD and HF, respectively. The K of NaPh was 38 and 14 ml/min for HD and HF, respectively. Despite high clearance of both NaPh and NaBz by HD and HF, the hyperammonemia was corrected.

Therapy of parapneumonic effusions in children: video-assisted thoracoscopic surgery versus conventional thoracostomy drainage.

OBJECTIVE: Controversy surrounds the optimal treatment of parapneumonic effusions. This trial of pediatric patients with community-acquired pneumonia and associated parapneumonic processes compared primary video-assisted thoracoscopic surgery with conventional thoracostomy drainage. DESIGN: A prospective, randomized trial was conducted at DeVos Children's Hospital (Grand Rapids, MI) between November 2003 and May 2005. All of the patients under 18 years of age with large parapneumonic effusions were approached for enrollment in the study. After enrollment, each patient was randomly assigned to receive either video-assisted thoracoscopic surgery or thoracostomy tube drainage of the effusion. Subsequent therapies (fibrinolysis, imaging, and further drainage procedures) were similar for each group per protocol. RESULTS: Eighteen patients were enrolled in the study: 10 in video-assisted thoracoscopic surgery and 8 in conventional thoracostomy. The groups were demographically similar. No mortalities were encountered in either group, and everyone was discharged from the hospital with acceptable outcomes. Yet, there were multiple variables that demonstrated statistical difference. Hospital length of stay, number of chest tube days, narcotic use, number of radiographic procedures, and interventional procedures were all less in the patients who underwent primary video-assisted thoracoscopic surgery. In addition, no patient in the video-assisted thoracoscopic surgery group required fibrinolytic therapy, which was also statistically different from the thoracostomy drainage group. CONCLUSIONS: The outcomes of this study strongly suggest that primary video-assisted thoracoscopic surgery for evacuation of parapneumonic effusions is superior to conventional thoracostomy drainage.