Association of viral load with TRAIL, IP-10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: A prospective, multicentre cohort study.

BACKGROUND: To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. STUDY DESIGN: In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. RESULTS: Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy. CONCLUSION: These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

Functional echocardiographic assessment of myocardial performance in anemic premature infants: a pilot study.

This prospective observational study conducted in a neonatal intensive care unit aimed to evaluate echocardiographic changes provoked by anemia and transfusion of packed red blood cells (pRBCs) in premature infants. In this study, 32 anemic premature infants had serial echocardiographic assessment of left ventricular (LV) systolic performance, LV preload, and afterload immediately before, within 48 h, and up to 120 h after the transfusion of pRBCs. Pretransfusional evaluations also were compared with similar assessments of 71 nonanemic inpatient premature infants analogous for sex, gestational age at birth, and postnatal age. Left ventricular systolic performance was estimated from fractional shortening, LV output, and LV myocardial performance index (LVMPI). The LV preload was estimated from the LV end-diastolic dimension and the ratio of left atrium-to-aortic root dimension (LA/Ao ratio). The LV afterload was estimated from end-systolic wall stress. The LVMPI was found to decrease with increasing corrected gestational age in both the nonanemic (R = 0.173; p = 0.03) and anemic (R = 0.460; p = 0.007) infants. The LVMPI was the only index that changed after transfusion of pRBCs, decreasing in the younger anemic infants (p = 0.011) and increasing in the older anemic infants (p = 0.012). Finally, a significant inverse relationship between pre- and posttransfusional LVMPI values (R = 0.730; p < 0.001) was noted. The LVMPI may allow for identification of preterm infants more likely to be helped by transfusion of pRBCs.

A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study.

OBJECTIVES: Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies have shown that a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon-γ-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. METHODS: This prospective, multicentre cohort study, entitled AutoPilot-Dx, aimed to validate signature performance and to estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data. RESULTS: In total, 1140 patients were recruited (February 2017-December 2018), of which 1008 met the eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with a sensitivity of 93.7% (95%CI 88.7-98.7), a specificity of 94.2% (92.2-96.1), positive predictive value of 73.0% (65.0-81.0), and negative predictive value of 98.9% (98.0-99.8); in 9.8% the test results were equivocal. The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients. CONCLUSIONS: The findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections.

Clonidine treatment for agitation in children after sevoflurane anesthesia.

Clonidine is effective in treating sevoflurane-induced postanesthesia agitation in children. We conducted a study on 169 children to quantify the risk reduction of clonidine agitation in patients admitted to our day-surgery pediatric clinic. Children were randomly allocated to receive clonidine 2 mug/kg or placebo before general anesthesia with sevoflurane that was also supplemented with a regional or central block. An observer blinded to the anesthetic technique assessed recovery variables and the presence of agitation. Pain and discomfort scores were significantly decreased in the clonidine group; the incidence of agitation was reduced by 57% (P = 0.029) and the incidence of severe agitation by 67% (P = 0.064). Relative risks for developing agitation and severe agitation were 0.43 (95% confidence interval, 0.24-0.78) and 0.32 (0.09-1.17), respectively. Clonidine produces a substantial reduction in the risk of postsevoflurane agitation in children.

The combined maternal administration of magnesium sulfate and aminophylline reduces intraventricular hemorrhage in very preterm neonates.

OBJECTIVE: To determine whether the adjunctive administration of aminophylline and magnesium sulfate to mothers at risk for preterm birth can reduce the rate of intraventricular hemorrhage in neonates born at less than 30 weeks of gestation. STUDY DESIGN: A prospective study was conducted to determine whether the rate of intraventricular hemorrhage was different in patients at risk for preterm delivery treated with ritodrine, magnesium sulfate, aminophylline, and corticosteroids (group A) versus patients treated with ritodrine and corticosteroids (group B). During the study period (January 1996 to December 2001), 125 patients enrolled in the study. Treatment was assigned by alternative allocation, and the study was designed to compare the rate of intraventricular hemorrhage in neonates born before the 30th week of gestation (primary outcome), 78 newborns in group A and 68 in group B. The proportion of neonates with intraventricular hemorrhage was calculated, and data were analyzed with Student t test, chi 2 , and logistic regression analysis. RESULTS: The frequency of severe respiratory distress syndrome needing surfactant replacement and high-pressure positive ventilation, patent ductus arteriosus, and retinopathy of prematurity was not different between the 2 groups. However, the rate of intraventricular hemorrhage was lower in neonates born before 30 weeks whose mothers received adjunctive aminophylline and magnesium sulphate (group A) than in the group that did not receive these 2 agents (group B). The overall frequency of intraventricular hemorrhage was 5.1% (4/78) versus 20.6% (14/68) ( P < .001), and the frequency of intraventricular hemorrhage grade 3-4 was 1.3% (1/78) versus 10.3 % (7/68; P < .001), respectively. CONCLUSION: Adjunctive maternal administration of aminophylline and magnesium sulfate was associated with a significant reduction in the rate of intraventricular hemorrhage in neonates born before 30 completed weeks.