Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in ...interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children.
We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score.
Common variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity.
We provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease.
To characterize the prevalence of pediatric critical illness from multisystem inflammatory syndrome in children (MIS-C) and to assess the influence of severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) strain on outcomes.
Retrospective cohort study.
Database evaluation using the Virtual Pediatric Systems Database.
All children with MIS-C admitted to the PICU in 115 contributing hospitals between January 1, 2020, and June 30, 2021.
Of the 145,580 children admitted to the PICU during the study period, 1,338 children (0.9%) were admitted with MIS-C with the largest numbers of children admitted in quarter 1 (Q1) of 2021 ( n = 626). The original SARS-CoV-2 viral strain and the D614G Strain were the predominant strains through 2020, with Alpha B.1.1.7 predominating in Q1 and quarter 2 (Q2) of 2021. Overall, the median PICU length of stay (LOS) was 2.7 days (25-75% interquartile range IQR, 1.6-4.7 d) with a median hospital LOS of 6.6 days (25-75% IQR, 4.7-9.3 d); 15.2% received mechanical ventilation with a median duration of mechanical ventilation of 3.1 days (25-75% IQR, 1.9-5.8 d), and there were 11 hospital deaths. During the study period, there was a significant decrease in the median PICU and hospital LOS and a decrease in the frequency of mechanical ventilation, with the most significant decrease occurring between quarter 3 and quarter 4 (Q4) of 2020. Children admitted to a PICU from the general care floor or from another ICU/step-down unit had longer PICU LOS than those admitted directly from an emergency department.
Overall mortality from MIS-C was low, but the disease burden was high. There was a peak in MIS-C cases during Q1 of 2021, following a shift in viral strains in Q1 of 2021. However, an improvement in MIS-C outcomes starting in Q4 of 2020 suggests that viral strain was not the driving factor for outcomes in this population.
New definitions of pediatric acute respiratory distress syndrome include criteria to identify a subset of children "at risk for pediatric acute respiratory distress syndrome." We hypothesized that, ...among PICU patients with bronchiolitis not immediately requiring invasive mechanical ventilation, those meeting at risk for pediatric acute respiratory distress syndrome criteria would have worse clinical outcomes, including higher rates of pediatric acute respiratory distress syndrome development.
Single-center, retrospective chart review.
Mixed medical-surgical PICU within a tertiary academic children's hospital.
Children 24 months old or younger admitted to the PICU with a primary diagnosis of bronchiolitis from September 2013 to April 2014. Children intubated before PICU arrival were excluded.
None.
Collected data included demographics, respiratory support, oxygen saturation, and chest radiograph interpretation by staff radiologist. Oxygen flow (calculated as FIO2 × flow rate L/min) was calculated when oxygen saturation was 88-97%. The median age of 115 subjects was 5 months (2-11 mo). Median PICU length of stay was 2.8 days (1.5-4.8 d), and median hospital length of stay was 5 days (3-10 d). The criteria for at risk for pediatric acute respiratory distress syndrome was met in 47 of 115 subjects (40.9%). Children who were at risk for pediatric acute respiratory distress syndrome were more likely to develop pediatric acute respiratory distress syndrome (15/47 31.9% vs 1/68 1.5%; p < 0.001), had longer PICU length of stay (4.6 d 2.8-10.2 d vs 1.9 d 1.0-3.1 d; p < 0.001) and hospital length of stay (8 d 5-16 d vs 4 d 2-6 d; p < 0.001), and increased need for invasive mechanical ventilation (16/47 34.0% vs 2/68 2.9%; p < 0.001), compared with those children who did not meet at risk for pediatric acute respiratory distress syndrome criteria.
Our data suggest that the recent definition of at risk for pediatric acute respiratory distress syndrome can successfully identify children with critical bronchiolitis who have relatively unfavorable clinical courses.
Background
Little is known about the airway microbiome in intubated mechanically ventilated children. We sought to characterize the airway microbiome longitudinally and in association with clinical ...variables and possible ventilator‐associated infection (VAI).
Methods
Serial tracheal aspirate samples were prospectively obtained from mechanically ventilated subjects under 3 years old from eight pediatric intensive care units in the United States from June 2017 to July 2018. Changes in the tracheal microbiome were analyzed by sequencing bacterial 16S ribosomal RNA gene relative to subject demographics, diagnoses, clinical parameters, outcomes, antibiotic treatment, and the Ventilator‐Associated InfectioN (VAIN) score.
Results
A total of 221 samples from 58 patients were processed and 197 samples met the >1000 reads criteria (89%), with an average of 43,000 reads per sample. The median number of samples per subject was 3 (interquartile range IQR: 2–5), with a median VAIN score of 2 (IQR: 1–3). Proteobacteria was the highest observed phyla throughout the intubation period, followed by Firmicutes and Actinobacteria. Alpha diversity was negatively associated with days of intubation (p = .032) and VAIN score (p = .016). High VAIN scores were associated with a decrease of Mycobacterium obuense, and an increase of Streptococcus peroris, Porphyromonadaceae family (unclassified species), Veillonella atypica, and several other taxa. No specific pattern of microbiome composition related to clinically diagnosed VAIs was observed.
Conclusions
Our data demonstrate decreasing alpha diversity with increasing VAIN score and days of intubation. No specific microbiome pattern was associated with clinically diagnosed VAI.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The use of high flow nasal cannula (HFNC) has become widely used in pediatric intensive care units (PICUs) throughout the world. The rapid adoption has outpaced the number of studies evaluating the ...safety and efficacy in a variety of pediatric diseases/conditions.
This scoping review begins with the definition and mechanisms of action of HFNC and then follows with a review of the literature focused on studies performed on critically ill children cared for in the PICU. The PubMed database was searched with a pediatric filter from the time period 2000 to 2021.
The rapid adoption of HFNC in PICUs has largely been driven by changes in institutional practices and small observational studies. There is a lack of adequately powered studies evaluating patient-centered outcomes, such as intubation rates, mortality, PICU, and hospital length of stay. Given the wide variability in flow rates and clinical indications, more research is needed to better define effective flow rates for different disease states as well as markers of treatment success and failure. One particular entity that is poorly studied is the use of HFNC in those at risk for developing pediatric acute respiratory distress syndrome (PARDS).
Neurologic and functional morbidity occurs in ~30% of PICU survivors, and young children may be at particular risk. Bronchiolitis is a common indication for PICU admission among children less than 2 ...years old. Two single-center studies suggest that greater than 10-25% of critical bronchiolitis survivors have neurologic and functional morbidity but those estimates are 20 years old. We aimed to estimate the burden of neurologic and functional morbidity among more recent bronchiolitis patients using two large, multicenter databases.
Analysis of the Pediatric Health Information System and the Virtual Pediatric databases.
Forty-eight U.S. children's hospitals (Pediatric Health Information System) and 40 international (mostly United States) children's hospitals (Virtual Pediatric Systems).
Previously healthy PICU patients less than 2 years old admitted with bronchiolitis between 2009 and 2015 who survived and did not require extracorporeal membrane oxygenation or cardiopulmonary resuscitation.
None. Neurologic and functional morbidity was defined as a Pediatric Overall Performance Category greater than 1 at PICU discharge (Virtual Pediatric Systems subjects), or a subsequent hospital encounter involving developmental delay, feeding tubes, MRI of the brain, neurologist evaluation, or rehabilitation services (Pediatric Health Information System subjects).
Among 3,751 Virtual Pediatric Systems subjects and 9,516 Pediatric Health Information System subjects, ~20% of patients received mechanical ventilation. Evidence of neurologic and functional morbidity was present at PICU discharge in 707 Virtual Pediatric Systems subjects (18.6%) and more chronically in 1,104 Pediatric Health Information System subjects (11.6%). In both cohorts, neurologic and functional morbidity was more common in subjects receiving mechanical ventilation (27.5% vs 16.5% in Virtual Pediatric Systems; 14.5% vs 11.1% in Pediatric Health Information System; both p < 0.001). In multivariate models also including demographics, use of mechanical ventilation was the only variable that was associated with increased neurologic and functional morbidity in both cohorts.
In two large, multicenter databases, neurologic and functional morbidity was common among previously healthy children admitted to the PICU with bronchiolitis. Prospective studies are needed to measure neurologic and functional outcomes using more precise metrics. Identification of modifiable risk factors may subsequently lead to improved outcomes from this common PICU condition.
No guidelines are available regarding initiation of enteral nutrition in children with bronchiolitis on high-flow nasal cannula (HFNC) support. We hypothesized that the incidence of feeding-related ...adverse events (AEs) would not be associated with HFNC support.
This retrospective study included children ≤24 months old with bronchiolitis receiving HFNC in a PICU from September 2013 through April 2014. Data included demographics, respiratory support during feeding, and feeding-related AEs. Feeding-related AEs were extracted from nursing documentation and defined as respiratory distress or emesis. Feed route and maximum HFNC delivery were recorded in 8-hour shifts (6 am-2 pm, 2 pm-10 pm, and 10 pm-6 am).
70 children were included, with a median age of 5 (interquartile range IQR 2-10) months. HFNC delivery at feed initiation varied widely, and AEs related to feeding occurred rarely. Children were fed in 501 of 794 (63%) of nursing shifts, with AEs documented in only 29 of 501 (5.8%) of those shifts. The incidence of AEs at varying levels of respiratory support did not differ (
= .092). Children in the "early feeding" (fed within first 2 shifts) group (
= 22) had a shorter PICU length of stay (2.2 days IQR 1.4-3.9 vs 3.2 IQR 2.5-5.3,
= .006) and shorter duration of HFNC use (26.0 hours IQR 15.8-57.0 vs 53.5 IQR 37.0-84.8,
= .002), compared with children in the "late feeding" group (
= 48).
In this small, single-institution patient cohort, feeding-related AEs were rare and not related to the delivered level of respiratory support.
OBJECTIVESAlthough closed head injuries occur commonly in children, most do not have a clinically important traumatic brain injury (ciTBI) and do not require neuroimaging. We sought to determine ...whether the utilization of computed tomography of the head (CT-H) in children presenting to an emergency department (ED) with a closed head injury changed after publication of validated clinical prediction rules to identify children at risk of ciTBI by the Pediatric Emergency Care Applied Research Network (PECARN).
METHODSWe used the nationwide ED sample (2008–2013) to examine children visiting an ED after a mild closed head injury. Multiple patient and hospital characteristics were assessed.
RESULTSOf the 4,552,071 children presenting to an ED with a mild closed head injury, 1,181,659 (26.0%) underwent CT-H. Care was most commonly received at metropolitan teaching hospitals (43.5%) and varied markedly by geographic region. Overall, there were no significant changes in the nationwide rates of CT-H utilization in the period immediately after publication of the PECARN prediction rules. However, compared with metropolitan teaching hospitals, CT-H utilization increased significantly for patients treated at nonteaching hospitals and at nonmetropolitan hospitals.
CONCLUSIONSThere was no overall reduction in CT-H utilization after publication of the 2009 PECARN prediction rules. However, patients treated at metropolitan teaching hospitals were significantly less likely to undergo CT-H after 2009, suggesting some penetration of the PECARN tool in that setting. Further research should study patterns of CT-H utilization in nonteaching hospitals and nonmetropolitan hospitals to assess challenges for adoption of validated pediatric ciTBI prediction rules.
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