Metagenomic next-generation sequencing of bronchoalveolar lavage fluid from children with severe pneumonia in pediatric intensive care unit.

Background: Severe pneumonia due to lower respiratory tract infections (LRTIs) is a significant cause of morbidity and mortality in children. Noninfectious respiratory syndromes resembling LRTIs can complicate the diagnosis and may also make targeted therapy difficult because of the difficulty of identifying LRTI pathogens. In the present study, a highly sensitive metagenomic next-generation sequencing (mNGS) approach was used to characterize the microbiome of bronchoalveolar lavage fluid (BALF) in children with severe lower pneumonia and identify pathogenic microorganisms that may cause severe pneumonia. The purpose of this study was to use mNGS to explore the potential microbiomes of children with severe pneumonia in a PICU. Methods: We enrolled patients meeting diagnostic criteria for severe pneumonia admitted at PICU of the Children's Hospital of Fudan University, China, from February 2018 to February 2020. In total, 126 BALF samples were collected, and mNGS was performed at the DNA and/or RNA level. The pathogenic microorganisms in BALF were identified and correlated with serological inflammatory indicators, lymphocyte subtypes, and clinical symptoms. Results: mNGS of BALF identified potentially pathogenic bacteria in children with severe pneumonia in the PICU. An increased BALF bacterial diversity index was positively correlated with serum inflammatory indicators and lymphocyte subtypes. Children with severe pneumonia in the PICU had the potential for coinfection with viruses including Epstein-Barr virus, Cytomegalovirus, and Human betaherpesvirus 6B, the abundance of which was positively correlated with immunodeficiency and pneumonia severity, suggesting that the virus may be reactivated in children in the PICU. There was also the potential for coinfection with fungal pathogens including Pneumocystis jirovecii and Aspergillus fumigatus in children with severe pneumonia in the PICU, and an increase in potentially pathogenic eukaryotic diversity in BALF was positively associated with the occurrence of death and sepsis. Conclusions: mNGS can be used for clinical microbiological testing of BALF samples from children in the PICU. Bacterial combined with viral or fungal infections may be present in the BALF of patients with severe pneumonia in the PICU. Viral or fungal infections are associated with greater disease severity and death.

Early metabolic derangements and unfavorable outcomes in pediatric traumatic brain injury: a retrospective multi-center cohort study.

Background: To study the association in moderate and severe pediatric traumatic brain injury (TBI) between hyperglycemia, hyperlactatemia, acidosis and unfavorable outcome, as assessed by Pediatric Cerebral Performance Category (PCPC) on discharge from the pediatric intensive care unit (PICU). Methods: Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h). Results: Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died. Conclusions: We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.

Early posttraumatic seizures in pediatric traumatic brain injury: a multicenter analysis.

OBJECTIVE: Early posttraumatic seizures (EPTSs) in children after traumatic brain injury (TBI) increase metabolic stress on the injured brain. The authors sought to study the demographic and radiographic predictors for EPTS, and to investigate the association between EPTS and death, and between EPTS and poor functional outcomes among children with moderate to severe TBI in Asia. METHODS: A secondary analysis of a retrospective TBI cohort among participating centers of the Pediatric Acute & Critical Care Medicine Asian Network was performed. Children < 16 years of age with a Glasgow Coma Scale (GCS) score ≤ 13 who were admitted to pediatric intensive care units between January 2014 and October 2017 were included. Logistic regression analysis was performed to study risk factors for EPTS and to investigate the association between EPTS and death, and between EPTS and poor functional outcomes. Poor functional outcomes were defined as moderate disability, severe disability, and coma as defined by the Pediatric Cerebral Performance Category scale. RESULTS: Overall, 313 children were analyzed, with a median age of 4.3 years (IQR 1.8-8.9 years); 162 children (51.8%) had severe TBI (GCS score < 8), and 76 children (24.3%) had EPTS. After adjusting for age, sex, and the presence of nonaccidental trauma (NAT), only younger age was significantly associated with EPTS (adjusted odds ratio [aOR] 0.85, 95% CI 0.78-0.92; p < 0.001). Forty-nine children (15.6%) in the cohort died, and 87 (32.9%) of the 264 surviving patients had poor functional outcomes. EPTS did not increase the risk of death. After adjusting for age, sex, TBI due to NAT, multiple traumas, and a GCS score < 8, the presence of EPTS was associated with poor functional outcomes (aOR 2.08, 95% CI 1.05-4.10; p = 0.036). CONCLUSIONS: EPTSs were common among children with moderate to severe TBI in Asia and were associated with poor functional outcomes among children who survived TBI.

Early Coagulopathy in Pediatric Traumatic Brain Injury: A Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) Retrospective Study.

BACKGROUND: Although early coagulopathy increases mortality in adults with traumatic brain injury (TBI), less is known about pediatric TBI. OBJECTIVE: To describe the prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet levels of children with moderate to severe TBI to identify predictors of early coagulopathy and study the association with clinical outcomes. METHODS: Using the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) TBI retrospective cohort, we identified patients <16 yr old with a Glasgow Coma Scale (GCS) ≤13. We compared PT, APTT, platelets, and outcomes between children with isolated TBI and multiple trauma with TBI. We performed logistic regressions to identify predictors of early coagulopathy and study the association with mortality and poor functional outcomes. RESULTS: Among 370 children analyzed, 53/370 (14.3%) died and 127/370 (34.3%) had poor functional outcomes. PT was commonly deranged in both isolated TBI (53/173, 30.6%) and multiple trauma (101/197, 51.3%). Predictors for early coagulopathy were young age (adjusted odds ratio [aOR] 0.94, 95% CI 0.88-0.99, P = .023), GCS < 8 (aOR 1.96, 95% CI 1.26-3.06, P = .003), and presence of multiple trauma (aOR 2.21, 95% confidence interval [CI] 1.37-3.60, P = .001). After adjusting for age, gender, GCS, multiple traumas, and presence of intracranial bleed, children with early coagulopathy were more likely to die (aOR 7.56, 95% CI 3.04-23.06, P < .001) and have poor functional outcomes (aOR 2.16, 95% CI 1.26-3.76, P = .006). CONCLUSION: Early coagulopathy is common and independently associated with death and poor functional outcomes among children with TBI.

Traumatic Brain Injury Outcomes in 10 Asian Pediatric ICUs: A Pediatric Acute and Critical Care Medicine Asian Network Retrospective Study.

OBJECTIVES: Traumatic brain injury remains an important cause of death and disability. We aim to report the epidemiology and management of moderate to severe traumatic brain injury in Asian PICUs and identify risk factors for mortality and poor functional outcomes. DESIGN: A retrospective study of the Pediatric Acute and Critical Care Medicine Asian Network moderate to severe traumatic brain injury dataset collected between 2014 and 2017. SETTING: Patients were from the participating PICUs of Pediatric Acute and Critical Care Medicine Asian Network. PATIENTS: We included children less than 16 years old with a Glasgow Coma Scale less than or equal to 13. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We obtained data on patient demographics, injury circumstances, and PICU management. We performed a multivariate logistic regression predicting for mortality and poor functional outcomes. We analyzed 380 children with moderate to severe traumatic brain injury. Most injuries were a result of road traffic injuries (174 [45.8%]) and falls (160 [42.1%]). There were important differences in temperature control, use of antiepileptic drugs, and hyperosmolar agents between the sites. Fifty-six children died (14.7%), and 104 of 324 survivors (32.1%) had poor functional outcomes. Poor functional outcomes were associated with non-high-income sites (adjusted odds ratio, 1.90; 95% CI, 1.11-3.29), Glasgow Coma Scale less than 8 (adjusted odds ratio, 4.24; 95% CI, 2.44-7.63), involvement in a road traffic collision (adjusted odds ratio, 1.83; 95% CI, 1.04-3.26), and presence of child abuse (adjusted odds ratio, 2.75; 95% CI, 1.01-7.46). CONCLUSIONS: Poor functional outcomes are prevalent after pediatric traumatic brain injury in Asia. There is an urgent need for further research in these high-risk groups.