New Insights Into Multicenter PICU Mortality Among Pediatric Hematopoietic Stem Cell Transplant Patients*

Pediatric Critical Care Medicine

et al. 2016

Self Cite

Objective Despite declining mortality, ARDS is still involved in up to one third of pediatric intensive care deaths. The recently convened Pediatric Acute Lung Injury Consensus Conference has outlined research priorities for the field, which include the need for accurate bedside risk-stratification of patients. We aimed to develop a simple yet robust model of mortality risk among pediatric patients with ARDS to facilitate the targeted application of high-risk investigational therapies and stratification for enrollment in clinical trials. Design Prospective, multi-center cohort. Setting Five academic pediatric intensive care units. Patients 308 children ages >1 month and ≤ 18 years, admitted to the intensive care unit, with bilateral infiltrates on chest x-ray and P/F ratio <300 in the clinical absence of left atrial hypertension. Interventions None. Measurements and Main Results Twenty clinical variables were recorded in the following 6 categories: demographics, medical history, oxygenation, ventilation, radiographic imaging, and multi-organ dysfunction. Data were measured 0–24 and 48–72 hours after ARDS onset (Day 1 and Day 3) and examined for associations with hospital mortality. Among 308 enrolled patients, mortality was 17%. Children with a history of cancer and/or hematopoietic stem cell transplant (HSCT) had higher mortality (47% vs. 11%, p<0.001). Oxygenation index (OI), the P/F ratio, extrapulmonary organ dysfunction, PRISM-3, and positive cumulative fluid balance were each associated with mortality. Using two statistical approaches, we found that a parsimonious model of mortality risk using only OI and cancer/HSCT history performed as well as other more complex models that required additional variables. Conclusions In the pediatric intensive care unit, OI and cancer/HSCT history can be used on ARDS Day 1 or Day 3 to predict hospital mortality without the need for more complex models. These findings may simplify risk assessment for clinical trials, counseling families, and high-risk interventions such as extracorporeal life support.

Section: Discussionmentioning

confidence: 99%

A Simple and Robust Bedside Model for Mortality Risk in Pediatric Patients With Acute Respiratory Distress Syndrome*

Spicer

Calfee

Pediatric Critical Care Medicine

et al. 2016

Self Cite

“…We also tested for relationships with a history of hematopoietic cellular transplantation (HCT), which we have previously shown to significantly impact pediatric ARDS outcomes and plasma biomarkers (26–28). …”

Section: Methodsmentioning

confidence: 99%

Incorporating Inflammation into Mortality Risk in Pediatric Acute Respiratory Distress Syndrome

Orwoll

Spicer

et al. 2017

Critical Care Medicine

Self Cite

Objective In pediatric ARDS, lung injury is mediated by immune activation and severe inflammation. Therefore, we hypothesized that patients with elevated pro- and anti-inflammatory cytokines would have higher mortality rates and that these biomarkers could improve risk-stratification of poor outcomes. Design Multicenter prospective observational study. Setting We enrolled patients from 5 academic PICUs between 2008–2015. Patients Patients were 1 month to 18 years old, used noninvasive or invasive ventilation, and met the American European Consensus Conference definition of ARDS. Interventions None. Methods Eight pro-inflammatory and anti-inflammatory cytokines were measured on ARDS day 1 and correlated with mortality, ICU morbidity as measured by survivor PELOD score, and biomarkers of endothelial injury, including angiopoietin-2, von Willebrand Factor, and soluble thrombomodulin. Measurements & Main Results We measured biomarker levels in 194 patients, including 38 ARDS nonsurvivors. IL-6, IL-8, IL-10, IL-18, and TNF-R2 were each strongly associated with all-cause mortality, multiple markers of ICU morbidity, and endothelial injury. A multiple logistic regression model incorporating OI, IL-8, and TNF-R2 was superior to a model of OI alone in predicting the composite outcome of mortality or severe morbidity (AUROC 0.77 [0.70–0.83] vs. 0.70 [0.62–0.77], p=0.042). Conclusions In pediatric ARDS, pro- and anti-inflammatory cytokines are strongly associated with mortality, ICU morbidity, and biochemical evidence of endothelial injury. These cytokines significantly improve the ability of the OI to discriminate risk of mortality or severe morbidity and may allow for identification and enrollment of high-risk subgroups for future studies.

“…While significant progress has been made in improving the safety of anti-neoplastic and transplantation-based therapies, the risk of infectious complications remains high (4). In particular, lower respiratory tract infections in children who have undergone HCT are associated with mortality rates exceeding 45% (5,6). Current microbiologic diagnostics are inadequate and fail to identify a pathogenic organism in over one third of such cases (7).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

Dvorak

Mayday

et al. 2018

Preprint

RATIONALEDespite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant morbidity and mortality.OBJECTIVESTo develop a highly sensitive metagenomic next generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.METHODSWe collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014-2016. Samples underwent mechanical homogenization, paired RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the NCBI nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.MEASUREMENTS & MAIN RESULTSWe identified a rich cross-domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median 0.58, IQR 0.33-0.62 vs. median 0.94, IQR 0.93-0.95, p<0.001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (p<0.001).CONCLUSIONSAn optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.