ABSTRACT
OBJECTIVES: Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions. DESIGN: Ambidirectional multisite cohort study. SETTING: Four tertiary children's hospitals. PATIENTS: Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication (p < 0.0001) and contributed to a decision to consult palliative care (p < 0.02). CONCLUSIONS: In this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.
ABSTRACT
BACKGROUND: Pediatric severe sepsis is a public health problem with significant morbidities in those who survive. In this article, we aim to present an overview of the important studies highlighting the limited data available pertaining to long-term outcomes of survivors of pediatric severe sepsis. MATERIALS AND METHODS: A review of literature available was conducted using PUBMED/Medline on pediatric severe sepsis outcomes. Long-term outcomes and health-related quality of life (HRQL) following severe sepsis was defined as any outcome occurring after discharge from the hospital following an episode of severe sepsis which affected either the survivor or the survivor's family members. RESULTS: Many children are discharged with worse clinical and functional outcomes, depending on their diagnosis, treatments received, psychological effects, and the impact of their illness on their parents. Additionally, they utilize healthcare services more than their peers and are often readmitted soon after discharge. However, pediatric HRQL studies with worthwhile outcome measures are limited and the current data on pediatric sepsis is mainly retrospective. CONCLUSIONS: There is significant and longstanding morbidity seen in children and their families following a severe sepsis illness. Further prospective data are required to study the long-term outcomes of sepsis in the pediatric population.