No abstract

Objective Septic shock heterogeneity has important implications for clinical trial implementation and patient management. We previously addressed this heterogeneity by identifying 3 putative subclasses of children with septic shock based exclusively on a 100-gene expression signature. Here we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. Design Prospective observational study involving microarray-based bioinformatics. Setting Multiple pediatric intensive care units in the United States. Patients Separate derivation (n=98) and validation (n=82) cohorts of children with septic shock. Interventions None other than standard care. Measurements and Main Results Gene expression mosaics of the 100 class-defining genes were generated for 82 individual patients in the validation cohort. Using computer-based image analysis, patients were classified into 1 of 3 subclasses (“A”, “B”, or “C”) based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. After subclassification, the clinical database was mined for phenotyping. Subclass A patients had higher illness severity relative to subclasses B and C, as measured by maximal organ failure, fewer ICU-free days, and a higher PRISM score. Patients in subclass A were characterized by repression of genes corresponding to adaptive immunity and glucocorticoid receptor signaling. Separate subclass assignments were conducted by 21 individual clinicians, using visual inspection. The consensus classification of the clinicians had modest agreement with the computer algorithm. Conclusions We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses have relevant clinical differences.

Objective-To develop a clinically feasible stratification strategy for pediatric septic shock using gene expression mosaics and a 100-gene signature representing the first 24 hours of admission to the pediatric intensive care unit.Design-Prospective observational study involving microarray-based bioinformatics. Setting-Multiple pediatric intensive care units in the United States.Patients-Ninety-eight children with septic shock. Interventions-None other than standard care.Measurements and Main Results-Patients were classified into 3 previously published, genome-wide, expression-based sub-classes (sub-classes A, B, and C) having clinically relevant phenotypic differences. The class-defining 100-gene signature was depicted for each individual patient using mosaics generated by the Gene Expression Dynamics Inspector (GEDI). Composite mosaics were generated representing the average expression patterns for each of the 3 sub-classes. Nine individual clinicians served as blinded evaluators. Each evaluator was shown the 98 individual patient mosaics and asked to classify each patient into one of the three sub-classes using the composite mosaics as the reference point. The respective sensitivities, specificities, positive predictive values, and negative predictive values of the sub-classification strategy were ≥84% across the 3 sub-classes. The classification strategy also generated positive likelihood ratios ≥16.8 and negative likelihood ratios ≤0.2 across the three sub-classes. The kappa coefficient across all possible inter-evaluator comparisons was 0.81.Conclusions-We have provided initial evidence (proof of concept) for a clinically feasible and robust stratification strategy for pediatric septic shock based on a 100 gene signature and gene expression mosaics.

Study objective The impact of public health interventions during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic on critical illness in children has not been studied. We seek to determine the impact of SARS‐CoV‐2 related public health interventions on emergency healthcare utilization and frequency of critical illness in children. Methods This was an interrupted time series analysis conducted at a single tertiary pediatric emergency department (PED). All patients evaluated by a provider from December 31 through May 14 of 6 consecutive years (2015‐2020) were included. Total patient visits (ED and urgent care), shock trauma suite (STS) volume, and measures of critical illness were compared between the SARS‐CoV‐2 period (December 31, 2019 to May 14, 2020) and the same period for the previous 5 years combined. A segmented regression model was used to explore differences in the 3 outcomes between the study and control period. Results Total visits, STS volume, and volume of critical illness were all significantly lower during the SARS‐CoV‐2 period. During the height of public health interventions, per day there were 151 fewer total visits and 7 fewer patients evaluated in the STS. The odds of having a 24‐hour period without a single critical patient were >5 times higher. Trends appeared to start before the statewide shelter‐in‐place order and lasted for at least 8 weeks. Conclusions In a metropolitan area without significant SARS‐CoV‐2 seeding, the pandemic was associated with a marked reduction in PED visits for critical pediatric illness.

Ventilator-associated tracheobronchitis is a clinically significant hospital-acquired infection in the PICU and is associated with longer duration of mechanical ventilation and healthcare costs, possibly through causing a longer PICU length of stay. Quality improvement efforts should be directed at reducing the incidence of ventilator-associated tracheobronchitis in the PICU.

To use improved situation awareness to decrease cardiopulmonary resuscitation events by 25% over 18 months and demonstrate process and outcome sustainability.

The best possible care of critically ill patients can be rendered when physicians of various specialties, nurses, and allied health professionals join forces and treat problems together." --Ake Grenvik

To report the prevalence of adverse events in children undergoing apnea testing as part of the determination of death by neurologic criteria (DNC). DESIGN: Single-center, retrospective study. SETTING: Academic children's hospital that is a Level I Trauma Center. PATIENTS: All children who underwent apnea testing to determine DNC from July 2013 to June 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:We abstracted the medical history, blood gases, ventilator settings, blood pressures, vasoactive infusions, intracranial pressures, chest radiographs, and echocardiograms for all apnea tests as well as any ancillary test. Adverse events were defined as hypotension, hypoxia, pneumothorax, arrhythmia, intracranial hypertension, and cardiac arrest. Fifty-eight patients had 105 apnea tests. Adverse events occurred in 21 of 105 apnea tests (20%), the most common being hypotension (15/105 [14%]) and hypoxia (4/105 [4%]). Five of 21 apnea tests (24%) with adverse events were terminated prematurely (three for hypoxia, one for hypotension, and one for both hypoxia and hypotension) but the patients did not require persistent escalation in care. In the other 16 of 21 apnea tests (76%) with adverse events, clinical changes were transient and managed by titrating vasoactive infusions or completing the apnea test. CONCLUSIONS:In our center, 20% of all apnea tests were associated with adverse events. Only 5% of all apnea tests required premature termination and the remaining 15% were completed and the adverse events resolved with medical care.