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Learning Objectives: Biomarker facilitated sepsis diagnosis is needed given specificity limitations of clinical diagnostics. Sepsis-mediated host immune gene expression may represent a novel diagnostic approach. An RT-qPCRbased test, SeptiCyte® Lab, that quantifies expression levels of 4 genes involved in the septic host response, has been validated for septic adults. Herein we report the first investigation of SeptiCyte® Lab in a pediatric critical care setting. Methods: We conducted an IRB-approved, prospective, observational study enrolling 12 children undergoing CPB surgery to repair congenital heart disease (CHD; infection negative) and 28 children with clinical severe sepsis (CSS; 16 culture+, 12 culture-). Septic children had confirmed/suspected infection (microbial culture orders, antimicrobial prescription), exhibited SIRS criteria, and demonstrated cardiovascular ± pulmonary organ dysfunction. Immune competent and incompetent patients were included in the sepsis cohort. Demographic and admission illness severity data were collected. Next-generation sequencing (Illumina Mi-Seq) and RT-qPCR were used to analyze the transcriptome from peripheral blood collected at PICU admission. Results: CHD◊CSS descriptive data included age: 8.0 ± 6.2◊9.6 ± 6.4; gender: 42◊50% male; PRISM III: 6.2 ± 5.0◊7.8 ± 5.7; PELOD: 5.0 ± 2.9◊4.5 ± 2.6. SeptiCyte® Lab gene expression biomarkers strongly differentiated CHD and CSS patients (AUC 0.955; 95% CI: 0.88-1.00). SeptiCyte® Lab performance was similar when the samples were reanalyzed using RT-qPCR. There was no correlation (R2=0.01) between the SeptiCyte® Lab score and PRISM score, indicating that information provided by SeptiCyte® Lab is independent of illness severity, but instead reflects of the probability of sepsis. Conclusions: Our pilot investigation of SeptiCyte® Lab in a pediatric critical care setting demonstrates that this adult-derived gene signature may also facilitate diagnosis of sepsis in critically ill children. A broader investigation of the performance of the test among children with more heterogeneous care settings and infection diagnoses is warranted.

Introduction: LFLG severe AS (stroke volume index <35 mL/m2 or cardiac index <3.0 L/min/m2 and transvalvular aortic gradient <40 mmHg) is associated with worse clinical outcomes following surgical aortic valve replacement. However, there is paucity of data regarding impact of low left ventricular flow and transvalvular gradient on outcomes following TAVR. We evaluated the impact of baseline LFLG on outcomes following TAVR in patients with severe AS at our institution. Hypothesis: Patients with LFLG severe AS undergoing TAVR will have a higher rate of adverse clinical outcomes. Methods: In a retrospective single center registry, we analyzed the clinical, 2D doppler-echocardiographic and outcome data in consecutive patients who underwent TAVR with the Edwards Sapien transcatheter aortic valve for symptomatic severe AS at our tertiary care hospital from March 2012 to April 2014. Patients with LFLG were compared to non-LFLG patients. Background medical data, clinical endpoints (defined by the Valve Academic Research Consortium-2), length of stay (LOS), readmissions and mortality, were compared between the two groups. Wilcoxon rank-sum and Fisher’s exact tests were used to evaluate the hypothesis. Results: LFLG was found in 66 (32%) out of 206 patients. Baseline characteristics were comparable between the LFLG and non-LFLG group, except significant difference in STS scores (12.1±8 vs. 9.9±8, p=0.011), prior aortic valve surgery (16.7% vs. 6.4%, p=0.041) and atrial fibrillation/flutter (57.6% vs. 29.3% (p<0.001). Overall, peri-procedural complications were similar between both groups, however, LFLG patients required: longer ICU monitoring (113.8±175 vs. 67.3±97 hours, p=0.01), longer hospital LOS (14.2±11.7 vs. 10.5±7.7 days, p=0.032). These patients had a non-significant trend toward 30 day mortality (7.6 vs. 4.3%, p=0.335) but a significantly higher 1-year all-cause mortality (19.7% vs. 9.3% p=0.044). Conclusions: LFLG patients had higher co-morbidities but comparable peri-procedural complications and short-term mortality. However this group was associated with longer hospitalizations and higher 1-year all-cause-mortality following TAVR. Further studies are needed to fully define outcomes in LFLG patients.