The pediatric sepsis biomarker risk model

Abstract

IntroductionThe intrinsic heterogeneity of clinical septic shock is a major challenge. For clinical trials, individual patient management, and quality improvement efforts, it is unclear which patients are least likely to survive and thus benefit from alternative treatment approaches. A robust risk stratification tool would greatly aid decision-making. The objective of our study was to derive and test a multi-biomarker-based risk model to predict outcome in pediatric septic shock.MethodsTwelve candidate serum protein stratification biomarkers were identified from previous genome-wide expression profiling. To derive the risk stratification tool, biomarkers were measured in serum samples from 220 unselected children with septic shock, obtained during the first 24 hours of admission to the intensive care unit. Classification and Regression Tree (CART) analysis was used to generate a decision tree to predict 28-day all-cause mortality based on both biomarkers and clinical variables. The derived tree was subsequently tested in an independent cohort of 135 children with septic shock.ResultsThe derived decision tree included five biomarkers. In the derivation cohort, sensitivity for mortality was 91% (95% CI 70 - 98), specificity was 86% (80 - 90), positive predictive value was 43% (29 - 58), and negative predictive value was 99% (95 - 100). When applied to the test cohort, sensitivity was 89% (64 - 98) and specificity was 64% (55 - 73). In an updated model including all 355 subjects in the combined derivation and test cohorts, sensitivity for mortality was 93% (79 - 98), specificity was 74% (69 - 79), positive predictive value was 32% (24 - 41), and negative predictive value was 99% (96 - 100). False positive subjects in the updated model had greater illness severity compared to the true negative subjects, as measured by persistence of organ failure, length of stay, and intensive care unit free days.ConclusionsThe pediatric sepsis biomarker risk model (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl) reliably identifies children at risk of death and greater illness severity from pediatric septic shock. PERSEVERE has the potential to substantially enhance clinical decision making, to adjust for risk in clinical trials, and to serve as a septic shock-specific quality metric.

Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

“…However, these studies used International Classification of Diseases, Ninth Revision (ICD-9), codes, which have been shown to capture a lower severity of illness and thereby underestimate mortality (5,7). In a recent database study using expanded ICD-9 coding, researchers reported a PICU mortality of 26.4% (6), and authors of prospective studies have reported short-term mortality rates up to 24% (2,5,19,46,47). The mortality in the present study also reflects the high rate of multiorgan dysfunction.…”

Сучасні Уявлення Про Патогенез І Діагностику Гнійно-Септичних Станів У Дітей (Частина 2)

“…Пошук чутливих маркерів ССЗР і сепсису залиша-ється актуальним питанням [23]. За даними аналітичних оглядів, за останні роки було вивчено більше ніж 178 біомаркерів сепсису [24][25][26].…”

“…А з іншого боку, його розглядають в якості перспективного маркера септичного процесу. Підвищення його рівня спостеріга-ється у хворих дітей з бактеріологічно підтвердженим сепсисом і септичною енцефалопатією [23].…”

“…Утворюється вна-слідок каскаду реакцій з mCD14 -мембранного рецеп-тора макрофагів при зв'язуванні бактерій рецептором TLR4 [21,23].…”

“…Після активації фа-гоцитозу катепсин D та інші протеїнази розщеплюють циркулюючий sCD14 з утворенням його вкороченого фрагменту sCD14-ST (субтипу), який і отримав назву пре-сепсин [23,33]. У нормі його концентрація дуже низька.…”