Biomarker Changes in Response to Tofacitinib Treatment in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis.

Objective: We examine levels of candidate blood-based biomarkers (CBBs) in patients with juvenile idiopathic arthritis (JIA) treated with tofacitinib.

Methods: Patients with JIA who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBBs (S100A8/9, S100A12, interleukin-18 [IL-18], serum amyloid A, resistin, vascular endothelial growth factor, angiopoietin-1, angiopoietin-2, matrix metalloproteinase 8 [MMP8], MMP2, tissue inhibitor of metalloproteinases 1, leptin, chemokine [C-X-C motif] ligand 9, soluble IL-2 receptor, intercellular adhesion molecule 1, soluble tumor necrosis factor receptor, IL-6, IL-23, monocyte chemotactic protein 1, chemokine [C-C motif] ligand 18 [CCL18], and CCL20).

Nuclear PTEN enhances the maturation of a microRNA regulon to limit MyD88-dependent susceptibility to sepsis.

Sepsis-induced organ damage is caused by systemic inflammatory response syndrome (SIRS), which results in substantial comorbidities. Therefore, it is of medical importance to identify molecular brakes that can be exploited to dampen inflammation and prevent the development of SIRS. We investigated the role of phosphatase and tensin homolog (PTEN) in suppressing SIRS, increasing microbial clearance, and preventing lung damage.

SOCS1 is a negative regulator of metabolic reprogramming during sepsis.

Sepsis can induce an overwhelming systemic inflammatory response, resulting in organ damage and death. Suppressor of cytokine signaling 1 (SOCS1) negatively regulates signaling by cytokine receptors and Toll-like receptors (TLRs). However, the cellular targets and molecular mechanisms for SOCS1 activity during polymicrobial sepsis are unknown.

Estimating the probability of bacterial infection using a novel biomarker among pediatric patients in the emergency department.

Context: IL-27 is a novel biomarker to identify bacterial infection in children.

Objective: IL-27 was evaluated among pediatric emergency department (ED) patients and compared with procalcitonin (PCT).

Methods And Results: Children undergoing blood, urine, or cerebrospinal fluid cultures had IL-27 and PCT assays performed.

Glucocorticoid Receptor Expression in Peripheral WBCs of Critically Ill Children.

Objectives: To characterize glucocorticoid receptor expression in peripheral WBCs of critically ill children using flow cytometry.

Design: Prospective observational cohort.

Setting: A university-affiliated, tertiary PICU.

Comparing the prognostic performance of ASSIST to interleukin-6 and procalcitonin in patients with severe sepsis or septic shock.

Context: We recently derived and validated a multi-biomarker-based model (ASSIST) to stratify patients with sepsis based on initial mortality risk.

Objective: The objective of this study was to compare the performance of ASSIST to interleukin-6 (IL6) and procalcitonin (PCT).

Methods: The area-under-the-receiver operating characteristic curve for predicting 28-d mortality using ASSIST was compared with that of IL6 (n = 452) and PCT (n = 235).

Performance of interleukin-27 as a sepsis diagnostic biomarker in critically ill adults.

Purpose: We recently identified interleukin-27 (IL-27) as a sepsis diagnostic biomarker in children. Here we assess IL-27 as a sepsis diagnostic biomarker in critically ill adults with systemic inflammatory response syndrome and sepsis.

Methods: IL-27 and procalcitonin (PCT) were measured from plasma samples in three groups: no sepsis (n = 78), pulmonary source of sepsis (n = 66), and non-pulmonary source of sepsis (n = 43).

A multibiomarker-based outcome risk stratification model for adult septic shock*.

Objectives: Clinical trials in septic shock continue to fail due, in part, to inequitable and sometimes unknown distribution of baseline mortality risk between study arms. Investigators advocate that interventional trials in septic shock require effective outcome risk stratification. We derived and tested a multibiomarker-based approach to estimate mortality risk in adults with septic shock.

Interleukin 27 as a sepsis diagnostic biomarker in critically ill adults.

Purpose: We previously identified interleukin 27 (IL-27) as a sepsis diagnostic biomarker in critically ill children. The current study tested the performance of IL-27 alone and in combination with procalcitonin (PCT) for diagnosing sepsis in critically ill adults.

Methods: Serum samples were made available from a prior prospective study of sepsis biomarkers in critically ill adults.

Genome-wide expression profiling in pediatric septic shock.

For nearly a decade, our research group has had the privilege of developing and mining a multicenter, microarray-based, genome-wide expression database of critically ill children (≤10 y of age) with septic shock. Using bioinformatic and systems biology approaches, the expression data generated through this discovery-oriented, exploratory approach have been leveraged for a variety of objectives, which are reviewed here. Fundamental observations include widespread repression of gene programs corresponding to the adaptive immune system and biologically significant differential patterns of gene expression across developmental age groups.

Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.

Human septic shock involves multiple genome-level perturbations. We have conducted microarray analyses in children with septic shock within 24 h of intensive care unit admission, using whole blood-derived RNA. Based on sequential statistical and expression filters, there were 2,482 differentially regulated gene probes (1,081 upregulated and 1,401 downregulated) between patients with septic shock (n = 42) and controls (n = 15).