Stefan Rußwurm

Outcome prediction by traditional and new markers of inflammation in patients with sepsis.

Abstract Patients (n = 242) admitted to intensive care unit for longer than 48 hours were categorised for sepsis according to American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference criteria. Body temperature, leukocyte count, C-reactive protein (CRP) and procalcitonin (PCT) as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, IL-10 and HLA-DR expression on monocytes were determined. Data of one randomly choosen day per patient entered analysis. Immunologic mediators contributing significantly to outcome were determined by logistic regression analysis. Area under the curves (AUC) of receiver operating characteristic curves of clinical markers of inflammation predicting prognosis were compared with AUC of relevant immunologic mediators. TNF-α, IL-6 and HLA-DR expression on monocytes were significantly associated with outcome; the AUCs were 0.835, 0.844 and 0.761 respectively. AUCs for clinical markers were 0.878, 0.811, 0.620 and 0.614 for PCT, CRP, leukocyte count and body temperature respectively. PCT had the highest AUC compared to other clinical markers. These data indicate that PCT might be a better marker than the classic criteria of inflammation, CRP, leukocyte count, and body temperature to identify patients endangered by severe infection or sepsis.

Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin‐ceramide pathway in human macrophages

© 1997 Federation of European Biochemical Societies.

A Transcriptomic Biomarker to Quantify Systemic Inflammation in Sepsis — A Prospective Multicenter Phase II Diagnostic Study

Development of a dysregulated immune response discriminates sepsis from uncomplicated infection. Currently used biomarkers fail to describe simultaneously occurring pro- and anti-inflammatory responses potentially amenable to therapy. Marker candidates were screened by microarray and, after transfer to a platform allowing point-of-care testing, validated in a confirmation set of 246 medical and surgical patients. We identified up-regulated pathways reflecting innate effector mechanisms, while down-regulated pathways related to adaptive lymphocyte functions. A panel of markers composed of three up- (Toll-like receptor 5; Protectin; Clusterin) and 4 down-regulated transcripts (Fibrinogen-like 2; Interleukin-7 receptor; Major histocompatibility complex class II, DP alpha1; Carboxypeptidase, vitellogenic-like) described the magnitude of immune alterations. The created gene expression score was significantly greater in patients with definite as well as with possible/probable infection than with no infection (median (Q25/Q75): 80 (60/101)) and 81 (58/97 vs. 49 (27/66), AUC-ROC = 0.812 (95%-CI 0.755–0.869), p < 0.0001). Down-regulated lymphocyte markers were associated with prognosis with good sensitivity but limited specificity. Quantifying systemic inflammation by assessment of both pro- and anti-inflammatory innate and adaptive immune responses provides a novel option to identify patients-at-risk and may facilitate immune interventions in sepsis.