Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study

• DOI: 10.1007/s00134-021-06574-0
• Publication Date: 2021-12-13T14:03:35Z
• Authors: Hessel Peters-Sen...; Joe M. Butler; Fabrice Uhel; Marcus J. Schultz; Marc J. Bonten; Olaf L. Cremer; Brendon P. Scicluna; Lonneke A. van Vught; Tom van der Poll; ; Friso M. de Beer; Lieuwe D. J. Bos; Gerie J. Glas; Roosmarijn T. M. ...; Janneke Horn; Laura R. A. Schouten; Marleen Straat; Luuk Wieske; Esther Witteveen; Tom D. Y. Reijnders; Alex R. Schuurman; Tjitske S. R. van...; Liza Pereverzeva; Arie J. Hoogendijk; Mischa A. Huson; Maryse A. Wiewel; Peter M. C. Klein...; David S. Y. Ong; Jos F. Frencken; Maria E. Koster-B...; Kirsten van de Groep; Diana M. Verboom
• Keywords: Endothelial Activation

There is limited knowledge on how the source of infection impacts host response to sepsis. We aimed compare in sepsis patients with a single, known at admission (< 24 h) intensive care unit.From molecular diagnosis and risk stratification (MARS) prospective cohort, we measured 16 plasma biomarkers reflective key pathways 621 patients. In subgroup (n = 335), blood leukocyte transcriptomes were compared between sources. Differences clinical patient profiles survival whole cohort 2019).The biomarker was categorized into originating from respiratory tract 334, 53.8%), abdomen 159, 25.6%), urinary 44, 7.1%), cardiovascular 41, 6.6%), central nervous system (CNS) 18, 2.9%), or skin 25, 4%). This analysis revealed stronger inflammatory cytokine responses, loss vascular integrity coagulation activation abdominal relative respiratory. Endothelial cell prominent urinary, infections, while CNS associated least aberrations. The transcriptional showed largest overlap pulmonary infections (76% common); notable differences sources detected regarding hemostasis, signaling, innate adaptive immune, metabolic pathways. After adjustment for confounders, remained an independent contributor 30-day mortality (unadjusted p 0.001, adjusted 0.028).Sepsis heterogeneity partly explained by source-specific dysregulations should be considered when selecting trials testing immune modulatory drugs.