Sepsis and Scientific Revolutions

Abstract

A sustained paradigm shift in the approach to treating sepsis has yet to emerge, but recent data suggest that an open-minded posture informed by novel pathobiologic findings may eventually bear fruit.

The future of murine sepsis and trauma research models

“…Although advances in critical care have substantially improved the initial mortality associated with sepsis and trauma, many patients who survive the initial injury succumb from complications [10][11][12][13][14]. To date, immune modulation therapy and pharmacotherapeutic agents have proven disappointing in regards to modifying any human outcome, despite promising results from preclinical studies [15] Much of this preclinical work was done in rodent models [15]. Thus, despite decades of promising preclinical and clinical investigations that have elucidated individual aspects of the complex pathophysiology present in infection and injury, our understanding of these entities remains incomplete, and few therapies have successfully improved outcome in these critically ill patients [16][17][18].…”

Sepsis ve Ekstrakorporeal Membran Oksijenizasyonu

“…Sistemik yanıtın mekanizması ile ilişkili patofizyoloji "Toll" benzeri reseptörler ("Toll-like receptors"; TLRs)'in keşfi ile daha net ortaya çıkmış ve felsefik açıdan sepsisin anlaşılmasına önemli katkılar yapmıştır. Bununla birlikte immun yetersizliğin de sepsiste düşünülenden daha etkin olduğunun ortaya konulması, Opal ve ekibinin önerdiği, üzerinde düşünülmesi gereken yeni tedavi algoritmasını gündeme getirmiştir (3,4).…”

Shedding metabo‘light’ on the search for sepsis biomarkers

“…Recent advances in ‘omic’ technologies have opened new opportunities for sepsis research. In a recent article published in Critical Care , Kamisoglu and colleagues [ 1 ] used metabolomics to assess whether responses elicited by endotoxin recapitulate, at least in part, those seen in clinical sepsis [ 2 ]. The study is primarily a retrospective in silico analysis of metabolomes obtained from subjects who participated in an experimental endotoxemia study [ 3 ] and from patients enrolled in the Community Acquired Pneumonia and Sepsis Outcome and Diagnostics (CAPSOD) study who after independent audit fulfilled criteria for sepsis and outcomes [ 4 ].…”

“…The important insights of the study are two: the clinical relevance of endotoxemia in sepsis, and the applicability of metabolomics as an analytical tool in sepsis. Because lipopolysaccharide acts through the TLR4, endotoxin challenge is a model of TLR4 agonist-induced SIRS [ 2 ]. The issue of the contribution of TLR signaling in sepsis will be difficult to unravel as these receptors are likely to be activated by both primary (pathogen-related) and secondary (host-related) events.…”