Abstract
Sepsis diagnosis remains based largely on clinical presentation despite significant advances in the understanding of underlying pathophysiology and host-pathogen interactions. The systematic review article by Zonneveld and colleagues in the previous issue of Critical Care describes another potential avenue of study for using biomarkers for sepsis diagnosis and prognostication. Soluble leukocyte adhesion molecules and their associated sheddase enzymes vary in detectable levels and activity in patients in relation to immunologic status, age, and systemic inflammation, including in the setting of sepsis. Unfortunately, studies of these molecules as diagnostic or prognostic aids (or both) in sepsis have thus far been disappointing. Zonneveld and colleagues propose two potential avenues to enhance the performance characteristics of soluble adhesion molecules and their sheddases in sepsis diagnosis and prognosis: (a) identifying age-adjusted normal values for soluble leukocyte adhesion molecules and their sheddases and (b) investigating simultaneous measurement of both soluble adhesion molecules and sheddases in integrated sepsis evaluation schema. This commentary discusses the proposed solutions of Zonneveld and colleagues in more detail and outlines additional considerations that should be addressed in order to develop robust and valid diagnostic and prognostic tools for clinicians managing patients with sepsis.
Highlights
The article by Zonneveld and colleagues [1] in the previous issue of Critical Care highlights the ongoing challenge in identifying and treating septic patients
Despite research describing much of the underlying pathophysiology, sepsis remains a diagnosis based primarily on clinical presentation [2]
The sheddase enzymes catalyzing the release of their soluble fragments into the bloodstream, participate in the homeostasis of immune responses that direct leukocytes to sites of injury, infection, and/or inflammation
Summary
The article by Zonneveld and colleagues [1] in the previous issue of Critical Care highlights the ongoing challenge in identifying and treating septic patients. Proposed avenues of inquiry First, the authors posit that understanding the variation in circulating levels of soluble adhesion molecules and sheddases by patient age will help better define normal values in neonatal, pediatric, and adult sepsis More accurately defining these normal ranges could improve the diagnostic and prognostic accuracy of these molecules in sepsis. As a simple rule of thumb, 10 mortality events are required for each potential predictor variable and 20% of patients with sepsis die, for 10 potential predictors (not including interactions) to be identified, a minimum of 500 patients with severe sepsis would need to be enrolled to perform such an analysis, which represents a major effort This commitment is critical, to developing tools and strategies to improve prognostication, incorporate evolving insights into sepsis pathophysiology, and use this information to better tailor therapy and improve outcomes
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