Authors
Sascha David, Rolf Erlebach, Alix Buhlmann, Mattia Müller
Published in
Medizinische Klinik, Intensivmedizin und Notfallmedizin. Sep 15, 2026. Epub Sep 15, 2026.
Abstract
Sepsis is a life-threatening organ dysfunction due to a pathological host response to infection. Despite decades of research, there is still very limited evidence for causal therapeutic approaches targeting this injurious host response. The discrepancy between steadily increasing biological understanding and limited clinical progress is often referred to as the "translational gap." On the one hand, randomized trial designs have focused on heterogeneous patient populations, and on the other, they have mostly used mortality as the primary endpoint. As a result, there is a risk that potentially effective interventions are diluted across biologically diverse patient groups, making relevant effects statistically undetectable. The large number of negative sepsis trials has not only led to fatigue among researchers, but also to concerns about financial risks within the research-driven pharmaceutical industry. More recent studies, however, suggest that precision medicine approaches could offer a way out of this situation. Recent investigations such as ANDROMEDA SHOCK 2, ImmunoSep, and Tigris use physiological or immunological phenotypes for patient selection and combine these with innovative endpoints and modern statistical methods. Together, they demonstrate that a stronger focus on the underlying pathophysiology can reveal clinically relevant benefits that remain hidden in conventional trial designs. These developments mark a fundamental shift in sepsis research: away from universal treatment concepts for everybody and toward individualized, biologically grounded, and adaptive therapeutic strategies.
PMID:
42742689
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.
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