Sepsis From one-size-fits-all to personalized medicine

This thesis explores strategies for managing sepsis, from one-size-fits-all to personalized medicine. We investigated early detection through the Modified Early Warning Score, which proved to be a sensitive predictor of ICU admission for patients with hematologic malignancies, a group particularly vulnerable to sepsis. Our examination of fluid management in sepsis and acute respiratory distress syndrome revealed that higher fluid balances are associated with adverse outcomes, including the deresuscitation phase post-septic shock. By utilizing blood transcriptomic profiling, we identified different sepsis endotypes that respond variably to common treatment modalities in the ICU. Our extensive scoping review of all literature available on immunotherapy in sepsis highlighted personalized approaches. We introduce the ImmunoSep trial aimed at providing immunotherapy based on individual immunological profiles. Finally, we explored a novel treatment targeting histones – key damage-associated molecular patterns in the pathogenesis of sepsis. A phase I trial in critically ill sepsis patients confirmed the safety and potential efficacy of the histone-neutralizing agent M6229, offering new directions for clinical application and research.