Aiming for precision: personalized medicine through sepsis subtyping.

According to the latest definition, sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to an infection. However, this definition fails to grasp the heterogeneous nature and the underlying dynamic pathophysiology of the syndrome. In response to this heterogeneity, efforts have been made to stratify sepsis patients into subtypes, either based on their clinical presentation or pathophysiological characteristics.

Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness.

Rationale: Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.

Objectives: To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality.

Methods: We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS).

Longitudinal assessment of immunoglobulin response and disease progression in critically ill patients with community acquired pneumonia.

Background: Low endogenous immunoglobulin(Ig)-levels are common in critically ill patients with sepsis, but it is unknown whether low Ig-levels are associated with poor outcome, and in which patients Ig-replacement therapy (IgRT) improves outcome. Given the crucial role of immunoglobulins in eliminating certain encapsulated pathogens, we examined the relationship between serial Ig-levels and disease course in critically ill patients with community acquired pneumonia (sCAP) caused by encapsulated or other pathogens.

Methods: We included a cohort of consecutive critically ill patients with CAP, and PaO/FiO-ratio < 200 with or without septic shock, from an existing biorepository where microbiological causes of infection had been adjudicated in a protocolized manner.

International multi-cohort analysis identifies novel framework for quantifying immune dysregulation in critical illness: results of the SUBSPACE consortium.

Progress in the management of critical care syndromes such as sepsis, Acute Respiratory Distress Syndrome (ARDS), and trauma has slowed over the last two decades, limited by the inherent heterogeneity within syndromic illnesses. Numerous immune endotypes have been proposed in sepsis and critical care, however the overlap of the endotypes is unclear, limiting clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine through the sharing of transcriptomic data.

Clinical Subtype Trajectories in Sepsis Patients Admitted to the ICU: A Secondary Analysis of an Observational Study.

Objectives: Sepsis is an evolving process and proposed subtypes may change over time. We hypothesized that previously established sepsis subtypes are dynamic, prognostic of outcome, and trajectories are associated with host response alterations.

Design: A secondary analysis of two observational critically ill sepsis cohorts: the Molecular diAgnosis and Risk stratification of Sepsis (MARS) and the Medical Information Mart for Intensive Care-IV (MIMIC-IV).