An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map.

Derivation and validation of a prognostic model for postoperative risk stratification of critically ill patients with faecal peritonitis.

Background: Prognostic scores and models of illness severity are useful both clinically and for research. The aim of this study was to develop two prognostic models for the prediction of long-term (6 months) and 28-day mortality of postoperative critically ill patients with faecal peritonitis (FP).

Methods: Patients admitted to intensive care units with faecal peritonitis and recruited to the European GenOSept study were divided into a derivation and a geographical validation subset; patients subsequently recruited to the UK GAinS study were used for temporal validation.

Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia.

Rationale: Heterogeneity in the septic response has hindered efforts to understand pathophysiology and develop targeted therapies. Source of infection, with different causative organisms and temporal changes, might influence this heterogeneity.

Objectives: To investigate individual and temporal variations in the transcriptomic response to sepsis due to fecal peritonitis, and to compare these with the same parameters in community-acquired pneumonia.

Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study.

Background: Effective targeted therapy for sepsis requires an understanding of the heterogeneity in the individual host response to infection. We investigated this heterogeneity by defining interindividual variation in the transcriptome of patients with sepsis and related this to outcome and genetic diversity.

Methods: We assayed peripheral blood leucocyte global gene expression for a prospective discovery cohort of 265 adult patients admitted to UK intensive care units with sepsis due to community-acquired pneumonia and evidence of organ dysfunction.

Association between trends in clinical variables and outcome in intensive care patients with faecal peritonitis: analysis of the GenOSept cohort.

Introduction: Patients admitted to intensive care following surgery for faecal peritonitis present particular challenges in terms of clinical management and risk assessment. Collaborating surgical and intensive care teams need shared perspectives on prognosis. We aimed to determine the relationship between dynamic assessment of trends in selected variables and outcomes.

Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort.

Introduction: Community acquired pneumonia (CAP) is the most common infectious reason for admission to the Intensive Care Unit (ICU). The GenOSept study was designed to determine genetic influences on sepsis outcome. Phenotypic data was recorded using a robust clinical database allowing a contemporary analysis of the clinical characteristics, microbiology, outcomes and independent risk factors in patients with severe CAP admitted to ICUs across Europe.

Sustained effects of thoracocentesis on oxygenation in mechanically ventilated patients.

Background And Objective: No consensus exists as to the benefit of pleural drainage in mechanically ventilated patients with conflicting data concerning the effects on gas exchange. We determined the effects on gas exchange over a 48-hour period of draining, by thoracocentesis, large volume pleural effusions.

Methods: A total of 15 thoracocenteses were performed in 10 mechanically ventilated patients with ultrasound evidence of pleural effusions predicted to be greater than 800 mL in volume.

Mannose-binding lectin polymorphisms in severe sepsis: relationship to levels, incidence, and outcome.

Mannose-binding lectin (MBL) genetic polymorphisms result in deficiency of the encoded protein and increased susceptibility to infection, especially in children and the immunocompromised. The objective of this study was to investigate the relationship between MBL-2 exon 1 and promoter -221 polymorphisms, plasma levels of the encoded protein, and the incidence and outcome of severe sepsis and septic shock. One hundred seventy-four white adult patients with severe sepsis or septic shock were recruited in a prospective multicenter study across eight intensive care units in the South of England, UK.

Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia.

Objective: To determine the diagnostic role of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in non-directed bronchial lavage fluid in ventilator-associated pneumonia (VAP).

Design: Non-directed bronchial lavage fluid and plasma were collected on alternate days in critically ill mechanically ventilated patients from the start of ventilatory support until complete weaning from the ventilator. Soluble TREM-1 levels were measured by an enzyme-linked immunosorbent assay.

Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia.

Objective: To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP).

Design: Non-directed bronchial lavage (NBL) was performed every 48 h in critically ill mechanically ventilated patients. Serial measurements of the cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-10 and the cytokine inhibitors soluble TNFalpha receptor type I (sTNFalphaRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA.