Biological Subphenotypes of Acute Respiratory Distress Syndrome Show Prognostic Enrichment in Mechanically Ventilated Patients without Acute Respiratory Distress Syndrome

Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment.Objectives: To determine whether these subphenotypes and their prognostic and potential for predictive enrichment could be extended to other patients in the ICU, irrespective of fulfilling the definition of ARDS.Methods: This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latentclass analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-day, 30-day mortality, and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and the presence of ARDS.Measurements and Main Results: We included 2,499 mechanically ventilated patients (674 with and 1,825 without ARDS). The cluster-derived "reactive" subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, higher 30-day mortality, and a lower probability of successful extubation while alive compared with the "uninflamed" subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles.Conclusions: The prognostic and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill patients

Characteristics of polyclonal endemicity of Pseudomonas aeruginosa colonization in intensive care units. Implications for infection control.

Division of Infectious Diseases, University Hospital Utrecht, The Netherlands. [email protected] We investigated the endemicity of Pseudomonas aeruginosa in intensive care units (ICUs) through analyses of surveillance cultures (from the rectum, stomach, oropharynx, and trachea; n = 1,089), and clinical cultures (n = 2,393) from 297 consecutive patients. Multiple isolates of P. aeruginosa (n = 353) were genotyped. Variables associated with acquisition of respiratory tract colonization (RTC) were tested in a risk factor analysis. The mean daily prevalence of colonization was 34%. On admission, 22 patients had intestinal colonization and 13 had RTC. Twenty patients acquired colonization in the intestinal and 24 in the respiratory tract. Forty-four different genotypes were found; 38 (86%) were isolated from individual patients only. In all, 37 patients had RTC with a total of 38 genotypes: 13 (34%) were colonized on admission, 9 (24%) acquired RTC with a novel genotype during a stay in the ICU, five (13%) acquired colonization from their intestinal tract and three (8%) were colonized via cross-acquisition. In eight patients (21%), no route could be demonstrated for colonization. Antibiotics providing P. aeruginosa with a selective growth advantage were associated with acquired RTC. Endemicity of colonization with P. aeruginosa is characterized by polyclonality, and seems to be maintained by continuous admittance of colonized patients and selection pressure from antibiotics rather than by cross-acquisition

Short-term outcomes and mortality after interhospital intensive care transportation: an observational prospective cohort study of 368 consecutive transports with a mobile intensive care unit

Objectives: To evaluate short-term outcomes and mortality after interhospital transportation of intensive care patients performed by a mobile intensive care unit (MICU). Setting: This study was performed in the tertiary care process of interhospital transportation using the local MICU system in the South East of the Netherlands. Participants: Between March 2009 and December 2011, all transports of adult patients being performed by the local MICU centre have been documented; data on 42 variables, including a 24 h follow-up Sequential Organ Failure Assessment (SOFA) score of 368 consecutive interhospital transports of intensive care patients, were recorded. In 24 cases, the follow-up SOFA score was missing, so 344 data sets were included. Interventions: No interventions have been done. Primary/secondary outcome measures: Primary outcome measures were the mean SOFA score before and 24 h after transport, and the 24 h post-transport mortality. Moreover, the differences between the groups of 24 h post-transport survivors and non-survivors have been analysed. Results: The mean SOFA score before transport was 8.8 for the whole population and 8.6 for those patients who were alive 24 h after transport, with a mean SOFA score of 8.4 after transport. The adverse events rate was 6.4%. Fourteen patients (4.1%) died within 24 h after transport. Patients in this group had a higher SOFA score, lower pH, higher age and more additional medical support devices than those patients in the survivor group. Conclusions: The non-significant decrease in the post-transport SOFA score and the lack of an association between transport and 24 h post-transport mortality indicates that in the study setting, interhospital transportation of intensive care patients performed by a MICU system was not associated with a clinically relevant deterioration of the patient

Precision medicine in Acute Respiratory Distress Syndrome

Many patients with acute respiratory failure fulfill the diagnosis of Acute Respiratory Distress Syndrome (ARDS), forming a very heterogeneous population. Clinical trials have not yielded beneficial treatment effects in ARDS, possibly caused by this heterogeneity. Dividing patients with ARDS into subgroups, each with similar characteristics, may result in improved treatment strategies as part of a precision medicine approach. In this systematic review, we summarize the subphenotypes identified so far, the current state, and future directions for precision medicine in ARDS. Multiple data-driven subphenotypes have been identified based on a wide range of variables. These subphenotypes are associated with differences in clinical outcomes, which could be used for prognostic-and predictive enrichment of future interventional studies. True treatable traits have not been identified yet, deeper phenotyping will hopefully reveal these along with mechanistic differences