Abstract
BACKGROUND: Sepsis and shock are common complications of necrotising soft tissue infections (NSTI). Sepsis encompasses different endotypes that are associated with specific immune responses. Hyperbaric oxygen (HBO(2)) treatment activates the cells oxygen sensing mechanisms that are interlinked with inflammatory pathways. We aimed to identify gene expression patterns associated with effects of HBO(2) treatment in patients with sepsis caused by NSTI, and to explore sepsis-NSTI profiles that are more receptive to HBO(2) treatment. METHODS: An observational cohort study examining 83 NSTI patients treated with HBO(2) in the acute phase of NSTI, fourteen of whom had received two sessions of HBO(2) (HBOx2 group), and another ten patients (non-HBO group) who had not been exposed to HBO(2). Whole blood RNA sequencing and clinical data were collected at baseline and after the intervention, and at equivalent time points in the non-HBO group. Gene expression profiles were analysed using machine learning techniques to identify sepsis endotypes, treatment response endotypes and clinically relevant transcriptomic signatures of response to treatment. RESULTS: We identified differences in gene expression profiles at follow-up between HBO(2)-treated patients and patients not treated with HBO(2). Moreover, we identified two patient endotypes before and after treatment that represented an immuno-suppressive and an immune-adaptive endotype respectively, and we characterized the genetic profile of the patients that transition from the immuno-suppressive to the immune-adaptive endotype after treatment. We discovered one gene MTCO2P12 that distinguished individuals who altered their endotype in response to treatment from non-responders. CONCLUSION: The global gene expression pattern in blood changed in response to HBO(2) treatment in a direction associated with clinical biochemistry improvement, and the study provides potential novel biomarkers and pathways for monitoring HBO(2) treatment effects and predicting an HBO(2) responsive NSTI-sepsis profile. TRIAL REGISTRATION: Biological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698) 04/02/2013.