JMIR Publications

ABSTRACT

Background:

Necrotizing soft tissue infections (NSTI) are complex multifactorial diseases characterized by rapid bacterial proliferation and progressive tissue death. Treatment is multidisciplinary with surgery, broad spectrum antibiotics and intensive care, and adjunctive treatment with hyperbaric oxygen (HBO2) treatment may be applied. Recent advances in molecular technologies and biological computation has given rise to new approaches in infectious diseases with identification of target groups, defined by activated pathophysiological mechanisms.

Objective:

We aim of to capture the NSTI disease signatures, its mechanisms and treatment responses in patients that are treated according to the highest standard of treatment, therefore we set out to investigate genome wide transcriptional responses to HBO2 treatment in host and bacteria during NSTI.

Methods:

The HBOmic study is a prospective cohort study including 95 patients admitted for NSTI at the Intensive Care Unit at the Copenhagen University Hospital (Rigshospitalet), Denmark between Jan. 2013- June 2017. All participants were treated according to a local protocol for management of NSTI and biological samples were obtained and stored according to a standard operational procedure. In the present study we will generate genome-wide expression profiles from whole blood and samples of infected tissue taken before and after HBO2 treatment during the initial acute phase of infection and analyze them with unsupervised hierarchical clustering and machine learning. Differential gene expression will be performed to compare samples before and after HBO2 treatment (n=85), and integration of profiles from blood and tissue will be performed. Furthermore, findings will be related to NSTI patients who have not received HBO2 treatment (n=10). Transcriptomic data will be integrated with clinical data to investigate for associations and predictors.

Results:

The first participant was enrolled on the 27th July 2021, and data analysis is expected to be begin during autumn 2022 with publication of results immediately thereafter.

Conclusions:

The longitudinal design of the HBOmic study with collection of sequential samples from two different immunological compartments (blood and infected tissue), combined with an analysis of all molecules pertaining to the transcriptome at time of sampling, enables us to capture the complex network of biomarkers and signaling pathways of NSTI and make associations to disease progression and treatment response. Clinical Trial: All participants were enrolled in a clinical study registered with ClinicalTrials.gov (NCT01790698), first posted: February 13, 2013.