TY - JOUR

T1 - Investigating the Effects of Hyperbaric Oxygen Treatment in Necrotizing Soft Tissue Infection With Transcriptomics and Machine Learning (the HBOmic Study)

T2 - Protocol for a Prospective Cohort Study With Data Validation

AU - Vinkel, Julie

AU - Rib, Leonor

AU - Buil, Alfonso

AU - Hedetoft, Morten

AU - Hyldegaard, Ole

N1 - Publisher Copyright: ©Julie Vinkel, Leonor Rib, Alfonso Buil, Morten Hedetoft, Ole Hyldegaard.

PY - 2022

Y1 - 2022

N2 - Background: Necrotizing soft tissue infections (NSTIs) are complex multifactorial diseases characterized by rapid bacterial proliferation and progressive tissue death. Treatment is multidisciplinary, including surgery, broad-spectrum antibiotics, and intensive care; adjunctive treatment with hyperbaric oxygen (HBO2) may also be applied. Recent advances in molecular technology and biological computation have given rise to new approaches to infectious diseases based on identifying target groups defined by activated pathophysiological mechanisms. Objective: We aim to capture NSTI disease signatures and mechanisms and responses to treatment in patients that receive the highest standard of care; therefore, we set out to investigate genome-wide transcriptional responses to HBO2 treatment during NSTI in the host and bacteria. Methods: The Effects of Hyperbaric Oxygen Treatment Studied with Omics (HBOmic) study is a prospective cohort study including 95 patients admitted for NSTI at the intensive care unit of Copenhagen University Hospital (Rigshospitalet), Denmark, between January 2013 and 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 proposed study, we will generate genome-wide expression profiles of whole-blood samples and samples of infected tissue taken before and after HBO2 treatment administered during the initial acute phase of infection, and we will analyze the profiles with unsupervised hierarchical clustering and machine learning. Differential gene expression will be compared in samples taken before and after HBO2 treatment (N=85), and integration of profiles from blood and tissue samples will be performed. Furthermore, findings will be compared to NSTI patients who did not receive HBO2 treatment (N=10). Transcriptomic data will be integrated with clinical data to investigate associations and predictors. Results: The first participant was enrolled on July 27, 2021, and data analysis is expected to begin during autumn 2022, with publication of results immediately thereafter. Conclusions: The HBOmic study will provide new insights into personalized patient management in NSTIs. Trial Registration: ClinicalTrials.gov NCT01790698; https://clinicaltrials.gov/ct2/show/NCT01790698 International Registered Report Identifier (IRRID): DERR1-10.2196/39252

AB - Background: Necrotizing soft tissue infections (NSTIs) are complex multifactorial diseases characterized by rapid bacterial proliferation and progressive tissue death. Treatment is multidisciplinary, including surgery, broad-spectrum antibiotics, and intensive care; adjunctive treatment with hyperbaric oxygen (HBO2) may also be applied. Recent advances in molecular technology and biological computation have given rise to new approaches to infectious diseases based on identifying target groups defined by activated pathophysiological mechanisms. Objective: We aim to capture NSTI disease signatures and mechanisms and responses to treatment in patients that receive the highest standard of care; therefore, we set out to investigate genome-wide transcriptional responses to HBO2 treatment during NSTI in the host and bacteria. Methods: The Effects of Hyperbaric Oxygen Treatment Studied with Omics (HBOmic) study is a prospective cohort study including 95 patients admitted for NSTI at the intensive care unit of Copenhagen University Hospital (Rigshospitalet), Denmark, between January 2013 and 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 proposed study, we will generate genome-wide expression profiles of whole-blood samples and samples of infected tissue taken before and after HBO2 treatment administered during the initial acute phase of infection, and we will analyze the profiles with unsupervised hierarchical clustering and machine learning. Differential gene expression will be compared in samples taken before and after HBO2 treatment (N=85), and integration of profiles from blood and tissue samples will be performed. Furthermore, findings will be compared to NSTI patients who did not receive HBO2 treatment (N=10). Transcriptomic data will be integrated with clinical data to investigate associations and predictors. Results: The first participant was enrolled on July 27, 2021, and data analysis is expected to begin during autumn 2022, with publication of results immediately thereafter. Conclusions: The HBOmic study will provide new insights into personalized patient management in NSTIs. Trial Registration: ClinicalTrials.gov NCT01790698; https://clinicaltrials.gov/ct2/show/NCT01790698 International Registered Report Identifier (IRRID): DERR1-10.2196/39252

KW - biomarker

KW - data

KW - genome

KW - host-pathogen interaction

KW - hyperbaric oxygen treatment

KW - immune system

KW - immunology

KW - infection

KW - longitudinal

KW - machine learning

KW - mechanism

KW - necrotizing soft tissue infection

KW - NSTI

KW - oxygen

KW - response

KW - sepsis

KW - signaling

KW - soft tissue infection

KW - study protocol

KW - tissue

KW - transcriptomic

KW - treatment

KW - validation

U2 - 10.2196/39252

DO - 10.2196/39252

M3 - Journal article

C2 - 36427229

AN - SCOPUS:85144793688

VL - 11

JO - J M I R Research Protocols

JF - J M I R Research Protocols

SN - 1929-0748

IS - 11

M1 - e39252

ER -