Abstract：
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.
BACKGROUND: ClinicalTrials.gov NCT01790698; https://clinicaltrials.gov/ct2/show/NCT01790698.
UNASSIGNED: DERR1-10.2196/39252.
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.
BACKGROUND: ClinicalTrials.gov NCT01790698; https://clinicaltrials.gov/ct2/show/NCT01790698.
UNASSIGNED: DERR1-10.2196/39252.
摘要：
背景：坏死性软组织感染（NSTIs）是复杂的多因素疾病，其特征是细菌快速增殖和进行性组织死亡。治疗是多学科的，包括手术,广谱抗生素,和重症监护；也可以使用高压氧（HBO2）辅助治疗。分子技术和生物学计算的最新进展已经产生了基于识别由激活的病理生理机制定义的目标组的传染病的新方法。
目的：我们的目标是获取接受最高标准护理的患者的NSTI疾病特征和机制以及对治疗的反应；因此，我们着手研究宿主和细菌在NSTI过程中对HBO2处理的全基因组转录反应。
方法：通过Omics（HBOmic）研究的高压氧治疗的效果是一项前瞻性队列研究，其中包括95名因NSTI入院的患者，丹麦,2013年1月至2017年6月。所有参与者都根据当地的NSTI管理方案进行治疗，根据标准操作程序获取并储存生物样本。在拟议的研究中，我们将生成全血样本和感染组织样本的全基因组表达谱，这些样本在感染的初始急性期进行HBO2治疗之前和之后采集，我们将通过无监督分层聚类和机器学习来分析配置文件。将在HBO2处理之前和之后采集的样品中比较差异基因表达(N=85),并且将进行来自血液和组织样本的谱的整合。此外，研究结果将与未接受HBO2治疗的NSTI患者进行比较(N=10).转录组数据将与临床数据整合以研究关联和预测因素。
结果：第一位参与者于2021年7月27日注册，数据分析预计将于2022年秋季开始，随后立即公布结果。
结论：HBOmic研究将为NSTIs的个性化患者管理提供新的见解。
背景：ClinicalTrials.govNCT01790698;https://clinicaltrials.gov/ct2/show/NCT01790698。
未经批准：DERR1-10.2196/39252。
目的：我们的目标是获取接受最高标准护理的患者的NSTI疾病特征和机制以及对治疗的反应；因此，我们着手研究宿主和细菌在NSTI过程中对HBO2处理的全基因组转录反应。
方法：通过Omics（HBOmic）研究的高压氧治疗的效果是一项前瞻性队列研究，其中包括95名因NSTI入院的患者，丹麦,2013年1月至2017年6月。所有参与者都根据当地的NSTI管理方案进行治疗，根据标准操作程序获取并储存生物样本。在拟议的研究中，我们将生成全血样本和感染组织样本的全基因组表达谱，这些样本在感染的初始急性期进行HBO2治疗之前和之后采集，我们将通过无监督分层聚类和机器学习来分析配置文件。将在HBO2处理之前和之后采集的样品中比较差异基因表达(N=85),并且将进行来自血液和组织样本的谱的整合。此外，研究结果将与未接受HBO2治疗的NSTI患者进行比较(N=10).转录组数据将与临床数据整合以研究关联和预测因素。
结果：第一位参与者于2021年7月27日注册，数据分析预计将于2022年秋季开始，随后立即公布结果。
结论：HBOmic研究将为NSTIs的个性化患者管理提供新的见解。
背景：ClinicalTrials.govNCT01790698;https://clinicaltrials.gov/ct2/show/NCT01790698。
未经批准：DERR1-10.2196/39252。
