Characterization of sepsis inflammatory endotypes using circulatory proteins in patients with severe infection: a prospective cohort study.

BACKGROUND: Sepsis is a heterogeneous syndrome due to a variable range of dysregulated processes in the host immune response. Efforts are made to stratify patients for personalized immune-based treatments and better prognostic prediction. Using gene expression data, different inflammatory profiles have been identified. However, it remains unknown whether these endotypes mirror inflammatory proteome profiling, which would be more feasible to assess in clinical practice. We aim to identify different inflammatory endotypes based on circulating proteins in a cohort of moderately ill patients with severe infection (Sepsis-2 criteria). METHODS: In this prospective study, 92 inflammatory plasma markers were profiled using a targeted proteome platform and compared between patients with severe infection (Sepsis-2 criteria) and healthy controls. To identify endotypes with different inflammatory profiles, we performed hierarchical clustering of patients based on the differentially expressed proteins, followed by clinical and demographic characterization of the observed endotypes. RESULTS: In a cohort of 167 patients with severe infection and 192 healthy individuals, we found 62 differentially expressed proteins. Inflammatory proteins such as TNFSF14, OSM, CCL23, IL-6, and HGF were upregulated, while TRANCE, DNER and SCF were downregulated in patients. Unsupervised clustering identified two different inflammatory profiles. One endotype showed significantly higher inflammatory protein abundance, and patients with this endotype were older and showed lower lymphocyte counts compared to the low inflammatory endotype. CONCLUSIONS: By identifying endotypes based on inflammatory proteins in moderately ill patients with severe infection, our study suggests that inflammatory proteome profiling can be useful for patient stratification.

Gut Microbiota Imbalance in Metastatic Colorectal Patients Treated With EGFRI and Long-Term Antibiotic Therapy for Cutaneous Toxicity: A Pilot Study.

Patients with metastatic colorectal cancer (mCRC) frequently experience epidermal growth factor inhibitors (EGFRI)-induced skin side effects. Antibiotic treatment with doxycycline is often required in order to manage the skin and mucosal toxicity. Since these patients already have significant gut dysbiosis, the long-term antibiotic treatment may destabilize their gut microbiome. Objectives The assessment of intestinal dysbiosis in patients undergoing treatment with EGFRI, who require antibiotic treatment with doxycycline in order to manage adverse skin effects. Methods We conducted a prospective pilot study between 2020 and 2021 involving 10 patients with mCRC. These patients were undergoing treatment with EGFRI and required either short-term or long-term treatment with doxycycline in order to manage skin toxicity. Results The patients with mCRC who were treated with doxycycline for 8 weeks showed overexpression of Escherichia coli, Candida, and Geotrichum species compared to the patients who only received doxycycline treatment for two weeks. Conclusions The elevated levels of Escherichia coli and Candida species in the patients who received doxycycline for eight weeks compared to the patients who received the treatment for two weeks could provide a starting point for the development of a standardized guideline regarding the use of pre-active or reactive antibiotic treatment. We also highlight the importance of analyzing the intestinal microbiome of these patients. The identification of overexpressed species, as well as the deficiency of certain protective species, could guide the administration of probiotics to cover and repair the affected intestinal flora.