Functional Epigenomics of Sepsis

Conditions: A41
A40
Streptococcal sepsis
Other sepsis

Registration Number: DRKS00018867

Lead Sponsor: Klinik für AnästhesiologieUniversitätsklinikum Heidelberg

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: All

Target Recruitment: 250

Inclusion Criteria

Patients with Sepsis:
Consent by the legal representative;
At least 2 SIRS criteria met:
- temperature <36ºC or> 38ºC
- tachycardia (> 90 /min)
- leukocytosis (> 12,000 /µl) OR leukopenia (<4,000 /µl) OR left shift (>10% immature blasts)
- Tachypnea (> 20 /min) OR paCO2 <32 mmHg OR oxygenation index (FiO2/paO2) <200 OR mechanical Ventilation;
Clinical or microbiological evidence of infection
Sepsis-associated organ dysfunction indicated by a change in the Sequential Organ Failure Assessment (SOFA) score by 2 or more points (compared to previous day)
Patients after surgery:
Informed consent;
Elective major surgery scheduled.
Healthy volunteers:
Informed consent.

Exclusion Criteria

Common exclusion criteria of all study groups:
Pregnancy;
Inclusion in an interventional study;
infectious viral diseases (HBV, HCV, HIV);
Iatrogenic immunosuppression.
Specific exclusion criteria of patients with sepsis:
Diagnosis sepsis >24 h.
Specific exclusion criteria of healthy volunteers:
One of the following states during the last 7 days:
- Influenza infection or flu
- Sports injuries or other trauma
- Large-scale dental interventions (e.g., tooth extraction)
- Blood or platelet donation.

Study & Design

Study Type: observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Measurement of the distribution of genome-wide histone modifications in isolated peripheral blood mononuclear cells (PBMCs) using chromatin immunoprecipitation sequencing

Secondary Outcome Measures

Name	Time	Method
Measurement of global gene expression in isolated PBMCs using RNA-Seq, validated by qPCR<br>Measurement of global DNA methylation in isolated PBMCs using microarray<br>Measurement of metabolic pathways in isolated PBMCs using Seahorse™ Technology<br>Measurement of phagocytic activity of immune cells using FACS<br>Measurement of PBMCs functional competence for cytokine release by stimulation and ELISA phenotyping of immune cell populations using FACS<br>Quantification of chemokines, cytokines, and metabolic metabolites in plasma by ELISA, or mass spectrometry<br>Composition of the gastrointestinal microbiome using 16S sequencing<br>Occurrence of secondary infections<br>28-day survival<br>stay in hospital and intensive care unit