Inflammatory Response Syndrome, Systemic, Severe Sepsis
Conditions
Keywords
Myeloid-Derivated suppressive cell, Sepsis, Inflammatory Response Syndrome, Systemic
Brief summary
Sepsis remains a major cause of death in developed countries. A better understanding of the mechanisms involved in the regulation of inflammatory and immune response of patients with severe sepsis is an important step that could open the way for new therapeutic approaches.
Interventions
BIOLOGICALResidue of blood further to NFS
BIOLOGICALResidue of blood further to preoperative workup
BIOLOGICALBone marrow collected during a myelogram carried out for hematological pathology workup
BIOLOGICALBone marrow collected during myelogram routinely performed during hospitalization in ICU
Sponsors
University Hospital, Limoges
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient ≥18 years old * Patient with two criteria of systemic inflammatory response syndrome and one of the four following criteria within 24 hours of hospitalization in ICU: * Lactate \>4 mmol/L * PaO2 / FiO2 \<200 in the presence of lung disease as infectious source * Vasopressor: adrenaline or noradrenaline ≥0.25 µg/kg/min for at least 6 hours to maintain a systolic blood pressure ≥90 mmHg or mean arterial pressure ≥65 mmHg * Thrombocytopenia linked to sepsis with platelet count \<100,000 / ml or a decrease ≤50% within 48 hours
Exclusion criteria
* Pregnancy * progressive solid cancer * HIV infection * History of blood or inflammatory disease * long-term immunosuppressive treatment * Prior episode of Sepsis in the previous month * Chronic Dialysis Patient * Patient under guardianship * Patient not affiliated with a social security system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peripheral Blood MDSC concentration during ICU hospitalization for Severe Sepsis | Average 30 days - Patients will be followed up until hospital discharge | Number of patients showing an increase of Myeloid derived suppressive cells from baseline at Day 30. Kinetic of Myeloid derived suppressive cells through weekly measures of Absolute Cell Counts (using flow cytometry) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MDSCs presence in the blood and bone marrow. | Day 0 | Concentration of MDSC in the blood determined by flow cytometry |
| Assessment of MDSC specific gene expressions | Day 0 vs Days 3, 7, 14, 21, 28 | Measurement of MDSC activation by real-time qRT-PCRMDSC cell culture |
| Assessment of MDSC functional status | Day 0 vs Days 3, 7, 14, 21, 28 | Inhibition of T cell proliferation capacity (co-culture assay in vitro)MDSC cell culture |
| Immuno- inflammatory status | Day 0, Day3, Day 7 and once a week until the intensive care unit discharge | Pro-inflammatory cytokines determined by flow cytometry |
| Incidence of hospital acquired secondary infections at Day 28 | Day 28 | Incidence of hospital acquired secondary infections at Day 28 |
| SOFA score | Day 0, Day3, Day 7 and once a week until the intensive care unit discharge | Calculating of SOFA score |
| Mortality | Day 28 and Day 90 | Dead or alive |
Countries
France
Outcome results
None listed