Health Condition 1: R652- Severe sepsis
Conditions
Interventions
Intervention1: Antemortem blood biomarkers and Post mortem Biopsy: A single blood sample will be collected in last 24 hours before death. Ultrasound-guided needle biopsy of the lung, liver, and kidney
Sponsors
All India Institute of Medical Sciences AIIMS
Eligibility
Inclusion criteria
Inclusion criteria: 1 Adult patients above 18 years dying in ICU due to septic shock as per Sepsis 3 criteria 2 Relatives provide written informed consent for post mortem needle biopsy
Exclusion criteria
Exclusion criteria: 1 Family refusal to consent 2 Pre existing chronic lung disease 3 Pre existing chronic liver disease 4 Pre existing chronic kidney disease 5 Shock of any other cause 6 Time elapsed since death more than 6 hours
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the relationship between circulating biomarkers of necroptosis (RIPK3) and immune-checkpoint activation (soluble PD-L1) with their corresponding tissue expression patterns in patients who die of sepsis or septic shock in a tertiary-care ICU.Timepoint: Blood biomarkers (RIPK3 and soluble PD-L1) will be measured once using a blood sample collected within the last 24 hours before death. Histopathological assessment of organ tissue will be performed on samples obtained within 6 hours after death.Post-mortem tissue biomarkers and histopathology will be assessed within 6 hours after death. | — |
Secondary
| Measure | Time frame |
|---|---|
| 2. Assess post-mortem tissue expression of RIPK1/MLKL, PD-L1 in liver, lung, & kidney using immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) biopsy samples.Timepoint: Once, using tissue samples obtained within 6 hours after death.;3. Correlate circulating biomarker levels with corresponding tissue IHC scores to determine whether blood levels reflect tissue activation states.Timepoint: Once, using blood samples collected within the last 24 hours before death & tissue samples obtained within 6 hours after death.;4. Examine associations between biomarker levels (plasma & tissue) & ante-mortem clinical indices of organ dysfunction (SOFA components, vasopressor dose, P/F ratio, creatinine, bilirubin).Timepoint: Clinical indices assessed during stay & biomarkers from sample taken during the last 24 hours before death.;1. Quantify plasma concentrations of RIPK3 & soluble PD-L1 in sepsis decedents performed on pre-mortem blood samplesTimepoint: Once, using blood samples collected within the last 24 hours before death.;5. Explore phenotypes by cross-classifying patients into biomarker clusters: a. High-RIPK3 / High-sPD-L1 (hyper-inflammatory + immune-exhausted), b. High-RIPK3 / Low-sPD-L1 (predominantly necroptotic), c. Low-RIPK3 / High-sPD-L1 (predominantly immunosuppressed), d. Low-RIPK3 / Low-sPD-L1 (resolving phenotype) Timepoint: Once, using blood samples collected within the last 24 hours before death. | — |
Countries
India
Contacts
Public ContactSiddhavivek Majage
All India Institute of Medical Sciences (AIIMS) New Delhi
Outcome results
None listed