Clinicopathologic and Biomarker Correlates of Sepsis-Associated Organ Injury: A Prospective Perimortem Study from a Tertiary-Care ICU

Adult ICU patients (>18 years) diagnosed with severe sepsis or septic shock will be screened. After obtaining consent from the relatives, blood samples wll be obtained within 24 hours prior to death and will be analyzed for soluble biomarkers of immune exhaustion (sPD-1) and necroptosis (sRIPK3). Additionally, immunohistochemistry will be performed for key biomarkers representing mechanistic pathways—endothelial injury (Syndecan-1), complement activation (C5b-9), apoptosis (Caspase-3), necroptosis (RIPK1/MLKL), regeneration (Ki-67), immune exhaustion (PD-1/PD-L1), and neutrophil extracellular traps (H3Cit ± MPO).

Ultrasound-guided core-needle biopsies of the liver, lung (non-dependent segment), and kidney will be performed within six hours of death using a sterile, disposable 14–18 G Tru-Cut needle under full biosafety precautions. Two to three cores will be obtained from each organ and immediately placed in 10 % neutral-buffered formalin, fixed for 24 hours, and processed into formalin-fixed, paraffin-embedded (FFPE) blocks. Routine H&E and appropriate special stains (PAS, MT, VVG, Reticulin, Perl’s, MSB) will be performed. Histopathological assessment will be carried out by pathologists blinded to clinical details.

All tissue and serum biomarker findings will be semiquantitatively graded or quantified, as applicable, and correlated with ante-mortem clinical and biochemical parameters of organ dysfunction.