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Reasons from acute physiology trajectories, modular organ dysfunction, and cluster-aware trial design through APACHE/SAPS/SOFA scoring, Berlin/Sepsis-3/KDIGO definitions, MIMIC-IV phenotyping, and target-trial emulation with clone-censor-weighting while treating immortal-time bias, cluster contamination, competing risks from early death, and sepsis-phenotype cohort inflation as first-class failure modes.