Longitudinal biomarker trajectories differ in burn sepsis survivors and non-survivors

ObjectiveTo assess the dynamic prognostic value of multicategory biomarkers in burn sepsis and identify patient phenotypes based on their longitudinal trajectories.MethodsThis retrospective cohort study included 712 adult patients with burn sepsis (Sepsis−3) admitted to a regional burn ICU (2022–2025). Seventeen biomarkers covering nutrition (albumin, ALB; prealbumin, PA; transferrin, TRF; nitrogen balance), immunity (immunoglobulins A/G/M; CD3+/CD4+/CD8+ T cells, CD4+/CD8+ ratio; natural killer, NK cells), and inflammation (interleukin−6, IL−6; C−reactive protein, CRP; procalcitonin, PCT; platelet count, lactate) were measured at five time points (days 1, 3, 7, 14, and 21). We compared survivor/non-survivor trajectories using linear mixed-effects models, assessed baseline biomarker associations with 21−day mortality via Cox regression, and evaluated predictive performance with Harrell’s C-index. Growth mixture modeling (GMM) identified phenotypes from integrated ALB, IL−6, and immunoglobulin G (IgG) trajectories.ResultsThe 21−day mortality was 17.9% (81 deaths). Survivor and non-survivor trajectories differed significantly for multiple biomarkers (P < 0.05). Growth mixture modeling identified two distinct patient phenotypes: a high-risk phenotype (n = 267, mortality 15.7%) characterized by persistently lower ALB and IgG and sustained IL−6 elevation over 21 days and a low-risk phenotype (n = 445, mortality 8.8%) with favorable biomarker trajectories (P = 0.005). Univariable analysis associated several baseline markers with mortality (e.g., ALB: HR = 0.97, P = 0.013; IL−6: HR = 1.004, P = 0.004). However, no biomarker retained independent significance in multivariable analysis, likely due to multicollinearity among nutritional markers [variance inflation factor (VIF) up to 8.4]. Harrell’s C-indices for baseline ALB, PA, and IgG were modest (0.604, 0.583, and 0.585, respectively).ConclusionsLongitudinal multicategory biomarker trajectories predict 21−day survival in burn sepsis. Trajectory-based phenotyping identifies patient subgroups with markedly different outcomes, offering superior prognostic stratification over static measurements. The integrated phenotype, reflecting the dynamic interplay of catabolism, immune paralysis, and inflammation, emerges as a robust prognostic marker, supporting personalized management approaches.