Integrated immune and endothelial profiling predicts 90-day mortality in postoperative sepsis and septic shock

Year: 2026

Type: article

Abstract: BACKGROUND: Sepsis and septic shock remain major causes of mortality in critically ill postoperative patients, largely because of the lack of reliable biomarkers for early risk stratification. The interplay between immune dysfunction and endothelial activation is key in the progression to multiorgan failure, however phenotypic characterisation of circulating endothelial subpopulations remains limited. METHODS: A Prospective multicentre study included 219 postoperative patients (Non-septic ICU patients, sepsis, septic shock). Peripheral Blood Mononuclear Cells were analysed using high-dimensional spectral flow cytometry. Both supervised gating strategies and high-dimensional unsupervised analyses (UMAP and FlowSOM) were applied to identify immune and endothelial cell subsets. Associations with 90-day mortality were assessed using univariate and multivariate Cox proportional hazards models, refined with LASSO-Cox regression, and integrated into a risk score. The predictive performance of this cellular risk score was compared with SOFA and APACHE II scores using ROC curves and survival analysis. Findings were further validated using publicly available single-cell RNA datasets. FINDINGS: ) were independently associated with 90-day mortality. The integrated risk score stratified patients into three groups with significantly different survival outcomes (log-rank p = 0.0009), outperformed SOFA and APACHE II (AUC 0.935 vs. 0.751-0.804). Transcriptomic validation confirmed the presence and dysfunction of endothelial clusters, reinforcing their prognostic relevance. INTERPRETATION: The combination of immune and endothelial profiling provides a robust cellular signature that improves the prognostic stratification in postoperative sepsis. These biomarkers may support treatment and guide therapeutic strategies aimed at restoring immune-endothelial homoeostasis. FUNDING: This work was supported by the Instituto de Salud Carlos III [grant numbers: PI24/00754, FI25/00242 and CIBERINFEC CB21/13/00051], Junta de Castilla y León [GRS 2782/A2/2023, GRS 2804/A1/2023].

Source: EBioMedicine

DOI: 10.1016/j.ebiom.2026.106372

Institutions: Instituto de Estudios de Ciencias de la Salud de Castilla y León, Hospital Clínico Universitario de Valladolid, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Universidad de Valladolid, Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina y Genética Molecular de Valladolid, Hospital Universitario de Toledo, Bellvitge University Hospital, Hospital Universitario Río Hortega, Universitat de València, Hospital Clínico Universitario de Valencia, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Erasmus MC

Language: English

Topic: Sepsis Diagnosis and Treatment

Subfield: Critical Care and Intensive Care Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,780

Funders: Centro de Investigación Biotecnológica en Red de Enfermedades Infecciosas, Junta de Castilla y León, Instituto de Salud Carlos III

Awards: G1560906439, G2696892683, G2743718077, G496409687, G6104980783, Secuenciación Unicelular de Células Endoteliales Circulantes, La llave del éxito para la medicina de precisión en sepsis (SUCCESS)

OpenAlex ID: W7168024642