Dynamic changes in plasma sphingosine-1-phosphate concentrations and mortality in sepsis: a prospective cohort study in the emergency department
- 1Taipei Medical University
Abstract
Background Sepsis is a dynamic process with evolving host responses, biomarker changes, and organ dysfunction. Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in endothelial and immune regulation. However, the clinical relevance of dynamic S1P changes in sepsis remains unclear. This study aimed to assess their association with mortality. Methods We conducted a prospective cohort study of adults recruited from the emergency department of Wan Fang Hospital between April 2022 and October 2024. Plasma S1P was measured by ELISA on days 1, 3, and before discharge or death. The primary outcome was 60-day mortality. S1P trajectories were defined by baseline concentrations and longitudinal slopes estimated using linear mixed-effects models. Low-decreasing, low-stable, and high-decreasing trajectories were grouped as descending; the others as ascending. Cox proportional hazards models assessed mortality associations with baseline S1P, trajectory groups, and time-varying S1P. Results Among 278 participants, 156 had sepsis. Baseline S1P concentrations were lower in patients with sepsis (82.2 [IQR, 47.8-141.1] ng/mL) than in those with non-septic infection (129.2 [IQR, 68.1-306.9] ng/mL) and non-infected controls (132.8 [IQR, 74.1-300.2] ng/mL). In the sepsis cohort, 101 patients were classified into the descending S1P trajectory group and 55 into the ascending group. The descending group had a higher hazard of 60-day mortality (adjusted hazard ratio [aHR] 3.43; 95% confidence interval [CI], 1.11-10.58; p = 0.032). Baseline S1P was not significantly associated with 60-day mortality (aHR 1.004 per 10 ng/mL decrease; 95% CI, 0.977-1.032; p = 0.803). Each 10 ng/mL decrease in time-varying S1P was associated with a 3.5% higher mortality hazard (aHR 1.035; 95% CI, 1.002-1.076; p = 0.041). Conclusions Declining plasma S1P over time was associated with higher mortality in sepsis. Dynamic changes in S1P may be clinically relevant beyond baseline levels.
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BibTeX
@misc{tran2026dynamic,
title = {{Dynamic changes in plasma sphingosine-1-phosphate concentrations and mortality in sepsis: a prospective cohort study in the emergency department}},
author = {B. V. Tran and C.-L. Chen and T. N. Nguyen and Y.-C. Lin and K.-C. Hu and C.-W. Hsu and S.-C. Hsu},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.26367220},
url = {https://www.medrxiv.org/content/10.64898/2026.11.03.26367220v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Dynamic changes in plasma sphingosine-1-phosphate concentrations and mortality in sepsis: a prospective cohort study in the emergency department
AU - B. V. Tran
AU - C.-L. Chen
AU - T. N. Nguyen
AU - Y.-C. Lin
AU - K.-C. Hu
AU - C.-W. Hsu
AU - S.-C. Hsu
PY - 2026
DA - 2026/11/03
PB - medRxiv
DO - 10.64898/2026.11.03.26367220
UR - https://www.medrxiv.org/content/10.64898/2026.11.03.26367220v1
AB - Background Sepsis is a dynamic process with evolving host responses, biomarker changes, and organ dysfunction. Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in endothelial and immune regulation. However, the clinical relevance of dynamic S1P changes in sepsis remains unclear. This study aimed to assess their association with mortality. Methods We conducted a prospective cohort study of adults recruited from the emergency department of Wan Fang Hospital between April 2022 and October 2024. Plasma S1P was measured by ELISA on days 1, 3, and before discharge or death. The primary outcome was 60-day mortality. S1P trajectories were defined by baseline concentrations and longitudinal slopes estimated using linear mixed-effects models. Low-decreasing, low-stable, and high-decreasing trajectories were grouped as descending; the others as ascending. Cox proportional hazards models assessed mortality associations with baseline S1P, trajectory groups, and time-varying S1P. Results Among 278 participants, 156 had sepsis. Baseline S1P concentrations were lower in patients with sepsis (82.2 [IQR, 47.8-141.1] ng/mL) than in those with non-septic infection (129.2 [IQR, 68.1-306.9] ng/mL) and non-infected controls (132.8 [IQR, 74.1-300.2] ng/mL). In the sepsis cohort, 101 patients were classified into the descending S1P trajectory group and 55 into the ascending group. The descending group had a higher hazard of 60-day mortality (adjusted hazard ratio [aHR] 3.43; 95% confidence interval [CI], 1.11-10.58; p = 0.032). Baseline S1P was not significantly associated with 60-day mortality (aHR 1.004 per 10 ng/mL decrease; 95% CI, 0.977-1.032; p = 0.803). Each 10 ng/mL decrease in time-varying S1P was associated with a 3.5% higher mortality hazard (aHR 1.035; 95% CI, 1.002-1.076; p = 0.041). Conclusions Declining plasma S1P over time was associated with higher mortality in sepsis. Dynamic changes in S1P may be clinically relevant beyond baseline levels.
ER -