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Title: Non-linear relationship between serum iron levels and 28-day mortality in sepsis patients : a retrospective study
Authors: Jin, J
Yu, L
Cheung, K 
Deng, Z
Zhou, Q
Liu, Y
Issue Date: 2025
Source: Scientific reports, 2025, v. 15, 28331
Abstract: Recent studies have shown a significant association between iron and the development and prognosis of sepsis, but the relationship between iron levels and mortality in sepsis patients remains unclear, with previous studies examining this relationship under a linear assumption. This retrospective observational study aimed to assess the possible non-linear relationship between serum iron (SI) levels and 28-day all-cause mortality (28-DACM) in individuals with sepsis. We used multiple imputation for data with less than 30% missing values and developed Cox models to calculate the hazard ratio (HR) with a 95% confidence interval (CI) for the main outcome (28-DACM). To accurately assess the relationship between SI levels and the HR for 28-DACM, we utilized a restricted cubic spline (RCS) regression model with five knots. We also conducted subgroup analyses to evaluate the robustness of the primary results. The study found that SI levels upon ICU admission are an independent predictor of 28-DACM in sepsis patients, showing a J-shaped correlation with mortality. Patients with extremely high and low SI levels had higher mortality compared to those within the normal range. However, this study has limitations inherent to its retrospective observational design, such as potential bias and unmeasured confounding factors. Future studies should address these limitations through prospective designs.
Keywords: MIMIC-IV
Mortality
Risk factor
Sepsis
Serum iron
Publisher: Nature Publishing Group
Journal: Scientific reports 
EISSN: 2045-2322
DOI: 10.1038/s41598-025-13341-4
Rights: Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
© The Author(s) 2025
The following publication Jin, J., Yu, L., Cheung, K. et al. Non-linear relationship between serum iron levels and 28-day mortality in sepsis patients: a retrospective study. Sci Rep 15, 28331 (2025) is available at https://doi.org/10.1038/s41598-025-13341-4.
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