Patel N, Patel V, Murugan Y, Patel K, Varma V, Surani S. Integrating serum ferritin and neutrophil-to-lymphocyte ratio with Sequential Organ Failure Assessment score improves mortality prediction in sepsis. World J Methodol 2026; 16(1): 109733 [DOI: 10.5662/wjm.v16.i1.109733]
Corresponding Author of This Article
Salim Surani, MD, Professor, Department of Medicine and Pharmacology, Texas A&M University, 40 Bizzell Street, College Station, TX 77843, United States. srsurani@hotmail.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Retrospective Cohort Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Mar 20, 2026 (publication date) through Feb 10, 2026
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Journal Information of This Article
Publication Name
World Journal of Methodology
ISSN
2222-0682
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Patel N, Patel V, Murugan Y, Patel K, Varma V, Surani S. Integrating serum ferritin and neutrophil-to-lymphocyte ratio with Sequential Organ Failure Assessment score improves mortality prediction in sepsis. World J Methodol 2026; 16(1): 109733 [DOI: 10.5662/wjm.v16.i1.109733]
Namra Patel, Vansh Varma, Department of Medicine, GMERS College and Hospital, Valsad 396001, Gujarāt, India
Viral Patel, Department of Internal Medicine, Baptist Hospital of Southeast Texas, Beaumont, TX 77701, United States
Yogesh Murugan, Department of Community Medicine, Shri M P Shah Government Medical College, Jamnagar 361008, India
Kunal Patel, Department of Medicine, GMERS Medical College and Hospital, Valsad 396001, Gujarāt, India
Salim Surani, Department of Medicine and Pharmacology, Texas A&M University, College Station, TX 77843, United States
Author contributions: Patel N and Murugan Y performed the formal analyses; Patel N, Patel V, Murugan Y, Patel K, and Varma V participated in writing the manuscript; Patel N, Patel V, Patel K, Varma V, and Surani S contributed to editing the manuscript; Patel N and Patel V performed the data extraction; Patel N conceptualized and designed the study and developed the methodology; Murugan Y and Surani S contributed to reviewing the manuscript.
Institutional review board statement: This retrospective study uses data from 2008-2022 available in Medical Information Mart for Intensive Care (MIMIC-IV v3.1) from Beth Israel Deaconess Medical Center. Using the deidentified public deidentified database do not require the consent/IRB approval.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Data sharing statement: Data are available upon request from the first and corresponding authors.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Salim Surani, MD, Professor, Department of Medicine and Pharmacology, Texas A&M University, 40 Bizzell Street, College Station, TX 77843, United States. srsurani@hotmail.com
Received: May 20, 2025 Revised: June 23, 2025 Accepted: September 26, 2025 Published online: March 20, 2026 Processing time: 266 Days and 22 Hours
Abstract
BACKGROUND
Sepsis causes significant mortality in patients. Typically, the Sequential Organ Failure Assessment (SOFA) score is used; however, recent studies have demonstrated improved predictive accuracy by using inflammatory biomarkers such as serum ferritin and the neutrophil-to-lymphocyte ratio (NLR). Serum ferritin, although traditionally associated with iron metabolism, also acts as an acute-phase reactant reflecting systemic inflammation.
AIM
To assess the prognostic value of integrating ferritin and NLR with SOFA in predicting mortality in critically ill patients with sepsis.
METHODS
Medical Information Mart for Intensive Care database-IV database was used to conduct this retrospective cohort study. Patients were divided into quartiles based on values of serum ferritin and NLR. Cox proportional hazards regression assessed the association with 30-day mortality, adjusted for age, sex, and the Charlson comorbidity index. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), calibration plot, and net reclassification index (NRI). Bootstrapped internal validation was performed using 1000 resamples.
RESULTS
Patients in the ferritin Q1 quartile (lowest ferritin quartile) had 30% lower adjusted mortality risk (hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.57-0.9; P = 0.005) compared to Q3 (highest ferritin quartile). Similarly, NLR Q1 (lowest NLR quartile) had 27% lower adjusted mortality risk (HR: 0.73, 95%CI: 0.59-0.91; P = 0.006). Moreover, patients with both serum ferritin and NLR in the Q1 (lowest) quartile had the lowest risk of mortality (HR: 0.56, 95%CI: 0.42-0.74; P < 0.001). With biomarker integration, the AUROC improved from 0.602 (95%CI: 0.574-0.630) for SOFA alone to 0.656 (0.629-0.683; P < 0.001), primarily driven by ferritin. NRI demonstrated a modest but significant improvement in reclassification. Old age was also found to be associated with a higher risk of mortality.
CONCLUSION
Lower ferritin and NLR are associated with reduced 30-day mortality, with ferritin markedly improving SOFA-based prediction and NLR offering minimal added benefit. Accessible biomarkers enhance early risk assessment in low-resource intensive care units.
Core Tip: This study evaluated the added prognostic value of combining serum ferritin and neutrophil-lymphocyte ratio with Sequential Organ Failure Assessment (SOFA) in predicting 30-day mortality among critically ill adult patients with sepsis. Using data from the Medical Information Mart for Intensive Care database, the integration of these inflammatory biomarkers with SOFA improved model discrimination and reclassification, supporting their potential role in enhancing early risk stratification in sepsis.
