Nonlinear Association Between Admission Neutrophil Count and 14-Day Mortality in Patients with Traumatic Brain Injury: A Retrospective Cohort Study

Summary

This protocol describes a standardized workflow for evaluating the association between admission neutrophil count and 14-day mortality in patients with traumatic brain injury through integrated analysis of clinical characteristics, laboratory parameters, and short-term outcomes.

Abstract

Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and early risk assessment remains clinically important because prognostic information is often required during the emergency admission period. This study evaluated the association between admission neutrophil count and 14-day all-cause mortality in adult patients with TBI. We analyzed an institutional cohort of 1,361 adults hospitalized with TBI between 2017 and 2023. Neutrophil count was obtained from the first complete blood count performed after emergency presentation or hospital admission. Patients were categorized according to neutrophil count tertiles, and 14-day all-cause mortality was defined as the primary outcome. The association between neutrophil count and mortality was assessed using univariable and multivariable logistic regression models. Potential nonlinear relationships and threshold effects were explored using generalized additive models and two-piecewise linear regression analyses. Fourteen-day mortality increased across neutrophil count tertiles, from 0.66% in the low tertile to 1.32% in the middle tertile and 5.73% in the high tertile. In the fully adjusted model, each 1 × 10⁹/L increase in neutrophil count was associated with higher odds of 14-day mortality (odds ratio [OR] = 1.093, 95% confidence interval [CI]: 1.003–1.190, P = 0.041). Threshold analysis identified a nonlinear association with an estimated inflection point of 3.81 × 10⁹/L. Below this threshold, the association was inverse, whereas above it, the association was positive. These findings demonstrate an association between admission neutrophil count and 14-day all-cause mortality in patients with TBI and suggest that admission neutrophil count may serve as a readily available marker for early risk stratification. The threshold finding should be interpreted as exploratory.

Introduction

Traumatic brain injury (TBI) is defined as a disruption of brain function, or other evidence of brain pathology, caused by an external physical force¹. It is still a significant concern in the world of public health. There are over 50 million people who suffer from TBI annually, and the situation in China is also serious. In China alone, over 120,000 acute TBI cases were recorded between 2001 and 2016, with road traffic accidents and falls being the most common causes². Since TBI can result in premature death, prolonged disability, and significant family and social costs, simple and reliable prognostic indicators are sti....

Protocol

This study used anonymized clinical records from Kunshan No.2 People’s Hospital and was approved by the hospital Ethics Committee (approval No. ksehllsp2024-005). The study followed the principles of the Declaration of Helsinki. Because patient information was anonymized before analysis, the requirement for written informed consent was waived by the ethics committee. The patient screening, grouping, and main analysis workflow are shown in Figure 1. The laboratory equipment, database systems, and statistical software used in this study are listed in the Table of Materials.

Results

Patient screening and baseline characteristics

A total of 2,555 hospitalized patients with suspected or confirmed TBI-related diagnostic records between 2017 and 2023 were initially screened from the hospital electronic medical record system. After excluding patients aged <18 years, repeated admissions, non-traumatic brain injury or unclear diagnosis, missing admission neutrophil count, missing key baseline clinical or laboratory variables, or missing 14-day mortality statu.......

Discussion

Using clinical data from 1,361 hospitalized patients with TBI, we found that admission neutrophil count was associated with 14-day mortality. The mortality rate increased across neutrophil tertiles, and this pattern remained evident after adjustment for demographic, clinical, coagulation, and biochemical variables. In the fully adjusted model, each 1 ×10⁹/L increase in neutrophil count was associated with higher odds of 14-day mortality. The smoothing curve and threshold analysis further suggested that th.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Automated biochemical analyzer	Beckman Coulter, Inc.	AU5800 clinical chemistry analyzer	Used for biochemical testing, including ALB, TC, TGs, HDL, LDL, Apo A-I, Apo B, CYS, ALT, AST, Cr, BUN, UA, and FBG.
Automated coagulation analyzer	Sysmex Corporation	CS-5100 coagulation analyzer	Used for coagulation testing, including PT, APTT, INR, FIB, and D-dimer.
Automated hematology analyzer	Sysmex Corporation	XN-1000 hematology analyzer	Used for complete blood count testing, including neutrophil count, platelet count, and hemoglobin.
Electronic medical record system	Kunshan No. 2 People’s Hospital	Institutional electronic medical record platform; not commercially cataloged	Used to identify hospitalized patients with suspected or confirmed traumatic brain injury and to extract demographic and clinical variables.
EmpowerStats	X&Y Solutions, Inc.	Online statistical platform (accessed on April 25, 2026)	Used for multivariable logistic regression, generalized additive modeling, smoothing curve generation, and threshold analysis.
Follow-up record system	Kunshan No. 2 People’s Hospital	Institutional follow-up record platform; not commercially cataloged	Used to determine and verify 14-day survival status after index admission.
ggplot2 R package	R package	Version used in analysis	Used for statistical plotting and figure generation.
Laboratory information system	Kunshan No. 2 People’s Hospital	Institutional laboratory information platform; not commercially cataloged	Used to retrieve admission laboratory test results.
patchwork R package	R package	Version used in analysis	Used to assemble multi-panel figures.
pdftools R package	R package	Version used in analysis	Used for PDF processing during figure preparation.
png R package	R package	Version used in analysis	Used for image processing during figure preparation.
R statistical software	R Foundation for Statistical Computing	Version 4.5.2	Used for data preprocessing, statistical analysis, and figure generation.
scales R package	R package	Version used in analysis	Used for axis formatting and percentage scaling in figures.