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基于机器学习的脓毒症白细胞轨迹临床亚型识别与特征识别

Clinical subtypes identification and feature recognition of sepsis leukocyte trajectories based on machine learning.

作者信息

Miao ShengHui, Liu YiJing, Li Min, Yan Jing

机构信息

The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, 322000, China.

Department of Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, 310053, Zhejiang, China.

出版信息

Sci Rep. 2025 Apr 10;15(1):12291. doi: 10.1038/s41598-025-96718-9.

Abstract

Sepsis is a highly variable condition, and tracking leukocyte patterns may offer insights for tailored treatment and prognosis. We used the MIMIC-IV database to analyze patients diagnosed with Sepsis-3 within 24 h of ICU admission. Latent class mixed models (LCMM) were applied to leukocyte trajectories to identify sepsis subtypes. The primary outcome was 28-day all-cause mortality, with secondary outcomes including the need for life-support therapies. Associations between leukocyte trajectories and outcomes were assessed using multivariate regression, and findings were externally validated with the eICU database. Use the XGBoost model to identify baseline characteristics of high-risk mortality sepsis subgroups for predicting subgroup allocation upon patient admission to the ICU, and apply the SHAP method to interpret the contributing variables of the model. Among 7410 sepsis patients, eight distinct leukocyte trajectory subtypes were identified. Among those subtypes, patients with persistently high leukocyte levels had the poorest prognosis (HR 3.00; 95% CI 2.48-3.62) and a significantly greater need for life-support therapies; Patients with persistently low white blood cell levels had a higher risk of death (HR 1.68; 95% CI 1.24-2.27) but were less likely to receive invasive mechanical ventilation. Incorporating early ICU baseline variables into an XGBoost algorithm enables effective prediction of high-mortality risk subgroups (AUC > 0.8). SHAP method reveals distinct early clinical characteristics between hyperinflammatory subtypes (class 4, 7, and 8) and the hypoinflammatory subtype (class 1). In ICU-admitted sepsis patients, eight leukocyte trajectories are identified, which is the key independent predictors of prognosis, separating from single leukocyte measurements. High-mortality risk subgroups exhibit distinct clinical characteristics at ICU admission, providing valuable insights for their prediction and personalized early intervention.

摘要

脓毒症是一种高度可变的病症,追踪白细胞模式可能为个体化治疗和预后提供见解。我们使用多重症监护病房数据库(MIMIC-IV)分析了在重症监护病房(ICU)入院24小时内被诊断为脓毒症-3的患者。将潜在类别混合模型(LCMM)应用于白细胞轨迹,以识别脓毒症亚型。主要结局是28天全因死亡率,次要结局包括对生命支持治疗的需求。使用多变量回归评估白细胞轨迹与结局之间的关联,并在电子ICU数据库中对结果进行外部验证。使用XGBoost模型识别高风险死亡脓毒症亚组的基线特征,以预测患者入住ICU时的亚组分配,并应用SHAP方法解释模型的贡献变量。在7410例脓毒症患者中,识别出八种不同的白细胞轨迹亚型。在这些亚型中,白细胞水平持续较高的患者预后最差(风险比3.00;95%置信区间2.48-3.62),对生命支持治疗的需求显著更高;白细胞水平持续较低的患者死亡风险较高(风险比1.68;95%置信区间1.24-2.27),但接受有创机械通气的可能性较小。将早期ICU基线变量纳入XGBoost算法能够有效预测高死亡风险亚组(曲线下面积>0.8)。SHAP方法揭示了高炎症亚型(4、7和8类)与低炎症亚型(1类)之间不同的早期临床特征。在入住ICU的脓毒症患者中,识别出八种白细胞轨迹,这是预后的关键独立预测因素,与单一白细胞测量结果不同。高死亡风险亚组在入住ICU时表现出不同的临床特征,为其预测和个性化早期干预提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f233/11986166/08b1f574ecbc/41598_2025_96718_Fig1_HTML.jpg

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