Development and validation of dynamic clinical subphenotypes in acute pancreatitis patients using vital sign trajectories in intensive care units: a multinational cohort study

作者：Zichen Wang, Wen Wang, Jiayue Xu, Qiao He, Che Sun, Shuangyi Xie, Kang Zou, Qing Xia, Xin Sun · 发表于：Signal Transduction and Targeted Therapy · 年份：2025 · DOI：10.1038/s41392-025-02261-4 · 被引用次数：14 · 研究领域：Pancreatitis Pathology and Treatment、Abdominal Surgery and Complications、Pancreatic and Hepatic Oncology Research

Acute pancreatitis (AP) is a heterogeneous inflammatory condition. Although emerging therapeutic strategies targeting pathways such as calcium signaling, TNF-α, the NLRP3 inflammasome, and HMGB1 have shown promise, their efficacy may be limited by the underlying biological heterogeneity of the disease. In this multinational retrospective cohort study across three large ICU databases (ICU-HAI, MIMIC-IV, and eICU-CRD), we used group-based trajectory modeling of early vital signs to identify four distinct AP subphenotypes: hyperinflammatory, hypertensive, hypotensive, and hypoinflammatory. These subtypes differed markedly in 30-day mortality, inflammatory burden, and hemodynamic stability. Compared to the hypertensive phenotype, hyperinflammatory and hypotensive patients had significantly higher 30-day mortality risks (HR = 3.38 and HR = 1.87, respectively), while the hypoinflammatory phenotype carried no excess risk. Fluid resuscitation responses were phenotype-specific: hyperinflammatory patients benefited from higher fluid volumes, whereas hypoinflammatory patients were at risk of fluid overload. Notably, distinct subphenotypes displayed unique responses to fluid intake over the first two ICU days. For hyperinflammatory phenotype, the algorithm-estimated lowest-risk fluid range was 4100-4300 mL on day 1 and 3400-3600 mL on day 2; for phenotype hypoinflammatory phenotype, the optimal ranges were 2800-3800 mL and 1400-2600 mL, respectively. Early use of lactated Ringer's soluti...