识别脓毒症患者的表型可能有助于实现精准医疗方法。然而，这些表型对特定患者群体的普遍性尚不清楚。鉴于脓毒症儿童癌症患者与非癌症患者相比具有不同的宿主反应和病原体特征以及更高的死亡率，我们确定了该特定患者群体中是否存在独特的、可重复的和临床相关的脓毒症表型。患有败血症的潜在恶性肿瘤入院于 25 个儿科重症监护病房 (PICU) 之一，参与欧洲 SCOTER 研究的两个大型、多中心观察队列（n = 383 名患者；研究期为 2018 年 1 月 1 日至 2020 年 1 月 1 日） ）和美国新型数据驱动的儿童脓毒症表型研究（n = 1898 名患者；研究期为 2012 年 1 月 1 日至 2018 年 1 月 1 日）。我们在两个队列中独立使用潜在类别分析 (LCA)，利用 PICU 入院前 24 小时的人口统计、临床和实验室数据来识别表型。然后，我们测试了两个队列中表型与临床结果的关联。LCA 确定了两个队列中具有可比性的两种不同表型。与表型 2 相比，表型 1 的特点是血清碳酸氢盐和白蛋白较低，乳酸明显增加，以及肝、肾和凝血异常。表型 1 患者的 90 天死亡率较高（欧洲队列为 29.2% 对比美国队列为 13.4%） 27.3% vs 11.4%，p < 0.001)，并且比表型 2 的患者接受更多的血管加压药和肾脏替代治疗。在调整器官功能障碍的严重程度、血液癌症、既往干细胞移植和年龄后，表型 1 与调整后的 OR 相关欧洲队列中 90 天的死亡人数为 1.9 (1.04-3.34)，美国队列中的死亡人数为 1.6 (1.2-2.2)。我们在儿科癌症患者中发现了两种临床相关的脓毒症表型，这些表型在两个国际多中心队列中可重复具有预后意义。这些结果可能会指导有关这些特定表型的治疗方法的进一步研究。这项研究的一部分由尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所资助。© 2023 作者。

Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population.We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n = 383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n = 1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24 h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts.LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p < 0.001) and received more vasopressor and renal replacement therapy than patients with phenotype 2. After adjusting for severity of organ dysfunction, haematological cancer, prior stem cell transplantation and age, phenotype 1 was associated with an adjusted OR of death at 90-day of 1.9 (1.04-3.34) in the European cohort and 1.6 (1.2-2.2) in the U.S. cohort.We identified two clinically-relevant sepsis phenotypes in paediatric cancer patients that are reproducible across two international, multicentre cohorts with prognostic implications. These results may guide further research regarding therapeutic approaches for these specific phenotypes.Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.© 2023 The Authors.