Uncovering heterogeneity in sepsis: a comparative analysis of subphenotypes

被引:41
作者
van Amstel, Rombout B. E. [1 ,2 ]
Kennedy, Jason N. [3 ]
Scicluna, Brendon P. [4 ,5 ]
Bos, Lieuwe D. J. [1 ,2 ]
Peters-Sengers, Hessel [6 ,7 ]
Butler, Joe M. [6 ]
Cano-Gamez, Eddie [8 ]
Knight, Julian C. [8 ]
Vlaar, Alexander P. J. [1 ,2 ]
Cremer, Olaf L. [9 ]
Angus, Derek C. [3 ]
van der Poll, Tom [6 ,10 ]
Seymour, Christopher W. [3 ]
van Vught, Lonneke A. [1 ,6 ]
机构
[1] Locat Univ Amsterdam, Dept Intens Care Med, Amsterdam UMC, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
[2] Locat Univ Amsterdam, Lab Expt Intens Care & Anesthesiol LEICA, Amsterdam UMC, Amsterdam, Netherlands
[3] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA
[4] Univ Malta, Mater Dei Hosp, Fac Hlth Sci, Dept Appl Biomed Sci, Msida, Malta
[5] Univ Malta, Ctr Mol Med & Biobanking, Msida, Malta
[6] Locat Univ Amsterdam, Ctr Expt & Mol Med, Amsterdam UMC, Amsterdam Infect & Immun, Amsterdam, Netherlands
[7] Locat Vrije Univ Amsterdam, Amsterdam UMC, Epidemiol & Data Sci, Amsterdam, Netherlands
[8] Univ Oxford, Wellcome Ctr Human Genet, Oxford OX3 7BN, England
[9] Univ Med Ctr Utrecht, Dept Intens Care, Utrecht, Netherlands
[10] Locat Univ Amsterdam, Dept Internal Med, Div Infect Dis, Amsterdam UMC, Amsterdam, Netherlands
基金
美国国家卫生研究院;
关键词
Sepsis; ARDS; Phenotype; Precision medicine; Intensive care; BURDEN;
D O I
10.1007/s00134-023-07239-w
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Purpose The heterogeneity in sepsis is held responsible, in part, for the lack of precision treatment. Many attempts to identify subtypes of sepsis patients identify those with shared underlying biology or outcomes. To date, though, there has been limited effort to determine overlap across these previously identified subtypes. We aimed to determine the concordance of critically ill patients with sepsis classified by four previously described subtype strategies. Methods This secondary analysis of a multicenter prospective observational study included 522 critically ill patients with sepsis assigned to four previously established subtype strategies, primarily based on: (i) clinical data in the electronic health record (alpha, beta, gamma, and delta), (ii) biomarker data (hyper- and hypoinflammatory), and (iii-iv) transcriptomic data (Mars1-Mars4 and SRS1-SRS2). Concordance was studied between different subtype labels, clinical characteristics, biological host response aberrations, as well as combinations of subtypes by sepsis ensembles. Results All four subtype labels could be adjudicated in this cohort, with the distribution of the clinical subtype varying most from the original cohort. The most common subtypes in each of the four strategies were gamma (61%), which is higher compared to the original classification, hypoinflammatory (60%), Mars2 (35%), and SRS2 (54%). There was no clear relationship between any of the subtyping approaches (Cramer's V=0.086-0.456). Mars2 and SRS1 were most alike in terms of host response biomarkers (p=0.079-0.424), while other subtype strategies showed no clear relationship. Patients enriched for multiple subtypes revealed that characteristics and outcomes differ dependent on the combination of subtypes made. Conclusion Among critically ill patients with sepsis, subtype strategies using clinical, biomarker, and transcriptomic data do not identify comparable patient populations and are likely to reflect disparate clinical characteristics and underlying biology.
引用
收藏
页码:1360 / 1369
页数:10
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