TY - JOUR
T1 - Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective study
AU - Wösten-van Asperen, Roelie M.
AU - la Roi-Teeuw, Hannah M.
AU - van Amstel, Rombout BE
AU - Bos, Lieuwe DJ
AU - Tissing, Wim JE
AU - Jordan, Iolanda
AU - Dohna-Schwake, Christian
AU - Bottari, Gabriella
AU - Pappachan, John
AU - Crazzolara, Roman
AU - Comoretto, Rosanna I.
AU - Mizia-Malarz, Agniezka
AU - Moscatelli, Andrea
AU - Sánchez-Martín, María
AU - Willems, Jef
AU - Rogerson, Colin M.
AU - Bennett, Tellen D.
AU - Luo, Yuan
AU - Atreya, Mihir R.
AU - Faustino, E. Vincent S.
AU - Geva, Alon
AU - Weiss, Scott L.
AU - Schlapbach, Luregn J.
AU - Sanchez-Pinto, L. Nelson
AU - Caballero, Marina
AU - Margarit, Adriana
AU - Campos, Roi
AU - Möller, Paula
AU - Serpe, Carmela
AU - Amigoni, Angela
AU - Damps, Maria
AU - Montaguti, Alessia
AU - Tardini, Giacomo
AU - Bubeck-Wardenburg, Juliane
AU - Farris, Reid Farris
AU - Hall, Mark
AU - Chong, Grace
AU - Shah, Sareen
AU - Khemani, Robinder
AU - Stroup, Emily
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/10/5
Y1 - 2023/10/5
N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
KW - Latent class analysis
KW - Oncology
KW - Paediatric intensive care
KW - Phenotype
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=85173678037&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2023.102252
DO - 10.1016/j.eclinm.2023.102252
M3 - Article
C2 - 37842550
AN - SCOPUS:85173678037
SN - 2589-5370
VL - 65
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 102252
ER -