Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes-an international multicentre retrospective study


Por: Wösten-van Asperen RM, la Roi-Teeuw HM, van Amstel RB, Bos LD, Tissing WJ, Jordán-García I, Dohna-Schwake C, Bottari G, Pappachan J, Crazzolara R, Comoretto RI, Mizia-Malarz A, Moscatelli A, Sánchez-Martín M, Willems J, Rogerson CM, Bennett TD, Luo Y, Atreya MR, Faustino EVS, Geva A, Weiss SL, Schlapbach LJ and Sanchez-Pinto LN

Publicada: 1 nov 2023 Ahead of Print: 1 oct 2023
Categoría: Medicine (miscellaneous)

Resumen:
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, multicentre, 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.Copyright (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Filiaciones:
Wösten-van Asperen RM:
 Department of Paediatric Intensive Care, University Medical Centre Utrecht/Wilhelmina Children's Hospital, Utrecht, the Netherlands

la Roi-Teeuw HM:
 Department of Paediatric Intensive Care, University Medical Centre Utrecht/Wilhelmina Children's Hospital, Utrecht, the Netherlands

van Amstel RB:
 Intensive Care, Amsterdam UMC-location AMC, University of Amsterdam, Amsterdam, the Netherlands

Bos LD:
 Intensive Care, Amsterdam UMC-location AMC, University of Amsterdam, Amsterdam, the Netherlands

Tissing WJ:
 Princess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands

 Department of Paediatric Oncology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands

Jordán-García I:
 Department of Paediatric Intensive Care and Institut de Recerca, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

 Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain

Dohna-Schwake C:
 Department of Paediatrics I, Paediatric Intensive Care, Children's Hospital Essen, Germany

 West German Centre for Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany

Bottari G:
 Paediatric Intensive Care Unit, Children's Hospital Bambino Gesù, IRCSS, Rome, Italy

Pappachan J:
 Department of Paediatric Intensive Care, Southampton Children's Hospital, UK

Crazzolara R:
 Department of Paediatrics, Paediatric Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria

Comoretto RI:
 Department of Paediatric Intensive Care, Department of Woman's and Child's Health, Padua University Hospital, Padua, Italy

Mizia-Malarz A:
 Department of Paediatric Oncology, Haematology and Chemotherapy Unit, Medical University of Silesia, Katowice, Poland

Moscatelli A:
 Neonatal and Paediatric Intensive Care Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy

Sánchez-Martín M:
 Department of Paediatric Intensive Care, Hospital Universitario La Paz, Madrid, Spain

Willems J:
 Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium

Rogerson CM:
 Department of Paediatrics, Division of Critical Care, Indianapolis University School of Medicine, Indianapolis, IN, USA

Bennett TD:
 Departments of Biomedical Informatics and Paediatrics, University of Colorado School of Medicine, Aurora, CO, USA

Luo Y:
 Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Atreya MR:
 Department of Paediatrics (Critical Care), University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Centre, Cincinnati, OH, USA

Faustino EVS:
 Department of Paediatrics, Yale School of Medicine, New Haven, CT, USA

Geva A:
 Department of Anaesthesiology, Critical Care, and Pain Medicine and Computational Health Informatics Program, Boston Children's Hospital, USA

 Department of Anaesthesia, Harvard Medical School, Boston, MA, USA

Weiss SL:
 Division of Critical Care, Department of Paediatrics, Nemours Children's Health, Delaware, USA

Schlapbach LJ:
 Department of Intensive Care and Neonatology and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland

 Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia

Sanchez-Pinto LN:
 Department of Paediatrics (Critical Care) and Preventive Medicine (Health & Biomedical Informatics), Northwestern University Feinberg School of Medicine and Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA
ISSN: 25895370





EClinicalMedicine
Editorial
ELSEVIER, RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS, Reino Unido
Tipo de documento: Article
Volumen: 65 Número:
Páginas: 102252-102252
WOS Id: 001094023300001
ID de PubMed: 37842550
imagen gold, Green Published

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