Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in context
Summary: 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...
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| Language: | English |
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Elsevier
2023-11-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023004297 |
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| author | Roelie M. Wösten-van Asperen Hannah M. la Roi-Teeuw Rombout BE. van Amstel Lieuwe DJ. Bos Wim JE. Tissing Iolanda Jordan Christian Dohna-Schwake Gabriella Bottari John Pappachan Roman Crazzolara Rosanna I. Comoretto Agniezka Mizia-Malarz Andrea Moscatelli María Sánchez-Martín Jef Willems Colin M. Rogerson Tellen D. Bennett Yuan Luo Mihir R. Atreya E.Vincent S. Faustino Alon Geva Scott L. Weiss Luregn J. Schlapbach L Nelson Sanchez-Pinto Marina Caballero Adriana Margarit Roi Campos Paula Möller Carmela Serpe Angela Amigoni Maria Damps Alessia Montaguti Giacomo Tardini Juliane Bubeck-Wardenburg Reid Farris Farris Mark Hall Grace Chong Sareen Shah Robinder Khemani Emily Stroup |
| author_facet | Roelie M. Wösten-van Asperen Hannah M. la Roi-Teeuw Rombout BE. van Amstel Lieuwe DJ. Bos Wim JE. Tissing Iolanda Jordan Christian Dohna-Schwake Gabriella Bottari John Pappachan Roman Crazzolara Rosanna I. Comoretto Agniezka Mizia-Malarz Andrea Moscatelli María Sánchez-Martín Jef Willems Colin M. Rogerson Tellen D. Bennett Yuan Luo Mihir R. Atreya E.Vincent S. Faustino Alon Geva Scott L. Weiss Luregn J. Schlapbach L Nelson Sanchez-Pinto Marina Caballero Adriana Margarit Roi Campos Paula Möller Carmela Serpe Angela Amigoni Maria Damps Alessia Montaguti Giacomo Tardini Juliane Bubeck-Wardenburg Reid Farris Farris Mark Hall Grace Chong Sareen Shah Robinder Khemani Emily Stroup |
| author_sort | Roelie M. Wösten-van Asperen |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-09T14:25:36Z |
| format | Article |
| id | doaj.art-321a489219864978bfeed9d74886200b |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-09T14:25:36Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-321a489219864978bfeed9d74886200b2023-11-28T07:26:41ZengElsevierEClinicalMedicine2589-53702023-11-0165102252Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in contextRoelie M. Wösten-van Asperen0Hannah M. la Roi-Teeuw1Rombout BE. van Amstel2Lieuwe DJ. Bos3Wim JE. Tissing4Iolanda Jordan5Christian Dohna-Schwake6Gabriella Bottari7John Pappachan8Roman Crazzolara9Rosanna I. Comoretto10Agniezka Mizia-Malarz11Andrea Moscatelli12María Sánchez-Martín13Jef Willems14Colin M. Rogerson15Tellen D. Bennett16Yuan Luo17Mihir R. Atreya18E.Vincent S. Faustino19Alon Geva20Scott L. Weiss21Luregn J. Schlapbach22L Nelson Sanchez-Pinto23Marina CaballeroAdriana MargaritRoi CamposPaula MöllerCarmela SerpeAngela AmigoniMaria DampsAlessia MontagutiGiacomo TardiniJuliane Bubeck-WardenburgReid Farris FarrisMark HallGrace ChongSareen ShahRobinder KhemaniEmily StroupDepartment of Paediatric Intensive Care, University Medical Centre Utrecht/Wilhelmina Children’s Hospital, Utrecht, the Netherlands; Corresponding author. Department of Paediatric Intensive Care, University Medical Centre Utrecht/Wilhelmina Children’s Hospital, Lundlaan 6, Utrecht 3584 EA, Netherlands.Department of Paediatric Intensive Care, University Medical Centre Utrecht/Wilhelmina Children’s Hospital, Utrecht, the NetherlandsIntensive Care, Amsterdam UMC—location AMC, University of Amsterdam, Amsterdam, the NetherlandsIntensive Care, Amsterdam UMC—location AMC, University of Amsterdam, Amsterdam, the NetherlandsPrincess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands; Department of Paediatric Oncology, University of Groningen, University Medical Centre Groningen, Groningen, the NetherlandsDepartment 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, SpainDepartment of Paediatrics I, Paediatric Intensive Care, Children’s Hospital Essen, Germany; West German Centre for Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, GermanyPaediatric Intensive Care Unit, Children’s Hospital Bambino Gesù, IRCSS, Rome, ItalyDepartment of Paediatric Intensive Care, Southampton Children’s Hospital, UKDepartment of Paediatrics, Paediatric Intensive Care Unit, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Paediatric Intensive Care, Department of Woman's and Child's Health, Padua University Hospital, Padua, ItalyDepartment of Paediatric Oncology, Haematology and Chemotherapy Unit, Medical University of Silesia, Katowice, PolandNeonatal and Paediatric Intensive Care Unit, IRCCS Istituto Giannina Gaslini, Genova, ItalyDepartment of Paediatric Intensive Care, Hospital Universitario La Paz, Madrid, SpainDepartment of Paediatric Intensive Care, Ghent University Hospital, Ghent, BelgiumDepartment of Paediatrics, Division of Critical Care, Indianapolis University School of Medicine, Indianapolis, IN, USADepartments of Biomedical Informatics and Paediatrics, University of Colorado School of Medicine, Aurora, CO, USADepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USADepartment of Paediatrics (Critical Care), University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH, USADepartment of Paediatrics, Yale School of Medicine, New Haven, CT, USADepartment 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, USADivision of Critical Care, Department of Paediatrics, Nemours Children’s Health, Delaware, USADepartment 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, AustraliaDepartment 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, USASummary: 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.http://www.sciencedirect.com/science/article/pii/S2589537023004297Paediatric intensive careOncologySepsisPhenotypeLatent class analysis |
| spellingShingle | Roelie M. Wösten-van Asperen Hannah M. la Roi-Teeuw Rombout BE. van Amstel Lieuwe DJ. Bos Wim JE. Tissing Iolanda Jordan Christian Dohna-Schwake Gabriella Bottari John Pappachan Roman Crazzolara Rosanna I. Comoretto Agniezka Mizia-Malarz Andrea Moscatelli María Sánchez-Martín Jef Willems Colin M. Rogerson Tellen D. Bennett Yuan Luo Mihir R. Atreya E.Vincent S. Faustino Alon Geva Scott L. Weiss Luregn J. Schlapbach L Nelson Sanchez-Pinto Marina Caballero Adriana Margarit Roi Campos Paula Möller Carmela Serpe Angela Amigoni Maria Damps Alessia Montaguti Giacomo Tardini Juliane Bubeck-Wardenburg Reid Farris Farris Mark Hall Grace Chong Sareen Shah Robinder Khemani Emily Stroup Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in context EClinicalMedicine Paediatric intensive care Oncology Sepsis Phenotype Latent class analysis |
| title | Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in context |
| title_full | Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in context |
| title_fullStr | Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in context |
| title_full_unstemmed | Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in context |
| title_short | Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective studyResearch in context |
| title_sort | distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes an international multicentre retrospective studyresearch in context |
| topic | Paediatric intensive care Oncology Sepsis Phenotype Latent class analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2589537023004297 |
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