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Boeddha NP, Driessen GJ, Hagedoorn NN, et al. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis. Crit Care Explor. 2021;3(11):e0569doi: 10.1097/CCE.0000000000000569.
Boeddha, N. P., Driessen, G. J., Hagedoorn, N. N., Kohlfuerst, D. S., Hoggart, C. J., van Rijswijk, A. L., Ekinci, E., Priem, D., Schlapbach, L. J., Herberg, J. A., de Groot, R., Anderson, S. T., Fink, C. G., Carrol, E. D., van der Flier, M., Martinón-Torres, F., Levin, M., Leebeek, F. W., Zenz, W., de Maat, M. P. M., Hazelzet, J. A., Emonts, M., & Dik, W. A. (2021). Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis. Critical care explorations, 3(11), e0569. https://doi.org/10.1097/CCE.0000000000000569
Boeddha, Navin P, et al. "Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis." Critical care explorations vol. 3,11 (2021): e0569. doi: https://doi.org/10.1097/CCE.0000000000000569
Boeddha NP, Driessen GJ, Hagedoorn NN, Kohlfuerst DS, Hoggart CJ, van Rijswijk AL, Ekinci E, Priem D, Schlapbach LJ, Herberg JA, de Groot R, Anderson ST, Fink CG, Carrol ED, van der Flier M, Martinón-Torres F, Levin M, Leebeek FW, Zenz W, de Maat MPM, Hazelzet JA, Emonts M, Dik WA. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis. Crit Care Explor. 2021 Nov 08;3(11):e0569. doi: 10.1097/CCE.0000000000000569. eCollection 2021 Nov. PMID: 34765980; PMCID: PMC8577672.
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Crit Care Explor. 2021 Nov 08;3(11):e0569. doi: 10.1097/CCE.0000000000000569. eCollection 2021 Nov.

Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis.

Critical care explorations

Navin P Boeddha, Gertjan J Driessen, Nienke N Hagedoorn, Daniela S Kohlfuerst, Clive J Hoggart, Angelique L van Rijswijk, Ebru Ekinci, Debby Priem, Luregn J Schlapbach, Jethro A Herberg, Ronald de Groot, Suzanne T Anderson, Colin G Fink, Enitan D Carrol, Michiel van der Flier, Federico Martinón-Torres, Michael Levin, Frank W Leebeek, Werner Zenz, Moniek P M de Maat, Jan A Hazelzet, Marieke Emonts, Willem A Dik

Affiliations

  1. Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  2. Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  3. Department of Paediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
  4. Department of General Paediatrics, Medical University of Graz, Graz, Austria.
  5. Section of Pediatrics, Imperial College London, London, United Kingdom.
  6. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY.
  7. Laboratory Medical Immunology, Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  8. Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  9. Child Health Research Center, The University of Queensland, Brisbane, QLD, Australia.
  10. Queensland Children`s Hospital, Brisbane, QLD, Australia.
  11. Pediatric and Neonatal Intensive Care Unit, University Children's Hospital Zurich, Zurich, Switzerland.
  12. Radboudumc Technology Center Clinical Studies, Radboudumc, Nijmegen, The Netherlands.
  13. Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands.
  14. Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, The Netherlands.
  15. MRC Unit The Gambia at the LSHTM, Banjul, The Gambia.
  16. Micropathology Ltd, University of Warwick Science Park, Venture Centre, Coventry, United Kingdom.
  17. Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
  18. Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, UMC Utrecht, Utrecht, The Netherlands.
  19. Paediatric Infectious Diseases and Immunology, Radboudumc, Nijmegen, The Netherlands.
  20. Translational Pediatrics and Infectious Diseases Section, Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
  21. Genetics-Vaccines-Infectious Diseases and Pediatrics research group GENVIP, Health Research Institute of Santiago IDIS/SERGAS, Santiago de Compostela, Spain.
  22. Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  23. Paediatric Infectious Diseases and Immunology Department, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
  24. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
  25. NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, Newcastle upon Tyne, United Kingdom.

PMID: 34765980 PMCID: PMC8577672 DOI: 10.1097/CCE.0000000000000569

Abstract

IMPORTANCE: A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking.

OBJECTIVES: To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome.

DESIGN: Data from two prospective cohort studies.

SETTING AND PARTICIPANTS: Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission).

MAIN OUTCOMES AND MEASURES: Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay.

RESULTS: In cohort 1 (

CONCLUSIONS AND RELEVANCE: In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.

Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

Keywords: A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein; bacterial infections; biomarkers; inflammation; mortality; sepsis

Conflict of interest statement

The authors have disclosed that they do not have any potential conflicts of interest.

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