Critical Care Explorations (Nov 2021)

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

  • Navin P. Boeddha, MD, PhD,
  • Gertjan J. Driessen, MD, PhD,
  • Nienke N. Hagedoorn, MD,
  • Daniela S. Kohlfuerst, MD,
  • Clive J. Hoggart, PhD,
  • Angelique L. van Rijswijk, MSc,
  • Ebru Ekinci, MD,
  • Debby Priem, BSc,
  • Luregn J. Schlapbach, MD, PhD,
  • Jethro A. Herberg, MD, PhD,
  • Ronald de Groot, MD, PhD,
  • Suzanne T. Anderson, MD, PhD,
  • Colin G. Fink, PhD,
  • Enitan D. Carrol, MD, PhD,
  • Michiel van der Flier, MD, PhD,
  • Federico Martinón-Torres, MD, PhD,
  • Michael Levin, MD, PhD,
  • Frank W. Leebeek, MD, PhD,
  • Werner Zenz, MD, PhD,
  • Moniek P. M. de Maat, PhD,
  • Jan A. Hazelzet, MD, PhD,
  • Marieke Emonts, MD, PhD,
  • Willem A. Dik, PhD,
  • on behalf of the EUCLIDS consortium,
  • Michael Levin,
  • Lachlan Coin,
  • Stuart Gormley,
  • Shea Hamilton,
  • Jethro Herberg,
  • Bernardo Hourmat,
  • Clive Hoggart,
  • Myrsini Kaforou,
  • Vanessa Sancho-Shimizu,
  • Victoria Wright,
  • Amina Abdulla,
  • Paul Agapow,
  • Maeve Bartlett,
  • Evangelos Bellos,
  • Hariklia Eleftherohorinou,
  • Rachel Galassini,
  • David Inwald,
  • Meg Mashbat,
  • Stefanie Menikou,
  • Sobia Mustafa,
  • Simon Nadel,
  • Rahmeen Rahman,
  • Clare Thakker,
  • S Bokhandi,
  • Sue Power,
  • Heather Barham,
  • N Pathan,
  • Jenna Ridout,
  • Deborah White,
  • Sarah Thurston,
  • S Faust,
  • S Patel,
  • Jenni McCorkell,
  • P Davies,
  • Lindsey Crate,
  • Helen Navarra,
  • Stephanie Carter,
  • R Ramaiah,
  • Rekha Patel,
  • Catherine Tuffrey,
  • Andrew Gribbin,
  • Sharon McCready,
  • Mark Peters,
  • Katie Hardy,
  • Fran Standing,
  • Lauren O’Neill,
  • Eugenia Abelake,
  • Akash Deep,
  • Eniola Nsirim,
  • A Pollard,
  • Louise Willis,
  • Zoe Young,
  • C Royad,
  • Sonia White,
  • PM Fortune,
  • Phil Hudnott,
  • Federico Martinón-Torres,
  • Antonio Salas,
  • Fernando Álvez González,
  • Ruth Barral-Arca,
  • Miriam Cebey-López,
  • María José CurrasTuala,
  • Natalia García,
  • Luisa García Vicente,
  • Alberto Gómez-Carballa,
  • Jose Gómez Rial,
  • Andrea Grela Beiroa,
  • Antonio Justicia Grande,
  • Pilar Leboráns Iglesias,
  • Alba Elena Martínez Santos,
  • Federico Martinón-Torres,
  • Nazareth Martinón-Torres,
  • José María Martinón Sánchez,
  • Beatriz Morillo Gutiérrez,
  • Belén Mosquera Pérez,
  • Pablo Obando Pacheco,
  • Jacobo Pardo-Seco,
  • Sara Pischedda,
  • Irene Rivero Calle,
  • Carmen Rodríguez-Tenreiro,
  • Lorenzo Redondo-Collazo,
  • Antonio Salas Ellacuriaga,
  • Sonia Serén Fernández,
  • María del Sol Porto Silva,
  • Ana Vega,
  • Lucía Vilanova Trillo,
  • Susana Beatriz Reyes,
  • María Cruz León León,
  • Álvaro Navarro Mingorance,
  • Xavier Gabaldó Barrios,
  • Eider Oñate Vergara,
  • Andrés Concha Torre,
  • Ana Vivanco,
  • Reyes Fernández,
  • Francisco Giménez Sánchez,
  • Miguel Sánchez Forte,
  • Pablo Rojo,
  • J.Ruiz Contreras,
  • Alba Palacios,
  • Cristina Epalza Ibarrondo,
  • Elizabeth Fernández Cooke,
  • Marisa Navarro,
  • Cristina Álvarez Álvarez,
  • María José Lozano,
  • Eduardo Carreras,
  • Sonia Brió Sanagustín,
  • Olaf Neth,
  • Mª del Carmen Martínez Padilla,
  • Luis Manuel Prieto Tato,
  • Sara Guillén,
  • Laura Fernández Silveira,
  • David Moreno,
  • R. de Groot,
  • A.M. Tutu van Furth,
  • M. van der Flier,
  • N.P. Boeddha,
  • G.J.A. Driessen,
  • M. Emonts,
  • J.A. Hazelzet,
  • T.W. Kuijpers,
  • D. Pajkrt,
  • E.A.M. Sanders,
  • D. van de Beek,
  • A. van der Ende,
  • H.L.A. Philipsen,
  • A.O.A. Adeel,
  • M.A. Breukels,
  • D.M.C. Brinkman,
  • C.C.M.M. de Korte,
  • E. de Vries,
  • W.J. de Waal,
  • R. Dekkers,
  • A. Dings-Lammertink,
  • R.A. Doedens,
  • A.E. Donker,
  • M. Dousma,
  • T.E. Faber,
  • G.P.J.M. Gerrits,
  • J.A.M. Gerver,
  • J. Heidema,
  • J. Homan-van der Veen,
  • M.A.M. Jacobs,
  • N.J.G. Jansen,
  • P. Kawczynski,
  • K. Klucovska,
  • M.C.J. Kneyber,
  • Y. Koopman-Keemink,
  • V.J. Langenhorst,
  • J. Leusink,
  • B.F. Loza,
  • I.T. Merth,
  • C.J. Miedema,
  • C. Neeleman,
  • J.G. Noordzij,
  • C.C. Obihara,
  • A.L.T. van Overbeek – van Gils,
  • G.H. Poortman,
  • S.T. Potgieter,
  • J. Potjewijd,
  • P.P.R. Rosias,
  • T. Sprong,
  • G.W. ten Tussher,
  • B.J. Thio,
  • G.A. Tramper-Strander,
  • M. van Deuren,
  • H. van der Meer,
  • A.J.M. van Kuppevelt,
  • A.M. van Wermeskerken,
  • W.A. Verwijs,
  • T.F.W. Wolfs,
  • Luregn J Schlapbach,
  • Philipp Agyeman,
  • Christoph Aebi,
  • Eric Giannoni,
  • Martin Stocker,
  • Klara M Posfay-Barbe,
  • Ulrich Heininger,
  • Sara Bernhard-Stirnemann,
  • Anita Niederer-Loher,
  • Christian Kahlert,
  • Paul Hasters,
  • Christa Relly,
  • Walter Baer,
  • Christoph Berger,
  • Enitan Carrol,
  • Stéphane Paulus,
  • Hannah Frederick,
  • Rebecca Jennings,
  • Joanne Johnston,
  • Rhian Kenwright,
  • Colin G Fink,
  • Elli Pinnock,
  • Marieke Emonts,
  • Rachel Agbeko,
  • Suzanne Anderson,
  • Fatou Secka,
  • Kalifa Bojang,
  • Isatou Sarr,
  • Ngane Kebbeh,
  • Gibbi Sey,
  • Momodou Saidykhan,
  • Fatoumatta Cole,
  • Gilleh Thomas,
  • Martin Antonio,
  • Werner Zenz,
  • Daniela S. Klobassa,
  • Alexander Binder,
  • Nina A. Schweintzger,
  • Manfred Sagmeister,
  • Hinrich Baumgart,
  • Markus Baumgartner,
  • Uta Behrends,
  • Ariane Biebl,
  • Robert Birnbacher,
  • Jan-Gerd Blanke,
  • Carsten Boelke,
  • Kai Breuling,
  • Jürgen Brunner,
  • Maria Buller,
  • Peter Dahlem,
  • Beate Dietrich,
  • Ernst Eber,
  • Johannes Elias,
  • Josef Emhofer,
  • Rosa Etschmaier,
  • Sebastian Farr,
  • Ylenia Girtler,
  • Irina Grigorow,
  • Konrad Heimann,
  • Ulrike Ihm,
  • Zdenek Jaros,
  • Hermann Kalhoff,
  • Wilhelm Kaulfersch,
  • Christoph Kemen,
  • Nina Klocker,
  • Bernhard Köster,
  • Benno Kohlmaier,
  • Eleni Komini,
  • Lydia Kramer,
  • Antje Neubert,
  • Daniel Ortner,
  • Lydia Pescollderungg,
  • Klaus Pfurtscheller,
  • Karl Reiter,
  • Goran Ristic,
  • Siegfried Rödl,
  • Andrea Sellner,
  • Astrid Sonnleitner,
  • Matthias Sperl,
  • Wolfgang Stelzl,
  • Holger Till,
  • Andreas Trobisch,
  • Anne Vierzig,
  • Ulrich Vogel,
  • Christina Weingarten,
  • Stefanie Welke,
  • Andreas Wimmer,
  • Uwe Wintergerst,
  • Daniel Wüller,
  • Andrew Zaunschirm,
  • Ieva Ziuraite,
  • Veslava Žukovskaja

DOI
https://doi.org/10.1097/CCE.0000000000000569
Journal volume & issue
Vol. 3, no. 11
p. e0569

Abstract

Read online

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 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. 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.