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

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

doi:10.1097/CCE.0000000000000569

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

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 MaatJan A Hazelzet, Marieke Emonts^*, Willem A Dik

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (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.

Original language	English
Article number	e0569
Number of pages	12
Journal	Critical care explorations
Volume	3
Issue number	11
DOIs	https://doi.org/10.1097/CCE.0000000000000569
Publication status	Published - 8 Nov 2021

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10.1097/CCE.0000000000000569Licence: CC BY-NC-ND

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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., ... 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), Article e0569. https://doi.org/10.1097/CCE.0000000000000569

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

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 (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.",

author = "Boeddha, {Navin P} and Driessen, {Gertjan J} and Hagedoorn, {Nienke N} and Kohlfuerst, {Daniela S} and Hoggart, {Clive J} and {van Rijswijk}, {Angelique L} and Ebru Ekinci and Debby Priem and Schlapbach, {Luregn J} and Herberg, {Jethro A} and {de Groot}, Ronald and Anderson, {Suzanne T} and Fink, {Colin G} and Carrol, {Enitan D} and {van der Flier}, Michiel and Federico Martin{\'o}n-Torres and Michael Levin and Leebeek, {Frank W} and Werner Zenz and {de Maat}, {Moniek P M} and Hazelzet, {Jan A} and Marieke Emonts and Dik, {Willem A}",

note = "Copyright {\textcopyright} 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.",

year = "2021",

month = nov,

day = "8",

doi = "10.1097/CCE.0000000000000569",

language = "English",

volume = "3",

journal = "Critical care explorations",

issn = "2639-8028",

publisher = "Lippincott Williams & Wilkins",

number = "11",

}

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 2021, 'Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis', Critical care explorations, vol. 3, no. 11, e0569. https://doi.org/10.1097/CCE.0000000000000569

TY - JOUR

T1 - Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis

AU - Boeddha, Navin P

AU - Driessen, Gertjan J

AU - Hagedoorn, Nienke N

AU - Kohlfuerst, Daniela S

AU - Hoggart, Clive J

AU - van Rijswijk, Angelique L

AU - Ekinci, Ebru

AU - Priem, Debby

AU - Schlapbach, Luregn J

AU - Herberg, Jethro A

AU - de Groot, Ronald

AU - Anderson, Suzanne T

AU - Fink, Colin G

AU - Carrol, Enitan D

AU - van der Flier, Michiel

AU - Martinón-Torres, Federico

AU - Levin, Michael

AU - Leebeek, Frank W

AU - Zenz, Werner

AU - de Maat, Moniek P M

AU - Hazelzet, Jan A

AU - Emonts, Marieke

AU - Dik, Willem A

PY - 2021/11/8

Y1 - 2021/11/8

N2 - 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.

AB - 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.

U2 - 10.1097/CCE.0000000000000569

DO - 10.1097/CCE.0000000000000569

M3 - Article

C2 - 34765980

SN - 2639-8028

VL - 3

JO - Critical care explorations

JF - Critical care explorations

IS - 11

M1 - e0569

ER -

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

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