Boeddha, Navin PNavin PBoeddhaDriessen, Gertjan JGertjan JDriessenHagedoorn, Nienke NNienke NHagedoornKohlfuerst, Daniela SDaniela SKohlfuerstHoggart, Clive JClive JHoggartvan Rijswijk, Angelique LAngelique Lvan RijswijkEkinci, EbruEbruEkinciPriem, DebbyDebbyPriemSchlapbach, Luregn JLuregn JSchlapbachHerberg, Jethro AJethro AHerbergde Groot, RonaldRonaldde GrootAnderson, Suzanne TSuzanne TAndersonFink, Colin GColin GFinkCarrol, Enitan DEnitan DCarrolvan der Flier, MichielMichielvan der FlierMartinón-Torres, FedericoFedericoMartinón-TorresLevin, MichaelMichaelLevinLeebeek, Frank WFrank WLeebeekZenz, WernerWernerZenzde Maat, Moniek PMMoniek PMde MaatHazelzet, Jan AJan AHazelzetEmonts, MariekeMariekeEmontsDik, Willem AWillem ADik2022-08-052022-08-052021-11Critical Care Explorations, 2021, 3 (11), pp.1-122639-8028http://hdl.handle.net/10044/1/98680IMPORTANCE: 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.© 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine. This is an open-access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CC BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 proteinbacterial infectionsbiomarkersinflammationmortalitysepsisJournal Articlehttps://www.dx.doi.org/10.1097/CCE.0000000000000569https://journals.lww.com/ccejournal/Fulltext/2021/11000/Detectable_A_Disintegrin_and_Metalloproteinase.12.aspx2791852639-8028