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.2639-8028Boeddha, Navin P <br />Driessen, Gertjan J <br />Hagedoorn, Nienke N <br />Kohlfuerst, Daniela S <br />Hoggart, Clive J <br />van Rijswijk, Angelique L <br />Ekinci, Ebru <br />Priem, Debby <br />Schlapbach, Luregn J <br />Herberg, Jethro A <br />de Groot, Ronald <br />Anderson, Suzanne T <br />Fink, Colin G <br />Carrol, Enitan D <br />van der Flier, Michiel <br />Martinón-Torres, Federico <br />Levin, Michael <br />Leebeek, Frank W <br />Zenz, Werner <br />de Maat, Moniek P M <br />Hazelzet, Jan A <br />Emonts, Marieke <br />Dik, Willem A <br />Journal Article <br />Crit Care Explor. 2021 Nov 8;3(11):e0569. doi: 10.1097/CCE.0000000000000569. eCollection 2021 Nov. <br />