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e1 References 1 Tantalean JA, Leon RJ, Santos AA, Sanchez E Multiple organ dysfunc tion syndrome in children Pediatr Crit Care Med 2003;4(2) 181 185 2 Weiss SL, Fitzgerald JC, Pappachan J, et al Globa[.]

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A, Jayanthan A, Behrens EM, Cron RQ Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: Case series with 12 patients Rheumatology (Oxford) 2011;50(2):417-419 40 De Benedetti F, Brunner HI, Ruperto N, et al Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis N Engl J Med 2012;367(25):2385-2395 e2 41 Record JL, Beukelman T, Cron RQ Combination therapy of abatacept and anakinra in children with refractory systemic juvenile idiopathic arthritis: A retrospective case series J Rheumatol 2011;38(1):180-181 42 Simon DW, Aneja R, Carcillo JA, Halstead ES Plasma exchange, methylprednisolone, IV immune globulin, and now anakinra support continued PICU equipoise in management of hyperferritinemia-associated sepsis/multiple organ dysfunction syndrome/ macrophage activation syndrome/secondary hemophagocytic lymphohistiocytosis syndrome* Pediatr Crit Care Med 2014;15(5): 486-488 43 Kinjo N, Hamada K, Hirayama C, Shimizu M Role of plasma exchange, leukocytapheresis, and plasma diafiltration in management of refractory macrophage activation syndrome J Clin Apher 2018; 33(1):117-120 44 Frimmel S, Hinz M, Schipper J, Bogdanow S, Mitzner S, Koball S Cytokine adsorption is a promising tool in the therapy of hemophagocytic lymphohistiocytosis Int J Artif Organs 2019;42(11): 658-664 45 Brouwer WP, Duran S, Kuijper M, Ince C Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day allcause mortality in ICU patients with septic shock: A propensityscore-weighted retrospective study Crit Care 2019;23(1):317 46 Malard B, Lambert C, Kellum JA In vitro comparison of the adsorption of inflammatory mediators by blood purification devices Intensive Care Med Exp 2018;6(1):12 47 Pickkers P, Vassiliou T, Liguts V, et al Sepsis management with a blood purification membrane: European experience Blood Purif 2019;47(suppl 3):1-9 48 Payen D, Faivre V, Miatello J, et al Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression A case series BMC Infect Dis 2019;19(1):931 49 Venet F, Monneret G Advances in the understanding and treatment of sepsis-induced immunosuppression Nat Rev Nephrol 2018;14(2):121-137 50 Krispinsky LT, Stark RJ, Parra DA, et al Endothelial-dependent vasomotor dysfunction in infants after cardiopulmonary bypass Pediatr Crit Care Med 2020;21(1):42-49 51 Kuiper JW, Tibboel D, Ince C The vulnerable microcirculation in the critically ill pediatric patient Crit Care 2016;20(1):352 52 Doyle NA, Bhagwan SD, Meek BB, et al Neutrophil margination, sequestration, and emigration in the lungs of L-selectin-deficient mice J Clin Invest 1997;99(3):526-533 53 Paddock CD, Sanden GN, Cherry JD, et al Pathology and pathogenesis of fatal Bordetella pertussis infection in infants Clin Infect Dis 2008;47(3):328-338 54 Richard JF, Roy M, Audoy-Remus J, Tremblay P, Vallieres L Crawling phagocytes recruited in the brain vasculature after pertussis toxin exposure through IL6, ICAM1 and ITGalphaM Brain Pathol 2011;21(6):661-671 55 Nguyen TC, Cruz MA, Carcillo JA Thrombocytopenia-associated multiple organ failure and acute kidney injury Crit Care Clin 2015;31(4):661-674 56 Chong M, Lopez-Magallon AJ, Saenz L, et al Use of therapeutic plasma exchange during extracorporeal life support in critically ill cardiac children with thrombocytopenia-associated multi-organ failure Front Pediatr 2017;5:254 57 Nguyen TC, Han YY, Kiss JE, et al Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure Crit Care Med 2008;36(10):2878-2887 58 Legendre CM, Licht C, Muus P, et al Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome N Engl J Med 2013;368(23):2169-2181 59 Charles PE, Tissieres P, Barbar SD, et al Mild-stretch mechanical ventilation upregulates toll-like receptor and sensitizes the lung to bacterial lipopeptide Crit Care 2011;15(4):R181 60 Wang C, Li Q, Ren J Microbiota-immune interaction in the pathogenesis of gut-derived infection Front Immunol 2019;10:1873 61 Lyons JD, Coopersmith CM Pathophysiology of the gut and the microbiome in the host response Pediatr Crit Care Med 2017; 18(3_suppl Suppl 1):S46-S49 62 Olofsson PS, Rosas-Ballina M, Levine YA, Tracey KJ Rethinking inflammation: Neural circuits in the regulation of immunity Immunol Rev 2012;248(1):188-204 63 Tracey KJ Reflex control of immunity Nat Rev Immunol 2009;9(6):418-428 64 Wang DW, Yin YM, Yao YM Vagal modulation of the inflammatory response in sepsis Int Rev Immunol 2016;35(5):415-433 65 Davis AL, Carcillo JA, Aneja RK, et al American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock Crit Care Med 2017;45(6): 1061-1093 66 Carcillo JA, Berg RA, Wessel D, et al A multicenter network assessment of three inflammation phenotypes in pediatric sepsis-induced multiple organ failure Pediatr Crit Care Med 2019;20(12):11371146 67 Rubio I, Osuchowski MF, Shankar-Hari M, et al Current gaps in sepsis immunology: New opportunities for translational research Lancet Infect Dis 2019;19(12):e422-e436 68 Fortenberry JD, Nguyen T, Grunwell JR, et al Therapeutic plasma exchange in children with thrombocytopenia-associated multiple organ failure: The thrombocytopenia-associated multiple organ failure network prospective experience Crit Care Med 2019;47(3):e173-e181 69 Sevketoglu E, Yildizdas D, Horoz OO, et al Use of therapeutic plasma exchange in children with thrombocytopenia-associated multiple organ failure in the Turkish thrombocytopenia-associated multiple organ failure network Pediatr Crit Care Med 2014;15(8):354 70 Proulx F, Fayon M, Farrell CA, Lacroix J, Gauthier M Epidemiology of sepsis and multiple organ dysfunction syndrome in children Chest 1996;109(4):1033-1037 71 Leteurtre S, Duhamel A, Grandbastien B, et al Daily estimation of the severity of multiple organ dysfunction syndrome in critically ill children CMAJ 2010;182(11):1181-1187 72 Leteurtre S, Duhamel A, Deken V, Lacroix J, Leclerc F, Groupe Francophone de Reanimation et Urgences Pediatriques Daily estimation of the severity of organ dysfunctions in critically ill children by using the PELOD-2 score Crit Care 2015;19:324 73 Leteurtre S, Martinot A, Duhamel A, et al Validation of the paediatric logistic organ dysfunction (PELOD) score: Prospective, observational, multicentre study Lancet 2003;362(9379):192-197 74 Graciano AL, Balko JA, Rahn DS, Ahmad N, Giroir BP The pediatric multiple organ dysfunction score (P-MODS): Development and validation of an objective scale to measure the severity of multiple organ dysfunction in critically ill children Crit Care Med 2005;33(7):1484-1491 75 Shime N, Kageyama K, Ashida H, Tanaka Y Application of modified sequential organ failure assessment score in children after cardiac surgery J Cardiothorac Vasc Anesth 2001;15(4):463-468 76 Sweney JS, Poss WB, Grissom CK, Keenan HT Comparison of severity of illness scores to physician clinical judgment for potential use in pediatric critical care triage Disaster Med Public Health Prep 2012;6(2):126-130 77 Matics TJ, Sanchez-Pinto LN Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the sepsis-3 definitions in critically ill children JAMA Pediatr 2017;171(10):e172352 78 Schlapbach LJ, Straney L, Bellomo R, MacLaren G, Pilcher D Prognostic accuracy of age-adapted SOFA, SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit Intensive Care Med 2018;44(2):179-188 79 Sandri M, Berchialla P, Baldi I, Gregori D, De Blasi RA Dynamic Bayesian networks to predict sequences of organ failures in patients admitted to ICU J Biomed Inform 2014;48:106-113 e3 80 Typpo KV, Petersen NJ, Hallman DM, Markovitz BP, Mariscalco MM Day multiple organ dysfunction syndrome is associated with poor functional outcome and mortality in the pediatric intensive care unit Pediatr Crit Care Med 2009;10(5):562-570 81 Proulx F, Joyal JS, Mariscalco MM, Leteurtre S, Leclerc F, Lacroix J The pediatric multiple organ dysfunction syndrome Pediatr Crit Care Med 2009;10(1):12-22 82 Lin JC, Spinella PC, Fitzgerald JC, et al New or progressive multiple organ dysfunction syndrome in pediatric severe sepsis: A sepsis phenotype with higher morbidity and mortality Pediatr Crit Care Med 2017;18(1):8-16 83 Andruszkow H, Fischer J, Sasse M, et al Interleukin-6 as inflammatory marker referring to multiple organ dysfunction syndrome in severely injured children Scand J Trauma Resusc Emerg Med 2014;22:16-16 84 Kraft R, Herndon DN, Finnerty CC, Shahrokhi S, Jeschke MG Occurrence of multiorgan dysfunction in pediatric burn patients: Incidence and clinical outcome Ann Surg 2014;259(2):381-387 85 Jeschke MG, Pinto R, Kraft R, et al Morbidity and survival probability in burn patients in modern burn care Crit Care Med 2015;43(4):808-815 86 Feickert HJ, Schepers AK, Rodeck B, Geerlings H, Hoyer PF Incidence, impact on survival, and risk factors for multi-organ system failure in children following liver transplantation Pediatr Transplant 2001;5(4):266-273 87 Jacobe SJ, Hassan A, Veys P, Mok Q Outcome of children requiring admission to an intensive care unit after bone marrow transplantation Crit Care Med 2003;31(5):1299-1305 88 Bestati N, Leteurtre S, Duhamel A, et al Differences in organ dysfunctions between neonates and older children: A prospective, observational, multicenter study Crit Care 2010;14(6):R202 89 Proulx F, Fayon M, Farrell CA, Lacroix J, Gauthier M Epidemiology of sepsis and multiple organ dysfunction syndrome in children Chest 1996;109(4):1033-1037 90 Lacroix J, Hebert PC, Hutchison JS, et al Transfusion strategies for patients in pediatric intensive care units N Engl J Med 2007; 356(16):1609-1619 91 Tucci M, Lacroix J, Fergusson D, et al The age of blood in pediatric intensive care units (ABC PICU): Study protocol for a randomized controlled trial Trials 2018;19(1):404 92 Agus MS, Wypij D, Hirshberg EL, et al Tight glycemic control in critically ill children N Engl J Med 2017;376(8):729-741 93 Leclerc F, Leteurtre S, Duhamel A, et al Cumulative influence of organ dysfunctions and septic state on mortality of critically ill children Am J Respir Crit Care Med 2005;171(4):348-353 94 Odetola FO, Gebremariam A, Freed GL Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis Pediatrics 2007;119(3):487-494 95 Matics TJ, Pinto NP, Sanchez-Pinto LN Association of organ dysfunction scores and functional outcomes following pediatric critical illness Pediatr Crit Care Med 2019;20(8):722-727 e4 Abstract: Pediatric multiple-organ dysfunction syndrome (MODS) represents the leading final pathway to death in children who suffer critical illness triggered by acute insults such as sepsis, trauma, burns, pancreatitis, inborn errors of metabolism, transplantation, and others Of children admitted to the pediatric intensive care unit (PICU), 14% to 30% have MODS on PICU day The incidence of new MODS during the PICU stay is estimated to be 22% to 39% The pathophysiologic host response to an injury and subsequent organ failure is complex, involving diverse cellular, immune, neurohumoral, and vascular responses: mitochondrial dysfunction; innate and adaptive immune alterations, microcirculatory dysfunction and ischemia-reperfusion injury, epithelial dysfunction, and neurohumoral changes Key words: organ dysfunction, multiple-organ failure, sepsis, thrombocytopenia-associated multiple-organ failure, TAMOF, immunoparalysis-associated multiple-organ failure, IPAMOF, sequential liver failure–associated multiple-organ failure, SMOF, therapeutic plasma exchange SECTION XII Pediatric Critical Care: Environmental Injury and Trauma 12.  Bites and Stings, 1318 113.  Hyperthermic Injury, 1327 114.  Accidental Hypothermia, 1332 115.  Drowning, 1337 116.  Burn and Inhalation Injury, 1347 117. Evaluation, Stabilization, and Initial Management After Trauma, 1363 118.  Traumatic Brain Injury, 1375 119.  Pediatric Thoracic Trauma, 1401 120.  Pediatric Abdominal Trauma, 1408 121.  Child Abuse, 1417 1317 ... Combination therapy of abatacept and anakinra in children with refractory systemic juvenile idiopathic arthritis: A retrospective case series J Rheumatol 2011;38(1):180-181 42 Simon DW, Aneja R,... Care Med 2017; 18(3_suppl Suppl 1):S46-S49 62 Olofsson PS, Rosas-Ballina M, Levine YA, Tracey KJ Rethinking inflammation: Neural circuits in the regulation of immunity Immunol Rev 2012;248(1):188-204... failure network Pediatr Crit Care Med 2014;15(8):354 70 Proulx F, Fayon M, Farrell CA, Lacroix J, Gauthier M Epidemiology of sepsis and multiple organ dysfunction syndrome in children Chest 1996;109(4):1033-1037

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