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10.1097/CCM.0000000000001402

http://scihub22266oqcxt.onion/10.1097/CCM.0000000000001402
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suck abstract from ncbi


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pmid26584195
      Crit+Care+Med 2016 ; 44 (2 ): 275-81
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  • Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial #MMPMID26584195
  • Shakoory B ; Carcillo JA ; Chatham WW ; Amdur RL ; Zhao H ; Dinarello CA ; Cron RQ ; Opal SM
  • Crit Care Med 2016[Feb]; 44 (2 ): 275-81 PMID26584195 show ga
  • OBJECTIVE: To determine the efficacy of anakinra (recombinant interleukin-1 receptor antagonist) in improving 28-day survival in sepsis patients with features of macrophage activation syndrome. Despite equivocal results in sepsis trials, anakinra is effective in treating macrophage activation syndrome, a similar entity with fever, disseminated intravascular coagulation, hepatobiliary dysfunction, cytopenias, and hyperferritinemia. Hence, sepsis patients with macrophage activation syndrome features may benefit from interleukin-1 receptor blockade. DESIGN: Reanalysis of deidentified data from the phase III randomized interleukin-1 receptor antagonist trial in severe sepsis. SETTING: Multicenter study recruiting through 91 centers from 11 countries in Europe and North America. PATIENTS: Sepsis patients with multiorgan dysfunction syndrome and/or shock (original study) were regrouped based on the presence or the absence of concurrent hepatobiliary dysfunction and disseminated intravascular coagulation as features of macrophage activation syndrome. The non-hepatobiliary dysfunction/disseminated intravascular coagulation group included patients with only hepatobiliary dysfunction, only disseminated intravascular coagulation, or neither. INTERVENTION: Treatment with anakinra or placebo. MEASUREMENTS AND MAIN RESULTS: Main outcome was 28-day mortality. Descriptive and comparative statistics were performed. Data were available for 763 adults from the original study cohort, randomized to receive either anakinra or placebo. Concurrent hepatobiliary dysfunction/disseminated intravascular coagulation was noted in 43 patients (5.6% of total; 18-75 years old; 47% women). The 28-day survival was similar in both anakinra and placebo-treated non-hepatobiliary dysfunction/disseminated intravascular coagulation patients (71.4% vs 70.8%; p = 0.88). Treatment with anakinra was associated with significant improvement in the 28-day survival rate in hepatobiliary dysfunction/disseminated intravascular coagulation patients (65.4% anakinra vs 35.3% placebo), with hazard ratio for death 0.28 (0.11-0.71; p = 0.0071) for the treatment group in Cox regression. CONCLUSIONS: In this subgroup analysis, interleukin-1 receptor blockade was associated with significant improvement in survival of patients with sepsis and concurrent hepatobiliary dysfunction/disseminated intravascular coagulation. A prospective randomized trial using features of macrophage activation syndrome for mortality risk stratification should be undertaken to confirm the role of interleukin-1 blockage.
  • |APACHE [MESH]
  • |Acute Kidney Injury/epidemiology [MESH]
  • |Adolescent [MESH]
  • |Adult [MESH]
  • |Age Factors [MESH]
  • |Aged [MESH]
  • |Aged, 80 and over [MESH]
  • |Biliary Tract Diseases/epidemiology [MESH]
  • |Disseminated Intravascular Coagulation/*epidemiology [MESH]
  • |Double-Blind Method [MESH]
  • |Female [MESH]
  • |Humans [MESH]
  • |Interleukin 1 Receptor Antagonist Protein/*therapeutic use [MESH]
  • |Liver Diseases/epidemiology [MESH]
  • |Macrophage Activation Syndrome/*epidemiology [MESH]
  • |Male [MESH]
  • |Middle Aged [MESH]
  • |Multiple Organ Failure/drug therapy/epidemiology [MESH]
  • |Receptors, Interleukin-1/*antagonists & inhibitors [MESH]
  • |Respiratory Distress Syndrome/epidemiology [MESH]
  • |Sepsis/*drug therapy/*epidemiology/mortality [MESH]
  • |Sex Factors [MESH]
  • |Shock, Septic/drug therapy/epidemiology [MESH]


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