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    Outcomes of Sepsis and Septic Shock in Cancer Patients: Focus on Lactate
    (2021)
    LOPEZ HERNANDEZ, RENE RAMON  
    ;
    Rodrigo Pérez-Araos
    ;
    Fernanda Baus
    ;
    Camila Moscoso
    ;
    Álvaro Salazar
    <jats:p>The number of oncological patients (OP) admitted to intensive care units (ICU) for sepsis/septic shock has dramatically increased in recent years. The definition of septic shock has been modified, adding hyperlactatemia as a severity biomarker for mortality. However, it remains poorly reported in septic OP. We performed a retrospective analysis from a prospective database of sepsis/septic shock patients admitted to our ICU between September 2017 and September 2019 and followed until day 90. We identified 251 patients and 31.9% had active oncological comorbidity, mainly solid tumor (81.3%). Septic shock criteria were met for 112 (44.6%). Hyperlactatemia was observed in 136 (54.2%) patients and this was associated with a lower survival rate. Overall 90-day mortality was 15.1%. In OP vs. non-OP, hyperlactatemia was more frequent (65% vs. 49.1%, <jats:italic>p</jats:italic> = 0.013) and associated with lower survival (65.4% vs. 85.7%, <jats:italic>p</jats:italic> = 0.046). In OP, poor performance status was also associated with lower survival (HR 7.029 [1.998–24.731], <jats:italic>p</jats:italic> = 0.002) In an adjusted analysis, cancer was associated with lower 90-day survival (HR 2.690 [1.402–5.160], <jats:italic>p</jats:italic> = 0.003). In conclusion, septic OP remains a high mortality risk group in whom lactate levels and performance status could help with better risk stratification.</jats:p>
    Scopus© Citations 18  1
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    Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
    (2023)
    Danyel Lee
    ;
    Jérémie Le Pen
    ;
    Ahmad Yatim
    ;
    Beihua Dong
    ;
    Yann Aquino
    <jats:p> Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of <jats:italic>OAS1</jats:italic> , <jats:italic>OAS2</jats:italic> , or <jats:italic>RNASEL</jats:italic> in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C. </jats:p>
      11Scopus© Citations 137