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Early osteopontin levels predict mortality in patients with septic shock

  • Author Footnotes
    1 These authors equally contributed as first authors
    Federico Carbone
    Correspondence
    Corresponding author.
    Footnotes
    1 These authors equally contributed as first authors
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa – Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
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  • Author Footnotes
    1 These authors equally contributed as first authors
    Aldo Bonaventura
    Footnotes
    1 These authors equally contributed as first authors
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Pauley Heart Center, 1200 East Marshall Street, 23298 Richmond, VA, US
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  • Alessandra Vecchiè
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Pauley Heart Center, 1200 East Marshall Street, 23298 Richmond, VA, US
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  • Jennifer Meessen
    Affiliations
    Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 19 Via Giuseppe La Masa, 20156 Milan, Italy
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  • Silvia Minetti
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa – Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
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  • Edoardo Elia
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Daniele Ferrara
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Anna Maria Ansaldo
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Giorgio Tulli
    Affiliations
    Regional Health Agency of Tuscany, Firenze, Italy
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  • Diletta Guarducci
    Affiliations
    UO Anestesia e Rianimazione, Ospedale Santa Maria Annunziata, 58 via Antella, 50012 Ponte a Niccheri, Bagno a Ripoli, Italy
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  • Nicola Rossi
    Affiliations
    Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 19 via della Commenda, 20122 Milan, Italy
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  • Francesco Bona
    Affiliations
    UO Anestesia, Rianimazione e Terapia Antalgica, Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia – IRCCS Strada Provinciale 142 Km 3,95 10060 Candiolo, Italy
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  • Marta Ferrari
    Affiliations
    Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy

    SCDU Anestesia e Rianimazione, Azienda Ospedaliero-Universitaria S. Luigi Gonzaga, Orbassano (TO), Italy
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  • Pietro Caironi
    Affiliations
    Dipartimento di Oncologia, Università degli Studi di Torino, Turin, Italy
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  • Roberto Latini
    Affiliations
    Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 19 Via Giuseppe La Masa, 20156 Milan, Italy
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  • Fabrizio Montecucco
    Affiliations
    IRCCS Ospedale Policlinico San Martino Genoa – Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy

    First Clinic of Internal Medicine, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Author Footnotes
    1 These authors equally contributed as first authors

      Highlights

      • Immune host dysregulation is critical for the evolution of sepsis to septic shock.
      • Osteopontin recently raised some interest in immune-related diseases (i.e. cancer, cardiovascular and autoimmune diseases).
      • Osteopontin predicts mortality, duration of hospitalization, and infection resolution in patients with septic shock

      Abstract

      Background

      Inflammatory biomarkers could be useful to stratify the risk of sepsis adverse outcome and potentially improving the clinical management. Here, we investigated the prognostic role of the inflammatory molecule osteopontin (OPN) in patients with severe sepsis with and without septic shock.

      Material and methods

      This is a sub-analysis of 957 patients with sepsis/septic shock from the Albumin Italian Outcome Sepsis (ALBIOS) study. Alongside demographic, clinical, and laboratory data, we assessed plasmatic values of OPN at day 1, 2 and 7 after enrolment. The primary outcome was the predictive role of OPN values at day 1on death for any cause at 28 days after enrolment.

      Results

      Plasma OPN values at day 1 were higher in patients with septic shock and correlated with the severity of multi-organ dysfunction. Once categorized for 28-day mortality, survivors were characterized by lower OPN levels at each time point and statistically significant drop overtime (p<0.001 for all). Similarly, OPN reduction during the first 7 days was associated with reduced hospitalization and mortality overtime. Multivariate logistic and Cox regression models confirmed plasma OPN at day 1 as predictor of both 28- and 90-day mortality and infection resolution as well, independently of demographic, clinical and therapeutic variables. However, this prognostic value was limited to septic shock patients.

      Conclusions

      In patients with septic shock, OPN plasma levels at day 1 predict a poor clinical outcome. These results provide the rationale for future pathophysiological studies aimed at clarifying the mechanisms triggered by OPN in septic shock (ALBIOS ClinicalTrials.gov Identifier: NCT00707122).

      Keywords

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