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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References
- Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (sepsis-3).JAMA. 2016; 315: 775-787
- Sepsis is a preventable public health problem.Crit Care. 2018; 22: 116
- Long-term mortality and quality of life in sepsis: a systematic review.Crit Care Med. 2010; 38: 1276-1283
- The immune system's role in sepsis progression, resolution, and long-term outcome.Immunol Rev. 2016; 274: 330-353
- Sepsis induces a dysregulated neutrophil phenotype that is associated with increased mortality.Mediators Inflamm. 2018; 20184065362
- Source of circulating pentraxin 3 in septic shock patients.Front Immunol. 2018; 9: 3048
- The clinical consequences of neutrophil priming.Curr Opin Hematol. 2019; 26: 22-27
- Serum osteopontin levels are upregulated and predict disability after an ischaemic stroke.Eur J Clin Invest. 2015; 45: 579-586
- Osteopontin at the crossroads of inflammation and tumor progression.Mediators Inflamm. 2017; 20174049098
- Serum levels of osteopontin predict major adverse cardiovascular events in patients with severe carotid artery stenosis.Int J Cardiol. 2018; 255: 195-199
- Radiologic cerebral reperfusion at 24 h predicts good clinical outcome.Transl Stroke Res. 2018;
- Serum levels of osteopontin predict diabetes remission after bariatric surgery.Diabetes Metab. 2018;
Carbone F, Dallegri F, Montecucco F, Poggi A, Nobili FM, Cacciapaglia F, et al. Serum osteopontin negatively impacts on intima media thickness in patients with SLE. Eur J Clin Invest. 2019:e13089.
- Albumin replacement in patients with severe sepsis or septic shock.N Engl J Med. 2014; 370: 1412-1421
- Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.Crit Care Med. 2013; 41: 580-637
- The ACCP-SCCM consensus conference on sepsis and organ failure.Chest. 1992; 101: 1481-1483
- The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the working group on Sepsis-related problems of the European society of intensive care medicine..Intensive Care Med. 1996; 22: 707-710
- Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial.Intensive Care Med. 2015; 41: 12-20
- Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial.Eur J Clin Invest. 2017; 47: 73-83
- Osteopontin impairs host defense during established gram-negative sepsis caused by Burkholderia pseudomallei (melioidosis).PLoS Negl Trop Dis. 2010; : 4
- Osteopontin is associated with inflammation and mortality in a mouse model of polymicrobial sepsis.Acta Anaesthesiol Scand. 2015; 59: 170-175
- Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung injury.Crit Care. 2015; 19: 53
- Neutralization of osteopontin ameliorates acute lung injury induced by intestinal ischemia-reperfusion.Shock. 2016; 46: 431-438
- Modulation of infection-mediated migration of neutrophils and CXCR2 trafficking by osteopontin.Immunology. 2017; 150: 74-86
- Osteopontin impairs host defense during pneumococcal pneumonia.J Infect Dis. 2011; 203: 1850-1858
- Osteopontin exacerbates Pseudomonas aeruginosa-induced bacteremia in mice.Cell Immunol. 2017; 318: 23-28
- Osteopontin protects against lung injury caused by extracellular histones.Mucosal Immunol. 2019; 12: 39-50
- Intracellular osteopontin (iOPN) and immunity.Immunol Res. 2011; 49: 160-172
- Pre- and post-translational regulation of osteopontin in cancer.J Cell Commun Signal. 2011; 5: 111-122
- Serum levels of osteopontin are increased in SIRS and sepsis.Intensive Care Med. 2008; 34: 2176-2184
- Persistently elevated osteopontin serum levels predict mortality in critically ill patients.Crit Care. 2015; 19: 271
- The role of osteopontin as a diagnostic and prognostic biomarker in sepsis and septic shock.Cells. 2019; : 8
- Assessing the feasibility of neutralizing osteopontin with various therapeutic antibody modalities.Scientific reports. 2018; 8: 7781
Article info
Publication history
Published online: May 11, 2020
Accepted:
April 15,
2020
Received in revised form:
February 25,
2020
Received:
September 23,
2019
Identification
Copyright
© 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
