Leukocyte activation in sepsis; correlations with disease state and mortality

Kobold, Anneke Muller; Tulleken, Jaap; Zijlstra, Jan G.; Sluiter, Willem; Hermans, J.; Kallenberg, Cornelis; Tervaert, Jwc

doi:10.1007/s001340051277

Cited by 182 publications

(123 citation statements)

References 24 publications

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“…However, we found that a CD64 index cut-off of 1.58 may be optimal for prediction of survival length in subjects with VAP-induced sepsis. The levels were significant (p = 0.046), and survival curve analysis showed much longer time of survival in subjects with lower CD64 index, similar to the findings of Song et al [33] and Muller et al [38]. In addition, the culturing methods are also of great importance because they identify the pathogen, and more focused and targeted antibiotic therapy could be applied, which could prolong the survival of the subject or even cure the disease.…”

Section: Discussionsupporting

confidence: 81%

CD64 index on neutrophils can diagnose sepsis and predict 30-day survival in subjects after ventilator-associated pneumonia

Muzlovič

Ihan

Stubljar

2016

J Infect Dev Ctries

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Introduction: Sepsis associated with ventilator-associated pneumonia (VAP) causes mortality in intensive care unit (ICU) patients. The time of diagnosis is crucial, and microbiological cultures take time. In this study, the diagnostic accuracy of CD64 index to predict VAP-induced sepsis and survival time in subjects requiring mechanical ventilation were evaluated and compared to conventional biomarkers and culturing methods. Methodology: A total of 32 subjects with VAP were included. Sepsis after VAP was diagnosed in 25 (78.1%) patients according to clinical signs, radiographic examination, and samples of blood and trachea taken for culturing. Simultaneously with cultures, CD64 index on neutrophils, C-reactive protein (CRP), procalcitonin (PCT), and count of leucocytes and neutrophils were determined. Results: Biomarker values were evaluated in both groups of subjects (with and without sepsis after VAP). The values of CD64 index and CRP were significantly higher in the sepsis group. Receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.929 for CD64 index in differentiating subjects with VAP-induced sepsis from those without sepsis. The biomarkers CRP and PCT showed comparable results (AUC of 0.869 and 0.909, respectively). Blood cultures were positive in 12 subjects, endotracheal aspirate in 19. CD64 index and isolation of pathogen with positive blood cultures or from endotracheal aspirate (positive in 24 cases) could predict survival time before application of more targeted antibiotic therapy. Conclusions: CD64 index may be used as a useful diagnostic tool to recognize VAP-induced sepsis; moreover, accompanied with an identified pathogen, can predict survival for ICU patients.

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Section: Discussionsupporting

confidence: 81%

CD64 index on neutrophils can diagnose sepsis and predict 30-day survival in subjects after ventilator-associated pneumonia

Muzlovič

Ihan

Stubljar

2016

J Infect Dev Ctries

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“…Neutrophil adhesion molecule expression increases with sepsis (18,19), but it is unclear whether statins alter neutrophil adhesion molecule expression during infections and whether this might improve or hinder cellular responses to infection. There are many unanswered questions about the non-cholesterol-lowering effects of statins, and there is considerable interest in how statins might improve inflammatory outcomes.…”

mentioning

confidence: 99%

Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin

Sapey

Patel

Greenwood

et al. 2017

Am J Respir Crit Care Med

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Rationale: Dysregulated neutrophil functions with age and sepsis are described. Statins are associated with improved infection survival in some observational studies, but trials in critically ill patients have not shown benefit. Statins also alter neutrophil responses in vitro.Objectives: To assess neutrophil migratory accuracy with age during respiratory infections and determine if and how a statin intervention could alter these blunted responses.Methods: The migratory accuracy of blood neutrophils from young (aged ,35 yr) and old (aged .60 yr) patients in health and during a lower respiratory tract infection, community-acquired pneumonia, and pneumonia associated with sepsis was assessed with and without simvastatin. In vitro results were confirmed in a double-blind randomized clinical trial in healthy elders. Cell adhesion markers were assessed. Measurements and Main Results:In vitro neutrophil migratory accuracy in the elderly deteriorated as the severity of the infectious pulmonary insult increased, without recovery at 6 weeks. Simvastatin rescued neutrophil migration with age and during mild to moderate infection, at high dose in older adults, but not during more severe sepsis. Confirming in vitro results, high-dose (80-mg) simvastatin improved neutrophil migratory accuracy without impeding other neutrophil functions in a double-blind randomized clinical trial in healthy elders. Simvastatin modified surface adhesion molecule expression and activity, facilitating accurate migration in the elderly.Conclusions: Infections in older adults are associated with prolonged, impaired neutrophil migration, potentially contributing to poor outcomes. Statins improve neutrophil migration in vivo in health and in vitro in milder infective events, but not in severe sepsis, supporting their potential utility as an early intervention during pulmonary infections.Clinical trial registered with www.clinicaltrialsregister.eu (2011-002082-38).

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“…Additionally, accumulation of neutrophils in the vasculature and peripheral organs can result in non-specific cell and tissue damage, further complicating sepsis-induced organ dysfunction (Brown et al, 2006). Paradoxically, however, decreased neutrophil function during acute phase sepsis (characterized by decreased chemotactic responses and impaired surface receptor expression) is correlated with decreased survival in human patients, suggesting that the suppression of the antimicrobial functions of neutrophils is not enough to protect against sepsis-induced mortality (Chishti et al, 2004;Muller Kobold et al, 2000). Importantly, neutrophils are critical for the clearance of many nosocomial infections, as well as central to the innate immune responses against many experimental models of "two-hit" post-septic immunosuppression.…”

Section: Immune Cell Dysfunction During Sirsmentioning

confidence: 99%