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Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study.

ABSTRACT: Intensive care unit (ICU)-acquired infections (IAI) result in increased hospital and ICU stay, costs and mortality. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine for the identification of patients at risk of IAI. We evaluated the association of the systemic mRNA expression of two host response biomarkers, CD74 and IL10, with IAI occurrence in a large cohort of ICU patients.ICU patients were prospectively enrolled in a multicenter cohort study. Whole blood was collected on the day of admission (D1) and on day 3 (D3) and day 6 (D6) after admission. Patients were screened daily for IAI occurrence and data were censored after IAI diagnosis. mRNA expression levels of biomarkers were measured using RT-qPCR. Fine and Gray competing risk models were used to assess the association between gene expression and IAI occurrence.A total of 725 patients were analyzed. At least one IAI episode occurred in 137 patients (19%). After adjustment for shock and sepsis status at admission, CD74 and IL10 levels were found to be significantly associated with IAI occurrence [subdistribution hazard ratio (95% confidence interval) 0.67 (0.46-0.97) for CD74 D3/D1 expression ratio and 2.21 (1.63-3.00) for IL10 at D3]. IAI cumulative incidence was significantly different between groups stratified according to CD74 or IL10 expression (Gray tests p < 0.001).Our results suggest that two immune biomarkers, CD74 and IL10, could be relevant tools for the identification of IAI risk in ICU patients.

SUBMITTER: Peronnet E

PROVIDER: S-EPMC5487586 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study.

Peronnet Estelle E Venet Fabienne F Maucort-Boulch Delphine D Friggeri Arnaud A Cour Martin M Argaud Laurent L Allaouchiche Bernard B Floccard Bernard B Aubrun Frédéric F Rimmelé Thomas T Thiolliere Fabrice F Piriou Vincent V Bohé Julien J Cazalis Marie-Angélique MA Barbalat Véronique V Monneret Guillaume G Morisset Stéphane S Textoris Julien J Vallin Hélène H Pachot Alexandre A Lepape Alain A

Intensive care medicine 20170505 7

<h4>Purpose</h4>Intensive care unit (ICU)-acquired infections (IAI) result in increased hospital and ICU stay, costs and mortality. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine for the identification of patients at risk of IAI. We evaluated the association of the systemic mRNA expression of two host response biomarkers, CD74 and IL10, with IAI occurrence in a large cohort of ICU patients.<h4>Methods</h4>ICU patients were prospectively enrolled i ...[more]

PMID: 28477143

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Project description:BACKGROUND:Neuroinflammation is thought to play an important role in the pathogenesis of ICU-acquired delirium, but the association between inflammatory and brain-specific proteins and ICU delirium is poor. We investigated whether or not serial determinations of markers may improve this association. METHODS:Critically ill patients with a high risk of ICU delirium and with an ICU length of stay of at least 6 days were included in the study. Blood was drawn on days 1, 2, 4 and 6 after ICU admission and analyzed for different markers of inflammation and several brain proteins. Differences in courses over time prior to and following the onset of delirium and absolute differences over time were analyzed in patients with and without delirium using repeated measurement analysis of variance. In addition, a cross-sectional analysis of levels of these markers before the first onset of delirium was performed. RESULTS:Fifty patients were included in this study. In the longitudinal analysis, there were no differences in the levels of any of the markers immediately prior to and following the onset of delirium, but overall, median levels of adiponectin (9019 (IQR 5776-15,442) vs. 6148 (IQR 4447-8742) ng/ml, p?=?0.05) were significantly higher in patients with delirium compared to patients without delirium. In the cross-sectional analysis, median levels of the brain protein Tau (90 (IQR 46-224) vs. 31 (IQR 31-52) pg/ml, p?=?0.009) and the ratio Tau/amyloid ?1-42 (1.42 ((IQR 0.9-2.57) vs. 0.68 (IQR 0.54-0.96), p?=?0.003) were significantly higher in patients with hypoactive delirium compared to patients without. Levels of neopterin (111 (IQR 37-111) vs. 29 (IQR 16-64) mmol/l, p?=?0.004) and IL-10 (28 (IQR 12-39) vs. 9 (IQR 4-12) pg/ml, p?=?0.001) were significantly higher in patients with hypoactive delirium compared to patients with mixed-type delirium. CONCLUSIONS:While there are differences in markers (adiponectin and several brain proteins) between patients with and without delirium, the development of delirium is not preceded by a change in the biomarker profile of inflammatory markers or brain proteins. Patients with hypoactive delirium account for the observed differences in biomarkers. TRIAL REGISTRATION:ClinicalTrials.gov, NCT 01274819 . Registered on 12 January 2011.

Project description:Daytime intensivist physician staffing is associated with improved outcomes in the ICU. However, it is unclear whether this association persists in the era of interprofessional, protocol-directed critical care. We sought to reexamine the association between daytime intensivist physician staffing and ICU mortality and determine if interprofessional rounding and protocols for mechanical ventilation in part mediate this relationship.Retrospective cohort study of ICUs in the Acute Physiology and Chronic Health Evaluation clinical information system from 2009 to 2010.Forty-nine ICUs in 25 U.S. hospitals.Adults (17 yr and older) admitted to a study ICU.None.We defined high-intensity daytime intensivist staffing as either a mandatory consult or closed ICU model; interprofessional rounds as rounds that included a respiratory therapist, pharmacist, physician and nurse; and protocol use as having protocols for liberation from mechanical ventilation and lung protective mechanical ventilation. Using multivariable logistic regression, we estimated the independent effect of daytime intensivist physician staffing on in-hospital mortality controlling for interprofessional rounds and protocols for mechanical ventilation, as well as other patient and hospital characteristics. Twenty-seven ICUs (55%) reported high-intensity daytime physician staffing, 42 ICUs (85%) reported daily interprofessional rounds, and 31 (63%) reported having protocols for mechanical ventilation. There was no association between daytime intensivist physician staffing and in-hospital mortality (adjusted odds ratio, 0.86; 95% CI, 0.65-1.14). After adjusting for interprofessional rounds and protocols for mechanical ventilation, the effect of daytime intensivist physician staffing remained nonsignificant (adjusted odds ratio, 0.90; 95% CI, 0.70-1.17).High-intensity daytime physician staffing in the ICU was not significantly associated with lower mortality in a modern cohort. This association was not affected by interprofessional rounds or protocols for mechanical ventilation.

Project description:BackgroundSyndrome of transient bone marrow suppression may result from various extra-hematological diseases, such as immunological deregulations, and viral infectious diseases secondarily affecting the function of hematopoietic stem cells.ObjectiveTo evaluate the pathogenic role of herpes viruses and their contraction with IL10 cytokine gene polymorphism, which can impair hematopoiesis in patients with transient bone marrow suppression.MethodsIn a cross-sectional study 30 patients who admitted to Namazi Hospital, affiliated to Shiraz University of Medical Sciences, with transient bone marrow suppression were recruited. Diagnosis of the transient bone marrow suppression was made by expert hematologists. A control group consisting of 100 healthy unrelated individuals was also included. One EDTA-treated blood sample was collected from each studied patients and plasma was isolated. The molecular prevalence of cytomegalovirus and HHV8 evaluated was evaluated using real-time and nested PCR protocols, respectively. The SNPs of the IL10 (rs 1800896-1082G/A) cytokine gene was evaluated by PCR-RFLP method.ResultsCytomegalovirus and HHV8 infections were found in 2 and 3 of studied patients with transient bone marrow suppression. Significant higher frequency of IL10 G allele and GG genotype were found in HHV8-infected patients comparing to uninfected ones. Higher frequencies of A allele and AG and AA genotypes of IL10 were found in cytomegalovirus-uninfected patients comparing to infected ones, respectively. The significant higher frequencies of IL10 AA and AG genotypes were found in controls compared to bone marrow suppressed patients.ConclusionIL10 genetic polymorphism might have determinative role in resistance to the cytomegalovirus, especially HHV8 infections, in patients with bone marrow suppression. Focus in new interaction between HHV8 infection and IL10 genetics in bone marrow suppressed patients should be completed by the analysis of the anti-herpes virus immunity in future studies.

Dataset Information

Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study.

Publications

Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study.

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