The study was approved by the local Institutional Human Research Committee and conducted according to the ethical guidelines and principles of the international Helsinki declaration. After informed consent, 20 healthy male subjects ≥20 years (31.4±7.9 years) with normal physical cardiac examination (with no systolic nor diastolic murmur), normal ECG, without history of any cardiovascular disease or history of current smoking, no chronic excessive alcohol consumption, not currently on medical therapy with cardio-active drugs were prospectively recruited. Every volunteer was asked not to practice Background-Cardiac magnetic resonance (CMR) is increasingly used for the diagnosis and management of cardiac diseases. Recent studies have reported immediate post-CMR DNA double-strand breaks in T lymphocytes. We sought to evaluate CMR-induced DNA damage in lymphocytes, alterations of blood cells, and their temporal persistence. Methods and Results-In 20 prospectively enrolled healthy men (31.4±7.9 years), blood was drawn before and after (1-2 hours, 2 days, 1 month, and 1 year) unenhanced 1.5T CMR. Blood cell counts, cell death, and activation status of lymphocytes, monocytes, neutrophils, and platelets were evaluated. The first 2-hour post-CMR were characterized by a small increase of lymphocyte B and neutrophil counts and a transient drop of total lymphocytes because of a decrease in natural killer cells. Among blood cells, only neutrophils and monocytes displayed slight and transient activation.DNA double-strand breaks in lymphocytes were quantified through flow cytometric analysis of H2AX phosphorylation (γ-H2AX). γ-H2AX intensity in T lymphocytes did not change early after CMR but increased significantly at day 2 ≤1 month before returning to baseline levels of 1-year post-CMR. Conclusions-Unenhanced CMR is associated with minor but significant immediate blood cell alterations or activations figuring inflammatory response, as well as DNA damage in T lymphocytes observed from day 2 until the first month but disappearing at 1-year follow-up. Although further studies are required to definitely state whether CMR can be used safely, our findings already call for caution when it comes to repeat this examination within a month. (Circ Cardiovasc Imaging. 2015;8:e003697.

BackgroundPlatelets have been involved in both immune surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients.MethodsThis single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury, and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48 h later, and then at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded.MethodsOf the 99 patients, 19 developed sepsis after a median time of 5 days. These patients had a higher SOFA score at admission; levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were also significantly increased compared to the other patients. Levels 48 h after ICU admission no longer differed between the two patient groups. Platelet-Fg % was an independent predictor of sepsis (P = 0.0031). By ROC curve analysis, cutoff point for Platelet-Fg (AUC = 0.75) was 50%. In patients with a SOFA cutoff of 8, the risk of sepsis reached 87% when Platelet-Fg levels were above 50%. Patients with sepsis had longer ICU and hospital stays and higher death rate.ConclusionsPlatelet-bound fibrinogen levels assayed by flow cytometry within 24 h of ICU admission help identifying critically ill patients at risk of developing sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-017-0145-2) contains supplementary material, which is available to authorized users.

The early identification of bacteremia is critical for ensuring appropriate treatment of nosocomial infections in intensive care unit (ICU) patients. The aim of this study was to use flow cytometric data of myeloid cells as a biomarker of bloodstream infection (BSI). An eight-color antibody panel was used to identify seven monocyte and two dendritic cell subsets. In the learning cohort, immunophenotyping was applied to (1) control subjects, (2) postoperative heart surgery patients, as a model of noninfectious inflammatory responses, and (3) blood culture-positive patients. Of the complex changes in the myeloid cell phenotype, a decrease in myeloid and plasmacytoid dendritic cell numbers, increase in CD14+CD16+ inflammatory monocyte numbers, and upregulation of neutrophils CD64 and CD123 expression were prominent in BSI patients. An extreme gradient boosting (XGBoost) algorithm called the “infection detection and ranging score” (iDAR), ranging from 0 to 100, was developed to identify infection-specific changes in 101 phenotypic variables related to neutrophils, monocytes and dendritic cells. The tenfold cross-validation achieved an area under the receiver operating characteristic (AUROC) of 0.988 (95% CI 0.985–1) for the detection of bacteremic patients. In an out-of-sample, in-house validation, iDAR achieved an AUROC of 0.85 (95% CI 0.71–0.98) in differentiating localized from bloodstream infection and 0.95 (95% CI 0.89–1) in discriminating infected from noninfected ICU patients. In conclusion, a machine learning approach was used to translate the changes in myeloid cell phenotype in response to infection into a score that could identify bacteremia with high specificity in ICU patients.

Sepsis in critically ill patients with injury bears a high morbidity and mortality. Extensive phenotypic monitoring of leucocyte subsets in critically ill patients at ICU admission and during sepsis development is still scarce. The main objective of this study was to identify early changes in leukocyte phenotype which would correlate with later development of sepsis. MethodsPatients who were admitted in a tertiary ICU for organ support after severe injury (elective cardiac surgery, trauma, necessity of prolonged ventilation or stroke) were sampled on admission (T1) and 48-72h later (T2) for phenotyping of leukocyte subsets by ow cytometry and cytokines measurements. Those who developed secondary sepsis or septic shock were sampled again on the day of sepsis diagnosis (Tx). ResultsNinety-nine patients were included in the nal analysis. Nineteen (19.2%) patients developed secondary sepsis or septic shock. They presented signi cantly higher absolute monocyte counts and CRP at T1 compared to non-septic patients (1030/µl versus 55/µl, p = 0.013 and 5.1mg/ml versus 2.5mg/ml, p = 0.046, respectively). They also presented elevated levels of monocytes with low expression of L-selectin (CD62L neg monocytes)(OR[95%CI]: 4.5 (1.4-14.5) p = 0.01) and higher SOFA score (p < 0.0001) at T1 and low mHLA-DR at T2 (OR[95%CI]: 0.003 (0.00-0.17) p = 0.049). Stepwise logistic regression analysis showed that both monocyte markers and high SOFA score (> 8) were independent predictors of nosocomial sepsis occurrence. No other leucocyte count or surface marker nor any cytokine measurement correlated with sepsis occurrence. ConclusionMonocyte counts and change of phenotype are predictive of secondary sepsis in critically ill patients with injury.

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