PurposeCellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients.MethodsMulti-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections.ResultsA total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00–4.74), 3.44 (1.58–7.47) and 2.41 (1.14–5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9.ConclusionsThis study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.Trial registrationThe study was registered with clinicaltrials.gov (NCT02186522).Electronic supplementary materialThe online version of this article (10.1007/s00134-018-5247-0) contains supplementary material, which is available to authorized users.

The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically.(ABSTRACT TRUNCATED AT 250 WORDS)

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BackgroundThe BD FACSPresto™ Near-Patient CD4 Counter was developed to expand HIV/AIDS management in resource-limited settings. It measures absolute CD4 counts (AbsCD4), percent CD4 (%CD4), and hemoglobin (Hb) from a single drop of capillary or venous blood in approximately 23 minutes, with throughput of 10 samples per hour. We assessed the performance of the BD FACSPresto system, evaluating accuracy, stability, linearity, precision, and reference intervals using capillary and venous blood at KEMRI/CDC HIV-research laboratory, Kisumu, Kenya, and precision and linearity at BD Biosciences, California, USA.MethodsFor accuracy, venous samples were tested using the BD FACSCalibur™ instrument with BD Tritest™ CD3/CD4/CD45 reagent, BD Trucount™ tubes, and BD Multiset™ software for AbsCD4 and %CD4, and the Sysmex™ KX-21N for Hb. Stability studies evaluated duration of staining (18–120-minute incubation), and effects of venous blood storage <6–24 hours post-draw. A normal cohort was tested for reference intervals. Precision covered multiple days, operators, and instruments. Linearity required mixing two pools of samples, to obtain evenly spaced concentrations for AbsCD4, total lymphocytes, and Hb.ResultsAbsCD4 and %CD4 venous/capillary (N = 189/ N = 162) accuracy results gave Deming regression slopes within 0.97–1.03 and R2 ≥0.96. For Hb, Deming regression results were R2 ≥0.94 and slope ≥0.94 for both venous and capillary samples. Stability varied within 10% 2 hours after staining and for venous blood stored less than 24 hours. Reference intervals results showed that gender—but not age—differences were statistically significant (p<0.05). Precision results had <3.5% coefficient of variation for AbsCD4, %CD4, and Hb, except for low AbsCD4 samples (<6.8%). Linearity was 42–4,897 cells/μL for AbsCD4, 182–11,704 cells/μL for total lymphocytes, and 2–24 g/dL for Hb.ConclusionsThe BD FACSPresto system provides accurate, precise clinical results for capillary or venous blood samples and is suitable for near-patient CD4 testing.Trial RegistrationClinicalTrials.gov NCT02396355