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Sepsis and septic shock frequently cause the admission or complicate the clinical course of critically ill patients admitted in the intensive care units (ICU). Genetic variations disrupting the immune sensing of infectious organisms, could affect the ability of the immune system to respond to infection, and may influence both the genetic predisposition to infection and the diversity of the clinical presentation of sepsis. The aim of this study was to uncover possible associations between common functional immune gene polymorphisms (of both innate and adaptive immunity) and ICU-acquired sepsis and mortality. The TLR4-D299G (rs4986790), TLR4-T399I (rs4986791), C2-c.841_849+19del28 (rs9332736), TACI-C104R (rs34557412), BAFFR-P21R (rs77874543), and BAFFR-H159Y (rs61756766) polymorphisms were detected in a cohort of 215 critically ill patients, admitted in an 8-bed medical/surgical ICU. Interestingly, TLR4-D299G, TLR4-T399I and BAFFR-P21R carriage was associated with a lower risk of ICU-acquired sepsis. This association applied particularly in medical patients, while in trauma and surgical patients no significant associations were observed. Moreover, carriers of TACI-C104R displayed an undiagnosed mild to moderate hypogammaglobulinemia along with a significantly lower survival rate in the ICU, although lethal events were not attributed to sepsis. These findings further elucidate the role that host immune genetic variations may play in the susceptibility to ICU-acquired sepsis and ICU mortality.

Objective This study investigated the clinical significance of HbA1c levels on admission in the intensive care unit (ICU) as a prognostic marker for morbidity and mortality in critically ill patients. Patients—methods This prospective observational study included consecutive patients admitted in an 8-bed multidisciplinary ICU. Patients were prospectively followed from ICU admission until ICU outcome (death/discharge). All patients had an HbA1c measurement upon admission in the ICU. Results Five hundred fifty-five consecutive patients (376 males, 179 females) were included in the study. In patients without prior diabetes mellitus (DM) diagnosis, a cutoff of 6.5% for HbA1c (diagnostic cutoff for DM) predicted more severe disease (as described by Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores at admission) and higher ICU mortality (adjusted odds ratio, 2.33; 95% confidence interval, 1.04 - 5.25). In the subgroup of patients with a history of DM, a cutoff of 7% for HbA1c (glycemic target) had no predicting ability for ICU mortality. Conclusions HbA1c is a useful tool for the diagnosis of a previously undiagnosed DM. This study showed that in critically ill patients with previously undiagnosed DM, HbA1c at admission is significantly associated with ICU mortality.

Our study investigated the impact of packed red blood cell (pRBC) transfusion on the occurrence of bloodstream infections (BSIs) in patients admitted in a multidisciplinary intensive care unit (ICU), further assessing potential associations with particular BSI types. A nested matched (1:1) case-control design was implemented. Sex, age, admission category, Acute Physiology and Chronic Health Evaluation score II (plus Injury Severity Score in trauma patients) were used for matching. Controls were selected to have an ICU length of stay at least equal to the time to first BSI episode of the corresponding cases. Propensity scores for receiving pRBC transfusion were calculated in the entire prospective cohort. Of 582consecutive ICU patients, 165 matched case-control pairs were formed. In multivariable analysis, pRBC transfusion was independently associated with 2-fold probability for BSI (adjusting for matching variables and propensity score). There was a significant dose-dependent association of BSI risk with regard to the number of pRBC units transfused (odds ratios [OR], 1.73, 2.09, 2.34 for 1-3, 4-6, and more than 6 pRBC units transfused, respectively, compared with nontransfused patients, P values .116, .018, and .015, respectively). In subgroup analysis, catheter-related BSIs displayed the strongest association with pRBC transfusion (OR = 5.01, P = .014).

To investigate the role of diabetes as risk factor for ICU-acquired bloodstream infections (BSI).Prospective observational study.A general eight-bed ICU of a tertiary hospital.Three hundred and forty-three consecutive patients (63 diabetic and 280 nondiabetic) admitted in the ICU.BSI episodes in the ICU were recorded and classified as primary, secondary, catheter-related and mixed according to strict criteria. In all patients, blood glucose was strictly controlled with a continuous insulin infusion within a range of 80-120 mg/dl.One-hundred and eighteen patients (34.4%) developed at least one BSI episode. Diabetic patients had an increased probability of developing at least one BSI episode compared with nondiabetic patients (hazard ratio = 1.66, 95% confidence interval 1.04-2.64, P = 0.034) in a Cox proportional hazards regression model adjusting for age, gender, admission category and APACHE II score at admission in the ICU and comorbidities.Despite strict glycemic control, diabetic patients have a 1.7-fold probability of developing an ICU-acquired BSI compared to nondiabetic subjects.

Introduction Although major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time. Methods The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer. Results Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis. Conclusions Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.

Dear Editor: Reintam et al. [1] discuss intra-abdominal hypertension (IAH) as an independent risk factor of mortality in a presumed risk population of critically ill patients. The authors use univariable logistic regression to identify risk factors for ICU mortality followed by multiple logistic regression to identify risk factors that are independently associated with ICU mortality. In a stepwise multiple regression analysis ([1, Table 3)], it is shown that APACHE II score at admission in the ICU was a strong independent predictor of ICU mortality. IAH during the ICU period and lactate at admission displayed only borderline association with ICU mortality (p values 0.033 and 0.034 for IAH and lactate, respectively). Consequently, areas under curves (AUCs) in receiver operating characteristic (ROC) analysis were good for APACHE II score (0.876), fair for lactate (0.771), and poor for intra-abdominal pressure (0.530) [2]. This suggests that intraabdominal pressure alone has very low predictive ability for ICU mortality, no better than tossing a coin [2]. A more informative approach would be to assess the predictive ability of the multiple regression model for ICU mortality. First, it should be ascertained with one of the goodness-of-fit tests (e.g., HosmerLemeshow test) that fitting of the model does not present serious problems. Then, a ROC curve, which is a plot of sensitivity as a function of 1-specificity, for the possible cutoffs of predicted probability by the model in regard to the binary outcome (ICU 28-day or 90-day death or survival), should be created [3]. The ROC curve of the full model would be rather more informative than ROC curves of single variables, because it summarizes predictive power for all possible values of ICU death probability, as predicted by the full model. The above approach would more precisely estimate the predictive ability of intra-abdominal pressure for ICU mortality, adjusting for the other two independent predictors (APACHE II score and lactate).