The implementation of a procalcitonin-based algorithm may reduce antibiotic exposure in critically ill, septic patients without compromising clinical outcomes, but further research is necessary before the wide adoption of this strategy.

The effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE) remains controversial. In this study, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until September 2006. A total of 22 articles were included in the analysis that was performed using random effects models. Eighteen papers, concerning patients without another known risk factor, comprised 2,644 cases and 3,739 controls. The alleles contrast (4G vs. 5G allele) yielded a statistically significant odds ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068-1.246). In a sub-analysis of five studies that included 256 cases with another genetic risk factor and 147 controls, the combined per-allele OR was still significant (OR: 1.833,95% CI: 1.325-2.536). On the contrary, the analysis of five studies regarding cases with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome, Behcet disease) provided insignificant results in all aspects. There was no evidence for heterogeneity and publication bias in all analyses. Based on our findings, the 4G allele appears to increase the risk of venous thrombosis, particularly in subjects with other genetic thrombophilic defects. Recommendation for detection of this polymorphism in evaluating thrombophilia in such patients might be considered.

No abstract

The erythrocyte represents a major component of the antioxidant capacity of the blood through the enzymes contained in the cell, the glutathione system, and the low-molecular-weight antioxidants of the erythrocyte membrane. A further major red blood cell contribution is in regenerating consumed redox equivalents via the oxidative pentose phosphate pathway and glutathione reductase. Moreover, its extracellular antioxidant capacity, its mobility, and the existence of reducing equivalents far in excess of its normal requirements make erythrocytes function as an effective oxidative sink in the organism. That is why red blood cell metabolism and homeostasis strongly affect the antioxidant properties of the whole body. Conversely, the relation between macrocytosis and oxidative stress has not been fully delineated. Reviewing the mechanisms involved in red blood cell homeostasis in cases of redox imbalance is crucial in identification of factors that could potentially improve erythrocyte survival and defense against oxidant damage.

Background: Procalcitonin (PCT) has been proposed as a diagnostic and prognostic sepsis marker, but has never been validated in febrile patients with prolonged ICU stay.

Hypercoagulability and thrombosis remain a challenge in severe coronavirus disease 2019 (COVID-19) infections. Our aim is to investigate the hemostatic profile of critically ill COVID-19 patients on therapeutic anticoagulant treatment. Forty one patients were enrolled into the study. We recruited 11 consecutive, COVID-19, patients who received therapeutic anticoagulant treatment on intensive care unit (ICU) admission. Disease severity indexes, biochemical, hematological and haemostatic parameters, endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1) activity and extrinsically activated rotational thromboelastometry assay (EXTEM) were recorded on days 1, 3, 7. We also enrolled 9 ICU non-COVID-19, 21 non-ICU COVID-19 patients and 20 healthy blood donors as control populations. Critically ill COVID-19 patients demonstrated a more hypercoagulable and hypofibrinolytic profile related to those with COVID-19 mild illness, based on EXTEM amplitude at 10 min (A10), maximum clot firmness (MCF) and lysis index at 60 min (LI60) variables (p = 0.020, 0.046 and 0.001, respectively). Similarly, a more hypercoagulable state was detected in COVID-19 ICU patients related to non-COVID-19 ICU patients based on A10 and MCF parameters (p = 0.03 and 0.04, respectively). On the contrary, ETP and EXTEM (clotting time) CT values were similar between patients with severe and mild form of the COVID-19 infection, probably due to anticoagulant treatment given. Critically ill COVID-19 patients showed a hypercoagulable profile despite the therapeutic anticoagulant doses given. Due to the small sample size and the study design, the prognostic role of the hypercoagulability in this clinical setting remains unknown and further research is required in order to be assessed.

The aim of the study was to develop and validate a prediction model for hemorrhage in critically ill neonates which combines rotational thromboelastometry (ROTEM) parameters and clinical variables. This cohort study included 332 consecutive full-term and preterm critically ill neonates. We performed ROTEM and used the neonatal bleeding assessment tool (NeoBAT) to record bleeding events. We fitted double selection least absolute shrinkage and selection operator logit regression to build our prediction model. Bleeding within 24 hours of the ROTEM testing was the outcome variable, while patient characteristics, biochemical, hematological, and thromboelastometry parameters were the candidate predictors of bleeding. We used both cross-validation and bootstrap as internal validation techniques. Then, we built a prognostic index of bleeding by converting the coefficients from the final multivariable model of relevant prognostic variables into a risk score. A receiver operating characteristic analysis was used to calculate the area under curve (AUC) of our prediction index. EXTEM A10 and LI60, platelet counts, and creatinine levels were identified as the most robust predictors of bleeding and included them into a Neonatal Bleeding Risk (NeoBRis) index. The NeoBRis index demonstrated excellent model performance with an AUC of 0.908 (95% confidence interval [CI]: 0.870–0.946). Calibration plot displayed optimal calibration and discrimination of the index, while bootstrap resampling ensured internal validity by showing an AUC of 0.907 (95% CI: 0.868–0.947). We developed and internally validated an easy-to-apply prediction model of hemorrhage in critically ill neonates. After external validation, this model will enable clinicians to quantify the 24-hour bleeding risk.

A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity. What is Known: • The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated. • Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis. What is New: • ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis. • ROTEM could be a useful tool in the early detection of sepsis in neonates.