Prospective validation of the EuroSCORE II risk model in a single Dutch cardiac surgery centre

Objective

The EuroSCORE I was one of the most frequently used pre-operative risk models in cardiac surgery. In 2011 it was replaced by its successor the EuroSCORE II. This study aims to validate the EuroSCORE II and to compare its performance with the EuroSCORE I in a Dutch hospital.

Methods

The EuroSCORE II was prospectively validated in 2,296 consecutive cardiac surgery patients between 1 April 2012 and 1 January 2014. Receiver operating characteristic curves on in-hospital mortality were plotted for EuroSCORE I and EuroSCORE II, and the area under the curve was calculated to assess discriminative power. Calibration was assessed by comparing observed versus expected mortality. Additionally, analyses were performed in which we stratified for type of surgery and for elective versus emergency surgery.

Results

The observed mortality was 2.4% (55 patients). The discriminative power of the EuroSCORE II surpassed that of the EuroSCORE I (area under the curve EuroSCORE II 0.871, 95% confidence interval (CI) 0.832–0.911; area under the curve additive EuroSCORE I 0.840, CI 0.798–0.882; area under the curve logistic EuroSCORE I 0.761, CI 0.695–0.828). Both the additive and the logistic EuroSCORE I overestimated mortality (predictive mortality additive EuroSCORE I median 5.0%, inter-quartile range 3.0–8.0%; logistic EuroSCORE I 10.7%, inter-quartile range 5.8–13.9), while the EuroSCORE II underestimated mortality (median 1.6%, inter-quartile range 1.0–3.5). In most stratified analyses the EuroSCORE II performed better.

Conclusion

Our results show that the EuroSCORE II produces a valid risk prediction and outperforms the EuroSCORE I in elective cardiac surgery patients.

     

Multi factorial interactions in the pathogenesis pathway of Alzheimer’s disease: a new risk charts for prevention of dementia

Background

The population longitudinal study named “The Conselice Study” has been the focus of the present investigation. 65 years old or older participants of this population study on brain aging were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 46 genetic, phenotypic, clinical and nutritional factors on incident cognitive decline and incident dementia cases were investigated.

Results

A new statistical approach, called the Auto Contractive Map (AutoCM) was applied to find relationship between variables and a possible hierarchy in the relevance of each variable with incident dementia. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Moreover, few variables resulted to be aggregation points in the variable connectivity map related to cognitive decline and dementia. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. A risk map for age associated cognitive decline and dementia has been constructed and will be presented and discussed.

Conclusion

This map of variables may be use to identify subjects with increased risk of developing cognitive decline end/or dementia and provide pivotal information for early intervention protocols for prevention of dementia.

     

Adiponectin and cardiovascular disease: state of the art?

The cardiometabolic syndrome, associated with increased cardiovascular disease risk in the industrialized world, is estimated to affect one in four adults. Although the mechanisms linking obesity and cardiovascular disease remain unclear, research continues to unravel the molecular pathways behind this pandemic. Adipose tissue has emerged as a metabolically active participant in mediating vascular complications, serving as an active endocrine and paracrine organ secreting adipokines, which participate in diverse metabolic processes. Among these adipokines is adiponectin, which seems to possess antiatherogenic and anti-inflammatory effects and may be protective against cardiovascular disease development. The current review describes the pathophysiology of adiponectin in atherosclerotic disease.     

The roles of O-linked β-N-acetylglucosamine in cardiovascular physiology and disease

More than 1,000 proteins of the nucleus, cytoplasm, and mitochondria are dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAc), an essential post-translational modification of metazoans. O-GlcNAc, which modifies Ser/Thr residues, is thought to regulate protein function in a manner analogous to protein phosphorylation and, on a subset of proteins, appears to have a reciprocal relationship with phosphorylation. Like phosphorylation, O-GlcNAc levels change dynamically in response to numerous signals including hyperglycemia and cellular injury. Recent data suggests that O-GlcNAc appears to be a key regulator of the cellular stress response, the augmentation of which is protective in models of acute vascular injury, trauma hemorrhage, and ischemia-reperfusion injury. In contrast to these studies, O-GlcNAc has also been implicated in the development of hypertension and type II diabetes, leading to vascular and cardiac dysfunction. Here we summarize the current understanding of the roles of O-GlcNAc in the heart and vasculature.     

The Role of Cohesiveness in the Permeability of the Spatial Assemblies of FG Nucleoporins

Nuclear pore complexes (NPCs) conduct selective, bidirectional transport across the nuclear envelope. The NPC passageway is lined by intrinsically disordered proteins that contain hydrophobic phenylalanine-glycine (FG) motifs, known as FG nucleoporins (FG nups), that play the key role in the NPC transport mechanism. Cohesive interactions among the FG nups, which arise from the combination of hydrophobic, electrostatic, and other forces, have been hypothesized to control the morphology of the assemblies of FG nups in the NPC, as well as their permeability with respect to the transport proteins. However, the role of FG nup cohesiveness is still vigorously debated. Using coarse-grained polymer theory and numerical simulations, we study the effects of cohesiveness on the selective permeability of in vitro FG nup assemblies in different geometries that have served as proxies for the morphological and transport properties of the NPC. We show that in high-density FG nup assemblies, increase in cohesiveness leads to the decrease in their permeability, in accordance with the accepted view. On the other hand, the permeability of low-density assemblies is a nonmonotonic function of the cohesiveness, and a moderate increase in cohesiveness can enhance permeability. The density- and cohesiveness-dependent effects on permeability are explained by considering the free-energy cost associated with penetrating the FG nup assemblies. We discuss the implications of these findings for the organization and function of the NPC.     

Predicting the risk of cardiovascular disease: where does lipoprotein-associated phospholipase A(2) fit in?

Although an atherogenic lipoprotein phenotype has been well recognized as an important predictor of cardiovascular disease, recent studies have demonstrated a number of additional lipid-related markers as emerging biomarkers to identify patients at risk for future coronary heart disease. Among them, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), seems to be a promising candidate that might be added to the clinical armamentarium for improved prediction of cardiovascular disease in the future. Of particular note, Lp-PLA(2) is the only enzyme that cleaves oxidized low-density lipoprotein (oxLDL) in the subendothelial space, with further generation of proinflammatory mediators such as lysophosphatidylcholine (LysoPC) and oxidized fatty acid (oxFA), thereby probably linking two important features of atherogenesis, namely oxidation of LDL and local inflammatory processes within the atherosclerotic plaque. This overview aims to summarize our current knowledge based on observations from recent experimental and clinical studies. Emphasis has been put on potential pathophysiological mechanisms of action and on the clinical relevance of Lp-PLA(2) in a wide variety of clinical settings, including apparently healthy individuals, patients with stable angina or acute coronary syndromes, after myocardial infarction, and with subclinical disease. Although a growing body of evidence from epidemiological and clinical studies suggests that Lp-PLA(2) may represent an independent and clinically relevant long-term risk marker for coronary heart disease and, probably, also for stroke, the role of this enzyme in the setting of the acute coronary syndrome remains to be established.     

A critical appraisal of the measurement of serum ‘cholesterol efflux capacity’ and its use as surrogate marker of risk of cardiovascular disease

The ‘cholesterol efflux capacity (CEC)’ assay is a simple in vitro measure of the capacities of individual sera to promote the first step of the reverse cholesterol transport pathway, the delivery of cellular cholesterol to plasma HDL.This review describes the cell biology of this model and critically assesses its application as a marker of cardiovascular risk. We describe the pathways for cell cholesterol export, current cell models used in the CEC assay with their limitations and consider the contribution that measurement of serum CEC provides to our understanding of HDL function in vivo.     

High-density lipoproteins： an emerging target in the prevention of cardiovascular disease

High-density lipoproteins （HDLs） have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target HDL and its ability to protect against the development of atherosclerotic plaque. This paper will review how the promotion of the functional properties of HDL inhibits the formation of atherosclerotic plaque and stabilises lesions in patients with established disease.     

The risk of extinction—the mutational meltdown or the overpopulation

The phase diagrams survival-extinction for the Penna model with parameters: (mutations rate)-(birth rate), (mutation rate)-(harmful mutations threshold), (harmful mutation threshold)-(minimal reproduction age) are presented. The extinction phase may be caused by either mutational meltdown or overpopulation. When the Verhulst factor is responsible for removing only newly born babies and does not act on adults the overpopulation is avoided and only genetic factors may lead to species extinction.     

The functional -765G→C polymorphism of the COX-2 gene may reduce the risk of developing crohn's disease

Background

Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1α/β, interferon-γ and tumor necrosis factor-α produced by inflammatory cells.

Aim

The aim of this study was to investigate the possible modulating effect of the functional COX-2 polymorphisms −1195 A→G and −765G→C on the risk for development of inflammatory bowel disease (IBD) in a Dutch population.

Methods

Genomic DNA of 525 patients with Crohn''s disease (CD), 211 patients with ulcerative colitis (UC) and 973 healthy controls was genotyped for the −1195 A→G (rs689466) and −765G→C (rs20417) polymorphisms. Distribution of genotypes in patients and controls were compared and genotype-phenotype interactions were investigated.

Results

The genotype distribution of the −1195A→G polymorphism was not different between the patients with CD or UC and the control group. The −765GG genotype was more prevalent in CD patients compared to controls with an OR of 1.33 (95%CI 1.04–1.69, p<0.05). The −765GC and −765CC genotype carriers showed a tendency to be less frequent in patients with CD compared to controls, with ORs of 0.78 (95%CI: 0.61–1.00) and 0.49 (95%CI 0.22–1.08), respectively. Combining homozygous and heterozygous patients with the −765C allele showed a reduced risk for developing CD, with an OR of 0.75 (95%CI: 0.59–0.96). In the context of this, the G₋₁₁₉₅G₋₇₆₅/A₋₁₁₉₅C₋₇₆₅ diplotype was significantly less common in patients with CD compared to controls, with an OR of 0.62 (95%CI: 0.39–0.98). For UC however, such an effect was not observed. No correlation was found between COX-2 diplotypes and clinical characteristics of IBD.

Conclusions

The −765G→C polymorphism was associated with a reduced risk for developing Crohn''s disease in a Dutch population.     

Is the association between optimistic cardiovascular risk perceptions and lower rates of cardiovascular disease mortality explained by biomarkers of systemic inflammation or endothelial function? A case-cohort study

Background  

More optimistic perceptions of cardiovascular disease risk are associated with substantively lower rates of cardiovascular death among men. It remains unknown whether this association represents causality (i.e. perception leads to actions/conditions that influence cardiovascular disease occurrence) or residual confounding by unmeasured factors that associate with risk perceptions and with physiological processes that promote cardiovascular disease (i.e. inflammation or endothelial dysfunction).     

Does antiperspirant use increase the risk of aluminium-related disease,including Alzheimer's disease?

Aluminium salts are the major constituent of many widely used antiperspirant products. The use of such antiperspirants has been linked with the systemic accumulation of aluminium and an increased risk of Alzheimer's disease. But can the frequent use of aluminium-based antiperspirants lead to the accumulation of toxic levels of aluminium? And are there measures that we can take to reduce such accumulation without reducing the effectiveness of antiperspirants?