Keywords Hyponatremia • COVID-19 • Interleukin-6 (IL-6) • PaO 2 /FiO 2 ratio • Tocilizumab Hyponatremia is the most common electrolyte disorder encountered in clinical practice and is associated with an increased risk of overall mortality in in-patients [1]. The most common cause of hyponatremia is the syndrome of inappropriate antidiuresis (SIAD), which accounts for up to 40-50% of cases, but the prevalence may be higher in some pathological conditions, such as subarachnoid haemorrhage, traumatic brain injury, and pneumonia [2]. Besides infectious diseases, several inflammatory conditions may be complicated by SIAD. In these situations, interleukin-6 (IL-6), released by monocytes and macrophages, plays a pathogenic role in causing electrolyte impairment by inducing the nonosmotic release of vasopressin [3]. Respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality in COVID-19 infection, but a secondary hyper-inflammation syndrome characterized by massive release of cytokines may contribute to fatal outcome, determining multiple organ failure [4]. IL-6 is one of the most important cytokines involved in COVID-19-induced pathology. Based on these data, tocilizumab, a humanized monoclonal antibody against the IL-6 * A.
Adiponectin, an adipocyte-derived protein, is an essential modulator of insulin sensitivity and several studies suggest an important role of adiponectin in the processes leading to atherosclerosis, thus indicating the adiponectin gene as a potential candidate for coronary artery disease (CAD). In the present study we have studied the association between two single nucleotide polymorphisms (SNPs) (+45T>G and +276 G>T) of the adiponectin gene and CAD, looking also into the possible influence of these SNPs on adiponectin plasma levels. The SNPs were analysed in a first cohort of 595 subjects, 325 with CAD and 270 matched controls. We observed a significant association (p<0.001) between the SNP +276G>T in the adiponectin gene and CAD. In multivariate analysis, carriers of the +276G>T SNP had an odds ratio (OR) for CAD of 4.99 (p<0.0007). A strong interaction between the +276G>T SNP and age was also present (OR, 1.03; p<0.0001). The increase in CAD risk was most evident among individuals with early-onset CAD (age T SNP was analysed in a second cohort of CAD and controls. The difference between CAD and controls in the +276G>T SNP frequencies showed a similar trend as before, although not significant. The combination of the two cohorts (1,046 subjects: 580 CAD and 466 controls) showed a statistically significant association, particularly in CAD subjects with early-onset of disease. In addition, we confirmed that in younger CAD subjects the SNP was a significant determinant of lower levels of adiponectin. In view of these results, it could be speculated that the adiponectin gene variant, or a mutation in linkage with it, determines lower adiponectin gene expression, causing in turn an increased risk to develop insulin resistance, atherosclerosis and cardiovascular disease. The significant association of the adiponectin gene in subjects with early-onset CAD also suggests that that genetic factors for late-onset diseases may exert a greater influence in younger persons, when other risk factors are not as prevalent as in older age groups.
Our study indicates strikingly better outcomes of percutaneous cardiovascular procedures with radial access versus femoral access in contemporary, real-world clinical settings.
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