Evaluation and treatment of hyperglycemia in critically ill patients.

The hyperglycemic reaction to stress is part of adaptive metabolic response to critical illness, especially hypoxia, hemorrhage and sepsis. It involves neuro-endocrine and immune pathways leading to the development of insulin resistance and hepatic glucose production by gluconeogenesis and glycogenolysis. Over the last years the concept of stress related hyperglycemia has been replaced by the concept of dysglycemia and its three domains: hyperglycemia, hypoglycemia and glycemic variability. Each of the three domains is independently associated with increased risk of mortality in patients admitted in intensive care unit and non critically ill patients, both medical and surgical. The strongest association with mortality is demonstrated for hypoglycemia, with additive negative effects for hyperglycemia and glycemic variability. The influence of pre-existing diabetes mellitus on the relation of the three domains of dysglycemia with mortality is not clear, suggesting that patients affected by diabetes mellitus may tolerate a larger glucose variability. Advances in continuous glucose monitoring systems and insulin therapy algorithms may reduce the development of glycemic variability and hypoglycemia, but the benefits in clinical practice have not yet been established in clinical trials.

Biologic Therapy in Inflammatory and Immunomediated Arthritis: Safety Profile.

The increasing insights into the pathogenetic mechanisms of inflammatory autoimmune arthritis and the development of innovative systems of industrial production have led to discover molecules that are able to target/block other molecules that play a critical role in the immune system functioning, and that have been introduced in clinical practice alone and/or in addiction with other "old" disease-modifying anti-rheumatic drugs. For this reason, such drugs are currently known as "biological drugs" and include molecules that induce the immunosuppression acting on several immune pathways. However, though the biological drugs have been employed from more than a decade, there still exist some drawbacks of their use, in particular about the high costs of this therapy and their overall safety, including the route of administration for the intravenous use. In this review we provide an update on the correct use and current therapeutic indications of such drugs, including some of the new biologic therapies that will be soon available for the clinical use, focusing on these biological drugs: • Tumor necrosis factor-alpha (TNF-alpha) inhibitors (adalimumab, certolizumab-pegol, etanercept, golimumab and infliximab); • The T cell co-stimulation inhibitor, abatacept; • The anti-CD20 receptor monoclonal B cell agent, rituximab; • The interlukin-6 (IL-6) receptor-blocking monoclonal antibody, tocilizumab; • The interlukin-1 (IL-1) inhibitor, anakinra; • The interlukin-IL17 (IL-17) pathway inhibitors (ustekinumab, secukinumab, brodalumab).

CHA2DS2-VASc in the prediction of early atrial fibrillation relapses after electrical or pharmacological cardioversion.

BACKGROUND: In hemodynamically stable patients, mortality and morbidity related to atrial fibrillation are mainly due to cardioembolic disorder. No difference in the survival rate and incidence of embolic events has been described in patients undergoing rhythm or rate control if the latter is combined with an appropriate anticoagulant therapy. CHA2DS2-VASc is a score that allows clinicians to stratify embolic risk in patients affected by nonvalvular atrial fibrillation. Each item can be involved in triggering and maintaining atrial fibrillation. Thus, we hypothesized that CHA2DS2-VASc may help to predict early recurrences after cardioversion. METHODS: A total of 319 consecutive patients, admitted to our emergency department or hemodynamically stable persistent atrial fibrillation, were enrolled and treated with electrical or pharmacological sinus rhythm restoration. Outcome was defined as recurrence of atrial fibrillation 5 days after cardioversion. Predicted probability of sinus rhythm stability was assessed with an ordinal regression model using CHA2DS2-VASc as an independent variable. RESULTS: The model showed a progressive decrease in the predicted probability of sinus rhythm stability after electrical or pharmacological cardioversion along with an increase in the CHA2DS2-VASc score. A logarithmic relationship was the best-fit trend among CHA2DS2-VASc ranks and the predicted probability of sinus rhythm stability in patients undergoing both electrical and pharmacological cardioversion (r(2) = 0.98, P < 0.05 for electrical cardioversion; r(2) = 0.91, P < 0.05 for pharmacological cardioversion). CONCLUSION: Our preliminary results suggest that CHA2DS2-VASc score could be useful in evaluating the risk of early recurrence of atrial fibrillation after cardioversion. This information may have implications for disease monitoring and treatment strategies in clinical practice.