Treatment of early stage chronic hepatitis C virus infection

Introduction: Treatment of Hepatitis C Virus (HCV) with direct acting antivirals (DAAs) is able to achieve the cure of infection in almost the totality of patients, independently of the characteristics of the individual and the virus, using short treatment schedules, and without the need of ribavirin. The high cost of DAAs is the main limiting factor for universal treatment of HCV. However, there is a strong evidence that treatment of infection at the early stage of disease may be the most rewarding approach.

Areas covered: This review evaluates the aspects underlying the benefit of treating chronic HCV infection at the early stage of disease. It outlines the considerations that have to be taken into account when planning treatment in patients with HCV and minimal liver disease, assessing the positive reflex of viral eradication on several HCV-associated extra-hepatic conditions such as the risk of lymphoma, insulin-resistance and glycaemic control, and renal function. Lastly, it also covers the improvement of patients’ quality of life and the pharmaco-economic aspects associated with early treatment.

Expert commentary: Treatment of patients with HCV and minimal liver disease is associated with a beneficial, pleiotropic effect of viral eradication that goes beyond the simplistic consideration of the improvement in liver disease-related outcomes.     

High Magnesium and Sirolimus on Rabbit Vascular Cells—An In Vitro Proof of Concept

Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.     

Thrombotic thrombocytopenic purpura-like syndrome in the absence of schistocytes

Thrombotic thrombocytopenic purpura is anuncommon disorder that if left untreated has a very high mortality. Schistocytes are generally considered essential for the diagnosis. A patient is presented with a thrombotic thrombocytopenic purpura-like syndrome in whom schistocytes were persistently absent and who responded to plasmapheresis.     

Assessing inter- and intra-individual cognitive variability in patients at risk for cognitive impairment: the case of minimal hepatic encephalopathy

Recent evidence reveals that inter- and intra-individual variability significantly affects cognitive performance in a number of neuropsychological pathologies. We applied a flexible family of statistical models to elucidate the contribution of inter- and intra-individual variables on cognitive functioning in healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty-five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the mean and the intra-variability of Reaction Times (RTs) as a function of socio-demographic and task related covariates. Furthermore, a Generalized Linear Mixed Model (GLMM) was fitted for modeling accuracy. When controlling for the covariates, patients without minimal hepatic encephalopathy (MHE) did not differ from patients with MHE in the low-demanding condition, both in terms of RTs and accuracy. Moreover, they showed a significant decline in accuracy compared to the control group. Compared to patients with MHE, patients without MHE showed faster RTs and higher accuracy only in the high-demanding condition. The results revealed that the application of GAMLSS and GLMM models are able to capture subtle cognitive alterations, previously not detected, in patients’ subclinical pathologies.     

Abnormal linear growth in paediatric adrenal diseases: Pathogenesis,prevalence and management

Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.     

Human cortical activity evoked by gaze shift observation: An intracranial EEG study

While is widely accepted that the posterior temporal region is activated during the observation of faces showing gaze shifts, it is still unclear whether its activity is stronger while observing direct or averted gaze. Furthermore, despite its assessed role in social cognition, studies describing an enhanced activity of the posterior temporal region during the observation of gaze aversion interpreted this activity in terms of spatial attention toward the target direction. This spatial attention interpretation is not easily reconcilable with the role of the posterior temporal region in social cognition, and an overarching view of its global cognitive function would be much more preferable. Here we used intracranial EEG to assess the precise spatial localization of the gaze shifts coding in the posterior temporal region, to assess its selectivity for direct versus averted gaze and to distinguish between a spatial‐attentional and a social interpretations of gaze aversion. We found stronger activation during gaze aversion than direct gaze and lateral side switch observation, the latter indicating that the crucial aspect of gaze aversion is the prior presence of the eye contact and its interruption, and not the gaze direction. These results suggest a more social‐oriented interpretation based on the view that among humans, gaze aversion signals a negative relational evaluation in social interaction. Hum Brain Mapp 35:1515–1528, 2014. © 2013 Wiley Periodicals, Inc.