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As our comprehension of the pathogenic mechanisms of inflammatory bowel disease (IBD) increases, the therapeutic armamentarium for its treatment can expand, and novel target therapies join the treatment pipeline. Interleukin (IL)-12 and IL23 are two key cytokines responsible for promoting and perpetuating bowel inflammation in IBD. Ustekinumab is a monoclonal antibody directed against the shared p40 subunit of both cytokines, and it was recently approved for the treatment of ulcerative colitis (UC). In the pivotal phase III UNIFI trial, ustekinumab showed a superiority over placebo in both clinical and endoscopic outcomes; furthermore, it was characterized by a favorable safety profile, with a similar rate of adverse events as compared with placebo. Recent evidence from real-life experiences have started accumulating, generally confirming the effectiveness and safety figures emerged from the registration studies. However, most of these observational studies enrolled multirefractory patients; moreover, comparative data with other target therapies are lacking, leaving physicians without clear indications about the appropriate positioning of ustekinumab in the therapeutic pipeline for UC. This review examines the basis of targeting IL12-23 in UC therapy and summarizes the data from both clinical trials and real-life studies, to highlight the main evidence already available and the research gaps that need to be filled for the optimal usage of ustekinumab in UC. more...

Hemodialysis (HD) may induce vascular stiffness through several mechanisms. We sought to determine the role of dialysis vintage (DV) on the development of cardiovascular alterations. We studied 14 patients in chronic HD and 24 newly diagnosed never treated hypertensive patients and 16 normotensive controls. The patients in HD were divided in two groups according to DV: 60-months (DV>60,n=7). After HD session, when dry weight was reached, we evaluated peripheral blood pressure (pBP), the parameters derived by tonometric analysis of the pulse waveform (central blood pressure-cBP-, Subendocardial Viability Ratio-SEVR-, carotid-femoral pulse wave velocity-cf-PWV-) and those derived from echocardiography: ejection fraction (EF-for systolic function) and E/e’ (for diastolic function), and the ultrafiltration volume (UV). Calcium/phosphate (Ca/P) levels, serum albumin, and Kt/V were evaluated retrospectively on repeated measurements over the past 5 years. All the groups were similar for sex and BMI, both DV60 were older than hypertensives and controls (58.33±3.71 and 59.83±7.98 vs 44.14±1.28 and vs 40.63±2.05 years, respectively, P60 presented similar levels of Ca/P, serum albumin, Kt/V and UV. pBP was increased and similar to hypertensives in DV>60 vs DV60 vs DV60 vs DV60 vs DV In conclusion, only patients with DV>60 presented increased aortic stiffness. This was associated to higher BP and diastolic dysfunction. Hence, chronic HD, particularly after 60 months, may play a putative role in developing cardiovascular alterations in patients with end-stage renal disease. more...

Hypertension and aging are characterized by vascular remodelling and stiffness as well as endothelial dysfunction. Endothelial function declines with age, since aging is associated with senescence of the endothelium due to increased rate of apoptosis and reduced regenerative capacity of the endothelium. Different phenotypes of hypertension have been described in younger and adult subjects with hypertension. In younger patients, functional and structural alterations of resistance arteries occur as the earliest vascular alterations which have prognostic significance and may contribute to stiffness of large arteries through wave reflection. In individuals above age of 50 years as well as in subjects with long-lasting elevated blood pressure, vascular changes occur predominantly in conduit arteries which become stiffer. Activation of renin-angiotensin-aldosterone and endothelin systems plays a key role in endothelial dysfunction, vascular remodelling, and aging by inducing reactive oxygen species production, and promoting inflammation and cell growth. more...