RESUMEN
Selexipag is an oral selective prostacyclin-receptor agonist that was approved for use in patients with World Health Organisation (WHO) functional class II-III pulmonary arterial hypertension (PAH). Treatment with individualised doses of selexipag resulted in significant reductions in the composite end point of death or a complication related to PAH in the phase III GRIPHON (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) study. In order to better understand the real-world approach to selexipag titration and to establish the individualised maintenance regimens used in our centre, we performed this retrospective study of the first 20 patients prescribed selexipag. Baseline characteristics differed from the GRIPHON study, with more combination therapy and comorbidities at drug initiation. Maintenance doses were stratified as low-dose in 10% (n=2), medium-dose in 70% (n=14) and high-dose in 20% (n=4). This study highlights that selexipag can be safely initiated, titrated and transitioned in an outpatient setting to achieve an individualised dosing regimen.
RESUMEN
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RESUMEN
The pathogenesis and complications of type 2 diabetes (T2DM) are closely linked with defective glucose metabolism, obesity, cardiovascular disease and an inability to mount an effective immune response to certain pathogenic organisms. Perturbations in key innate immune receptors known as Toll-like receptors (TLRs) and inflammatory mediators such as IL-6, TNFα and IL-1ß have been linked with T2DM. Herein, we sought to establish whether patients with T2DM and underlying complications exhibit perturbations in cytokine and TLR expression. Serum cytokine and mRNA levels of cytokines/TLRs in monocytes (M) and neutrophils (N) were measured in a cohort of 112 diabetic patients: good glycaemic control without complications (GC), good glycaemic control with complications (GCC), poor glycaemic control without complications (PC) and poor glycaemic control with complications (PCC) and compared them with 34 non-diabetic volunteers (NGT). Serum cytokine levels were normal in all study participants. In the GC group, cytokine and TLR gene expression were enhanced compared to NGT. In contrast, suppressed cytokine and TLR gene expression were evident in PC, GCC & PCC groups when compared to the GC. In conclusion, whereas serum pro-inflammatory cytokine levels are unaltered in T2DM patients, differences in inflammatory gene profiles exist among the T2DM patient groups.