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Pulmonary arterial hypertension (PAH) is an important cause of death in systemic sclerosis (SSc), despite the improvement of therapies. An early diagnosis and the use of drugs interfering with the main pathogenic pathways of PAH is pivotal for the improvement of prognosis in primary PAH and PAH secondary to autoimmune rheumatic diseases, mainly SSc. Lately, new specific therapies have been developed targeting prostacyclin, endothelin, and nitric oxide pathways, the major pathogenic pathways leading to endothelial dysfunction in PAH. Epoprostenol improved life expectancy of patients with primary and secondary PAH, but its continuous intravenous administration requires experienced centers. More stable analogues of prostacyclin, administrated by intravenous (iloprost, treprostinil), subcutaneous, inhalatory (treprostinil, iloprost), and oral route (Beraprost) have shown efficacy in PAH. Bosentan, the first oral endothelin receptor antagonist (with affinity for endothelin A and B receptors) improves exercise function and survival in PAH, both primary and secondary to autoimmune rheumatic diseases. This is confirmed also for Sitaxsentan and Ambrisentan, selective A receptor antagonists. Because of its short half-life and systemic side effects, short-term NO inhalation is used only in short-term management of PAH in critically ill adults. Inhibitors of NO degradation, such as sildenafil, a phosphodiesterase (PDE) type 5 inhibitor, improved functional and hemodynamic parameters without significant side effects. Vardenafil and taladafil, longer-acting PDE inhibitors, also have vascular pulmonary selectivity. All these drugs may be used in combination, to maximize their clinical benefit not only in patients unresponsive to single drugs, but also potentially as initial therapy of PAH. [ABSTRACT FROM AUTHOR]

Objective An important internal quality control system used in the Cancer Prevention and Research Institute cytopathology laboratory in Florence is the peer review procedure, based on the review of all abnormal cytological smears which routinely emerge. Peer review is an important training opportunity for all cytologists, especially for those with less experience. This article shows the results of the peer review procedure. Methods Of the 63 754 Papanicolaou (Pap) smears screened in 2011, 1086 were considered to be abnormal [at least atypical squamous cells of undetermined significance ( ASC- US+)] on primary screening (selected by a single cytologist) and were subjected to the peer review procedure. The overall performance of the laboratory's cytologists was evaluated using a multiple rater analysis and the comparison of each cytologist with the final diagnosis. Further, the agreement was assessed by means of Cohen's kappa and weighted kappa statistics. Results In general, a moderate/substantial level of agreement between the ten cytologists and the final diagnoses was evident. Kappa values for each reader compared with the final diagnosis ranged from 0.54 to 0.69. The overall kappa value was 0.62 [95% confidence interval ( CI), 0.58-0.66] and overall weighted kappa value was 0.76 (95% CI, 0.74-0.79). The category-specific agreement showed the lowest values for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion ( ASC- H). Conclusion In summary, peer review represents an important internal quality control in the evaluation and improvement of inter-observer agreement and of the functioning of the laboratory as a whole. Multi-head microscope sessions may improve particularly the reproducibility of borderline diagnoses and, above all, can be an important training contribution for cytologists. [ABSTRACT FROM AUTHOR]