ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

What Are They Gonna Think About Me? An Innovative Text Analysis on Social Anxiety and Taijin Kyofusho Through MADIT Methodology

Meaning and translation are never-ending issues that constantly challenge researchers who work in cross-cultural settings, especially when the focus is on how people use language to express and interact in relation to their distress experiences. Many efforts have been undertaken in order to try to understand and manage the content variance that can emerge from context and linguistic differences. The present study aims at offering its contribution on this topic by presenting MADIT methodology, an innovative textual analysis that focuses on the processual use of language. Using the theoretical references of Dialogic Science, language is analysed as an interactive process, leading the researchers to observe the modalities through which language is used (the how) instead of the different contents brought by speakers (the what). After discussing the theoretical differences between content and processual analysis, we present MADIT methodology through a comparative explorative study on the discursive production about taijin kyofusho and social anxiety in Japanese and Italian contexts. The results pointed out how, going beyond the content differences and focusing on the processual interactive reality generated through language, it is possible to observe cross-cultural similarities in the use of language to shape distress experiences

Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype

The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15–140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24–3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype