Development and Role in Therapy of Canakinumab in Adult-Onset Still's Disease

Adult-onset Still's disease (AOSD) is a rare inflammatory disease of unknown etiology typically characterized by episodes of spiking fever, evanescent rash, arthralgia, leukocytosis, and hyperferritinemia. The pivotal role of interleukin (IL)-1 and other pro-inflammatory cytokines gives rise to the development of new targeted therapies. Currently, AOSD patients can benefit from efficient and well tolerated biologic agents, such as IL-1, IL-6, and tumour necrosis factor (TNF)-\u3b1 antagonists. Canakinumab, a human monoclonal anti-IL-1\u3b2 antibody, is indicated for the treatment of different autoinflammatory syndromes in adults, adolescents, and children and it has recently been approved for AOSD treatment. In this article, we summarize the structural and biochemical data describing the molecular interactions between Canakinumab and its target antigen. Some special considerations of the pharmacological properties of Canakinumab are included. We also review the safety, efficacy and tolerability of this drug for the treatment of AOSD

Dynamics and stability of vortex-antivortex fronts in type II superconductors

The dynamics of vortices in type II superconductors exhibit a variety of patterns whose origin is poorly understood. This is partly due to the nonlinearity of the vortex mobility which gives rise to singular behavior in the vortex densities. Such singular behavior complicates the application of standard linear stability analysis. In this paper, as a first step towards dealing with these dynamical phenomena, we analyze the dynamical stability of a front between vortices and antivortices. In particular we focus on the question of whether an instability of the vortex front can occur in the absence of a coupling to the temperature. Borrowing ideas developed for singular bacterial growth fronts, we perform an explicit linear stability analysis which shows that, for sufficiently large front velocities and in the absence of coupling to the temperature, such vortex fronts are stable even in the presence of in-plane anisotropy. This result differs from previous conclusions drawn on the basis of approximate calculations for stationary fronts. As our method extends to more complicated models, which could include coupling to the temperature or to other fields, it provides the basis for a more systematic stability analysis of nonlinear vortex front dynamics.Comment: 13 pages, 8 figure

Decolonização, Sul global e colonialidade do poder

Este texto é a versão em português de "Decolonizzazione, Sud del mondo e colonialità del potere", de Marina De Chiara, capítulo do livro Sud immaginari. Colonialità del potere, chicane ribelli, interferenze blues, publicado na Itália em 2019 e organizado pela mesma autora. O artigo apresenta os principais conceitos advindos de perspectivas críticas sobre a modernidade como produto da empresa colonial e o sistema dela resultante, chamado por Aníbal Quijano de colonialidade do poder, ainda em operação. Tais reflexões são consideradas úteis para se pensar a oposição epistemológica entre norte e sul do mundo, fratura que atua inclusive no corpo das nações, promovendo uma forma de colonialismo interno. Nesse sentido, De Chiara faz referência às questões italianas, especialmente em relação à marcada divisão entre o mezzogiorno (o sul) e o norte do país desde a Unificação (1861), às migrações internas do sul ao norte no século XX e, mais recentemente, à migração do continente africano à Itália, que tem no sul italiano o seu ponto de chegada. Dessa forma, De Chiara mostra a produtividade de um pensamento subalterno - oriundo especialmente de grupos de estudos asiáticos e latino-americanos - para se pensar questões do Norte global

Endomyocardial biopsy in the clinical context: current indications and challenging scenarios

Endomyocardial biopsy (EMB) is an invasive procedure originally developed for the monitoring of heart transplant rejection. Over the year, this procedure has gained a fundamental complementary role in the diagnostic work-up of several cardiac disorders, including cardiomyopathies, myocarditis, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Major advances in EMB equipment and techniques for histological analysis have significantly improved diagnostic accuracy of EMB. In recent years, advanced imaging modalities such as echocardiography with three-dimensional and myocardial strain analysis, cardiac magnetic resonance and bone scintigraphy have transformed the non-invasive approach to diagnosis and prognostic stratification of several cardiac diseases. Therefore, it emerges the need to re-define the current role of EMB for diagnostic work-up and management of cardiovascular diseases. The aim of this review is to summarize current knowledge on EMB in light of the most recent evidences and to discuss current indications, including challenging scenarios encountered in clinical practice

Sex differences in natural history of cardiovascular magnetic resonance- and biopsy-proven lymphocytic myocarditis

Aims: the role of sex in determining the profile and the outcomes of patients with myocarditis is largely unexplored. We evaluated the impact of sex as a modifier factor in the clinical characterization and natural history of patients with definite diagnosis of myocarditis. Methods and results: we retrospectively analysed a single-centre cohort of consecutive patients with definite diagnosis of myocarditis (i.e. endomyocardial biopsy or cardiac magnetic resonance proven). Specific sub-analyses were performed in cohorts of patients with chest pain, ventricular arrhythmias, and heart failure as different main symptoms at presentation. The primary outcome measure was a composite of all-cause mortality or heart transplantation (HTx). We included 312 patients, of which 211, 68% of the whole population, were males. Despite no clinically relevant differences found at baseline presentation, males had a higher indexed left ventricular end-diastolic volume (62 ± 23 mL/m2 vs. 52 ± 20 mL/m2, P = 0.011 in males vs. females, respectively) at follow-up evaluation. At a median follow-up of 72 months, 36 (17%) males vs. 8 (8%) females experienced death or HTx (P = 0.033). Male sex emerged as predictors of all-cause mortality or HTx in every combination of covariates (HR 2.600; 1.163–5.809; P = 0.020). Results were agreeable regardless of the main symptom of presentation. Conclusions: in a large cohort of patients with definite diagnosis of myocarditis, females experienced a more favourable long-term prognosis than males, despite a similar clinical profile at presentation

Metabolic Syndrome and All-Cause and Cardiovascular Mortality in an Italian Elderly Population: The Progetto Veneto Anziani (Pro.V.A.) Study

OBJECTIVE—The purpose of this study was to explore the association of metabolic syndrome and each of its components with all-cause and cardiovascular mortality in a general Italian elderly population

Current treatment and immunomodulation strategies in Acute Myocarditis

Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarise the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis

Vitamin D and Physical Performance in Elderly Subjects: The Pro.V.A Study

Background The role of Vitamin D in musculoskeletal functionality among elderly people is still controversial. We investigated the association between serum 25-hydroxyvitamin D (25OHD) levels and physical performance in older adults. Methods 2694 community-dwelling elderly women and men from the Progetto Veneto Anziani (Pro.V.A.) were included. Physical performances were assessed by: tandem test, 5 timed chair stands (TCS), gait speed, 6-minute walking (6 mW) distance, handgrip strength, and quadriceps strength. For each test, separate general linear models and loess plots were obtained in both genders, in relation to serum 25OHD concentrations, controlling for several potential confounders. Results Linear associations with 25OHD levels were observed for TCS, gait speed, 6 mW test and handgrip strength, but not for tandem test and quadriceps strength. After adjusting for potential confounders, linear associations with 25OHD levels were still evident for the 6 mW distance in both genders (p = .0002 in women; <.0001 in men), for TCS in women (p = .004) and for gait speed (p = .0006) and handgrip strength (p = .03) in men. In loess analyses, performance in TCS in women, in gait speed and handgrip strength in men and in 6 mW in both genders, improved with increasing levels of 25OHD, with most of the improvements occurring for 25OHD levels from 20 to 100 nmol/L. Conclusion lower 25OHD levels are associated with a worse coordination and weaker strength (TCS) in women, a slower walking time and a lower upper limb strength in men, and a weaker aerobic capacity (6 mW) in both genders. For optimal physical performances, 25OHD concentrations of 100 nmol/L appear to be more advantageous in elderly men and women, and Vitamin D supplementation should be encouraged to maintain their 25OHD levels as high as this threshold