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

Linking food web functioning and habitat diversity for an ecosystem based management: A Mediterranean lagoon case-study

We propose a modelling approach relating the functioning of a transitional ecosystem with the spatial extension of its habitats. A test case is presented for the lagoon of Venice, discussing the results in the context of the application of current EU directives. The effects on food web functioning due to changes related to manageable and unmanageable drivers were investigated. The modelling procedure involved the use of steady-state food web models and network analysis, respectively applied to estimate the fluxes of energy associated with trophic interactions, and to compute indices of food web functioning. On the long term (hundred years) temporal scale, the model indicated that the expected loss of salt marshes will produce further changes at the system level, with a lagoon showing a decrease in the energy processing efficiency. On the short term scale, simulation results indicated that fishery management accompanied by seagrass restoration measures would produce a slight transition towards a more healthy system, with higher energy cycling, and maintaining a good balance between processing efficiency and resilience. Scenarios presented suggest that the effectiveness of short term management strategies can be better evaluated when contextualized in the long term trends of evolution of a system. We also remark the need for further studying the relationship between habitat diversity and indicators of food web functioning

how the mediterranean diet and some of its components modulate inflammatory pathways in arthritis

Arthritis encompasses a heterogeneous group of diseases characterised by inflammation that leads not only to joint damage, bone erosion, severe pain and disability, but also affects other organs of the body, resulting in increased morbidity and mortality. Although the mechanisms underlying the pathogenesis of joint diseases are for the most part unknown, a number of nutrient and non-nutrient components of food have been shown to affect the inflammatory process and, in particular, to influence clinical disease progression. The Mediterranean diet model has already been linked to a number of beneficial health effects: both fat and non-fat components of the Mediterranean dietary pattern have been shown to exert important anti-inflammatory activities by affecting the arachidonic acid cascade, the expression of some proinflammatory genes, and the activity of immune cells. N-3 polyunsaturated fatty acids, in particular, have been shown to affect lymphocyte and monocyte functions, crucially involved in adaptive and innate immunity. Although some aspects concerning the mechanisms of action through which the Mediterranean diet pattern exerts its beneficial effects remain to be elucidated, arthritis patients may potentially benefit from it in view of their increased cardiovascular risk and the treatment they require which may have side effects

MonitorNet: studio italiano osservazionale multicentrico per la valutazione del profilo rischio-beneficio dei farmaci biologici nella pratica clinica reumatologica

Over the last decade, several new biologic agents have become available for the treatment of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and psoriasis (Ps). In contrast to conventional disease modifying anti-rheumatic drugs (DMARDs), these biological agents have rapid onset of action and pronounced disease reducing activity when administered as monotherapy or in combination with MTX. Pre-registration randomised clinical trials have compared biological agents against placebo over a limited time span (1-3). Wider use of biologics has resulted in reports of a wide range of adverse events (4), including evidence of reactivation of latent tuberculosis, increased incidence..

The enthesopathy of vitamin D-resistant osteomalacia in adults

A case of an adult patient with vitamin D-resistant osteomalacia or X-linked hypophosphatemic osteomalacia (XLH) with diffuse calcification of entheses was reported. XLH is the most frequent cause of rickets in developed countries. It is characterized by an impaired renal transport of the phosphate and mutation of PFEX (phosphate regulating gene, with homologies to endopeptidase on the X-chromosome). In childhood, the classic clinical presentation includes short stature and bow leg. While at this age the main radiographic features are characterised by rickets, in adult life they are dominated by a generalised calcific enthesopathy. Concerning the pathogenesis of the enthesopathic lesions of XLH, no convincing hypothesis has yet been made. As in our patient, the extension and the severity of enthesopathy seems not related to the severity of the biochemical changes nor to the treatment with calcitriol. The calcified enthesopathy is an integral part of XLH and it is possible that it is found in adult because many years are necessary to produce it

Imaging in major salivary gland diseases

Most of the salivary glands diseases are characterized only by a few distinct clinical patterns. Medical history and clinical examination are still considered of great relevance. However, in order to obtaine a definite diagnosis, imaging techniques are required in most of the cases. Salivary glands ultrasonography (US) is the technique to be used as the first because US can easily differentiate calculosis, inflammatory diseases and tumors. Sonography is also frequently needed to perform needle aspiration or biopsy (FNAC). Sialography should be used essentially for assessing chronic sialoadenitis as well as Sjogren's syndrome. At present, Magnetic Resonance sialography should be preferred because of the greater sensibility in diagnosing inflammatory diseases of the salivary glands. It allows to evaluate both intraglandular oedema and nodules, so that incannulation of the salivary duct is not required. Computer Tomography (CT) and Magnetic Resonance imaging (MR) are useful when neoplasm are suspected, particularly if deep areas of the gland, which cannot be visualized by US, are involved. Sequential scintigraphy is currently employed for assessing the functional status of all the 4 major salivary glands and evaluating the chronic evolution of glandular damage

Long-term data prove useful to keep track of non-indigenous seaweed fate

The Mar Piccolo of Taranto (southern Italy, Mediterranean Sea), a site of the European LTER network, is a transitional water system, where a century-old intensive mussel farming activity has been carried out, together with an intense import-export business of bivalve mollusks. Previous studies showed that this basinisthirdforNISseaweedintroductionintheMediterraneanSea,aftertheThau LagoonandtheVeniceLagoon.Thepresentpaperdealswiththeresultsof11-year monitoring activity on non-indigenous species (NIS) of seaweeds, which was performed in the Mar Piccolo. In the studied period (2011–2021), two different time frames (i.e., 2011–2015 and 2016–2021) were considered, since they were based on a different number of sampling sites. To investigate spatial and temporal differences in the seaweed assemblage, a multivariate analysis was performed considering the NIS and the most important native species in terms of temporal occurrence. Fourteen NIS were recorded in total in the Mar Piccolo of Taranto duringthisperiod,withvariableabundancesamongsitesandyears:ninespeciesin the firsttimeperiod,andthirteenspeciesinthesecondone.Caulerpacylindracea, recorded with negligible biomass in the first period, was absent in the secondperiod samplings. Molecular analyses confirmed the taxonomy of three species (i.e., Grateloupia minima, Neopyropia koreana, and Polysiphonia morrowii), previously identified only through morphological features. The most abundant specieswasHypneacorona,whichalmostdoubleditsbiomassinthesecondtime period compared to the first one. Three species (i.e., Caulacanthus okamurae, G. minima, and P. morrowii) increased their biomass by an order of magnitude in the second time period. No significant differences were found over years. Site 1 resulted in significant differences among the sites and different seasonal pattern occurred among the investigated sites. No significant long-term changes occurred in the seaweed assemblages, suggesting the absence of strong disturbances due to the settlement of NIS

TNFα blockers and infectious risk in rheumatoid arthritis

Patients suffering from rheumatoid arthritis have increased risk of infections when compared with general population. The risk depends directly from disease activity and severity. Furthermore, risk increases with aging, immunosuppressive agents and comorbidities such as diabetes, pulmonary and cardiac diseases. In particular corticosteroids, even at low doses, are a major risk factor. Due to disease related risk it is difficult to separate the risk deriving from the use of TNF alpha blockers. Data from clinical trials, meta-analysis and national registers are somewhat contradictory. In patients with rheumatoid arthritis on routine follow-up, treatment with TNF alpha blockers seems to carry an increased risk of infections compared to traditional DMARDs but not associated with increased risk of overall serious infection. Physicians should carefully monitor for signs of infection when using TNF alpha blockers, particularly shortly after treatment initiation

Balance between the reliability of classification and sampling effort: A multi-approach for thewater Framework Directive (WFD) ecological status applied to the Venice Lagoon (Italy)

The Water Framework Directive (WFD) requires Member States to assess the ecological status of water bodies and provide an estimation of the classification confidence and precision. This study tackles the issue of the uncertainty in the classification, due to the spatial variability within each water body, proposing an analysis of the reliability of classification, using the results of macrophyte WFD monitoring in the Venice Lagoon as case study. The level of classification confidence, assessed for each water body, was also used as reference to optimize the sampling effort for the subsequent monitorings. The ecological status of macrophytes was calculated by the Macrophyte Quality Index at 114 stations located in 11 water bodies. At water body scale, the level of classification confidence ranges from 54% to 100%. After application of the multi-approach (inferential statistics, spatial analyses, and expert judgment), the optimization of the sampling effort resulted in a reduction of the number of stations from 114 to 84. The decrease of sampling effort was validated by assessing the reliability of classification after the optimization process (54-99%) and by spatial interpolation of data (Kernel standard error of 22.75%). The multi-approach proposed in this study could be easily applied to any other water body and biological quality element