No abstract available
|Implications of juvenile idiopathic arthritis genetic risk variants for disease pathogenesis and classification|
Purpose of review We assess the implications of recent advances in the genetics of juvenile idiopathic arthritis (JIA) for the evolving understanding of inflammatory arthritis in children. Recent findings JIA exhibits prominent genetic associations with the human leukocyte antigen (HLA) region, extending perhaps surprisingly even to the hyperinflammatory systemic JIA category. Some HLA associations resemble those for adult-onset inflammatory arthritides, providing evidence for pathogenic continuity across the age spectrum. Genome-wide association studies have defined an increasing number of JIA-linked non-HLA loci, many again shared with adult-onset arthritis. As most risk loci contain only noncoding variants, new experimental methods such as SNP-seq and innovative big-data strategies help identify responsible causative mutations, termed functional SNPs (fSNPs). Alternately, gene hunting in multiplex families implicates new genes in monogenic childhood arthritis, including MYD88 and the intriguing innate immune gene LACC1. Summary Genetic data indicate a continuity between JIA and adult arthritis poorly reflected in current nomenclature. Advancing methodologies will help to identify new pathogenic mechanisms that inform the understanding of biologic subdivisions within JIA. Resulting insights will facilitate the application of lessons learned across the age spectrum to the treatment of arthritis in children and adults.
|Cutaneous manifestations of pediatric lupus|
Purpose of review To review recent evidence on cutaneous manifestations of lupus, with a focus on evidence for pediatric patients. Recent findings Cutaneous manifestations of SLE are common and may precede signs or symptoms of systemic disease. Early recognition and initiation of therapy improves quality of life by reducing cutaneous disease activity. Antimalarials are first line for moderate-to-severe disease. Photo protection is a critical component of therapy and perhaps the only modifiable risk factor for SLE. Recognition of cutaneous vasculopathy may reduce mortality from vascular occlusion. Summary There is a critical need for better understanding of pathogenesis, risk factors and outcomes in cutaneous lupus to determine optimal treatment and surveillance strategies. Correlation of clinical phenotypes with biomarkers may help to stratify patients, optimize targeted interventions, and influence prognosis.
|Interleukin-18 in pediatric rheumatic diseases|
Purpose of review IL-18 is a pleiotropic cytokine involved in the regulation of innate and adaptive immune responses. IL-18 pro-inflammatory activities are finely regulated in vivo by the inhibitory effects of the soluble IL-18-binding protein (IL-18BP). The elevation of circulating levels of IL-18 has been described in children with systemic juvenile idiopathic arthritis (sJIA). In the recent years, the role of IL-18 in the pathogenesis of secondary haemophagocytic lymphohistiocytosis (sHLH), also referred to as macrophage activation syndrome (MAS), in the context of autoinflammatory diseases, including sJIA, is emerging. Recent findings A large number of studies in patients and animal models pointed to the imbalance in IL-18/IL-18BP levels, causing increased systemic levels of free bioactive IL-18, as a predisposing factor in the development of MAS. Although the exact mechanisms involved in the development of MAS are not clearly understood, increasing evidence demonstrate the role of IL-18 in upregulating the production of interferon (IFN)-γ. Summary On the basis of the first emerging data on the possibility of blocking IL-18, we here discuss the scientific rationale for neutralizing the IL-18/IFNγ axis in the prevention and treatment of sHLH and MAS.
|Treatment of juvenile idiopathic arthritis: what's new?|
Purpose of review The present review highlights the advances in disease outcome achieved with currently available biologic medications and future perspectives for JIA management. Recent findings In the last two decades, the management of juvenile idiopathic arthritis (JIA) has been revolutionized by appropriate legislative initiatives, the existence of very large collaborative networks and the increased availability of the novel biologic medications. Summary A more rational approach to the management of JIA is being fostered by the recent publication of therapeutic recommendations, consensus treatment plans and for a treat-to-target strategy.
|Predicting disease severity and remission in juvenile idiopathic arthritis: are we getting closer?|
Purpose of review To summarize current research on the prediction of severe disease or remission in children with juvenile arthritis, and define further steps needed towards developing prediction tools with sufficient accuracy for clinical use. Recent findings High disease activity, poor patient-reported outcomes, ankle or wrist involvement, and a longer time from onset to the start of treatment herald a severe disease course and a low chance of remission. Other studies confirmed that age less than 7 years and positive ANA are the strongest predictors of uveitis development. Preliminary evidence suggests ultrasound findings may predict flare in patients with clinically inactive disease, and several new biomarkers show promise. A few prediction tools that combine predictors to estimate the chance of remission or a severe disease course in the medium-term to long-term have shown good accuracy when internally validated in the population in which they were developed. Summary Promising candidate tools for predicting disease severity and long-term remission in juvenile arthritis are now available. These tools need external validation in other populations, and ideally formal trials to assess whether their use in practice improves patient outcomes. We are definitively getting closer, but we are not there yet.
|The role of epigenetics in paediatric rheumatic disease|
Purpose of review Autoimmune/inflammatory disorders can be stratified along a spectrum based on the primary involvement of innate vs. adaptive mechanisms. Stratifying patients based on molecular mechanisms rather than clinical phenotypes may allow for target-directed and individualized treatment. Recent findings Epigenetic events are gene regulatory mechanisms that contribute to inflammation across inflammatory diseases and resemble shared mechanisms that may be used as disease biomarkers and treatment targets. Significant progress has been made dissecting the epigenome in paediatric rheumatic diseases and identifies associations with clinical phenotypes, treatment responses and disease outcomes. Here, we will summarize and discuss epigenetic patterns in autoimmune/inflammatory disorders, underlying molecular alterations and their effects on gene expression and immune phenotypes. Summary Structured investigation of epigenetic events, their causes and effects on immune phenotypes in autoimmune/inflammatory, will improve our understanding of disease, deliver new diagnostic tools and treatment options.
|Update on the treatment and outcome of systemic lupus erythematous in children|
Purpose of review Provide an update of studies published in last 2 years on the outcomes and therapies in childhood-onset systemic lupus erythematous (cSLE). Recent findings Additional evidence has been provided about the benefits of universal hydroxychloroquine in SLE patients, although antimalarial maculopathy may be more prevalent than previously thought. Recent studies support lower glucocorticoid doses than used in the past may provide comparable therapeutic benefits, and cSLE patients can mount adequate immunogenic response and sustain long-term seroprotective titers when vaccinated. Long-term studies of adults with cSLE confirmed that damage accrual increases with disease duration. Cardiovascular disease, renal transplants, replacement arthroplasties, and myocardial infarctions occur between 20 and 40 years of age. Higher prednisone doses predicted higher damage trajectory and antimalarial exposure was protective. There were no prospective clinical trials published in pediatric patients with cSLE, but positive results from phase II trials with bariticinib and ustekinumab in adult SLE may raise the expectation that these drugs could be beneficial when used in cSLE. Summary The dire need for more clinical trials and licensed medications for cSLE persist as well as decreasing damage accrual.
|Microbiome and autoimmune diseases: cause and effect relationship|
Purpose of review The human body is the host of trillions of different prokaryotic microorganisms that colonize the skin and the mucosae. The interaction between human cells and these organisms is mediated by the immune system, sustaining a very complex and fragile balance. The immune cells need to prevent uncontrolled growth of pathogenic microbes and promote tolerance toward the existence of the beneficial ones. Growing evidence associates the disruption of this symbiotic relationship with the development of autoimmune diseases. Recent findings Human studies led to the identification of gut dysbiosis patterns in patients with rheumatoid arthritis, lupus and multiple sclerosis. Interestingly, the inoculation of pathogenic bacteria in animal models was associated with the development of these autoimmune diseases. Summary A better understanding of the microbiota–human interaction will enable the development of novel treatment choices. Currently, new molecules using helminth compounds are under investigation and have already revealed promising results.
|The role of Epstein–Barr virus infection in primary Sjögren's syndrome|
Purpose of review The purpose of this article is to draw attention to the role of Epstein–Barr virus (EBV) virus in the pathogenesis of the primary Sjögren's syndrome. The article introduces the problem of consequences of EBV acute infection, and its reactivation, in association with the immune response modulation by the virus and with an increased risk of developing systemic autoimmune diseases and EBV-associated cancers. Recent findings The knowledge about the mechanisms by which the virus may stay for years in a latent phase, unrecognized by the host response immune cells is constantly expanding. There are several mechanisms and theories about EBV influence on the autoimmune process in Sjogren's syndrome (pSS), including the similarity (molecular mimicry) between viral EBNA-2 protein and Ro-60 antigen or EBER-1 and EBER-2 viral proteins and La antigen. Summary The influence of EBV infection on the development and course of pSS has been proven. It has also been established that both EBV and pSS result in the increased risk of tumor (especially lymphoma) development. In the light of these findings, new ways to manage EBV infections are being sought. Optimal methods for assessing EBV infection status are being devised. Research also aims at finding therapies, which target EBV through the inhibition of the autoimmune process and of viral activity. The present article is an attempt to discuss the most important phenomena and elements linking EBV infection to the primary Sjögren's syndrome.
Τρίτη, 30 Ιουλίου 2019
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