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ID PMID Title PublicationDate abstract
26636425 Brief Report: Monoclonal Gammopathy and Risk of Lymphoma and Multiple Myeloma in Patients 2016 May OBJECTIVE: To assess the link between monoclonal gammopathy (MG), disease activity, and incidence of malignant hematologic disorders (MHDs), including lymphoma and multiple myeloma (MM), in patients with primary Sjögren's syndrome (SS). METHODS: Screening for the presence of MG was performed in 352 primary SS patients. Each patient with MG was paired with 2 age- and sex-matched primary SS controls without MG. Their characteristics were compared for the presence of risk factors for MG and for the relationship between MG and MHD. RESULTS: Twenty-six of the 352 primary SS patients (7.4%) had MG; 88% were women, with a median age of 62.7 years (interquartile range [IQR] 50.3-69.1 years) and a median disease duration of 7.8 years (IQR 3.6-12.8 years). The parameters associated with MG on multivariate analysis were higher disease activity, as measured by either the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI; adjusted odds ratio [OR] 9.7, P = 0.0002) or the Clinical ESSDAI (adjusted OR 6.7, P = 0.001), and low C4 level (adjusted OR 3.4, P = 0.04). After a median follow-up of 6.3 years (IQR 3.1-9.5 years), 10 patients with MG had developed an MHD (38.5%; 4 had lymphomas and 6 had MM), as compared with 4 patients in the control group (7.7%; all had lymphomas) (OR 7.5, P = 0.002). The only factor associated with the risk of MHDs was the presence of MG (adjusted OR 5.5, P = 0.02), which was principally associated with an increased risk of MM (23% versus 0%; P = 0.0009), but not lymphoma (15% versus 8%; P = 0.3). CONCLUSION: The presence of MG was associated with higher disease activity and an increased risk of MHD in primary SS. In the presence of MG, the risk of MM was even higher than the risk of lymphoma. These results suggest that regular monitoring of primary SS patients with MG for the emergence of both lymphoma and MM is necessary.
25545344 Direct infection of primary salivary gland epithelial cells by human T lymphotropic virus 2015 Apr OBJECTIVE: To investigate whether human T lymphotropic virus type I (HTLV-I) directly infects salivary gland epithelial cells (SGECs) and induces the niche of the salivary glands in patients with Sjögren's syndrome (SS). METHODS: SGECs were cultured with the HTLV-I-producing CD4+ T cell line HCT-5 or with Jurkat cells. Antibody arrays, immunofluorescence analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the profiles of inflammation-related molecules, and the profiles of apoptosis-related molecules were determined by antibody array and immunofluorescence analysis. The presence of HTLV-I-related molecules was assessed by immunofluorescence analysis and in situ polymerase chain reaction. Apoptosis of SGECs was evaluated by TUNEL staining. RESULTS: Among the SGECs, 7.8 ± 1.3% (mean ± SD) were positive for HTLV-I-related proteins after 96-hour coculture with HCT-5 cells. Nuclear NF-κB p65 was also detected in 10% of the SGECs. The presence of HTLV-I proviral DNA in SGECs after coculture with HCT-5 cells was detected by in situ polymerase chain reaction. After coculture of SGECs with HCT-5, the expression of cytokines and chemokines, including soluble intercellular adhesion molecule 1, RANTES, and interferon γ-induced protein 10 kd (IP-10/CXCL10) was increased in a time-dependent manner. The expression of proapoptotic molecules (e.g., cytochrome c and Fas) and antiapoptotic molecules (e.g., Bcl-2, Heme oxygenase 2, and Hsp27) was increased in the SGECs cocultured with HCT-5, showing that apoptosis of SGECs was not detected after coculture with HCT-5 or Jurkat cells. CONCLUSION: HTLV-I is thought to infect SGECs and alter their cellular functions. These changes may induce the niche of SS and contribute to the development of SS in anti-HTLV-I antibody-positive individuals.
26690894 Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK 2016 Apr The prevalence of cognitive impairment in rheumatoid arthritis (RA) patients was increasingly serious nowadays. The purpose of the current study was to explore whether salidroside (Sal) could alleviate arthritis-induced cognition deficits and examine the relationship between the impairment and Rho/ROCK/NF-κB pathway. Collagen-induced arthritis (CIA) was established by the injection of chicken type II collagen (CII), complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA). Arthritic lesions of CIA rats were assessed by arthritis index score, swelling of paws and histological analysis. Cognitive deficits symptoms of CIA rats were monitored through Morris water maze test. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and serum were significantly reduced with salidroside (20 mg/kg, 40 mg/kg) treatment compared with those in the CIA group. In parallel, we demonstrated that the expressions of RhoA, ROCK1, ROCK2, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were enhanced accompanying the investigation arthritis-induced cognition deficits, which were remarkably down-regulated by salidroside and confirmed by the results obtained from western blot and immunohistochemistry. LC-MS/MS results ascertained that Sal could enter into the blood and brain tissues to exhibit the protective effect on arthritis-induced cognitive dysfunction. Therefore, it was assumed that Sal might be a potential therapeutic candidate to treat arthritis-induced brain cognition deficits through the regulation of Rho/ROCK/NF-κB signaling.
25989609 Medically Significant Infections Are Increased in Patients With Juvenile Idiopathic Arthri 2015 Sep OBJECTIVE: The association between anti-tumor necrosis factor therapy and increased rates of infection is widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less well documented. The aims of this analysis were to compare the rates of medically significant infections (MSIs) in children with JIA treated with etanercept (ETN) versus methotrexate (MTX) and to compare the rates between combination therapy with ETN plus MTX and monotherapy with ETN. METHODS: A total of 852 ETN-treated children and 260 MTX-treated children had been recruited to the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN). MSIs included infections that resulted in death or hospitalization or were deemed medically significant by the clinician. This on-drug analysis followed the patients until the first MSI, treatment discontinuation, the last followup, or death. Cox proportional hazards models, which were adjusted using propensity deciles, were used to compare rates of MSI between cohorts. Sensitivity analyses were conducted specifically with regard to serious infections (SIs), which were defined as those requiring hospitalization or treatment with intravenous antibiotics/antivirals. RESULTS: The ETN-treated cohort was older and had a longer disease duration, but the disease activity was similar between the cohorts. A total of 133 first MSIs were reported (109 with ETN and 24 with MTX). Patients receiving ETN had higher rates of MSI than did the controls (propensity decile adjusted hazard ratio 2.13 [95% confidence interval 1.22-3.74]). The risk of MSI was higher whether patients were receiving combination or monotherapy. Sensitivity analysis showed no between-group difference in the rate of SIs, which were much less common. CONCLUSION: ETN therapy is associated with an increased risk of MSI; however, this increased risk disappears when considering only SIs, which suggests that either there were differences in the severity of infections and/or there was a possible reporting bias.
26003010 Enhanced therapeutic anti-inflammatory effect of betamethasone on topical administration w 2015 Sep The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm(2), spatial-peak, temporal-peak intensity) ultrasound, delivered with a lightweight (<100 g), tether-free, fully wearable, battery-powered applicator, is capable of reducing inflammation in a mouse model of rheumatoid arthritis. The therapeutic, acute, anti-inflammatory effect was estimated from the relative swelling induced in mice hindlimb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near-infrared labeled 2-deoxyglucose. The outcome of the experiments indicated that the combination of ultrasound exposure and topical application of 0.1% (w/w) betamethasone gel resulted in statistically significantly (p < 0.05) enhanced anti-inflammatory activity in comparison with drug or ultrasound treatment alone. The present study underscores the potential benefits of low-frequency, low-intensity ultrasound-assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, tolerable low-frequency, low-intensity ultrasound-promoted non-invasive drug delivery.
26852847 Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With 2016 Jan The aims of this study were to prepare fine intra-articular-administrated chitosan thermosensitive hydrogels combined with alginate microspheres and to investigate the possibility of those hydrogels as a drug delivery system for promoting the anti-inflammation effect. Diclofenac sodium containing alginate microspheres was prepared by a modified emulsification and/or gelation method and then dispersed into injectable thermosensitive hydrogels, consisting of chitosan and β-glycerophosphate. The final combined hydrogels were evaluated in terms of their morphology properties, rheological properties, in vitro drug release, and in vivo biocompatibility and pharmacodynamics behaviors. The optimized formulation exhibited sol-gel transition at 31.72 ± 0.42°C and quickly turned into gel within 5 min, with sustained drug release characteristics followed Ritger-Peppas equation, which could prolong the in vitro drug release to 5 days. In addition, the anti-inflammation efficacy of the combined hydrogels in rabbits with experimental rheumatoid arthritis was higher than that of drug solution and pure chitosan hydrogels. Those results demonstrated that these combined hydrogels could become a potential drug delivery system for improving the therapeutic effect of diclofenac sodium and suggested an important technology platform for intra-articular administration.
27173727 Reduced TCR-dependent activation through citrullination of a T-cell epitope enhances Th17 2016 Jul Citrullination is a post-translational modification of arginine that commonly occurs in inflammatory tissues. Because T-cell receptor (TCR) signal quantity and quality can regulate T-cell differentiation, citrullination within a T-cell epitope has potential implications for T-cell effector function. Here, we investigated how citrullination of an immunedominant T-cell epitope affected Th17 development. Murine naïve CD4(+) T cells with a transgenic TCR recognising p89-103 of the G1 domain of aggrecan (agg) were co-cultured with syngeneic bone marrow-derived dendritic cells (BMDC) presenting the native or citrullinated peptides. In the presence of pro-Th17 cytokines, the peptide citrullinated on residue 93 (R93Cit) significantly enhanced Th17 development whilst impairing the Th2 response, compared to the native peptide. T cells responding to R93Cit produced less IL-2, expressed lower levels of the IL-2 receptor subunit CD25, and showed reduced STAT5 phosphorylation, whilst STAT3 activation was unaltered. IL-2 blockade in native p89-103-primed T cells enhanced the phosphorylated STAT3/STAT5 ratio, and concomitantly enhanced Th17 development. Our data illustrate how a post-translational modification of a TCR contact point may promote Th17 development by altering the balance between STAT5 and STAT3 activation in responding T cells, and provide new insight into how protein citrullination may influence effector Th-cell development in inflammatory disorders.
27023113 Long-Term Effects of (-)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PI 2016 Rheumatoid arthritis (RA)--a widespread chronic inflammatory disease in industrialized countries--is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the pharmacological mode of action of this polyphenol.
26097196 Rational design of antirheumatic prodrugs specific for sites of inflammation. 2015 Oct OBJECTIVE: Biologic drugs, such as the anti-tumor necrosis factor (anti-TNF) antibody adalimumab, have represented a breakthrough in the treatment of rheumatoid arthritis. Yet, concerns remain over their lack of efficacy in a sizable proportion of patients and their potential for systemic side effects such as infection. Improved biologic prodrugs specifically targeted to the site of inflammation have the potential to alleviate current concerns surrounding biologic anticytokine therapies. The purpose of this study was to design, construct, and evaluate in vitro and ex vivo the targeting and antiinflammatory capacity of activatable bispecific antibodies. METHODS: Activatable dual variable domain (aDVD) antibodies were designed and constructed to target intercellular adhesion molecule 1 (ICAM-1), which is up-regulated at sites of inflammation, and anti-TNF antibodies (adalimumab and infliximab). These bispecific molecules included an external arm that targets ICAM-1 and an internal arm that comprises the therapeutic domain of an anti-TNF antibody. Both arms were linked to matrix metalloproteinase (MMP)-cleavable linkers. The constructs were tested for their ability to bind and neutralize both in vitro and ex vivo targets. RESULTS: Intact aDVD constructs demonstrated significantly reduced binding and anti-TNF activity in the prodrug formulation as compared to the parent antibodies. Human synovial fluid and physiologic concentrations of MMP enzyme were capable of cleaving the external domain of the antibody, revealing a fully active molecule. Activated antibodies retained the same binding and anti-TNF inhibitory capacities as the parent molecules. CONCLUSION: The design of a biologic prodrug with enhanced specificity for sites of inflammation (synovium) and reduced specificity for off-target TNF is described. This construct has the potential to form a platform technology that is capable of enhancing the therapeutic index of drugs for the treatment of RA and other inflammatory diseases.
26044780 Gait characteristics associated with the foot and ankle in inflammatory arthritis: a syste 2015 Jun 5 BACKGROUND: Gait analysis is increasingly being used to characterise dysfunction of the lower limb and foot in people with inflammatory arthritis (IA). The aim of the systematic review was to evaluate the spatiotemporal, foot and ankle kinematic, kinetic, peak plantar pressure and muscle activity parameters between patients with inflammatory arthritis and healthy controls. METHODS: An electronic literature search was performed on Medline, CINAHL, SportsDiscus and The Cochrane Library. Methodological quality was assessed using a modified Quality Index. Effect sizes with 95% confidence intervals (CI) were calculated as the standardised mean difference (SMD). Meta-analysis was conducted if studies were homogenous. RESULTS: Thirty six studies with quality ranging from high to low met the inclusion criteria. The majority of studies reported gait parameters in Rheumatoid arthritis (RA). The gait pattern in RA was characterised by decreased walking speed (SMD 95% CI -1.57, -2.25 to -0.89), decreased cadence (SMD -0.97, -1.49 to -0.45), decreased stride length (SMD -1.66, -1.84 to -1.49), decreased ankle power (SMD -1.36, -1.70 to -1.02), increased double limb support time (SMD 1.03, 0.84 to 1.22), and peak plantar pressures at the forefoot (SMD 1.11, 0.76 to 1.45). Walking velocity was reduced in psoriatic arthritis and gout with no differences in ankylosing spondylitis. No studies have been conducted in polymyalgia rheumatica, systemic sclerosis or systemic lupus erythematosus. CONCLUSIONS: The review identified the majority of studies reporting gait adaptations in RA, but limited evidence relating to other IA conditions. Poor data reporting, small sample sizes and heterogeneity across IA conditions limit the interpretation of the findings. Future studies may consider a standardised analytical approach to gait analysis that will provide clinicians and researchers with objective evidence of foot function in people with IA.
27217286 Quality measures for total ankle replacement, 30-day readmission and reoperation rates wit 2016 May 23 OBJECTIVE: To report on the rate of 30-day readmission and the rate of additional or revision surgery within 12 months following total ankle replacement (TAR). DESIGN: A data-linkage study of the UK National Joint Registry (NJR) data and Hospital Episodes Statistics (HES) database. These two databases were linked in a deterministic fashion. HES episodes 12 months following the index procedure were isolated and analysed. Logistic regression was used to model predictors of reoperation and revision for primary ankle replacement. PARTICIPANTS: All patients who underwent primary and revision ankle replacements according to the NJR between February 2008 and February 2013. RESULTS: The rate of 30-day readmission following primary and revision ankle replacement was 2.2% and 1.3%, respectively. In the 12 months following primary and revision ankle replacements, the revision rate (where implants needed to be removed) was 1.2% with increased odds in those orthopaedic units preforming <20 ankle replacements per year and patients with a preoperative fixed equinus deformity. The reoperation other than revision (where implants were not removed) in the 12 months following primary and revision TARs was 6.6% and 9.3%, respectively. Rheumatoid arthritis, cemented prosthesis and high ASA grade significantly increased the odds of reoperation. CONCLUSIONS: TAR has a 30-day readmission rate of 2.2%, which is similar to that of knee replacement but lower than that of total hip replacement. 6.6% of patients undergoing primary TAR require a reoperation within 12 months of the index procedure. Early revision rates are significantly higher in low-volume centres.
27747536 Consensus Decision Models for Biologics in Rheumatoid and Psoriatic Arthritis: Recommendat 2015 Dec INTRODUCTION: Biologic therapies are efficacious but costly. A number of health economic models have been developed to determine the most cost-effective way of using them in the treatment pathway. These models have produced conflicting results, driven by differences in assumptions, model structure, and data, which undermine the credibility of funding decisions based on modeling studies. A Consensus Working Party met to discuss recommendations and approaches for future models of biologic therapies. METHODS: Our working party consisted of clinical specialists, modelers, and policy makers. Two 1-day meetings were held for members to arrive at consensus positions on model structure, assumptions, and appropriate data sources. These views were guided by clinical aspects of rheumatoid and psoriatic arthritis and the principles of evidence-based medicine. Where opinions differed, we sought to identify a research agenda that would generate the evidence needed to reach consensus. RESULTS: We gained consensus in four areas of model development: initial response to treatment; long-term disease progression; lifetime costs and benefits; and model structure. Consensus was also achieved on some key parameters such as choices of outcome measures, methods for extrapolation beyond trial data, and treatment switching. A research agenda to support further consensus was also identified. CONCLUSION: Consensus guidance that fully reflects current evidence and clinical understanding was gained successfully. In addition, research needs have been identified. Such guidance can be updated as evidence develops and policy questions change and need not be prescriptive as long as deviations from consensus are clearly explained and justified. FUNDING: Arthritis Research UK and the UK Medical Research Council Network of Hubs for Trials Methodology Research.
27434917 The implant surface characteristics and peri-implantitis. An evidence-based update. 2016 Mar Peri-implantitis is an inflammatory disease of the peri-implant mucosa with the loss of supporting bone. Because of the absence of an un-inflamed connective tissue zone between the healthy and diseased sites, peri-implant lesions are thought to progress more rapidly than periodontal lesions, suggesting the importance of early diagnosis and intervention if possible. A number of risk factors have been identified that may lead to the initiation and progression of peri-implant mucositis and peri-implantitis, eg., previous periodontal disease, poor plaque control, inability to clean, residual cement, smoking, genetic factors, diabetes, occlusal overload, rheumatoid arthritis, increased time of loading and alcohol consumption. At present there is not much literature available, highlighting the relationship between implant surface characteristics and peri-implant diseases. Implant surface characteristics vary with respect to topography, roughness and clinical composition, including turned, blasted, acid etched, porous sintered, oxidized, plasma sprayed and hydroxyapatite coated surfaces and their combinations. So the aim of this review is to explore the relationship between the characteristics of implant surface, the prevalence and incidence of peri-implantitis. This would help to identify plausible influence of surface characteristics, oral hygiene instructions and maintenance of implants for the long-term uneventful success of implant therapy.
27322636 Intra-articular injections of mesenchymal stem cells (MSCs) as a treatment for hemophilic 2016 Aug Intraarticular (IA) injections of mesenchymal stem cells (MSCs) in idiopathic osteoarthritis (OA) have shown encouraging results in the literature. Hemophilic arthropathy (HA) represents an enormous societal burden. The similarity between OA and HA is very limited. HA resembles much more to the rheumatoid arthritis because a presence of thick synovial membrane and large lymphocytes infiltration. However, in its final stages, HA resembles OA and that is when IA injections of MSCs are commonly used. In this article, we review the concept of IA injections of MSCs as a treatment for HA, using the literature on OA as an example. Regarding HA, only two experimental studies have been reported to date. Such studies stated that IA injections of MSCs appear to be efficacious for decreasing pain in patients with OA and HA. The use of IA injections of MSCs is thus a promising therapeutic modality for treating HA.
27228639 Vitamin D and Systemic Lupus Erythematosus: Myth or Reality? 2016 Mar There is growing interest in the contribution of vitamin D deficiency to autoimmunity. Several studies have shown an association between low levels of vitamin D and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid diseases, celiac disease, and systemic lupus erythematosus (SLE). Vitamin D receptor ligands can mediate immunosuppressive effects. It has been suggested that low levels of this hormone contribute to the immune activation in lupus and other autoimmune diseases. This review updates and summarizes the literature on the association between vitamin D and SLE, and discusses the various correlations between vitamin D and SLE activity, clinical expressions, serology, and gene polymorphisms of vitamin D receptors.
26942035 The Use of IL-1 Receptor Antagonist (Anakinra) in Idiopathic Recurrent Pericarditis: A Nar 2016 Recurrent pericarditis is a complication of acute pericarditis in 20-30% of the patients and is usually idiopathic in nature. The underlying pathogenesis of this condition remains unclear, although immune-mediated mechanisms seem likely. A subgroup of these patients with refractory symptoms can be challenging to manage, and multiple immunosuppressive medications have been used without consistent benefit. Anakinra, an interleukin-1 receptor antagonist, has been used in treatment of rheumatoid arthritis and autoinflammatory syndromes. Preliminary evidence suggests that anakinra could be a promising therapy for idiopathic recurrent pericarditis. In this narrative review, we summarize the current understanding of the etiopathogenesis of idiopathic recurrent pericarditis, mechanism of action of anakinra, and the preliminary evidence, supporting the use of anakinra in pericarditis.
26648937 SLE: Another Autoimmune Disorder Influenced by Microbes and Diet? 2015 Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. Despite years of study, the etiology of SLE is still unclear. Both genetic and environmental factors have been implicated in the disease mechanisms. In the past decade, a growing body of evidence has indicated an important role of gut microbes in the development of autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. However, such knowledge on SLE is little, though we have already known that environmental factors can trigger the development of lupus. Several recent studies have suggested that alterations of the gut microbial composition may be correlated with SLE disease manifestations, while the exact roles of either symbiotic or pathogenic microbes in this disease remain to be explored. Elucidation of the roles of gut microbes - as well as the roles of diet that can modulate the composition of gut microbes - in SLE will shed light on how this autoimmune disorder develops, and provide opportunities for improved biomarkers of the disease and the potential to probe new therapies. In this review, we aim to compile the available evidence on the contributions of diet and gut microbes to SLE occurrence and pathogenesis.
25895577 Protective and detrimental roles of inflammasomes in disease. 2015 Jul Over recent years, inflammasomes have emerged as key regulators of immune and inflammatory responses. They induce programmed cell death and direct the release of danger signals and the inflammatory cytokines interleukin (IL)-1β and IL-18. The concerted actions of inflammasomes are of utmost importance for responding adequately to harmful environmental agents and infections. However, deregulated inflammasome signaling is increasingly linked to a diversity of human pathologies, including rheumatoid arthritis, inflammatory bowel disease, and rare, hereditary periodic fever syndromes. In this review, we discuss recent insight in the protective and detrimental roles of inflammasomes in selected infectious, autoinflammatory and autoimmune diseases, and cover clinically approved therapies that interfere with inflammasome signaling. These findings highlight the importance of fine-balancing the Ying and Yang activities of inflammasomes for sustained homeostasis and suggest that further understanding of inflammasome mechanisms may offer new cures for human diseases.
25705640 Cardiovascular disease in systemic sclerosis. 2015 Jan Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis. The mechanisms promoting ATS in SSc are not fully understood, but it is believed to be secondary to multi-system organ inflammation, endothelial wall damage and vasculopathy. Both traditional risk factors and endothelial dysfunction have been proposed to participate to the onset and progression of ATS in such patients. In particular, endothelial cell injury induced by anti-endothelial antibodies, ischemia/reperfusion damage, immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism that determine a defective vasculogenesis. Aim of this review is to analyse both causes and clinical manifestations of macrovascular involvement and ATS in SSc.
25666238 Photosensitivity and double vision as initial symptoms of colon cancer. 2015 Feb 9 A 75-year-old man suffering from rheumatoid arthritis, myxoedema and type II diabetes mellitus, presented with occasional double vision and photosensitivity. The patient underwent an MRI of the brain showing a tumour located in the right of the sphenoid bone. A subsequent diagnostic CT scan of the thorax, abdomen and pelvis revealed a left-sided colon tumour, which biopsy proved as being an adenocarcinoma.