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ID PMID Title PublicationDate abstract
29311111 Dual Blockade of Interleukin-1β and Interleukin-17A Reduces Murine Arthritis Pathogenesis 2018 Mar Despite the efficacy of biologics for treatment of rheumatoid arthritis (RA), many patients show inadequate responses and likely require neutralization of multiple mediators. Neutralization of both interleukin (IL)-1β and IL-17A with monoclonal antibodies showed greater efficacy than either agent alone in a mouse arthritis model with cooperative inhibition of key inflammatory factors, IL-6, granulocyte colony-stimulating factor (G-CSF), and CXC chemokine ligand (CXCL)1. Given the potential clinical benefit in RA, we generated a human dual variable domain antibody Ig, ABBV-615, capable of simultaneous binding and neutralization of IL-1β and IL-17A. ABBV-615 was characterized and evaluated in cynomolgus monkeys for pharmacokinetics and toxicity to enable clinical development. ABBV-615 exhibited affinities (K(D)) of 12 and 3 pM on human IL-1β and IL-17A, respectively, and potencies (IC(50)) of 3 and 58 pM, respectively, as well as excellent drug-like properties. ABBV-615 pharmacokinetics in cynomolgus monkeys was dose proportional from 20 to 100 mg/kg with a mean half-life of 16 days. However, a 13-week repeat-dose toxicity study in cynomolgus monkeys revealed time-dependent spontaneous infections exclusively in skin at all doses tested and not historically seen with single-agent anti-IL-1α/β or anti-IL-17A. Consistent with reduced resistance to skin infections, IL-1β- and IL-17A-stimulated human keratinocytes demonstrate cooperative or compensatory production of key antibacterial and inflammatory mediators such as lipocalin-2, G-CSF, CXCL1, IL-8, tumor necrosis factor, and IL-6, which aid in defense against skin bacterial infections. These results illustrate the skin-specific antimicrobial mechanisms of IL-1β and IL-17A and highlight the importance of understanding unique combinatorial effects of biologic agents.
29648521 Understanding angiogenesis during aging: opportunities for discoveries and new models. 2018 Dec 1 Microvascular network growth and remodeling are common denominators for most age-related pathologies. For multiple pathologies (myocardial infarction, stroke, hypertension), promoting microvascular growth, termed angiogenesis, would be beneficial. For others (cancer, retinopathies, rheumatoid arthritis), blocking angiogenesis would be desirable. Most therapeutic strategies, however, are motivated based on studies using adult animal models. This approach is problematic and does not account for the impaired angiogenesis or the inherent network structure changes that might result from age. Considering the common conception that angiogenesis is impaired with age, a need exists to identify the causes and mechanisms of angiogenesis in aged scenarios and for new tools to enable comparison of aged versus adult responses to therapy. The objective of this article is to introduce opportunities for advancing our understanding of angiogenesis in aging through the discovery of novel cell changes along aged microvascular networks and the development of novel ex vivo models.
30207568 Prevalence of Rheumatoid Arthritis and Spondyloarthritis in Turkey: A Nationwide Study. 2018 Jun OBJECTIVES: This study aims to estimate the prevalence of rheumatoid arthritis (RA) and spondyloarthritis (SpA) in Turkey using the same telephone questionnaire developed for screening RA and SpA in France and used in Serbia and Lithuania. MATERIAL AND METHODS: The study was performed in two steps. In step I, the French questionnaire was translated into Turkish and validated through a group of 200 patients (80 males, 120 females; mean age 44.0±13.1 years; range 19 to 75 years) followed up at the rheumatology departments of University Hospitals in Antalya and Ankara. In step II, the validated Turkish questionnaire was administered face-to-face to randomly selected 4,012 subjects (1,670 males, 2,342 females; mean age 41.5±16.8 years; range 16 to 97 years) by trained general practitioners across the country, in 25 prov- inces for case detection. The subjects who were suspected of having RA or SpA in accordance with the questionnaire were invited to the nearest university hospital for rheumatologic examination in order to confirm the diagnosis. RESULTS: In step II, a total of 25 subjects (2 males, 23 females) were diagnosed as RA. The standardized RA prevalence for the general population of Turkey was calculated as 0.56% (95% confidence interval [CI]; 0.33-0.79), 0.10% (95% CI; -0.05-0.25) for males and 0.89% (95% CI; 0.51-1.27) for females. A total of 18 subjects (3 males, 15 females) were diagnosed as SpA. The standardized SpA prevalence for the general population of Turkey was 0.46% (95% CI; 0.25-0.67), 0.17% (95% CI; -0.03-0.37) for males and 0.65% (95% CI; 0.32-0.98) for females. The prevalence of RA was highest in the Northern region (2.00%) and the prevalence of SpA was highest in the Central region (1.49%). CONCLUSION: The prevalences of RA and SpA in Turkey are close to each other and there are significant inter-regional variations in prevalences of both RA and SpA.
28815559 Characteristic elevation of soluble TNF receptor II : I ratio in macrophage activation syn 2018 Mar To investigate the clinical significance of soluble tumour necrosis factor receptor (sTNF-R) II/I ratio as an indicator of the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA), we measured the serum sTNF-RI and II levels in 117 patients with s-JIA, including 29 patients with MAS, 15 with Epstein-Barr virus-induced haemophagocytic lymphohistiocytosis (EBV-HLH), 15 with Kawasaki disease (KD) and 28 healthy controls (HCs). We determined their correlation with measurements of disease activity and severity. Furthermore, we measured serum interleukin (IL)-18 levels in patients with EBV-HLH and compared these in levels in patients with MAS. The sTNF-RII/I ratio was elevated significantly in MAS and EBV-HLH patients compared with those in the acute phase of s-JIA and KD patients, whereas there were no significant differences between HCs and those in the acute phase of s-JIA. The sTNF-RII/I ratio increased profoundly as MAS developed and correlated positively with disease activity. Serum IL-18 levels were elevated significantly in MAS patients compared with EBV-HLH patients. The monitoring of serum IL-18 and sTNF-RII/I might be useful for the diagnosis of MAS and the differentiation between MAS and EBV-HLH.
30086205 Interventions for dry mouth and hyposalivation in Sjögren's syndrome: A systematic review 2019 May OBJECTIVES: Systematic review with meta-analysis of interventions for dry mouth symptoms and hyposalivation of Sjögren's syndrome (SS). MATERIALS AND METHODS: We searched MEDLINE, Cochrane Central and EMBASE up to February 2018 for randomized trials of interventions for dry mouth and hyposalivation of SS. The primary outcome was the mean change in xerostomia symptoms. The secondary outcomes included changes in salivary flow and quality of life. We used the Cochrane risk of bias tool for individual studies and the GRADE method to summarize the quality of evidence across studies for the included outcomes. RESULTS: Thirty-six studies (3,274 patients) were included in the systematic review. Results from the meta-analyses showed high-quality evidence that pilocarpine was superior to placebo in reducing dry mouth symptoms. We found moderate quality of evidence that pilocarpine, rituximab and interferon-alpha were more effective than placebo in increasing salivary flow, with the relevant effect size being large for pilocarpine, and notably smaller for rituximab and interferon-alpha. CONCLUSION: Clinicians should be very confident in the beneficial effects of pilocarpine upon dry mouth symptoms of SS and moderately confident that pilocarpine, rituximab and interferon-alpha can have beneficial effects upon salivary flow. Adverse events are common. The use of other treatment modalities cannot be supported on the basis of current evidence.
28969936 The DNA methylation landscape of CD4(+) T cells in oligoarticular juvenile idiopathic arth 2018 Jan Juvenile idiopathic arthritis (JIA) is presumed to be driven by an adverse combination of genes and environment. Epigenetic processes, including DNA methylation, act as a conduit through which the environment can regulate gene activity. Altered DNA methylation has been associated with adult autoimmune rheumatic diseases such as rheumatoid arthritis, but studies are lacking for paediatric autoimmune rheumatic diseases including JIA. Here, we performed a genome-scale case-control analysis of CD4(+) T cell DNA methylation from 56 oligoarticular JIA (oJIA) cases and 57 age and sex matched controls using Illumina HumanMethylation450 arrays. DNA methylation at each array probe was tested for association with oJIA using RUV (Remove Unwanted Variation) together with a moderated t-test. Further to this 'all-inclusive' analysis, we stratified by age at diagnosis (≤6yrs, >6yrs) and by sex as potential sources of heterogeneity. Following False Discovery Rate (FDR) adjustment, no probes were associated with oJIA in the all-inclusive, >6yrs-diagnosed, or sex-stratified analyses, and only one probe was associated with oJIA in the ≤6yrs-diagnosed analysis. We attempted technical validation and replication of 14 probes (p(unadj)<0.01) at genes of known/potential relevance to disease. At VPS53, we demonstrated a regional shift towards higher methylation in oJIA (all-inclusive) compared to controls. At REEP3, where polymorphism has been previously associated with JIA, we demonstrated higher DNA methylation in male oJIA compared to male controls. This is the most comprehensive JIA case-control analysis of DNA methylation to date. While we have generated some evidence of altered methylation in oJIA, substantial differences are not apparent in CD4(+) T cells. This may indicate a lesser relevance of DNA methylation levels in childhood, compared to adult, rheumatic disease.
28284773 Extranodal marginal zone B cell lymphoma: An unexpected complication in children with Sjö 2018 Jul Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by the infiltration of lymphocytes into exocrine glands, resulting in the typical sicca symptoms. Unlike adults, primary SS is a very rare condition in childhood, and the risk of malignancy in juvenile SS (JSS) has not been defined. We report the detection of extranodal marginal zone B-cell lymphoma (EMZL) occurring in two children with SS. Fine needle aspiration of the salivary glands (SG) showed nonspecific findings that led to delayed diagnosis of SS. The diagnosis of B-cell lymphoma associated with JSS was based on morphologic and immunohistochemical staining done during the biopsy. To highlight awareness of EMZL as a timely and appropriate update of an unusual complication in children with SS.
29395257 Assessing health-related quality of life in primary Sjögren's syndrome-The PSS-QoL. 2018 Aug OBJECTIVES: To develop a questionnaire for the assessment of health-related quality of life (HRQL) in primary Sjögren's syndrome (PSS), and to test its psychometric properties. METHODS: Based on the concepts of a previous qualitative study, a questionnaire for the assessment of HRQL in PSS (PSS-QoL) was developed. Psychometric testing of PSS-QoL was performed after revising the first draft with feedback of patients (n = 6) and clinicians (n = 4). Convergent construct validity was assessed by correlating the score with the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Euro-QoL 5D (EQ-5D). Reliability was examined by asking patients to complete the questionnaire twice 1-2 weeks apart. An English Version of the PSS-QoL was developed by using standard methodology with forward and back translation. RESULTS: Out of the 75 PSS patients, 91% were female, mean (±SD) age was 58.5 ± 12.5 years. PSS-QoL consists of 25 questions and can be divided into two main categories: physical (discomfort and dryness) and psychosocial. The internal consistency of the PSS-QoL revealed a Crohnbach's α of 0.892. Strong and moderate correlations were found between the PSS-QoL and ESSPRI (corr(coeff) = 0.755) and EQ. 5D-pain/discomfort (corr(coeff) = 0.531). Reproducibility of the PSS-QoL was high, yielding an ICC of 0.958 (95% CI: 0.926-0.981). CONCLUSIONS: The PSS-QoL is the first specific tool for the assessment of patients' HRQL in PSS and showed good psychometric properties. It may serve as a novel patient-reported outcome measure in future clinical studies.
29946647 [The value of ultrasonic elastography in diagnosis of salivary gland lesions in patients w 2018 Feb PURPOSE: The present study was aimed to clinically evaluate transitional treatment of pulpitis during pregnancy. METHODS: Sixty pregnant women with pulpitis were divided into the first, second and third trimester. They were anesthetized locally using STA system combined with psychological intervention during treatment. The teeth were given one-appointment root canal preparation and filled with vitapex pasta. Normal obturation of the root canal was conducted after delivery. The effects of dental treatment, pregnancy outcomes and neonatal health status were observed. Data of the survey were analyzed by SPSS 20.0 software package, including Student's t test and chi-square test. RESULTS: The symptoms of pulpitis were significantly improved 24h after treatment,and the effective rate was 96.7%. The difference of VAS before and after treatment was statistically significant (P<0.05). Patients had no discomfort till the end of pregnancy,and the success rate was 98.3%. No adverse pregnancy outcomes were observed after treatment during different periods of pregnancy. Neonatal health was good. Significant differences were not found in birth gestational age, body weight, malformations, and neonatal complications between three treatment periods (P>0.05). CONCLUSIONS: Transitional treatment of pulpitis during pregnancy is a safe and effective procedure and worthy of wide use clinically.
29890347 Endoplasmic reticulum stress in autoimmune diseases: Can altered protein quality control a 2018 Aug For many years, researchers in the field of autoimmunity have focused on the role of the immune components in the etiopathogenesis of autoimmune diseases. However, some studies have demonstrated the importance of target tissues in their pathogenesis and the breach of immune tolerance. The immune system as well as target tissue cells (plasmatic, β-pancreatic, fibroblast-like synoviocytes, thyroid follicular and epithelial cells of the lachrymal glands, salivary glands, intestine, bronchioles and renal tubules) share the characteristic of secretory cells with an extended endoplasmic reticulum (ER). The function of these cells depends considerably on a normal ER function and calcium homeostasis, so they can produce and secrete their main components, which include glycoproteins involved in antigenic presentation such as major histocompatibility complex (MHC) class I and II. All these proteins are synthesized and modified in the ER, and for this reason disturbances in the normal functions of this organelle such as protein folding, protein quality control, calcium homeostasis and redox balance, promote accumulation of unfolded or misfolded proteins, a condition known as ER stress. Autoimmune diseases are characterized by inflammation, which has been associated with an ER stress condition. Interestingly, patients with these diseases contain circulating auto-antibodies against chaperone proteins (such as Calnexin and GRP94), thus affecting the folding and assembly of MHC class I and II glycoproteins and their loading with peptide. The main purpose of this article is to review the involvement of the protein quality control and unfolded protein response (UPR) in the ER protein homeostasis (proteostasis) and their alterations in autoimmune diseases. In addition, we describe the interaction between ER stress and inflammation and evidences are shown of how autoimmune diseases are associated with an ER stress condition, with a special emphasis on the second most prevalent autoimmune rheumatic disease, Sjögren's syndrome.
29602165 Sonographic evaluation of salivary glands in juvenile Sjögren's syndrome. 2018 Jan IIntroduction: Sjögren's syndrome in childhood is a rare autoimmune disease and mostly under-diagnosed. The aim of this study is to highlight the importance of ultrasonographic assessment of the salivary glands in children with recurrent parotitis and positive autoantibodies. Two cases of ultrasonographic patterns typical of Sjögren's syndrome have been described below. Case 1: Female, 7 years old, reporting for 2 years recurrent parotitis, xerophthalmia, xerostomia, polyarthralgia and fever. Immunological tests were positive for antinuclear antibodies, rheumatoid factor, anti-SSA/Ro and anti-SSB/La. Salivary glands ultrasound was consistent with Grade 4 by the B-mode method and the spectral Doppler with presence of intense Power Doppler signal and decreased vessels internal resistance, supporting the diagnosis of juvenile Sjögren's syndrome. Case 2: Female, 10 years old, reporting recurrent parotitis for 1 year and polyarthritis for 10 days. The supplementary tests revealed positive antibodies for Sjögren's syndrome. Salivary glands Ultrasound and Spectral Doppler were consistent with chronic and active inflammatory process of the salivary glands in the juvenile Sjögren's syndrome. DISCUSSION: Salivary glands ultrasound can be a useful exam in the diagnosis of juvenile Sjögren's syndrome.
30218790 The limitations of using simple definitions of glucocorticoid exposure to predict fracture 2018 Dec PURPOSE: To evaluate the effects of different definitions of glucocorticoid (GC) exposure on the magnitude and pattern of fracture risk using the same dataset. METHODS: Data from patients with rheumatoid arthritis (RA) were extracted from the Clinical Practice Research Datalink, a primary care database with electronic health records in the United Kingdom. Patients exposed to oral GCs were matched to up to two unexposed patients by age, gender and location. The first osteoporotic fracture was identified and adjusted and unadjusted cox proportional hazard ratios (HR) and 95% confidence intervals (CI) produced for fracture risk following GC therapy using different models of risk attribution. These include models demonstrating the effect of dose, duration and recency of GC exposure. RESULTS: There were 16,507 patients included. Exposed patients were older and had more comorbidities. GC therapy was associated with an increased risk of fracture, with the effect size influenced by risk attribution model. The risk of fracture decreased with less recent exposure from HR (95% CI) 1.66 (1.27, 2.16) during the first month of stopping GCs to 1.11 (0.79, 1.57) for between 1 and 3 months. The risk of fracture increased with current daily dose, HR 1.44 (1.17, 1.77) for 5-9.9 mg prednisolone equivalent dose (PEQ) to 3.02 (1.77, 5.15) for 15-19.9 mg PEQ. Risk of fracture increased with cumulative dose, a function of dose and duration, from HR 1.22 (1.03, 1.44) for <1 g to 1.83 (1.35, 2.48) for 7.5-10 g. CONCLUSION: GC exposure was associated with excess fracture risk, with effect size differing according to definition of exposure. This highlights the need to incorporate all exposure dimensions (dose, duration and recency) in these patient's fracture risk assessments.
30390695 The involvement of C5a in the progression of experimental arthritis with Porphyromonas gin 2018 Nov 3 BACKGROUND: Epidemiological evidence to suggest that periodontal disease (PD) is involved in the progression of rheumatoid arthritis (RA) is increasing. The complement system plays a critical role in immune responses. C5a has been implicated in chronic inflammatory diseases, including PD and RA. Porphyromonas gingivalis is the major causative bacteria of PD and can produce C5a. Therefore, it is hypothesized that P. gingivalis infection is involved in the progression of RA by elevating C5a levels. In the present study, P. gingivalis-infected RA model mice were established to investigate the involvement of C5a. METHODS: SKG mice orally infected with P. gingivalis were immunized with intraperitoneal injection of laminarin (LA) to induce arthritis. Arthritis development was assessed by arthritis score (AS), bone destruction on the talus, histology, and serum markers of RA. In order to investigate the effects of serum C5a on bone destruction, osteoclast differentiation of bone marrow mononuclear cells was examined by using serum samples from each group of mice. The relationship between C5a levels and antibody titers to periodontal pathogens in patients with RA was investigated by enzyme-linked immunosorbent assay. RESULTS: P. gingivalis oral infection increased AS, infiltration of inflammatory cells, bone destruction on the talus, and serum markers of RA in mice immunized with LA. The addition of serum from LA-injected mice with the P. gingivalis oral infection promoted osteoclast differentiation, and the addition of a neutralization antibody against C5a suppressed osteoclast differentiation. C5a levels of serum in RA patients with positive P. gingivalis antibody were elevated compared with those in RA patients with negative P. gingivalis antibody. CONCLUSIONS: These results suggest that P. gingivalis infection enhances the progression of RA via C5a.
30061892 Streptococcal Endo-β-N-Acetylglucosaminidase Suppresses Antibody-Mediated Inflammation In 2018 Endo-β-N-acetylglucosaminidase (EndoS) is a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes. Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG. Here, we report that EndoS and IgG hydrolyzed by EndoS induced suppression of local immune complex (IC)-mediated arthritis. A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice. The presence of EndoS disturbed larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining. Neither complement binding in vitro nor antigen-antibody binding per se were affected. Thus, EndoS could potentially be used for treating patients with IC-mediated pathology.
30390267 Nutritional Considerations in Preventing Muscle Atrophy. 2018 Muscle atrophy may occur under different circumstances throughout a person's life. These conditions include periods of immobilization of a limb or of the whole body and aging accompanied by the onset of sarcopenia. Muscle mass is reduced as a result of decreased protein synthesis or increased protein degradation. Most studies aim to prevent the degradation of muscle proteins, but the way in which protein synthesis can be stimulated is often neglected. This study will provide an up-to-date review regarding nutritional considerations and resistance exercise countermeasures in the prevention of muscle mass loss and recovery of muscle mass in muscle atrophy secondary to immobilization or in sarcopenic obesity. We do not address muscle atrophy in disease states associated with inflammation (rheumatoid arthritis, COPD, cancer cachexia, AIDS, burns, sepsis, and uremia) which are governed by particular mechanisms of muscle loss.
30315072 Risk factors of hippocampal sclerosis in the oldest old: The 90+ Study. 2018 Nov 6 OBJECTIVE: To examine the risk factors and comorbidities of hippocampal sclerosis (HS) in the oldest-old. METHODS: A total of 134 participants with dementia from The 90+ Study with longitudinal evaluations and autopsy were included in this investigation. Participants were divided into 2 groups, one with and one without HS pathology, and differences in clinical and pathologic characteristics were compared. RESULTS: Persons with HS tended to have a longer duration of dementia compared to participants without HS (mean 4.0 years vs 6.7 years, odds ratio [OR] 1.26; 95% confidence interval [CI] 1.11-1.42; p < 0.001). HS was more likely in participants with a history of autoimmune diseases (rheumatoid arthritis or thyroid disease, OR 3.15; 95% CI 1.30-7.62; p = 0.011), high thyroid-stimulating hormone (OR 4.94; 95% CI 1.40-17.46; p = 0.013), or high thyroid antibodies (OR 3.45; 95% CI 1.09-10.88; p = 0.035). Lewy body disease (LBD) pathology was also associated with an increased likelihood of HS (OR 5.70; 95% CI 1.22-26.4; p = 0.027). CONCLUSION: We identified autoimmune conditions (rheumatoid arthritis and thyroid disease) as potential risk factors for HS in our cohort. LBD was the only pathology that was associated with increased odds of HS and those harboring HS pathology had a longer duration of dementia. This suggests multiple pathways of HS pathology among the oldest-old.
29935983 In vivo exposure to hydroquinone during the early phase of collagen-induced arthritis aggr 2018 Sep 1 Robust correlation between the severity of rheumatoid arthritis (RA) and cigarette smoking has been clinically demonstrated. Nevertheless, cigarette compounds responsible for this toxic effect and their mechanisms have not been described. Considering that hydroquinone (HQ) is an abundant, pro-oxidative compound of the matter particle phase of cigarette smoke, we investigated whether HQ exposure during the initial phase of collagen-induced arthritis (CIA) could aggravate the disease. For this purpose, male Wistar rats were exposed to aerosolized HQ (25 ppm), saline or 5% ethanol solution (HQ vehicle) for 1 h per day during 14 days. CIA was induced through s.c. injection of bovine collagen Type II (0.4 mg/100 μL) at days seven and 14 of exposure. Clinical signs of disease and the cell profile and chemical mediators in the synovial fluid and membrane were analysed at day 35 after the beginning of exposure. HQ exposure aggravated CIA-related paw edema and increased the cell infiltrate and interleukin-6 (IL-6) levels in the synovial fluid, promoted intense tissue collagen deposition and enhanced synoviocyte proliferation and higher frequency of aryl hydrocarbon receptor (AhR(+)) and interleukin (IL-17(+)) neutrophils in the synovial membrane. in vitro data also highlighted that neutrophils expressed increased levels of AhR, IL-17 and reactive oxygen species (ROS) generation. However, only AhR expression and ROS generation were blocked by in vitro treatment with AhR antagonist. Therefore, we conclude that in vivo HQ exposure at the early phase of AR onset worsens RA, leading to high frequency of AhR/IL-17(+) neutrophils into the joint.
30518996 Analysis of drug utilization and health care resource consumption in patients with psorias 2018 OBJECTIVES: To describe the therapeutic pathways of patients with psoriasis (PSO) and psoriatic arthritis (PsA) before and after treatment with biological therapies in a real-world setting and to determine the relative consumption of health care resources. DESIGN: Retrospective observational study. SETTING: Real-life clinical setting in 5 Italian local health units. PARTICIPANTS: A total of 351 male and female patients with at least 1 prescription for a biological drug from January 1, 2010 to December 31, 2013; patients with concomitant rheumatoid arthritis, ankylosing spondylitis, or Crohn's disease were excluded. RESULTS: The major health care cost (excluding drug costs) was represented by hospitalizations, mainly related to PSO /PsA-associated disorders and cardiometabolic disorders. Use of conventional drugs among biologics-naïve patients reached 50% in PSO and 80% in PsA; their use decreased following initiation of biological therapy. After the start of biological treatment, the incidence of hospitalization decreased both for PSO (from 12.3% to 3.2% in day hospital regimen and from 2.4% to 0.4% for conventional admission) and for PsA (from 11.1% to 8.1% and from 10.1% to 3.0%, respectively). Mean annual costs for hospitalization before biological treatment were €217 and €537 for PSO and PsA, respectively, while mean annual cost for concomitant drugs slightly increased after biologics initiation: from €249.8 to €269.4 for PSO and from €331.8 to €346.9 for PsA. The major consumption of health care resources occurred in the quarter preceding the beginning of biological treatment. CONCLUSION: The consumption of health resources is mostly related to hospitalization, seems to peak during the quarter before the beginning of biologics therapies, and subsequently decreases after biologics initiation. Further studies should focus on prescription scheme and economic burden of PSO and PsA in Italy to help optimize health care resources and potentiate services for patients.
30046349 Anti-Inflammatory, Antioxidative, and Hepatoprotective Effects of Trans Δ9-Tetrahydrocann 2018 Rheumatoid arthritis (RA) is a painful chronic autoimmune disease affecting the joints. Its first-line therapy, Methotrexate (MTX), although effective in ameliorating the progress of the disease, induces hepatotoxicity over long-term usage. Thus, seeking natural compounds with fewer side effects could be an alternative therapeutic approach. This study aimed to investigate the anti-inflammatory, antiarthritic, and antioxidative effects of synthetic trans-Δ9-tetrahydrocannabinol (Δ9-THC) dissolved in sesame oil (Dronabinol) against MTX in adjuvant-induced arthritis (AIA) rat model. Daily oral administration of Δ9-THC/sesame oil, over a period of 21 days, was well tolerated in arthritic rats with no particular psychoactive side effects. It markedly attenuated the severity of clinical manifestations, recovered the histopathological changes in tibiotarsal joints, and repressed the splenomegaly in arthritic rats. Δ9-THC/sesame oil therapy showed similar effects to MTX in neutralizing the inflammatory process of AIA, through attenuating erythrocyte sedimentation rate (ESR) scores and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and interleukin-6 (IL-6) levels, to normal values. As opposed to MTX, this natural combination markedly protected the liver of arthritic rats and downregulated the induced oxidative stress by increasing the antioxidant defense system such as activities of catalase and superoxide dismutase (SOD) and levels of glutathione (GSH). These results suggest promising effects for the clinical use of Δ9-THC/sesame oil therapy in alleviating arthritic clinical signs as well as arthritis-induced liver injury.
30202131 Spectrum of central nervous system involvement in rheumatic diseases: pictorial essay. 2018 Jul The rheumatic diseases, which include systemic lupus erythematosus, rheumatoid arthritis, Behçet's disease, scleroderma, and ankylosing spondylitis, are characterized by involvement of connective tissue, with multiple manifestations. In those diseases, there can be involvement of the peripheral or central nervous system, and that involvement can be primary, presenting as a major feature of the clinical presentation, or secondary, as an effect of the drugs used in order to control a given disease or its complications. Knowledge of the wide variety of imaging findings is crucial to the diagnosis of a rheumatic disease, especially in the early stages, enabling effective treatment and minimizing disability. This pictorial essay, presenting cases from the records of two tertiary teaching hospitals, encompasses cases of patients diagnosed with rheumatic disease and illustrates the neuroradiological findings on magnetic resonance imaging and computed tomography, in order to emphasize the importance of these methods for properly diagnosing rheumatic diseases.