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ID PMID Title PublicationDate abstract
24889264 A systematic review of observational studies evaluating implant placement in the maxillary 2015 Jun BACKGROUND: Even though the efficacy of implant treatment and the excellent success rates that modern implant surfaces yield remain unchallenged, there is limited information available on implant success rates in medically compromised patients. PURPOSE: The aim of this systematic review was to evaluate the survival of implants placed in the maxillary jaws of medically compromised patients. MATERIALS AND METHODS: Two reviewers using predefined selection criteria performed an electronic search complemented by a manual search, independently and in duplicate. RESULTS: After the final selection, 11 studies reporting on four distinct medical conditions were included out of 405 potentially eligible titles. In detail, three studies reported on implants placed in diabetic patients, six on implants placed in patients with a history of oral cancer, one on implants in patients with a history of epilepsy, and one on implants in patients with autoimmune rheumatoid arthritis. CONCLUSIONS: Placement of maxillary implants in medically compromised patients seems to yield acceptable survival rates. Implant survival in well-controlled diabetic patients, patients diagnosed with rheumatoid arthritis, and patients treated for severe epilepsy is comparable to that in healthy patients. Implants placed in the maxillae of patients treated for oral cancer may attain osseointegration less predictably than in the mandible.
25414238 Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis. 2016 Feb OBJECTIVE: Arthritis is a chronic inflammatory disease characterised by immune cell infiltration and mesenchymal cell expansion in the joints. Although the role of immune cells in arthritis is well characterised, the development of mesenchymal cell hyperplasia needs to be better defined. Here, we analysed the role of the ribosomal S6 kinase Rsk2, which we found to be highly activated in joints of patients with arthritis, in the development of mesenchymal cell hyperplasia. METHODS: We genetically inactivated Rsk2 in the tumour necrosis factor (TNF)-α transgenic (TNFtg) mice, an animal model for human inflammatory arthritis. Clinical and histological signs of arthritis as well as molecular markers of inflammation and joint destruction were quantified. Fibroblast-like synoviocytes (FLS) were characterised in vitro and the effect of Rsk2 deletion on the pattern of gene expression was determined. RESULTS: Rsk2 deficiency in TNFtg mice results in earlier and exacerbated inflammation as well as increased bone and cartilage destruction. The production of inflammatory cytokines, matrix metalloproteinases and osteoclastogenic molecules was significantly increased in vivo upon Rsk2 inactivation. Bone marrow deficient in Rsk2 could not transfer this phenotype, indicating that Rsk2 expression in mesenchymal cells controls the course of arthritis. Indeed, Rsk2 deficiency was associated with a more activated phenotype and higher proliferative capacity of FLS, thereby increasing cytokines and production of matrix proteinases. CONCLUSIONS: Rsk2 emerges as a key regulator of mesenchymal cell numbers in the joint and thereby could be targeted to control the inflammatory and tissue-destructive feature of joints in arthritis.
25022614 Outcome After Operative Fusion of the Tarsal Joints: A Systematic Review. 2015 Jul Arthrodesis of 1 or more joints of the hindfoot is performed to treat severe functional impairment due to pain, deformity, and/or instability. Evaluation of the results of hindfoot arthrodesis from the published data has been difficult owing to the great variety of pathologic entities and surgical techniques reported in the studies. A comprehensive search for relevant reports, reference lists, and citation tracking of the included studies was conducted using the PubMed(®), Embase(®), and CINAHL(®) databases. The studies had to have been prospective, included patients with hindfoot problems, evaluated arthrodesis of 1 or more tarsal joints, and had at least 1 of the following primary clinical outcome parameters: pain, function, or complications. Two of us independently selected the relevant studies using predefined criteria and graded the quality of evidence using a 0 to 9 star scale according to the Newcastle-Ottawa Scale. A total of 16 prospective case series were included; 5 studies scored 6 stars, 8 scored 5 stars, 2 scored 4 stars, and 1 scored 3 stars. A best evidence synthesis was performed, and improvement in function and pain was found for 3 combinations: talonavicular arthrodesis for rheumatoid arthritis, triple arthrodesis for rheumatoid arthritis, and subtalar arthrodesis for post-traumatic arthritis showed good results for pain and function, the last especially when performed arthroscopically. The best evidence syntheses revealed good results for pain and function for these disease-operative technique combinations.
25895652 Psoriatic arthritis under a proteomic spotlight: application of novel technologies to adva 2015 May Psoriatic arthritis is a form of inflammatory arthritis that is frequently associated with psoriasis. Individuals with this disease present with heterogeneous clinical manifestations, making it challenging to diagnose and select optimal treatment strategies. Perhaps, not unsurprisingly, there are currently no molecular diagnostic or prognostic tests to confirm if a patient has the disease or predict how they may respond to therapy. Instead, a range of classification criteria have been developed, and the experience of the treating clinician is heavily relied upon. It is therefore widely accepted that there is a significant and as yet unmet need for effective molecular markers in psoriatic arthritis. Protein mediators drive disease pathogenesis and, therefore, represent logical potential biomarkers. Indeed, significant advances have recently been made by the introduction of multiplexed protein biomarker tests for monitoring disease activity in rheumatoid arthritis. At the same time, recent advances in proteomics have enhanced the capabilities for the detection and discovery of protein biomarkers. These advances offer renewed opportunities for the development of multi-protein biomarker signatures to support clinical decision-making in the diagnosis, prognosis and treatment of psoriatic arthritis. This review summarises the pathogenesis of psoriatic arthritis, highlighting specific areas of unmet clinical need. Furthermore, it seeks to illustrate how the latest developments in proteomic technologies could be used to enhance our understanding of the molecular pathology of psoriatic arthritis and improve clinical outcomes and quality of life for patients.
28013554 The emerging roles of B cells as partners and targets in periodontitis. 2017 Feb Initial studies of periodontal disease suggested that T cell-mediated immunity against oral Gram-negative microorganisms is a key player in the pathogenesis of this inflammatory disease. Recent investigations, however, revealed that B cells are also engaged. Given their chief role in innate-like and adaptive immune responses, B cells could exert protective functions in periodontitis. However, the periodontal bacteria-specific antibody response is generally unable to halt disease progression in affected subjects, suggesting that the antibodies produced could exhibit low anti-bacterial blocking functions or opsonophagocytic potential, and/or unfavorable effects. Moreover, although microbial antigens are involved in the induction of the inflammatory responses in human adult periodontitis, endogenous antigens also may contribute to the chronicity of this common disease. Not only antibodies to self-antigens, such as collagen, are locally produced, but the autoreactivities observed in aggressive periodontitis are more severe and diverse than those observed in chronic periodontitis, suggesting that autoimmune reactivity could play a role in the tissue destruction of periodontal disease. Further support for a pathological role of B cells in periodontitis comes from the finding that B cell-deficient mice are protected from bacterial infection-induced alveolar bone loss. Studies in patients indicate that B cells and plasma cells, together with osteoclastogenic factors (RANKL and osteoprotegerin) and specific cytokines involved in their growth and differentiation (BAFF and APRIL) participate in the induction of the pathological bone loss in periodontitis. This novel insight suggests that selective targeting of B cells could represent a future therapeutic avenue for severe periodontal disease.
26225264 Semiphysiologically Based Pharmacokinetic Model of Leflunomide Disposition in Rheumatoid A 2015 Jun A semiphysiologically based pharmacokinetic (semi-PBPK) population model was used to evaluate the influence of enterohepatic recycling and protein binding, as well as the effect of genetic variability in CYP1A2, CYP2C19, and ABCG2, on the large interindividual variability of teriflunomide (active metabolite) concentrations following leflunomide administration in rheumatoid arthritis (RA) patients. The model was developed with total and free teriflunomide concentrations determined in RA patients taking leflunomide, as well as mean teriflunomide concentrations following the administration of leflunomide or teriflunomide extracted from the literature. Once developed, the 15-compartment model was able to predict total and free teriflunomide concentrations and was used to screen demographic and genotypic covariates, of which only fat-free mass and liver function (ALT) improved prediction. This approach effectively evaluated the effects of multiple covariates on both total and free teriflunomide concentrations, which have only been explored previously through simplistic one-compartment models for total teriflunomide.
26962595 2015 Jul Rheumatoid arthritis (RA) is a chronic, inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. Disease prevalence in Canada is about 1% (0.9% in 2010), and it is expected to increase to 1.3% by 2040. Treatment guidelines for RA emphasize the use of non-drug interventions, which include exercise therapy, electro-physical modalities, orthoses and assistive devices, and self-management interventions (including education), in addition to pharmacological therapy. Non-pharmacological care affords symptomatic relief without altering the course of disease progression. The pharmacological therapy of RA aims to achieve remission and, if that is not possible, to minimize disease activity while controlling symptoms, halting joint damage, preventing disability, and improving quality of life. Traditional synthetic, disease-modifying antirheumatic drugs (DMARDs) have been shown to alter the clinical course of RA and slow or halt radiographic progression when used early and aggressively in the treatment of RA. Methotrexate is the preferred DMARD with respect to efficacy and safety, and is recommended as the first-line DMARD treatment in patients with RA unless contraindicated or not tolerated. Nonsteroidal anti-inflammatory drugs (NSAIDs) and/or glucocorticoids (in the lowest effective dose possible) can be added to the initial treatment with DMARD as a bridge therapy while waiting for DMARD to take effect, to manage flares, or for symptom control if no other options exist. It is recommended that patients with an inadequate response to the target dose of at least two DMARDs in mono- or combination therapy after three months be considered for biologic therapies, including currently available subcutaneous (SC) golimumab that targets specific mechanisms of inflammation. The objective of this report is to evaluate the beneficial and harmful effects of IV golimumab (Simponi IV) at recommended doses in combination with methotrexate for the treatment of adult patients with moderately to severely active RA.
25836921 Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and 2015 May Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways.
26693225 Sexual Dimorphisms of Adrenal Steroids, Sex Hormones, and Immunological Biomarkers and Pos 2015 Innate immunity and immunological biomarkers are believed to be interrelated with sex hormones and other neuroendocrine factors. Sexual dimorphism mechanisms may be operating in certain rheumatic and inflammatory diseases which occur more frequently in women than men, as rheumatoid arthritis (RA). Less data have been available on altered interrelations of the combined neuroendocrine and immune (NEI) systems as risk factors for development of certain diseases. In this study, serological interrelations of NEI biomarkers are analyzed before symptomatic onset of RA (pre-RA) versus control (CN) subjects, stratified by sex. Sexual dimorphism was found in serum levels of acute serum amyloid A (ASAA), soluble interleukin-2 receptor alpha (sIL-2Rα), and soluble tumor necrosis factor receptor 1 (sTNF-R1). Multiple steroidal and hormonal (neuroendocrine) factors also showed highly (p < 0.001) significant sexual dimorphism in their assayed values, but less for cortisol (p = 0.012), and not for 17-hydroxyprogesterone (p = 0.176). After stratification by sex and risk of developing RA, differential NEI correlational patterns were observed in the interplay of the NEI systems between the pre-RA and CN groups, which deserve further investigation.
26458405 In Vitro Inhibition Of Three Different Drugs Used In Rheumatoid Arthritis Treatment On Hum 2016 We studied in vitro effects of three different drugs (ibuprofen, meloxicam and methotrexate) which are often used in rheumatoid arthritis (RA) treatment on human serum paraoxanase1 (PON1) enzyme activity. The drugs used in RA treatment decreased the in vitro PON1 activity. The inhibition mechanism of ibuprofen and methotrexate were noncompetitive whereas meloxicam was a competitive inhibitor. The IC50 values for ibuprofen, meloxicam and methotrexate were calculated to be 0.35 mM, 0.10 mM, and 0.18 mM, respectively, and the Ki constants were calculated to be 0.890 mM, 0.125 mM, and 0.260 mM, respectively. The IC50 and Ki values showed the maximum inhibition of meloxicam drugs. We propose a prediction scheme for the interaction of meloxicam with the PON1 active site because we thought that meloxicam interacts with the amino acids which are in the PON1 enzyme active site. The results we found showed that these drugs which are often used in RA treatment in vitro inhibit the activity of the enzyme with different inhibition mechanisms at low doses.
26403928 Design, synthesis, and biological evaluation of aminopyrazine derivatives as inhibitors of 2015 Nov 15 Several series of novel non-thiourea-containing aminopyrazine derivatives were designed based on the MK-2 inhibitors 1-(2-aminopyrazin-3-yl)methyl-2-thioureas. These compounds were synthesized and evaluated for their inhibitory activity against MK-2 enzyme in vitro. Compounds with low micromolar to sub-micromolar IC50 values were identified, and several compounds were also found to be active in suppressing the lipopolysaccharide (LPS)-stimulated TNFα production in THP-1 cells with minimum shift compared to their enzyme activity.
27590039 The toxicity of methotrexate in male fertility and paternal teratogenicity. 2017 Jan There is a high prevalence of methotrexate (MTX) use in males of reproductive age. The scope of this paper reviews what is known regarding risks to fertility and partners' pregnancy outcomes with regard to MTX use in men. Areas covered: This paper reviews the evidence for current recommendations for MTX use and male fertility and aims to educate professionals regarding MTX use in reproducing males so that patients may be counseled appropriately. A literature search included peer-reviewed sources from PubMed searches and the literature referenced within. Expert opinion: There is a lack of evidence regarding effects of MTX on male fertility. The recommendation to stop MTX three months prior to conception is safe, but is not evidenced by an understanding of the impact of MTX on spermatogenesis or paternal-mediated teratogenicity but rather the timeframe of spermatogenesis. Given the unclear evidence, patients treated with MTX must be counseled on the likelihood of adverse effects of MTX and role of sperm cryopreservation. Future studies are needed to help elucidate the unclear evidence of MTX effects on male fertility and pregnancy outcomes.
26490479 Synthetic Peptide-Based ELISA and ELISpot Assay for Identifying Autoantibody Epitopes. 2016 Enzyme-linked immunosorbent assay (ELISA) is an invaluable diagnostic tool to detect serum autoantibody binding to target antigen. To map the autoantigenic epitope(s), overlapping synthetic peptides covering the total sequence of a protein antigen are used. A large set of peptides synthesized on the crown of pins can be tested by Multipin ELISA for fast screening. Next, to validate the results, the candidate epitope peptides are resynthesized by solid-phase synthesis, coupled to ELISA plate directly, or in a biotinylated form, bound to neutravidin-coated surface and the binding of autoantibodies from patients' sera is tested by indirect ELISA. Further, selected epitope peptides can be applied in enzyme-linked immunospot assay to distinguish individual, citrullinated peptide-specific autoreactive B cells in a pre-stimulated culture of patients' lymphocytes.
26303149 Reduction in orthopaedic surgery in patients with rheumatoid arthritis: a Norwegian regist 2016 Jan OBJECTIVES: The disease course of patients with rheumatoid arthritis (RA) has become milder in recent years. In this study we investigated the incidence of orthopaedic surgery in patients with RA. METHOD: From the Norwegian Arthroplasty Register we selected joint replacement procedures conducted during the years 1994-2012 (n = 11 337), and from the Norwegian Patient Register we obtained data on synovectomies (n = 4782) and arthrodeses (n = 6022) during 1997-2012. Using Poisson regression we analysed the time trends in the incidence of procedures performed. RESULTS: There was a significant decrease in the incidence of arthroplasty surgery (coefficient of -0.050 per year) and synovectomies (coefficient of -0.10) and a declining trend of arthrodeses in patients with RA in the study periods. The greatest reduction was found in procedures involving the wrist and hand. CONCLUSIONS: We found a decrease in orthopaedic surgery in patients with RA that continued into the biologic era and throughout the study period. The general increasing trend in the use of synthetic and biological disease-modifying anti-rheumatic drugs (DMARDs) thus coincides with less joint destruction and an improved long-term prognosis of patients with RA.
24842475 Effects of anti-IL-6 receptor antibody on human monocytes. 2015 Jan OBJECTIVE: To explore the effects of anti-IL-6 receptor antibody, tocilizumab on function of human monocytes. METHODS: Monocytes from healthy donors were cultured in the presence of staphylococcal enterotoxin B (SEB) with pharmacologically attainable concentrations of tocilizumab or control IgG. The expression of IL-6 mRNA was determined using quantitative RT-PCR. The expression of CD80 and CD86 and the induction of apoptosis of monocytes were measured using flow cytometry. RESULTS: Tocilizumab promoted apoptosis of SEB-stimulated monocytes. The induction of apoptosis of monocytes by tocilizumab were reversed by addition of IgG, but not IgG F(ab')â‚‚ fragments. Tocilizumab significantly suppressed the expression of CD80, but not that of CD86, on SEB- stimulated monocytes. Finally, tocilizumab significantly suppressed the expression of mRNA for IL-6 of monocytes stimulated with SEB. CONCLUSIONS: These results demonstrate that one of the mechanism of action of tocilizumab involves the induction of apoptosis of monocytes, which requires interaction with Fc receptor on monocytes. Moreover, the data also indicate that tocilizumab inhibit IL-6 production of monocytes at mRNA levels.
27623319 Review of the bioanalytical methods for the determination of methotrexate and its metaboli 2017 Jan Methotrexate is an old drug that has found use in several therapeutic areas, such as cancer to treat various malignancies, rheumatoid arthtritis and inflammatory bowel disease. Owing to its structural properties of possessing two carboxylic acid groups and having low native fluorescence, it has provided technical challenges for development of bioanalytical methods. Also, in vivo metabolism leading to circulatory metabolites such as 7-hydroxymethotrexate and 2,4-diamino N(10) -methylpteroic acid, as well as the formation of polyglutamate metabolites intracellularly have added further complexity for the assays in terms of the analytes that need to be quantified in addition to methotrexate. The present review is aimed at providing a concise tabular summary of chromatographic assays with respect to method nuances including assay/chromatographic conditions, key validation parameters and applicable remarks. Several case studies are reviewed under various subheadings to provide the challenges involved in the method development for methotrexate and metabolites. Finally, a discussion section is devoted to overall perspectives obtained from this review.
27975029 Barriers to Reconstructive Hand Surgery for Rheumatoid Arthritis in China: A Multicenter S 2016 Nov BACKGROUND: China has a similar rheumatoid arthritis (RA) disease burden compared with other countries, yet RA patients rarely receive surgical treatment for hand deformities that limit function and impact appearance. We investigated potential barriers to rheumatoid hand surgery in China. METHODS: Patients with RA, rheumatologists, and hand surgeons at 3 large tertiary hospitals in Beijing completed questionnaires that assess knowledge and attitudes surrounding RA hand surgery. We calculated descriptive statistics and compared responses among groups using chi-square and Fisher exact tests as appropriate. RESULTS: One hundred RA patients with hand deformities and 94 physicians completed the surveys. No patients had received hand surgery, and just 13% were aware of this treatment option. Patients and physicians most frequently cited uncertain effectiveness of surgery, high cost, and risk of surgical complications as potential barriers to hand reconstruction. Rheumatologists reported low rates of referral to hand surgeons (39% referred <5% of the time and 31% never referred). Most hand surgeons (69%) had not performed metacarpophalangeal arthroplasty, a common procedure for RA hand deformities, within the past year. Some had never performed this operation. CONCLUSIONS: This survey revealed multiple barriers that support previous observations of infrequent reconstruction of RA hand deformities in China. These obstacles can be addressed through patient education, coordination between specialists, and more robust hand surgeon training in common RA procedures through the application of international plastic surgery collaborations.
27891058 IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity. 2016 Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is expressed in antigen-presenting cells, including B cells and dendritic cells, but affects inflammatory responses in the autoimmune context specifically by acting in B cells to modulate T cell help in multiple model systems. Given that expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2 should be considered a potential therapeutic target for autoimmune disorders.
25333886 Growing up with juvenile idiopathic arthritis. 2015 Jan Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric illness in the United States. The disease encompasses a group of heterogeneous chronic arthritis conditions that begin before age 16 years and persist for more than 6 weeks. Formerly termed juvenile rheumatoid arthritis (JRA), JIA now includes polyarticular, oligoarticular, psoriatic, enthesitis-related arthritis, systematic arthritis, and undifferentiated arthritis. Diagnosis is based on clinical and laboratory features. Treatment includes immunosuppressant therapy, non-steroidal anti-inflammatory drug (NSAIDS), and biologic therapies. This can affect all aspects of an adolescent's life including physiologic, psychosocial, and spiritual components; therefore, this article discusses a comprehensive approach to care management with transition of care as a critical feature in adolescent healthcare.
27009079 Analysis of Total Ankle Arthroplasty Survival in the United States Using Multiple State Da 2016 Aug The aim of this study was to evaluate survivorship and risk factors for failure of total ankle arthroplasty (TAA) in the United States using large statewide, multipayer databases of inpatient discharges. TAA patients from 2005 to 2009 were identified from the Healthcare Cost and Utilization Project databases for 5 states (California, Florida, Nebraska, North Carolina, and Utah) and the New York Department of Health Statewide Planning and Research Cooperative System database. Patient demographics and clinical characteristics were extracted, and a multivariable logistic regression model was developed to assess risk factors for 90-day all-cause readmission and failure. Failure was defined as revision, arthrodesis, amputation, or implant removal. During the period of interest, 1545 patients received 1593 TAA. The coded etiology of arthritis was primary osteoarthritis (n = 854, 55.2%), posttraumatic arthritis (n = 466, 30.2%), rheumatoid arthritis (n = 129, 8.4%), and other (n = 96, 6.2%). The 5-year survival rate was 90.1%. Patients with a coded diagnosis of rheumatoid arthritis (odds ratio [OR] = 2.18; 95% confidence interval [CI] = 1.04-4.01) or who were readmitted within 90 days of TAA (OR = 3.41; 95% CI = 1.67-6.97) had significantly increased risk of failure. Risk factors for readmission were Charlson-Deyo Score ≥2 (OR = 3.05; 95% CI = 1.51-6.15) and increased length of stay during the arthroplasty (OR = 1.30; 95% CI = 1.16-1.47). LEVELS OF EVIDENCE: Therapeutic, Level IV: Observational study.