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ID PMID Title PublicationDate abstract
29148411 Vitamin D status in spondyloarthritis: results of the ASAS-COMOSPA international study. 2018 Mar OBJECTIVES: Spondyloarthritis (SpA) encompasses both bone production and bone loss, and the latter is particularly linked to inflammation. Vitamin D deficiency has been associated with several inflammatory conditions (i.e. cardiovascular disease, rheumatoid arthritis), but it has been poorly evaluated in SpA patients. We aimed to a) describe the prevalence of vitamin D deficiency in SpA patients worldwide; b) compare SpA patients with and without vitamin D deficiency in terms of disease phenotype, activity severity and comorbidities. METHODS: This is an ancillary study of the ASAS-COMOSPA study initiative, an international cross-sectional study of patients with SpA. Demographics, patients' phenotype, disease activity/severity measures and comorbidities were assessed. Serum 25-hydroxyvitamin D (25OHD) deficiency was defined as <20 ng/mL (<50 nmol/L). STATISTICAL ANALYSIS: a) prevalence of vitamin D deficiency; b) comparison of the disease presentation/activity/severity and comorbidities in the group of patients with and without vitamin D deficiency by bi-variable and multivariable analysis. RESULTS: Vitamin D deficiency was observed in 527(51.2%) of the 1030 patients with available data who were not receiving any supplementation. Vitamin D deficiency was independently associated with the presence of radiographic sacroiliitis (OR=2.1 [95%CI1.3; 3.3]) and a 25OHD measured in winter and spring (OR=1.88 [95%CI 1.2; 2.9]). No independent association between vitamin D deficiency and comorbidities was found. CONCLUSIONS: This study suggests that vitamin D deficiency is common in SpA worldwide and is associated with season but also with more severe forms of SpA.
28555160 Boi-ogi-to (TJ-20), a Kampo Formula, Suppresses the Inflammatory Bone Destruction and the 2017 TJ-20 is a formula consisting of 6 herbs that has been used in the clinical treatment of rheumatoid arthritis (RA) in China and Japan for centuries. However, scientific evidence of the effects of TJ-20 has not been established. In the present study, we focused on the therapeutic effects and investigated the main function of TJ-20 on adjuvant arthritis (AA), an animal model of RA, which was induced with complete Freund's adjuvant (CFA). TJ-20 was administered orally at 600 mg/kg once a day from 0, 7, and 10 days to 8 weeks after the CFA treatment. TJ-20 significantly ameliorated inflammatory progression and bone destruction in AA in a time-dependent manner. Furthermore, TJ-20 significantly reduced the increased changes in a number of macrophages and helper T cells. Moreover, TJ-20 suppressed the expression of TNF-α whereas it augmented the expression of IL-10 and attenuated Th1 cells responses in the synovia of the ankle joint. Therefore, TJ-20 regulated the expression of proinflammatory and anti-inflammatory cytokines in macrophages and Th1/Th2 balance in the synovia of ankle joints in AA rats. These results suggest the positive anti-inflammatory effect of TJ-20 and provide a scientific basis for the clinical use of TJ-20 for RA.
29257800 A Case of Osteonecrosis of the Jaw in a Patient with Crohn's Disease Treated with Inflixim 2017 Dec 19 Patient: Female, 49 Final Diagnosis: Medication related osteonecrosis of the jaw Symptoms: Painful bone exposure • pus discharge Medication: Infliximab Clinical Procedure: Surgical removal of necrotic bone Specialty: Surgery OBJECTIVE: Unusual clinical course BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse drug reaction, occurring in patients undergoing treatments with antiresorptive or antiangiogenic agents, such as bisphosphonates, denosumab, or bevacizumab, for different oncologic and non-oncologic diseases. The aim of this study was to report a case of MRONJ in a patient taking infliximab, an anti-TNF-α antibody used to treat Crohn’s disease, rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. CASE REPORT: A 49-year-old female patient affected by Crohn’s disease, who had been undergoing 250 mg intravenous infliximab every six weeks for 12 years, with no history of antiresorptive or antiangiogenic agent administration, came to our attention for post-surgical MRONJ, associated with a wide cutaneous necrotic area of her anterior mandible. Following antibiotic cycles, the patient underwent surgical treatment with wide bone resection and debridement of necrotic tissues; after prolonged follow-up (16 months), the patient completely healed without signs of recurrence. CONCLUSIONS: Prevention of MRONJ by dental check-up before and during treatments with antiresorptive treatments (bisphosphonates or denosumab) is a well-established procedure. Although further studies are required to confirm the role of infliximab in MRONJ, based on the results of this study, we propose that patients who are going to be treated with infliximab should also undergo dental check-up before starting therapy, to possibly avoid MRONJ onset.
28168545 Prevalence of musculoskeletal disorders in Azar cohort population in Northwest of Iran. 2017 Apr Musculoskeletal disorders (MSDs) are considered as major public health problems. The purpose of this study was to determine the prevalence of MSDs in Azar cohort population in northwest of Iran. Azar cohort study is a state level of a national cohort project (PERSIAN) which began in 2014. All adults over 35 years old in Khamene city in East Azarbaijan province were recruited for the pilot phase of the Azar cohort. For the purpose of the current study, a total of 952 subjects age range of 35-70 who completed the Community Oriented Program for the Control of Rheumatic Disease (COPCORD) questionnaire as supplementary were included. 299 subjects had MSDs and were introduced to the rheumatologist, only 237 of them referred for further assessment. 33.4% of subjects had MSDs within the past 7 days. The most frequent complaint was pain and the most common sites of complaints were knee, lumbar spine, and shoulder, respectively. Osteoarthritis was the most common rheumatic disease (53.2%) and the knee was the most common region affected (47.7%) followed by low back pain (28.2%). Osteoarthritis and knee osteoarthritis were present in 56.1 and 51.8% of females and 46.6 and 38.4% of males, respectively. Furthermore, low back pain was present in 32.9% of males and 26.2% of females. Peri-arthritis was more prevalent in males (12.3%), whilst fibromyalgia, psychologic pain, and heel spur were prevalent among females (9.1, 5.1, and 1.2%, respectively). Rheumatoid arthritis was observed in 1.4% of males and 1.8% of females, respectively. Prevalence of MSDs is very high in this area. Therefore, it calls for action by heath officials and professionals to plan for appropriate programs of prevention and management of MSDs in society.
28752178 Inhibitory effect of JAK inhibitor on mechanical stress-induced protease expression by hum 2017 Nov OBJECTIVE: To investigate whether janus kinase (JAK) inhibitor exhibits a chondro-protective effect against mechanical stress-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinase (MMPs) in human chondrocytes. MATERIALS AND METHODS: Normal human articular chondrocytes were seeded onto stretch chambers and incubated with or without tofacitinib (1000 nM) for 12 h before mechanical stimulation or cytokine stimulation. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation, 30 min) was applied and the gene expression levels of type II collagen α1 chain (COL2A1), aggrecan (ACAN), ADAMTS4, ADAMTS5, MMP13, and runt-related transcription factor 2 (RUNX-2) were examined by real-time polymerase chain reaction. Nuclear translocation of RUNX-2 and nuclear factor-κB (NF-κB) was examined by immunocytochemistry, and phosphorylation of mitogen-activated protein kinase (MAPK) and signaling transducer and activator of transcription (STAT) 3 was examined by western blotting. The concentration of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the supernatant was examined by enzyme-linked immunosorbent assay. RESULTS: COL2A1 and ACAN gene expression levels were decreased by CTS, but these catabolic effects were canceled by tofacitinib. Tofacitinib significantly down-regulated CTS-induced expression of ADAMTS4, ADAMTS5, MMP13, and RUNX2, and the release of IL-6 in supernatant by chondrocytes. Tofacitinib also reduced CTS-induced nuclear translocation of RUNX-2 and NF-κB, and phosphorylation of MAPK and STAT3. CONCLUSION: Tofacitinib suppressed mechanical stress-induced expression of ADAMTS4, ADAMTS5, and MMP13 by human chondrocytes through inhibition of the JAK/STAT and MAPK cascades.
29287995 Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor E 2018 Jan 16 Interleukin-23 (IL-23), an IL-12 family cytokine, plays pivotal roles in pro-inflammatory T helper 17 cell responses linked to autoimmune and inflammatory diseases. Despite intense therapeutic targeting, structural and mechanistic insights into receptor complexes mediated by IL-23, and by IL-12 family members in general, have remained elusive. We determined a crystal structure of human IL-23 in complex with its cognate receptor, IL-23R, and revealed that IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. The structural and functional hotspot of this interaction partially restructured the helical IL-23p19 subunit of IL-23 and restrained its IL-12p40 subunit to cooperatively bind the shared receptor IL-12Rβ1 with high affinity. Together with structural insights from the interaction of IL-23 with the inhibitory antibody briakinumab and by leveraging additional IL-23:antibody complexes, we propose a mechanistic paradigm for IL-23 and IL-12 whereby cognate receptor binding to the helical cytokine subunits primes recruitment of the shared receptors via the IL-12p40 subunit.
28551723 National variation in the composition of rheumatology multidisciplinary teams: a cross-sec 2017 Sep The objective of this study is to describe the composition of multidisciplinary teams (MDT) working within rheumatology departments across the UK. All rheumatology departments in the United Kingdom (UK) were invited to participate in a national electronic survey between February 2014 and April 2015 as a part of a national audit for the management of rheumatoid and early inflammatory arthritis commissioned by Healthcare Quality Improvement Partnership. Rheumatology departments were asked to report their MDT composition; defined as a rheumatologist (consultant or specialist trainee), specialist nurse, occupational therapist physiotherapist, and podiatrist. The data were collected as Whole Time Equivalent (WTE) of each professional group at each department adjusted to 100,000 population. The data were grouped according to British Society for Rheumatology regions to study regional variations. The survey was completed by 164/167 departments (98% response rate). All departments reported an MDT comprising a rheumatologist (consultant or specialist trainee) and almost all included a specialist nurse but only 28 (17%) of the departments had MDTs comprising all the professional groups. There was a high degree of regional variation in the provision of Allied Health Professionals (physiotherapists, occupational therapists, and podiatrists) in the UK. MDT care is recommended for the management of inflammatory arthritis, but few UK rheumatology departments have a full complement of healthcare professionals within their MDT. There is a high degree of regional variation in the composition and staffing levels of the rheumatology MDT across the UK; the impact of which warrants further investigation.
28368343 A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analges 2017 Apr 3 The seeds of Strychnosnux-vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnosnux-vomica. Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.
28770709 Timing of onset affects arthritis presentation pattern in antisyntethase syndrome. 2018 Jan OBJECTIVES: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). METHODS: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). RESULTS: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). CONCLUSIONS: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.
28970488 Single-cell analysis reveals sexually dimorphic repertoires of Interferon-γ and IL-17A pr 2017 Oct 2 The development of Sjögren's syndrome (SjS) is a dynamic and temporal process with a female predilection. Following the initial influx of immune cells, T cell clusters develop, accelerating the pathology in the salivary glands. Proinflammatory cytokines, IFN-γ and IL-17A, produced by T cells contribute synergistically to the disease. In this study, we examined the sexual dimorphism in cellular infiltrates of the salivary glands by using functional single-cell microengraving analysis. Using high-throughput sequencing, we investigated the clonal diversity of the T cell receptors (TCRs) of infiltrating IFN-γ and IL-17A-producing T cells in male and female SjS-susceptible (SjS(s)) C57BL/6.NOD-Aec1Aec2 mice. There were elevated frequencies of IFN-γ and IL-17A-producing effector T cell populations in female SjS(S) mice compared to male SjS(S) mice. MEME analysis shows high frequency and unique, sexually dimorphic motifs in the TCR hypervariable regions in the SjS(S) mice. Male mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG) TCR genes in Th1 cells and TRBV16/(TRBD1/2)TRBJ1-7 (CGGKRRLESIFR) in Th1 and Th17 cells. Female SjS(S) mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG), TRAV13D-2/TRAJ23 (CVYLEHHFE), and TRBV23/(TRBD2)TRBJ2-2 (CRKLHSCATCALNFL) in Th1 cells. These findings suggest that there is an elevated prevalence of pathogenic effector T cells in the glands with a sexually dimorphic selection bias of TCR repertoires.
28798231 P2X7 receptor antagonism prevents IL-1β release from salivary epithelial cells and reduce 2017 Oct 6 Salivary gland inflammation is a hallmark of Sjögren's syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated nonselective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1β and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome. Here, our results show that in primary mouse submandibular gland (SMG) epithelial cells, P2X7R activation also induces the assembly of the NLRP3 inflammasome and the maturation and release of IL-1β, a response that is absent in SMG cells isolated from mice deficient in P2X7Rs (P2X7R(-/-)). P2X7R-mediated IL-1β release in SMG epithelial cells is dependent on transmembrane Na(+) and/or K(+) flux and the activation of heat shock protein 90 (HSP90), a protein required for the activation and stabilization of the NLRP3 inflammasome. Also, using the reactive oxygen species (ROS) scavengers N-acetyl cysteine and Mito-TEMPO, we determined that mitochondrial reactive oxygen species are required for P2X7R-mediated IL-1β release. Lastly, in vivo administration of the P2X7R antagonist A438079 in the CD28(-/-), IFNγ(-/-), NOD.H-2(h4) mouse model of salivary gland exocrinopathy ameliorated salivary gland inflammation and enhanced carbachol-induced saliva secretion. These findings demonstrate that P2X7R antagonism in vivo represents a promising therapeutic strategy to limit salivary gland inflammation and improve secretory function.
28526422 Temporary ipsilateral stiff shoulder after operative fixation of distal radial fractures. 2017 Jun BACKGROUND: This study was conducted to identify variables affecting the development of temporary stiff shoulder after operative fixation for distal radial fractures (DRF). MATERIALS AND METHODS: The study retrospectively analyzed 167 patients who had undergone internal fixation using volar locking plate for DRF between 2010 and 2013. Group 1 was denoted as the "normal group," and group 2 was denoted as the "stiff shoulder group." Basic demographic factors evaluated included age, sex, bone mineral density (BMD), and the dominancy. Also investigated were radiologic variables, including concurrent fractures of the styloid process, positive ulnar variances, classification of DRF, and morphologic type of the distal radioulnar joint. Finally, the type of plate, methods used for postoperative protection, and time of union were analyzed. RESULTS: Group 1 consisted of 114 patients, and group 2 consisted of 53 patients. On overall univariate analysis, BMD, hand dominancy, and the protective methods after plating were significantly different between the 2 groups. On multivariate analysis, a lower BMD and injury on the nondominant side were significant factors for shoulder stiffness. Stiffness was significantly higher in patients with a mean BMD < -2.6 than in patients with a mean BMD ≥ -2.6. At the final follow-up, all of the 53 patients in group 2 were relieved of the symptoms of a stiff shoulder. CONCLUSIONS: A lower BMD and injury on the nondominant distal radius were distinct factors for the development of a stiff shoulder after operative fixation in DRF. Fortunately, nonoperative treatments, such as stretching exercises/injections, were useful for the relief of these symptoms in the short-term follow-up.
28234966 The single nucleotide variant rs12722489 determines differential estrogen receptor binding 2017 We studied functional effect of rs12722489 single nucleotide polymorphism located in the first intron of human IL2RA gene on transcriptional regulation. This polymorphism is associated with multiple autoimmune conditions (rheumatoid arthritis, multiple sclerosis, Crohn's disease, and ulcerative colitis). Analysis in silico suggested significant difference in the affinity of estrogen receptor (ER) binding site between alternative allelic variants, with stronger predicted affinity for the risk (G) allele. Electrophoretic mobility shift assay showed that purified human ERα bound only G variant of a 32-bp genomic sequence containing rs12722489. Chromatin immunoprecipitation demonstrated that endogenous human ERα interacted with rs12722489 genomic region in vivo and DNA pull-down assay confirmed differential allelic binding of amplified 189-bp genomic fragments containing rs12722489 with endogenous human ERα. In a luciferase reporter assay, a kilobase-long genomic segment containing G but not A allele of rs12722489 demonstrated enhancer properties in MT-2 cell line, an HTLV-1 transformed human cell line with a regulatory T cell phenotype.
28459776 Postoperative Regression of Retro-odontoid Pseudotumor After Atlantoaxial Posterior Fixati 2017 Dec 1 STUDY DESIGN: Case series study. OBJECTIVE: The aim was to investigate the incidence of retro-odontoid pseudotumor in patients with atlantoaxial instability (AAI) and evaluate pseudotumor regression after posterior fixation. SUMMARY OF BACKGROUND DATA: The incidence of retro-odontoid pseudotumor in atlantoaxial instability patients remains uncertain. Moreover, the regression of retro-odontoid pseudotumor after posterior fixation in patients with various underlying diseases needs to be further investigated. METHODS: From July 2004 to August 2015, 175 patients with AAI underwent posterior fixation operations at our institution. After excluding 11 patients (previous operation, n = 4; history of tumor, n = 7), the final study population comprised 164 patients. The final study population was categorized according to their underlying diseases (rheumatoid arthritis [RA], os odontoideum, atlanto-occipital assimilation, dens fracture, AAI of unknown cause, etc.) and age (adult and pediatric groups). The incidence of retro-odontoid pseudotumor in each group was analyzed. Pre- and postoperative magnetic resonance or computed tomography images were reviewed to assess its regression following surgery. RESULTS: Of the 164 patients included, 38 had retro-odontoid pseudotumor (23.2%). Three were diagnosed with RA and the rest were non-RA patients including os odontoideum (n = 12), dens fracture (n = 6), atlanto-occipital assimilation (n = 4), Morquio syndrome (n = 1), and AAI of unknown cause (n = 12). Pseudotumor size regressed in all 38 patients after atlantoaxial posterior fixation. There was a statistically significant decrease in pseudotumor size (the length between the anterior border of the odontoid process to the posterior border of the pseudotumor) from a mean length of 17.7 to 14.9 mm (P < 0.001). CONCLUSIONS: The patients had various underlying diseases and the overall incidence of retro-odontoid pseudotumor in patients with symptomatic AAI was 23.2% at our institution during the past 11 years. All patients who underwent posterior fixation for AAI showed a statistically significant decrease in pseudotumor size. LEVEL OF EVIDENCE: 4.
28962565 A novel data-driven workflow combining literature and electronic health records to estimat 2017 Sep 29 BACKGROUND: Data collected in EHRs have been widely used to identifying specific conditions; however there is still a need for methods to define comorbidities and sources to identify comorbidities burden. We propose an approach to assess comorbidities burden for a specific disease using the literature and EHR data sources in the case of autoimmune diseases in celiac disease (CD). METHODS: We generated a restricted set of comorbidities using the literature (via the MeSH® co-occurrence file). We extracted the 15 most co-occurring autoimmune diseases of the CD. We used mappings of the comorbidities to EHR terminologies: ICD-10 (billing codes), ATC (drugs) and UMLS (clinical reports). Finally, we extracted the concepts from the different data sources. We evaluated our approach using the correlation between prevalence estimates in our cohort and co-occurrence ranking in the literature. RESULTS: We retrieved the comorbidities for 741 patients with CD. 18.1% of patients had at least one of the 15 studied autoimmune disorders. Overall, 79.3% of the mapped concepts were detected only in text, 5.3% only in ICD codes and/or drugs prescriptions, and 15.4% could be found in both sources. Prevalence in our cohort were correlated with literature (Spearman's coefficient 0.789, p = 0.0005). The three most prevalent comorbidities were thyroiditis 12.6% (95% CI 10.1-14.9), type 1 diabetes 2.3% (95% CI 1.2-3.4) and dermatitis herpetiformis 2.0% (95% CI 1.0-3.0). CONCLUSION: We introduced a process that leveraged the MeSH terminology to identify relevant autoimmune comorbidities of the CD and several data sources from EHRs to phenotype a large population of CD patients. We achieved prevalence estimates comparable to the literature.
29259959 Fexaramine Inhibits Receptor Activator of Nuclear Factor-κB Ligand-induced Osteoclast For 2017 Nov BACKGROUND: Osteoclasts are bone resorbing cells and are responsible for bone erosion in diseases as diverse as osteoporosis, periodontitis, and rheumatoid arthritis. Fexaramine has been developed as an agonist for the farnesoid X receptor (FXR). This study investigated the effects of fexaramine on receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast formation and signaling pathways. METHODS: Osteoclasts were formed by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL. Bone resorption assays were performed using dentine slices. The mRNA expression level was analyzed by real-time polymerase chain reaction. Western blotting assays were conducted to detect the expression or activation level of proteins. Lipopolysaccharide-induced osteoclast formation was performed using a mouse calvarial model. RESULTS: Fexaramine inhibited RANKL-induced osteoclast formation, without cytotoxicity. Furthermore, fexaramine diminished the RANKL-stimulated bone resorption. Mechanistically, fexaramine blocked the RANKL-triggered p38, extracellular signal-regulated kinase, and glycogen synthase kinase 3β phosphorylation, resulting in suppressed expression of c-Fos and NF of activated T cells (NFATc1). Consistent with the in vitro anti-osteoclastogenic effect, fexaramine suppressed lipopolysaccharide-induced osteoclast formation in the calvarial model. CONCLUSIONS: The present data suggest that fexaramine has an inhibitory effect on osteoclast differentiation and function, via downregulation of NFATc1 signaling pathways. Thus, fexaramine could be useful for the treatment of bone diseases associated with excessive bone resorption.
29254239 Association between CD40 rs1883832 and immune-related diseases susceptibility: A meta-anal 2017 Nov 24 BACKGROUND/OBJECTIVE: It has been reported that CD40 rs1883832 might be associated with immune-related diseases susceptibility. Owing to mixed and inconclusive results, we conducted a meta-analysis of case-control studies to summarize and clarify this association. METHODS/MAIN RESULTS: A systematic search of studies on the association between CD40 rs1883832 and immune-related diseases susceptibility was conducted in databases. Odds ratios and 95% confidence intervals were used to pool the effect size. 40 articles were included in our meta-analysis. CONCLUSIONS: CD40 rs1883832 is associated with decreased risk of Graves' disease, especially in Asian; CD40 rs1883832 is associated with increased risk of multiple sclerosis; CD40 -1C>T (rs1883832) is not associated with the susceptibility of Hashimoto's thyroiditis, systemic sclerosis or Asthma; there is insufficient data to fully confirm the association between CD40 rs1883832 and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Behçet's disease (BD), myasthenia gravis (MG), Crohn's disease (CD), ulcerative colitis (UC), Sarcoidosis, Fuch uveitis syndrome (FUS), Vogt-Koyanagi-Harada syndrome (VKH), Kawasaki disease (KD), giant cell arteritis (GCA) or Immune thrombocytopenia (ITP).
29231235 The perioperative use of synthetic and biological disease-modifying antirheumatic drugs in 2017 Disease-modifying antirheumatic drugs (DMARDs) have become essential treatments in the management of patients with inflammatory rheumatic diseases. Their use has resulted in a marked improvement of disease control and a limitation of joint damage, although some patients still require subsequent corrective or joint replacement surgery. Due to their immunosuppressive effects, some DMARDs are associated with an increased risk of infection. The aim of this review is to discuss the available literature on the management of DMARDs during the perioperative period, particularly in the case of orthopaedic surgery. Conventional synthetic DMARDs such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine appear to be safe during the perioperative period. Conflicting results on biological DMARDs, mainly tumour necrosis factor antagonists, are reported in the literature, including both increased and unchanged risk of superimposed infections after surgery. Taking into account the available literature, we included some propositions for the management of patients who will undergo surgical interventions.
29211140 Pharmacotherapeutic profile of users and expenditure on high-cost drugs in São Leopoldo, 2017 Oct OBJECTIVE: to describe the pharmacotherapeutic profile of users of the Specialized Program for Pharmaceutical Assistance, and to measure the expenditure on the most prevalent and the most expensive medications. METHODS: descriptive study conducted in São Leopoldo-RS, Brazil, with secondary data regarding information about requests accepted in 2014, through administrative proceedings; delivery notes of the State Health Department/RS were used to assess the costs. RESULTS: 1,528 users were included in the study, mostly women (56.7%), and the average age was 52 years (standard deviation=17.9); the most frequent diagnoses were allergic asthma (17.1%), chronic kidney disease (11.5%) and rheumatoid arthritis (8.4%); the most prevalent drug was budesonide+formoterol fumarate (18.3%); among the most prevalent drugs, the highest total monthly expense was with epoetin alfa (BRL37,922.34) and among the most expensive drugs, infliximab (BRL72,503.28). CONCLUSION: the data show the importance of the Specialized Program for Pharmaceutical Assistance in the high-cost treatment of highly prevalent.
29133662 A tiny tick can cause a big health problem. 2017 Nov Ticks are tiny crawling bugs in the spider family that feed by sucking blood from animals. They are second only to mosquitoes as vectors of human disease, both infectious and toxic. Infected ticks spread over a hundred diseases, some of which are fatal if undetected. They spread the spirochete (which multiplies in the insect's gut) with a subsequent bite to the next host. We describe the only reported cases of peri ocular tick bite from India that presented to us within a span of 3 days and its management. Due suspicion and magnification of the lesions revealed the ticks which otherwise masqueraded as small skin tags/moles on gross examination. The ticks were firmly latched on to the skin and careful removal prevented incarceration of the mouth parts. Rickettsial diseases that were believed to have disappeared from India are reemerging and their presence has recently been documented in at least 11 states in the country. Among vector borne diseases, the most common, Lyme disease, also known as the great mimicker, can present with rheumatoid arthritis, fibromyalgia, depression, attention deficit hyperactivity disorder, multiple sclerosis, chronic fatigue syndrome, cardiac manifestations, encephalitis, and mental illness, to name some of the many associations. Common ocular symptoms and signs include conjunctivitis, keratitis, uveitis, and retinitis. Early detection and treatment of tick borne diseases is important to prevent multi system complications that can develop later in life.