Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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29542415 | Cardiovascular Disease in Primary Sjögren's Syndrome. | 2018 | BACKGROUND: A close relationship between rheumatic diseases and cardiovascular disease (CVD) has been reported, accounting for the higher mortality and morbidity observed in these patients. In the last years, it has been clearly reported that patients affected by primary Sjögren's syndrome (pSS) experienced an increased risk of CVD. OBJECTIVE: This review aimed at investigating CVD, traditional cardiovascular (CV) risk factors and possible targeted therapeutic strategies in pSS patients. METHOD: Available literature concerning CV risk factors in pSS patients has been selected and discussed. CONCLUSION: Disease-related characteristics and traditional CV risk factors contribute to observed atherosclerotic damage in pSS patients. The pro-inflammatory mediators together with hypertension and type 2 diabetes, which are more prevalent in pSS patients, determine the increased CV burden. Future studies are needed to fully elucidate the role of possible targeted therapies. | |
28621153 | Depression in primary Sjögren's syndrome: a systematic review and meta-analysis. | 2018 Feb | There is substantial uncertainty regarding the prevalence of depression in Primary Sjögren's syndrome (pSS). We conducted a systematic review aiming to evaluate the association of pSS with depression. PubMed, Web of Science, VIP, CNKI and Wanfang database were searched to find the published literatures (from these databases established to October 2016). Studies were screened according to inclusion and exclusion criteria and the qualities of included studies were evaluated. The data was analyzed using Revman5.2 software. A total of 12 studies including 1917 patients were eligible for inclusion in the systematic review and meta-analysis. In this meta-analysis, Severity of depression was assessed using psychometric measures, such as PHQ-9; HADS; CES-D; Zung depression scale and BDI. The result revealed that pSS was associated with an increased prevalence of depression (summary odds ratio (OR) = 5.36, 95% CI: 4.05-7.09, P < 0.01). The depression score in pSS patients (standardized mean difference (SMD) = 1.47, 95% CI: 0.81-2.12, P < 0.01) were higher than in the control group. Depression is highly prevalent in pSS than in healthy controls. Early recognition and appropriate intervention are therefore essential to reduce the negative impact of depression on the patient's quality of life and outcome of their disease. | |
29924754 | Oral lesions in Sjogren's syndrome: A systematic review. | 2018 Jul 1 | BACKGROUND: Sjogren's syndrome (SS) is an autoimmune disease related to two common symptoms: dry mouth and eyes. Although, xerostomia and hyposialia have been frequently reported in these patients, not many studies have evaluated other oral manifestations. The aim of this systematic review was to investigate prevalence rates of oral lesions (OL) in SS patients and to compare it to a control group (CG), when available. MATERIAL AND METHODS: An exhaustive search of the published literature of the Pubmed, Scopus, Web of Science and the Cochrane Library databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) for relevant studies that met our eligibility criteria (up to September 1st 2017). RESULTS: Seventeen cross-sectional studies and one cohort study were finally included. The results showed that SS patients presented more OL compared to non-SS patients. The most frequent types of OL registered in primary and secondary SS were angular cheilitis, atrophic glossitis, recurrent oral ulcerations and grooves or fissurations of the tongue, also when compared to a CG. CONCLUSIONS: OL are common and more frequent in SS patients when compared to a CG. This may be a consequence of low levels of saliva. More studies where these OL and all the possible cofounding factors are taken into account are needed. | |
30396617 | Effects of a massage-like essential oil application procedure using Copaiba and Deep Blue | 2018 Nov | BACKGROUND AND PURPOSE: Existing research suggests that both massage and essential oils may have analgesic and anti-inflammatory benefits. We investigate the benefits of the AromaTouch Hand Technique(®) (ATHT), a procedure that combines a moderate pressure touch with the application of essential oils to the hand, in individuals with hand arthritis. METHODS AND MATERIALS: Thirty-six participants with rheumatoid arthritis, osteoarthritis, and/or chronic inflammation received ATHTs with either a 50/50 preparation of Deep Blue(®) and Copaiba oil or a coconut oil placebo twice daily for 5 consecutive days. Changes in maximum flexion in finger and thumb joints, items from the Arthritis Hand Function Test, and hand pain scores were evaluated. RESULTS: Participants treated with the essential oil preparation required significantly less time to complete dexterity tasks and showed about 50% decrease in pain scores, increased finger strength, and significantly increased angle of maximum flexion compared to subjects treated with coconut oil. CONCLUSION: The ATHT with Copaiba and Deep Blue may have ameliorative effects on hand arthritis. | |
29203716 | Immune tolerance therapies for autoimmune diseases based on heat shock protein T-cell epit | 2018 Jan 19 | Experimental models of autoimmune diseases have revealed the disease protective role of heat shock proteins (HSPs). Both the administration of exogenous extracellular, mostly recombinant, HSP and the experimental co-induction of endogenous intracellular HSP in models have been shown to lead to production of disease protective regulatory T cells (Tregs). Similar to HSP taken up from extracellular bodily fluids, due to stress-related autophagy upregulated HSP also from intracellular sources is a major provider for the major histocompatibility class II (MHCII) ligandome; therefore, both extracellular and intracellular HSP can be prominent targets of Treg. The development of therapeutic peptide vaccines for the restoration of immune tolerance in inflammatory diseases is an area of intensive research. In this area, HSPs are a target for tolerance-inducing T-cell therapy, because of their wide expression in inflamed tissues. In humans, in whom the actual disease trigger is frequently unknown, HSP peptides offer chances for tolerance-promoting interventions through induction of HSP-specific Treg. Recently, we have shown the ability of a bacterial HSP70-derived peptide, HSP70-B29, to induce HSP-specific Tregs that suppressed arthritis by cross-recognition of their mammalian HSP70 homologues, abundantly present in the MHCII ligandome of stressed mouse and human antigen-presenting cells in inflamed tissues.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'. | |
29717035 | Predictors of Flare Following Etanercept Withdrawal in Patients with Rheumatoid Factor-neg | 2018 Jul | OBJECTIVE: To evaluate the rate of flare after etanercept (ETN) withdrawal in patients with juvenile idiopathic arthritis (JIA) who attained clinical remission while taking medication, and to identify predictors of flare. METHODS: Patients were included with oligo- (oJIA) and rheumatoid factor-negative polyarticular JIA (pJIA) who received a first course of ETN for at least 18 months, maintained clinically inactive disease (CID) for at least 6 months during treatment, and were followed for 12 months after ETN withdrawal. Demographic and clinical features were collected at onset, at baseline (initiation of ETN), and at time of disease flare. RESULTS: After ETN withdrawal, 66 of the 110 patients enrolled (60%) flared with arthritis (of whom 7 flared with concurrent anterior uveitis; none with uveitis alone). The median time to flare was 4.3 months (interquartile range 2.5-6.4) with no evident differences between oJIA and pJIA. The number and type of joints involved at baseline and characteristics of ETN treatment/discontinuation were not associated with flare. Patients who flared were more frequently males (p = 0.034), positive for antinuclear antibody (ANA; p = 0.047), and had higher values of C-reactive protein (CRP; p = 0.012) at baseline. These variables remained significantly associated with flare in a multivariate logistic analysis, a model accounting for only 14% of the variability of the occurrence of the flare. CONCLUSION: Our results show that a significant proportion of patients with JIA who maintain CID for at least 6 months experience a relapse after ETN withdrawal. Male sex, presence of ANA, and elevated CRP at baseline were associated with higher risk of flare. | |
30305930 | Low salivary cortisol levels in patients with rheumatoid arthritis exposed to oral glucoco | 2018 | BACKGROUND: Glucocorticoids (GCs) suppress endogenous cortisol levels which can lead to adrenal insufficiency (AI). The frequency of GC-induced AI remains unclear. In this cross-sectional study, low morning salivary cortisol (MSC) levels were used as a measure of adrenal function. The study aim was to investigate the prevalence of low MSC in patients with rheumatoid arthritis (RA) currently and formerly exposed to oral GCs, and the association with potential risk factors. METHODS: Sample collection was nested within UK primary care electronic health records (from the Clinical Practice Research Datalink). Participants were patients with RA with at least one prescription for oral GCs in the past 2 years. Self-reported oral GC use was used to define current use and current dose; prescription data were used to define exposure duration. MSC was determined from saliva samples; 5 nmol/L was the cut-off for low MSC. The prevalence of low MSC was estimated, and logistic regression was used to assess the association with potential risk factors. RESULTS: 66% of 38 current and 11 % of 38 former GC users had low MSC. Among former users with low MSC, the longest time since GC withdrawal was 6 months. Current GC dose, age and RA duration were significantly associated with increased risk of low MSC. CONCLUSION: The prevalence of low MSC among current GC users is high, and MSC levels may remain suppressed for several months after GC withdrawal. Clinicians should therefore consider the risk of suppressed cortisol and remain vigilant for symptoms of AI following GC withdrawal. | |
31431948 | The 8-foot up and go test is the best way to assess physical function in the rheumatoid ar | 2018 | OBJECTIVES: RA is characterized by poor physical function, which compromises patients' quality of life and outcome. Clinical assessment of function is usually performed using self-reported questionnaires, such as the Multi-Dimensional HAQ (MDHAQ) and the Short Form-36 (physical component) (SF36-PC). However, such subjective measures may not accurately reflect real functional status. This study aimed to determine: (i) which clinically practicable objective test best represents overall physical function; and (ii) the extent to which self-reported subjective functional measures reflect objectively assessed function. METHODS: Objective [isometric knee extensor strength, handgrip strength, sit-to-stands in 30 s, 8-foot up and go (8'UG), 50-foot walk (50'W) and estimated aerobic capacity (V̇O(2)max)] and subjective (MDHAQ and SF36-PC) measures of function were correlated with one another to determine the best overall test of functional status in 82 well-controlled RA patients (DAS28 (s.d.) = 2.8 (1.0)). RESULTS: In rank order of size, averaged correlations (r) to the other outcome measures were as follows: 8'UG: 0.650; 50'W: 0.636; isometric knee extensor strength: 0.502; handgrip strength: 0.449; sit-to-stands in 30 s: 0.432; and estimated V̇O(2)max: 0.358. The MDHAQ was weakly (0.361) and the SF36-PC moderately correlated (0.415) with objective measures. CONCLUSION: Our results show that the most appropriate measure of objective physical function in RA patients is the 8'UG, followed by the 50'W. We found discordance between objectively and subjectively measured function. In clinical practice, an objective measure that is simple and quick to perform, such as the 8'UG, is advocated for assessing real functional status. | |
30551501 | The applications of anti-CD20 antibodies to treat various B cells disorders. | 2019 Jan | B-lymphocyte antigen CD20 (called CD20) is known as an activated-glycosylated phosphoprotein which is expressed on the surface of all B-cells. CD20 is involved in the regulation of trans-membrane Ca(2+) conductance and also play critical roles in cell-cycle progression during human B cell proliferation and activation. The appearance of monoclonal antibody (mAb) technology provided an effective field for targeted therapy in treatment of a variety of diseases such as cancer, and autoimmune diseases. Anti-CD20 is one of important antibodies which could be employed in treatment of several diseases. Increasing evidences revealed that efficacy of different anti-CD20 antibodies is implicated by their function. Hence, evaluation of anti-CD20 antibodies function could provide and introduce new anti-CD20 based therapies. In the present study, we summarized several applications of anti-CD20 antibodies in various immune related disorders including B-CLL (B-cell chronic lymphocytic leukemia), rheumatoid arthritis (RA), multiple sclerosis (MS) and melanoma. | |
30498332 | Analysis of real-world treatment patterns in a matched rheumatology population that contin | 2018 | PURPOSE: This study compared treatment patterns of Turkish patients with a diagnosis of rheumatoid arthritis (RA) who were treated with innovator Remicade(®) (infliximab [IFX]) and either continued IFX or switched to CT-P13. MATERIALS AND METHODS: Adult RA patients with ≥1 IFX claim were identified from the Turkish Ministry of Health database. Eligible patients initiated and continued IFX treatment (continuers cohort [CC]) or initiated IFX and switched to CT-P13 (switchers cohort [SC]) during the study period. The initial IFX claim date was defined as the index date. The switch/reference date was defined as the CT-P13 switch date for the SC or a random IFX date during the period of CT-P13 availability for the CC. Cohorts were matched by age, sex, and number of IFX prescriptions during baseline. Patient demographics, discontinuation, and switching were summarized. The baseline period was defined as the period from the index date to the switch/reference date. The follow-up period ranged from the switch/reference date to the end of data availability. RESULTS: After matching, 697 patients were selected: 605 patients for the CC and 92 patients for the SC. Mean IFX duration for the baseline period was 422 days in the CC and 438 days in the SC. Median time on any infused tumor necrosis factor (TNF) antagonist therapy was 1,080 days in the CC and 540 days in the SC during the study period. During the follow-up period, discontinuation was lower in the CC (CC=33.9% vs SC=87.5%; P<0.001). The mean time to discontinuation was longer in the CC (CC=276 days vs SC=132 days; P<0.001). A switch to another biologic medication during the follow-up period was observed in 19.0% of patients in the CC (n=115) and 81.5% of patients in the SC (n=75; P<0.001). CONCLUSION: Treatment patterns differed between patients prescribed IFX and CT-P13. In Turkey, RA patients maintained on IFX had greater treatment persistence (ie, fewer and later discontinuations) than those who initiated IFX and switched to CT-P13. | |
29724649 | Anatomical variations of vertebral artery and C2 isthmus in atlanto-axial fusion: Consecut | 2018 Jul | VA anomalies in extra- and intraosseous regions of the craniovertebral junction (CVJ) is considered very carefully during the posterior screw fixation for the atlantoaxial instability (AAI). This study aims to compare the incidence and variations of VA anomalies, isthmus and pedicle size of C2 in 100 patients with AAI due to congenital skeletal anomaly (CSA) and acquired disease by using three-dimensional CT angiograms (3D CTA) before surgery. The CSA group contained 48 patients and the acquired disease group consisted of 52. In the CSA group, Os odontoideum was the major cause with 43 patients. The causes of acquired disease were RA in 16 patients and OA in 36 patients. Five patients had the anomalous VA in only CSA group; fenestration 2 patients and persistent first intersegmental (PFIS) artery 3 patients. Between CSA and acquired disease groups, no significant differences were found in the isthmus height, internal height, and pedicle width of C2 except the right internal height that is bigger in CSA group. The high-riding VA (isthmus height <4 mm or internal height <2 mm) had no significant difference between CSA group (27.1%) and acquired disease group (34.6%). However, in acquired disease group, patients with rheumatoid arthritis had smaller left internal height (4.21 ± 1.63 vs. 5.51 ± 1.83 mm) and pedicle width (4.11 ± 1.05 vs. 5.05 ± 1.66 mm) of C2 than those of patients with degenerative osteoarthritis. Therefore, in the case of atlantoaxial fusion, we should contemplate VA anomaly and the high-riding VA, especially in patients with CSA and RA. | |
29144542 | Autoimmune diseases and breast cancer risk by tumor hormone-receptor status among elderly | 2018 Mar 15 | The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ-specific autoimmune diseases and risk of breast cancer by tumor estrogen receptor (ER)- and progesterone receptor (PR)- status. Here, we evaluate associations between selected systemic and organ-specific autoimmune diseases and breast cancer risk overall and by tumor ER- and PR-status. We used linked Surveillance, Epidemiology and End Results (SEER)-Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992-2011; N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer-free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR = 0.84; 99.9% CI 0.79-0.89), systemic lupus erythematosus (OR = 0.82; 99.9% CI 0.70-0.97) and pernicious anemia (OR = 0.90; 99.9% CI 0.83-0.97) and increased risk among those with psoriasis (OR = 1.16; 99.9% CI 1.06-1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER-positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER-status were statistically significant (p-heterogeneity = 0.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment. | |
28196776 | EBV-induced lymphoproliferative disorders in rheumatic patients: A systematic review of th | 2018 Jan | OBJECTIVES: Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. METHODS: We reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital. We excluded those cases without an underling rheumatic condition, a specific IST or not reporting univocal data. RESULTS: In the cumulative cohort of 159 patients, most were affected by rheumatoid arthritis (83.0%) and treated with methotrexate (75.4%). 68.5% of LPDs developed between the age of 40 and 70 years, after 13.3±9.6 years from rheumatic disease onset and 58.7±47.0 months of IST. LPDs were mostly B-cell lineage derived (39.0%), Ann Arbor disease's stage I (38.3%) and presented with extra-nodal involvement in 63.1%, which was most frequently represented by central nervous system (17.6%). The most common approach was IST withdrawal (93.3%), variably associated with radiotherapy(RT)/chemotherapy(CT) in 38.3% of cases. Overall, 61.7% of patients achieved a complete remission (CR; 30.2±24.0 months). Among published cases of patients that only suspended IS as first line treatment approach, 67.2% achieved CR. No significant demographic, clinical and histological differences between patients who achieved CR and who did not, and between who achieved CR by IST withdrawal alone and who did not were observed (P>0.05 in all comparison). CONCLUSIONS: The current study reviews all the published evidences of EBV-induced LPDs in patients receiving IST treatment for rheumatic conditions. | |
30881554 | Evaluation and Management of Septic Arthritis and its Mimics in the Emergency Department. | 2019 Mar | Septic arthritis is a dangerous medical condition associated with significant morbidity and mortality. However, the differential diagnosis can be broad with conditions that mimic this disease and require different evaluation and treatment. This narrative review presents the emergency medicine evaluation and management, as well as important medical conditions that may mimic this disease. Septic arthritis commonly presents with monoarticular joint pain with erythema, warmth, swelling, and pain on palpation and movement. Fever is present in many patients, though most are low grade. Blood testing and imaging may assist with the diagnosis, but the gold standard is joint aspiration. Management includes intravenous antibiotics and orthopedic surgery consult for operative management vs. serial aspirations. Clinicians should consider mimics, such as abscess, avascular necrosis, cellulitis, crystal-induced arthropathies, Lyme disease, malignancy, osteomyelitis, reactive arthritis, rheumatoid arthritis, and transient synovitis. While monoarticular arthritis can be due to septic arthritis, other medical and surgical conditions present similarly and require different management. It is essential for the emergency clinician to be aware how to diagnose and treat these mimics. | |
30559579 | 2-D speckle-tracking assessment of left and right ventricular function in rheumatoid arthr | 2019 Jan | OBJECTIVES: Disease activity has been considered as independent cardiovascular risk factor in rheumatoid arthritis (RA) patients. We aimed to evaluate the effect of RA disease activity on left ventricular (LV) and right ventricular (RV) functions by speckle tracking echocardiography (STE). METHODS: 120 patients with RA without evidence of cardiovascular disease and 40 healthy control subjects were included. Disease activity was evaluated according to Simplified Disease Activity Index (SDAI) score and Disease Activity Score 28 (DAS28). LV and RV functions were assessed using conventional echocardiography and global longitudinal strain (GLS) technique measured by STE. RESULTS: 81 patients had active disease while 39 patients were in remission. The LV and RV GLS value for active RA patients was reduced compared to RA patients in remission and control group (p = <0.001). There was a significant correlation between RA disease activity scores level and LV GLS value, increasing levels of disease activity was associated with worse LV GLS (r = -0.802, p value = <0.001) and r = -0.824, p value = <0.001) for SDAI and DAS28 scores respectively. Also, there were significant correlations between RA disease activity scores level and RV GLS value as the disease activity level increases the RV GLS value become worse (r = -0.682, p value = <0.001) and r = -0.731, p value = <0.001) for SDAI and DAS28 scores respectively Receiver operating characteristic (ROC) curve analysis showed that SDAI score and DAS28 were predictive for reduced LV GLS with a cut off value of >7 and >2.8 respectively with sensitivity of 77.6%, specificity of 85.0% and area under ROC curve = 90.4 for SDAI score and with sensitivity of 89.7%, specificity of 71.7% and area under ROC curve = 89.4 for DAS28 score. Also, SDAI score and DAS28 were predictive for reduced RV GLS with a cut off value of >11 and >3 respectively with sensitivity of 73.1%, specificity of 93.5% and area under ROC curve = 91.6 for SDAI score and with sensitivity of 84.6%, specificity of 80.4% and area under ROC curve = 90.8 for DAS28 score. CONCLUSION: Disease activity in patients with rheumatoid arthritis is associated with lower left and right ventricular function. Disease activity scores can predict subclinical left and right ventricular dysfunction. | |
29875847 | Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Metho | 2018 May 20 | AIM: This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). METHODS: In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. RESULTS: Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic progression comparing to the group of patients with monotherapy. CONCLUSIONS: Based on our results achieved during 2 years we can conclude that ETN in combination with MTX reduced disease activity, slowed radiographic progression and improved clinical manifestations more effectively than MTX alone. No serious adverse events were noticed in the group with combination treatment. | |
29660314 | Nrf2 as a therapeutic target for rheumatic diseases. | 2018 Jun | Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of cellular protective processes. Rheumatic diseases are chronic conditions characterized by inflammation, pain, tissue damage and limitations in function. Main examples are rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis and osteoporosis. Their high prevalence constitutes a major health problem with an important social and economic impact. A wide range of evidence indicates that Nrf2 may control different mechanisms involved in the physiopathology of rheumatic conditions. Therefore, the appropriate expression and balance of Nrf2 is necessary for regulation of oxidative stress, inflammation, immune responses, and cartilage and bone metabolism. Numerous studies have demonstrated that Nrf2 deficiency aggravates the disease in experimental models while Nrf2 activation results in immunoregulatory and anti-inflammatory effects. These reports reinforce the increasing interest in the pharmacologic regulation of Nrf2 and its potential applications. Nevertheless, a majority of Nrf2 inducers are electrophilic molecules which may present off-target effects. In recent years, novel strategies have been sought to modulate the Nrf2 pathway which has emerged as a therapeutic target in rheumatic conditions. | |
30402304 | Acute Streptococcus mitis Sacroiliitis in a Teenager with Unclear Source of Bacteremia: A | 2018 | Septic arthritis is an orthopedic emergency that is commonly caused by Staphylococcus aureus. Old age, diabetes mellitus, rheumatoid arthritis, prosthetic joint, and recent surgery are the main predisposing risk factors. Most cases of septic arthritis are caused by hematogenous spread of infection. Infectious sacroiliitis is a rare form of septic arthritis which is often clinically challenging to diagnose due its various and nonspecific presentations. Streptococcus mitis belongs to viridans group streptococci (VGS) bacteria, which is a component of body flora that is commonly involved in bacterial endocarditis. VGS in general and S. mitis specifically is an uncommon cause of osteoarticular infections. Here, we report a case of spontaneous Streptococcus mitis bacteremia complicated by septic sacroiliitis in a healthy teenager in the absence of infective endocarditis or a clear source of bacteremia. | |
29440397 | Sex bias in MHC I-associated shaping of the adaptive immune system. | 2018 Feb 27 | HLA associations, T cell receptor (TCR) repertoire bias, and sex bias have independently been shown for many diseases. While some immunological differences between the sexes have been described, they do not fully explain bias in men toward many infections/cancers, and toward women in autoimmunity. Next-generation TCR variable beta chain (TCRBV) immunosequencing of 824 individuals was evaluated in a multiparametric analysis including HLA-A -B/MHC class I background, TCRBV usage, sex, age, ethnicity, and TCRBV selection/expansion dynamics. We found that HLA-associated shaping of TCRBV usage differed between the sexes. Furthermore, certain TCRBVs were selected and expanded in unison. Correlations between these TCRBV relationships and biochemical similarities in HLA-binding positions were different in CD8 T cells of patients with autoimmune diseases (multiple sclerosis and rheumatoid arthritis) compared with healthy controls. Within patients, men showed higher TCRBV relationship Spearman's rhos in relation to HLA-binding position similarities compared with women. In line with this, CD8 T cells of men with autoimmune diseases also showed higher degrees of TCRBV perturbation compared with women. Concerted selection and expansion of CD8 T cells in patients with autoimmune diseases, but especially in men, appears to be less dependent on high HLA-binding similarity than in CD4 T cells. These findings are consistent with studies attributing autoimmunity to processes of epitope spreading and expansion of low-avidity T cell clones and may have further implications for the interpretation of pathogenic mechanisms of infectious and autoimmune diseases with known HLA associations. Reanalysis of some HLA association studies, separating the data by sex, could be informative. | |
30191145 | The INCLUDE study: INtegrating and improving Care for patients with infLammatory rheUmatol | 2018 | BACKGROUND: Patients with inflammatory rheumatic conditions such as rheumatoid arthritis, polymyalgia rheumatica and ankylosing spondylitis are at increased risk of common comorbidities such as cardiovascular disease, osteoporosis and anxiety and depression which lead to increased morbidity and mortality. These associated morbidities are often un-recognized and under-treated. While patients with other long-term conditions such as diabetes are invited for routine reviews in primary care, which may include identification and management of co-morbidities, at present this does not occur for patients with inflammatory conditions, and thus, opportunities to diagnose and optimally manage these comorbidities are missed. OBJECTIVE: To evaluate the feasibility and acceptability of a nurse-led integrated care review (the INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community (INCLUDE) review) for people with inflammatory rheumatological conditions in primary care. DESIGN: A pilot cluster randomized controlled trial will be undertaken to test the feasibility and acceptability of a nurse-led integrated primary care review for identification, assessment and initial management of common comorbidities including cardiovascular disease, osteoporosis and anxiety and depression. A process evaluation will be undertaken using a mixed methods approach including participant self-reported questionnaires, a medical record review, an INCLUDE EMIS template, intervention fidelity checking using audio-recordings of the INCLUDE review consultation and qualitative interviews with patient participants, study nurses and study general practitioners (GPs). DISCUSSION: Success of the pilot study will be measured against the engagement, recruitment and study retention rates of both general practices and participants. Acceptability of the INCLUDE review to patients and practitioners and treatment fidelity will be explored using a parallel process evaluation. TRIAL REGISTRATION: ISRCTN12765345. |