Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 34674623 | Assessment and Management of Loose Bodies in the Knee Joint and Related Disease: A Narrati | 2022 | BACKGROUND: Loose bodies are frequently encountered during clinical activity and are a common finding during knee arthroscopy. Usually, treatment consists of the removal of loose bodies, which can be challenging even for experienced surgeons. The excision alone is not always the complete treatment, because loose bodies are generally secondary to other diseases that can cause persistent symptoms with the risk of new loose body formation. The aim of this narrative review is to show the clinical, imaging, and arthroscopic evaluation of loose bodies in order to plan optimal treatment. METHODS: A comprehensive search of PubMed was conducted to find the most recent and relevant studies investigating aetiopathogenesis, the assessment tools, and the therapeutic strategies for loose bodies in the knee and their related diseases. RESULTS: When dealing with a loose body, the first issue is the evaluation of the intra-articular fragment (location, size, number, symptoms) and its aetiopathogenesis by identifying the underlying pathology (e.g., osteochondritis dissecans, osteoarthritis, chondral defect, tumour-like lesions, rheumatoid arthritis, etc.). In the case of symptomatic intra-articular loose bodies, treatment consists of fragment removal and the management of related diseases (e.g.., lifestyle modification, physiotherapy, pharmacological, and surgical treatment). CONCLUSION: Loose bodies are not separate entities and in addition to their pathological aspect, must be evaluated within the context of the underlying disease. Correct assessment and comprehensive management allow for relief of symptomatology and prevention of loose body formation by removal and treatment of the associated diseases. | |
| 35652047 | Fisetin: An Integrated Approach to Identify a Strategy Promoting Osteogenesis. | 2022 | Flavonoids may modulate the bone formation process. Among flavonoids, fisetin is known to counteract tumor growth, osteoarthritis, and rheumatoid arthritis. In addition, fisetin prevents inflammation-induced bone loss. In order to evaluate its favorable use in osteogenesis, we assayed fisetin supplementation in both in vitro and in vivo models and gathered information on nanoparticle-mediated delivery of fisetin in vitro and in a microfluidic system. Real-time RT-PCR, Western blotting, and nanoparticle synthesis were performed to evaluate the effects of fisetin in vitro, in the zebrafish model, and in ex vivo samples. Our results demonstrated that fisetin at 2.5 µM concentration promotes bone formation in vitro and mineralization in the zebrafish model. In addition, we found that fisetin stimulates osteoblast maturation in cell cultures obtained from cleidocranial dysplasia patients. Remarkably, PLGA nanoparticles increased fisetin stability and, consequently, its stimulating effects on RUNX2 and its downstream gene SP7 expression. Therefore, our findings demonstrated the positive effects of fisetin on osteogenesis and suggest that patients affected by skeletal diseases, both of genetic and metabolic origins, may actually benefit from fisetin supplementation. | |
| 35428712 | Giant Geode at the Humeral Head in the Rheumatoid Shoulder Treated With Allograft Bone Gra | 2022 Apr 15 | Geodes are subarticular cystic lesions caused by inflammatory changes in the synovial lining of the articular cavity and can destroy cartilage and bone. This lesion occurs with rheumatoid arthritis (RA), but a single giant geode is rare.(1). | |
| 34610609 | Association and Risk of Axial Spondyloarthritis of Scoliosis Patients: A Database Study. | 2022 Mar 1 | STUDY DESIGN: Retrospective longitudinal cohort study. OBJECTIVE: To investigate the incidence and risk of axial spondyloarthritis (axSpA) in patients with scoliosis in Taiwan. SUMMARY OF BACKGROUND DATA: Scoliosis and axSpA causes back pain which reduces quality of life in many patients. Both scoliosis and axSpA had attracted numerous research attention, but the association between the two was hardly known. METHODS: In this retrospective study, the data of 25,566 patients were obtained from Taiwan's National Health Insurance Research Database. We identified patients diagnosed with scoliosis and included them in the study cohort. We included age- and sex-matched patients without scoliosis in the control cohort. The total follow-up period was 7 years. Cox proportional hazards models were used to analyze the retrieved data. Hazard ratios (HRs) and adjusted HRs were calculated. RESULTS: The study and control cohorts included 4261 and 21,305 patients, respectively. The incidences of axSpA were 141 and 46 per 100,000 person-years in the study and control cohorts, respectively. The crude HRs and adjusted HRs for patients with scoliosis were 2.98 (95% confidence interval, 1.87-4.73; P < 0.001) and 2.78 (95% confidence interval, 1.74-4.43; P < 0.001), respectively. The prevalence of comorbidities such as chronic obstructive pulmonary disease, osteoporosis, depression, autoimmune diseases (rheumatoid arthritis and systemic lupus erythematosus), and thyroid disease was significantly higher in the study cohort. CONCLUSION: Our findings indicate an association between scoliosis and axSpA. Additional studies should be performed to explain this phenomenon.Level of Evidence: 3. | |
| 35493452 | Cumulative Evidence for Associations Between Genetic Variants in Interleukin 6 Receptor Ge | 2022 | BACKGROUND: Genetic studies have linked polymorphisms in the interleukin 6 receptor (IL6R) gene to the risk of multiple human diseases and phenotypes, yet have reported inconsistent results. We aimed to synthesize current knowledge of variants in the IL6R gene on the risk of diseases and phenotypes. METHODS: We searched the Medline and Embase databases to identify relevant publications. Meta-analysis was performed utilizing DerSimonian and Laird random-effects model. We also graded cumulative evidence for significant associations. Furthermore, phenome-wide analyses and functional annotations were performed for variants with strong evidence. RESULTS: We included 155 studies for evaluating the associations between 80 polymorphisms in the IL6R gene and the risk of 102 human diseases and 98 phenotypes. We conducted 58 main meta-analyses, and 41 significant associations were identified. Strong evidence was assigned to 29 associations that investigated ten variants (rs2228145, rs4129267, rs7529229, rs4537545, rs7518199, rs4845625, rs4553185, rs4845618, rs4845371, and rs6667434) related to the risk of four cardiovascular diseases (coronary heart disease, coronary artery disease, atherosclerosis, and abdominal aortic aneurysms), four inflammatory diseases (rheumatoid arthritis, Crohn's disease, dermatitis, and asthma), and concentration of four phenotypes (C-reactive protein, fibrinogen, IL-6, and sIL-6R). Furthermore, phenome-wide analysis verified that rs2228145 associated with asthma and dermatitis risk. Functional analyses indicated that these polymorphisms fall within exon, enhancer regions. CONCLUSIONS: Our study comprehensively summarizes current data on the genetic architecture of the IL6R gene and highlights the pharmacological targeting potential of IL-6R on cardiovascular and inflammatory diseases. | |
| 35616591 | Medical cannabis use by rheumatology patients in routine clinical care: results from The O | 2022 May 23 | OBJECTIVES: Medical cannabis is often used to alleviate common symptoms in patients with chronic conditions. With cannabis legalisation in Canada and easier access, it is important that rheumatologists understand its potential impact on their practice. Among patients attending rheumatology clinics in Ontario we assessed: the prevalence of medical cannabis use; symptoms treated; rheumatologists' perceptions. METHODS: Eight rheumatology clinics recruited consecutive adult patients in a 3-part medical cannabis survey: the first completed by rheumatologists; the second by all patients; the third by medical cannabis users. Student's t-test and Chi-square test were used to compare medical cannabis users to never users. RESULTS: 799 patients participated, 163 (20.4%) currently using medical cannabis or within <2 years and 636 never users; most had rheumatoid arthritis (37.8%) or osteoarthritis (34.0%). Compared to never users, current/past-users were younger; more likely to be taking opioids/anti-depressants, have psychiatric/gastrointestinal disorders, and have used recreational cannabis (p<0.05); had higher physician (2.9 vs. 2.1) and patient (6.0 vs. 4.2) global scores, and pain (6.2 vs. 4.7) (p<0.0001). Pain (95.5%), sleeping (82.3%) and anxiety (58.9%) were the most commonly treated symptoms; 78.2% of current/past-users reported medical cannabis was at least somewhat effective. Most rheumatologists reported being uncomfortable to authorise medical cannabis, primarily due to lack of evidence, knowledge, and product standardisation. CONCLUSIONS: Medical cannabis use among rheumatology patients in Ontario was two-fold higher than that reported for the general population of similar age. Use was associated with more severe disease, pain, and prior recreational use. Reported lack of research, knowledge, and product standardisation were barriers for rheumatologist use authorisation. | |
| 35569791 | Primary repair of extensor pollicis longus rupture after volar locking plating for distal | 2022 May 13 | We presumed that primary repair would be possible if the extensor pollicis longus (EPL) rupture after volar locking plating (VLP) for distal radius fracture (DRF) was diagnosed earlier. Thus, five cases of EPL ruptures were resolved via primary repair rather than extensor indicis proprius (EIP) transfer, so we reported the clinical outcomes of at least 2 years follow-up since EPL repair. Of 588 consecutive patients with the fractures treated between January 2016 and December 2019, 501 who met out inclusion/exclusion criteria were initially investigated. We informed patients of: (1) the ordinary range of motion of thumb at full wrist flexion/extension; (2) the proper tone of thumb extension compared to the contralateral thumb; and (3) the degree of pain/discomfort during thumb exercise. After discharge, we called each patient monthly commencing at 8 weeks postoperatively to enquire if any of those had worsened, by telephone. Five patients had ruptured EPLs diagnosed at a mean of postoperative-12.8 weeks. Three came to outpatient department for suspected tendon rupture just after telephone survey with the authors. The other two visited after detecting insufficiency in the three items, during the period between telephone inquiries. In four, the torn EPL were encapsulated by tendon sheathes. Extension lag at interphalangeal joint was absent and other clinical outcomes associated with DRF were all satisfactory at final follow-up. Primary repair of EPL rupture (rather than EIP transfer) is possible if patients are properly followed up after VLP for DRF. LEVEL OF EVIDENCE: Level IV, retrospective case series. | |
| 35016701 | Low frequency of disease flare in patients with rheumatic musculoskeletal diseases who rec | 2022 Jan 11 | BACKGROUND: Little is known about the safety of SARS-CoV-2 vaccination in patients with rheumatic musculoskeletal disease (RMD). We evaluated the occurrence of adverse events following immunization (AEFI) in RMD patients and heathy subjects who received anti-SARS-CoV-2 mRNA vaccine. METHODS: We performed a telephone interview collecting any adverse event (AE) following immunization (AEFI) that occurred in RMD patients and healthy controls after the two doses of mRNA vaccine including common local reactogenicity and systemic events (for example, fever, fatigue/malaise, joint and muscle pain). We also investigated the onset of new signs or symptoms of the RMD after the vaccination. RESULTS: We evaluated 126 patients with RMDs [105 females and 19 males, median age 51(IQR 17)] and 85 controls [62 females and 23 males, (median age 49 (20)]. Seventy patients (55.6%) were taking immunosuppressants, conventional synthetic (n=31, 43.3%) and/or biological [TNF inhibitors (n=49, 68.6%)], and 30 (23.8%) were taking hydroxychloroquine; treatment remained unchanged in 77% of patients. Eleven out of 126 patients and none of the 85 controls previously contracted COVID-19. The median follow-up from the completion of vaccination was 15 (3) weeks both in patients and controls. We reviewed 5 suspected cases confirming mild articular flares in 3 women (2.8) with inflammatory arthritis (2 psoriatic arthritis and 1 rheumatoid arthritis) while no disease reactivation was recorded in patients with connective tissue diseases; the incidence rate of RMD reactivation was 0.007 person/month. Multivariable logistic regression analysis showed similar frequencies of local and systemic AEFI in patients and controls with no effect of therapies or previous COVID-19. Local reaction-pain in the injection site-was the most frequently reported AEFI both in RMD and controls (71% and 75% of all the AEFI, respectively) after the first dose. Overall, up to 66% of patients experienced at least one AEFI at the second dose and up to 62% in the control group. Most of AEFI occurred within 2 days of vaccine administration. Two RMD patients developed pauci-symptomatic COVID-19 after the first dose of vaccine. CONCLUSION: The low incidence rate of disease reactivation and the similar AEFI occurrence compared to controls should reassure on mRNA vaccine safety in RMD patients. | |
| 34289032 | Treatment strategies for Sjögren's syndrome with childhood onset: a systematic review of | 2022 Mar 2 | OBJECTIVES: SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarize and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset. METHODS: PubMed and MEDLINE/Scopus databases up to December 2020 were screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 reporting checklist. Animal studies were excluded. RESULTS: A total of 43 studies (34 case reports, 8 mini case series and 1 pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence levels. HCQ was prescribed for parotid swelling, as well as in association with MTX and NSAIDs in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and i.v. methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for mucosa-associated lymphoid tissue lymphoma and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extraglandular manifestations. CONCLUSION: Various therapies are used for the management of juvenile SS and are prescribed based on expert clinician's opinion. There are currently no good-quality studies that allow clinical recommendations for treatment of SS with childhood onset. | |
| 34999914 | Coincidence of juvenile idiopathic arthritis and type 1 diabetes: a case-based review. | 2022 Feb | The study was aimed to review a rare coexistence of type 1 diabetes (T1D) and juvenile idiopathic arthritis (JIA) regarding different clinical approaches to the management and treatment options. Medical complications of the two autoimmune disorders in children and adolescents have been evaluated, particularly in those treated with glucocorticosteroids (GCS) and insulin. A review of the literature regarding reports on concomitant T1D and JIA was conducted using resources available in Medline, Google Scholar, and Web of Science databases, with a specific focus on the combination of T1D and JIA in a pediatric population. The review was extended by our analysis of two patients treated in a single center for this comorbidity. Eligible reports of four cases were found, and including our two original records, a total of six pediatric patients (5 females) were analyzed, of which three had also other autoimmune diseases (thyroiditis, coeliac disease, autoimmune hepatitis), whereas four had been treated with a long-term GCS, and two were receiving biological therapy (etanercept or adalimumab). Only one of them had good metabolic control of diabetes. Diabetes in childhood may coexist with other autoimmune diseases, including rheumatologic conditions. Hyperglycemia can worsen JIA therapy by induction and maintaining inflammation. Using modern diabetes technologies (like personal insulin pumps and continuous glucose monitoring) helps to minimize the deteriorating effect of JIA exacerbations and the rheumatoid treatment on metabolic control of diabetes. | |
| 35616672 | What Do We Know About Toll-Like Receptors Involvement In Gout Arthritis. | 2022 May 23 | Toll-like receptors (TLRs) are a well-characterized family of cell-bound pattern recognition receptors able to identify and respond to conserved structures of external microorganisms or Pathogen Molecular-Associated Pattern (PAMPs). They can also interact with Damage-Associated Molecular Patterns (DAMPs) involved with any infectious and sterile cell stress of tissue injury. Accumulated knowledge about TLRs had revealed that these receptors and intracellular signaling pathways triggered through TLR activation contribute to the physiopathology of different inflammatory diseases, including arthritic conditions. Mostly, the literature focuses on exploring TLR in rheumatoid and osteoarthritis, however, TLRs also seem to be an essential mediator for monosodium urate (MSU) crystals induced gouty arthritis, both in animal models and humans. Accordingly, naked MSU crystals have a highly negatively charged surface recognized by TLRs; intracellular adapter protein MyD88 are significant mediators of MSU crystals-induced IL1β production in mice, and gouty patients demonstrate a robust positive correlation between TLR4 mRNA level and serum IL1β. Here, we revised the literature pieces of evidence surrounding the involvement of TLRs in gout arthritis pathogenesis, with particular reference to TLR2 and TLR4, by analyzing the actual literature data. | |
| 35069205 | Perceptions About Biosimilar Medicines Among Belgian Patients in the Ambulatory Care. | 2021 | Background and objectives: Biosimilar medicines have been on the European market for 15Â years. Despite the extensive and positive experience with biosimilars across Europe, their uptake remains limited in Belgium. One of the possible factors limiting uptake in clinical practice is the inadequate understanding and lack of trust in biosimilars among patients. This study aimed to assess the level of knowledge and perceptions about biosimilar medicines among Belgian patients in the ambulatory care. Methods: This study consisted of online questionnaires among Belgian patients in the ambulatory care (i.e., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease, ulcerative colitis, diabetes mellitus type I and II). The results were collected between December 2020 and February 2021. The data were analyzed with descriptive and inferential statistics. Results: In total, 657 patients across all disease areas of interest participated in this study. Only 38% of patients had heard of biosimilars before. Of those patients, most (58%) were aware that biosimilars are as safe and effective as their reference product. The vast majority of respondents (68%) would agree with transitioning to a biosimilar if their physician prescribed it, only 3% would never agree with a transition to a biosimilar. If a physician would propose to change their current originator biological therapy with its biosimilar, nearly all patients (95%) want their physician to explain the decision and inform them. For additional information about biosimilars, Belgian patients prefer brochures or folders (41%), or available resources on the internet (35%). Physicians were indicated as the preferred source of information (95%), followed by pharmacists (51%), academia (39%), and patient associations (35%). Most patients require information regarding the safety and efficacy (78%), price and reimbursement (64%), and the clinical development process (56%) of the biosimilar. Conclusion: Belgian patients require information about biosimilar medicines. However, most patients are open and positive towards transitioning their current biological therapy with its biosimilar if sufficiently supported by their healthcare providers. | |
| 35456714 | Tolmetin Sodium Fast Dissolving Tablets for Rheumatoid Arthritis Treatment: Preparation an | 2022 Apr 18 | Tolmetin sodium (TLM) is a non-steroidal anti-inflammatory drug (NSAIDs). TLM is used to treat inflammation, skeletal muscle injuries, and discomfort associated with bone disorders. Because of the delayed absorption from the gastro intestinal tract (GIT), the currently available TLM dosage forms have a rather protracted start to the effect, according to pharmacokinetic studies. The aim of this study was to create a combination for TLM fast dissolving tablets (TLM-FDT) that would boost the drug's bioavailability by increasing pre-gastric absorption. The TLM-FDTs were developed using a Box-Behnken experimental design with varied doses of crospovidone (CP), croscarmellose sodium (CCS) as super-disintegrants, and camphor as a sublimating agent. In addition, the current study used response surface approach to explore the influence of various formulation and process factors on tablet qualities in order to verify an optimized TLM-FDTs formulation. The optimized TLM-FDTs formula was subsequently evaluated for its in vivo anti-inflammatory activity. TLM-FDTs have good friability, disintegration time, drug release, and wetting time, as well as fast disintegration and dissolution behavior. Significant increase in drug bioavailability and reliable anti-inflammatory efficacy were also observed, as evidenced by considerable reductions in paw thickness in rats following carrageenan-induced rat paw edema. For optimizing and analyzing the effect of super-disintegrants and sublimating agents in the TLM-FDTs formula, the three-factor, three-level full factorial design is a suitable tool. TLM-FDTs are a possible drug delivery system for enhancing TLM bioavailability and could be used to treat rheumatoid arthritis. | |
| 35242041 | Beyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Compl | 2022 | Evidence about the relevance of the complement system, a highly conserved constituent of the innate immunity response that orchestrates the elimination of pathogens and the inflammatory processes, has been recently accumulated in many different rheumatologic conditions. In rheumatoid arthritis, complement, mainly the classical pathway, contributes to tissue damage especially in seropositive subjects, with complement activation occurring in the joint. Data about complement pathways in psoriatic arthritis are dated and poorly consistent; among patients with Sjögren syndrome, hypocomplementemia exerts a prognostic role, identifying patients at risk of extra-glandular manifestations. Hints about complement involvement in systemic sclerosis have been recently raised, following the evidence of complement deposition in affected skin and in renal samples from patients with scleroderma renal crisis. In vasculitides, complement plays a dual role: on one hand, stimulation of neutrophils with anti-neutrophil cytoplasmic antibodies (ANCA) results in the activation of the alternative pathway, on the other, C5a induces translocation of ANCA antigens, favouring the detrimental role of antibodies. Complement deposition in the kidneys identifies patients with more aggressive renal disease; patients with active disease display low serum levels of C3 and C4. Even though in dermatomyositis sC5b-9 deposits are invariably present in affected muscles, data on C3 and C4 fluctuation during disease course are scarce. C3 and C1q serum levels have been explored as potential markers of disease activity in Takayasu arteritis, whereas data in Behçet disease are limited to in vitro observations. Pregnancies in women with rheumatologic conditions are still burdened by a higher rate of pregnancy complications, thus the early identification of women at risk would be invaluable. A fine-tuning of complement activation is required from a physiological progression of pregnancy, from pre-implantation stages, through placentation to labour. Complement deregulation has been implicated in several pregnancy complications, such as recurrent abortion, eclampsia and premature birth; low complement levels have been shown to reliably identify women at risk of complications. Given its physiologic role in orchestrating pregnancy progression and its involvement as pathogenic effector in several rheumatologic conditions, complement system is an attractive candidate biomarker to stratify the obstetric risk among women with rheumatologic conditions. | |
| 34792869 | Optimization of Human Mesenchymal Stem Cells for Rheumatoid Arthritis: Implications for Im | 2022 Feb | OBJECTIVE: Seropositive rheumatoid arthritis (RA) is a chronic autoimmune disease that is rarely "cured." Human mesenchymal stem cells (hMSCs) are known to reduce inflammation and restore immune homeostasis. However, methods for predicting therapeutic hMSC potency have not been established. The goal of these studies was to use and refine an ex vivo functional assay that determines potency of hMSCs and can then be validated in clinical trials as a potency measure of hMSCs used therapeutically to treat RA. METHODS: Allogeneic hMSCs were cytokine-stimulated, and a conditioned medium (CM) was harvested. The CM was tested for the potential to attenuate RA CD4+ T cell proliferation using suppression assays. Indoleamine 2, 3-dioxygenase (IDO) mRNA, and protein were quantified in hMSCs as a measure to compare hMSCs across (prior) studies. RESULTS: To mimic a proinflammatory environment that resembles that in RA, interleukin-1(IL1β), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) (alone or in combination) were used to precondition hMSCs. Treating hMSCs with a combination of these cytokines generated a CM "secretome" that suppressed T cell proliferation between 70 and 83%. Forty-eight hours of cytokine preconditioning hMSCs was required to maximize this effect. T cell suppression positively correlated with increases in hMSC cellular IDO mRNA and protein. CONCLUSION: By standardizing assays to measure hMSC effects, their potency on T cell suppression can be quantified. These studies demonstrate that hMSCs can be compared functionally to identify optimal preparation(s) for therapeutic use in RA and that the potency of hMSC-dependent T cell suppression may differ between hMSC donors. Clinical studies are warranted to validate the hypothesis that ex vivo potency in suppressing T cells will positively correlate with a reduction in RA disease activity and increase in immunological quiescence. | |
| 34371516 | Autoantibodies in Patients With Immune-Related Adverse Events From Checkpoint Inhibitors: | 2022 Mar 1 | BACKGROUND: Immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) are sometimes associated with autoantibodies, but we do not know how frequently or whether these autoantibodies are present before ICI initiation. Our aim was to determine the positivity rate of autoantibodies in patients with organ-specific ICI-associated irAEs and determine their value as pretreatment biomarkers. METHODS: We searched for all English, peer-reviewed publications from MEDLINE, Embase, and Cochrane Library through February 20, 2020, and included any publication describing patients with irAEs and reporting results of any autoantibody investigation. Three reviewers independently extracted data, and 1 reviewer verified all data for accuracy and quality of reporting. RESULTS: We identified 515 publications. Most reports described endocrine, rheumatic, gastrointestinal/hepatic, and myositis/myasthenia/myocarditis irAEs. Autoantibodies were present in close to 50% of patients with ICI-associated endocrinopathies. Anti-BP180 was found in more than 50% of patients with skin irAEs. Antibodies were also common in patients with the triad of myositis/myasthenia/myocarditis including striational antibodies (49%), acetylcholine receptor antibodies (40%), and myositis-associated antibodies (27%). Only 11% of patients with arthritis had either rheumatoid factor or cyclic citrullinated peptide antibodies, and only 30% of patients with sicca had Sjögren antibodies. Autoantibodies were also relatively uncommon in patients with hepatitis (antinuclear antibody, 18%) and colitis (perinuclear antineutrophil cytoplasmic antibody, 19%). Some cohort studies analyzing pre-ICI seropositivity suggest there may be a role for autoantibodies as biomarkers of irAEs. CONCLUSIONS: Reported autoantibody positivity is high in irAEs involving the endocrine organs, skin, and muscle, but lower in irAEs affecting other organ systems. Autoantibody investigations in pre-ICI treatment patients have yielded mixed results regarding their utility as a biomarker of irAEs. | |
| 34407928 | Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects | 2022 Feb | OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA. | |
| 35232804 | Frequency of Symptomatic Adverse Events in Rheumatoid Arthritis: An Exploratory Online Sur | 2022 Mar 1 | OBJECTIVE: To generate initial data on the frequency and effect of symptomatic adverse events (AEs) associated with rheumatoid arthritis (RA) drug therapy from the patient perspective. METHODS: We conducted an exploratory online survey asking patients with RA to indicate whether they currently or had ever experienced the 80 different symptomatic AEs included in the Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Results were summarized to report their frequency, and regression models were used to estimate their associations with RA medication use and overall bother. RESULTS: The 560 patients who completed the survey and reported taking ≥ 1 RA medication (disease-modifying antirheumatic drugs [DMARDs], steroids, nonsteroidal antiinflammatory drugs [NSAIDs]), had a mean disease duration of 8 years, and were on a wide range of DMARDs. The number of symptomatic AEs experienced in the past 7 days was none (6%), 1-10 (28%), 11-20 (28%), and > 20 (38%). Overall, most participants reported that side effects bothered them somewhat (28%), quite a bit (24%), or very much (15%). In multivariable regression analyses, current prednisone and NSAID use were associated with the greatest number of current side effects (26 and 22, respectively). Many of the strongest associations between current symptomatic AEs and medication use aligned with known side effect profiles. CONCLUSION: In this exploratory online survey, patients with RA reported frequent symptomatic AEs with their medications that are bothersome. Further work is needed to develop and validate a measure for use in patients with rheumatic disease. | |
| 35595051 | Significance of IL-7 and IL-7R in RA and autoimmunity. | 2022 May 17 | While physiological levels of IL-7 are essential for T cell proliferation, survival and co-stimulation, its escalated concentration has been associated with autoimmune diseases such as Rheumatoid arthritis (RA). Expression of IL-7 and IL-7R in RA monocytes is linked to disease activity score and TNF transcription. TNF stimulation can modulate IL-7 secretion and IL-7R frequency in myeloid cells, however, only IL-7R transcription levels are downregulated in anti-TNF responsive patients. Elevated levels of IL-7 in RA synovial tissue and fluid are involved in attracting RA monocytes into the inflammatory joints and remodeling them into proinflammatory macrophages and mature osteoclasts. Further, IL-7 amplification of RA Th1 cell differentiation and IFNγ secretion, can directly prime myeloid IL-7R expression and thereby exacerbate IL-7-mediated joint inflammatory and erosive imprints. In parallel, IL-7 accentuates joint angiogenesis by expanding the production of proangiogenic factors from RA macrophages and endothelial cells. In preclinical models, blockade of IL-7 or IL-7R can effectively impair joint inflammation, osteoclast formation, and neovascularization primarily by impeding monocyte and endothelial cell infiltration as well as inhibition of pro-inflammatory macrophage and Th1/Th17 cell differentiation. In conclusion, disruption of IL-7/IL-7R signaling can uniquely intercept the crosstalk between RA myeloid and lymphoid cells in their ability to trigger neovascularization. | |
| 35487762 | A robust Bayesian bias-adjusted random effects model for consideration of uncertainty abo | 2022 Apr 29 | Meta-analysis is a statistical method used in evidence synthesis for combining, analyzing and summarizing studies that have the same target endpoint and aims to derive a pooled quantitative estimate using fixed and random effects models or network models. Differences among included studies depend on variations in target populations (ie, heterogeneity) and variations in study quality due to study design and execution (ie, bias). The risk of bias is usually assessed qualitatively using critical appraisal, and quantitative bias analysis can be used to evaluate the influence of bias on the quantity of interest. We propose a way to consider ignorance or ambiguity in how to quantify bias terms in a bias analysis by characterizing bias with imprecision (as bounds on probability) and use robust Bayesian analysis to estimate the overall effect. Robust Bayesian analysis is here seen as Bayesian updating performed over a set of coherent probability distributions, where the set emerges from a set of bias terms. We show how the set of bias terms can be specified based on judgments on the relative magnitude of biases (ie, low, unclear, and high risk of bias) in one or several domains of the Cochrane's risk of bias table. For illustration, we apply a robust Bayesian bias-adjusted random effects model to an already published meta-analysis on the effect of Rituximab for rheumatoid arthritis from the Cochrane Database of Systematic Reviews. |