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Existing challenges with the early diagnosis of rheumatoid arthritis (RA) and active disease, mainly by non-rheumatologists, have prompted the search for novel biomarkers. Elevations in indices derived from blood cell counts, e.g., the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), have been reported in RA patients. However, their diagnostic accuracy has not been comprehensively assessed. Therefore, we conducted a systematic review and meta-analysis of studies reporting the sensitivity and specificity of the NLR and PLR, obtained by receiver operating characteristic (ROC) curve analysis, for the presence of RA and active disease. We searched electronic databases from inception to 15 March 2024 and assessed the risk of bias using the JBI Critical Appraisal Checklist (PROSPERO registration number: CRD42024533546). In 15 studies, the NLR exhibited acceptable accuracy for the presence of RA (area under the curve, AUC = 0.76, 95% CI 0.72 to 0.80) and active disease (AUC = 0.70, 95% CI 0.66 to 0.74). The PLR exhibited good accuracy for the presence of RA (AUC = 0.80, 95% CI 0.76 to 0.83). There were insufficient studies to assess the accuracy of the PLR for the presence of active disease. Our systematic review and meta-analysis suggests that the NLR and the PLR are promising biomarkers of RA (NLR and PLR) and active disease (NLR). Further research is required to investigate whether the NLR and PLR can significantly enhance the capacity to diagnose RA and active disease in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effectiveness of a novel digital patient education (PE) programme in improving self-management in patients newly diagnosed with rheumatoid arthritis (RA). Methods This was a parallel, open-label, two-armed, randomized controlled trial with superiority design. Patients from five rheumatology clinics were randomized into digital PE (intervention) or face-to-face PE (control). The primary outcome was self-efficacy, measured by average difference in the Rheumatoid Arthritis Self‐Efficacy (RASE) score from baseline to month 12. Secondary outcomes were RA knowledge, health literacy, adherence and quality of life. Healthcare utilization data and digital PE programme usage were recorded. Self-efficacy, knowledge and health literacy data were analysed using mixed-effects repeated measures modelling; adherence using logistic regression, and quality of life and healthcare utilization using descriptive statistics with the Wilcoxon rank-sum test. Results Of the 180 patients randomized (digital PE, n  = 89; face-to-face PE, n  = 91), 175 had data available for analysis. Median age was 59.0 years and 61% were women. The average difference in self-efficacy between groups from baseline to month 12 was significant by a −4.34 difference in RASE score, favouring the intervention group (95% CI: −8.17 to −0.51; P  = 0.026). RA knowledge, health literacy and quality of life showed minor improvements over time but no difference between groups, except out-patient clinic contacts, which were fewer in the intervention group. Conclusion The findings suggest that digital PE is effective in improving self-efficacy and therefore self-management in patients with early RA. This intervention has potential to lower healthcare costs by decreasing out-patient clinic contacts. Trial registration number clinicaltrials.gov , NCT04669340. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical characteristics of patients who presented with concomitant carpal tunnel syndrome (CTS) at the initial diagnosis with rheumatoid arthritis (RA). Methods: We analyzed patients with newly diagnosed RA at a single institution between 2012 and 2021. Patient demographic and laboratory data, the 2010 ACR/EULAR classification criteria, and the duration from the initial visit to RA diagnosis were compared between RA patients with concomitant CTS (RA with CTS group) and those without CTS (RA without CTS group). Results: The study included 235 patients (157 females), of which 11 patients (4.7%) presented with CTS at the initial diagnosis with RA. In the RA with CTS group, the age was significantly higher (P = .033), all patients were female, and anti-cyclic citrullinated peptide antibody (ACPA) was negative, and the duration to RA diagnosis was longer than in the RA without CTS group. Among all RA with CTS patients, ultrasonography showed power Doppler signal-positive tenosynovitis in the carpal tunnel, which is not usually detected in idiopathic CTS. Conclusions: Patients with concomitant CTS at the initial diagnosis with RA were characterized by old age, female sex, and negative ACPA. Patients with symptoms of CTS should undergo ultrasonography for early diagnosis of RA. [ABSTRACT FROM AUTHOR]

Background: Administrative healthcare databases, such as Medicare, are increasingly used to identify groups at risk of a crash. However, they only contain information on crash-related injuries, not all crashes. If the driver characteristics associated with crash and crash-related injury differ, conflating the two may result in ineffective or imprecise policy interventions. Methods: We linked 10 years (2008–2017) of Medicare claims to New Jersey police crash reports to compare the demographics, clinical diagnoses, and prescription drug dispensings for crash-involved drivers ≥ 68 years with a police-reported crash to those with a claim for a crash-related injury. We calculated standardized mean differences to compare characteristics between groups. Results: Crash-involved drivers with a Medicare claim for an injury were more likely than those with a police-reported crash to be female (62.4% vs. 51.8%, standardized mean difference [SMD] = 0.30), had more clinical diagnoses including Alzheimer's disease and related dementias (13.0% vs. 9.2%, SMD = 0.20) and rheumatoid arthritis/osteoarthritis (69.5% vs 61.4%, SMD = 0.20), and a higher rate of dispensing for opioids (33.8% vs 27.6%, SMD = 0.18) and antiepileptics (12.9% vs 9.6%, SMD = 0.14) prior to the crash. Despite documented inconsistencies in coding practices, findings were robust when restricted to claims indicating the injured party was the driver or was left unspecified. Conclusions: To identify effective mechanisms for reducing morbidity and mortality from crashes, researchers should consider augmenting administrative datasets with information from police crash reports, and vice versa. When those data are not available, we caution researchers and policymakers against the tendency to conflate crash and crash-related injury when interpreting their findings. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients. Methods: Patients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA). Results: A total of 480 patients with RA were included in the study (90% female, with the largest number in the 45-59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795-0.9498) and 0.907 (95% CI: 0.8552-0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility. Conclusion: This study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients. [ABSTRACT FROM AUTHOR]

Objectives Extracellular vesicles (EVs) are abundant in body fluids, contributing to intercellular signalling by transferring cargo that includes microRNAs (miRs)—themselves implicated in pathobiology. For the first time we evaluated the potential of EV miRs to contribute diagnostic information in early RA, predict methotrexate (MTX) efficacy or shed light on the drug's mechanism of action. Methods Seven hundred and ninety-eight miRs isolated from serum-derived EVs of 46 patients with untreated RA, 23 with untreated polymyalgia rheumatica (PMR; inflammatory disease control group) and 12 in whom significant inflammatory disease had been excluded (non-inflammatory controls; NICs) were profiled (NanoString); the same measurements were made for RA patients after 6 months' MTX treatment. Analyses took multiple testing into account. Results Twenty-eight EV miRs were robustly differentially expressed between early RA (but not PMR) patients and NICs after correction for age and sex, suggesting discriminatory value. Cross-validated partial least squares-discriminant analysis also indicated the predictive potential of a distinct baseline EV miR signature with respect to MTX-induced remission at 6 months. The change in expression of 13 miRs over the course of MTX treatment differed significantly between responders and non-responders, and four of those exhibiting increased relative abundance amongst responders have known roles in regulating the pathogenic potential of synovial fibroblasts, namely miR-212-3p, miR-338-5p, miR-410-3p and miR-537. Conclusion Our data highlight the potential of serum EV miRs as diagnostic and therapeutic biomarkers, highlighting a novel potential mechanism by which MTX may exert its therapeutic effect in early RA that warrants further investigation. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis. Materials and methods:. The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL). Results and discussion:. Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(–) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691–0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%. In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(–) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(–) RA group. Conclusions:. We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(–) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more "erosive" subtype of the disease than ACPA(+) anti-CarP(–) patients. In ACPA(–) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(–) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the features of the clinical picture of the disease in patients with ACPA–negative and ACPA-positive variants of rheumatoid arthritis. Materials and methods. : The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the ACPA values, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease, and therapy. The nature of the onset and course of the disease and the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices). Results and discussion. : The study involved 79 patients with ACPA-negative variant of RA and 79 ACPA-positive patients. The age of patients (Me [IR] (in years)) with the ACPA(–) variant was 52 [39; 62]; with the ACPA(+) variant, 54 [42; 62]; the duration of the disease (in months) was 59 [23; 122] and 48 [17; 84], respectively. In ACPA(+) patients, a higher disease activity was determined (by the indices DAS 28crp, DAS28esr, SDAI, CDAI), higher values of C-reactive protein and erythrocyte sedimentation rate, and a greater number of painful and swollen joints (p < 0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(–) (17.7%) patients. Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, whereas a tendency to a higher frequency of neuropathy, sclerites, and episcleritis was revealed in ACPA(–) patients. Conclusions:. In patients with ACPA(–) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less "bright" course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pauci‐immune necrotizing glomerulonephritis (PING) is a small vessel renal vasculitis usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase or proteinase. A small proportion of PING patients do not have ANCA antibodies. A condition known as Pauci‐immune necrotizing glomerulonephritis, or PING for short, is a type of kidney inflammation that affects small blood vessels. This condition is typically linked with the existence of certain antibodies, specifically antineutrophil cytoplasmic antibodies or ANCA, which target myeloperoxidase or proteinase. However, it's worth noting that a minor percentage of individuals diagnosed with PING do not possess these ANCA antibodies. A 24‐year‐old woman with no previous medical history arrived at the ER due to various symptoms including joint pain, fever, difficulty swallowing, and shortness of breath. Despite multiple symptoms suggesting systemic lupus erythematosus (SLE), this diagnosis was ruled out based on the EULAR/ACR 2019 classification criteria and laboratory tests. Other potential diagnoses such as rheumatoid arthritis (RA) and eosinophilic garnulomatosis with polyaniitis (EGPA) were also excluded based on respective criteria. The patient was treated with a 3‐day course of methylprednisolone, followed by prednisolone, which improved her creatinine levels. Subsequent tests for P‐ANCA and C‐ANCA were negative. A kidney biopsy confirmed necrotizing glomerulonephritis, consistent with pauci‐immune vasculitis. A bronchoscopy revealed bleeding and hemorrhage in her lungs, but bacterial culture analysis was negative. The patient was given piperacillin, tazobactam, and vancomycin for septic coverage, as well as intravenous immunoglobulin (IVIg), which led to symptom improvement. [ABSTRACT FROM AUTHOR]

Due to their primary and well-known antiresorptive activity, bisphosphonate (BPs) are commonly prescribed as first-line drugs for osteoporosis treatment. Some reports suggest that they may also possess immunomodulatory and anti-inflammatory properties, along with potential benefits in preventing structural joint damage in inflammatory rheumatic diseases. However, despite the promising outcomes observed with BP use in treating rheumatic disorders, numerous reports have implicated these drugs as potential contributors to the development of arthritis. In this case report, two female patients aged 71 and 55 years who developed arthritis in the wrist and dactylitis in the finger after zoledronic acid infusion are presented. This study is significant because, to our knowledge, one of our patients is the first to have been diagnosed with dactylitis, and the other case is one of the few cases in the literature presenting oligoarticular involvement of joints after zoledronic acid administration. [ABSTRACT FROM AUTHOR]

A 78-year-old man with a previous diagnosis of rheumatoid arthritis on prolonged treatment with corticosteroids presented with intense and progressive pain at the cervical level that prevented him from resting his head and walking, in addition to an ulcerative lesion covering 80% of the lingual area that was previously treated as oral candidiasis without improvement. On arrival, with no clinical or serological data of rheumatoid arthritis, immunosuppressive treatment was suspended, and a biopsy of the oral cavity was requested, confirming the diagnosis of lingual tuberculosis, an extremely rare disease, occurring in less than 1% of extrapulmonary cases. MRI of the cervical spine showed a crush fracture of the C6 and C7 bodies associated with spondylitis of probably infectious etiology that required surgical treatment, and histopathological studies confirmed Pott's disease. The patient displayed no evidence of pulmonary tuberculosis from arrival until the end of the follow-up. [ABSTRACT FROM AUTHOR]

Objectives: Rheumatoid arthritis (RA) is a severe and common autoimmune disease. Conventional diagnostic methods are often subjective, error-prone, and repetitive works. There is an urgent need for a method to detect RA accurately. Therefore, this study aims to develop an automatic diagnostic system based on deep learning for recognizing and staging RA from radiographs to assist physicians in diagnosing RA quickly and accurately. Methods: We develop a CNN-based fully automated RA diagnostic model, exploring five popular CNN architectures on two clinical applications. The model is trained on a radiograph dataset containing 240 hand radiographs, of which 39 are normal and 201 are RA with five stages. For evaluation, we use 104 hand radiographs, of which 13 are normal and 91 RA with five stages. Results: The CNN model achieves good performance in RA diagnosis based on hand radiographs. For the RA recognition, all models achieve an AUC above 90% with a sensitivity over 98%. In particular, the AUC of the GoogLeNet-based model is 97.80%, and the sensitivity is 100.0%. For the RA staging, all models achieve over 77% AUC with a sensitivity over 80%. Specifically, the VGG16-based model achieves 83.36% AUC with 92.67% sensitivity. Conclusion: The presented GoogLeNet-based model and VGG16-based model have the best AUC and sensitivity for RA recognition and staging, respectively. The experimental results demonstrate the feasibility and applicability of CNN in radiograph-based RA diagnosis. Therefore, this model has important clinical significance, especially for resource-limited areas and inexperienced physicians. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life‐threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life‐threatening evolution and to derive patient subsets accordingly. Methods: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult‐Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life‐threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. Results: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life‐threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07–1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life‐threatening evolution (OR 3.36; 95% CI 1.81–6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48–2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14–4.49; P = 0.042) both significantly predicted life‐threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. Conclusion: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life‐threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted. [ABSTRACT FROM AUTHOR]

Objectives Paraneoplastic arthritis (PA) is one of the paraneoplastic syndromes. Both laboratory and clinical findings similar to rheumatological diseases can be seen. In this study we aimed to present the clinical and laboratory findings, malignancy types and pathological diagnoses of patients with paraneoplastic arthritis. Methods In a multicentre retrospective study, 92 patients with PA from the last 10 years were included. Results Patients with PA and haematological malignancies exhibited the highest ratio of lymphomas (25.6%). The most common cancer detected in patients with solid malignancy and PA was lung cancer (41.5%). All malignant patients with PA had significant anti-CCP positivity compared with the healthy control group (P  = 0.014). Conclusion Although PA is a rare condition, it can be confused with many rheumatological diseases. The most commonly involved joint is the knee joint, followed by the ankle and hand/wrist. Autoantibody negativity, high lactate dehydrogenase level and arthritis unresponsive to treatment constitute important clues for diagnosis. [ABSTRACT FROM AUTHOR]

Background Hashimoto's thyroiditis (HT) is an autoimmune disease that is frequently associated with other autoimmune conditions. Objective To perform serological screening for rheumatoid arthritis (RA) in patients with HT. Methods Our study included 88 consecutive serum specimens of patients with confirmed HT and 88 sex- and age-matched healthy subjects. All study participants were tested for anti-cyclic citrullinated peptides antibodies (CCP-Ab) and rheumatoid factor (RF). CCP-Ab and RF were performed using ELISA commercial kits. Statistical analysis was conducted using Epi Info, version 3. Results Out of 88 patients with HT, 15 (17.0%) had CCP-Ab or RF. The frequency of serological markers of RA was significantly higher in patients than in control individuals (17.0% vs 4.5%; P =.007). RF was more frequent in patients than in the control group, and the difference was statistically significant (13.6% vs 3.4%; P =.01). Isolated RF-IgM was absent in all controls and present in 6 patients with HT (6.8% vs 0%; P =.02). Out of 14 male patients, 3 (21.4%) had antibodies of RA. There was no significant difference in age between patients with CCP-Ab or RF and those without. Conclusion A high frequency of serological markers of RA was highlighted in patients with HT. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to research the frequency of Human Leukocyte Antigen (HLA)-B27 antigen positivity and relationship between HLA-B27 positivity and other autoantibodies and between HLA-B27 positivity and treatment in patients diagnosed with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Material and Method: The study is a retrospective study. Patients diagnosed with RA and AS as a result of the examinations performed at Physical Medicine and Rehabilitation outpatient clinic between January 2017 and September 2022 were retrospectively screened, and patients whose HLA-B27 antigen was tested were included in study. Results: A total of 569 patients, 199 with RA and 370 with AS were included in study. While HLA-B27 was positive in 11% of patients with RA, it was 37.5% in patients with AS and there was a significant difference between the groups. When we analyzed the correlation of autoantibodies with HLA-B27, we found that HLA-B27 was not correlated with RF, Anti-cyclic citrullinated peptides (Anti-CCP) or Anti-nuclear antibody (ANA). When we analyzed the relationship between HLA-B27 and the treatment method, there was no significant relationship between HLA-B27 and treatment method. Conclusion: While HLA-B27 was found to be 5% positive in the general population in the literature, we found 11% in 199 patients with RA. This study is important because it shows that HLA-B27 positivity is not very common in patients diagnosed with AS recently contrary to popular belief. More studies are needed to evaluate HLA-B27 frequency in RA and AS. [ABSTRACT FROM AUTHOR]

Objectives Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. Methods The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Results Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD. Conclusion In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline. [ABSTRACT FROM AUTHOR]

Background: The early diagnosis and treatment of rheumatoid arthritis (RA) are essential to prevent joint damage and enhance patient outcomes. Diagnosing RA in its early stages is challenging due to the nonspecific and variable clinical signs and symptoms. Our study aimed to identify the most predictive features of hand ultrasound (US) for RA development and assess the performance of machine learning models in diagnosing preclinical RA. Methods: We conducted a prospective cohort study with 326 adults who had experienced hand joint pain for less than 12 months and no clinical arthritis. We assessed the participants clinically and via hand US at baseline and followed them for 24 months. Clinical progression to RA was defined according to the ACR/EULAR criteria. Regression modeling and machine learning approaches were used to analyze the predictive US features. Results: Of the 326 participants (45.10 ± 11.37 years/83% female), 123 (37.7%) developed clinical RA during follow-up. At baseline, 84.6% of the progressors had US synovitis, whereas 16.3% of the non-progressors did (p < 0.0001). Only 5.7% of the progressors had positive PD. Multivariate analysis revealed that the radiocarpal synovial thickness (OR = 39.8), PIP/MCP synovitis (OR = 68 and 39), and wrist effusion (OR = 12.56) on US significantly increased the odds of developing RA. ML confirmed these US features, along with the RF and anti-CCP levels, as the most important predictors of RA. Conclusions: Hand US can identify preclinical synovitis and determine the RA risk. The radiocarpal synovial thickness, PIP/MCP synovitis, wrist effusion, and RF and anti-CCP levels are associated with RA development. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to investigate the diagnostic values of different musculoskeletal ultrasound (MSUS) signs, serum uric acid (SUA), and their combined detection for gouty arthritis (GA). Patients and methods: In this retrospective study, 70 patients (62 males, 8 females; mean age: 46.1±14.1 years; range, 25 to 86 years) diagnosed with GA (the GA group) between August 2022 and March 2023 and 70 patients (54 females, 16 males; mean age: 49.0±14.1 years; range, 21 to 75 years) diagnosed with rheumatoid arthritis and osteoarthritis during the same period (the non-GA group) were included. The positive rate of MSUS signs and SUA in both groups was recorded to compare the differences. The correlations of MSUS signs and SUA with GA were analyzed using Spearman's rank correlation analysis. The diagnostic values of different MSUS signs, SUA, and their combined detection for GA were analyzed using a receiver operating characteristic, the area under the curve (AUC), sensitivity, specificity, and the Youden index. Results: The positive rate of the double contour (DC) sign (chi-squared [Χ²]=102.935, p<0.001), hyperechoic spots (Χ²=56.395, p<0.001), bone erosions (Χ²=10.080, p<0.001), and SUA (Χ²=41.117, p<0.001) were higher in the GA group than in the non-GA group. The positive rate of the DC sign (rs=0.829, p=0.001), hyperechoic spots (rs=0.631, p<0.001), bone erosion (rs=0.268, p=0.001), and SUA (rs=0.542, p<0.001) were positively correlated with GA. Among the single-indicator measures, the DC sign exhibited the highest diagnostic value (AUC=0.907, sensitivity=81.4%, specificity=100%, p<0.001). Among the combined-indicator measures, the DC sign combined with SUA exhibited the highest diagnostic value (AUC=0.929, sensitivity=91.4%, specificity=94.3%, p<0.001), higher than DC sign detection alone. Conclusion: The DC sign combined with SUA yielded a high diagnostic value and can thus provide a reliable basis for effectively and efficiently diagnosing GA. [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G‐PROB) has been developed to aid diagnosis has not yet been tested in a real‐world setting. Our aim was to assess whether G‐PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. Methods: Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G‐probabilities (0%–100%) were created for each patient based on known disease‐associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or "other diseases." Performance of the G‐probabilities compared with clinician diagnosis was assessed. Results: We tested G‐PROB on 1,047 patients. Calibration of G‐probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G‐probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84–0.86). G‐probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G‐probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G‐probability corresponded to clinician diagnosis. Conclusion: G‐PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease frequently treated with immunosuppressive agents such as methotrexate (MTX). Although MTX is generally well-tolerated, it can lead to adverse effects, including renal impairment. We present a case of a patient with newly diagnosed RA who developed severe renal impairment shortly after initiating MTX therapy. A 50-year-old male with recently diagnosed RA presented with vomiting, skin itching, mouth ulcers, and a pruritic rash, all occurring shortly after starting MTX treatment. These symptoms led to acute kidney injury (AKI), necessitating hemodialysis. The patient's symptoms and laboratory findings were indicative of ANCA-associated small-vessel vasculitis with a picture of rapidly progressive glomerulonephritis (RPGN). Treatment included discontinuation of MTX, hemodialysis, immunosuppressive therapy with corticosteroids and cyclophosphamide, and patient education. This case emphasizes the need for close monitoring of RA patients initiated on MTX therapy and prompt evaluation of renal function. Clinicians should be vigilant for signs of renal impairment and be prepared to initiate appropriate interventions, including discontinuation of MTX and consideration of immunosuppressive therapy, to optimize patient outcomes. Further research is warranted to understand better the mechanisms underlying renal complications in RA patients receiving MTX treatment. [ABSTRACT FROM AUTHOR]

Objective Anti-peptidyl arginine deaminase 4 (anti-PAD4) antibody has been a subject of investigation in RA in the last two decades. This meta-analysis investigated the diagnostic values, association with disease activity and possible risk factors of anti-PAD4 antibody in rheumatoid arthritis. Method We searched studies from five databases up to 1 December 2022. Bivariate mixed-effect models were used to pool the diagnostic accuracy indexes, and the summary receiver operating characteristics (SROC) curve was plotted. The quality of diagnostic studies was assessed using QUADAS-2. Non-diagnostic meta-analyses were conducted using the random-effects model. Sensitivity analysis, meta-regression, subgroup analyses and Deeks' funnel plot asymmetry test were used to address heterogeneity. Result Finally, 24 journal articles and one letter were included. Anti-PAD4 antibody had a good diagnostic value between RA and healthy individuals, but it might be lower between RA and other rheumatic diseases. Moreover, anti-PAD4 could slightly enhance RA diagnostic sensitivity with a combination of ACPA or ACPA/RF. Anti-PAD4 antibody was positively correlated with HLA-SE and negatively correlated with ever or current smoking in patients with RA. RA patients with anti-PAD4 antibody had higher DAS28, ESR, swollen joint count (SJC) and the possibility of having interstitial lung disease (ILD) and pulmonary fibrosis compared with those without. Conclusion Our study suggests that anti-PAD4 antibody is a potentially useful diagnostic biomarker and clinical indicator for RA. Further mechanistic studies are required to understand the impact of HLA-SE and smoking on the production of anti-PAD4 antibody. [ABSTRACT FROM AUTHOR]

Objectives To investigate the 5-year all-cause mortality in patients with RA compared with the general population. Methods This was a nationwide population-based matched cohort study. RA patients diagnosed between 1996 and the end of 2015 were identified using administrative heath registries and followed until the end of 2020 allowing 5 years of follow-up. Patients with incident RA were matched 1:5 on year of birth and sex with non-RA individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. Results Compared with matched controls in 1996–2000, the risk difference for RA patients ranged from 3.5% (95% CI 2.7%, 4.4%) in 1996–2000 to –1.6% (95% CI –2.3%, –1.0%) in 2011–15, and the relative risk from 1.3 (95% CI 1.2, 1.4) in 1996–2000 to 0.9 (95% CI 0.8, 0.9) in 2011–15. The age-adjusted 5-year cumulative incidence proportion of death for a 60-year-old RA patient decreased from 8.1% (95% CI 7.3%, 8.9%) when diagnosed in 1996–2000 to 2.9% (95% CI 2.3%, 3.5%) in 2011–15, and for matched controls from 4.6% (95% CI 4.2%, 4.9%) to 2.1% (95% CI 1.9%, 2.4%). Excess mortality persisted in women with RA throughout the study period, while the mortality risk for men with RA in 2011–15 was similar to their matched controls. Conclusions Enhanced improvement in mortality was found in RA patients compared with matched controls, but for sex-specific differences excess mortality was only persistent in women with RA. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are widely recognized in the pathogenesis of autoimmune disease. As a key regulatory factor, miRNAs have introduced new biomarkers for the early diagnosis of rheumatoid arthritis (RA) and provided a favorable research direction for the development of novel therapeutic targets. This study aimed to explore the hotspots of miRNA research related to RA published from different countries, organizations, and authors. Methods: From 2001 to 2022, publications on miRNA related to RA were identified in the Web of Science database. The total and annual number of publishments, citations, impact factor, H‐index, productive authors, and involved journals were collected for quantitative and qualitative comparisons. Results: A total of 29 countries/regions in the world have participated in the research of miRNAs and RA over the past two decades, and China (760, 53.18%) and the United States (233, 16.31%) account for the majority of the total publications. China dominated in total citation (17881) and H‐index (62). A total of 507 academic journals have published articles in related fields, and Frontiers in Immunology published the most (53, 3.71%). Chih‐hsin Tang of the China Medical University has published the most papers (16, 1.2%). Stanczyk (2008) published the most cited article Altered expression of miRNAs in synovial fibroblasts and synovial tissue in rheumatoid arthritis in Arthritis and Rheumatism, with 660 citations. Inflammation is the high‐frequency keyword outside of RA and miRNAs, and related researches have mainly focused on miR‐146a and miR‐155. Conclusions: In the past two decades, extensive and continuous research has been conducted to investigate the role of miRNAs in RA, and miRNAs are widely recognized in the pathogenesis of RA. Related research has mainly focused on miR‐146a and miR‐155 that have shown promising results as key factors in RA experimental models. Focusing on clinical applications and translational research may be the future research direction and hotspot based on molecular biology basic research and mechanism exploration. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRs) are defined as noncoding small RNAs that are involved in the regulation of various immune functions, indicating they could be possible biomarkers for immune-mediated disorders. We aimed to evaluate miR-124a and miR-34a levels in serum as diagnostic biomarkers for rheumatoid arthritis (RA) and to investigate their correlation with the disease activity in RA patients. Methods: Our study consisted of 40 patients with RA and 40 controls. The disease activity for the RA patients was evaluated using the Disease Activity Score in 28 joints (DAS28). Relative quantification of miR‑124a and miR‑34a expressions in serum was conducted by reverse transcriptase quantitative real-time polymerase chain reaction. Results: Expression levels of miR-124a and miR-34a in serum were significantly lower in RA patients (median: 0.64 and 0.30, respectively) compared to controls (median: 3.12 and 1.88, respectively), P < 0.001. Their serum levels were negatively associated with disease activity and inversely correlated with DAS28, C‑reactive protein, and erythrocyte sedimentation rate (P < 0.001). Conclusion: Serum miR-124a and miR-34a could serve as potential noninvasive biomarkers for RA diagnosis and reflect the disease activity in RA patients [ABSTRACT FROM AUTHOR]

Background and Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually destroyed. Early diagnosis and treatment before joint deformation or destruction is important. The detection of novel RA biomarkers in saliva may facilitate early detection of RA before disease onset. This study aimed to evaluate salivary concentration of α1-antitrypsin (A1AT) in healthy patients and those with RA, and to assess the diagnostic value of salivary A1AT. Materials and Methods: In total, 80 participants were included: 20 healthy participants, and 60 patients with RA. Saliva and serum samples were obtained from all the patients. Levels of A1AT and cytokines, including interleukin-1 beta (IL-1β), IL-6, and IL-10 in saliva and serum, were evaluated using an enzyme-linked immunosorbent assay kit and Luminex assay. Data were analyzed using SPSS for Windows. Results: There was a higher level of A1AT in the saliva of patients with RA (median: 2388.66 ng/mL) than that in healthy controls (1579.06 ng/mL). There was a positive mild-to-moderate accuracy (area under the curve: 0.57–0.85) of A1AT in saliva to diagnose RA. The cut-off level (ng/mL) of A1AT in saliva for detecting RA was 1689.0. Conclusions: The obtained data can promote the application of the measurements of A1AT in saliva to diagnose RA. [ABSTRACT FROM AUTHOR]

Objective: Spinal involvement in rheumatoid arthritis (RA) is limited to the upper cervical spine, leading to cervical spine instability. This study aimed to evaluate the prevalence of anterior atlantoaxial subluxation (aAAS) and its associated risk factors in patients with RA. Method: This single‐centre cross‐sectional study 240 patients consecutively were recruited. Radiographs of the cervical spine were obtained in the flexion and neutral neck positions and read by two blinded observers. The diagnosis of aAAS was based on the distance between the anterior aspect of the dens and the posterior aspect of the anterior arch of the atlas, which was >3 mm during flexion. Statistical analysis was performed to determine the predictive factors of aAAS. Results: Two hundred and forty patients with a mean ± SD age of 56.4 ± 11.4 years were recruited, and 191 (78%) were female. The mean ± SD duration of the disease was 10.2 ± 8.5 years. Of all 25 cases (10.4%) diagnosed with aAAS, the mean anterior atlantodental interval in patients with AAS was 4.19 ± 1.20 mm. One in three patients with aAAS had no neck pain. Patients with aAAS had longer disease duration, lower age at diagnosis, lower body mass index, higher anti‐cyclic citrullinated peptide autoantibodies (anti‐CCP), more frequent erosion, joint restriction, and joint prostheses. In the multivariate regression model, joint limitation, history of joint prostheses, low BMI, and higher anti‐CCP levels were independent predictors of the aAAS. Conclusion: Thirty‐three percent of patients with cervical involvement do not experience neck pain. Cervical involvement should be considered even without neck pain, particularly in established diseases. [ABSTRACT FROM AUTHOR]

Physical therapists (PTs) should know how to best treat patients with inflammatory arthritis. To document interventions chosen by PTs for patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and whether choices follow evidence-based practice. Licensed musculoskeletal PTs in Quebec, Canada responded to an online survey. Descriptive statistics illustrated proportions for each treatment choice and inferential statistics explored associations with demographic and practice-related factors. There were 298 PTs who responded to the survey. For both RA and AS respectively, most common interventions were mobility exercises (91.0%; 98.3%) and patient education (90.1%; 92.8%). For both cases, slightly >60% selected strengthening exercises. Passive forms of therapy were chosen by 36% of PTs for RA and 58% for AS. Aerobic exercise was rarely selected. PTs working in the public sector were less likely to use manual therapy for both RA (Odds Ratio (OR) 0.43, 95% confidence interval (CI) 0.22,0.86) and AS (OR 0.46, 95% CI 0.22,0.97). Most PTs chose mobility exercises and patient education, representing evidence-based approaches. Despite current recommendations, strengthening and especially aerobic exercises were not used as much. There is a need to increase awareness regarding the benefits of strengthening and aerobic exercise for these patients. [ABSTRACT FROM AUTHOR]

Objective To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA. Methods A cohort of 275 patients with early RA, recruited in 2012–2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0–100 mm). Unacceptable pain was defined as VAS pain >40, and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis. Results After 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures. Conclusion A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA. [ABSTRACT FROM AUTHOR]

Objective Monoclonal gammopathy of undetermined significance (MGUS) is common, but there are scarce data regarding the effect of DMARDs on this premalignant condition. We aimed to evaluate the impact of JAK inhibitors (JAKis) on MGUS when initiated for an active rheumatic disease. Methods Patients with monoclonal abnormality prior to JAKi initiation for an active rheumatic disease were identified through the MAJIK-SFR Registry, a French multicentre prospective study. Clinical and biological data were collected using a standardized case report form. Results Twenty patients were identified with a mean age of 65 years and a diagnosis of RA (n  = 15), PsA (n  = 3), and axial SpA (n  = 2). The JAKi prescribed was baricitinib (n  = 9), tofacitinib (n  = 6) or upadacitinib (n  = 5), with a mean duration of 15.5 months. Seventeen patients had individualized serum monoclonal protein (IgG kappa n  = 9; IgG lambda n  = 4; IgM kappa n  = 3; IgA lambda n  = 1) ranging from 0.16 to 2.3 g/dl, and three patients did not have an initial measurable spike but they had a positive serum immunofixation. With a follow-up of 4–28 months, the serum monoclonal protein level decreased in 8 of 17 patients (47%), remained stable in 8 patients (47%) and increased in 1 patient (6%). The maximal decrease observed was an initial IgG kappa of 2.3 g/dl, decreasing to 0.2 g/dl at month 14. Conclusion This study provides reassuring and promising data on MGUS evolution in patients treated with JAKis for rheumatic diseases, which may guide the choice of treatment in patients with both conditions. [ABSTRACT FROM AUTHOR]

Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA. [ABSTRACT FROM AUTHOR]

There is an interesting and complex relationship between rheumatic diseases and malignancy. Paraneoplastic arthritis is caused by the effects of many hormones and cytokines secreted from the underlying hidden tumor tissue. There is no direct invasion or mechanical pressure of the tumor tissue. In particular, in the early rheumatological disease period, the diagnosis should be reconsidered in cases unresponsive to conventional treatment. It should be noted that there may be another underlying etiological factor in cases unresponsive to treatment. In this review, we discussed in detail three breast cancer cases that presented with early arthritis and were found to have breast cancer in the follow-up. In the literature, serological markers, pathological diagnosis, and imaging in breast cancer-associated paraneoplastic arthritis cases are not presented in detail. In our cases, serological markers, pathological diagnosis, and breast magnetic resonance imaging are presented in detail. [ABSTRACT FROM AUTHOR]

Background: Detection of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) in sera support the diagnosis of rheumatoid arthritis (RA); however, these markers are not detected in about 20% of RA patients. More recently, antibodies against carbamylated proteins (anti-CarP) have emerged with implications for preclinical RA diagnosis. The objective of this study was to assess the clinical performance of anti-CarP and correlate with disease severity in routine clinical practice. Methods: Retrospective chart review of 331 subjects submitted for RA panel serology: 136 clinically defined RA-positive and 195 RA-negative patients. Fifty additional individuals were recruited for healthy controls. Patients' sera were tested for anti-CCP, anti-CarP, and RF antibodies. Clinical performance characteristics were evaluated for anti-CarP individually and in combination with anti-CCP and RF. Documented erosions and synovitis were correlated with anti-CarP positivity. Results: Anti-CarP had a clinical sensitivity and specificity of 27% and 94%, respectively, for established RA. This sensitivity was lower than anti-CCP (79%) and RF (85%). The specificity of anti-CarP was similar to anti-CCP (93%) and higher than RF (69%). Anti-CarP in combination with anti-CCP and RF increased specificity (100%) but decreased sensitivity (21%). There was no correlation of anti-CarP positivity with presence of bone erosions; however, there was an increase in anti-CarP positivity among patients with synovitis. Conclusions: Anti-CarP demonstrates high specificity in diagnosis of established RA but lacks clinical sensitivity. In combination, anti-CarP does not improve clinical performance of anti-CCP and RF but may be useful in anti-CCP negative patients and in identifying patients with more active disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION Rheumatoid Arthritis (RA) is the most common form of chronic symmetrical inflammatory arthritis and often results in joint damage and physical disability. RA may result in a variety of extra-articular manifestations, including fatigue, subcutaneous nodules, lung involvement pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities. Anti-CCP antibodies are auto antibodies which contains citrulline appears early phase of RA patients. During the course of the disease RA patients need to be diagnosed very early, possibly before diagnostic criteria are fulfilled or may be even before clinical symptoms are apparent. Materials and methods: The study was conducted in the department of Microbiology in a tertiary care hospital after obtaining approval from Institutional Ethical Committee. Samples were collected under aseptic precautions from the patients attending orthopaedic department and general medicine department. The total serum samples were 186 and were tested and interpreted by LA method (SPAN DIAGNOSTICS, SACHIN SURAT) for Rheumatoid factor and anti-CCP antibodies by IMUNOSCAN CCPLUS ELISA (EURODIAGNOSTICA, AB, SWEDEN). Results Among 48 anti-CCP positives in suspected RA cases, females were 33 (68.75%), males were 15 (31.25%). And among 7 ACCP positive in controls, females were 5 (71.43 %) and males were 2 (28.57 %). Based on the cut off value >10 IU/ml among 80 clinically suspected cases of RA, 50 sera were positive for RF by LA. In 106 participants who are controls, only 23 (21.7%) samples were positive. The prevalence is 43%. The sensitivity was 62.50%. The specificity was 78.3 %. Among 50 rheumatoid factor positives in case group, 48 sera were positive for anti-CCP test. Among 23 rheumatoid factor positives in control group, 7 were positive for anti-CCP test (as shown in table 2). Rheumatoid factor test could showed false positive result and those were observed as negative by anti-CCP test which is specific test. CONCLUSION: The anti-CCP antibody assay is a valuable tool for the classification criteria of RA as they may predict the eventual development into RA when found in undifferentiated arthritis patients. Because of its low sensitivity it does not allow its use as a screening test, but because of its high specificity when compared to Rheumatoid factor, it is one of the most useful specific serological test for the diagnosis of RA. Combined use of RF and anti-CCP is a better tool for the diagnosis of RA. [ABSTRACT FROM AUTHOR]

Background: Assessment of disease activity in rheumatoid arthritis (RA) is crucial to optimize the response to treatment and prevent radiographic progression. DAS28 is the most commonly used disease activity index, which incorporates either erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Several studies showed that using ESR and/or CRP in assessing disease activity falls short of detecting a significant portion of patients with active disease. Calprotectin (CLP) is an interesting protein that was found to be a promising biomarker of disease activity in RA patients' sera when CRP is normal. This study aimed to measure serum CLP level in 50 RA patients with different grades of disease activity and compare its level with age- and sex-matched control. Results: In this case–control study, the mean serum CLP level was significantly lower in RA patients (25.94 ± 25.87 ng/ml) compared to the control group values (53.02 ± 77.93 ng/ml), p < 0.001. The measured serum CLP in RA patients was lower than its level in other published studies. No significant difference was found between patients with different disease activity grades in the serum CLP level (H = 4.28, p = 0.23). Serum samples were collected and stored from RA patients over 4 months and from the control subjects over 1.5 months and were stored at –80 °C until analysis was performed according to the manufacturer's instruction. Conclusion: The low level of serum CLP among RA patients is most probably due to proteolysis related to storage conditions. Pre-analytic factors like the type of blood sample, whether the sample is fresh or frozen, and duration of storage exert an effect on serum CLP level when measured by enzyme-linked immunosorbent assay. [ABSTRACT FROM AUTHOR]

Objective: Developing and evaluating new treatment guidelines for rheumatoid arthritis (RA) based on observational data requires a quantitative understanding of patterns in current treatment practice with biologic and targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs). Methods: We used data from the CorEvitas RA registry to study patients starting their first b/tsDMARD therapy, defined as the first line of therapy, between 2012 and the end of 2021. We identified treatment patterns as unique sequences of therapy changes following and including the first‐line therapy. Therapy cycling was defined as switching back to a treatment from a previously used therapeutic class. Results: A total of 6015 b/tsDMARD‐naïve patients (77% female) were included in the analysis. Their median age was 58 years, and their median disease duration was 3 years. In 2012–2014, 80% of the patients started a tumor necrosis factor inhibitor (TNFi) as their first b/tsDMARD. However, the use of TNFi decreased in favor of Janus kinase inhibitors since 2015. Although the number of treatment patterns was large, therapy cycling was relatively common. For example, 601 patterns were observed among 1133 patients who changed therapy at least four times, of whom 85.3% experienced therapy cycling. Furthermore, the duration of each of the first three lines of therapy decreased over the past decade. For example, the median duration of the first‐line therapy was 153 days in 2018–2021 compared to 208 days in 2015–2017 (P < 0.001). Conclusion: First‐line therapy was almost always TNFi, but diversity in treatment choice was high after that. This practice variation allows for proposing and evaluating new guidelines for sequential treatment of RA. It also presents statistical challenges to compare patients with different treatment sequences. [ABSTRACT FROM AUTHOR]

The article describes the case of a 52-year-old woman diagnosed with ACPA+/RF+ difficult-to-treat erosive rheumatoid arthritis (RA), which had been progressing since 1998. Topics discussed include observation on a synovial biopsy of the knee, results of combined therapy initiation, and a diagnosis of lymph node granulomatosis due to a Tropheryma whipplei infection in an immunocompromised patient.

Introduction: Rheumatoid arthritis is the most common form of chronic systemic inflammatory arthritis. Research participants with a recent diagnosis of RA will have their cardiovascular autonomic functioning assessed by measuring their resting heart rate variability. Materials & Methods: The present study was a case-control investigation undertaken at the Neurophysiology laboratory, specifically within the Department of Physiology, GMC Siddipet, Telangana, India. The study was conducted from June 2022 to May 2023. A total of 20 individuals who had just received a diagnosis of rheumatoid arthritis were selected for participation in this study. These individuals were recruited from the Rheumatology outpatient department at the GMC Siddipet, Telangana, India. Result: In RA patients, the heart rate and systolic blood pressure were higher. Patients with RA had significantly lower SDNN, SDSD, RMSSD, NN50, LF and HF power in nu and total power than healthy controls. Seropositive patients had higher LF power in the normalized unit than seronegative individuals. When compared to seronegative patients, the LF/HF ratio rose in seropositive patients. Seropositive participants had lower HF power in the normalized unit than seronegative subjects did. We also noticed that the study group had higher RF, CRP, and platelet counts, which were related to higher sympathovagal imbalance. This shows how significant these factors are in the development of cardiovascular risk in RA patients. Conclusion: The standard basic investigation of RA can include the straightforward, noninvasive resting HRV analysis. Regular evaluation of the biomarker's platelet count, CRP and RF may aid in the early detection of cardiovascular complications in RA patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to establish whether the Rheumatoid Arthritis Work Instability Scale (RA‐WIS), in its current form, is applicable for use with employed people with fibromyalgia (FM) to identify the risk of work disability and need for work rehabilitation. Methods: Content validity was first investigated using cognitive debriefing interviews. Participants completed a postal questionnaire. Construct validity was assessed using Rasch analysis. Concurrent validity included testing between the RA‐WIS and work (e.g., Workplace Activity Limitations Scale) and health (FM Impact Questionnaire‐Revised (FIQ‐R) scales. Two weeks later, participants were mailed a second questionnaire to measure test‐retest reliability. Results: Interviews were conducted with 13 participants with FM. All RA‐WIS items were considered very or extremely relevant by almost all participants, with only one suggesting other items (anxiety and brain fog). Questionnaire responses were analysed from 156 employed participants: 94% women; 45.71 (SD 10.05) years of age; with time since FM diagnosis 2.99 (4.17) years (symptom duration 8.36 (SD 7.16) years). The RA‐WIS mostly satisfied Rasch model requirements and a Rasch transformation scale was created. Concurrent validity was generally good (rs = 0.55–0.66) with work scales and the FIQ‐R. Internal consistency (Person Separation Index values) was consistent with group use in FM, not individual level use. Test‐retest reliability was excellent, with intraclass coefficient (2, 1) = 0.90. Discussion: The RA‐WIS is valid and reliable for group use in employed people with FM. However, further work is needed to develop a WIS for individual use in FM. [ABSTRACT FROM AUTHOR]

Objective: Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA); however, prior studies have been small and/or uncontrolled; this study aimed to address that gap. Methods: This randomized, double‐blind, sham‐controlled trial enrolled patients aged 18 to 75 years with active RA who had failed conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) and were naïve to biologic and/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C‐reactive protein (DAS28‐CRP) and Health Assessment Questionnaire‐Disability Index (HAQ‐DI). Results: A total of 113 patients (mean age 54 years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation versus 26.9% for sham (difference vs. sham, −1.9; 95% CI, −18.8, 14.9, P = 0.823). The least square mean ± SE change in DAS28‐CRP was −0.95 ± 0.16 for active stimulation and −0.66 ± 0.16 for sham (P = 0.201); in HAQ‐DI it was −0.19 ± 0.06 for active stimulation and −0.02 ± 0.06 for sham (P = 0.044). Adverse events occurred in 17 patients (15%); all were mild or moderate. Conclusion: Auricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility. [ABSTRACT FROM AUTHOR]

Background: Inflammatory pseudotumors (IPTs) are rare benign conditions of unknown etiology that can affect any part of the body. IPTs are most commonly associated with Immunoglobulin G4 (IgG4)-related disease. Central nervous system IPTs, especially with pituitary involvement, are even rarer entities. The presence of an IgG4-negative pituitary IPT with simultaneous extracranial involvement has not been reported. Case report: We present the case of a 41-year-old female with past medical history of rheumatoid arthritis and a diagnosis of pituitary IPT with coexisting sphenoidal (extracranial) involvement mimicking a pituitary macroadenoma at presentation. The patient underwent multiple consecutive biopsies, and an extensive workup prior to establishing the diagnosis. Laboratory work-up showed normal serum IgG4 and unremarkable liver function tests. Conclusion: Pituitary lesions with simultaneous sphenoidal involvement in patients with IgG4-negative systemic inflammatory disease should raise the clinical suspicion for intracranial IPTs, as these tumors can mimic aggressive counterparts causing adjacent bony erosion, and local invasion. [ABSTRACT FROM AUTHOR]

Depression is a common and disabling comorbidity in rheumatoid arthritis that not only decreases the likelihood of remission and treatment adherence but also increases the risk of disability and mortality in patients with rheumatoid arthritis. Compelling data that link immune mechanisms to major depressive disorder indicate possible common mechanisms that drive the pathology of the two conditions. Preclinical evidence suggests that pro-inflammatory cytokines, which are prevalent in rheumatoid arthritis, have various effects on monoaminergic neurotransmission, neurotrophic factors and measures of synaptic plasticity. Neuroimaging studies provide insight into the consequences of inflammation on the brain (for example, on neural connectivity), and clinical trial data highlight the beneficial effects of immune modulation on comorbid depression. Major depressive disorder occurs more frequently in patients with rheumatoid arthritis than in the general population, and major depressive disorder also increases the risk of a future diagnosis of rheumatoid arthritis, further highlighting the link between rheumatoid arthritis and major depressive disorder. This Review focuses on interactions between peripheral and central immunobiological mechanisms in the context of both rheumatoid arthritis and major depressive disorder. Understanding these mechanisms will provide a basis for future therapeutic development, not least in depression. Depression is a common comorbidity in rheumatoid arthritis, and shared immune mechanisms link the two conditions. This Review explores potential peripheral and central interactions between the immune system and brain, the understanding of which could aid in the development of novel therapeutics. Key points: Rheumatoid arthritis (RA) and depression have overlapping features, including similar implicated immuno-mechanistic pathways. Crosstalk between the peripheral immune response and central nervous system provides compelling evidence of a role for immune-mediated inflammation in the pathophysiology of depression, including in RA. Pro-inflammatory molecules can signal to the brain through humoral routes (via the blood–brain barrier and circumventricular organs) and neural routes (via vagal nerve and dorsal root ganglia afferent signalling). Neuroimmune communication in the brain involves the production of inflammatory proteins by both recruited myeloid cells from the periphery and resident microglial cells and can result in activation of glial cells. The peripheral immune system could modulate neurological processes through various mechanisms, including through modulation of the glutamatergic and serotonergic systems, the kynurenine pathway, inflammasome activation and neuroplasticity. Determining the mechanisms that link immune-mediated disorders such as RA with depression should aid in the identification of molecular targets and development of targeted therapy. [ABSTRACT FROM AUTHOR]

Objective: Older adults with rheumatoid arthritis (RA) account for up to one‐third of the RA population and are less likely to receive optimal treatment. For the subgroup of older adults with late‐onset RA (LORA), who experience more symptomatic and progressive disease, suboptimal treatment could be more consequential than the general population who age with RA. We evaluated use of disease‐modifying antirheumatic drugs (DMARDs) in older adults with a new diagnosis of LORA. Methods: In this retrospective observational study, we identified adults 66 years of age or older with a new diagnosis of LORA using Medicare data from 2008 to 2017. Information on baseline patient characteristics and DMARD initiation during the first 12 months after LORA diagnosis were collected. We also assessed concomitant use of glucocorticoids (GCs). Results: We identified 33,373 older adults with new diagnosis of LORA. Average age at LORA diagnosis was 76.7 (SD 7.6); 75.4% were female, 76.9% were White, and 35.6% had low‐income subsidy (LIS). Less than one‐third were initiated on a DMARD (28.9%). In multivariable analyses, DMARD initiation was associated with younger age, fewer comorbidities, and absence of LIS status. Concomitant long‐term (>3 months) GC use was higher among those on any DMARD (44.3%) compared with those without (15.2%). Conclusions: DMARD initiation after new diagnosis of LORA is low despite current clinical practice guidelines recommending early aggressive initiation of treatment. Long‐term GC use is common among those on any DMARDs, raising concern for suboptimal DMARD use. Further studies are needed to understand drivers of DMARD use in older adults. [ABSTRACT FROM AUTHOR]

Background: Despite the recent advances in the management of inflammatory arthritis, a considerable proportion of arthritis patients remain symptomatic. This cohort has recently been identified as 'difficult to treat' (D2T). In view of the limited evidence base, management of these patients has been a challenge particularly in view of its associated significant economic health burden. A better understanding of the D2T may help recognise or develop new therapeutic targets and facilitate earlier intervention in the disease course to prevent the progression of such condition. The aim of this work is to address the unmet needs in the management of D2T arthritis and develop a comprehensive approach towards the identification and proper assessment of those patients. Results: At the completion of round 3 Delphi process, a total of 20 items were obtained and divided into 5 domains. From 88.9 to 100% of respondents agreed with the recommendations (ranks 7–9). All 20 of the clinical standards that the scientific committee identified were agreed upon in terms of wording, recommendation grade, and level of evidence (i.e. 75% of respondents strongly agreed or agreed). Conclusion: D2T inflammatory arthritis remains a relevant clinical challenge, despite the endorsement of the treat-to-target approach and the availability of a broad range of targeted arthritis medications. This study provided a comprehensive definition of the condition to facilitate the identification of this patients' group. It also highlighted the goals and principles aiming at providing an effective framework for D2T assessment, closely monitor and set up a strategy to intervene in standard clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Inflammation around the tendons of the hand interosseous muscles (interosseous tendon inflammation [ITI]) was recently identified on magnetic resonance imaging (MRI) in a set of patients with rheumatoid arthritis (RA) and arthralgia. We conducted a large MRI study to assess the prevalence of ITI at diagnosis of RA and of other arthritides, as well as its relationship with clinical signs. Methods: A total of 1,205 patients presenting with various types of early arthritis between 2010 and 2020 underwent contrast‐enhanced hand MRI as part of the prospective Leiden Early Arthritis Cohort. MRI was evaluated with blinding for clinical data, for ITI lateral of metacarpophalangeal (MCP) joints 2–5, and for synovitis/tenosynovitis/osteitis. We assessed ITI presence at baseline per diagnosis and its relationship with clinical characteristics (ie, presence of hand arthritis, increased acute phase reactants, and local joint swelling and tenderness). Logistic regression and generalized estimating equations were used with adjustment for age and established local inflammation features (synovitis/tenosynovitis/osteitis). Results: A total of 36% of patients with early RA (n = 532) had ITI; this was similar in patients with anti–citrullinated protein antibody (ACPA)‐negative RA (37%) and those with ACPA‐positive RA (34%; P = 0.53). ITI occurred regularly in remitting seronegative symmetrical synovitis with pitting edema (60%) and connective tissue diseases (44%) and less frequently in undifferentiated arthritis (14%), psoriatic arthritis (14%), inflammatory osteoarthritis (8%), reactive arthritis (7%), crystal arthritis (7%), and peripheral spondylarthritis (4%). ITI occurred more often in diagnoses with frequent arthritis of the hands (P < 0.001) and increased acute‐phase reactants (P < 0.001). Within RA, ITI occurred together with local MCP joint synovitis (odds ratio [OR] 2.4, 95% confidence interval [95% CI] 1.7–3.4), tenosynovitis (OR 2.4, 95% CI 1.8–3.3), and osteitis (OR 2.2, 95% CI 1.6–3.1) on MRI. Moreover, ITI presence was associated with local MCP joint tenderness (OR 1.6, 95% CI 1.2–2.1) and swelling (OR 1.8, 95% CI 1.3–2.6), independent of age and MRI‐detected synovitis/tenosynovitis/osteitis. Conclusion: ITI occurs regularly in RA and other arthritides with preferential involvement of hand joints and increased acute‐phase reactants. At the MCP joint level, ITI associates independently with joint tenderness and swelling. Hence, ITI is a newly identified inflamed tissue mainly found in arthritides with particularly extensive and symptomatic inflammation. [ABSTRACT FROM AUTHOR]

Background & Objective: Uncontrolled active rheumatoid arthritis patients have a progressive disability, pain, swelling problems, and stiffness that often lead to systemic complications, early death, socioeconomic costs, and comorbidity. The objectives of this study were to measure the serum levels of Tripartite motifcontaining protein 72 in Iraqi patients with rheumatoid arthritis and healthy individuals, assessment of the efficiency of Tripartite motif-containing protein 72, determine their essential serum rates in association with disease activity, sociodemographic and clinical specifications of the diseases. Materials & Methods: In this case-control study, 117 Iraqi patients with rheumatoid arthritis were investigated according to the 2010 American College of Rheumatology / European League Against Rheumatism from December 2020 to March 2022. The patients were divided into two groups. Group 1 were the RA patients with active disease, Group 2 were the RA patients with inactive disease, and healthy subjects served as the control group. Results: Serum levels of Tripartite motif-containing protein 72 in the active RA groups (101.92±160.18 Pg/mL) were significantly higher as compared with the inactive RA group (64.58±54.34 Pg/mL) and the control group (41.06 ±32.48 Pg/mL) (P˂0.005). Tripartite motif-containing protein 72 could not discriminate between RA and the controls (since its AUC ≥0.689). Conclusion: There was a positive relationship between DAS-28ESR and Tripartite motif-containing protein 72 levels, which induces bone erosion. The serum Tripartite motif-containing protein 72 level showed a significant elevation in rheumatoid arthritis patients compared with healthy controls. Tripartite motifcontaining protein 72 had a poor discriminative ability between RA and the control group. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by inflammatory arthritis and periarticular structural damage. Available evidence suggests that RA results from complex interactions between genetic susceptibility (e.g., HLA-DRB1), environmental factors (e.g., smoking), and immune dysregulation. Alongside joint-related symptoms, individuals with RA may also experience a wide array of skin issues, including the development of nodules, neutrophilic dermatoses, vasculitis, and vasculopathy. Treatment strategies for these manifestations vary but routinely involve corticosteroids, disease-modifying anti-rheumatic drugs, and biologics, with individualized approaches guided by disease severity. In this review, we provide comprehensive insights into the skin-related issues associated with RA, outlining their clinical characteristics and histopathological findings. Our aim is to facilitate early diagnosis and personalized treatment to improve the quality of life of affected individuals. [ABSTRACT FROM AUTHOR]

Multimorbidity, the presence of multiple chronic conditions, is highly prevalent in people with RA. An essential characteristic of multimorbidity is the interrelatedness of the different conditions that may develop in a multimorbid person. Recent studies have begun to identify and describe the Multimorbidity Web by elucidating unique multimorbidity patterns in people with RA. The primary multimorbidity patterns in this web are cardiopulmonary, cardiometabolic, and mental health and chronic pain multimorbidity. Once caught in the Multimorbidity Web, the consequences can be devastating, with reduced quality of life, physical function, survival, and treatment responses observed in multimorbid RA persons. The development of effective management and preventive approaches for multimorbidity in people with RA is in its infancy. Determining how best to assess, intervene, and prevent multimorbidity in RA is crucial to optimize long-term outcomes in people with RA. [ABSTRACT FROM AUTHOR]

This study examined the psychological well-being (PWB) and spiritual well-being (SWB) of older adult individuals with rheumatoid arthritis (RA) who experienced the difficulties of both aging and RA. This descriptive and cross-sectional study was conducted in two centers located in the capital city of Turkey. A total of 136 individuals with a diagnosis of RA who met the inclusion criteria constituted the sample group of the study. Participant Information Form, SWB, and PWB Scales were used for data collection. The results showed that participants' PWB score was positively and significantly difference with marital status, presence of children, and regular participation in social activities. It was concluded that pain severity was not significantly difference with PWB and SWB. However, there was a significant negative correlation between PWB score and total SWB score and its two sub-dimensions, transcendence and anomie. Results emphasize the necessity of supportive interventions to increase psychological and spiritual well-being of older adult individuals with RA. [ABSTRACT FROM AUTHOR]