Diagnosis Of Rheumatoid Arthritis Research Articles

Anti-citrullinated α-enolase peptide as a highly sensitive autoantigen in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease in Taiwan. Anti-cyclic citrullinated peptide (anti-CCP) assay is widely used for RA diagnosis; however, not all anti-CCPs are detectable in RA-joint lesions. Citrullinated α-enolase peptide (CEP), which has a unique immunodominant epitope, can be detected in synovial fluid. Here, we aimed to evaluate the potential of anti-CEP as a serologic marker for the early diagnosis of RA and a prognostic predictor of joint destruction. We also determined the association of single-nucleotide polymorphisms (SNPs) in genes with the serological status and clinical characteristics of RA. Clinical records of 30 patients with RA were collected, and their serum and DNA samples were evaluated using enzyme-linked immunosorbent assay (ELISA) and SNP cross-reaction analysis. A considerable amount of anti-CEP was detected in patients with RA, a trend similar to that of anti-CCP. Moreover, anti-CEP was considerably associated with the protein-arginine deiminase type-2 SNP rs1005753.

The impact of COVID-19 on clinical research: the PIPPRA and MEDRA experience.

Coronavirus disease 2019 (COVID-19) has had a significant impact on clinical research. This paper aims to provide an insight into how the COVID-19 pandemic, associated public health restrictions and international guidance on the conduct of clinical research impacted two clinical rheumatology research trials - the Physiotherapist-led Intervention to Promote Physical Activity in Rheumatoid Arthritis (PIPPRA) and the MEDiterranean diet in Rheumatoid Arthritis (MEDRA) projects. The March 2019 public health restrictions imposed to mitigate the risk of COVID-19 occurred at a time when PIPPRA was in the process of delivering assessment and intervention on a face-to-face basis (n=48) and MEDRA had commenced recruitment. Participants in PIPPRA and MEDRA had a diagnosis of rheumatoid arthritis, with some being immunosuppressed and thus at a higher risk for COVID-19. The decision-making processes of both trials is outlined to demonstrate the required amendments to continue in the context of the COVID-19 pandemic. Amendments to PIPPRA and MEDRA trial protocols were agreed and received ethical and funder approval. Both trials switched from a face-to-face delivery to a telehealth using online platforms. The PIPPRA study was paused for five months (April-August 2020), resulting in n=33 (60%) negative deviations from assessment protocol. MEDRA switched from face-to-face to online recruitment with 20% (n=35/44) negative deviations in recruitment. Of the n=18 participants who consented to participating in a face-to-face trial, just n=2 (11%) opted to engage with telehealth delivery of the intervention. MEDRA assessment and intervention deviations were 100% as no sessions were completed as planned in 2020. The COVID-19 pandemic has severely impacted the PIPPRA and MEDRA clinical trials. Moving face-to-face clinical research to telehealth delivery may not be the panacea it is purported to be. Our experiences may be of benefit to researchers, clinicians, and funders in seeking to continue clinical research during a global pandemic.

Fluoroscopy-based robotics in total hip arthroplasty mitigates laterality-based differences in acetabular cup placement when compared to the manual, fluoroscopic- assisted technique

BACKGROUND: Robotic assistance in total hip arthroplasty (RA-THA) has been shown to minimize laterality-based differences in acetabular cup positioning. OBJECTIVE: To determine if the use of a novel, fluoroscopy-based RA-THA system mitigates differences in acetabular cup placement between left (L) and right (R) side hip procedures, when compared to manual, fluoroscopic-assisted technique. METHODS: We conducted a retrospective review of 106 consecutive mTHA (40 L/66 R) and 102 RA-THA (48 L/54 R) primary direct anterior approach procedures. All cases were performed by a single right-hand-dominant surgeon, for a pre-operative diagnosis of osteoarthritis, avascular necrosis, or rheumatoid arthritis. Outcomes included acetabular cup inclination and anteversion, and the proportion of cups within the Lewinnek safe-zone. RESULTS: The average inclination of mTHA L cases was smaller than that of mTHA R cases (41.10∘± 7.38 vs. 43.97∘± 6.27; p= 0.04). For RA-THA, L and R cup angles were similar. There were fewer overall mTHA hips within the Lewinnek safe-zone compared to RA-THA (0.59 vs. 0.78; p= 0.003), as well as fewer mTHA R cases than RA-THA R cases (0.59 vs. 0.80; p= 0.03) within safe zone. CONCLUSION: Use of a novel, fluoroscopy-based robotic system mitigates laterality-based differences in acetabular cup placement that were observed in a manual, fluoroscopic-assisted cohort.

Fluoroscopy-based robotic assistance for total hip arthroplasty improves acetabular cup placement accuracy for obese patients compared to the manual, fluoroscopic- assisted technique.

Patient obesity is a risk factor for poor acetabular cup positioning in total hip arthroplasty (THA). To assess the impact of using a novel, fluoroscopy-based robotic THA system on acetabular cup placement in obese versus non-obese patients. A review of 105 consecutive manual unassisted (mTHA) (47 Obese/58 Non-obese) and 102 robotic-assisted (RA-THA) (50 Obese/52 Non-obese) primary, direct anterior approach THA procedures was conducted. All cases were performed by a single surgeon, for a pre-operative diagnosis of osteoarthritis, avascular necrosis, or rheumatoid arthritis. Obesity was defined as a Body Mass Index (BMI) ⩾ 30 kg/m2. Outcomes included acetabular cup inclination and anteversion, and the proportion of cups within the Lewinnek safe-zone. Obese patients in the mTHA cohort had larger cup inclination angles on average compared to non-obese patients (44.82∘± 6.51 vs. 41.39∘± 6.75; p= 0.009). Obese mTHA patients were less likely to have cup placement within the Lewinnek zone compared to non-obese mTHA patients (0.48 vs. 0.67; p= 0.027). Obesity had no effect on the accuracy of RA-THA. Obesity affects the placement of the acetabular component in manual THA. The novel, fluoroscopy-based robotic THA system in this study demonstrated accurate cup placement regardless of obesity status.

Association Between Herpes Simplex Virus II Infection and Rheumatoid Arthritis in US Adults: A Population-Based Propensity Score-Matching Study.

The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. A case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.

Abstract 19163: A Rare Case of Pericarditis as an Initial Manifestation of Rheumatoid Arthritis

Case Presentation: A 69-year-old male with a history of chronic recurrent pericarditis presented with a 3-week episode of chest pain. Despite treatment with ibuprofen, colchicine, prednisone, and anakinra, he experienced multiple flares upon attempting to wean off anakinra. His current workup revealed an elevated C-reactive protein and an echocardiogram showing a small pericardial effusion. Cardiac magnetic resonance imaging showed mild pericardial late gadolinium enhancement and increased pericardial signal on T2 STIR imaging, confirming a flare of recurrent pericarditis. The patient was started on rilonacept while being weaned off anakinra. During a follow-up after 3 months, the patient reported new onset polyarthralgia, prompting a referral to rheumatology. Rheumatoid factor was negative, but anti-citrullinated protein antibodies were positive, leading to a diagnosis of rheumatoid arthritis (RA). Azathioprine was added to the treatment regimen alongside rilonacept. Discussion: The patient's recurrent pericarditis was initially considered idiopathic but, with the subsequent RA diagnosis, it was suspected that RA may have been the underlying cause. While pericarditis is a known cardiac complication of RA, it is uncommon for pericarditis to be the initial manifestation of RA. Anakinra and rilonacept are both interleukin-1 (IL-1) inhibitors, with anakinra being FDA-approved for RA treatment. However, rilonacept has not been extensively studied in patients with RA. The case suggests that the use of certain medications may have masked RA symptoms, and as those medications were tapered, the RA symptoms became more evident. This case highlights the possibility of idiopathic pericarditis evolving into an autoimmune etiology, such as RA, over time. The combination of rilonacept and azathioprine for treating RA has limited evidence, emphasizing the need for further research in this area.

Are the cut-offs of the rheumatoid factor and anti-cyclic citrullinated peptide antibody different to distinguish rheumatoid arthritis from their primary differential diagnoses?

Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) are commonly used for diagnosis of rheumatoid arthritis (RA), although other rheumatic diseases with arthritis can test positive. This study aimed to determine the cutoff values for RF and anti-CCP with the best diagnostic performance in a sample of patients with RA, compared with other rheumatic diseases. This was a descriptive, prospective study. EUROINMMUN enzyme-linked immunosorbent assays for RF isotypes immunoglobulin (Ig) A (IgA), IgG and IgM and third-generation assay IgG for anti-CCP were used in serum samples of patients with RA, other rheumatic diseases and healthy subjects. The cutoff with the best diagnostic performance was determined by the Youden Index and receiver operating characteristic analysis Results: Three hundred and thirty-two serum samples were analysed. The cutoffs proposed in our population were for RF in RA patients versus other rheumatic diseases, and healthy subjects IgM 135 IU/mL, for each disease, compared with RA, were psoriatic arthritis (Psa) IgA 47.2 IU/mL, clinically suspicious arthralgia (CSA) IgA 39.5 IU/mL, primary Sjögren's syndrome (pSS) IgM 180.6 IU/mL, systemic lupus erythematosus (SLE) IgA 42.6 IU/mL, primary fibromyalgia (pFM) IgM 68.6 IU/mL, osteoarthritis (OA) IgM 48 IU/mL, gout IgM 117 IU/mL and healthy IgM 16.3 IU/mL. For anti-CCP, in RA patients versus other rheumatic diseases, and healthy subjects 6.95 IU/mL, for each disease, compared with RA, were Psa 6.8 IU/mL, CSA 9.95 IU/mL, pSS 20.7 IU/mL, SLE 6 IU /mL, pFM 11.8 IU/mL, OA 11.9 IU/mL, gout 5 IU/mL and healthy 5 IU/mL. Irrespective of the manufacturer's suggested cutoff, the RA versus differential diagnosis cutoffs must be considered.

Rapid diagnosis of rheumatoid arthritis and ankylosing spondylitis based on Fourier transform infrared spectroscopy and deep learning

ObjectiveRheumatoid arthritis and Ankylosing spondylitis are two common autoimmune inflammatory rheumatic diseases that negatively affect activities of daily living and can lead to structural and functional disability, reduced quality of life. Here, this study utilized Fourier transform infrared (FTIR) spectroscopy on dried serum samples and achieved early diagnosis of rheumatoid arthritis and ankylosing spondylitis based on deep learning models. MethodA total of 243 dried serum samples were collected in this study, including 81 samples each from ankylosing spondylitis, rheumatoid arthritis, and healthy controls. Three multi-scale convolutional modules with different specifications were designed based on the multi-scale convolutional neural network (MSCNN) to effectively fuse the local features to enhance the generalization ability of the model. The FTIR was then combined with the MSCNN model to achieve a non-invasive, fast, and accurate diagnosis of ankylosing spondylitis, rheumatoid arthritis, and healthy controls. ResultsSpectral analysis shows that the curves and waveforms of the three spectral graphs are similar. The main differences are distributed in the spectral regions of 3300–3250 cm−1, 3000–2800 cm−1, 1750–1500 cm−1, and 1500–1300 cm−1, which represent: Amides, fatty acids, cholesterol, proteins with a carboxyl group, amide II, free amino acids, and polysaccharides. Four classification models, namely artificial neural network (ANN), convolutional neural network (CNN), improved AlexNet model, and multi-scale convolutional neural network (MSCNN) were established. Through comparison, it was found that the diagnostic AUC value of the MSCNN model was 0.99, and the accuracy rate was as high as 0.93, which was much higher than the other three models. ConclusionThe study demonstrated the superiority of MSCNN in distinguishing ankylosing spondylitis from rheumatoid arthritis and healthy controls. FTIR may become a rapid, sensitive, and non-invasive means of diagnosing rheumatism.

Estimation of life expectancy and healthcare cost in rheumatoid arthritis patients with and without depression: a population-based retrospective cohort study.

This study aimed to estimate the lifetime healthcare costs and loss of life expectancy (loss-of-LE) among patients with incident rheumatoid arthritis (RA) with and without depression. This 18 years longitudinal cohort study used data from Taiwan's National Health Insurance Research Database. In total, 43,311 patients with RA were included. Among them, 1,663 patients had depressive disorders in the year preceding the RA diagnosis. The survival function for patients with RA with or without depression was estimated and extrapolated over a lifetime using the rolling extrapolation algorithm. The loss-of-LE was calculated by comparing the sex, age, and calendar year-matched referents from vital statistics. The average monthly cost was calculated as the sum of the monthly costs for all patients divided by the number of surviving patients. Lifetime healthcare costs were estimated by multiplying the monthly average cost by the monthly survival probability. The loss-of-LE for RA patients with and without depression was 5.60 years and 4.76 years, respectively. The lifetime costs of RA patients with and without depression were USD$ 90,346 and USD$ 92,239, respectively. However, the annual healthcare costs were USD$ 4,123 for RA patients with depression and USD$ 3,812 for RA patients without depression. Regardless of sex or age, RA patients with depression had higher annual healthcare costs than those without depression. Patients with RA and depression have a high loss-of-LE and high annual healthcare costs. Whether treating depression prolongs life expectancy and reduces healthcare costs warrants further investigation.

Abstract 12 — Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Study

Background Rheumatoid arthritis (RA) is a debilitating and financially burdensome disease because of frequent presence of comorbidities including metabolic and cardiovascular abnormalities. Growing evidence suggests a link between RA and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and explore the risk factors of developing NAFLD in RA population. Methods This population-based, cross-sectional study utilized data on US adults aged [Formula: see text]20 years old from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, a representative sample of the general US population. Diagnosis of RA was derived from questionnaire data. NAFLD was defined by controlled attenuation parameter (CAP) scores of [Formula: see text]278 dB/m using vibration controlled transient elastography (VCTE) in the absence of other liver disease. Weighted multiple regression analysis was further performed to assess the independent risk factors. Results Of 2,848 people included in this study, 224 of them had self-reported RA. The prevalence of NAFLD in the overall sample was 41%, with a numerically higher prevalence in RA patients than those without arthritis (47% vs. 40%, p=0.30). Compared to those without NAFLD, RA patients with concomitant NAFLD had more prevalent metabolic comorbidities including obese (75% vs. 32%, p=0.006), central obesity (100% vs. 71%, p=0.008), diabetes (39% vs. 14%, p=0.003) and hyperlipidemia (88% vs. 76%, p=0.042). Regarding laboratory findings, RA patients with NAFLD exhibited higher levels of triglyceride (188 mg/dL vs. 131 mg/dL, p=0.010), fasting plasma glucose (131 mg/dL vs. 109 mg/dL, p=0.010) and HbA1c (5.77% vs. 6.41%, p=0.002). Meanwhile, elevated levels of liver enzymes (ALT: 29 U/L vs. 19 U/L, p=0.015; AST: 25 U/L vs. 19 U/L, p=0.007) and inflammatory indicator CRP (5.1 mg/dL vs. 3.4 mg/dL, p<0.001]) were more frequently reported in RA patients with NAFLD as compared with those without. Further, weighted multivariate logistic regression analysis showed that the presence of central obesity (adjusted OR=1.56 [95% CI 1.16-2.11], p=0.008) and diabetes (adjusted OR=1.28 [95% CI 1.07-1.54], p=0.014) were significantly associated with prevalent NAFLD in patients with RA. Conclusion In this population-based study, about one in two patients with RA had NAFLD, which is higher than its overall prevalence among general population. Central obesity and diabetes are predisposing factors for NAFLD in RA. Our results highlight the importance of active NAFLD screening in RA population, especially for high-risk subsets.

Register-based observational study of associations between inflammatory remission, formal treatment targets and the use of disease-modifying antirheumatic drugs among patients with early rheumatoid arthritis

ObjectiveTo assess associations between inflammatory remission, formal treatment targets and the likelihood of starting a new disease-modifying antirheumatic drug (DMARD), among patients with early rheumatoid arthritis (RA).MethodsPatients newly diagnosed with...

Abstract 8 — Risk of Liver Injury in Psoriasis and Rheumatoid Arthritis is Associated with Metabolic Risk Factors Rather than Methotrexate and Leflunomide

Objectives To assess the associations of hepatic injury and fibrosis in patients with psoriasis (PsO) and rheumatoid arthritis (RA). Methods A total of 318 patients attending dermatology and/or rheumatology out-patient clinics in Queen Mary Hospital, with clinical diagnosis of PsO, psoriatic arthritis (PsA) or RA were consecutively recruited from July 2020 to August 2022. Demographic data, comorbidities, and medications were recorded. Body mass index (BMI) was measured. Serum biomarkers for hepatic injury including autotaxin, matrix metalloproteinase (MMP) 3, MMP 8, and MMP 9 were determined. Transient elastography (TE) was performed to determine liver stiffness measure (LSM) and controlled attenuation parameter (CAP). Regression models were built to determine the association between methotrexate and leflunomide cumulative dosage, serum biomarkers and TE scores. Results A total of 67 (20.4%) patients had LSM>7.1 kPa. Multivariate linear regression showed methotrexate cumulative dosage was associated with autotaxin level (B=4.77, 95% CI 1.39; 8.15, p=0.001). There was no association between methotrexate cumulative dosage and MMP 3, MMP 8, MMP 9, LSM, CAP. There was also no association between leflunomide cumulative dosage and autotaxin, MMP 3, MMP 8, MMP 9, LSM, CAP. BMI (B=6.18, 95% CI 4.95; 7.41, p<0.001), hypertension (B=18.98, 95% CI 4.15; 31.82, p=0.01), hyperlipidaemia (B=20.21, 95% CI 3.50; 36.92, p=0.02) were associated with CAP. Conclusion Methotrexate and leflunomide have minimal hepatic risk in patient with PsO and RA. Metabolic risk factors had strong associations with hepatic injury.

Rheumatoid Arthritis: Current and Emerging Paradigms of Diagnosis and Treatment

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation and damage to joints andtissues. While previous reviews exist, there still needs to be more in understanding risk factors, diagnostic methods, and treatmentoptions. This review aims to fill these gaps by providing a comprehensive overview of recent advancements in the field. To addressthe limitations of previous reviews, this article incorporates updated information on risk factors, including the influence ofenvironmental factors in industrialized nations. It highlights the significance of early RA diagnosis and emphasizes the utility ofdynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for effective disease management. Moreover, this reviewintroduces innovative nanotechnology-based treatment approaches for RA. It explores the potential of gold nanoparticles, carbonnanotubes, polymer-based nanomedicine, and nanoliposomes in targeting specific inflammatory sites and improving treatmenteffectiveness. This review aims to present an up-to-date and comprehensive analysis of RA, bridging gaps in previous literature byintroducing novel diagnostic techniques and exploring emerging treatment modalities. By synthesizing current knowledge andoutlining future research prospects, this review aims to advance the understanding and treatment of rheumatoid arthritis.Additionally, this review discusses the systemic complications associated with RA, such as rheumatoid vasculitis and Feltysyndrome. It also sheds light on the long-term consequences of untreated RA, including the potential need for joint replacementsurgery (arthroplasty) and splenectomy. By providing a comprehensive analysis of these aspects, this review aims to enhance theholistic understanding of RA and guide future research toward improved management and patient outcomes.

Utilisation of cardiovascular preventive services in a rheumatoid arthritis population-based cohort

ObjectivesThe objective is to examine utilisation of cardiovascular preventive services in patients with rheumatoid arthritis (RA), compared with a non-RA population, and to examine cardiovascular disease (CVD) screening rates among...

Experience with the interleukin 6 inhibitor (Olokizumab) in patients with rheumatoid arthritis in real clinical practice: Influence on inflammatory activity and disease outcomes

The aim of the study was to evaluate in real clinical practice the effectiveness of therapy with an interleukin-6 inhibitor (olokizumab) in patients with rheumatoid arthritis (RA) in terms of clinical and laboratory activity of the disease, as well as patient-reported outcomes (PROs). Material and methods. 10 patients with a reliable diagnosis of RA were examined: the average age of the patients was 45.70±17.9 years, the duration of the disease was 9.0 (3.0; 12.0) years. Patients were with moderate or high disease activity: DAS28-ESR – 5.13 (4.34; 5.80) points; CDAI – 30.00 (24.00; 35.00); SDAI – 31.86 (24.36; 38,59). All patients were prescribed treatment with olokizumab (OKZ) at a dose of 64 mg subcutaneously every 4 weeks against the background of therapy with methotrexate, leflunomide, non-steroidal anti-inflammatory drugs and glucocorticoids (GC) (up to 10 mg/day in terms of prednisolone). Three patients had previously received tocilizumab (intravenously once a month at a dose of 8 mg/kg), the administration of which was discontinued for administrative reasons 6–12 months before the appointment of OKZ. The results of treatment were assessed by the dynamics of clinical, laboratory parameters (DAS28-ESR, SDAI, СDAI, CRP, ESR, IgM RF, ACCP) and outcomes assessed by the patients themselves (PROs): HAQ-DI index, general assessment of the health status of patients (OSZB) according to VAS, pain according to VAS; scales FACIT, SF-36. As psychometric methods, the questionnaire “Type of attitude towards the disease (TOBOL)”, the Hospital Anxiety and Depression Scale (HADS), and the Toronto Alexithymic Scale (TAS-26) were used. Observation was carried out before treatment, after 3 and 6 months of therapy. Results. Against the background of OKZ therapy, after 3 and 6 months, compared with the baseline, there was a significant decrease in the clinical indices of RA activity: DAS28-ESR – 5.13 (4.34; 5.80), 3.53 (2.83; 4.26) and 3.48 (2.8; 4.10) points respectively; CDAI – 30.00 (24.00; 35.00), 11.00 (6.0; 16.00) and 10.0 (5.0; 15.0) points respectively; SDAI – 31.86 (24.36; 38.59), 11.05 (6.07; 16.07) and 10.17 (7.02; 15.02) points respectively; CRP – 14.30 (7.00; 24.70), 0.70 (0.40; 0.90) and 0.65 (0.20; 3.0) mg/l respectively. No significant dynamics of ESR, RF IgM and ACCP was noted. After 3 and 6 months of treatment with OKZ, there was a significant decrease in OSZB and pain severity according to the VAS scale, and an improvement in the functional state of patients was observed according to the HAQ-DI questionnaire of fatigue indicators (FACIT-F) (p<0.05). The physical component of the SF-36 scale increased significantly only by the 6th month of therapy (p<0.01), while the mental component did not undergo significant changes (p>0.05). In the process of treatment of OKZ, the attitude of patients to the disease changed from the ergopathic, neurasthenic and sensitive components in the TOBOL profile, before it began, then by its end, the dominant ones were harmonious, ergopathic and sensitive profiles. In addition, starting from the 3rd month of treatment in patients with RA, an adaptive response to the disease prevailed. A decrease in the level of anxiety was revealed, compared with the baseline, after 3 and 6 months of observation, depression indicators did not change significantly. Conclusion. In general, the results of this study indicate the effectiveness of ICD in RA, not only in terms of reducing the clinical and laboratory activity of the disease, but also in terms of outcomes reported by the patient himself, characterizing the quality of life and the psycho-emotional state of patients.

Precise Lipidomics Decipher Circulating Ceramide and Sphingomyelin Cycle Associated with the Progression of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a long-term autoimmune condition that causes joint and surrounding tissue inflammation. Lipid mediators are involved in inflammation and deterioration of the joints. Despite attempts to discover effective drug targets to intervene with lipid metabolism in the disease, progress has been limited. In this study, precise lipidomic technology was employed to quantify a broad range of serum ceramides and sphingomyelin (SM) in a large cohort, revealing an association between the accumulation of circulating ceramides and disturbed ceramide/SM cycles during the progression of RA. In our investigation, we discovered that eight ceramides exhibited a positive correlation with the activity of RA, thereby enhancing the accuracy of RA diagnosis, particularly in patients with serum antibody-negative RA. Furthermore, the enzyme SM phosphodiesterase 3 (SMPD3) was found to disrupt the circulating SM cycle and accelerate the progression of RA. The activity of SMPD3 can be inhibited by methotrexate, resulting in decreased metabolic conversion of SM to ceramide. These findings suggest that targeting the SM cycle may provide a new therapeutic option for RA.

The Diagnostic Significance of Serum Sclerostin in Early Detection of Rheumatoid Arthritis in Syrian Patients

Background: Rheumatoid arthritis (RA) is associated with joint deformities and local bone erosions. Sclerostin is an inhibitor of the Wnt pathway and drives to reduce bone formation. Aims: Our study aimed to compare the diagnostic significance of sclerostin with anti-CCP (anti-cyclic citrullinated peptide; normal level<20 IU/ml, and rheumatoid factor (RF; normal level<16 IU/ml) for the early diagnosis of rheumatoid arthritis in Syrian patients. Methods: This study contained fifty-eight RA patients and thirty healthy individuals who were equally age- and sex-matched. Serum sclerostin and serum anti-CCP (IgG) levels were evaluated by using the enzyme-linked immunosorbent assay (ELISA). RA activity was assessed based on disease activity scores (DAS28). Results: Our results indicated that serum levels of sclerostin levels were higher in the RA group than in the healthy group (p<0.001). There was a positive correlation between serum sclerostin and DAS28-ESR (r=0.413, p=0.001). By ROC curve, the most optimal cut-off value of sclerostin was 249.69 pg/ml (AUC was 0.910 with 95% confidence interval (CI) values (0.852-0.969), sensitivity of 87.9%, and specificity of 93.3%) [Odds Ratio (OR) and P-value: 102, P< 0.0001]. In RA patients, the sensitivity and specificity of anti-CCP were 74.1% and 90%, and 70.6% and 86.6% of RF, respectively. Conclusion: Increased serum sclerostin may aid as a new prognostic biomarker for evaluating the activity of RA. Sclerostin showed higher sensitivity and specificity than anti-CCP and RF-IgM antibodies. Therefore, sclerostin is a sensitive and specific biomarker for early diagnosis of rheumatoid arthritis.

Knowledge about Rheumatoid Arthritis among Senior Undergraduate Medical Students of a Medical College in South India

Background: Rheumatoid arthritis (RA) is the most common form of autoimmune inflammatory arthritis with an Indian prevalence of around 0.75%. Nearly 55% of Indians resort to primary health-care centers as their first point of contact. MBBS students must be well equipped to diagnose and treat patients with RA within the community and refer the relevant cases appropriately to higher medical facilities. Materials and Methods: A cross-sectional study was conducted assessing the basic knowledge of RA in senior medical undergraduate students in two domains. The first domain included assessment, clinical features, and diagnosis of RA while the second domain included treatment, radiological features, and therapeutics of RA. The total score was summed up for each domain. Self-assessment of knowledge was also inquired. The questionnaire was validated after a pilot study. The analysis was done using SPSS software using Pearson’s Chi-square test for correlation and paired t-test for comparison with basic descriptive statistics. Results: A total of 142 students participated, classified by year of study. There were 69% of female respondents. The mean self-assessment value was 4.82 ± 1.944, and the mean score in the questionnaire was 7.27 ± 2.183. The mean score out of 9 for Domain A was 5.09 ± 1.63 and for Domain B out of 4 was 2.17 ± 0.977. Students performed better in Domain B. A significant association was found between final assessment score and year of study (P < 0.01) as well as self-assessment and year of study (P < 0.01). Conclusion: Participants had less confidence in themselves as compared to how they performed. Female students performed better. Awareness about Domain B was higher, and senior students performed better.

Identification of shared disease marker genes and underlying mechanisms between major depression and rheumatoid arthritis

Both depression and rheumatoid arthritis (RA) have a very high comorbidity rate. A bilateral association is estimated to increase the mutual risk and the common denominator is inflammation being observed in both diseases. Previous studies have mainly focused on assessing peripheral blood's inflammatory and pro-inflammatory cytokines levels.We aimed to extend insights into the molecular mechanisms of depression based on hub RA genes. To do so, we prioritized RA-related genes using in-silico tools. We then investigated whether RA-related genes undergo altered expression in patients with unipolar and bipolar depression without a concurrent RA diagnosis and any exponents of active inflammation. In addition, we selected a homogeneous group of patients treated with lithium (Li), which has immunomodulatory properties.The study was performed on patients with bipolar depression (BD, n = 45; Li, n = 20), unipolar depression (UD, n = 27), and healthy controls (HC, n = 22) of both sexes. To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software.We selected a list of 180 hub genes whose altered expression we analyzed using the expression microarray results. In the entire study group, we identified altered expression of 93 of the 180 genes, including 35 down-regulated (OPRM1 gene with highest FC > 3) and 58 up-regulated (TLR4 gene with highest FC > 3). In UD patients, we observed maximally up-regulated expression of the TEK gene (FC > 3), and in BD of the CXCL8 gene (FC > 5). On the other hand, in lithium-treated patients, the gene with the most reduced expression was the TRPV1 gene.The study proved that depression and RA are produced by a partially shared “inflammatory interactome” in which the opioid and angiogenesis pathways are important.

Adverse events that occurred in patients with rheumatoid arthritis during long-term follow-up

Comorbid diseases and adverse events that occur in patients with rheumatoid arthritis (RA) negatively affect the outcomes of RA (radiological progression, joint function, the occurrence of low-energy fractures, thrombotic events, etc.). Objective: to study the structure of comorbid diseases and adverse events that occurred in patients with RA over the period of long-term prospective follow-up, to study the impact of these events on the dynamics of the functional status and working capacity of patients. Materials and methods. Аn open, cohort, prospective, long-term non-interventional study included 103 women with a definite diagnosis of RA (mean age 63.5 ± 8.3 years, follow-up period 8,5 ± 1,3 years). At baseline and in dynamics, standard laboratory and X-ray examinations were carried out. Results and discussion. There was a decrease in the DAS28 index and the number of patients with high or moderate activity [from 82 (85 %) to 67 (69 %), p = 0.02] against the background of an increase in the number of patients with remission or low activity [from 15 (15 %) to 30 (31 %), p = 0.012], at the same time there was an increase in the number of patients with ankylosis of joints [from 25 (24 %) to 41 (40 %), p = 0.017], functional class III [from 3 (3 %) to 15 (15 %), p=0.004], concomitant diseases [from 81 (79 %) to 94 (91 %), p = 0.015], thrombotic events [from 7 (7 %) to 18 (17 %), p = 0.027]. In 43 (42 %) patients 55 low-energy fractures were registered, in 24 (56 %) of them fractures occurred for the first time and in 19 (44 %) – repeatedly. Conclusion. As the prospective long-term follow-up shows, despite the decrease in RA activity, the number of patients with ankylosis, joint dysfunction and concomitant diseases increased. In the structure of concomitant diseases coronary heart disease and arterial hypertension dominated. A high incidence of thrombotic events, repeated and first-time low-energy fractures was noted. The number of disabled patients increased fivefold.