Diagnostic and prognostic role of serum interleukin-6 and carotid ultrasonography to detect subclinical atherosclerosis in patients with RA and ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV.

The COVID-19 pandemic's impact on rheumatic disease patients' satisfaction with access to medical services.

The COVID-19 hurt various lifestyle aspects, especially the treatment and follow-up of patients with chronic diseases such as autoimmune inflammatory rheumatic diseases (RD). The new circumstances changed the frequency of medical examinations and the way patients with rheumatic diseases are followed up. The objective is to study the impact of COVID-19 on RD patients' satisfaction with access to medical services. A national multicenter observational cross-sectional anonymous online survey was conducted on patients with RD using a specially developed web-based platform and structured questionnaire https://rheumatologycovid19.bg/ . The study was carried out with the support of intra-university project №6/2022 MU-Plovdiv. 1288 patients participated, with an average age of 47.03 (SD ± 12.80 years), of whom 992 (81.6%) were women. The questionnaire contained 41 questions grouped into 5 panels. Descriptive statistics were used-mean, alternative analysis, logistic regression and Decision Tree using the CRT (classification and regression trees) method. The study found that RD patients' satisfaction with access to medical services was influenced by communication type and the frequency of visits to the rheumatologist, difficulties in prescribing and finding medicines and the presence of comorbidities. The likelihood of patients' satisfaction with their rheumatologist was 5.5 and 3 times higher for in-person and other means of communication, respectively, compared to those without any communication. The relative share of patients who communicated by phone was larger (59%) compared to pre-pandemic (41%), where direct contact with the physician prevailed (80%). The results of the study confirmed the need to optimize remote access to medical care for patients with RD during the pandemic.

Serum and Synovial Levels of Cathepsin G and Cathepsin K in Patients with Psoriatic Arthritis and Their Correlation with Disease Activity Indices.

This retrospective case-control study examined the relationship between the serum and synovial levels of cathepsin G (CatG) and cathepsin K (CatK) in patients with psoriatic arthritis (PsA) and their association with disease activity. Methods: This case-control study involved 156 PsA patients, 50 patients with gonarthrosis (GoA), and 30 healthy controls. The target parameters were measured using enzyme-linked immunosorbent assay (ELISA) kits. The serum levels of CatG and CatK were found to be significantly higher in PsA patients compared to both control groups (p < 0.001). Moreover, they could distinguish PsA patients from healthy controls with 100% accuracy. Synovial fluid CatG and CatK were positively associated with the following indicators of disease activity: the VAS (rs = 0.362, rs = 0.391); the DAPSA (rs = 0.191, rs = 0.182); and the mCPDAI (rs = 0.378, rs = 0.313). Our results suggest that serum and synovial fluid CatG and CatK levels could serve as biomarkers for PsA. In PsA patients with synovial fluid crystals, elevated synovial CatG levels demonstrated a sensitivity of 89.54% and a specificity of 86.00% in distinguishing them from PsA patients without crystals. Similarly, elevated synovial CatK levels had a sensitivity of 93.67% and a specificity of 94.34% for distinguishing PsA patients with synovial fluid crystals from those without. Furthermore, the synovial fluid levels of both CatG and CatK showed positive associations with key indicators of disease activity, including the visual analog scale (VAS) (rs = 0.362, rs = 0.391), the disease activity in psoriatic arthritis (DAPSA) (rs = 0.191, rs = 0.182), and the modified composite psoriatic disease activity index (mCPDAI) (rs = 0.378, rs = 0.313). In conclusion, our findings suggest that the serum and synovial fluid levels of CatG and CatK hold promise as potential biomarkers for assessing disease activity in psoriatic arthritis.

High-resolution musculoskeletal ultrasonography and elastography for eosinophilic fasciitis diagnosis and follow-up: a case-based review.

Eosinophilic fasciitis (EF) remains a rare condition without precise diagnostic criteria due to common symptoms with other autoimmune diseases requiring broad differential diagnosis. This paper describes the use of high-resolution musculoskeletal ultrasonography and elastography in the diagnosis and follow-up of eosinophilic fasciitis through the case of a 56-year-old male patient. In addition to laboratory data, instrumental data, and biopsy, musculoskeletal ultrasonography (US) was used both in the diagnostic process and in the follow-up period for an objective assessment of the changes in the patient's condition and response to treatment. The US showed disorganization of the myofibrils adjacent to the superficial fascia, edema, and thickening of the fascia and subcutaneous edema. In addition, the use of shear-wave elastography (SWE) demonstrated significantly reduced skin elasticity. High-frequency musculoskeletal ultrasound in combination with SWE is an effective method both for the diagnosis of EF and for the follow-up of the changes occurring after therapy. Based on the fact that it can easily differentiate the substrate of involvement, such as skin, subcutaneous tissue, or muscle fascia, ultrasound can be used to distinguish EF from other skin and muscle diseases.

Assessment of serum and synovial fluid MMP-3 and MPO as biomarkers for psoriatic arthritis and their relation to disease activity indices.

Research on biomarkers for the diagnosis and monitoring of psoriatic arthritis (PsA) is ongoing. The purpose of this study was to assess the potential of serum and synovial fluid matrix metalloproteinase-3 (MMP-3) and myeloperoxidase (MPO) as biomarkers for PsA and their relation to disease activity indices. This case-control study involved 156 psoriatic arthritis patients, 50 gonarthrosis patients, and 30 healthy controls. The target parameters were measured with the enzyme-linked immunosorbent assay (ELISA) kits. Serum MMP-3 and MPO levels were elevated in the PsA patients in comparison to the two control groups (p < 0.001) and distinguished PsA from GoA patients and healthy controls with 100% accuracy. Synovial MMP-3 discriminated PsA from GoA patients irrespective of the presence of crystals (AUC = 1.00). PsA patients with crystals in the synovial fluid had elevated synovial MPO (p < 0.001) and were distinguished from PsA patients without crystals with accuracy of 88.50% and from GoA patients with accuracy of 88.30%. Synovial fluid MPO was positively associated with the following indicators of disease activity: VAS (rs = 0.396); DAPSA (rs = 0.365); mCPDAI (rs = 0.323). Synovial MMP-3 showed a weaker positive association with DAPSA (rs = 0.202) and mCPDAI (rs = 0.223). Our results suggest that serum MMP-3 and MPO could serve as biomarkers for PsA. Synovial fluid MMP-3 showed a potential as a biomarker for PsA versus GoA. Synovial MPO could be utilized as a marker for the presence of crystals in PsA patients.

Assessment of TNF-α expression in unstable atherosclerotic plaques, serum IL-6 and TNF-α levels in patients with acute coronary syndrome and rheumatoid arthritis.

The role of inflammatory cytokines is well researched in acute coronary syndrome (ACS) and rheumatoid arthritis (RA), but not in the presence of both conditions. This study aimed to compare TNF-α expression, serum TNF-α, IL-6, and hs-CRP in ACS patients with RA (n = 46) with ACS patients without RA (n = 49) and healthy controls (n = 50). TNF-α expression was assessed from coronary artery samples, taken during coronary artery bypass surgery. Serum levels TNF-α, IL-6, and hs-CRP were measured 24 and 48 h after cardiac surgery. Stronger TNF-α expression was observed in the ACS patients with RA versus the ACS patients without RA, p = 0.001. Serum TNF-α, IL-6, and hs-CRP at the 24th h were significantly elevated in both patient groups and distinguished them from the healthy controls with accuracy ranging from 80 to 99%. At the 48th h, serum TNF-α and IL-6 in the ACS group without RA decreased to those of the healthy controls but remained high in the group with RA. ACS cases with RA could be correctly identified from the levels of IL-6 (AUC = 0.885, 95% CI 0.791 to 0.938) and TNF-α (AUC = 0.852, 95%CI 0.720 to 0.922). Our results suggest that the presence of RA in ACS cases is likely to provoke stronger TNF-α expression on atherosclerotic plaques, aggravate the pro-inflammatory response, and sustain it even after the cardiac stress is lowered. In ACS cases with RA, long-term monitoring and control of TNF-α and IL-6 levels can be a useful preventive strategy.

Drug-neutralizing Antibodies against TNF-α blockers as Biomarkers of Therapy Effect Evaluation.

INTRODUCTION: TNF-α blocker therapy is part of the treatment with biologics used in the management of inflammatory joint diseases. In recent years, drug-induced neutralizing antibodies have been shown to have a negative effect on the course of the disease process. AIM: To investigate drug-induced neutralizing antibodies against TNF-α blocking drugs used in patients with inflammatory joint diseases and their effect on the clinical course of the disease. MATERIALS AND METHODS: The study included 121 (56.8%) patients with rheumatoid arthritis, 50 (23.5%) patients with ankylosing spondylitis, 42 (19.7%) patients with psoriatic arthritis, and 31 sex and age-matched healthy controls. The patients were monitored at 0, 6, 12, and 24 months after initiation of TNF-α blocker treatment. The demographic data, vital signs and the parameters of inflammatory activity (C-reactive protein, erythrocyte sedimentation rate, and disease activity indices) were analyzed in all patients. Drug-induced anti-TNF-α blockers antibodies (adalimumab and etanercept) were analyzed using ELISA. Statistical analysis was performed with SPSS v. 24. RESULTS: Drug-induced neutralizing antibodies against adalimumab were obtained in 11.57% of patients at 6 month, in 17.64% at 12 month, and in 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not demonstrated in patients followed up at 6 months, at 7.77% at 12 months, and at 9.63% at 24 months. Between the presence of neutralizing antibodies to blockers of TNF-α and indices available for disease activity, there is a strong positive correlation and Pearson Correlation = 0.701, p=0.001. Patients with poor clinical response and available antibodies against adalimumab at 12 months were 82.36% and patients treated with etanercept 71.42%. The difference between the two groups was non-significant (U = 0.527, p> 0.05). Patients with poor clinical response and available anti-adalimumab antibodies at 24 month were 75%, and in patients treated with etanercept - 87.50%, the difference between the two groups not being able to reach significance (U = 0.623, p> 0.05). CONCLUSION: Drug-induced neutralizing antibodies against TNF-α blockers (adalimumab and etanercept) have a negative effect on the course of inflammatory joint disease and can be used as reliable biomarker to assess the effect of the treatment with these drugs.

Comparison of RANKL expression, inflammatory markers, and cardiovascular risk in patients with acute coronary syndrome with and without rheumatoid arthritis.

The mechanisms responsible for increased cardiovascular risk in patients with rheumatoid arthritis (RA) involve local and systemic inflammatory processes. We aimed to compare inflammatory markers and mortality risk in patients with acute coronary syndrome (ACS) with and without RA. The study involved 95 ACS patients (46 with RA and 49 without RA) and 40 healthy controls. Serum levels of Receptor Activator of Nuclear Factor Kappa B Ligand (sRANKL), Osteoprotegerin (sOPG), high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity Tropinin I (hs-TnI) were tested in all participants. Additionally, ACS patients were assessed on RANKL expression (exRANKL) on coronary arteries and mortality risk on the Global Registry of Acute Coronary Events scale (GRACE). exRANKL was established in 35 (76%) ACS patients with RA, vs. 19 (39%) patients without RA, p < 0.001. RA patients had significantly higher levels of sRANKL and sOPG at 24 h and 48 h compared to ACS patients without RA and healthy controls (sRANKL 24 h: 121.33 vs. 51.67 vs. 36.94, p = 0.019; sRANKL 48 h: 89.21 vs. 36.95 vs. 36.94, p = 0.004; sOPG 24 h: 207.71 vs. 69.39 vs. 111.91, p < 0.001; sOPG 48 h: 143.36 vs. 69.38 vs. 111.91, p < 0.001). RA patients had significantly higher RANKL:OPG ratio at 48 h (0.062 vs. 0.53 vs. 0.33, p < 0.001), hs-CRP (28.82 vs. 23.67 vs. 2.60, p < 0.001) and hs-TnI (0.90 vs. 0.76 vs. 0.012). GRACE risk score was significantly higher in RA patients vs. those without RA (140.45 vs. 125.50, p = 0.030) and correlated with exRANKL, RANKL:OPG, hs-CRP, and hs-TnI. Our results indicate that exRANKL, inflammatory markers and mortality risk are amplified in ACS patients with RA compared to ACS patients without RA.