Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie.

OBJECTIVES: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients often experience secondary non-response to a first-line tumour necrosis factor alpha inhibitor (TNFαi). This pooled analysis of six observational studies in Europe (GO-BEYOND program) provides an estimate of second-line golimumab (GLM) effectiveness for these rheumatic diseases. METHODS: The GO-BEYOND studies included common disease-specific endpoints allowing for a pooled analysis. Patients had discontinued one prior TNFαi (due to loss of efficacy, tolerability, or inconvenience) and were followed for 12 months after GLM initiation. Primary endpoints included the proportion of patients achieving low disease activity (LDA, DAS28-CRP<3.2) in RA, minimal disease activity (MDA, fulfilment of 5 of 7 outcome measures) in PsA, or low disease activity (ASDAS<2.1) in axSpA at 6 months. Disease activity at 3 and 12 months and quality of life (QoL; EQ-5D-3L) were also assessed. Adverse events were monitored. Protocol-specified analyses were based on observed data. RESULTS: In 712 patients, (n=325, RA; 186, PsA; 201, axSpA), mean age was 54 years, 64% were female, and median disease duration was 5 years. Primary endpoints were achieved in 58.3% (RA), 45.5% (PsA), and 45.4% (axSpA) of patients; disease activity improvements were observed at 3 and 12 months and EQ-5D-3L results showed improved QoL over time. The treatment persistence rate at 12 months was 67.8% of patients. No new safety signals were observed. CONCLUSIONS: This pooled analysis of the GO-BEYOND studies showed that treatment with GLM was effective and represented a valid second-line option for RA, PsA, and axSpA patients.

JAK inhibitors improve ATP production and mitochondrial function in rheumatoid arthritis: a pilot study.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.

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.

An observational study of the radiofrequency echographic multi-spectrometry (REMS)-based fragility score of the lumbar spine and total fracture risk at 5 years in women.

A novel fragility score (FS) parameter, obtained during radiofrequency echographic multi-spectrometry (REMS), was developed to estimate the ultrasound-based skeletal fragility. The aim of our study is to assess the REMS-based FS of the lumbar spine (LS) among the Bulgarian women and to compare their characteristics acquired with REMS between fracture risk classes corresponding to a total fracture risk at 5 years for major osteoporotic fractures (MOF). A total of 100 Bulgarian women, who underwent a screening for osteoporotic fracture risk using the REMS technology, were included in a prospective observational study. The mean age was 60 years (years) ± 13.9 standard deviations. We assessed the FS of the LS and for each subject. The fracture risk class (R1-R7) was identified using a table combining measured REMS T score and FS values. The mean FS was 36.9 ± 17.4 SD (range: 18.5-84.3). Twelve subjects (12%) were classified into the R6 group, twenty-three (23%) into the R5, sixty-one (61%) into R4, and four (4%) into R3. Statistical analysis showed significant difference in age, height, BMD, T score, Z score, age of menopause, FRAX for MOF, and FRAX for hip fractures between the risk class groups. This is the first study which showed the REMS-based FS of the lumbar spine among the Bulgarian women. T score alone is not a good predictor of fractures. Our study showed that its use in combination with the fragility score obtained during REMS offers a robust assessment of the fracture risk at 5 years for MOF.

Adherence to biological therapies in patients with rheumatoid arthritis: a retrospective cohort study.

The advent of biologic disease-modifying antirheumatic drugs has dramatically changed the comprehensions of treatment and long-term prognosis in patients with rheumatoid arthritis. The potent therapeutic results can only be achieved if the patients adhere to prescribed medications. The objective of this study was to estimate the impact of age, gender, duration of the disease, concomitant Methotrexate therapy, prior exposure to biologic agents, disease activity, functional capacity, and health-related quality of life on adherence to biologic treatment among Bulgarian population with rheumatoid arthritis. This was a retrospective observational cohort study that included 179 patients. At the baseline visit and subsequent follow-up assessments at 6, 12, 24 and 36 months, patients were interviewed by a physician and underwent physical examinations. We monitored the changes in disease activity, functional capacity and health-related quality of life on each time point. Univariate and multivariate binary logistic regression was used to determine the prognostic value of possible predictors of treatment adherence. Our findings showed that only DAS28 score [odd ratio (OR) = 1.174; 95% CI 1.74-2.362] and HAQ score (OR 2.803; 95% CI 1.428-5.503) remained significant for the treatment adherence throughout the study period. The adherence to the biologic disease-modifying anti-rheumatic drugs among Bulgarian patients with rheumatoid arthritis is suboptimal. A multifaceted and comprehensive knowledge of the influencing factors can be useful for the development of different strategies that can improve treatment adherence.

Effect of the body mass index, basal metabolic rate, and body fat on the radiofrequency echographic multi-spectrometry (REMS)-based bone mineral density and fracture risk: a cross-sectional study.

Radiofrequency echographic multi-spectrometry (REMS) is a method to assess bone mineral density (BMD) of the axial skeleton, fragility score (FS), body mass index (BMI), basal metabolic rate (BMR), and body fat (BF) in %. The aim of the study was to investigate the influence of the BMI, BMR, and BF on the BMD and fracture risk with REMS. We conducted a cross-sectional study among 313 women, aged 20-90 years who underwent a screening for osteoporosis with REMS. Kruskal-Wallis was used to analyze the differences in BMI, BMR, and BF between the groups according to the BMD: normal BMD, osteopenia and osteoporosis and differences in the FS, fracture risk assessment (FRAX) for major osteoporotic fractures and for hip fractures (HF) according to the BMI groups: underweight, normal weight, overweight, obese, and extreme obese. Linear regression was used to assess the correlations BMI-BMD, BMR-BMD, and BF-BMD. BMI, BMR, and BF differed significantly between the groups according to the BMD (p < 0.001, p = 0.028, and p < 0.001, respectively). BMR showed high positive correlation to BMD (R = 0.765) with 95% confidence interval (CI) [0.715, 0.807] and significance of p < 0.001. BMI correlated significantly to BMD (p < 0.001), the correlation was low positive (R = 0.362) with 95% CI [0.262, 0.455]. In the BMI groups, there was significant difference in FRAX for HF and FS with p value 0.014 and < 0.001, respectively. Subjects with low BMI, BMR, and BF are at high risk for osteoporosis. Underweight women show significantly high fracture risk, assessed with FRAX and FS.

First multi-center retrospective study assessed the compliance with and persistence of biological therapies in Bulgarian population with rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory joint disease that causes progressive joint damage, leading to severe disability. Early diagnosis, optimal therapy, and strict adherence to the prescribed medication are key factors that allow for the cessation of the disease progression and the preserving of the patient's quality of life. The objective of this study was to estimate the compliance to and persistence of biologic disease-modifying anti-rheumatic drugs (bDMARDs) among the Bulgarian population with RA. This retrospective observational cohort study included 179 patients, who were tracked over a 36-month period. During baseline and subsequent follow-up visits (at months 6, 12, 24, and 36), we monitored the disease activity, side effects, medication tolerability and effectiveness, compliance, and persistence to the prescribed biologic agent. The compliance with bDMARDs among Bulgarian patients with RA was 85.5% in the first year, 76.0% in the second year, and 63.7% in the third year. The Infliximab cohort showed the lowest compliance rate (50%), with the other subgroups bDMARDs having similar results (64-70%) during the period of observation. The median therapy duration across all patient cohorts is 61.9 months (IQR 55.7-67.6). Our study did not establish any significant impact of gender, age and disease duration, concomitant treatment with methotrexate, type of biologic agent and previous exposure to biological agents on the treatment adherence. The compliance with and persistence of the prescribed bDMARD among the Bulgarian population with RA is unsatisfactory. Therapy interruption and nonadherence to recommended therapy are associated with disease progression and patient disability. The consequences include not only financial burdens but also psychosocial and physical impacts.

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.

Efficacy and safety of secukinumab in patients with spondyloarthritis and enthesitis at the Achilles tendon: results from a phase 3b trial.

OBJECTIVE: ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles' tendon enthesitis in spondyloarthritis (SpA) patients. METHODS: Patients ≥18 years (n = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab. RESULTS: At week 24, a higher, yet statistically non-significant (P = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (-2.8 [3.0] vs -1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes. CONCLUSION: A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT02771210.

Ochronotic arthropathy in the context of spondyloarthritis differential diagnosis: a case-based review.

Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.

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.

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.

Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.

Serum protein levels of YKL-40 and plasma miR-214 expression in patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease with incompletely revealed etiology and pathophysiology. There are still no specific and reliable biomarkers. Here we examined YKL-40 as a biomarker of inflammation and fibrosis, and suggest a possible mechanism for its regulation. METHODS: Forty female patients with SSc (26 with diffuse cutaneous (dcSSc) and 14 with limited cutaneous SSc (lcSSc)) and 14 healthy female controls were enrolled in this cross-sectional study. Bioinformatic tools identified miR-214 binding site in the 3'-untranslated region (3'UTR) of YKL-40 mRNA. Serum levels of YKL-40 were examined by ELISA, while YKL-40 mRNA and miR-214 was measured by qPCR. RESULTS: The in silico analysis revealed several microRNAs (miRNAs) targeting YKL-40 mRNA, from which miR-214 was selected. YKL-40 serum levels were significantly higher in patients compared to controls (p = .0042). In contrary, miR-214 expression in plasma of SSc patients was significantly down-regulated compared to controls (p = .0058). Receiver operating characteristic (ROC) and area under the curve (AUC) analysis showed that both serum YKL-40 and plasma miR-214 levels had good capacity to distinguish patients with SSc, dcSSc and lcSSc from healthy subjects. CONCLUSION: YKL-40 and miR-214 have different expression profile in SSc. Increased serum levels of YKL-40 could be associated with down-regulation of miR-214 expression in plasma. Both, YKL-40 concentrations and miR-214 plasma fold change values might serve as possible biomarkers in SSc.

Enthesopathy and involvement of synovio-entheseal complex in systemic sclerosis: an ultrasound pilot study.

OBJECTIVES: SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients. METHODS: One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis. RESULTS: In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0-7.0) than in controls (median 1.0, interquartile range 0.0-3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035). CONCLUSION: These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.

Hand ultrasound patterns in rheumatoid and psoriatic arthritis: the role of ultrasound in the differential diagnosis.

Many rheumatic diseases may present with an inflammatory joint syndrome, affecting the small joints of the hands, of which rheumatoid (RA) and psoriatic arthritis (PsA) being one of the most common. The aim of this systematic review was to focus on the literature evidence regarding the added value of ultrasound (US) of the hand in the differential diagnosis between RA and PsA. Pubmed and Scopus were searched to identify original manuscripts, published in the last 20 years utilising ultrasonography to reveal specific hand US patterns. Studies were eligible if they: (1) included adults (over 18 years) with a diagnosis of RA/PsA; (2) were published in the English language; (3) were published in peer-reviewed journals; (4) included description of the US machine; (5) used US for assessment of hand joints, periarticular tissues and nails. The search yielded 322 published studies, of which 16 were deemed relevant and were included in the present study. Overall, there was heterogeneity with regard to the pathology examined. Based on the included studies analysis, hand US patterns have several basic features to be considered-location of gray scale (GS) inflammatory findings, involvement of periarticular soft tissue, distribution and extent of Doppler signal (intra- and peri-articular), bone reaction, shape and location of erosions, involvement of tendons without synovial sheath, involvement of enthesis and nail abnormalities. Future research could focus on determining the sensitivity and specificity of the different US detected hand patterns in patients with early arthritis.

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.

Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62 ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28 ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80 pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46 pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52 ng/ml ± 102.81; median 136.20 ng/ml) vs. lcSSc patients (89.31 ng/ml ± 50.36; median 68.03 ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64 pg/ml ± 46.37; median 16.36 pg/ml) vs. lcSSc patients (13.22 pg/ml ± 8.95; median 8.65 pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc.

Musculoskeletal ultrasound for predicting remission in patients with rheumatoid arthritis: results from a 1-year prospective study.

To assess the role of musculoskeletal ultrasound as a predictor for the achievement of DAS28 remission in patients with rheumatoid arthritis (RA). One hundred and forty-one patients underwent physical and ultrasound examination at five visits (at baseline and after 1, 3, 6 and 12 months). Patients were divided into two groups according to the type of treatment, which involved synthetic (sDMARDs) and biologic (bDMARDs) disease-modifying antirheumatic drugs. Ultrasound assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint (the German US7 score) was performed on gray scale (GS) and on power Doppler ultrasound (PDUS). The rate of clinical remission and clinical and sonographic predictors for the achievement of DAS28 remission at month 12 were assessed. In the sDMARDs group at month 12, 43.6% of the patients achieved DAS28 remission, 5.1%-SDAI, 3.8%-CDAI, and 3.8%-Boolean remission. In the bDMARDs group, 49.2% achieved DAS28 remission, 6.3%-SDAI, 4.8%-CDAI, and 4.8%-Boolean remission. Predictors for DAS28 clinical remission in the sDMARDs group were low baseline DAS28 (p = 0.002), short disease duration (p = 0.007) and lower baseline PDUS score (p = 0.038). In the bDMARDs group low baseline DAS28 (p < 0.001) and PDUS score (p = 0.035) predicted DAS28 remission. Shorter disease duration, lower baseline DAS28 and PDUS scores are associated with a higher probability of achieving DAS28 remission at month 12 in patients with RA. Musculoskeletal ultrasound and in particular the German US7-scoring system may be used as a predictor for the achievement of clinical remission in RA patients.

Pathobiochemical Mechanisms Relating Iron Homeostasis with Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis.

AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative for evaluation of the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.