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    Assessment of left atrial volume and function in patients with Sjogren's syndrome using three-dimensional echocardiography
    (Wiley, 2020) Hidayet, Siho; Yagmur, Julide; Karaca, Yucel; Bayramoglu, Adil; Yolbas, Servet; Hidayet, Emine; Ulutas, Zeynep
    Objective We used real time, three-dimensional transthoracic echocardiography (3DTTE) to evaluate left atrial (LA) volume and mechanical function in patients with primary Sjogren's syndrome (SS). Methods We prospectively included 42 consecutive patients with primary SS and 42 controls who were similar in terms of basal characteristics. 3DTTE was used to assess LA function. Results Maximum LA volume, minimum LA volume, pre-atrial contraction LA volume, LA Active Stroke Volume (ASV), LA Total Stroke Volume (TSV), maximal left atrial volume index (LAVImax), Left atrial pre-contraction volume index, and Left atrial minimum volume index, ASV index, and TSV index were significantly higher in the SS group, and the LA Total Emptying Fraction, LA Expansion Index, and LA Passive Emptying Fraction were significantly lower. Although the active emptying fraction was higher in the SS group, the difference was not statistically significant. LAVImax was positive correlated with disease duration (r = .753). Conclusion Left atrial function is impaired in SS patients and serves as an early marker of subclinical cardiac involvement.
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    Association of TRPM Channel Gene Polymorphisms with Systemic Sclerosis
    (Int Inst Anticancer Research, 2015) Oztuzcu, Serdar; Onat, Ahmet M.; Pehlivan, Yavuz; Alibaz-Oner, Fatma; Donmez, Salim; Cetin, Gozde Y.; Yolbas, Servet
    Background/Aim: Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc. Materials and Methods: A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system. Results: There were marked increases in the CC genotype (94.7% vs 81.8%, p<0.0001) and C allele frequencies (97.0% vs. 90.1%, p<0.0001) in the TRPM3 rs1328142, and TT genotype (19.0% vs. 7.8%, p=0.0002) in TRPM5 rs34551253 (Ala456Thr) polymorphism in SSc patients when compared to controls. TRPM3 gene rs1328142 polymorphism was also markedly associated with disease phenotype. However, no associations with the other 23 polymorphisms studied were found. Conclusion: This is the first study to examine the involvement of TRPM channel gene variations on the risk of SSc incidence. Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of SSc in the Turkish population.
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    Can nailfold capillaroscopy findings be a marker for uveitis in Behçet’s syndrome?
    (Clinical and Experimental Rheumatology S.A.S., 2025) Zontul, Sezgin; İnanç, Elif; Can, Ahmet; Tay, Şeyma Tokay; Çolak, Hüseyin; Cumurcu, Tongabay; Yolbas, Servet
    Objective To evaluate the differences between BS patients with uveitis and BS patients without uveitis and healthy controls in terms of nailfold capillaroscopic examination. Methods The study was performed on patients with a definite diagnosis of BS according to the International Criteria for Behçet’s Disease, and healthy controls without BS. The participants were divided into three groups: BS patients with uveitis, BS patients without uveitis and healthy controls. All volunteers were examined by nailfold capillaroscopy for microvascular changes. Results A sample size of 90 participants, including 32 patients with BS with uveitis, 29 patients with BS without uveitis and 29 healthy controls, were included in our study. Fourteen (15.6%) BS patients with uveitis, 14 (15.6%) BS patients without uveitis and 16 (17.8%) healthy controls were female. In our study, we found microhaemorrhage occurrence to be significantly higher in BS patients with uveitis compared to the healthy control group (p=0.028). Although there was no significant difference compared to the BS without uveitis group, microhaemorrhage was approximately 2.5 times more common in the BS with uveitis group. The crossing medians were determined as 2.0 (0.8-3.3) in the BS with uveitis group, 1.3 (0.6-2.7) in the BS without uveitis group and 1.2 (0-3.2) in the healthy control group, showing a statistically significant difference across groups (p<0.001). In the post hoc crossing analysis, a significant difference was detected in the BS with uveitis group compared to the other two groups. A giant capillary was detected in one of the patients with uveitis, but no giant capillary was detected in the volunteers in the other groups. Conclusion Our findings show that microhemorrhage and crossing are associated with uveitis in BS patients. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2025.
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    Can T1W and T2W Dixon Sequences Replace the Standard MRI Protocol in Diagnosing Sacroiliitis?
    (Ubiquity Press Ltd, 2024) Karatoprak, Nur Betul; Ozdemir, Zeynep Maras; Karatoprak, Sinan; Kahraman, Aysegul Sagir; Karaca, Leyla; Yolbas, Servet
    Objectives: This study aims to assess the performances of T1-weighted (T1W) and T2-weighted (T2W) Dixon sequences as replacements for the standard magnetic resonance imaging (MRI) protocol for diagnosing active and chronic sacroiliitis. Materials/Methods: This single-centre, prospective study included 107 patients who underwent 3 Tesla MRIs. The patients with inflammatory low-back pain (aged 18-50 years) were included. The exclusion criteria included pregnancy, pelvic infection/malignancy history, pelvic metal implants or foreign body artefacts. The imaging protocol comprised standard T1W and T2W fat-saturated (T2W-FS) sequences and T1W-T2W Dixon sequences. Active sacroiliitis signs were assessed by comparing T2W-FS images with T2W Dixon water-only (WO) images. Chronic sacroiliitis signs were evaluated by comparing the standard T1W sequence with T1W-T2W Dixon fat-only (FO), in-phase (IP) and out-of-phase (OP) images. The quantitative analysis involved calculating signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) for bone marrow edema (BME) and periarticular fat deposition (PFD). Descriptive statistics, correlation, diagnostic performance tests and interobserver reliability tests were performed in the qualitative analysis. Results: There were no statistically significant differences in BME detection between the T2W-FS and T2W Dixon-WO images. T2W Dixon exhibited significantly greater SNRs-CNRs than did the standard protocol for BME and periarticular fat deposition assessments. T1W-T2W Dixon imaging demonstrated sufficiently high diagnostic performance for detecting erosions, periarticular fat deposition and ankylosis compared with the standard protocol. Conclusions: The T2W Dixon sequence has the potential to replace the standard protocol, which would reduce acquisition time. However, we do not recommend the use of the T1W Dixon sequence in routine practice, since standard T1W images provide similar or superior results to T1W Dixon images.
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    Carotid artery stiffness in Behcet's disease
    (Aves, 2017) Yolbas, Servet; Gozel, Nevzat; Dagli, Mustafa Necati; Koca, Suleyman Serdar; Donder, Emir
    Objective: Increased carotid arterial stiffness (CAS) is a predictor of subclinical early atherosclerosis as well as carotid intima-media thickness (cIMT). We aimed to determine CAS and cIMT in Behcet's disease (BD). Material and Methods: BD (n= 49) and rheumatoid arthritis (RA) (n= 64) patients and healthy controls (HC) (n= 40) were included in the study. cIMT was measured. CAS indices, including arterial compliance (AC), arterial distensibility (AD), Young's elastic modulus (YEM), Peterson's elastic modulus (Ep), and beta stiffness index (beta SI) were measured based on the diameter-pressure relationship. Results: When compared to the HC group, the mean cIMT was significantly higher in the RA group (p= 0.033), but it was not higher in the BD group. The CAS indices, including AD, AC, Ep, and beta SI were not significantly different among the study groups. Moreover, the cIMT and CAS indices were not significantly different between active (n= 20) and inactive BD patients, and these indices were not correlated with the scores of disease activity. AD, AC and Ep were significantly lower in the BD patients with a positive pathergy reaction than in those with a negative reaction. Conclusion: These results suggest that BD does not directly lead to arterial stiffness or to an increase in cIMT.
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    A Case of Isolated Central Nervous System Rosai-Dorfman Disease
    (Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2024) Algul, Fatma Ebru; Erdem, Beguem Y. E. N., I; Yegen, Guelcin; Yolbas, Servet
    Rosai-Dorfman disease (RDD) is a benign histiocytosis with unknown etiology. It generally occurs in cervical lymph nodes. Isolated central nervous system (CNS) RDD is very rare in the literature. We reported a case of no systemic involvement Rosai-Dorfmann which is rarely seen and shows CNS involvement by mimicking meningioma. A 32 -year -old man presented with diplopia and a headache he has been experiencing for the past two years. His neurological examination showed left facial paresthesia, consistent with trigeminal nerve trace. Tendon reflexes were increased at the right side and the right plantar reflex was extensor. Brain magnetic resonance imaging demonstrated irregularly shaped, tumorlike lesions in the bilateral cerebellopontin area that were compressing pons. Rosai-Dorfman disease can be differentiated from IgG4 related disease (IgG4-RD) by its characteristic features such as plasma cell density and emperipolesis seen in its histopathology. Rosai-Dorfman disease can be confused with other diseases radiologically and histopathologically, especially the IgG4-RD, so be careful about differential diagnosis.
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    Colchicine-Tolerant vs. Resistant Familial Mediterranean Fever: Comparative Analysis of Clinical, Psychosocial Characteristics and Quality of Life
    (Mdpi, 2026) Kaya, Zeynep; Sag, Sinem; Kaya, Mehmet Nur; Zontul, Sezgin; Yolbas, Servet
    Background/Objectives: Familial Mediterranean Fever (FMF) is a chronic autoinflammatory disease in which some patients develop resistance to colchicine, resulting in persistent attacks and increased disease burden. This study aimed to compare clinical characteristics, disease activity, psychological status, and quality of life between colchicine-tolerant and colchicine-resistant FMF patients, and to identify clinical factors independently associated with colchicine resistance. Methods: This exploratory cross-sectional observational study was conducted in 120 FMF patients followed at a tertiary rheumatology center. Patients were classified as colchicine-tolerant or colchicine-resistant. Disease activity and damage were assessed using the International Severity Scoring System for FMF (ISSF) and the Autoinflammatory Disease Damage Index (ADDI). Quality of life was evaluated using the FMF-Health-Related Quality of Life (FMF-HQL) and WHO Quality of Life-BREF (WHOQoL-BREF) questionnaires. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Results: Colchicine-resistant patients had significantly higher attack frequency and disease activity scores (p < 0.001). Quality of life was impaired, with higher FMF-HQL and lower WHOQoL-BREF scores across all domains (p < 0.001). Anxiety and depression scores were also higher. ISSF and Doctor Global Assessment (DGA) were independently associated with colchicine resistance. Conclusions: Colchicine resistance in FMF was associated with increased disease activity, impaired quality of life, and greater psychological burden.
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    Effect of psoriatic arthritis on the strength, proprioception, skill, coordination, and functional condition of the hand
    (Wiley, 2022) Candiri, Busra; Talu, Burcu; Karaoba, Dilan Demirtas; Ozaltin, Gulfem Ezgi; Yolbas, Servet
    Background This study was planned to evaluate the strength, proprioception, skill, coordination, and functional condition of the hand in individuals with psoriatic arthritis and to correlate disease activity with these parameters. Methods Fifty-six individuals (psoriatic arthritis group, n = 36; control group, n = 20) were included in the study. Evaluations were performed of disease activity with Disease Activity Score 28; grip strength with a dynamometer and pinch strength with pinch gauge dynamometers; joint position sensation with a goniometer; finger skills with a mobile application; and coordination and skill of both hands with the Purdue Pegboard test. The Michigan Hand Outcomes Questionnaire (MHQ) was used for hand functional evaluation. Results There was a significant difference between the grip and pinch strength of the psoriatic arthritis group and the control group (P < 0.05). There was no significant difference between the joint position sense measurements and the mobile application scores between the groups (P > 0.05). Purdue Pegboard scores showed a significant difference only in both hands and assembly subsections (P < 0.05). With Disease Activity Score 28, significant correlations were found between grip and pinch strength, mobile application scores, Purdue Pegboard all subsections, and left-hand joint position sense average error amount, and between MHQ and grip and pinch strength. Conclusions This study is the first to show that psoriatic arthritis has a negative effect especially on hand strength; grip strength decreases as disease severity increases and, skill, coordination, and functionality of hand deteriorate.
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    Evaluation of right ventricular function in patients with Behcet's disease by four-dimensional echocardiography
    (Wiley, 2024) Ulutas, Zeynep; Tasolar, Hakan; Karaagac, Mirac; Hidayet, Siho; Karaca, Yucel; Bayramoglu, Adil; Yolbas, Servet
    AimBehcet's disease (BD) is a systemic disorder characterized by vasculitis, resulting in thickened vascular walls that reduce elasticity and impair function. BD can involve the cardiovascular system in three ways: cardiac, arterial, and venous. In this study, our objective was to evaluate the efficacy of pulmonary arterial stiffness (PAS) and pulmonary pulse transit time (PPTT) measures in demonstrating right ventricular functions in asymptomatic BD patients. We aimed to objectively evaluate right ventricular function in patients with BD using four-dimensional echocardiography (4DE).MethodThis study included 40 patients diagnosed with BD and 40 healthy subjects. Demographic, clinical, laboratory, and echocardiographic parameters were compared. In addition to standard transthoracic echocardiographic evaluation, right ventricle quantification (RVQ) by using the 4DE and 2D-speckle tracking echocardiography were performed.ResultsThe sPAP, 4D RVQ, and right ventricular strain values exhibited significant differences between the BD and control groups. Right ventricular end-diastolic diameter (RVDD), right ventricular end-systolic diameter (RVSD), right atrium (RA) area, right ventricular myocardial performance index (RVMPI), and PAS were increased in BD patients compared to the control group. Right ventricular ejection fraction (RVEF), right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), Tricuspid S', and PPTT were decreased in BD patients compared to control subjects. PPTT correlated with right ventricular free wall strain (RV-FWS) and PAS. In a multivariate linear regression analysis, PAS and RVFAC were found to be independent predictors of RVFWS. In addition, RVFAC and TAPSE are independent predictors for PPTT.ConclusionPatients with BD may have elevated pulmonary arterial stiffness (PAS) in correlation with decreased PPTT. To ascertain the prognosis for these individuals, right ventricular (RV) functions must be evaluated. Measurements of RVFAC and RVEF via 4DE and deformation imaging techniques may be more useful in identifying subclinical impairment of RV. Individuals with BD, PAS, and PPTT may suggest a link between early pulmonary vascular remodeling and RV subclinical impairment. Four-dimensional transthoracic echocardiography evaluation of right ventricular function allows more detailed and comprehensive imaging in BD patients. image
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    GASTROINTESTINAL INVOLVEMENT IN SJÖGREN’S DISEASE
    (2025) Atayan, Yahya; Yolbas, Servet; İnanç, Elif; Albayram, Fuat
    Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands, which can also affect the gastrointestinal (GI) tract, hepatobiliary system, and pancreatic exocrine tissues. Approximately one-third of patients experience GI-related symptoms, with xerostomia, dysphagia, dyspepsia, and atrophic gastritis being the most commonly reported manifestations. SjD is also associated with autoimmune liver diseases, including autoimmune hepatitis and primary biliary cholangitis. Pancreatic involvement is less frequent, but may present as autoimmune pancreatitis or exocrine pancreatic insufficiency. The complexity of SjD and the variety of its manifestations underscore the importance of a multidisciplinary management approach, where collaboration among healthcare professionals is crucial for optimising patient outcomes.
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    The importance of pulmonary pulse transit time in indicating right ventricular dysfunction and pulmonary arterial stiffness in rheumatoid arthritis
    (Wiley, 2023) Ulutas, Zeynep; Tasolar, Hakan; Bayramoglu, Adil; Yigit, Yakup; Kuloglu, Huseyin Emre; Karaca, Yucel; Yolbas, Servet
    Subject Rheumatoid arthritis patients are at risk of developing cardiovascular disease such as right heart failure and pulmonary hypertension (PH). Arterial stiffness can be used to assess pulmonary hemodynamics. Noninvasive approaches can also be used to assess pulmonary hemodynamics. Recently, there have been reports that pulmonary pulse transit time (PPTT) may also be a useful measure. This study aims to examine the effects of pulmonary hemodynamic alterations on PPTT in RA patients.Methods Forty RA patients and 40 healthy controls were included in the study. Sociodemographic characteristics, laboratory data, and echocardiographic examinations were performed in both groups. Conventional echocardiographic examination included left and right ventricular systolic and diastolic diameters, right ventricular myocardial performance index (RVMPI), right ventricular diastolic function, estimated pulmonary artery systolic pressure (sPAP), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery stiffness (PAS), and PPTT. Right ventricular diastolic and systolic volumes, right ventricular ejection fraction (RVEF), and right ventricular fractional area change (RVFAC) were determined by four-dimensional echocardiography (4DE).Results There was no difference between the sPAP values of the patients. RVMPI and PAS were increased in RA patients compared with controls. The PPTT was shortened in RA patients and correlated with RVEF, RVFAC, RVMPI, TAPSE/sPAP, disease duration, and C-reactive protein (CRP). In univariate linear regression analysis, PPTT (p < .001) was thought to be an independent predictor of PAS. RVFAC, disease duration, and PAS were also independent predictors of PPTT.Conclusion In RA patients, PPTT may be the first evidence of early abnormalities in pulmonary vascular hemodynamics. PPTT and PAS are the values that may predict each other in RA patients. Due to its more practical application, PPTT can be used instead of PAS to assess pulmonary hemodynamics.
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    Increased Musculoskeletal Surgery Rates During Diagnostic Delay in Psoriatic Arthritis: A Retrospective Cohort Study
    (Mdpi, 2025) Yolbas, Servet; Gunduz, Ilyas; Kara, Mahmut; Cay, Emrah; Yamancan, Guelsah; Yalcin, Nevra; Inanc, Elif
    Background/Objectives: Delayed diagnosis in psoriatic arthritis (PsA) is associated with significant health consequences. We hypothesize that musculoskeletal (MSK) surgery rates may be higher during the diagnostic delay period. This study aimed to compare the frequency of MSK surgeries in PsA patients during the period of diagnostic delay with the frequency of MSK surgeries post-diagnosis. Methods: This retrospective cohort study included PsA patients who fulfilled CASPAR criteria and were followed up on in our outpatient clinic. The pre-diagnosis symptomatic period was considered as the period of diagnostic delay. Data on MSK surgeries were obtained from patient records. The annual number of surgeries was calculated separately for the diagnostic delay and post-diagnosis periods. Results: The study included 84 PsA patients. The mean diagnostic delay in PsA patients was 7.49 years. During this period, 27.4% of patients underwent at least one MSK surgery. The mean annual number of MSK surgeries was significantly higher during the diagnostic delay period compared to the post-diagnosis period (Z = -3.18, p = 0.001, r = 0.35). Conclusions: Following PsA diagnosis, a reduction in MSK surgery rates was observed compared to during the diagnostic delay period. This suggests that inflammatory symptoms in PsA patients, which could have been managed with medical therapy, may have led to avoidable MSK surgeries. These findings highlight the potential for early diagnosis to reduce the rate of musculoskeletal surgery and associated healthcare costs.
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    INCREASED PREVALENCE OF SCOLIOSIS IN PSORIATIC ARTHRITIS: A CROSS-SECTIONAL CASE-CONTROL STUDY
    (2025) Gözükara Bag, Harika Gözde; Ergen, Emre; Yolbas, Servet; Aydogdu, Mesude Seda; Kaya, Zeynep; Zontul, Sezgin; İnanç, Elif
    Aim: Psoriatic arthritis (PsA) is expected to cause an increased risk of scoliosis because it affects the axial skeleton asymmetrically. In this study, we compared the frequency of scoliosis in PsA patients with that in healthy controls (HC) and axial spondyloarthritis (axSpA) patients. Thus, we aimed to explore whether scoliosis might be a clinical feature of PsA and to assess its potential role in differentiating PsA from axSpA. Material and Methods: The study included 60 PsA patients, 60 axSpA patients and 40 HC. All individu-als in the study were assessed for the presence of scoliosis by physical examination. Scoliosis radiog-raphy was performed in those with a positive scoliosis test on physical examination. The Cobb angle was measured using the appropriate method. A two-tailed significance level of 0.05 was considered in all analyses. Results: Within this research, the frequency of scoliosis in PsA patients was compared with the axSpA and HC groups. The Cobb angle value was notably higher in the PsA group compared to axSpA and HC (p=0.006 and p=0.007, respectively). On physical examination, scoliosis findings and coronal spinal curvature, were observed at elevated rates in the PsA group relative to the other two groups (p>0.05 for all, indicating no statistical significance). Scoliosis was more frequent in the PsA group than in the axSpA group (p=0.046). All scoliosis cases in PsA were in mild or moderate severity. Conclusion: Both the frequency of scoliosis and Cobb angle values were greater in PsA than those in axSpA. This outcome may be associated with the asymmetric involvement of lateral spinal structures typical of PsA. Overall, these results indicate that scoliosis could serve as a supportive marker for PsA and may aid in differentiating PsA from axSpA.
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    Is combining methotrexate and leflunomide a safe option for treating rheumatoid arthritis?
    (2025) Aktürk, Semra; Yolbas, Servet; Güneş, Hatice Kübra; Kürüm, Kübra Orhan; Zontul, Sezgin; İnanç, Elif; Çulcu, Sena Cengiz
    Rheumatoid arthritis (RA) is a chronic immune-mediated disease marked by synovial inflammation and systemic features. Early management typically relies on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), with methotrexate (Mtx) serving as the primary therapeutic agent. When Mtx is contraindicated, leflunomide (Lef) can be used as a treatment strategy. There are concerns about hepatotoxicity, cytopenia, pneumonia, and increased risk of infection when these therapies are combined. In this study, we aimed to evaluate the side effects and treatment duration of the Mtx/Lef combination in patients with RA. All patients admitted to the Rheumatology clinic between 2016 and 2023 and diagnosed with RA were retrospectively reviewed. Patients who received Mtx/Lef combination therapy during this period were identified. The data for patients who continued Mtx/Lef combination therapy were recorded at the last visit, and those who discontinued the combination therapy were recorded at the visit of discontinuation. Adverse effects associated with Mtx/Lef combination therapy were assessed through retrospective review of clinical follow-up notes, laboratory test results, and drug safety monitoring forms. Adverse events leading to treatment discontinuation were classified as either due to side effects or lack of therapeutic response. This study was conducted with a total of 222 participants, comprising 184 females (82.9%) and 38 males (17.1%). No side effects were observed in 141 (63.5%) patients after Mtx/Lef use. Gastrointestinal system side effects were observed in 16.7% of the participants, followed by elevated liver function tests in 11.3%. It was determined that 55% of the participants were unable to continue treatment due to treatment ineffectiveness or side effects. Our study results offer a good safety profile and long-term drug survival. Survival in long-term treatment may contribute to reducing treatment costs.
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    Liver Enzyme Elevations in Rheumatoid Arthritis: Clinical Relevance and Influence on Treatment Strategies
    (Mdpi, 2025) Atayan, Yahya; Yolbas, Servet; Bodakci, Emin
    Background and Aim: Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis of unknown etiology that symmetrically involves the synovial joints and leads to erosive arthritis. However, when inflammation remains uncontrolled, it not only affects the joints but also increases the risk of various systemic complications, particularly cardiovascular diseases, osteoporosis, and malignancies such as lymphoma. Early initiation of disease-modifying antirheumatic drugs (DMARDs) has been shown to yield superior outcomes in terms of both clinical response and the prevention of joint damage. Nevertheless, the development of hepatotoxicity during treatment may necessitate dose adjustments or even modifications of the therapeutic protocol. Our aim in this study was to retrospectively evaluate the changes in liver enzyme levels in RA patients before and during treatment, especially in MTX and combination therapies using MTX, and to evaluate how these abnormalities affect treatment strategies. Materials and Methods/Results: Among the 33 patients included in this study, 15 exhibited elevated liver enzymes prior to treatment, whereas 18 developed hepatic enzyme abnormalities during therapy. Of the 12 patients receiving methotrexate (MTX) monotherapy and the 15 patients using MTX within a combination regimen, a total of 7 patients (21%) continued to present with elevated liver enzymes during follow-up. Among these, 5 patients (19%) were managed successfully by reducing the MTX dose, while MTX therapy had to be completely discontinued in 2 patients (7%). Notably, all 7 patients who required treatment modification due to persistent enzyme elevation belonged to the group with pre-existing liver enzyme abnormalities and were receiving MTX as part of a combination therapy regimen. Conclusions: These findings indicate that hepatotoxicity risk in RA patients can be effectively managed through close laboratory monitoring and timely dose reduction, with treatment discontinuation being required only in rare cases.
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    Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates experimentally induced arthritis
    (Tubitak Scientific & Technological Research Council Turkey, 2018) Yolbas, Servet; Yildirim, Ahmet; Tektemur, Ahmet; Celik, Zulfinaz Betul; Onalan Etem, Ebru; Ozercan, Ibrahim Hanifi; Akin, Mehmet Mustafa
    Background/aim: The Wnt/beta-catenin pathway has important biological activities, including the differentiation of cells and joint formations. The aim of our study was to determine the effect of paricalcitol on experimentally induced arthritis. Materials and methods: Type II collagen combined with Freund's adjuvant was applied to induce arthritis in Wistar albino female rats. Paricalcitol (0.3 mu g/kg daily) was subcutaneously injected starting 1 day after collagen applications (prophylactic group) or 1 day after the onset of arthritis (therapeutic group), until day 29. Results: The 29th day arthritis scores were lower compared to the 13th day scores in the paricalcitol groups (P < 0.05), while they were higher in the arthritis group (P < 0.05). Marked cartilage-bone destruction and extensive perisynovial inflammation were detected in the arthritis group. Decreased cartilage-bone destruction and perisynovial inflammation in the paws were observed in the paricalcitol groups. The tissue mRNA levels of DKK1, Wnt5a, and axin-2 were higher in the arthritis group than in the control group. In the paricalcitol groups, mRNA expressions were lower than in the arthritis group. Conclusion: The present study shows that the Wnt/beta-catenin signaling pathway is active in arthritis. Moreover, paricalcitol ameliorates arthritis via inhibiting the Wnt/beta B-catenin pathway. Paricalcitol and the Wnt/beta-catenin pathway are candidates for research in human rheumatoid arthritis.
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    Paricalcitol inhibits the wnt/beta-catenin signaling pathway and ameliorates experimentally inducedarthritis
    (Tubıtak scıentıfıc & technıcal research councıl turkey, ataturk bulvarı no 221, kavaklıdere, ankara, 00000, turkey, 2018) Yolbas, Servet; Yildirim, Ahmet; Tektemur, Ahmet; Celik, Zulfinaz Betul; Onalan Etem, Ebru; Ozercan, Ibrahim Hanifi; Akin, Mehmet Mustafa; Koca, Suleyman Serdar
    Background/aim: The Wnt/beta-catenin pathway has important biological activities, including the differentiation of cells and joint formations. The aim of our study was to determine the effect of paricalcitol on experimentally induced arthritis. Materials and methods: Type II collagen combined with Freund's adjuvant was applied to induce arthritis in Wistar albino female rats. Paricalcitol (0.3 mu g/kg daily) was subcutaneously injected starting 1 day after collagen applications (prophylactic group) or 1 day after the onset of arthritis (therapeutic group), until day 29. Results: The 29th day arthritis scores were lower compared to the 13th day scores in the paricalcitol groups (P < 0.05), while they were higher in the arthritis group (P < 0.05). Marked cartilage-bone destruction and extensive perisynovial inflammation were detected in the arthritis group. Decreased cartilage-bone destruction and perisynovial inflammation in the paws were observed in the paricalcitol groups. The tissue mRNA levels of DKK1, Wnt5a, and axin-2 were higher in the arthritis group than in the control group. In the paricalcitol groups, mRNA expressions were lower than in the arthritis group. Conclusion: The present study shows that the Wnt/beta-catenin signaling pathway is active in arthritis. Moreover, paricalcitol ameliorates arthritis via inhibiting the Wnt/beta B-catenin pathway. Paricalcitol and the Wnt/beta-catenin pathway are candidates for research in human rheumatoid arthritis.
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    Resveratrol inhibits Src tyrosine kinase, STAT3, and Wnt signaling pathway in collagen induced arthritis model
    (Wiley, 2019) Oz, Burak; Yildirim, Ahmet; Yolbas, Servet; Celik, Zulfinaz Betul; Etem, Ebru Onalan; Deniz, Gulnihal; Akin, Mustafa
    Resveratrol, a phytochemical, acts several cellular signaling pathways and has anti-inflammatory potentials. The purpose of this study is to research the therapeutic effect of resveratrol in collagen-induced arthritis (CIA) model in rats and whether resveratrol affects the activities of signaling pathways those are potent pathogenic actors of rheumatoid arthritis. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant in Wistar albino rats. One day after the onset of arthritis (day 14), resveratrol (20 mg/kg/day) was given via oral gavage, until day 29. The paws of the rats were obtained for further analysis. Tissue Wnt5a, mitogen-activated protein kinase (MAPK), Src tyrosine kinase and signal transducer, and activator of transcription-3 (STAT3) mRNA expressions were determined by real-time polymerase chain reaction. Resveratrol ameliorated the clinical and histopathological (perisynovial inflammation and cartilage-bone destruction) findings of inflammatory arthritis. The tissue mRNA expressions of Wnt5a, MAPK3, Src kinase, and STAT3 were increased in the sham group compared to the control group. Resveratrol supplement decreased their expressions. The present study shows that Src kinase, STAT3, and Wnt signaling pathway are active in the CIA model. Resveratrol inhibits these signaling pathways and ameliorates inflammatory arthritis. (c) 2018 BioFactors, 45(1):69-74, 2019
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    The role of A268V exon-7 polymorphism of PPARA in development of axial spondyloarthritis
    (Walter De Gruyter Gmbh, 2022) Akbulut, Ekrem; Yolbas, Servet; Ozgen, Metin
    Objectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton. Peroxisome proliferator activated receptor alpha (PPARA) is an intracellular transcription factor, which play a role in inflammation and osteoblasting activity. This study is designed to investigate the relationship of NG_012204.2:p.A1a268Val polymorphism of PPARA with axSpA risk and its role in disease development. Methods: This study was conducted with 168 patients and 181 controls. Genotyping was done with MALDITOF. Gene expression level was analyzed by quantitative real time PCR (RT-qPCR). The protein homology models of PPARA were created with ProMod3. Ligand binding dynamics were tested using the AutoDock4 docking program. Statistical evaluations were made with SPSS (ver24) and GeneGlobe. Results: Our results showed that C>T polymorphism causing NG_012204.2:p.A1a268Val change was associated with disease risk (p=0.024) and T allele increased disease risk 1.7 times (95% CI=1.070-2.594). PPARA expression decreased (p<0.05) in individuals carrying the T allele. We determined that the ligand entry pocket was opened 1.1 A in the polymorphic PPARA. Polymorphic change caused a decrease in the ligand binding affinity. Conclusions: Our results provide an important contribution to elucidating the development of axSpA and demonstrate the potential of PPARA as a marker for the diagnosis of axSpA.
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    The rs3768777-G allele of ITGAV gene is associated with rheumatoid arthritis
    (Springer Heidelberg, 2014) Koca, Suleyman Serdar; Kara, Murat; Ozgen, Metin; Dagli, Mustafa Necati; Gozel, Nevzat; Yolbas, Servet; Gundogdu, Baris
    Integrin alpha v beta 3 (vitronectin receptor) plays a prominent role in angiogenesis, a key pathogenic feature of rheumatoid arthritis (RA). Moreover, integrin alpha(V) (ITGAV) subunit gene has been associated with a susceptibility to RA. The aim of the present study was to detect the potential association between ITGAV gene polymorphisms and a susceptibility to RA in a Turkish cohort. DNA samples were harvested from 160 patients with RA and 144 healthy controls (HC). Three single-nucleotide polymorphisms of ITGAV gene (rs3738919, rs3768777, and rs10174098) were genotyped using real-time PCR. Serum vitronectin levels were analyzed in 30 RA patients, 28 Beh double dagger et's disease (BD) patients, and 30 HC subjects. There was no significant difference between the RA and HC groups in terms of the genotypic and allelic distributions of rs3738919 and rs10174098 polymorphisms. However, the prevalence of rs3768777-G allele was higher in the RA group than in the HC group (OR 2.3, 95 % CI 1.6-3.2, p < 0.0001). Moreover, there was a significant association between RA and the genotypic distribution of rs3768777 (GG + AG vs. AA: OR 2.1, 95 % CI 1.3-3.4; GG vs. AG + AA: OR 4.1, 95 % CI 2.1-7.8). Serum vitronectin levels were lower in the RA and BD groups than in the HC group (p (ANOVA) = 0.002). The rs3738919 and rs10174098 polymorphisms of the ITGAV gene seem not to be associated with susceptibility to RA in Turkish patients. However, rs3768777 increases the risk of RA in this group. These results suggest that the ITGAV gene may be a candidate gene for the etiopathogenesis of RA.
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