Person: ALİBAZ ÖNER, FATMA
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ALİBAZ ÖNER
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FATMA
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Publication Open Access Assessment of the frequency of cardiovascular risk factors in patients with Takayasu's arteritis(OXFORD UNIV PRESS, 2017-11-01) ÇIKIKÇI, CEYLAN; Alibaz-Oner, Fatma; Koster, Matthew J.; Unal, Ali U.; Yildirim, Hale G.; Cikikci, Ceylan; Schmidt, Jean; Crowson, Cynthia S.; Makol, Ashima; Ytterberg, Steven R.; Matteson, Eric L.; Direskeneli, Haner; Warrington, Kenneth J.Objectives. The prevalence of atherosclerotic risk factors and disease in Takayasu's arteritis (TAK) has not been well defined. We aimed to assess the frequency of cardiovascular (CV) risk factors and the incidence of CV events (CVEs) in patients with TAK from two ethnically different populations. Methods. Patients with TAK followed at Mayo Clinic, Rochester, MN, USA and Marmara University, Istanbul, Turkey were included in this retrospective study. Patients with TAK were compared with age-, sex- and calendar year-matched controls from the same geographical region without TAK. The 2008 Framingham 10-year general CV risk score (FRS) was used for the evaluation of CV risk at the time of TAK incidence/index date. Results. In total, 191 patients with TAK and 191 non-TAK controls were included. Hypertension and the prevalence of lipid-lowering treatments were significantly more frequent in TAK. Prior to the incidence/index date, occurrence of CVE was significantly higher in TAK. The FRS was significantly higher in TAK compared with non-TAK at incidence/index date. The cumulative incidence of CVE was 15.4% at 10 years in TAK vs 5.8% in non-TAK; the risk of CVE was increased among patients with TAK (hazard ratio = 4.36; 95% CI: 1.25, 15.13). Conclusion. CV risk factors are more common in patients with TAK, particularly hypertension. The FRS is higher in patients with TAK at the time of diagnosis. The cumulative incidence of CVE was also significantly higher during follow-up in TAK. Our results suggest that patients with TAK should undergo careful assessment of CV risk factors, and an aggressive risk modification approach is warranted.Publication Open Access Advances in the Treatment of Behcet's Disease(SPRINGER, 2021-06) ALİBAZ ÖNER, FATMA; Alibaz-Oner, Fatma; Direskeneli, HanerPurpose of Review To assess current management of Behcet's disease (BD). Controversies on therapeutic approaches to different manifestations, whether conventional immunosuppressives (IS) or biologic agents, should be chosen, and options for refractory disease are discussed. Recent Findings Glucocorticoids are still the main agents for remission-induction and azathioprine the first-line conventional IS in maintenance phase to prevent relapses of major organ involvement. Apremilast is shown to be a safe and effective option approved by the FDA for oral ulcers. Large case series confirmed the efficacy and safety of TNF alpha inhibitors and Interferon-alpha. Promising results are observed with IL-1 inhibitors, ustekinumab, secukinumab, and tocilizumab for refractory BD. Although both conventional IS and biologic agents are effectively used to suppress inflammation in BD, there is still an unmet need for clear therapeutic strategies in the management for different manifestations. Further controlled studies with new biologic agents, anticoagulants and the benefit of concomitant IS usage with biologics are needed to optimize the management of BD.Publication Open Access Biologic treatments in Behcet's disease(AVES, 2021-11-22) ALİBAZ ÖNER, FATMA; Alibaz-Oner, Fatma; Direskeneli, HanerBehcet's disease (BD) significantly increases morbidity and mortality, especially in young men. While vascular involvement is the most frequent cause of mortality, ocular involvement, which can cause visual loss, is the most important cause of morbidity in BD. Immunosuppressive treatment is the mainstay for major organ involvement. However, despite optimal immunosuppressive treatment, relapses and disease-related damage develop in a subgroup of patients, especially among those with ocular or vascular involvement. With the recent understanding of the immuno-pathogenesis, biologic treatments targeting potential pathogenic cells, cytokines or pathways are better optimized in BD. Data from large series showed that tumor necrosis factor-alpha inhibitors and interferon-alpha are effective and safe treatment options for the treatment of refractory and major organ involvement, such as ocular, neurologic, vascular, and gastrointestinal. Anakinra and ustekinumab also seem to be promising agents for refractory mucocutaneous disease. IL-1 inhibitors and tocilizumab may be alternatives for the treatment of patients with refractory eye involvement. Still, randomized controlled trials of biologic agents, especially for the treatment of major organ involvement, are insufficient, and further prospective, long-term follow-up studies are needed to clarify the efficacy, safety, and optimal treatment duration of biologic agents in BD.Publication Open Access IS RELAPSE RATE OF GIANT CELL ARTERITIS IN REAL-LIFE EXPERIENCE LOWER THAN IN THE CONTROLLED TRIALS? RESULTS OF A RETROSPECTIVE, MULTI-CENTRE COHORT STUDY(BMJ PUBLISHING GROUP, 2018-06) ALİBAZ ÖNER, FATMA; Alibaz-Oner, F.; Balci, M. A.; Pamuk, O. N.; Zengin, O.; Tasci, M.; Dogru, A.; Bayindir, O.; Yavuz, S.; Cefle, A.; Tezcan, M. E.; Oksuz, M. F.; Kucuksahin, O.; Omma, A.; Bilge, S. Yasar; Kasifoglu, T.; Erturk, Z.; Bes, C.; Unal, A. U.; Armagan, B.; Gonullu, E.; Yazici, A.; Karadag, O.; Dalkilic, E.; Aksu, K.; Keser, G.; Direskeneli, H.Publication Open Access Pulmonary artery wall thickness is increased in behcet's disease(2022-06-01) DİRESKENELİ, RAFİ HANER; ALİBAZ ÖNER, FATMA; Agackiran S. K. , Sunbul M., Kocakaya D., Kayaci S., DİRESKENELİ R. H. , Alibaz-Oner F.Publication Open Access Development of a Core Set of Outcome Measures for Large-vessel Vasculitis: Report from OMERACT 2016(2017-12) ALİBAZ ÖNER, FATMA; Sreih, Antoine G.; Alibaz-Oner, Fatma; Kermani, Tanaz A.; Aydin, Sibel Z.; Cronholm, Peter F.; Davis, Trocon; Easley, Ebony; Gul, Ahmet; Mahr, Alfred; McAlear, Carol A.; Milman, Nataliya; Robson, Joanna C.; Tomasson, Gunnar; Direskeneli, Haner; Merkel, Peter A.Objective. Among the challenges in conducting clinical trials in large-vessel vasculitis (LVV), including both giant cell arteritis (GCA) and Takayasu arteritis (TA), is the lack of standardized and meaningful outcome measures. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group initiated an international effort to develop and validate data-driven outcome tools for clinical investigation in LVV. Methods. An international Delphi exercise was completed to gather opinions from clinical experts on LVV-related domains considered important to measure in trials. Patient interviews and focus groups were completed to identify outcomes of importance to patients. The results of these activities were presented and discussed in a “Virtual Special Interest Group” using telephone- and Internet-based conferences, discussions through electronic mail, and an in-person session at the 2016 OMERACT meeting. A preliminary core set of domains common for all forms of LVV with disease-specific elements was proposed. Results. The majority of experts agree with using common outcome measures for GCA and TA, with the option of supplementation with disease-specific items. Following interviews and focus groups, pain, fatigue, and emotional effect emerged as health-related quality of life domains important to patients. Current disease assessment tools, including the Birmingham Vasculitis Activity Score, were found to be inadequate to assess disease activity in GCA and standardized assessment of imaging tests were felt crucial to study LVV, especially TA. Conclusion. Initial data from a clinician Delphi exercise and structured patient interviews have provided themes toward an OMERACT-endorsed core set of domains and outcome measures.Publication Metadata only Femoral vein wall thickness measurement: A new diagnostic tool for Behcet's disease(OXFORD UNIV PRESS, 2021) ALİBAZ ÖNER, FATMA; Alibaz-Oner, Fatma; Ergelen, Rabia; Yildiz, Yasin; Aldag, Mustafa; Yazici, Ayten; Cefle, Ayse; Koc, Ertan; Esen, Bahar Artim; Mumcu, Gonca; Ergun, Tulin; Direskeneli, HanerObjectives. Diagnosing Behcet's disease (BD) is a challenge, especially in countries with a low prevalence. Recently, venous wall thickness (VWT) in lower extremities has been shown to be increased in BD patients. In this study, we aimed to investigate the diagnostic performance of common femoral vein (CFV) thickness measurement in BD and whether it can be used as a diagnostic tool. Methods.. Patients with BD (n=152), ankylosing spondylitis (n=27), systemic vasculitides (n=23), venous insufficiency (n=29), antiphospholipid syndrome (APS; n=43), deep vein thrombosis due to non-inflammatory causes (n=25) and healthy controls (n=51) were included in the study. Bilateral CFV thickness was measured with ultrasonography by a radiologist blinded to cases. Results. Bilateral CFV thickness was significantly increased in BD compared with all control groups (P < 0.001 for all). The area under the receiver operating characteristic curve for bilateral CFV thicknesses in all comparator groups was >0.95 for the cut-off value (0.5 mm). This cut-off value also performed well against all control groups with sensitivity rates >90%. The specificity rate was also >80% in all comparator groups except APS (positive predictive value: 79.2-76.5%, negative predictive value: 92-91.8% for right and left CFV, respectively). Conclusion. Increased CFV thickness is a distinctive feature of BD and is rarely present in healthy and diseased controls, except APS. Our results suggest that CFV thickness measurement with ultrasonography, a non-invasive radiological modality, can be a diagnostic tool for BD with sensitivity and the specificity rates higher than 80% for the cut-off value >= 0.5mm.Publication Open Access Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement(2023-06-02) ALİBAZ ÖNER, FATMA; Casares-Marfil D., Esencan D., Alibaz-Oner F., Çefle A., Yazıcı A., Duzgun N., Aşık M. A., Özbek S., Cinar M., Alpsoy E., et al.Behçet’s disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet’s disease in a group of patients with > 20 years of follow up. A total of 436 patients with Behçet’s disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet’s disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR=1.85, 95% CI=1.35-2.52, p-value=1.1x10-4 ). The genetic risk score was significantly higher in Behçet’s disease patients with ocular lesions compared with those without ocular involvement, and is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet’s disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A (rs6062789: OR=0.41 (95% CI=0.30-0.58), p-value=1.92x10-7 ), and neurological involvement with DDX60L (rs62334264: OR= 4.12 (95% CI 2.34 to 7.24), p-value = 8.85x10-7 ). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet’s disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet’s disease presentation across populations.Publication Metadata only Kronik aerobik egzersizin takayasu arteritinde kardiyopulmoner sağlamlık ve vasküler fonksiyon üzerine olası koruyucu etkilerinin araştırılması(2022-05-12) ALİBAZ ÖNER, FATMA; DİRESKENELİ, RAFİ HANER; KASIMAY ÇAKIR, ÖZGÜR; Harman Yerli N., Abacar K., Alibaz Öner F., Direskeneli R. H., Kasımay Çakır Ö.Giriş: Takayasu arteriti (TA), büyük damarları etkileyen nadir bir vaskülittir.Amaç: Kronik aerobik egzersiz uygulamasının TA hastalığında olası koruyucu etkisininaraştırılması.Yöntem: Araştırmaya 20-55 yaş arasında 17 kadın TA hastası ve yaş ve Beden Kitle İndeksi(BKİ) eşleştirilmiş 11 kadın sağlıklı kontrol dahil edilmiştir (KON). TA hastaları; egzersizyapmayan grup (TAK, n=9) ve 12 hafta süreyle egzersiz yapan grup (TAK+Egz, n=8) olarakayrılmışlardır. Çalışma iki aşama olarak bazal ve deney sonu ölçümleri şeklindeplanlanmıştır; her iki aşamada da bütün katılımcılar antropometrik ölçümler, koşu bandıüzerinde kardiyopulmoner egzersiz testi (KPET), yakın kızılötesi spektroskopisi (NIRS)ölçümü, akım aracılı dilatasyon (FMD) ölçümleri, kan örnekleri, yaşam kalitesi anketi içinteste tabii tutulmuşlardır. Bazal ölçümleri alındıktan sonra TAK+Egz grubu 12 haftalıksüreçte haftada 3 gün ortayüksek şiddette zumba egzersizi yapmıştır. KON ve TAK grubuyapılandırılmış herhangi bir fiziksel aktiviteye katılmamışlardır.Bulgular: TAK ve TAK+Egz gruplarının maksimum oksijen tüketimi (VO2maks) ve%FMD’si bazal ölçümlerde kontrole göre daha düşüktü (p<0.05-0.01); TAK+Egz grubununVO2maks düzeyleri ve %FMD’si yükselmiştir (p<0.05). Anaerobik eşikteki oksijen tüketimi(VO2AT) TAK grubunda ilk ve son ölçümlerde KON grubundan daha düşüktü, TAK+Egzgrubunda ise egzersiz sonrasında bazale göre VO2AT değerleri yükselmiştir (p<0.05-0.01).İlk ölçümlerde TAK ve TAK+Egz grubunun maksimum kalp hızı (KHmaks) değerlerikontrolden daha düşükken egzersiz antrenmanıyla TAK+Egz grubunda ilk ölçüme kıyasla sonölçümde artmıştır (p<0.05). NIRS ölçümlerinde KON grubuna kıyasla TA gruplarında birfarklılık görülmezken, TAK+Egz grubunda egzersizle birlikte izometrik egzersizi sırasındaminimum % satürasyon ve derlenmede ortalama satürasyon artmıştır (p<0.05).Tartışma ve Sonuç: Çalışmamız egzersiz antrenmanının TA’de kardiyopulmoner sağlamlığıarttırdığını ve vasküler fonksiyonu iyileştirdiğini düşündürmektedir.Anahtar Sözcükler: Takayasu arteriti, egzersiz, endotelyal fonksiyon, VO2maks, anaerobikeşik.Publication Open Access Vascular Behcet's disease: a comparative study from Turkey and France(2022-08-01) ALİBAZ ÖNER, FATMA; DİRESKENELİ, RAFİ HANER; Alibaz-Oner F., Vautier M., Aksoy A., Mirouse A., Le Joncour A., Cacoub P., Ilgin C., Saadoun D., DİRESKENELİ R. H.Objective Vascular Behcet\"s disease (VBD) is a systemic vasculitis involving both arterial and venous vessels of all sizes and occurring in up to 40% of patients with BD. VBD is the main cause of mortality in BD. Although commonly seen around the Mediterranean region, comparative studies in VBD are lacking. We aimed to compare the course and therapeutic approaches of VBD in two large cohorts from Turkey and France. Methods We included 291 VBD patients (female/male:63/228, mean age: 41.2 +/- 11.3 years) who were followed up in the Department of Internal Medicine and Clinical Immunology at Pitie-Salpetriere Hospital, Sorbonne University, Paris, France (n=131) and Rheumatology Division of Marmara University School of Medicine, Istanbul, Turkey (n=160). All clinical and demographical data were acquired from patient charts retrospectively. Results Smoking, family history for BD, HLA-B*51 presence and pathergy positivity were significantly higher in Turkish patients (TR), while neurologic involvement was more prominent in the French (FR) group. After a median follow-up of 77 months, 562 vascular events occurred including 440 venous events, 115 arterial events and 7 cardiac thrombi. In 79 (29%) patients, first vascular event developed before BD diagnosis and for 77 (28%) of them, vascular involvement was the presenting sign of the disease. First relapse developed in 130 (44.7%) patients after median 24.5 (1-276) months of follow-up (TR: 46.3% (n=74), FR: 42.7% (n=56), p=0.56). Survival graph revealed that FR cohort has 1.64 times increased recurrent event risk compared to TR cohort (HR=1.64 (1.1-2.44), p=.014) and although did not reach to statistical significance, IS treatment after the first vascular event decreased further vascular events (HR= 0.66 (0.43-1.01, p=.057). Conclusion Almost half of patients relapsed of VBD within 2 years after the first vascular event. Immunosuppressants decrease VBD relapses.