Person: DİRESKENELİ, RAFİ HANER
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DİRESKENELİ
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RAFİ HANER
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Publication Open Access 2022 American college of rheumatology/EULAR classification criteria for Takayasu arteritis(2022-12-01) DİRESKENELİ, RAFİ HANER; Grayson P. C., Ponte C., Robson J. C., Gribbons K. B., Judge A., Craven A., Khalid S., Hutchings A., Danda D., Luqmani R. A., et al.Objective: To develop and validate new classification criteria for Takayasu arteritis (TAK). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate criteria items, 2) collection of candidate items present at diagnosis, 3) expert panel review of cases, 4) data-driven reduction of candidate items, 5) derivation of a points-based classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large-vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1), and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% confidence interval [95% CI] 0.94–0.99) with a sensitivity of 93.8% (95% CI 88.6–97.1%) and specificity of 99.2% (95% CI 96.7–100.0%). Conclusion: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.Publication Metadata only Mo174fibroscan detection of fatty liver and liver fibrosis in systemic lupus erythematosus(2021-05-01) BARUTÇU ATAŞ, DİLEK; VELİOĞLU, ARZU; ARIKAN, İZZET HAKKI; ALİBAZ ÖNER, FATMA; DİRESKENELİ, RAFİ HANER; TUĞLULAR, ZÜBEYDE SERHAN; AŞICIOĞLU, EBRU; Yetginoğlu Ö., BARUTÇU ATAŞ D., VELİOĞLU A., ARIKAN İ. H., YILMAZ Y., ALİBAZ ÖNER F., DİRESKENELİ R. H., TUĞLULAR Z. S., AŞICIOĞLU E.BACKGROUND AND AIMS: Systemic Lupus Erythematosus (SLE) is a chronic, multi-organ, systemic autoimmune disease that is more common in women than men and is typically diagnosed during the reproductive age. Although liver dysfunction is not considered the main organ pathology in SLE, the frequency of liver dysfunction or abnormal liver enzyme values may be observed in 50-60% of patients. Liver-related complications may present as asymptomatic hepatomegaly, subclinical steatosis and abnormal liver enzymes. The most common causes are drug-associated liver injury, lupus-associated hepatitis, and fatty liver disease. The aim of this study was to assess fatty liver and liver fibrosis in SLE patients using the FibroScan method as well as associated factors such as immunosuppressive medications. METHOD: Sixty SLE patients and 30 healthy controls were included. Patients with HBV, HCV or cirrhosis, malignancy, cardiac disease, or patients on dialysis were excluded. All participants underwent FibroScan measurements. Demographic data and cumulative doses of immunosuppressive medications were extracted from patient charts. Fasting blood was collected for analysis RESULTS: Demographic and clinical characteristics of the study groups are shown in Tables 1. The prevalence of fatty liver disease was similar between SLE patients and healthy controls (21.7% vs 26.7%, p= 0.597) and was associated with body mass index (BMI) (p= 0.026) and C-reactive protein (CRP) (p= 0.046) in multivariate analysis. Liver fibrosis was also similar between the two groups (26.7% vs 10.0%, p= 0.069). There was no relationship between cumulative drug doses including glucocorticoids with either fatty liver disease or liver fibrosis. Since the majority of SLE patients were female, we performed a subgroup analysis in female patients (n=51) and healthy controls (n=25). Fatty liver disease was similar between female SLE patients and healthy controls (23.5% vs 24.0%, p= 0.964). However, liver fibrosis in female patients with SLE was increased compared to the female healthy population (29.4% vs 4.0%, p= 0.011) and was associated with age (p= 0.034) and low-dose cumulative glucocorticoid use (p = 0.034). Low-dose cumulative glucocorticoid use was defined as less than 17.45 g, which was the 75th percentile value. Only 1 out of 15 female patients with fibrosis had high-dose cumulative glucocorticoid use (>17.45 g), while the remaining 14 patients had used lower doses (<17.45 g). CONCLUSION: The prevalence of fatty liver was similar between SLE patients and healthy controls, while liver fibrosis was increased in the female patient group as compared to controls. Furthermore, liver fibrosis was associated with age and low dose cumulative glucocorticoid use. Interestingly, fatty liver did not precede liver fibrosis in the majority of cases, contrary to what is observed in the general population. We hypothesized that liver fibrosis may be the result of subclinical inflammation and autoimmunity associated with SLE itself and the use of steroids may prevent or prolong fibrosis formation in the liver.Publication Open Access 2022 American college of rheumatology/EULAR classification criteria for giant cell arteritis(2022-12-01) DİRESKENELİ, RAFİ HANER; Ponte C., Grayson P. C., Robson J. C., Gribbons K. B., Judge A., Craven A., Khalid S., Hutchings A., Watts R. A., Merkel P. A., et al.Objective: To develop and validate updated classification criteria for giant cell arteritis (GCA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data-driven reduction of candidate items, 5) derivation of a points-based risk classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C-reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88–0.94) with a sensitivity of 87.0% (95% CI 82.0–91.0%) and specificity of 94.8% (95% CI 91.0–97.4%). Conclusion: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.Publication Open Access 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Granulomatosis With Polyangiitis(2022-03-01) DİRESKENELİ, RAFİ HANER; Robson J. C., Grayson P. C., Ponte C., Craven A., Judge A., Khalid S., Hutchings A., Watts R. A., Merkel P. A., Luqmani R. A., et al.Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting, or sino-nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (+5); pulmonary nodules, mass, or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci-immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (−1); and eosinophil count ≥1 × 109/liter (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% confidence interval [95% CI] 87–96%) and the specificity was 94% (95% CI 89–97%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research.Publication Open Access Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?(2023-10-01) ÇANDERELİ, ZEHRA ÖZGE; ŞİŞMAN KİTAPÇI, NUR; AKSOY, AYSUN; ŞAHİN, ALİ; ALİBAZ ÖNER, FATMA; İNANÇ, GÜZİDE NEVSUN; DİRESKENELİ, RAFİ HANER; MUMCU, GONCA; ÇANDERELİ Z. Ö., Arslan T., Özdamar Ö., Yay M., Karaçayli Ü., ŞİŞMAN KİTAPÇI N., Adesanya A., AKSOY A., Belem J. M. F. M., Taş M. N., et al.OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet\"s syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.Publication Open Access A disease-associated gene desert directs macrophage inflammation through ETS2(2024-06-13) DİRESKENELİ, RAFİ HANER; Stankey C., Bourges C., Haag L., Turner-Stokes T., Piedade A., Palmer-Jones C., Papa I., Silva dos Santos M., Zhang Q., Cameron A., et al.Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3–6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.Publication Open Access Frequency and the effects of spondyloarthritis-spectrum disorders on the clinical course and management of Takayasu arteritis: an observational retrospective study(2024-01-01) DİRESKENELİ, RAFİ HANER; ALİBAZ ÖNER, FATMA; Abacar K., Kaymaz-Tahra S., Bayındır Ö., İnce B., Kutu M. E., YAZICI A., Ediboğlu E. D., Demirci-Yıldırım T., Ademoğlu Z., Omma A., et al.Objectives: Extravascular findings of Takayasu arteritis (TAK) often share features with the spondyloarthritis (SpA) spectrum of disorders. However, the characteristics of this overlap and its effect on the vascular manifestations of TAK are not fully known. Therefore, we aimed to investigate the frequency of SpA-related features in TAK patients. Material and methods: In this observational retrospective study, 350 patients with TAK classified according to ACR 1990 criteria, from 12 tertiary rheumatology clinics, were included and evaluated for the presence of axSpA, IBD, or psoriasis. Demographic, clinical features, angiographic involvement patterns, disease activity, and treatments of TAK patients with or without SpA were analyzed. Results: Mean age was 45.5 ± 13.6 years and mean follow-up period was 76.1 ± 65.9 months. Among 350 patients, 31 (8.8%) had at least one additional disease from the SpA spectrum, 8 had IBD, 8 had psoriasis, and 20 had features of axSpA. In the TAK-SpA group, TAK had significantly earlier disease onset, compared to TAK-without-SpA (p = 0.041). SpA-related symptoms generally preceded TAK symptoms. Biological treatments, mostly for active vasculitis, were higher in the TAK-SpA group (70.9%) compared to TAK-without-SpA (27.9%) (p < 0.001). Vascular involvements were similar in both. Conclusion: Our study confirmed that diseases in the SpA spectrum are not rare in TAK. Vascular symptoms appeared earlier in such patients, and more aggressive therapy with biological agents was required in the TAK-SpA group, suggesting an association between TAK and SpA spectrum. (Table presented.)