Neslihan Yılmaz

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

Objective. To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases. Methods. Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics. Results. We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4–48) and bladder cancer was 8 years (6–10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis. Conclusion. Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

Investigation of the association between Rho/Rho-kinase gene polymorphisms and systemic sclerosis

Systemic sclerosis (SSc) is a disease characterized by inflammation, vascular abnormalities and fibrosis. The role of Rho/Rho-kinase pathway was demonstrated in the pathogenesis of fibrosis, inflammation and vascular abnormalities. This study was aimed to investigate the relation between SSc and Rho/Rho-kinase gene polymorphisms. The study included 339 patients with SSc and 302 healthy subjects who were apparently healthy and at similar age and gender. Genotype distributions and allele frequencies were detected by using Chi-square test or Fisher’s exact Chi-square test between groups, and the haplotype analysis was applied using online program (SHEsis). Significant association was found in a polymorphism in the ROCK1 gene (rs35996865), a polymorphism in ROCK2 gene (rs10178332), a polymorphism in RhoA gene (rs2177268) and two polymorphisms in RhoC gene (rs11102522 and rs11538960) with SSc disease (pxa0<xa00.0022). In this study, association between SSc disease and Rho/Rho-kinase gene polymorphisms was investigated for the first time; significant associations between ROCK1, ROCK2, RhoA and RhoC gene polymorphisms and SSc disease were demonstrated. The results strongly suggest that this SNP may be an important risk factor for development of SSc. However, further validation of these findings in an independent cohort is necessary.

Analysis of the genetic component of systemic sclerosis in Iranian and Turkish populations through a genome-wide association study

ObjectivesnSSc is an autoimmune disease characterized by alteration of the immune response, vasculopathy and fibrosis. Most genetic studies on SSc have been performed in European-ancestry populations. The aim of this study was to analyse the genetic component of SSc in Middle Eastern patients from Iran and Turkey through a genome-wide association study.nnnMethodsnThis study analysed data from a total of 834 patients diagnosed with SSc and 1455 healthy controls from Iran and Turkey. DNA was genotyped using high-throughput genotyping platforms. The data generated were imputed using the Michigan Imputation Server, and the Haplotype Reference Consortium as a reference panel. A meta-analysis combining both case-control sets was conducted by the inverse variance method.nnnResultsnThe highest peak of association belonged to the HLA region in both the Iranian and Turkish populations. Strong and independent associations between the classical alleles HLA-DRB1*11: 04 [P = 2.10 × 10-24, odds ratio (OR) = 3.14] and DPB1*13: 01 (P = 5.37 × 10-14, OR = 5.75) and SSc were observed in the Iranian population. HLA-DRB1*11: 04 (P = 4.90 × 10-11, OR = 2.93) was the only independent signal associated in the Turkish cohort. An omnibus test yielded HLA-DRB1 58 and HLA-DPB1 76 as relevant amino acid positions for this disease. Concerning the meta-analysis, we also identified two associations close to the genome-wide significance level outside the HLA region, corresponding to IRF5-TNPO3 rs17424921-C (P = 1.34 × 10-7, OR = 1.68) and NFKB1 rs4648133-C (P = 3.11 × 10-7, OR = 1.47).nnnConclusionnWe identified significant associations in the HLA region and suggestive associations in IRF5-TNPO3 and NFKB1 loci in Iranian and Turkish patients affected by SSc through a genome-wide association study and an extensive HLA analysis.

Karaciğer nakli yapılan bir hastada multifokal osteonekroz ve osteomiyelit

Osteonekroz (ON), kemiklerin kanlanmasinin kalici ya da gecici olarak kesilmesi ile meydana gelen kemik yikimidir. En sik nedenleri arasinda; travma, ilaclar, enfeksiyonlar, hiperkoagulabilite ve solid organ nakli sayilabilir. Bir cok olgu serisinde, bobrek, karaciger ve kalp nakli sonrasinda ozellikle kalcada olmak uzere, eklem cevresinde osteonekroz gelisebildigi bildirilmistir. Bu makalede karaciger nakli sonrasinda ortaya cikan, tibianin diafiz bolgesi dahil olmak uzere multifokal yerlesimli, osteomiyelitin eslik ettigi bir osteonekroz olgusu sunuldu

THU0366 Does being a hepatitis B virus carrier decrease applying to hospital in patients with rheumatoid arthritis and ankylosing spondylitis

Background Immunosupressive therapy, especially tumor necrosis factor-α (TNF-α) inhibitors can induce viral reactivation and potentially fatal liver failure in patients with concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. But the prevalence of HBV and HCV infections could differ according to geographic regions. Although it is suspected as the prevalance of HBV and HCV in patients with rheumatoid artritis (RA) and ankylosing spondilitis (AS) in not different from general population, multicenter countrywide studies are required to support this idea Objectives The aim of this study was to investigate the prevalence of HBsAg and Anti HCV seropositivity in RA and AS patients. Methods Totally 1514 (F:M=1176/338) RA and 854 (F:M=388/466) AS consecutive patients who were fulfilling ACR 1987 RA and ASAS-EULAR 2009 Spondyloarthropathies criteria and being regularly followed in Rheumatology outpatient clinic from the six different geographic areas of Turkey were recruited in this study. The prevalence of HBsAg and Anti HCV were retrospectively investigated and compared with general population data from “Turkish Hepatology Society” prevalence study that included 5465 healthy subjects. Results The mean age was 48.7±13.9 years in RA and 36.9±10.8 years in AS patients. The mean disease duration was 6.4±6.1 and 6.3±5.9 years, respectively. HBsAg prevalance was lower both RA and AS patients than general population [33 (2.2%), 25 (2.9%) and 218 (3.99%), respectively; p<0.01]. On the other hand Anti HCV prevalence was not different among the groups [15 (1%), 8 (0.9%) and 52 (0.95%), respectively; p>0.05] (see Table 1). Table 1. HBsAg and Anti HCV prevalence in RA,AS patients and general population HBsAg, n (%) Anti HCV, n (%) General population (n: 5465) 218 (3.99)* 52 (0.95) RA (n: 1514) 33 (2.2) 15 (1.0) AS (n: 854) 25 (2.9) 8 (0.9) *p<0.01, *vs RA and AS patients. HBsAg and Anti HCV seropositivity were higher in female than male patients in RA group (HBsAg; 3.9% vs 1.7, p=0.01 and Anti HCV; 1.3% vs 0%, respectively, p=0.03). However, no difference was observed in HBsAg and Anti HCV results between gender in the AS group. (HbsAg; 3.5% vs 2.6% and Anti HCV; %0.8 vs %1.1, respectively p>0.05). Conclusions Prevalence of HBsAg seropositivity in patients with RA and AS is lower than general population. Further studies are required about this low prevalence. Being a HBV carrier might decrease applying to hospital in patients with RA and AS. Disclosure of Interest None Declared