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Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration., Conclusions: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests., What Is Known: • During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring., What Is New: • There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. • This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Neuropsychiatric (NP) involvement is a restricted area in juvenile-onset systemic lupus erythematosus (jSLE)., Aim: To investigate the prevalence, demographic and clinical features, and outcomes of the neurological involvement in the Turkish jSLE population., Methods: This study was based upon 24 referral centers' SLE cohorts, multicenter and multidisciplinary network in Turkey. Patient data were collected by a case report form which was standardized for NP definitions according to American Collage of Rheumatology (ACR). Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) neuropsychiatric part was used to determine NP damage. Variables were evaluated Ward's hierarchical clustering analyses, univariate, and multivariate logistic regression analyses., Results: A hundred forty-nine of 1107 jSLE patients had NP involvement (13.5%). The most common NPSLE findings were headache (50.3%), seizure (38.3%), and acute confusional state (33.6%). Five clusters were identified with all clinical and laboratory findings. The first two clusters involved neuropathies, demyelinating diseases, aseptic meningitis, and movement disorder. Cluster 3 involved headache, activity markers and other SLE involvements. Idiopathic intracranial hypertension, cerebrovascular disease, cognitive dysfunction, psychiatric disorders and SLE antibodies were in the fourth, and acute confusional state was in the fifth cluster. In multivariate analysis, APA positivity; OR: 2.820, (%95CI: 1.002-7.939), P: 0,050, plasmapheresis; OR: 13.804 (%95CI: 2.785-68.432), P: 0,001, SLEDAI scores; OR: 1.115 (%95CI: (1.049-1.186), P: 0,001 were associated with increased risk for neurologic sequelae., Conclusion: We detected the prevalence of juvenile NPSLE manifestations in Turkey. We have identified five clusters that may shed light pathogenesis, treatment and prognosis of NP involvements. We also determined risk factors of neurological sequelae. Our study showed that new definitions NP involvements and sequelae for childhood period are needed., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was - 1.64 (- 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was -2.81 ([- 3.79] to [- 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Low glutamine levels have been shown in tumor environments for several cancer subtypes. Therefore, it has been suggested that cancer cells rewire their metabolism to adopt low nutrient levels for survival and proliferation. Although glutamine is a non-essential amino acid and can be synthesized de novo, many cancer cells including malignant hematopoietic cells have been indicated to be addicted to glutamine. This study aimed to investigate the proliferation of leukemia cell lines in glutamine-deprived conditions., Materials and Methods: Cell proliferation of K562, NB-4, and HL-60 cells was determined by calculating cell numbers in normal vs. low glutamine media. Changes in mRNA expressions were investigated using qRT-PCR. The glutamine synthetase (GS)-encoding GLUL gene was knocked out (KO) in HL-60 cells using the CRISPR/Cas9 method and protein expression was evaluated with immunoblotting., Results: The proliferation of all cell lines was decreased in glutamine-deprived medium. GS protein expression was increased in glutamine-limited medium although the mRNA level did not change. Increased protein expression was confirmed with inhibition of new protein synthesis by treating cells with cycloheximide. To further investigate the role of GS protein, the GS-encoding GLUL gene was KO in HL-60 cells using the CRISPR/Cas9 method. GS KO cells proliferated less compared to control cells in glutamine-limited medium., Conclusion: Our results indicate that upregulated GS protein expression is responsible for glutamine addiction of leukemia cell lines. Exploiting the genetic and metabolic mechanisms responsible for GS protein expression could lead to the identification of new anti-cancer drug targets.

Anti-interleukin 1 agents are used successfully in colchicine-resistant or intolerant Familial Mediterranean Fever (FMF) patients. Sixty-five patients with FMF who received canakinumab treatment for at least 6 months due to colchicine resistance or intolerance between 2016 and 2020 in our department were retrospectively analyzed. Canakinumab treatment was given subcutaneously every 4 weeks. After completing monthly canakinumab therapy over 12 months, in patients with complete remission, the dosing interval was extended to every 1.5 months for 6 months, then every 2 months for 6 months, and finally every 3 months for a year. In patients without disease activation, canakinumab treatment was discontinued at the end of 3 years and followed up with colchicine treatment. Patients who had a flare switched to the previous dosing interval. In patients with renal amyloidosis, monthly canakinumab treatment was continued without extending the dose intervals. The mean duration of canakinumab use in our patients was 31.4 ± 10.57 months (6-52 months). The mean age at onset of symptoms was 4.65 ± 3.84 (range, 1-18) years, and the mean age at diagnosis was 5.59 ± 3.9 (range, 4-19) years. Complete remission was achieved in 57 (87.6%) and partial remission in seven (10.7%) patients. One patient was unresponsive to treatment. Canakinumab treatment was discontinued in three patients with complete remission and one patient with drug resistance. Erythrocyte sedimentation rate (ESR) (51.85 ± 15.7 vs. 27.80 ± 13.73 mm/h) and C-reactive protein (CRP) [26 (3-73) vs. 5 (1-48) mg/L] values were compared before and after canakinumab treatment in attack-free periods, a significant decrease was found after canakinumab treatment ( p < 0.001, p < 0.001, respectively). Bodyweight Z -scores (respectively -0.80 ± 0.86 vs. -0.49 ± 0.92) were compared, similarly, a statistically significant increase after canakinumab treatment ( p < 0.001), but no significant increase in height Z scores (-1.00 ± 0.88 vs. -0.96 ± 0.94) ( p = 0.445) was detected. Four patients had FMF-related renal amyloidosis. The decrease in proteinuria with canakinumab treatment was not statistically significant ( p = 0.068). Cervical lymphadenitis developed in one and local reactions in two patients. No severe adverse effects requiring discontinuation of canakinumab treatment were observed. Our study showed that canakinumab treatment was highly effective, well-tolerated in pediatric FMF patients, and controlled extension of the canakinumab dose interval was safe., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yücel, Aydog, Nalcacioglu and Yılmaz.)

Haemolytic uraemic syndrome (HUS) is most commonly associated with Shiga toxin-producing Escherichia coli (STEC) while the recurrent hereditary atypical (aHUS) form secondary to complement system control protein mutations is relatively rare. A 6-year-old boy with complement factor H (CFH) and factor B (CFB) mutations and a history of bloody diarrhoea and PCR positivity for Shiga toxin was initially diagnosed as STEC+HUS. Acute kidney injury resolved with Eculizumab but he remains with chronic renal failure. Although the exact role of STEC in the pathogenesis of aHUS in this patient is not certain, there seems to be a relationship. However, several issues remain to be explained including the effect of genetic and environmental factors in modifying susceptibility to develop aHUS in some patients following STEC infection. Abbreviations : aHUS: atypical haemolytic uraemic syndrome; ANA: anti-nuclear antibody; ANCA: anti-neutrophil cytoplasmic antibody; ASO: anti-streptolysin O; BUN: blood urea nitrogen; CFB: complement factor B; CFH: complement factor H; EHEC: enterohaemorrhagic Escherichia coli ; MCP: membrane co-factor protein; PD: peritoneal dialysis; STEC: Shiga toxin-producing Escherichia coli ; STX 1-2: Shiga toxins 1-2.

Background: Posterior urethral valve (PUV) is the most serious form of congenital anomalies of kidney and urinary tract (CAKUT) in boys with significant risk of progression to chronic kidney disease (CKD). We present our long-term results in children with PUV., Methods: Retrospective chart review of 113 children with PUV followed within the years of 1996-2018 was performed. Clinical, laboratory and epidemiologic parameters were analyzed for their impact on renal outcome., Results: The median age of diagnosis was 1.00 month (1.00-132.00) and the median follow-up period was 70 months (60.00-216.00). Antenatal diagnosis was present in 33 patients (51.5%) mainly with bilateral hydronephrosis and oligohydramnios. The most common postnatal presentation was recurrent urinary tract infection (UTI) in 14 cases (21.9%) and incontinence in three cases (4.7%). Vesicoureteral-reflux (VUR) was present in 31 cases (48.4%). All patients had surgery and urinary diversion was needed in 18 (28.2%). Varying stages of chronic kidney disease (CKD) developed in 23 cases (35.9%) and rise in serum creatinine was especially prominent after the 4th year of follow-up. Of 23 CKD patients, seven (10.9%) were in ESRD and on dialysis. Mortality occurred in one (1.5%) patient. Hypertension, proteinuria and high initial serum creatinine (>1.28 mg/dL) were statistically significant risk factors for CKD, as expected. Surprisingly VUR and UTI did not show such a significant impact on CKD development. Antenatal detection was with significantly less risk for CKD., Conclusions: Our results confirm that PUV has a considerable risk for CKD development. Antenatal diagnosis, management of proteinuria and hypertension may modify this progression. But already injured kidneys still have a potential risk. The need for further research to evaluate the impact of any intervention on long term renal outcome is obvious.

Objective: This study aims to investigate the validity and reliability of the Turkish Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R-TR)., Methods: A methodological and cross-sectional design was used. This study included a total of 250 surgical patients (98 males, 152 females) between January 2015 and January 2016. Data were collected using a demographic questionnaire and the APSPOQ-R. Language equivalence, content and construct validity, and reliability of the scale were evaluated., Results: The Pearson correlation coefficient of the scale for parallel test reliability was 0.362, and the Cronbach's alpha value was determined as 0.88 in the APS-POQ-R-TR. According to fit indexes of the confirmatory factor analysis [x2/SD=362.53/125=2.90; RMSEA=0.087 (90% CI: 0.077-0.098); CFI=0.95; IFI=0.95; NNFI=0.94], three factors were found to be appropriate for the APSPOQ-R-TR., Conclusion: The adaptation of the translated APS-POQ-R in Turkey is reliable and valid to measure and evaluate the quality of postoperative pain management in the Turkish population.

The objective in this study is to determine the knowledge and attitudes of the Faculty of Theology students on organ transplantation. The study that was planned as a descriptive study took place between March-May 2014 with the participation of 119 students enrolled at the Faculty of Theology. It was determined as a result of the study that the students see lack of knowledge (49.6%) as the top obstacle for organ transplantation followed by religion (21%), that 52.1% accept that organ transplantation is not forbidden in Islam; that 27.7% agree with the thought that considers it disturbing and unnerving to carry an organ or tissue from another body; that 80.7% agree with the idea stating that organ transplantation should be carried out even if it provides only a possibility for treatment or for prolonging one's life and that 82.4% agree with the opinion that statements in favor of organ transplantation to be declared by the Directorate of Religious Affairs will increase organ transplantation. Clergymen play an important role in affecting the behavior and attitudes of large public masses, and thus it is important that the positive ideas of these individuals with regard to organ donation will thus have indirect but positive effects on the attitudes of the public with regard to organ transplantation. Hence, it is thought that determining the attitudes of clergymen candidates who will educate the public both at schools and at places of prayer and increasing their awareness in this subject will contribute to increasing the awareness of the public with regard to organ donation.

Aim: The aim of this study was to investigate the associations between human leukocyte antigen (HLA)-DRB1 alleles with genetic susceptibility to rheumatoid arthritis (RA) and production of antibodies against cyclic citrullinated peptide (anti-CCP antibody) and rheumatoid factor (RF) in Turkish RA patients., Methods: We studied 291 RA patients and 253 controls. Genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes hybridization method. Serum levels of anti-CCP antibody, IgM-RF and high sensitive C-reactive protein titers were measured by commercial kits using immunological methods., Results: We found that HLA-DRB1*04 and *09 alleles were associated in anti-CCP+ and anti-CCP+ RA patients (P < 0.0001 and P < 0.001, respectively), while DRB1*01 and *04 were determined to be higher in RF+ RA patients (P < 0.001 and P < 0.0001, respectively). Moreover, DRB1*11 and DRB1*13 alleles were determined to be lower in RF and anti-CCP/RF+ RA patients (P < 0.001 for both). HLA-DRB1*04 was identified as a common responsible allele for susceptibility to the disease in anti-CCP, RF and anti-CCP/RF- RA patients (P = 0.0018, P = 0.0004 and P = 0.0023, respectively). HLA-DRB1*13 allele alone was found to be protective against to anti-CCP+ and RF- RA (P = 0.0003 and P = 0.006, respectively). On the contrary, there was no protective allele in anti-CCP/RF- RA as well as anti-CCP- RA patients., Conclusion: This study indicates that associate and protective HLA-DRB1 allele distributions are different in autoantibody (anti-CCP or RF or anti-CCP/RF)+ RA and autoantibody- RA patients, with exceptions of DRB1*04 and DRB1*13., (© 2012 The Authors. International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.)

Rheumatoid arthritis (RA [MIM 180300]) is a complex, polygenic inflammatory autoimmune disease, resulting from interactions between genetic and environmental factors. Some of the RA-associated HLA-DRB1 alleles have shared epitope, but their distribution varies among different racial/ethnic groups. This study was aimed at investigating the distribution of HLA-DRB1 alleles in patients with RA in eastern Black Sea region of Turkey. DNA samples of 320 patients with RA and 360 healthy controls were studied for the determination of HLA-DRB1 allele distribution using PCR-SSP method. The allele frequencies of HLA-DRB1*01, *04, and *09 were higher in patients with RA compared with the controls (P < 0.005, P < 0.0001, and P < 0.01, respectively). On the other hand, in patients with RA, HLA-DRB1*13 allele was lower than the controls (P < 0.001). Of the HLA-DRB1*04 subgroups, *0401 (40.83% vs. 18.75%, P < 0.001) was the most frequent allele in patients with RA, while DRB1*0402 (30.00% vs. 12.50%, P < 0.005) allele in the controls. HLA-DRB1 allele frequencies in the patients with RA and the controls showed Hardy-Weinberg rule compliance. Results of this study indicate that HLA-DRB1*01, *04, and *09 alleles were associated with RA, and HLA-DRB1*13 was protective allele against RA. Among the subgroups of HLA-DRB1*04, *0401 was detected to be RA associated, while *0402 was being protective. These results have some differences compared with previous reports originating from other regions of Turkey.

Background and Aims: An association of homozygous MTHFR 677T genotypes with elevated plasma homocysteine level has been documented, but results are still controversial. We aimed to investigate prevalence of the C677T polymorphism in patients with acute myocardial infarction (MI) in the Eastern Black Sea region of Turkey., Methods: We studied genomic DNA of 231 unrelated patients (aged 59 ± 13 years; 175 male, 56 female) with first anterior acute MI and 242 healthy controls (aged 54 ± 19 years; 182 male, 60 female) using real-time polymerase chain reaction kits for the MTHFR C677T mutation., Results: Prevalence of MTHFR C677T mutant genotype was 49.1% (CT: 45.8%, TT: 3.3%) in controls and 48.45% (CT: 38.5%, TT: 9.95%) in patients with acute MI. The TT mutation was more frequent in patients with acute MI than in controls (9.95 vs. 3.3%) (OR; 3.23, 95% CI; [1.34-8.05], p = 0.003)., Conclusions: The MTHFR gene homozygote TT mutation is a risk factor for patients with MI in the eastern Black Sea Turkish Population., (Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.)

Background and Aims: A relationship between acute leukemia and HLA alleles has been demonstrated in several studies. However, the frequencies of HLA class I (A, B) and class II (DRB1) alleles and haplotypes has not already been determined in Turkish patients with acute leukemia., Methods: We investigated the relation of the HLA alleles and haplotypes in 237 adult acute leukemia patients [103 acute lymphoblastic leukemia (ALL), 134 acute myeloid leukemia, (AML)] and 360 unrelated normal subjects by PCR-SSOP method using Luminex technology., Results: Allele frequencies of HLA-A*03, and B*51 were higher in patients with AML compared with the controls (p = 0.019, and p = 0.001; respectively). Furthermore, HLA-A*11 and DRB1*01 allele frequencies were determined to be higher in patients with ALL (p = 0.01, p = 0.001; respectively), whereas DRB1*13 allele frequencies lower than controls (p = 0.003). The most observed haplotypes A*03 B*51 DRB1*11 (3.73 vs. 0%) in patients with AML; A*02 B*35 DRB1*01 (2.91 vs. 0%) and A*02 B*51 DRB1*11 (2.91 vs. 1.96%) in patients with ALL were determined. On the contrary, the most observed haplotype was A*02 B*35 DRB1*13 (2.19%) in the controls. We found A*02 B*39 DRB1*16 haplotype negatively associated with AML, whereas A*02 B*35 DRB1*13 was in ALL (p = 0.015, and p = 0.017; respectively)., Conclusions: These results suggest that HLA-A*03 and B*51 alleles may play a presumptive predisposing factor in AML. In addition, HLA-A*11 and DRB*01 alleles have been found to be associated with ALL, whereas DRB1*13 allele was determined to be negatively associated., (Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.)