Differentiating children with familial Mediterranean fever from other recurrent fever syndromes: The utility of new Eurofever/PRINTO classification criteria.

Objectives: In this study, we aimed to investigate the performance of Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria in pediatric patients with familial Mediterranean fever (FMF). Patients and methods: This retrospective, cross-sectional study included a total of 130 pediatric FMF patients (67 males, 63 females; mean age: 12.4±3.6 years; range, 2.5 to 17.7 years) with at least one M694V mutation in MEFV gene between July 2010 and July 2019. Demographic features and disease characteristics were recorded. The control group was consisted of 41 patients (19 males, 22 females; mean age: 7.8±4.0 years; range, 2.1 to 17.8 years) with other hereditary autoinflammatory diseases (AIDs), including periodic fevers with aphthous stomatitis, pharyngitis, and adenitis syndrome (n=30), mevalonate kinase deficiency (n=9), and tumor necrosis factor receptor-associated periodic syndrome (n=2). Sensitivity and specificity of the Eurofever/PRINTO classification criteria were calculated. Results: The sensitivity and specificity were 97.7% and 56.1% for Yalcinkaya-Ozen criteria, respectively and 93.1% and 90.2% for Tel Hashomer criteria, respectively. The Eurofever/PRINTO classification criteria reached a sensitivity and specificity of 94.6% and 82.9% and 93.1% and 80.5%, respectively, when genetic plus clinical criteria and clinical-only criteria were applied. Conclusion: The Eurofever/PRINTO classification criteria have a comparable sensitivity for avoidance of FMF underdiagnosis in childhood. The Yalcinkaya-Ozen criteria have the highest sensitivity without a significant specificity. The Tel Hashomer criteria and Eurofever/PRINTO classification criteria were superior to Yalcinkaya-Ozen criteria to differentiate FMF from other AIDs, thus leading to less complications relevant to underdiagnosis of other AIDs.

Evaluation of different classification criteria in children with Behcet disease: results from a single referral center.

OBJECTIVES: Behcet Disease (BD) is a systemic vasculitis, first described with a triad of oral aphthous ulcers, genital ulcers, and uveitis. The authors aimed to share the clinical properties and utilities of three distinct classification criteria for BD in this study. METHODS: This case-control study was conducted in pediatric BD patients, diagnosed between January 2012 and July 2019. The control group included 53 children with other rheumatic disorders. Sensitivity and specificity for International Study Group (ISG), International Criteria for BD (ICBD), and pediatric criteria for BD (PEDBD) criteria were tested. RESULTS: The mean age at symptom onset and diagnosis of the 16 BD patients (6 females, 10 males) were 11.2 ± 3.6 and 13 ± 3.1 years, respectively. The sensitivity and specificity of ISG criteria were 87.5% and 100%. Furthermore, ICBD criteria had a sensitivity and specificity of 93.7% and 98.1%, whereas the authors found sensitivity and specificity as 93.7% and 96.2% for PEDBD. CONCLUSION: ICBD and PEDBD reached higher sensitivity for pediatric BD diagnosis and ICBD had the highest specificity. The authors speculate that the utilization of ICBD may provide early diagnosis of BD in childhood, prevent related morbidities and misdiagnosis.

Diagnostic Modalities Based on Flow Cytometry for Chronic Granulomatous Disease: A Multicenter Study in a Well-Defined Cohort.

BACKGROUND: Chronic granulomatous disease (CGD) is characterized by defective microbial killing due to mutations affecting subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Definitive genetic identification of disease subtypes may be delayed or not readily available. OBJECTIVE: Sought to investigate the role of intracellular staining of NADPH oxidase enzyme subunits in predicting the respective genetic defects in patients with CGD and carriers. METHODS: Thirty-four patients with genetically inherited CGD, including 12 patients with X-linked CGD (gp91phagocyte oxidase (phox) deficiency due to cytochrome b-245, beta polypeptide [CYBB] mutations) and 22 patients with autosomal-recessive CGD (p22phox, p47phox, and p67phox deficiency due to cytochrome b-245, alpha polypeptide [CYBA], neutrophil cytosolic factor 1 [NCF1] and NCF2 mutations, respectively) were recruited from different immunology centers and followed up prospectively. Dihydrorhodamine testing and NADPH oxidase subunit expression in white blood cells were determined by flow cytometry. RESULTS: gp91phox and p22phox defects, which result in simultaneous loss of both proteins due to their complex formation, were differentiated only by comparative analysis of patients' and mothers' intracellular staining. p47phox and p67phox protein expression was almost undetectable in patients compared with carrier mothers and healthy controls. The expression values of the respective subunits were found to be significantly higher in all controls as compared with carrier mothers, which in turn were higher than those of patients. CONCLUSIONS: Analysis of NADPH oxidase enzyme subunits by flow cytometry in patients and carriers is useful in the rapid prediction of the genetic defect of patients with CGD, thus guiding targeted sequencing and aiding in their early diagnosis.

Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey.

BACKGROUND: A better understanding of cystic fibrosis transmembrane conductance regulator biology has led to the development of modulator drugs such as ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, and elexacaftor-tezacaftor-ivacaftor. This cross-sectional study evaluated cystic fibrosis (CF) patients eligible for modulator drugs. METHODS: Data for age and genetic mutations from the Cystic Fibrosis Registry of Turkey collected in 2018 were used to find out the number of patients who are eligible for modulator therapy. RESULTS: Of registered 1488 CF patients, genetic analysis was done for 1351. The numbers and percentages of patients and names of the drugs, that the patients are eligible for, are as follows: 122 (9.03%) for ivacaftor, 156 (11.54%) for lumacaftor-ivacaftor, 163 (11.23%) for tezacaftor-ivacaftor, and 57 (4.21%) for elexacaftor-tezacaftor-ivacaftor. Among 1351 genotyped patients total of 313 (23.16%) patients are eligible for currently licensed modulator therapies (55 patients were shared by ivacaftor and tezacaftor-ivacaftor, 108 patients were shared by lumacaftor-ivacaftor and tezacaftor-ivacaftor, and 22 patients were shared by tezacaftor-ivacaftor and elexacaftor-tezacaftor-ivacaftor groups). CONCLUSIONS: The present study shows that approximately one-fourth of the registered CF patients in Turkey are eligible for modulator drugs. As, frequent mutations that CF patients have in Turkey are different from North American and European CF patients, developing modulator drugs effective for those mutations is necessary. Furthermore, as modulator drugs are very expensive currently, financial support of the government in developing countries like Turkey is noteworthy.

FT-IR, FT-Raman vibrational spectra and molecular structure investigation of 2-chloro-4-methylaniline: a combined experimental and theoretical study.

In this work, the experimental and theoretical vibrational spectra of 2-chloro-4-methylaniline (2Cl4MA, C(7)H(8)NCl) were studied. FT-IR and FT-Raman spectra of 2Cl4MA in the liquid phase have been recorded in the region 4000-400cm(-1) and 3500-50cm(-1), respectively. The structural and spectroscopic data of the molecule in the ground state have been calculated by using Hartree-Fock (HF) and density functional method (B3LYP) with the 6-31G(d), 6-31G(d,p), 6-31+G(d,p), 6-31++G(d,p) and 6-311G(d), 6-311G(d,p), 6-311+G(d,p), 6-311++G(d,p) basis sets. The vibrational frequencies have been calculated and scaled values have been compared with experimental FT-IR and FT-Raman spectra. The observed and calculated frequencies are found to be in good agreement. The complete assignments were performed on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method. The DFT-B3LYP/6-311++G(d,p) calculations have been found more reliable than the ab initio HF/6-311++G(d,p) calculations for the vibrational study of 2Cl4MA. The optimized geometric parameters (bond lengths and bond angles) were compared with experimental values of aniline and p-methylaniline molecules.