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Background: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%-10% of patients may respond inadequately to colchicine, and anti-interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy., Methods: Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment., Results: In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidity were found to be statistically more frequent in the group whose biological therapy could not be discontinued (p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively)., Conclusions: Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Disorders of Consciousness are divided into two major categories such as vegetative and minimally conscious states. Objective measures that allow correct identification of patients with vegetative and minimally conscious state are needed. EEG microstate analysis is a promising approach that we believe has the potential to be effective in examining the resting state activities of the brain in different stages of consciousness by allowing the proper identification of vegetative and minimally conscious patients. As a result, we try to identify clinical evaluation scales and microstate characteristics with resting state EEGs from individuals with disorders of consciousness. Our prospective observational study included 28 individuals with a disorder of consciousness. Control group included 18 healthy subjects with proper EEG data. We made clinical evaluations using patient behavior scales. We also analyzed the EEGs using microstate analysis. In our study, microstate D coverage differed substantially between vegetative and minimally conscious state patients. Also, there was a strong connection between microstate D characteristics and clinical scale scores. Consequently, we have demonstrated that the most accurate parameter for representing consciousness level is microstate D. Microstate analysis appears to be a strong option for future use in the diagnosis, follow-up, and treatment response of patients with Disorders of Consciousness., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs)., Methods: This observational, retrospective, multicenter study was conducted from 2010 to 2022 in patients under 18 years of age with rheumatic diseases who were receiving interleukin-1 antibodies (Anti-IL1), interleukin-6 antibodies (Anti-IL6), and tumor necrosis factor alpha inhibitors (anti-TNF). Efficacy, AEs, and timing of AEs were collected from electronic medical records., Results: Three hundred and fifteen BAs were prescribed to 237 patients. Fifty AEs occurred in 44 patients (18.6%). Anti-TNF exposure was present in 8 (72.2%) of 11 patients with latent tuberculosis (TB) and in all 7 patients with herpes infections. Four of 6 patients (66.7%) with recurrent upper respiratory tract infections and 7 of 8 patients (87.5%) with local skin reactions were on Anti-IL1. The cutoff value for latent TB development was determined as 23.5 months by ROC analysis (AUC: 0.684 ± 0.072, p = 0.038, 95% CI: 0.54-0.82). In patients who used BA for 23.5 months or more, the risk of latent TB was 5.94-fold ( p  = 0.024, 95% CI: 1.26-27.97). Drug rash with eosinophilia and systemic symptoms (DRESS) occurred in 2 patients on anakinra, and anaphylaxis occurred in 1 patient on anti-IL6. There were no cases of malignancy or death in any patient., Conclusion: The physician should be vigilant for latent TB in patients exposed to BA for more than 2 years. While local skin reactions are more prevalent in patients receiving anti-IL1, severe skin reactions such as DRESS may also occur.

Introduction: In this study, we aim to evaluate the treatment responses and prognostic characteristics of Myasthenia Gravis (MG) patients followed in a tertiary neuromuscular diseases center in Turkey., Methods: One hundred seventy four MG patients (between years 2011 and 2022) in Antalya, Turkey were diagnosed, and evaluated on a classification of MG was based on Myasthenia. Gravis Foundation of America (MGFA) clinical classification. Exclusion of other possible diseases in the differential diagnosis and support by beneficial response to treatment with acetylcholinesterase inhibitors were also taken into consideration., Results: Mean age of participants was 54.86 (SD = 14.856; min-max = 22-84). Ninety (51.7%) were female. MG was more common in women under the age of 65 (58%) and in men over the age of 65 (64%). Generalized MG was seen in 75.3% of the patients. Anti-AChR positivities were detected in 52.3%, Anti-MuSK positivity in 4.6%, and seronegativity in 22.4%. Thymoma was detected in nearly 9.8% and thymectomy was performed in 28.7 percent. Most of the patients (57.5%) were using corticosteroids. Azathioprine was used by 39% and mycophenolate mofetil by 10.3% of patients. Mortality was higher and disease was more severe in late-onset (>50 years) MG patients (especially in the COVID-19 pandemic). Eight patients (four women, four men, mean age 75.5 years) died during follow-up. None of them died due to myasthenic worsening, two died due to malignancy and two due to infection. During the COVID pandemic, 16 patients (9.2%) had COVID infection. Four patients died due to COVID-19 infection, these four patients had serious comorbidities, and three of them were elderly (>75 years)., Conclusion: In conclusion, MG is more common in women between the ages of 20-40 and in men over the age of 65. The use of corticosteroids was more common under the age of 50, and the use of non-steroidal immunosuppressant agents was more common over the age of 50. Thymectomy is still an important supportive treatment approach in anti-AChR positive and seronegative generalized patients under 50 years of age. IVIG and plasmapheresis are effective treatments during acute exacerbations and bridging periods of treatments. Specific treatments are needed especially for resistant group of patients., 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 © 2023 Yaman and Kurtuluş Aydın.)

Objectives: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Recurrent fever, serositis, and arthritis are common findings of the disease. In addition, musculoskeletal complaints such as exertional leg pain can be overlooked, although they are common and affect patients' quality of life. The aim of this study was to evaluate the frequency of exertional leg pain in pediatric FMF patients and to analyze the association of this finding with other characteristics of FMF., Methods: The files of FMF patients were retrospectively evaluated. The clinical characteristics and disease severity of the patients with exertional leg pain were compared with the patients without exertional leg pain. International severity scoring system for FMF (ISSF) and Mor severity score were used for assessment., Results: The study included 541 FMF patients (287 females), 149 (27.5%) with exertional leg pain. The median colchicine dosage was significantly higher in patients with exertional leg pain ( p  = 0.02), arthritis ( p  = 0.001) and arthralgia (p˂0.001) were encountered more frequently in the attacks of these patients. The median disease severity scores calculated by both Mor severity scale and ISSF were significantly higher in patients with exertional leg pain compared to those without (p˂0.001). In the group of patients with exertional leg pain, the M694V mutation, either in one allele or in two alleles, was found to be significantly more common ( p  = 0.006 and p˂0.001, respectively)., Conclusions: Exertional leg pain in pediatric FMF patients is the component of moderate-to-severe disease course, and this may be considerably associated with the presence of M694V mutation.

It has been shown that there is an increased risk of cardiovascular events such as heart failure and death in nephrotic syndrome. Left ventricle global longitudinal strain (LVGLS) is a more sensitive measure of assessing myocardial dysfunction and is more reproducible than left ventricle ejection fraction (LVEF%). LVGLS can detectsubclinical deterioration in the left ventricle early. In this study, we aimed to investigate LVGLS in Primary Nephrotic Syndrome (PNS) patients with normal LVEF%. Patients with histopathologically confirmed PNS were evaluated for this prospective single-center study. Patients with similar age and gender characteristics without nephrotic syndrome were included as the control group. LVGLS measurements were performed by 2D speckle tracking echocardiography. A total of 171 patients, 57 with PNS and 114 in the control group, were included in the study. The mean age was 38±12 years in the study population, and 95(56%) of the patients were women. LVEF% was 60.2±4.2 in the PNS group and 61.1±3.2 in the control group, and there was no significant difference between the two groups (p=0.111). LVGLS was found to be significantly lower in the PNS group (-19.3±2.3% vs.-20.8±1.5 %, p<0.001). A significant relationship was observed between PNS and LVGLS in the multivariable linear regression analysis (β= 4.428, CI 95% =0.57?1.48, p<0.001). A significant relationship was observed between PNS and LVGLS, and LVGLS was found to be lower in PNS patients. In patients with PNS, subclinical left ventricular systolic dysfunction may be detected in the early period by measuring LVGLS., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most serious complication affecting long-term prognosis. Understanding the risk factors and markers for the development of IgAVN is essential. The aim of this study is to identify IgAVN-associated factors and to evaluate the usability of Pediatric Vasculitis Activity Score (PVAS) at diagnosis as an early marker for the development of IgAVN., Methods: We conducted a retrospective case-control study of 314 patients divided into two groups: those with nephritis (IgAVN) and without nephritis (non-IgAVN). The groups were compared in terms of clinical symptoms, laboratory values, and PVAS values., Results: In total, 18.5% of the patients had IgAVN; they were older than the non-IgAVN patients (median age was 8.8, p < 0.05). Arthritis/arthralgia, abdominal pain, and intestinal bleeding were more common, systolic and diastolic BP were higher in IgAVN (p < 0.05). CRP, serum creatinine, and urine protein/Cr, PVAS were higher, while serum albumin was lower in IgAVN (p < 0.05). The receiver operator characteristic curve (ROC) analysis showed that IgAV patients with a determined cut-off PVAS value greater than 3 had 70.7% sensitivity in predicting whether or not they would develop IgAVN. Logistic regression analysis found that PVAS > 3 and low serum albumin at the time of diagnosis were independent risk factors for IgAVN., Conclusion: Our study revealed that PVAS > 3 at diagnosis is an independent predictor of IgAVN. Patients with PVAS > 3 should be followed more closely to ensure early diagnosis and management of IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: The purpose of this study was to compare the demographic, clinical and laboratory characteristics of patients with enthesitis-related arthritis (ERA), familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD), which are inflammatory diseases that may develop sacroiliitis. Thus, it was aimed to reveal various findings that may indicate primary disease in patients with sacroiliitis., Methods: Pediatric patients aged 6-18 years, who were being followed with a diagnosis of ERA (n = 62), FMF (n = 590), and IBD (n = 56) over the period 2013-2021 were included in the study. Sacroiliitis (n = 55) was diagnosed by magnetic resonance imaging of the sacroiliac joint, obtained from clinically suspected patients., Results: Sacroiliitis was detected in 54.8% of ERA patients, 2.3% of FMF patients, and 12.5% of IBD patients. The mean follow-up period was 4.1 ± 2.8 years (10 months-8 years) for the entire study group. The most common MRI finding for sacroiliitis was bone marrow edema. Peripheral joint involvement (73.5%) and HLA B27 positivity (64.7%) was significantly higher in ERA patients, and ERA was diagnosed more frequently in patients presenting with sacroiliitis. Non-steroidal anti-inflammatory drugs (NSAIDs) were the first choice of treatment agent when sacroiliitis developed in all three patient groups., Conclusions: The clinical and laboratory findings of ERA, FMF and IBD can sometimes be intertwined or can even coexist. Treatment may differ depending on the disease associated with sacroiliitis, although NSAIDs may be used in the first-line treatment of all three diseases. Sacroiliitis patients with HLA B27 positivity and peripheral arthritis may need to be addressed as ERA., (© 2023 Japan Pediatric Society.)

Objective: In this study, it was aimed to evaluate the demographic, clinical and laboratory characteristics of MIS-C patients in our hospital, to share our treatment approach, and to assess the outcomes of short- and long-term follow-up., Methods: MIS-C patients who were admitted and treated in our hospital between July 2020 and July 2021 were evaluated. Demographic, clinical, laboratory, and follow-up data were collected from patient records retrospectively., Results: A total of 123 patients with MIS-C (median age, 9.6 years) were included the study. Nineteen (15.4%) were mild, 56 (45.6%) were moderate, and 48 (39%) were severe MIS-C. High CRP, ferritin, pro-BNP, troponin, IL-6, and D-dimer values were found in proportion to the severity of the disease (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, p < 0.001), respectively. Two (1.6%) patients died. The mean follow-up period was 7.8 months. Valve failure, left ventricular dysfunction/hypertrophy, coronary involvement, and pericardial effusion were the most common cardiac pathologies in the short- and long-term follow-up of the patients. In the long-term follow-up, the most common reasons for admission to the hospital were recurrent abdominal pain (14.2%), cardiac findings (14.2%), pulmonary symptoms (8%), fever (7.1%), neuropsychiatric findings (6.2%) and hypertension (3.5%). Neuropsychiatric abnormalities were observed significantly more common in severe MIS-C patients at follow-up (p = 0.016). In the follow-up, 6.2% of the patients required recurrent hospitalization., Conclusion: MIS-C is a serious and life-threatening disease, according to short-term outcomes. In addition to the cardiac findings of patients with MIS-C, long-term outcomes such as neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms should be monitored. Key Points • In MIS-C patients, attention should be paid not only to cardiac findings, but also to symptoms related to other systems. • Patients should be followed up in terms of neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms that may occur during follow-up., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Introduction: Intra-articular corticosteroid injection (IACI) is generally used in the management of juvenile idiopathic arthritis (JIA) to obtain rapid relief of active synovitis and functional recovery and to prevent the need for regular systemic therapy. The aim of this study was to investigate the outcome of IACI treatment and the factors associated with remission of synovitis., Methods: The clinical records of JIA patients who received IACI between January 2014 and December 2020 in two pediatric rheumatology centers were reviewed. The procedure was evaluated in terms of efficacy, factors that may affect the duration of remission, procedural and drug-related complications., Results: During the study period, 134 patients received 227 injections and 37 joints were injected more than once. One hundred and six (79%) patients had persistent oligoarticular disease. At the time of injection, all patients were receiving non-steroidal anti-inflammatory drugs, 74 patients were on methotrexate, and 14 patients were on biologics. The median duration of remission without exacerbation of synovitis treated with IACI was 15 (range 1-64) months. The inactivity rate was 81% at the 6th month after the injection. It has been shown that being less than 7 years old at disease onset and low initial CRP levels were correlated with a long remission period (p < 0.05). Despite the differences were not statistically significant, the duration of remission was longer in boys, in ANA positives, in HLA-B27 negatives, in patients with concurrent methotrexate treatment and in patients not receiving biologic therapy (p > 0.05). Only two patients (1.5%, 95% CI - 0.6 to 3.5) developed cutaneous hypopigmentation and subcutaneous atrophy as side effects of injection., Conclusion: Intra-articular corticosteroid injection was more effective especially in patients with low initial CRP levels and younger than 7 years of age. The duration of remission was longer in these patients. Key Points • Intra-articular corticosteroid injection is an effective method for controlling joint inflammation and achieving long-term remission without significant side effects. • Intra-articular corticosteroid injection can be preferred in all forms of juvenile idiopathic arthritis as primary therapy or to relieve the patient while waiting for the effect of systemic agents or to avoid increasing the dose of systemic drugs. • It can be recommended as a treatment option at any stage of the disease, especially in young patients and patients with low initial CRP values., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: Erysipelas-like erythema is the pathognomonic skin manifestation of familial Mediterranean fever although not frequently seen in the pediatric population. This study aims to describe the differences between patients presenting with and without erysipelas-like erythema and to examine the relation of erysipelas-like erythema with subclinical inflammation in a large pediatric cohort of familial Mediterranean fever patients., Materials and Methods: This retrospective study from a single pediatric rheumatology referral center included familial Mediterranean fever patients with a follow-up for at least 6 months in the last 5 years. Patients were grouped according to the presence of erysipelas-like erythema and subclinical inflammation., Results: Among 515 patients with familial Mediterranean fever, 35 patients (6.8%) were found to present with erysipelas-like erythema, and the earliest age for erysipelas-like erythema was 2.9 years. All erysipelas-like erythema lesions were defined on lower extremities with concurrent arthritis in 21 patients (60.0%). Compared to other patients in the cohort, patients presented with erysipelas-like erythema had significantly higher frequencies of acute arthritis, subclinical inflammation, and biallelic exon 10 mutations, and they used significantly higher doses of colchicine at the latest visits (all P ≤ .002). Patients with subclinical inflammation more frequently presented with erysipelas-like erythema compared to others without subclinical inflammation (21.7% vs. 2.9%, P &lt; .001)., Conclusion: Erysipelas-like erythema is an uncommon but important finding that can be a sign of severe disease course and subclinical inflammation in the pediatric population with familial Mediterranean fever.

Background: To determine the interval between disease onset and admission to pediatric rheumatology clinic of patients with juvenile idiopathic arthritis (JIA) and, to identify the factors that affect the admission time (AT) to rheumatology center., Methods: We designed a retrospective observational study in children with JIA. The study variables were age, gender, JIA subtype, acute phase reactants (APR), disease activity scales, presence of a pediatric rheumatologist, and distance to a pediatric rheumatology center. Outcome parameter was the duration between onset of symptoms and first visit of rheumatologist. The parameters were evaluated with variance analysis and regression models., Results: 198 patients (female:120 (60.6%)) were included. There were 112 (56.5%) patients in oligo-articular JIA, 27 (13.6%) in rheumatoid factor negative poly-articular JIA, 22 (11.1%) in enthesitis related arthritis (ERA), 29 (14.6%) in systemic-JIA, 4 (2%) in rheumatoid factor positive poly-JIA, two patients each in undifferentiated and psoriatic arthritis. The median AT in the systemic-JIA and other groups was 16 (IQR 10.5-27.5) and 71 (IQR 33.5-211) days, respectively. There was a significantly longer AT in the ERA group than others (p=0.005). We found a correlation between longer AT and older age, low back pain, enthesitis, and low erythrocyte sedimentation rate (ESR). In the multivariate analysis, only low ESR and enthesitis contributed an increase in AT [OR 2.05 (1.07-3.93), 6.22 (1.29-29.99)]., Conclusions: The older age, low back pain, enthesitis and low ESR contribute to the late AT. JIA requires high suspicion in children with poorly defined findings and low APR.

Background: Reduced memory specificity (i.e., overgeneral memory) is a characteristic of autobiographical memories widely studied in clinical populations, and it is explained by rumination, functional avoidance, and executive dysfunction. Though the relationship of autobiographical memory specificity with mood and anxiety disorders has been shown, how it relates to dissociation is not well-established. Thus, we aimed to investigate whether dissociative experiences are related to overgeneral memory while considering concurrent depression as a possible confounding factor., Methods: We conducted a systematic review in compliance with The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and searched PubMed and Web of Science databases using autobiograph* and dissoc* as our keywords., Results: Of the 768 studies identified, 9 studies fulfilled the inclusion criteria. A meta-regression analysis was conducted to analyze the relationship between dissociative experiences and depression scores with autobiographical memory test scores. Our research revealed that depression scores, but not dissociative experiences, are significantly related to reduced memory specificity., Conclusion: While the possible overlap between dissociation and depression should be considered in the interpretation of the findings, dissociative experiences do not seem to pose vulnerability for reduced specificity of autobiographical memory. The number of studies on the topic is limited, and they do not have longitudinal follow-ups. The heterogeneous reporting of memory scores and low scores of dissociative experiences in the samples are also limitations of the existing studies., (2022 authors.)

Objective: Interleukin-1 inhibitors are effective agents used in colchicine resistance or intoler- ance during the treatment of familial Mediterranean fever. This study aims to review the char- acteristics of patients treated with interleukin-1 inhibitors and their long-term follow-up in a large pediatric cohort of familial Mediterranean fever patients., Materials and Methods: The study was conducted in a pediatric rheumatology reference cen- ter. The patients treated with interleukin-1 inhibitors for at least 6 months were included and compared to other patients with familial Mediterranean fever. Clinical and laboratory charac- teristics of the cohort were recorded., Results: Among 542 patients with familial Mediterranean fever, 6.1% (n = 33) were treated with interleukin-1 inhibitors. Colchicine resistance was the reason in 82.8% and renal amyloidosis in 17.2% of the patients. Patients with interleukin-1 inhibitors had earlier disease onset and higher frequencies of acute arthritis, chest pain, and erysipelas-like erythema with pathogenic exon 10 mutations of the MEFV gene (all P < .04). All patients diagnosed with renal amyloidosis also received interleukin-1 inhibitors. Six patients were switched from anakinra to canakinumab or vice versa to control ongoing disease activity. Attack frequency was reduced in all patients., Conclusion: Interleukin-1 inhibitors are used in a relatively small number of pediatric patients with familial Mediterranean fever. Patients presenting with earlier disease onset, acute arthri- tis, chest pain, and erysipelas-like erythema and carrying pathogenic exon 10 mutations of the MEFV gene may show a higher need for interleukin-1 inhibitors. In pediatric familial Mediterranean fever patients who are resistant to colchicine, interleukin-1 inhibitors seem to be highly effective agents.

Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease that can present with various forms of arthritis. This retrospective study aims to evaluate the characteristics of patients with arthritis in a large pediatric cohort of FMF patients., Methods: The demographic and clinical data were extracted from electronic medical records. Patients with arthritis were grouped as arthritis of FMF and arthritis of FMF-associated diseases., Results: A total of 541 patients were followed with a diagnosis of FMF in the last 5 years. Acute arthritis of FMF (n: 138) was the most common cause. It showed a recurrent course in the majority with a longer duration than other attack symptoms. Significantly higher frequencies of biallelic exon 10 and M694V mutations, erysipelas-like erythema, and protracted febrile myalgia were detected in these patients, particularly in those older than 2 years of age. Sacroiliitis of FMF was the second most common cause (n: 19). Patients with acute arthritis and sacroiliitis of FMF needed higher doses of colchicine. One patient with neonatal-onset FMF and M694V homozygosity was diagnosed with protracted arthritis. Arthritides of FMF-associated diseases including IgA vasculitis (n: 10), juvenile idiopathic arthritis (n: 9), chronic nonbacterial osteomyelitis (n: 5), and inflammatory bowel disease (n: 2) were detected in 26 patients., Conclusions: Arthritis is an important clinical finding of FMF mostly associated with M694V mutations. The frequency of protracted arthritis is declined, whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis. This study represents the changing face and current perspectives of arthritis in FMF. Key Points • Arthritis is an important clinical finding of familial Mediterranean fever (FMF) that can present in various forms • Arthritis is most likely associated with M694V mutations • The frequency of protracted arthritis is declined whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis in FMF., (© 2022. International League of Associations for Rheumatology (ILAR).)

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening hyperinflammation syndrome emerging after COVID-19. The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is evaluated in infection and inflammation. The aim of this study is to evaluate the usefulness of DNI as a diagnostic marker in patients with MIS-C and to assess its role in determining the severity of MIS-C. This retrospective, observational study included 83 patients with MIS-C and 113 patients with COVID-19, and 102 healthy controls. C-reactive protein (CRP), the absolute neutrophil count (ANC), absolute lymphocyte count (ALC), DNI, and the platelet count were recorded. The DNI levels were 4.60 ± 5.70% in the MIS C group, 0.30 ± 0.99% in the COVID group, and 0.20 ± 0.56% in the control group (p < 0.001). According to the severity of MIS-C, the DNI level was found to be 1.22% in mild MIS-C, 4.3% in moderate MIS-C, and 5.7% in severe MIS-C. There was a statistically significant correlation between DNI levels and the severity of MIS-C. The cutoff value of DNI for predicting MIS-C was 0.45%. In the analysis of the diagnostic performance of DNI compared with CRP, ANC, ALC and platelet counts, sensitivity, specificity, positive predictive value, and negative predictive value were found to be 79.5%, 97.1%, 95.7%, and 85.3%, respectively.Conclusions: The delta neutrophil index was identified as a diagnostic marker for MIS-C such as ANC, ALC, platelet count, and CRP. DNI levels in hemogram analysis may guide clinicians in determining the diagnosis and severity of MIS-C. What is Known: • Although CRP, sedimentation, ALC, ANC, platelet count, sodium, and albumin are used as first step tests, there is no specific laboratory marker used in the diagnosis of MIS C. • The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is elevated in infection and inflammation. What is New: • DNI is a promising and easily accessible marker that can be used with other markers in the diagnosis and determines the severity of MIS C. • DNI is an easily accessible, inexpensive, and dynamic marker and its levels in simple hemogram analysis will guide pediatricians in determining the diagnosis and severity in MIS C., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and aim Acute kidney injury (AKI) is part of the multiple organ dysfunction syndrome in critically ill patients and is a common condition in intensive care units (ICUs). Renal replacement therapy (RRT) is the cornerstone of treatment for AKI in critically ill patients. This patient population has a high mortality rate despite RRT. There are two methods of RRT for patients in ICUs: intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT). Both CRRT and IHD similarly provide adequate metabolic control. We aimed to compare these two RRT modalities in terms of ICU stay, mortality, and laboratory recovery in these patients with high mortality. Materials and methods A total of 120 patients with AKI who needed RRT in the ICU were included in the study (CRRT, n:40; IHD, n:80). Acute Physiology and Chronic Health Evaluation (APACHE) II, Sepsis-related Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score (SAPS)-II scores at the time of admission to the ICU were calculated. Mean arterial pressure, urea, creatinine, sodium, potassium, calcium, pH, lactate, and bicarbonate levels were measured before and after dialysis. Patients were classified as living and deceased. Factors affecting the length of stay in the intensive care unit and 30-day mortality were evaluated. The variability in laboratory parameters between groups before and after dialysis was examined. The groups were compared with these parameters. Results Sixty-one point seven percent (61.7%, n:74) of the patients were female. The mean age was 62.90±13.64 years. At the time of admission to the ICU, the patients' SAPS II score was 45.05±12.76, APACHE II score was 22.05±6.32, and SOFA score was 8.26±2.48. 66.7% (n:80) of the patients included in the study died, and the length of stay of these patients in the ICU was 12.85±10.23 days. When the groups were compared, SAPS II, APACHE II scores, and SOFA scores were significantly higher in the CRRT group than in the IHD group (p:0.038, p:0.015, p:0.027, respectively). Although the length of stay in the ICU was shorter in the CRRT group, it was not statistically significant (p:0.075). There was no statistically significant difference between the groups in terms of mortality (p: 0.891). SAPS-II, APACHE II, and SOFA score affected 30-day mortality while age, gender, and RRT modalities were not associated with mortality. The improvement in laboratory parameters between the pre and post-RRT groups was statistically more significant in the IHD group (p<0.001). It was determined that there was a statistically greater decrease in mean arterial pressure in the IHD group (p<0.001). Conclusions It was determined that there was no difference between the CRRT and IHD modalities applied in patients with AKI admitted to the ICU in terms of mortality and length of stay in the ICU. It was observed that both modalities improved on laboratory parameters, but the improvement was greater in the IHD group. However, it was determined that there was a statistically greater decrease in mean arterial pressure in the IHD group., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Yılmaz Aydın et al.)

Behçet's disease is an inflammatory vasculitic disease of unknown etiology characterized by recurrent oral and genital ulcers, ocular findings, and multiple organ involvement. Mucocutaneous findings are the most common symptoms. The most used diagnostic criteria are International Criteria for BD (ICBD), International Study Group (ISG) criteria and pediatric Behçet's disease criteria (PEDBD). Although diagnostic criteria have been defined, the diagnosis is still difficult due to clinical findings developed in pediatric patients. The aim of this study was to evaluate the clinical findings, phenotype characteristics, sensitivity and specificity of diagnostic criteria, and the course of pediatric Behçet's disease (BD). We evaluated retrospectively the files of 67 (29 M/38 F) patients diagnosed with BD according to expert opinion. The patients were reclassified according to ISG, ICBD, and PEDBD criteria. The control group consisted of a total of 69 patients with BD-mimicking diseases or presenting at least one major BD sign followed at the same center. Sensitivity and specificity were evaluated for the criteria. The mean age of diagnosis was 13.38 ± 3.2 years. There were oral aphthous ulcers in 98.5%, genital ulcers in 68.7%, skin lesions in 31.3%, vascular involvement in 17.9%, neurological involvement in 11.9%, positive pathergy test in 33.8%, and positive HLA-B51 in 57.1% of patients. The sensitivity of ICBD, ISG and PEDBD criteria was 88.1, 43.3, and 37.3%, respectively. The specificity of ICBD, ISG, and PEDBD criteria was 100%. Diagnosis of BD in childhood is still difficult. ICBD criteria have the highest sensitivity among the diagnostic criteria. These criteria can also be used in childhood., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Chronic non-bacterial osteomyelitis is a chronic sterile inflammatory bone condition. We aimed to describe patients' clinical and radiographic findings and to evaluate their response to therapy and their quality of life., Methods: This cross-sectional study included 18 patients from a single center in Turkey whose clinical, radiological features, and outcomes were reviewed retrospectively. The quality of the patients' lives after treatment was compared with healthy controls using the Pediatric Quality of Life Inventory 4.0., Results: The median age of disease onset was 12 years (IQR 10-14 years) and 11 (61.1%) patients were male. The median follow-up duration was 15 months (IQR 12-22 months). The persistent form of chronic non-bacterial osteomyelitis was the most common pattern in 15 (83.3%) patients and a recurrent pattern was defined in three (16.7%) patients. The lesions were multifocal in all patients and 15 (83.3%) patients had symmetric distribution in whole-body magnetic resonance imaging. The most common sites of arthritis were the knee and sacroiliac joints. Methotrexate was used in 16 (88.9%) patients as first-line therapy. However, some patients were unresponsive to the first-line therapy and needed tumor necrosis factor-α inhibitors (55.6%) and bisphosphonates (16.7%). We observed remission in only four (22.2%) patients, and three (16.7%) patients were unresponsive. The patients had a significantly poorer quality of life than controls (P = 0.005)., Conclusions: Chronic non-bacterial osteomyelitis is an insidious disease that requires detailed analysis for diagnosis and whole-body magnetic resonance imaging is an effective tool for its diagnosis. Despite the advanced treatment, patients with chronic non-bacterial osteomyelitis have a poor quality of life., (© 2022 Japan Pediatric Society.)

Introduction: Monocyte to high-density lipoprotein (HDL) cholesterol ratio (MHR) has emerged as a novel marker of endothelial injury, inflammation, and oxidative stress. This study aimed to investigate the effect of MHR on primary nephrotic syndrome (NS) and its relationship with the severity of proteinuria., Methods:  This study enrolled 161 patients newly diagnosed with primary NS and 100 healthy individuals. Demographic characteristics of the patients, primary NS diagnosis, basal laboratory parameters, the amount of 24-hour urinary protein excretion, and MHR were recorded. The groups were compared regarding these parameters., Results:  MHR was significantly higher in patients with primary NS compared with the healthy group (12.89 ± 4.86 and 9.71 ± 2.30, respectively; p < 0.001). There was no difference between the groups in terms of age and sex. The amount of protein in the 24-hour urine in patients with a diagnosis of primary NS was 6.91 ± 3.73 g/day. The correlation analysis showed a positive correlation between MHR and the amount of proteinuria (r = 0.519, p < 0.001) and creatinine level (r = 0.167, p = 0.034). The multivariate regression analysis found that the severity of proteinuria was independently correlated to MHR (p < 0.001). According to the receiver operating characteristic curve analysis, the optimal cut-off level for MHR in NS was 10.08 (area under the curve of 0.704, sensitivity of 68%, and a specificity of 62%)., Conclusion:  Our study is the first to compare the severity of proteinuria and renal functions with MHR in patients with primary NS. We believe that MHR can be used as a biomarker to determine inflammation, endothelial injury, and the level of oxidative stress, and may be useful to predict prognosis in patients with primary NS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Yılmaz Aydın et al.)

Objectives: The aims of this study were to describe the clinical features, comorbidities and outcome of systemic childhood polyarteritis nodosa (PAN) and to evaluate PAN-like diseases in differential diagnosis., Methods: The study group consisted of patients who were diagnosed as PAN in a referral center in Turkey. The files of all patients were reviewed retrospectively. Disease activity was evaluated with pediatric vasculitis activity score (PVAS)., Results: A total of 19 (13 boys/six girls) patients were enrolled in the study. The mean age of patients was 10.37 ± 3.6 years. The mean duration of follow-up was 5.73 ± 3.74 years. Eight patients (42.1%) were also diagnosed with familial Mediterranean fever (FMF). The cutaneous involvement was higher in patients with PAN than those with FMF-associated PAN ( p  = .03). The median (min-max) PVAS at diagnosis was 5 (3-7). There was no correlation between PVAS scores at the time of diagnosis and age, clinical findings and relapse. CECR1 mutation was detected in one patient leading to deficiency of adenosine deaminase 2., Conclusion: The clinical presentation is variable in children with PAN. PAN-like diseases characterized by necrotizing vasculitis should be considered. The possibility of FMF should be kept in mind if inflammation cannot be controlled.

Objective: The aim of this study is to describe clinical features of patients with oligoarticular juvenile idiopathic arthritis (JIA) who achieved inactive disease at 3rd month and also to determine the predictors of relapse and extended course., Methods: In the cohort study, 88 patients with oligoarticular JIA were retrospectively analyzed. The demographic data, clinical features, medications, relapse rates were recorded. Juvenile Arthritis Disease Activity Score (JADAS) and American College of Rheumatology Pediatric criteria were used to measure disease activity and treatment response at 3, 6 and 12 months., Results: Fifty-nine (67%) patients were females and the mean age at diagnosis was 7.9 ± 4.3 years. The odds of achieving inactive disease (JADAS ≤1) at 3rd month were increased by a lower JADAS27 score at admission. Forty-one (48.8%) of 84 patients relapsed. Ankle involvement at onset, high JADAS27 score at admission, increased ESR at admission and presence of synovial hypertrophy in imaging were risk factors for occurrence of relapse., Conclusion: Our results show that a significant proportion of oligoarticular JIA patients relapse after inactive period. JADAS is a useful tool to guide the treatment decisions of patients who may be at risk of high disease activity and relapse.

Aims: Recently, multisystem inflammatory syndrome in children (MIS-C) has been recognized in association with coronavirus disease 2019 as a cytokine storm syndrome. MIS-C presents with symptoms similar to Kawasaki disease and macrophage activation syndrome (MAS). We aimed to better understand this cytokine storm syndrome by comparing the initial laboratory findings of MIS-C and MAS., Methods: Patients who were diagnosed with MAS due to systemic juvenile idiopathic arthritis in our clinic between March 2002 and November 2020 and with MIS-C between 20 September and 20 October 2020 were enrolled into the study. The medical files of all patients were reviewed retrospectively., Results: A total of 13 MAS (9 boys, 4 girls) and 26 MIS-C (16 boys,10 girls) patients were included in the study. Hemoglobin, absolute neutrophil and lymphocyte counts, C-reactive protein (CRP), ferritin, fibrinogen and lactate dehydrogenase (LDH) levels showed significant differences between the two groups (P < 0.05). Patients with MAS had lower hemoglobin (10.10 g/dL) and fibrinogen (2.72 g/dL), but higher ferritin (17 863 mg/dL) and LDH (890.61 U/L) at the time of diagnosis. Patients with MIS-C had higher absolute neutrophil count (12 180/mm 3 ) and CRP (194.23 mg/dL) values, but lower absolute lymphocyte count (1140/mm 3 ) at the time of diagnosis. Left ventricle ejection fraction was significantly lower in the MIS-C group in echocardiographic evaluation (P < 0.001)., Conclusion: Ferritin, hemoglobin, LDH, and fibrinogen levels were significantly changed in MAS compared with MIS-C. However, patients with MIS-C have more severe signs than MAS, such as cardiac involvement., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The diagnosis of Familial Mediterranean fever (FMF) based on clinical findings supported by genetic mutation. Recently, the new Eurofever/PRINTO classification criteria including genetic analysis were established. The aim of this study is to evaluate the performance of the new criteria in FMF patients with a single exon 10 mutation in childhood. The study group consisted of FMF patients who had a single exon 10 mutation in a referral center in Turkey. Patients with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome were included as a control group. The medical charts of all patients were reviewed retrospectively. A total of 106 FMF patients (59 boys) were enrolled in the study group. The median age at first symptom was 5; the median age at diagnosis was 7 years. The mean follow-up was 33 ± 35.4 months. Majority of the patients (n = 58, 54.7%) had heterozygous M694V, 16 (15%) patients had M694V/E148Q and 13 (13.8%) patients had heterozygous M680I mutation. The sensitivity of the Yalcinkaya-Ozen criteria was 98.1% and it was 97.1% for the Eurofever/PRINTO classification criteria. The specificity of the new Eurofever/PRINTO classification criteria was 96.7% and it was 74.1% for the Yalcinkaya-Ozen criteria. The new Eurofever/PRINTO classification criteria have a good sensitivity as the Yalcinkaya-Ozen criteria in patients with a single exon 10 mutation. Additionaly, the new criteria have better specificity. It should be useful to apply the clinical only criteria where the carrier rate is high.

Autoinflammatory diseases (AIDs) are a recently described group of conditions caused by mutations in multiple genes that code for proteins of the innate immune system. Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory diseases comprising three clinically overlapping disorders: familial cold urticarial syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). CAPS have been associated with gain-of-function variations in NLRP3 (NOD-like receptor family, pyrin containing domain-3). However, a new class of autoinflammatory disease resembling FCAS or MWS has been described in patients with NLRP12 mutations. Here, we report a 6-year-old boy diagnosed with AID who developed an unexpected C3 glomerulopathy during attacks and carried a novel variation in NLRP12. Following treatment with IL (interleukin) 1 targeting agents, all symptoms and inflammation resolved. This is the first case in the literature affected by both autoinflammatory disease and C3 glomerulopathy.

Background and Objective: Fluid overload is a common and serious problem that leads to severe complications in dialysis patients. We aimed to compare hydration status as measured with bioimpedance analysis (BIA) method in hemodialysis (HD) and peritoneal dialysis (PD) patients, as well as investigating the association between blood pressure, left ventricular mass index (LVMI) and hydration status., Materials and Methods: We examined 43 HD and 33 PD patients. Blood pressure was recorded. In each group, echocardiographic examinations were performed on all patients. Hydration status was assessed using multifrequency bioelectrical impedance analysis. Overhydration was defined as an overhydration (OH)/extracellular water (ECW) ratio of >0.15., Results: The OH/ECW ratio was significantly higher in PD patients compared to post-HD patients. Overhydration was statistically more frequent in PD than in post-HD patients (30.3% vs. 11.6%, P=0.043). Systolic blood pressure (SBP) in both post-HD and PD groups, and LVMI in the PD group were found to be significantly higher in overhydrated patients than non-overhydrated patients. In multiple linear regression analyses, increased OH/ECW ratio was independently associated with higher SBP and LVMI., Conclusions: Fluid overload may be an even more prevalent and serious problem in PD patients. Overhydration is closely associated with increased blood pressure and LVMI. OH/ECW ratio, a derived parameter of fluid load measured by BIA, was a significant and independent determinant of SBP and LVMI., (Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

The title molecule (C19H17N5O4S·H2O) was synthesized and characterized by IR-NMR spectroscopy, MS and single-crystal X-ray diffraction. The molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) 1H and 13C NMR chemical shift values of the compound in the ground state have been calculated by using the density functional theory (DFT) method with 6-31G(d) basis set, and compared with the experimental data. All the assignments of the theoretical frequencies were performed by potential energy distributions using VEDA 4 program. The calculated results show that the optimized geometries can well reproduce the crystal structural parameters, and the theoretical vibrational frequencies and 1H and 13C NMR chemical shift values show good agreement with experimental data. To determine conformational flexibility, the molecular energy profile of the title compound was obtained with respect to the selected torsion angle, which was varied from -180° to +180° in steps of 10°. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis and thermodynamic properties of the compound were investigated by theoretical calculations., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This study was aimed to isolate and identify Mycobacterium bovis and non-tuberculous mycobacteria (NTM) species in raw milk samples from cattles and to compare the diagnostic performance of the methods used for that purpose. A total of 145 raw milk samples from cattles were collected from five villages in Mersin province (located on Mediterrenean region of Turkey) between April and June 2008. Presence of mycobacteria was investigated by Ehrlich Ziehl Neelsen (EZN) staining method, culture in Löwenstein- Jensen (LJ) medium and polymerase chain reaction (PCR). Only 1 (0.7%, 1/145) raw milk sample was found to be acid fast bacilli (AFB) positive with EZN staining. Eleven (7.6%) samples were positive by culture and mycobacterial DNA was detected in 6 (4.1%) samples by PCR. Mycobacterium was isolated from both creamy and pellet layer of a culture positive sample. Identification was carried out with conventional biochemical tests, PCR-Restriction Fragment Length Polymorphisms (PCR-RFLP) and spoligotyping (spacer oligonucleotide typing) methods. One isolate was identified as Mycobacterium tuberculosis complex (MTC) and 11 isolates were identified as NTM out of 12 isolates those were isolated from culture. According to PCR-RFLP analysis of these 11 NTM isolates, 6 (54.5%) were Mycobacterium genavense, 2 (18.2%) were Mycobacterium simiae, 2 (18.2%) were Mycobacterium szulgai and 1 (9.1%) was Mycobacterium fortuitum. MTC isolate was identified as M.bovis by spoligotyping. According to the results of our study, both pellet and creamy layers from raw milk samples should be cultured to selective LJ medium (without glycerol, with 0.4% sodium pyruvate) to improve the chance of isolation and must be incubated for up to eight weeks. In our region, NTM were isolated in 6.9% and M.bovis in 0.7% of the raw milk samples from cattles and this emphasized the risk of transmission of mycobacteria to man via direct contact or ingestion of unpasteurized milk products.

Penicillin-binding proteins (PBPs) are the natural targets of beta-lactam antibiotics and mutations in pbp1a, pbp2b, and pbp2x genes, which encode PBPs, are responsible for resistance to beta-lactams in Streptococcus pneumoniae. In the present study, we intended to determine how often the common mutation patterns occurred within the pbp1a, pbp2b, and pbp2x PBP gene regions and evaluate the PBP genotype mutations which were associated with penicillin resistance in several penicillin-susceptible and - resistant S.pneumoniae isolates in Mersin, Turkey. A total of 62 S.pneumoniae strains isolated from different clinical specimens (32 nasopharyngeal swab, 16 sputum, 3 blood, 3 wound, 2 cerebrospinal fluids and one of each urine, abscess, bronchoalveolar lavage, conjunctival swab, tracheal aspirate, middle ear effusion) were included in the study. Penicillin susceptibilities of the isolates were searched by disc diffusion and E-test methods, and 23 of them were identified as susceptible, 31 were intermediate susceptible, and eight were resistant to penicillin. A rapid DNA extraction procedure was performed for the isolation of nucleic acids from the strains. Distribution of PBP gene mutations in pbp1a, pbp2b, and pbp2x gene regions related to penicillin resistance was determined by using a wild-type specific polymerase chain reaction (PCR) based technique. PBP gene alterations of those isolates were also evaluated in relation to penicillin susceptibility and resistance patterns. Twenty two (95.7%) of 23 penicillin-susceptible S.pneumoniae isolates exhibited no mutation in the three PBP genes (pbp1a, pbp2x, and pbp 2b), while 1 (4.3%) of these harbored mutations in all of the three PBP genes. The penicillin-intermediate susceptible S.pneumoniae isolates exhibited various combinations of mutations. One (3.2%) of 31 penicillin-intermediate susceptible isolates exhibited no mutation in the three PBP genes, while 22 (71%) of them yielded mutations in all of the three PBP genes. The remaining 8 (25.8%) isolates harbored mutations for dual PBP genes (in five strains pbp1a and pbp2b; in two strains pbp2x and pbp2b; in one strain pbp1a and pbp2x). Seven (87.5%) out of eight penicillin-resistant S.pneumoniae isolates (MIC ≥ 2 µg/ml) revealed mutations in all of the three PBP genes and the other penicillin-resistant isolates exhibited no mutation in the PBP genes. The present study supplied important data on the frequency of different patterns of mutations occurring at various regions of PBP genes related to penicillin resistance in S.pneumoniae isolates in our restricted region. The results supported the notion that penicillin resistance in S.pneumoniae was mainly attributed to alterations in pbp1a, pbp2x, and pbp2b gene regions and wild-type sequence specific PCR could be applied to characterize genotypic background of penicillin resistance in S.pneumoniae strains.