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Oseltamivir is an antiviral drug and is used in the treatment of all influenza viruses. It is the most effective antiviral option against all influenza viruses that can infect humans. UV and LC methods have been developed and validated according to ICH guidelines for various parameters like selectivity, linearity, accuracy, precision, LOD and LOQ, robustness for the quantitative determination of oseltamivir in pharmaceutical formulations. LC method has been performed using reverse phase technique on a C-18 column with a mobile phase consisting of 20 mM potassium dihydrogen phosphate solution and acetonitrile (60:40, v/v) at 25 °C. The mobile phase flow rate was 1.2 mL min−1. For the determination of oseltamivir, UV spectrum has been recorded between 200 and 800 nm using methanol as solvent and the wavelength of 215 nm has been selected. Both methods have demonstrated good linearity, precision and recovery. No spectral and chromatographic interferences from the capsule excipients were found in UV and LC methods. In both methods, correlation coefficients were greater than 0.999 within a concentration range of 10–60 mg mL−1 using UV and LC. Intra-day and inter-day precision with low relative standard deviation values were observed. The accuracy of these methods was within the range 99.85–100.17% for LC and from 99.26 to 100.70% for UV. Therefore UV and LC methods gave the most reliable outcomes for the determination of oseltamivir in pharmaceutical formulation.

Apomorphine is currently used as a dopamine agonist to treat advanced Parkinson Disease. In the present study, we developed a sensitive, simple, reliable, and robust HPLC method for quality control of apomorphine hydrochloride in bulk drug and pharmaceutical formulations. C18 column was used for separation. Isocratic elution was performed using mobile phase A: 50 mM potassium dihydrogen phosphate solution (pH:3 with ortho-phosphoric acid), B: acetonitrile in the ratio of 85:15 (A: B), and the mobile-phase flow rate was kept at 1 mL min-1. Analyses were carried out at 272 nm using a UV detector. A perfect linear relationship between peak-area versus drug concentration in the range of 10‑100 μg mL-1 was observed (r2, 0.9999). It has been found that the developed method is sensitive (Detection and quantification limits were determined as 1.3 μg mL-1 and 3.8 μg mL-1, respectively), precise (RSD

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene. This retrospective study aims to evaluate the clinical manifestations and brain magnetic resonance images (MRI) analysis in 60 genetically confirmed NF1 patients. The results of next-generation sequencing (NGS), Sanger sequencing, and MLPA of NF1 gene were evaluated. A total of 54 different variants were identified. Fourteen out of them were novel variants (25.9%). Patients who complied with NIH criteria had most frequently frameshift variants (11/32 patients), and those with only CALMs had missense variants (9/28 patients). Neurofibromatosis type 1 bright objects (NBOs) on T2-weighted MRI were detected in 42 patients (42/56; 75%). These brain lesions were detected mostly in basal ganglia and in cerebellar vermis. NBOs were detected more in the patients who complied with NIH criteria (80.6%) compared to those who were only CALMs (68%). While frameshift variants (33.3%) were the most common type variants in the patients who had NBOs, the most common variants were splicing (35.7%) and missense (35.7%) variants in the patients whose MRIs were normal. Frameshift variants (11/28 patients; 39.3%) were the most common in the patients with more than one brain locus involvement. Therefore, we consider that frameshift variants may be associated with increased incidence of NBOs and involvement of more than one brain locus. In addition, NBOs may occur less frequently in the patients with splicing variants. To our knowledge, this is the first study evaluated the relationship between NF1 gene variants and NBOs. Future studies may help us understand the etiology of NBOs.

Vincristine (VCR), which is a key component of chemotherapy, is important for survival. VCR is associated with a well-known side effect, including neurotoxicity. The aim of this study was to evaluate the features of vincristine-induced peripheral neuropathy (VIPN) and the effectiveness of pyridoxine plus pyridostigmine therapy in children with acute lymphoblastic leukemia. The WHO and NCI CTCAE neurotoxicity scorings were used to evaluate VIPN at diagnosis, in the first month, and after the third month of the treatment. The clinical features of 23 patients having acute lymphoblastic leukemia with VIPN during the period of July 2013–February 2016 were prospectively evaluated. The mean age was 72.8 ± 51.6 months, and 26.1%, 56.5%, and 17.4% were in standard, moderate, and high-risk groups, respectively. Neuropathy frequently occurred at induction (82.6%) and reinduction (17.4%) of the protocol. Drop foot (82.6%), leg pain (82.6%), and difficulty in walking (82.6%) were observed. The mean total cumulative dose of neuropathy occurrence was 5.6 ± 2.03 mg/m2. Our study showed that both the WHO and NCI CTCAE scorings were significantly improved via pyridoxine plus pyridostigmine therapy. The WHO and NCI CTCAE scorings may be used for evaluating neuropathy at diagnosis and follow-up of neurotoxicity with treatment. Pyridoxine plus pyridostigmine therapy may be an effective option in the treatment of VIPN.

Donepezil HCl is a hydrochloride salt of a piperidine derivative acetylcholinesterase inhibitor and, it uses in treatment demantia of Alzheimer’s disease. In this study, a sensitive and rapid HPLC-UV method was developed and validated for determination of Donepezil HCl in API and tablet dosage forms. Chromatographic separation was performed using a Ace 5 C18 (5 ?m, 250 x 4.6 mm) by using isocratic phosphate buffer at pH:2.0 and acetonitrile (55:45, v/v) mobile phase was used at the rate of 1.2 mL/min. The column temperature was set at 30 ?C and the UV detection was recorded at 268 nm. The method was validated with respect to specificity, precision, accuracy, linearity, repeatability and reproducibility parameters in a concentration range of 25-125 µg/mL. The limit of detection (LOD) and limit of quantification (LOQ) were determined as 1.40 and4.20 µg/mL, respectively. The uncertainty budget of the measurement for Donepezil HCl was estiamted as 5.80 % at 95% confidence level (k = 2).

L-Asparaginase (L-Asp) is a critical component of chemotherapy for acute lymphoblastic leukemia (ALL). However, toxic effects associated with L-Asp, such as hepatic dysfunction, pancreatitis, hypercholesterolemia, and hyperglycemia, have occurred. In addition, acute pancreatitis is a significant life-threatening adverse event associated with ALL. We describe 2 patients with ALL who had L-Asp-associated pancreatitis (AAP), with one patient presenting with hyperglycemia and the other presenting with hypoglycemia during induction treatment. When octreotide was administered to both of these patients, the clinical findings and laboratory data were improved. AAP was not repeated after treatment with pegylated asparaginase. Although AAP has a high risk of mortality and morbidity in childhood, APP treatment with appropriate agents, such as octreotide, can be successful. (C) 2020 Elsevier Inc.

In this case study, we report an 11-year-old male patient who had jaundice, hepatosplenomegaly, and chronic mild congenital non-autoimmune hemolytic anemia. In our patient, a novel homozygous missense mutation in the PIEZO1 gene was detected using a gene-targeted Next-Generation Sequencing panel: c.3364G>A (p.Glu1122Lys), confirming the diagnosis of DHS.

Objective Stroke is one of the major complications of sickle cell disease (SCD). Stroke features either occlusion of, or stenosis at, the origin of one of the large intracerebral arteries, the internal carotid artery (ICA), and/or the middle cerebral artery (MCA). Purpose We sought correlations between cerebral blood flow velocities and the laboratory and clinical findings of patients with SCD. Materials and methods Fifty-three pediatric SCD patients (39 with HbSS, 14 with HbSβ0) were analyzed. The mean patient age was 12.9±3.9 years. The control group contained 24 healthy individuals. The time-averaged maximum mean velocity (TAMMV) and resistive index (RI) of the MCA, the TAMMVs of the ICA and vertebral artery (VA), and the diameter of the VA were estimated through transcranial Doppler ultrasonography using a 2.5 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. We evaluated the relationships between the TAMMVs, laboratory parameters, and clinical findings. Results The mean±SD MCA TAMMV was 161.2±35.4 cm/s in patients with HbSS and 185.8±62.9 cm/s in patients with HbSβ0. The mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 168.5±43.9 cm/s, 0.63±0.06, 116.8±25.5 cm/s, 69.2±18.5 cm/s, and 3.5±0.61 mm for all SCD patients, respectively. In the control group, the mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 103.8±28.8 cm/s, 0.53±0.04, 96.4±27.8 cm/s, 40.3±12.1 cm/s, and 3.4±0.6 mm, respectively. Although the differences were not significant, TAMMVs were higher in HbSβ0 patients taking hydroxyurea; those with hemoglobin levels 1000 ng/dL, mean platelet volume >12 fL, or red cell distribution width >18%; or required chelation, or were below the third percentiles of weight and height. The TAMMV was significantly higher only in SCD patients who complained of headache. Conclusions High ferritin and low hemoglobin levels, a high mean platelet volume, a high red cell distribution width, low weight (below the third percentile), and a short height (below the third percentile) may be associated with elevated cerebral blood flow velocities and an increased stroke risk in children with SCD. Children with such features should be closely followed-up through transcranial Doppler ultrasonography examination.

The objective of this study was to assess the difference in irritability and perceived expressed emotion (EE) between adolescents with iron deficiency (ID) or iron deficiency anemia (IDA) and their healthy peers. In addition, we aimed to investigate the relationship between hemogram parameters, irritability, and perceived EE in adolescents with ID and IDA. The sample of this single-center cross-sectional case-control study consisted of 89 adolescents from 12 to 17 years of age. Of the participants, 19 had been diagnosed with ID, 31 had IDA, and 39 were healthy controls. Significant differences in the self-reported and parent-reported irritability scores were observed between the ID group and the control group and between the IDA group and the control group. There was also a significant difference in the subscale of irritability between the ID group and the control group. The difference between the IDA and control groups in the intrusiveness subscale was found to be significant as well. Adolescents with IDA and ID exhibited significantly perceived irritability compared with the control group. In terms of irritability, adolescents with IDA and ID revealed greater irritability than their healthy peers. The results of this study suggest that irritability and perceived EE should be investigated in cases of ID, whether with or without anemia. As chronic diseases may benefit substantially from psychiatric consultation, psychosocial evaluation and intervention should be considered a complementary treatment option in the management of ID and IDA.

Background Acute viral respiratory infections are common causes of febrile episodes in children. There are still limited data about distribution of acute viral respiratory infections in children with cancer. Objective The first aim of this study was to evaluate the viral etiology and seasonality of acute viral respiratory infection in pediatric patients with cancer in a 3-year study. Our second aim was to evaluate the impact of viral infections on delaying the patients' chemotherapy or radiotherapy. Materials and methods This cross-sectional study was conducted from January 2014 to July 2017. Nasopharyngeal aspirates were analyzed in patients younger than 21 years with acute respiratory infections. Patients were treated in the Pediatric Hematology and Oncology Department of Dr. Behcet Uz Children's Hospital with real-time multiplex polymerase chain reaction. Data were analyzed to determine the frequency and seasonality of infections. The χ or the Fisher exact tests were used. Results A total of 219 samples of nasopharyngeal aspirates and blood were analyzed. The mean patient age was 76.8±59.3 months, with 46.3% female and 53.7% male children in a total of 108 patients. Of this total, 55% (60/108 cases) had multiple acute respiratory infections. Acute lymphoblastic leukemia (48.1%) was the most prevalent disease. The 3 most prevalent viruses were human rhinovirus (HRV) (33.1%), parainfluenza (PI) (18.7%), and coronavirus (CoV) (14.8%). In terms of the seasonal distribution of viruses, PI was most common in winter 2014, HRV in spring 2014, HRV in fall 2014, PI in winter 2015 and summer 2015, CoV in spring 2015, HRV in fall 2015, both influenza and HRV in winter 2016, both human metapneumovirus and bocavirus in spring 2016, HRV in summer 2016, both HRV and PI in fall 2016, both respiratory syncytial virus and influenza in winter 2017, HRV in spring 2017, and both HRV and adenovirus in summer 2017. The mean duration of neutropenia for patients with viral respiratory infection was 17.1±13.8 (range: 2 to 90) days. The mean duration of symptoms of viral respiratory infection was 6.8±4.2 (range: 2 to 31) days. A delay in chemotherapy treatment owing to viral respiratory infection was detected in 73 (33.3%) patients. The mean duration of delay in chemotherapy treatment was 9.6±5.4 (range: 3 to 31) days. Conclusions In conclusion, we report our 3-year experience about the frequency and seasonality of respiratory viruses in children with cancer.

Objective: Anthracyclines which are the main drug of chemotherapy protocols had cardiotoxicity as the most frequent and well-known side effect. We aimed to evaluate prospectively the heart rate variability with 24-hour Holter electrocardiography (ECG) in children with cancer who treated with anthracycline drugs. Material and Methods: The 24-hour Holter ECG monitoring was performed at the baseline, at time of 120 mg/m2 and ≥240 mg/m2 of cumulative anthracycline dose in patients with cancer who treated with anthracycline. The time-domain and frequency-domain measurements of heart rate variability (HRV) were obtained. The patients were classified into three groups as Group1:at baseline (n=54), Group 2:≥120mg/m2 (n=54), Group 3:≥240mg/m2 (n=54).Results: The median age was 48 months (range 9-192 months). All types of cancer were 38 patients (70.4%) of acute leukemia, two patients (3.8%) of T lymphoblastic lymphoma, and 14patients (25.8%) of other childhood cancer who treated with anthracycline. However, all heart rate variability parameters were decreased after each increased cumulative anthracycline dose, especially time-domain parameters such as nSDNN index, rMSSD, pNN50, frequency parameters such as LF, HF, and Total power were significantly altered among Group1 and Group 3. LF/HF ratio was also statistically significantly increased in Group 3. According the heart rate parameters, the mean average heart rate, mean minimum heart rate and mean RR were statistically significantly prolonged from Group1 to Group 3.Conclusion: Heart rate variability parameters are a noninvasive technique to demonstrate cardiac autonomic neural dysfunction and early myocardial injury. The 24-hour Holter ECG may be used for detecting early cardiac dysautonomia effect during anthracycline treatment with each elevated 120mg/m2 anthracycline of cumulative dose., Amaç: Kemoterapi protokollerinin temel ilacı olan antrasiklinler en sık kardiyotoksisite yan etkisine sahiptir. Antrasiklin ile tedavi edilen kanserli çocuklarda kalp hızı değişkenliğini 24 saatlik Holter elektrokardiyografi (EKG) ile prospektif olarak değerlendirmeyi amaçladık.Gereç ve Yöntemler: Antrasiklin ile tedavi edilen kanserli hastalarda hiç tedavi almadan, 120mg/m2 ve ≥240 mg/m2 kümülatif antrasiklin dozunda 24 saatlik Holter EKG monitörizasyonu yapıldı. Kalp atış hızı değişkenliğinin (HRV) zaman alanı ve frekans alanı ölçümleri elde edildi. Hastalar üç gruba ayrıldı: hiç tedavi almadan Grup 1 (n = 54), Grup 2 :≥120 mg/m2 (n = 54), Grup 3: ≥240 mg/m2 (n = 54) seklinde ayrıldı.Bulgular: Ortanca yaş 48 aydı (aralık 9-192 ay). 38 (% 70.4) hasta akut lösemi, iki hasta T lenfoblastik lenfoma (% 3.8) ve 14 hasta (% 25.8) diğer çocukluk çağı kanserleridir. Bununla birlikte, tüm kalp hızı değişkenleri, nSDNN indeksi, rMSSD, pNN50 gibi zaman parametreleri ve LF, HF ve Toplam güç gibi frekans parametreleri gibi her artan kümülatif antrasiklin dozu ile azalma görüldüğü belirlendi. LF/HF oranı da Grup 3’te istatistiksel olarak anlamlı şekilde artış gösterdiği saptandı. Kalp hızı parametrelerine göre, ortalama kalp hızı, ortalama minimum kalp hızı ve ortalama RR, kümülatif doz artıkça istatistiksel olarak anlamlı şekilde uzadığı belirlendi.Sonuç: Kalp hızı değişkenleri, kardiyak otonomik nöral disfonksiyonu ve erken miyokardiyal hasarın gösterilmesi için invazif olmayan bir tekniktir. 24 saatlik Holter EKG’si, her artan 120 mg/m2 antrasiklin kümilatif dozu ile antrasiklin tedavisi sırasında erken kardiyak dysautonomia etkisini saptamak için kullanılabilir.

Giriş: Akut lenfoblastik löseminin (ALL) tanı ve prognozu için immünofenotip alt gruplarının tanımlanması çok önemlidir.Gereç ve Yöntem: Çalışmaya TR-ALL 2000 (modifiye) BFM tedavi protokolü uygulanan 105 ALL olgu (65 erkek, 40 kadın; ortalama yaş 5.9 ± 3.8 yıl) çalışmaya dahil edildi.Bulgular: EGIL sınıflaması dağılımları pro-B ALL (n = 1), common B ALL (n = 46), pre-B ALL (n = 40), pre-T ALL (n = 8), kortikal T ALL (n = 6) ve matür T ALL (n = 4). T ALL grubunda lökosit ≥100.000 / mm³, lenfadenopati ≥2 cm, mediastinal tutulum yaygın olarak tespit edildi. T ALL, 8.gün periferik kan yaymasında blast sayısı ve 15. gün kemik iliği aspirasyonu (KİA)’ nundaki blast sayısına göre kemoterapiye kötü yanıt gösterdiği saptandı. Tedavinin indüksiyon döneminde nüks, mortalite ve ölüm oranı T ALL grubunda sık olarak görüldü. Tek değişkenli analizle gösterilen prognostik potansiyele sahip olan değişkenler tanı anında lökosit sayısı, hepatomegali, splenomegali ve lenfadenopati, 8. gün steroid yanıtı, 15. gün KİA yanıtı, risk grubu, nüks ve immünofenotip idi. Çok değişkenli Cox regresyon analizinde ise sadece lökosit sayısının (HR 2.51, p, Background: The identification of immunophenotype subgroups is very important for the diagnosis and prognosis of acute lymphoblastic leukemia(ALL).Material and Methods: The study included 105 children with ALL(65 males, 40 females; mean age 5.9±3.8 years) who were treated TR-ALL 2000(modified) BFM treatment protocol. Results: The distributions of EGIL classification were pro-B ALL(n=1), common B ALL(n=46), pre-B ALL(n=40), pre-T ALL(n=8), cortical T ALL(n=6), and mature T ALL(n=4). Leukocyte≥100,000/mm³, lymphadenopathy≥2 cm, mediastinal involvement were commonly identified in T ALL group. T ALL had a poor response to chemotherapy according to 8th-day peripheral circulation blast counts and 15th-day bone marrow aspiration(BMA) blast counts. The recurrence, mortality, and death rate in the induction period of treatment were frequently detected in T ALL group. The variables that had prognostic potential, as indicated by univariate analyses, were leukocyte count, hepatomegaly, splenomegaly, and lymphadenopathy at the time of diagnosis, 8th-day steroid response, 15th-day BMA response, risk group, recurrence, and immunophenotyping. Multivariate Cox regression analysis demonstrated that only the leukocyte count(HR 2.51, p < 0.001) was a predictor of prognosis. Conclusion: Immunophenotyping may be effective in the diagnosis and prognosis of ALL, identification of risk groups, and in risk-based treatment planning. T ALL had a poor prognosis.

Hemophagocytic lymphohystiocytosis (HLH) may be primary (inherited/familial) or secondary to infections, malignancies, rheumatologic disorders, immune deficiency syndromes and metabolic diseases. Cases including lysinuric protein intolerance, multiple sulfatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis have previously been reported. It is unclear how the metabolites trigger HLH in metabolic diseases. A 2-month-old infant with lethargy, pallor, poor feeding, hepatosplenomegaly, fever and pancytopenia, was diagnosed with HLH and the HLH-2004 treatment protocol was initiated. Analysis for primary HLH gene mutations and metabolic screening tests were performed together; primary HLH gene mutations were negative, but hyperammonemia and elevated methyl citrate were detected. Propionic acidemia was diagnosed with tandem mass spectrometry in neonatal dried blood spot. We report this case of HLH secondary to propionic acidemia. Both metabolic disorder screening tests and gene mutation analysis may be performed simultaneously especially for early diagnosis in infants presenting with HLH.La linfohistiocitosis hemofagocítica (LHH) puede ser primaria (hereditaria) o secundaria a infecciones, tumores malignos, trastornos reumatológicos, síndromes de inmunodeficiencia y metabolopatías. Se informaron casos de intolerancia a la proteína lisinúrica, deficiencia de múltiples sulfatasas, galactosemia, enfermedad de Gaucher, síndrome de Pearson y galactosialidosis. No se sabe cómo se desencadena la LHH en las metabolopatías. Se diagnosticó LHH en un lactante de 2 meses con letargo, palidez, alimentación deficiente, hepatoesplenomegalia, fiebre y pancitopenia, y se instauró el protocolo HLH-2004. Se realizaron, en conjunto, análisis para detectar mutaciones genéticas y pruebas metabólicas; los resultados fueron negativos para las mutaciones genéticas de LHH primaria, pero se detectaron hiperamoniemia y concentración elevada de metilcitrato. Se diagnosticó acidemia propiónica. Aquí informamos sobre un caso de LHH secundaria a acidemia propiónica. Es posible la realización simultánea de pruebas de detección de trastornos metabólicos y de mutaciones genéticas para el diagnóstico temprano en los lactantes con LHH.

Introduction Infantile hemangioma (IH) is a common vascular tumor in children. It is reported that IHs are associated with immunochemical markers such as vascular endothelial growth factor (VEGF)-A, glucose transporter isoform 1 (GLUT1), and insulin-like growth factor-2 (IGF-2). Material and methods This cross-sectional study focused on pediatric patients with IH. A total of 46 patients (mean age 14.2 ± 21.9 months) with IH and 45 healthy controls (mean age 21.8 ± 15.08 months) were enrolled. Demographic data, clinical findings, and laboratory parameters were recorded. Blood samples were collected. Serum GLUT1, IGF-2, VEGF-A, fibroblast growth factor 1 (FGF1), and angiopoietin 2 levels were assessed by enzyme-linked immunosorbent assay. Results Serum GLUT1, IGF-2, and VEGF-A levels were significantly higher in patients with IH than in healthy controls (8.80 ± 4.07 pg/mL vs. 5.66 ± 4.34 pg/mL, 281.10 ± 84.12 pg/mL vs. 234.19 ± 75.38 pg/mL, 1196.99 ± 389.34 pg/mL vs. 996.99 ± 349.16 pg/mL, respectively, p = 0.026, p = 0.030, and p = 0.036). Serum GLUT1, IGF-2, and VEGF-A levels in patients with complicated hemangioma were significantly higher than in healthy controls (9.69 ± 3.94 pg/mL vs. 5.66 ± 4.34 pg/mL, 289.94 ± 83.18 pg/mL vs. 234.19 ± 75.38 pg/mL, 1276.22 ± 388.24 pg/mL vs. 996.99 ± 349.16 pg/mL, respectively, p = 0.017, p = 0.022, and p = 0.011). Serum GLUT1, IGF-2, and VEGF-A levels in patients with hemangioma receiving propranolol treatment were significantly higher than in healthy controls. Serum FGF1 levels were higher in patients with IH, complicated hemangioma, and hemangioma receiving propranolol treatment than in healthy controls but the difference was not statistically significantly. Conclusion Serum GLUT1, IGF-2, and VEGF-A levels were positively correlated with disease severity in patients with hemangioma, for example, in complicated hemangioma and hemangioma requiring propranolol treatment. However, further research on larger and different age subgroups is warranted to assess these markers.

Objective: Although there is increased survival and quality of lifefor thalassemia patients, which results from a genetic defect in globinsynthesis, heart diseases are still important causes of morbidity and mortalityrelated to the iron burden. Therefore, we aimed to evaluate the cardiacfunctions of thalassemia patients followed up in Hatay State Hospital using echocardiography.Method: A total of 101 patients with 7 thalassemia intermediaand 94 thalassemia major who were followed at Hatay state hospital wereexamined retrospectively. Of patients, 47were male and 54 were female. Their ages ranged between 1-17 years (mean8.6±4.6 years). M-mode echocardiography was used to measure LVEDd (leftventricular end-diastolic diameter) and EF (ejection fraction). The demographicand laboratory values of the patients were obtained from their files.Results: The mean of LVEDd (mm) and EF (%) were evaluated as 34.8±6.1,and 66.36±1.4 with M-mode echocardiography, respectively. When the correlation between age, ferritin and LVEDdand EF were evaluated; it was determined that there was a high positivecorrelation (r=0.649) between age and LVEDd (p2000, although it was notstatistically significant.Conclusions: In our study, it was shown that EF was decreased with increasingferritin and LVEDS was increased with increasing age of patients withthalassemia. The ideal ferritin level which was ensured aftersuitable chelation therapy should be an important goal to reduce cardiacinvolvement.

The clinical presentation of Non-Hodgkin lymphoma (NHL) is frequently associated with the involvement of the abdomen and mediastinal lymphadenopathies, but rarely the kidney, ovaries, and testicles. Here, we report a rare case of T-cell lymphoblastic lymphoma (T-LBL) presenting with bilateral nephromegaly without acute renal failure (ARF) as the first manifestation. A 30-month-old boy was admitted to the department of pediatric nephrology exhibiting abdominal distension. Physical examination revealed bilateral renal palpation up to the inguinal region. Elevated lactate dehydrogenase (LDH) levels were detected in his blood. Bilateral diffuse enlarged kidneys with increased hypoechogenicity were found on abdominal ultrasonography. In the next step, contrast-enhanced computed tomography showed diffusely enlarged kidneys, which were compressing the intestinal bowels and midline structures. Renal biopsy demonstrated precursor T-LBL. We wish to report our patient with renal T-LBL presenting with diffuse renal enlargement, which has rarely been reported in the literature.

Aim: In spite of special supplemental programs for infants, iron deficiency anemia remains relatively common, depending on ethnicity and socioeconomic status. In Turkey, free iron supplement (IS) to infants started in 2004. The aim of this current study is to evaluate the IS in infants. Materials and Methods: Between October 2014 and June 2015, a survey to evaluate the prophylactic use of iron in infants was applied at the polyclinics to the mothers of children aged 6-24 months. Results: Two hundred children were included in the study. IS was not given to 16% of the children. There was no difference in the time of attendance of IS between the premature and mature infants. Only 29% of the children had been given IS for longer than 6 months. While 36% of the children stopped receiving IS due to negligence, 8.5% of them stopped getting it it because of the adverse effect of the drug, and 39.5% of them were informed that IS had been stopped by the doctors. Advisable supplement dosage was used in 40% of the children. Conclusion: A low ratio of reasonable attendance time and dosage for prophylaxis was found. A total of 58 children had used IS for longer than 6 months and for 48 of them (82.7%) IS had been stopped by the doctor. It was thought that regularly examining a healthy child in infancy augmented the attendance time of IS.

Congenital dyserythropoietic anemias (CDAs) are rare hereditary blood disorders characterized by ineffective erythropoiesis, hemolysis, and erythroblast morphologic abnormalities in the bone marrow. The 3 main types of CDA, I to III, and variant types of CDA, IV-VIII, have been described. The causative genes have been identified as CDAN1, C15ORF41, SEC23B, KIF23, KLF1, and GATA1. CDA type II is the most frequent form. Typical symptoms are jaundice, hepatosplenomegaly, mild-to-severe normocytic anemia, and inadequate reticulocyte response. We report an 18-year-old boy who had chronic mild congenital anemia, jaundice, and splenomegaly mimicking nonautoimmune hemolytic anemia since 18 months of age. Compound heterozygous mutations in SEC23B gene were detected by the use of a gene-targeted next-generation sequencing panel: the already reported missense mutation c.40C>T (p.Arg14Trp), and a new frameshift deletion (c.489_489delG, p.Val164Trpfs*3), confirming the diagnosis of CDA type II. The study underlines the molecular heterogeneity of CDA II and the importance of a precise diagnosis in rare congenital diseases such as CDA II. In consequence, it can be difficult to diagnose because of limited resources, financial constraint, and rarity of disease in the developing country. Advanced laboratories and new molecular approaches may help in diagnosing rare anemias.

BACKGROUND Hemophilia, which is a chronic illness associated with recurrent bleeding, may occur with psychosocial and behavioral problems. AIM The aim of this study was to evaluate the clinical characteristics and demographic features and changes in the self-image of adolescents with hemophilia. MATERIALS AND METHODS Data about hemophilia type, the severity of hemophilia, secondary prophylaxis received, and annual bleeding rate (ABR) were recorded from patient files. Hemophilia Joint Health Score (HJHS) and the Offer Self-Image Questionnaire (OSIQ) (as a measure of self-esteem) were applied to hemophilia patients and a healthy control group. RESULTS Thirty-two hemophilia patients (mean age=16.2±3.06 y) and 35 healthy male individuals (mean age=16.02±1.4 y) were enrolled in the study. Hemophilia patients had lower total OSIQ score than their peers (P=0.007). There was no difference between patients who received and who did not receive secondary prophylaxis (P=0.408) in terms of total OSIQ score. The median total OSIQ score of patients with pathologic HJHS (>0 points) was lower than that of patients with normal HJHS (0 points) (P=0.010). The median of ABR was 6 (range: 0 to 20) in the whole hemophilia group. There were no differences between hemophilia patients with ABR≤4 and >4 (P=0.084). All of the subscale parameters of the OSIQ were lower for hemophilia patients compared with their peers, besides one. The subscale of sexuality attitudes was better for hemophilia patients than for the healthy control group (P=0.028). CONCLUSIONS Low self-esteem in hemophilia patients indicates the importance of lifelong psychosocial support. Patients with pathologic HJHS are at risk of low-esteem. Using OSIQ with HJHS during follow-up of hemophilia patients may be useful for management.

Objectives Since the civil war in Syria began, millions of Syrians have left the country and been forced to migrate to other countries. Turkey is the country with the most refugees hosting 3.6 million refugees. This study aimed to compare the PIM-3 score, PELOD-2 score, PELOD-2 predicted death rate (PDR), mortality rates, demographic data, and outcomes of patients admitted to pediatric intensive care units between refugee children living in Turkey, pediatric patients brought directly from the border by the emergency services, and the general Turkish population. Methods This was a retrospective study performed between February 2018 and February 2019 at Hatay State Hospital, very close to the Syrian border. The study included 158 patients. Patients were divided into three groups: Turkish citizens, those living in Turkey as refugees, and those brought from the border. Results Of the patients, 57 were Turkish citizens, 33 were refugees, and 68 were brought from the border. For patients, the mean PIM-3 score was 25.62 ± 27.70, the PELOD-2 score was 8.03 ± 4.72, and PELOD2-PDR was 16.07 ± 23.45. The median scores for PIM-3, PELOD-2, and PELOD2-PDR of patients brought from the Syrian border were higher compared with Turkish citizens and refugees. There was no significant difference between refugees and Turkish citizens. Of the patients, 27 died, with the distribution being 15% Turkish citizens, 26% refugees, and 59% brought from the border. The mortality of patients transported from the border was statistically significant (P = 0.03). Conclusion We consider that the source of the difference between patients brought from the border and those living in Turkey may be associated with the continuing war beyond our borders and children experiencing insufficient care conditions. In conclusion, it is not just weapons that cause death in war, and children unfortunately suffer because of this situation.

Pyrimidine-5-nucleotidase (P5'N-1) deficiency is a rare nonspherocytic hemolytic anemia due to pyrimidine nucleotide deposition within erythrocytes. This rare erythrocyte disorder shows autosomal recessive inheritance with mutation of the pyrimidine-5'-nucleotidase gene, which is localized on 7p15-p14. Consanguinity of parents increases the probability of disease with novel mutations. Here, we report a 12-year-old boy with a delayed diagnosis of P5'N deficiency whose parents were consanguineous. He had a hemoglobin level of 7.5 g/dL, mean corpuscular volume of 93 fL, 7% reticulocyte, and lactate dehydrogenase of 678 IU/L. A peripheral blood smear showed polychromasia, marked anisopoikilocytosis with schistocytes, elliptocytes, stomatocytes, spherocytes, dacryocyte, and basophilic stippling in red blood. Decreased purine/pyrimidine ratio was 1.07 (normal range=1.4 to 2.98). Molecular analysis with direct DNA sequencing of the NT5C3 gene, codifying for P5'N-1, revealed the presence of a novel homozygous mutation, c393-394delTA, in the gene coding P5'N enzyme in the patient. To our knowledge, this is a newly defined mutation in P5'N deficiency.

The aim of this chapter is to arrange KANBAN shelving in order to calculate the optimum order quantity of the materials supplied for the TV main boards in an electronic factory and to minimize the stacking of material waiting in the production area. To optimize this problem, a mathematical model is developed and solved in an optimization program. In addition, a number of proposals have been submitted under an Industry 4.0 to manage deficiencies in material following. The performance measures of both cases were compared, and the results evaluated. Due to the shortage of material following the next step of the problem, the company has been recommended to apply radio frequency identification (RFID). With the project management approach, all the critical information needed to manage materials, such as the materials themselves, production processes and stock information, has been clearly updated to keep the entire process under control.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively. None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

Chronic neutropenia (CN) is defined as neutropenia that persists for >3 months; it is caused by a heterogeneous group of diseases in children. The aim of the present study was to evaluate the significance and clinical manifestations of CN in children at a single children's hospital. Between October 2004 and April 2014, CN patient data were evaluated retrospectively. Thirty-one patients were assessed in this study. Thirteen of them (41.9%) were younger than 12 months of age at initial diagnosis. There was no difference in the absolute number of neutrophils at diagnosis between the children aged younger than 12 months and those aged 12 months and older at CN onset. Twenty-two of the patients (70.9%) were diagnosed during treatment for acute infections. A total of 11 patients (35.5%) were hospitalized because of recurrent infections. Most of the recurrent infections occurred in the lungs (81.8%). Congenital neutropenia (CoN) was identified in 14 patients (45.1%). Eight of 14 patients (57.1%) required granulocyte-colony stimulating factor treatment, and none of them experienced adverse effects from this treatment. Fifteen patients (48.3%) were diagnosed with idiopathic neutropenia. Comparison between the idiopathic and CoN groups revealed no differences in age, the absolute number of neutrophils, or the presence of infection at diagnosis; however, differences were detected in sex and the rate of spontaneous recovery from neutropenia. Ten of the patients (32.2%) experienced spontaneous recovery from neutropenia during a follow-up period of 7 to 52 months. In current study, we found a higher CoN ratio in the CN patients compared with previous reports, which may be due to the high rate of consanguineous marriages in our country. However, the finding of CN requires several laboratory investigations, prolonged follow-up, and advanced molecular analysis, and its etiology can remain idiopathic.

Background and objectives Autoimmune cytopenias are a group of heterogeneous disorders characterized by immune-mediated destruction of one or more hematopoietic lineage cells. The differential diagnosis of children with autoimmune cytopenias requires much time and laboratory investigations. The aim of the present study was to evaluate the clinical course and significance of autoimmune cytopenias due to immunodeficiency or autoimmune diseases in children at a single children`s hospital. Method Between February 1997 and September 2015, chronic/refractory autoimmune cytopenias patient data were evaluated retrospectively. Twenty-three patients were assessed in this study. Results The median duration of following was 2.6 years (4 months-18.5 years). The median age of diagnosis was 3.1 years (6 months-16 years). A total of 13 patients (56.5%) had single-lineage and 10 (46.5%) had multilineage cytopenias. The most frequent single-lineage cytopenia was thrombocytopenia, followed by anemia. In 22 of the patients, cytopenias was detected before the primary diseases. All of the patients were treated with corticosteroids or intravenous immune globulin as first-line treatment. Ten patients (43.5%) needed second or further-line immunosuppressive therapies that patients diagnosed as systemic lupus erythematosus, hypogammaglobulinemia, or common variable immunodeficiency. A total of 8 patients (34.7%) recovered from autoimmune cytopenias after the treatment of primer disease. Cytopenias were continued in 14 patients. Conclusion Cytopenia may be the first finding of an immunodeficiency or autoimmune disease and primary disease may be diagnosed in the clinical course. Taking the new targeted treatment options into consideration; early diagnosis is likely to become more important in the near-future in order to begin the treatment for the underlying disease as early as possible.

Thymomas are the most common masses located in the anterior mediastinum, and they are often associated with autoimmune disorders including myasthenia gravis, polymyositis, and aplastic anemia (AA). Autoreactive T-cell clones generated by the thymoma may lead to autoimmune disorders. We report the case of a 14-year-old boy who was examined for AA, and the underlying cause was determined to be an immune-mediated complication of thymoma. He had no matched sibling donors. He underwent thymectomy, and 3 months later he was treated with immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A. The duration of the IST was determined to be a period of 12 months. He has recently been in complete response condition for 6 months since IST stopped. IST is a successful treatment choice for thymomas associated with AA in childhood.

Background Congenital afibrinogenemia is characterized by the absence of fibrinogen. Congenital fibrinogen disorders result from several mutations in FGA, FGB, or FGG. Their epidemiology is not well known. Observation The present study reports on 2 children with congenital afibrinogenemia. The first child, a male who is now 9 years old, was diagnosed with afibrinogenemia after spontaneous intracranial bleeding at the age of 3 years. The second child is a 2-year-old female cousin of the first patient, who was diagnosed with afibrinogenemia after coagulation tests were carried out due to frequent epistaxis and mucocutaneous bleeding. At follow-up, blood samples of the patients and their parents were sent to the Department of Genetic Medicine and Development, University Medical Center, Switzerland, for polymerase chain reaction analysis. In both patients, the novel homozygous frameshift mutation in the FGA exon 3: c.196 delT was detected. The parents of the patients were both heterozygous for the same mutation. Conclusions Congenital afibrinogenemia is a rare coagulation disease. The molecular epidemiology of congenital fibrinogen disorders is complex, and the identification of new mutations will help shed light on this complex molecular structure. Therefore, a genetic analysis that includes more centers is needed.

Pyruvate kinase deficiency (PKD) is the most common glycolytic defect leading to hemolytic anemia. PKD is caused by the mutations in the PKLR gene; however, the detection of a decreased PK activity should be first measured for rapid diagnosis. We report here the case of a 1-year-old girl with mild hemolysis and PKD. At the time of the study, the patient showed a hemoglobin level of 9.5 g/dL, mean corpuscular volume of 93 fL, reticulocyte of 6.7%, and lactate dehydrogenase of 218 IU/L. Peripheral blood smear showed polychromasia, anisocytosis, tear drop cells, fragmented eyrtrocytes, and target cells. When a biochemical analysis was performed in our patient and her parents who had consanguinity, a decreased PK activity was detected in the patient and her father. After the molecular study of PKLR gene, a new homozygote variant, c.1708G>T (pVal570Leu), was found in our patient and her father. Her father had a misdiagnosis of Gilbert syndrome because he had unconjugated hyperbilirubinemia and not anemia. Her mother was also a carrier of the mutation in heterozygous state. Patients presenting with hemolytic anemia, either severe or mild hemolytic anemia, should be screened for PKD in the first year of life. Patients with mild hemolytic findings can be followed-up with misdiagnoses.