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Objectives Acute myeloid leukemia (AML) is a highly heterogeneous disease. Although patients can be classified into risk groups based on their genetic changes, the prognosis of disease within these categories varies widely. This situation raises the need to search for new molecular markers related to AML. Serine peptidase inhibitor Kazal type 2 (SPINK2) has recently been reported to be upregulated in AML and associated with poor outcomes by meta-analysis and in a limited number of AML patients. Methods We analyzed SPINK2 mRNA expression in 62 patients (45 adult and 17 pediatric) with AML and 11 cell lines using quantitative Real-Time PCR (qRT-PCR). SPINK2 protein level was determined using ELISA in cell lines. Results We found that the expression of SPINK2 mRNA and protein levels in AML cell lines (HL60 and NB4) have increased compared to other cell lines (K562, Jurkat and NALM6, MCF7, HeLa, HUVEC, hFOB, 293T, U87). SPINK2 mRNA expression was upregulated in patients with AML compared to controls (p=0.004) and significantly lower in t(8;21)-positive patients compared to negative patients (p=0.0006). Conclusions Our results suggest that SPINK2 serves an important role in AML development. Further studies are needed to evaluate SPINK2 expression in AML patients with t(8.21) and investigate to clarify its prognostic value in various subgroups of AML.

Resumen Objectivos La leucemia mieloide aguda (AML, por sus siglas en inglés) es una enfermedad muy heterogénea. Aunque se puede clasificar a los pacientes en grupos de riesgo según sus mutaciones genéticas, el pronóstico dentro de cada categoría varía sustancialmente. Es perentorio identificar nuevos marcadores moleculares de la AML. Recientemente, se ha descrito la elevación del inhibidor de la serina peptidasa Kazal tipo 2 (SPINK2) en la AML, habiendo sido relacionada con peores resultados clínicos en metaanálisis, así como en un número limitado de pacientes con AML. Métodos Analizamos la expresión de SPINK2 en 62 pacientes (45 adultos y 17 niños) con AML y en 11 líneas celulares mediante PCR cuantitativa (qRT-PCR). Los niveles de la proteína SPINK2 se determinaron en líneas celulares mediante ELISA. Resultados Observamos un aumento de expresión del ARNm de SPINK2 y de los niveles de la proteína en las líneas celulares de AML (HL60 y NB4), frente a otras líneas celulares (K562, Jurkat y NALM6, MCF7, HeLa, HUVEC, hFOB, 293T, U87). Los pacientes con AML mostraron una expresión elevada de ARNm de SPINK2 frente a los controles (p=0,004) y esta fue significativamente menor en los pacientes t(8;21) positivos, frente a los pacientes negativos (p=0,0006). Conclusions Estos resultados sugieren que el gen SPINK2 tiene un papel relevante en el desarrollo de la AML. Son necesarios más estudios para evaluar la expresión de SPINK2 en los pacientes con AML con la mutación t(8.21) e investigar su valor pronóstico en varios subgrupos de pacientes con AML.

Introduction: Inherited factor VII (FVII) deficiency (FVIID) is the most common of inherited rare bleeding disorders. Other determinants of clinical severity apart from FVII level (FVIIL) include genetic and environmental factors. We aimed to identify the cut-off FVIILs for general and severe bleedings in patients with FVIID by using an online national registry system including clinical, laboratory, and demographic characteristics of patients. Methods: Demographic, clinical, and laboratory data of patients with FVIID extracted from the national database, constituted by the Turkish Society of Hematology, were examined. Bleeding phenotypes, general characteristics, and laboratory features were assessed in terms of FVIILs. Bleeding rates and prophylaxis during special procedures/interventions were also recorded. Results: Data from 197 patients showed that 46.2% of patients had FVIIL< 10%. Most bleeds were of mucosal origin (67.7%), and severe bleeds tended to occur in younger patients (median age: 15 (IQR:6-29)). Cut-off FVIILs for all and severe bleeds were 16.5% and 7.5%, respectively. The major reason for long-term prophylaxis was observed as central nervous system bleeding (80%). Conclusion: Our data are consistent with most of the published literature in terms of cut-off FVIIL for bleeding, as well as reasons for prophylaxis, showing both an increased severity of bleeding and younger age at diagnosis with decreasing FVIIL. However, in order to offer a classification similar to that in Hemophilia A or B, data of a larger cohort with information about environmental and genetic factors are required.

Objective: Prophylaxis is the gold standard in patients with severe hemophilia. In recent years, personalisation of prophylaxis treatment according to pharmacokinetic properties has been used in treatment. In this study, personalisation treatment experience based on the pharmacokinetic dosing tool my-PKfit results in pediatric and adult patients from three centers is shared. Material and Methods: myPKfit (www1.mypkfit.com) was used to evaluate pharmacokinetic parameters in hemophilia A patients receiving recombinant Factor VIII (Takeda Advate ®) prophylaxis. 75 samples in 34 patients (3 samples in 7 patients, 2 samples in 27 patients) were analysed for pharmacokinetic evaluation. Age, weight and baseline FVIII level of the patients were recorded. Pharmacokinetic curves were obtained after entering sampling times, factor dose and sample results. The annual bleeding rate (ABR) of the patients were evaluated before and after the changes made after the pharmacokinetic evaluation. Results: The median age of 34 patients with severe hemophilia A without inhibitors was 12.3±8.7 (1.5-37) years, and the mean weight was 40.0±22.0 (10-83) kg. All patients had a baseline FVIII level of less than or equal to 2 IU/dl. All patients were receiving primary or secondary/tertiary prophylaxis. The mean half-life of the factors of the patients was 9.6±1.4 (7.0-13.4) hours, and the mean time reached below 1 IU/dl was 48.9±11.2 (16.0-77.0) hours. Prophylactic factor therapy was changed in 17 patients after myPKfit, dose increased in 9 patients, the frequency increased in 6 patients, and both dose and frequency increased in 2 patients. With a mean follow-up period of 23.7 +16 (2-49) months, in 17 patients whose prophylaxis regimen was changed after the PK evaluation by myPkyfit, ABR was found to be significantly lower in the post-change period, compared to the last one year before the change of regimen (2.94 + 2.19 and 0.58 + 1.00 respectively) P: 0.028. Discussion: A pharmacokinetic study by the Bayesian method is an increasingly used method for personalised prophylaxis regimen. We believe that myPKfit is beneficial in providing effective and appropriate prophylaxis.

Children with cancer have an increased risk for hepatitis B virus (HBV) infections due to chemotherapy-induced secondary immunodeficiency and frequent blood transfusions. The aim of this study is to evaluate the efficacy and safety of hepatitis B vaccination during the intensive induction chemotherapy in children with cancer found to be seronegative for hepatitis B on admission.Children newly diagnosed with cancer were evaluated for the presence of hepatitis B surface antigen (HBsAg) and antibody on admission. The children negative for both were included in the study. A super-accelerated vaccination scheme (3 booster doses at days 1-5, 8-12, and 28-33) was administered to these seronegative children concurrently with induction chemotherapy. Antibody response was checked 4-8 weeks after the last vaccination and 6 months after the end of the treatment.Eleven out of 122 children were seronegative for hepatitis B on admission (9%). Acute lymphoblastic leukemia, lymphoma, and solid tumors were diagnosed in 5, 4, and 2 children, respectively. Complete seroconversion was achieved in 4-8 weeks after the last vaccination with high titers of anti-HBs antibody, and all patients remained antibody-positive until 6 months after the completion of chemotherapy.The risk of transfusion-related infections increases with a number of transfused products and donor exposures, and it is more significant for immunosuppressed children with hematologic and oncologic malignancies. Hepatitis B vaccination could safely be applied with brisk and sustained responses in this vulnerable population, based on the local epidemiological data.

Objective Polycythemia is a rare condition in which an increase in erythrocyte mass is observed. It can be primary or secondary. Primary polycythemia occurs as a result of congenital or acquired mutations that regulate erythroid development. Although secondary polycythemia is mostly seen secondary to hypoxia due to cardiac/pulmonary reasons, it also develops as a result of congenital mutations. Globin gene mutations that increase the affinity of hemoglobin for oxygen are one of these rare causes. Materials and Methods We present a male case who was referred to us for polycythemia. Results A 15-year-old male patient with no known disease was referred to us after his school screening revealed high hemoglobin (18 g/dL). In complete blood count, other series were normal (wbc 5.8 × 103/µL neu 3.3 × 103/µL plt 174 × 103/µL), bilirubins and liver functions were within normal limits. On physical examination, conjunctiva and hands were pletoric, there was no hepatosplenomegaly, intermittent headaches were present, and neurological examination was normal. The patient was examined for the etiology of polycythemia. Hyperchromic erythrocytes were found in peripheral smear, no signs of hemolysis were observed. EPO level (8 mIU/ml) was in the normal range and JAK2 (V617F) mutation was negative. The patient's cardiac and pulmonary functions were within normal limits. Hemoglobin electrophoresis was sent from the patient. HbA was determined as 59.2, HbA2 2.8, Variant Hb 38. c.435G>T mutation was detected in the HBB genetic analysis, and this was considered to be compatible with Hemoglobin Andrew-Minneapolis. It was learned that the patient's mother and her cousins had similar findings, and some of them had undergone phlebotomy. Phlebotomy was planned in the presence of the patient's hemoglobin value > 18 g/dL and clinical findings. Phlebotomy was performed 3 times, aspirin was not started because there was no history of thromboembolism. In our 1-year follow-up, the hemoglobin value was 17-17.5 g/dL. Conclusion More than a hundred globin gene mutations associated with erythrocytosis have been described. Hemoglobin Andrew-Minneapolis mutation is one of them. Hemoglobin's affinity for oxygen has increased and EPO level is normal/increased. Due to the low number of cases, treatment recommendations were prepared based on polycythemia vera guidelines. Patients should be closely monitored in terms of hyperviscosity and thromboembolism, aspirin prophylaxis and phlebotomy are recommended according to symptoms. While investigating the etiology of polycythemia, hemoglobin electrophoresis is necessary, although it is very rare.

Objective: HLA class I and II alleles are shown to be associated with certain diseases. A restricted numbers of alleles were found to be related to alloimmunisation in thalassemia population. The role of human leucocyte antigens in thalassemia is trend topic. In this study, the aim was to evaluate the differences in HLA frequencies of beta thalassemia patients comparing with healthy controls. Methodology: The data were collected of 100 patients who were diagnosed with beta thalassemia and 100 healthy controls were included in the study. The low resolution HLA-A, -B, -DRB1, tissue group data were performed Istanbul University, Faculty of Medicine, Medical Biology Department HLA typing laboratory. All data were analyzed retrospectively and their HLA allele frequencies were analyzed by SPSS (v22) program. Results: We found an increased frequency of HLA-B*14 (8% versus 2%) and HLA-B*52 (17% versus 2%) compared to the control group (p=0.05, OR=4.26; p

Coagulation factor XIII (FXIII) is a fibrin-stabilizing factor with additional roles in wound healing and interactions between the decidua and fetus. Congenital FXIII deficiency is rare bleeding disorder. Inhibitor development against FXIII in inherited FXIII deficency is also uncommon, but may cause severe, life-threatening bleeding. FXIII is the last step in the coagulation cascade with normal coagulation paramaters (PT, aPTT), the detection of inhibitor to FXIII is quite difficult. The treatment of inhibitor-positive congenital FXIII deficiency is challenging due to the lack of a role of by-pass agents such as FVII. The best known ways of treatment in these cases are the use of high-dose FXIII concentrates and immunosuppression. Herein, we report the management of postoperative bleeding diathesis in a patient with FXIII deficiency who developed inhibitors, and to follow the clinical course of the disease with FXIII concentrate and immunosuppression.

Congenital factor VIII (FVIII) deficiency causes hemophilia A due to different types of defects in the FVIII gene. Although the chromogenic measurement is the reference method and shows less variability, a one-stage assay is the most commonly preferred method for measurement of FVIII. In this study, we aimed to evaluate the analytical performances of chromogenic and one-stage assays, and compare the results prior to introduction of newly developed extended half-life recombinant FVIII products.Sixty-six blood samples from residual material of Istanbul Faculty of Medicine, Central Laboratory workflow comprised the study group. Samples were classified; plasma FVIII40 IU and FVIII40 IU. FVIII activities were measured using one-stage clotting and chromogenic assays on a CS-2500 analyzer. Analytical performances were determined through precision, linearity, carryover, and comparability studies.The within-run CV% of the one-stage assay on the CS-2500 had 1.6%, 2.6%, the between day CV% were 8.5%, 4.9 % for low and high controls, respectively. The within-run CV% of chromogenic method had 1.2% and 0.9%. Both methods demonstrated good linearity (R20.998), and the comparisons of both assays exhibited good agreement with minor bias for FVIII activity40 IU. However, a significant bias was obtained for FVIII activity40 IU.We obtained higher results using the one-stage assay compared with the chromogenic assay, and a significant bias was found for the samples lower than 40 IU. The discrepancy can explained by the presence of a weak agreement for samples lower than 10 IU due to the lower detection limit of the chromogenic assay used in this study (1.5%).

Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children.The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia.The diagnosis was chronic ITP in 89 patients and acute refractory ITP in 16 patients. The mean age of patients was 9.5±4.5 years (minimum-maximum: 1.2-18 years) at the beginning of EPAG treatment. The overall response rate was 74.3% (n=78). The mean time for platelet count of ≥50x109/L was 11.6±8 weeks (range: 1-34 weeks). The treatment was stopped for 27 patients (25.7%) at an average of 6.8±9 months (range: 1-38 months). The reason for discontinuation was lack of response in 18 patients, nonadherence in 4 patients, and hepatotoxicity in 2 patients. Response to treatment continued for an average of 4 months after cessation of EPAG in 3 patients.Results of the current study imply that EPAG is an effective therapeutic option in pediatric patients with acute refractory and chronic ITP. However, patients must be closely monitored for response and side effects during treatment, and especially for iron deficiency.İmmün trombositopeni (İTP) nadir otoimmün bir hastalık olup, platelet sayısındaki azalmaya bağlı olarak peteşi, ekimoz, epistaksis gibi kanama semptomları ile karakterizedir. Trombopoietin reseptör agonisti eltrombopag (EPAG), yetişkinlerde ve çocuklarda kronik immün trombositopeni tedavisinde kullanılan ikinci basamak bir ajandır.Bu retrospektif çalışma, akut refrakter ve kronik immün trombositopenili çocuk hastalarda EPAG tedavisinin etkinliğini, güvenilirliğini, yan etkilerini özellikle de demir eksikliği anemisi gelişimini değerlendirmiştir.Hastalarımızın 89’u kronik İTP, 16’sı ise akut refrakter İTP tanısı ile takip edilmekte idi. Tedavi başlangıcı sırasında hastalarımızın yaş ortalamaları 9,5±4,5 yıl (1,2-18 yıl) idi. Toplam yanıt oranımız %74,3 (n=78) idi. Platelet sayısının ≥50x109/L olması için geçen ortalama süre 11,6±8 hafta (1-34 hafta) idi. Tedavi 27 hastamızda (%25,7) ortalama 6,8±9 ayda (1-38 ay) kesildi. Tedavi kesim nedenlerimiz; 18 hastada yanıtsızlık, 4 hastada tedaviye uyumsuzluk, 2 hastamızda ise hepatotoksisite idi. Üç hastada ise EPAG tedavisi kesilmesinden sonra yanıt ortalama 4 ay devam etti.Çalışmamız, EPAG tedavisinin akut refrakter ve kronik İTP’li pediyatrik hastalarda etkili bir terapötik seçenek olduğunu göstermektedir. Bununla birlikte, hastalar EPAG tedavisi sırasında yanıt ve yan etkiler ve özellikle demir eksikliği açısından yakından izlenmelidir.

Pediatrik tromboz epidemiyolojisi, patofizyolojisi ve tedavi oncelikleri nedeniyle eriskin tromboz yonetiminden cok farkli ozelliklere sahiptir. Tromboz teshisi konan cocuklar, multidisipliner bir ekip tarafindan tani, tedavi ve takip suresince degerlendirilmelidir. Burada pediatrik tromboz hastalarimizin yonetildigi 2 yillik multidisipliner tromboz konseyi deneyimimizi sunuyoruz. Kasim 2017-Agustos 2019 tarihleri arasinda 61 cocuk (95 basvuru) icin tromboz konseyi olgu sunumlarini ve konsey sonuclarini geriye donuk olarak inceledik. Degerlendirilen hastalarda erkek/kadin orani 1,54 saptandi, cocuklar ve adolesanlar cogunluktaydi. Hastalarin klinik ve radyolojik durumlarina gore tedavi ve profilaksi sureleri belirlendi. Olgularimiz icinde serebral arteriyel ve sinovenoz tromboz olgulari daha fazla idi. Kazanilmis risk faktorleri, kalitsal olanlardan daha fazla olup, infeksiyon ve Faktor VIII yuksekligi sik idi. Otuz dokuz hastaya (%64) farkli sureler boyunca K vitamini antagonistleri, aspirin veya LMVH ile primer veya sekonder profilaksi uygulandi. Pediatrik trombozda kanita dayali kilavuzlarin iyilestirilmesi icin tedavi ve profilaksi yonetimi uzerine daha fazla calismaya ihtiyac vardir. Multidisipliner tromboz konseyi komplike pediatrik trombozlu cocuk hastalarda hasta bakimini iyilestirebilir.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy caused by a variety of genetic abnormalities and epigenetic dysregulation. The incidence of AML is strongly related to age, with the highest incidence rates being in older adults. The loss of function mutations in BCOR and BCORL1 genes have been identified in AML. BCL6 corepressor (BCOR) and BCL6 corepressor like 1 (BCORL1) are important epigenetic regu-lators as a member of Polycomb repressive complex 1 (PRC1.1), involved in histone modification processes.We analyzed the BCOR and BCORL1 mRNA expression in 74 adult and 22 pediatric patients with AML by Real-Time quantitative PCR in this study.Our results indicated that both BCOR and BCORL1 mRNA expressions decrease with age (p = 0.009 and p = 0.008, respectively) and there is a positive correlation between BCOR and BCORL1 mRNA expression (p0.001). BCOR and BCORL1 mRNA expressions were not significantly different in both adult and pediatric patients with AML compared to control (p0.05).Our findings indicate that expression of BCOR and BCORL1 mRNA are down-regulated with age. The increase in AML incidence with age suggests that age-associated BCOR and BCORL1 down-regulation might potentially contribute to age-related epigenetic alterations and form a predisposing condition for the development of elderly AML.

Objective: PTEN/AKT pathway deregulations have been reported to be associated with treatment response in acute leukemia. This study examined pediatric T-cell acute lymphoblastic leukemia (T-ALL) samples for PTEN and AKT1 gene variations and evaluated the clinical findings. Materials and Methods: Fifty diagnostic bone marrow samples of childhood T-ALL cases were investigated for the hotspot regions of the PTEN and AKT1 genes by targeted next-generation sequencing. Results: A total of five PTEN variations were found in three of the 50 T-ALL cases (6%). Three of the PTEN variations were first reported in this study. Furthermore, one patient clearly had two different mutant clones for PTEN. Two intronic single-nucleotide variations were found in AKT1 and none of the patients carried pathogenic AKT1 variations. Conclusion: Targeted deep sequencing allowed us to detect both lowlevel variations and clonal diversity. Low-level PTEN/AKT1 variation frequency makes it harder to investigate the clinical associations of the variants. on the other hand, characterization of the PTEN/ AKT signaling members is important for improving case-specific therapeutic strategies. Amaç: PTEN/AKT yolak düzensizliklerinin akut lösemide tedavi yanıtı ile ilişkili olduğu bildirilmiştir. Çalışmanın kapsamı, pediatrik T-ALL hastalarının PTEN ve AKT1 genlerinin sıcak bölge varyasyonları için incelenmesi ve klinik bulgularla değerlendirilmesidir. Gereç ve Yöntemler: Elli pediatrik T-ALL olgusunun tanı zamanı kemik iliği örnekleri, PTEN ve AKT1 genlerinin sıcak bölgeleri için hedefe yönelik yeni nesil dizileme ile dizilenmiştir. Bulgular: Elli T-ALL olgusunun %6’sında PTEN varyasyonu saptanmıştır. Tespit edilen varyasyonlardan üçü ilk defa bu çalışmada gösterilmiştir. Ayrıca bir hastanın PTEN açısından iki farklı mutant klon taşıdığı belirlenmiştir. AKT1 geninde iki intronik tek nükleotid polimorfizmi tespit edilirken hiçbir olguda patojenik AKT1 varyasyonu saptanmamıştır. Sonuç: Derin dizileme, hem düşük düzeydeki varyasyonların hem de klonal çeşitliliğin belirlenmesine olanak sağlamıştır. T-ALL hastalarındaki düşük düzey PTEN/AKT1 varyasyon sıklığı, varyantların klinikle ilişkisinin ortaya çıkarılmasını zorlaştırmaktadır. Diğer yandan, PTEN/AKT sinyal yolağının karakterizasyonu hasta spesifik terapötik stratejilerin uygulanabilirliği için önemlidir.

Ince Z, Bulut O, Tugrul-Aksakal M, Unuvar A, Devecioglu O, Coban A. Asymptomatic intracranial hemorrhage in a newborn with congenital factor VII deficiency and successful treatment with recombinant activated factor VII. Turk J Pediatr 2018; 60: 562-565. Intracranial hemorrhage is considered the most common cause of death in newborns with congenital factor VII (FVII) deficiency. Recombinant activated FVII (rFVIIa) provides specific replacement therapy, however there is limited experience with its neonatal use. We describe our experience about the treatment of intracranial hemorrhage in a newborn with congenital FVII deficiency and emphasize the importance of imaging in asymptomatic patients. She presented with ecchymoses on her skin, no other pathological clinical signs, prolonged PT, normal PTT and FVII activity of 2%. Intracranial hemorrhage was diagnosed while screening for internal bleedings. Treatment with rFVIIa resulted in stabilization and regression of the hematoma.

To investigate the clinical impact of vancomycin-resistant enterococci (VRE) colonization in patients with hematologic malignancies and associated risk factors.Patients colonized and infected with VRE were identified from an institutional surveillance database between January 2010 and December 2013. A retrospective case-control study was performed to identify the risk factors associated with development of VRE infection in VRE-colonized patients.Fecal VRE colonization was documented in 72 of 229 children (31.4%). Seven VRE-colonized patients developed subsequent systemic VRE infection (9.7%). Types of VRE infections included bacteremia (n=5), urinary tract infection (n=1), and meningitis (n=1). Enterococcus faecium was isolated in all VRE infections. Multivariate analysis revealed severe neutropenia and previous bacteremia with another pathogen as independent risk factors for VRE infection development in colonized patients [odds ratio (OR): 35.4, confidence interval (CI): 1.7-72.3, p=0.02 and OR: 20.6, CI: 1.3-48.6, p=0.03, respectively]. No deaths attributable to VRE occurred.VRE colonization has important consequences in pediatric cancer patients.Amaç: Hematolojik malignitesi olan pediatrik hastalarda vankomisine dirençli enterokok (VDE) kolonizasyonunun klinik öneminin araştırılması ve eşlik eden risk faktörlerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Ocak 2010-Aralık 2013 tarihleri arasında yapılan VDE sürveyans kayıtlarından faydalanılarak VRE ile kolonize ve/veya enfekte olmuş hastalar belirlenmiştir. VDE ile kolonize hastalarda VRE enfeksiyonu gelişimi ile ilişkili risk faktörlerini belirlemek amacıyla retrospektif olgu-kontrol çalışması yapılmıştır. Bulgular: Çalışma süresince yatırılan 229 hastanın 72’sinde (%31,4) rektal VRE kolonizasyonu saptanmıştır. VRE kolonize hastaların yedisinde (%9,7) kolonizasyon sonrası sistemik VRE enfeksiyonu gelişmiştir. Beş hastada bakteriyemi (n=5), bir hastada idrar yolu enfeksiyonu (n=1) ve bir hastada menenjit (n=1) gözlenmiştir. Tüm enfeksiyonlarda ilgili klinik örneklerde Enterococcus faecium üretilmiştir. Multivaryant analiz sonucunda, ciddi nötropeni ve başka bir patojene bağlı bakteriyemi öyküsü VDE kolonize hastalarda VDE enfeksiyonu gelişimi için risk faktörleri olarak bulunmuştur [odds ratio (OR): 35,4; güven aralığı (GA): 1,7-72,3; p=0,02 ve OR: 20,6; GA: 1,3-48,6; p=0,03; sırasıyla]. VDE enfeksiyonuna bağlı mortalite saptanmamıştır. Sonuç: Pediatrik kanser hastalarında VDE kolonizasyonunun önemli klinik sonuçları olduğu gözlenmiştir.

Aim: Cervical lymphadenopathy (LAP) is a common sign and may raise fears about serious illnesses. The aim of our study was to evaluate the patients with cervical LAPs in a general pediatrics clinic setting, and to evaluate follow-up results for potential causes and risk factors for malignancies. Material and methods: Two hundred-eighteen patients aged between 79.4 ± 46.7 months with LAP were enrolled in this prospective cohort study. The patients were examined in terms of demographics, clinical, radiologic and serologic aspects like Epstein-Barr virus (EBV), cytomegalovirus (CMV), parvovirus B19. A lymph node biopsy was performed in selected patients. The patients were followed-up for 8 weeks and risk factors for malignancy were evaluated. Results: Seventy patients (41.3%) had specific etiology and 6 (2.7%) had malignant causes. The causes were as follows: 27% (n = 59) infections; 2.7% (n = 6) malignancies; 11.4% (n = 25) other causes. EBV was responsible for 27% of infectious causes. The other common infectious etiologies were CMV 4.3%, parvovirus B-19 2.9%, and group-A beta-hemolytic streptococcus (GAS) 10.8%. Four of the six malignancies were lymphomas. Predictive factors for malignancy were having LAP larger than 30 mm, rubbery lymph node, high serum CRP and LDH values, no hilum in ultrasonography, and enlargement of lymph node in follow-up. High uric acid levels and leucopenia were also common in the malignancy group. Conclusion: Etiology of cervical LAPs was diagnosed in 41.3% patients. Infectious causes were the most common cause with 27%. Malignancy was diagnosed in 2.7% and lymphoma was the most common malignancy. © 2016 Elsevier Ireland Ltd.

Background: Thiamine responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder characterized by non type 1 diabetes mellitus (DM), sensorineural hearing loss and megaloblastic anemia and caused by mutations in SLC19A2 gene, encoding a thiamine transporter protein. Case: A 3-month-old male infant presented with megaloblastic anemia, DM, patent ductus arteriosus and hypertriglyceridemia. His autoimmune markers for DM were positive but with the additional finding of sensorineural deafness he was diagnosed with TRMA and thiamine therapy was started. His anemia was improved and insulin needs decreased and his genetic studies revealed a homozygous frameshift mutation, c.641del within coding region of SLC19A2 gene. Conclusion: Clinical presentation of TRMA could be highly variable and some co-existence could perplex physicians, but this diagnosis should be considered in all patients with DM and anemia and further assessment should be done.

Mild bleeding symptoms are commonly seen in the general population. The aim of this study was to determine the final clinical and laboratory features of children referred for a first evaluation with a suspected bleeding disorder in the pediatric outpatient clinic of İstanbul University.The medical records of 26,737 outpatients who were admitted to the Division of Ambulatory Pediatrics between 31 October 2011 and 31 October 2012 were evaluated retrospectively. Ninety-nine patients were initially diagnosed as having probable bleeding disorders and were followed up. The symptoms of bleeding in addition to coagulation tests were analyzed.Of the 99 patients, 52 (52.5%) were male and 47 were female, and the mean age of the entire study group was 9.1±4.1 years (minimum-maximum: 2-18 years). Major bleeding symptoms were epistaxis in 36 patients (36.4%), easy bruising in 32 (32.3%), and menorrhagia in 6 (6.1%). After initial tests ordered by the pediatrician, 36 of 99 patients (36.4%) were diagnosed as having bleeding disorders that included von Willebrand disease in 12 (12.1%), hemophilia A or B in 9 (9.1%), and other rare factor deficiencies in 9 (9.1%). Six patients (6.1%) were found to have combined deficiencies. Seven of 36 patients had a family history of bleeding.Among the patients referred for bleeding disorders, 36.4% were diagnosed with a bleeding disorder with the help of primary screening tests ordered in the outpatient clinic.Amaç: Hafif kanama bozukluğu belirtileri toplumda sık görülmektedir. Bu çalışmanın amacı İstanbul Üniversitesi İstanbul Tıp Fakültesi Genel Pediatri Polikliniği’ne kanama bozukluğu şüphesi ile sevk edilen hastaların klinik ve laboratuvar özelliklerini belirlemektir. Gereç ve Yöntemler: 31 Ekim 2011 ile 31 Ekim 2012 tarihleri arasında kanama bozukluğu şüphesiyle yönlendirilen 99 hastanın tıbbi kayıtları incelenmiştir. Başvuru semptomları ile pıhtılaşma testlerinin sonuçları değerlendirilmiştir. Bulgular: Olguların 47’si kız çocuğu olup ve yaş ortalaması 9,1±4,1 yıl (2-18 yıl) idi. Kanama semptomları 36 hastada (%36,4) burun kanaması, 32 (%32,3) hastada kolay morarma ve 6 hastada (%6,1) menoraji idi. Birinci basamak testleri sonrasında, 99 hastanın 36’sında (%36,4) primer kanama bozukluğu saptandı. Bunlardan 12’sinde (%12,1) von Willebrand hastalığı, 9’unda (%9,1) hemofili A veya B, 9’unda (%9,1) diğer nadir faktör eksiklikleri ve 6 hastada (%6,1) kombine faktör eksiklikleri saptandı. Otuz altı hastanın 7’sinde ailede kanama öyküsü vardı. Sonuç: Kanama bozukluğu şüphesi ile sevk edilen hastaların %36,4’ünde birinci basamak koagulasyon testleri ışığında kanama bozukluklarından biri saptandı.

Chediak–Higashi syndrome (CHS) is caused by autosomal recessive mutations in LYST, resulting in enlarged lysosomal compartments in multiple cell types. CHS patients display oculocutaneous albinism and may develop life-threatening hemophagocytic lymphohistiocytosis (HLH). While NK cell-mediated cytotoxicity has been reported to be uniformly defective, variable defects in T cell-mediated cytotoxicity has been observed. The latter has been linked to the degree of HLH susceptibility. Since the discrepancies in NK cell- and T cell-mediated cellular cytotoxicity might result from differences in regulation of cytotoxic granule release, we here evaluated perforin-containing secretory lysosome size and number in freshly isolated lymphocytes from CHS patients and furthermore compared their exocytic capacities. Whereas NK cells from CHS patients generally contained a single, gigantic perforin-containing granule, cytotoxic T cells predominantly contained several smaller granules. Nonetheless, in a cohort of 21 CHS patients, cytotoxic T cell and NK cell granule exocytosis were similarly impaired upon activating receptor stimulation. Mechanistically, polarization of cytotoxic granules was defective in cytotoxic lymphocytes from CHS patients, with EEA1, a marker of early endosomes, mislocalizing to lysosomal structures. The results leads to the conclusion that lysosome enlargement corresponds to loss of distinct organelle identity in the endocytic pathway, which on a subcellular level more adversely affects NK cells than T cells. Hence, vesicular size or numbers do not per se dictate the impairment of lysosomal exocytosis in the two cell types studied.

Gardner Diamond syndrome is a rare condition characterized with painful ecchymoses in different parts of the body and cutaneous and mucosal hemorrhages. The etiology is not known fully and psychogenic factors are thought to be involved. Cutaneous lesions and hemorrhages develop mostly following emotional stress and rarely minor traumas and may recur. Although the extremities are involved with the highest rate, the lesions may be observed in any part of the body. Hemostatic tests are generally normal. The majority of the subjects is composed of young women. It is observed more rarely in men and children. In this article, a patient who presented with recurring painful echymoses and bleeding disorder and diagnosed with Gardner Diamond syndrome by intracutaneous injection of autologous blood was presented to emphasize that this syndrome is observed rarely in the childhood and should be considered not only in the differential diagnosis of cutaneous lesions, but also in the differential diagnosis of various system hemorrhages.