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OBJETIVO: Analisar comparativamente a dispersão da onda P (DOP) em pacientes com talassemia beta maior (β-TM) e indivíduos saudáveis (controles) para a detecção precoce do risco de arritmias. MÉTODOS: Oitenta e uma crianças com β-TM, com idades entre 4 e 19 anos, e 74 crianças saudáveis (grupo controle) foram submetidas a exame eletrocardiográfico e ecocardiograma transtorácico de rotina para avaliação cardíaca. A DOP foi calculada como a diferença entre as durações máxima e mínima da onda P. RESULTADOS: Houve uma diferença estatisticamente significativa entre o grupo de estudo e o grupo controle no pico de velocidade do fluxo transmitral no início da diástole (E) e na razão E/fluxo transmitral tardio (A). A duração máxima da onda P e a DOP foram significativamente maiores nos pacientes com β-TM do que nos indivíduos controles. CONCLUSÕES: O aumento da DOP em nossos pacientes com β-TM pode estar relacionado à depressão na condução intra-atrial, devido à dilatação atrial, e ao aumento da atividade simpática. Estes pacientes devem ser acompanhados atentamente devido à possibilidade de ocorrência de arritmias com risco de vida.OBJECTIVE: To comparatively evaluate P-wave dispersion (PWD) in patients with β-thalassemia major (TM) and healthy control subjects for the early prediction of arrhythmia risk. METHODS: Eighty-one children with β-TM, aged 4-19 years, and 74 healthy children (control group) underwent routine electrocardiography and transthoracic echocardiography for cardiac evaluation. PWD was calculated as the difference between the maximum and the minimum P-wave duration. RESULTS: There was a statistically significant difference between study and control groups in peak early (E) mitral inflow velocity and E/late (A) velocity ratio. Maximum P-wave duration and PWD were found to be significantly higher in β-TM patients than in control subjects. CONCLUSIONS: Increased PWD in our β-TM patients might be related to depression of intra-atrial conduction due to atrial dilatation and increased sympathetic activity. These patients should be closely followed up for risk of life-threatening arrhythmias.

Most common causes of microcytic anemia in children are iron deficiency anemia (IDA) and thalassemia. Differentiation of these and detection of coexistence is essential for genetic counseling and to set a treatment plan. Aim is to characterize the frequency of IDA and thalassemia trait (TT) in children presenting with hypochromic, microcytic anemia and to define the significance of blood count parameters in differential diagnosis. Of the 200 enrolled, 107 were male (53.5%). In total 154 had IDA (77%), 27 had β-TT (13.5%), and in 11 (5.5%) both conditions coexisted. Eight patients had α-thalassemia gene mutations, 3 of these also had IDA. RBC, MCV, Mentzer index, serum iron, TIBC, ferritin were significantly different between IDA and β-TT patients (P<0.001); however, RDW was not different between the 2 groups (P>0.05). Sensitivity and specificity of Mentzer index for the detection of β-TT were 100% and 69.4%, respectively. The positive and negative predictive values of Mentzer index in diagnosing β-TT were 36.6% and 100%, respectively. Differential diagnosis of microcytic anemia is important in children, especially in regions where IDA and thalassemia are both prevalent. We found that 7% of children referred to our clinic for hypochromic, microcytic anemia had both TT and IDA. Our data showed that serum iron, ferritin, TIBC, MCV, and Mentzer index were all valuable markers in diagnosing IDA and were significantly different compared with β-TT patients; RDW was not different between the 2 groups.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening inherited disease leading to early-onset atherosclerosis and associated morbidity. Because of its rarity, longitudinal data on the management of HoFH in the real world are lacking, particularly on the impact the condition has on quality of life (QoL), including the impact of the extracorporeal lipid removal procedure apheresis (LA)., Methods: The A-HIT1 study included 88 patients with HoFH aged ≥12 years receiving regular LA in 19 centers in Turkey. Demographic and disease characteristics data were obtained. For patients aged ≥18 years, additional data on psychosocial status were obtained via the SF-36 score, the Hospital Anxiety and Depression Scale, and a HoFH-specific questionnaire., Results: There was no standardized approach to therapy between centers. Mean (±SD) frequency of LA sessions was every 19.9 (±14) days, with only 11.6% receiving LA weekly, and 85% of patients were not willing to increase LA frequency. The most common concerns of patients were disease prognosis (31%), and physical, aesthetic, and psychological problems (27.5%, 15.9%, and 11.6%, respectively). Lower age at diagnosis was associated with better QoL, lower anxiety, improved functioning, and greater emotional well-being compared to later diagnosis., Conclusions: These findings demonstrate that adult patients with HoFH undergoing LA, experience significant impairment of QoL with an increased risk of depression. From patients' point of view, LA is time-consuming, uncomfortable, and difficult to cope with. The speed of diagnosis and referral has a considerable impact on patient well-being., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey., Methods: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 μg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice., Results: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 μg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 μg/L), SCA (1655.5 to 1260 μg/L), and across age groups of 2-6 years (1971.5 to 1499 μg/L), 7-12 years (1688.5 to 1159.8 μg/L), and 13-18 years (1496.5 to 1107 μg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range., Conclusions: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of large-scale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2)., Methods: A-HIT1 is a survey of homozygous FH patients undergoing low density lipoprotein (LDL) apheresis (LA). A-HIT2 is a registry of adult FH patients (homozygous and heterozygous) admitted to outpatient clinics. Both registries used clinical diagnosis of FH., Results: A-HIT1 evaluated 88 patients (27 ± 11 years, 41 women) in 19 centers. All patients were receiving regular LA. There was a 7.37 ± 7.1-year delay between diagnosis and initiation of LA. LDL-cholesterol levels reached the target only in 5 cases. Mean frequency of apheresis sessions was 19 ± 13 days. None of the centers had a standardized approach for LA. Mean frequency of apheresis sessions was every 19 ± 13 (7-90) days. Only 2 centers were aware of the target LDL levels. A-HIT2 enrolled 1071 FH patients (53 ± 8 years, 606 women) from 31 outpatients clinics specialized in cardiology (27), internal medicine (1), and endocrinology (3); 96.4% were heterozygous. 459 patients were on statin treatment. LDL targets were attained in 23 patients (2.1% of the whole population, 5% receiving statin) on treatment. However, 66% of statin-receiving patients were on intense doses of statins. Awareness of FH was 9.5% in the whole patient population., Conclusions: The first nationwide FH registries revealed that FH is still undertreated even in specialized centers in Turkey. Additional effective treatment regiments are urgently needed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Homozygous familial hypercholesterolemia (HoFH) is a genetic condition characterized by lethally high levels of low-density lipoprotein cholesterol (LDL-C) from birth, and requires rapid and aggressive intervention to prevent death due to coronary heart disease and/or atherosclerosis. Where available, lipoprotein apheresis (LA) is the mainstay of treatment to promote survival., Methods: A-HIT1 registry was conducted with the aim of providing insight to the real-life management of HoFH patients undergoing LA in Turkey, where LA procedures are fully reimbursed and widely available. Participating centers provided patient information, including family history, treatment patterns and relevant laboratory values, via a standard questionnaire., Results: The study evaluated 88 patients (mean age: 27 ± 11 years, 41 women) in 19 centers. All patients were receiving regular LA with a clinical diagnosis of HoFH. Mean age at first symptom disease was 10 ± 10 years, and at diagnosis it was 12 ± 11 years; 74.7% were diagnosed before age 15 years; and only 31% before the age of 7. First referral of most patients was to pediatricians. Early onset coronary artery disease was present in 57.8% of patients. Mean age at first LA was 21 ± 12 years. Only 11 (12.5%) patients were undergoing LA weekly. Mean frequency of apheresis sessions was 19 ± 13 days. For the last four LA sessions, LDL-C levels reached the target in only in 5.7% of patients., Conclusions: Diagnosis of HoFH is delayed, and LDL targets are not reached. LA frequencies are not optimal. Urgent attention is needed to support the survival of patients with HoFH., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Achromobacter xylosoxidans is an aerobic gram-negative bacillus and important cause of bacteremia in immunocompromised patients. We describe a leukemia pediatric patient with severe neutropenia who developed bacteremia with A xylosoxidans resistant to multiple antibiotics, and treated the patient with tigecycline and piperacillin-tazobactam in addition to supportive medications.

Background: Rare factor deficiencies (RFDs) are autosomal recessively inherited coagulation factor deficiencies encountered at a frequency of between one in 500, 000 and one in two million., Materials and Methods: One hundred and ninety-two patients, diagnosed as having RFD, followed and treated in our clinic between 1990 and 2013 were retrospectively evaluated in this study., Results: From the 192 patients, 142 had FVII, 15 had FX, 14 had FXI, 10 had fibrinogen, six had FV, two had FXIII, two had FV + FVIII and one had FII deficiency. One hundred and thirty of the cases were boys and 62 were girls. The age range was 2 weeks to 24 years and the ages at the admission were between 2 weeks and 16 years. The rate of consanguinity was 49.4%. Eighty-eight of our patients were asymptomatic (45.8%) and 104 were symptomatic (54.2%). Asymptomatic patients were diagnosed by family histories (39.8%), preoperative laboratory studies (54.6%) and operational bleeding (5.6%). Sixty-eight of our symptomatic patients displayed grade II (65.4%) and 36 displayed grade III bleeding symptoms (34.6%). First bleeding regions were skin (33%), nose (28%), central nervous system (CNS) (15.5%), oral cavity (10.5%), soft tissue (6%), joint (3%), urinary system (2%) and gastrointestinal system (GIS) (2%), respectively. The bleeding prevalence rates of our symptomatic patients are listed as epistaxis 62.5%, skin bleedings 53%, oral cavity bleeding 28.8%, haematomas 18.3%, CNS bleedings 17.3%, haemarthrosis 14.4%, GIS bleedings 3.8%, menorrhagia 2.9%, haematuria 1.9%, bleeding because of operations 1.9% and iliopsoas bleedings 1.9%. CNS bleedings (41%) take the first place among the serious bleedings of our cases, followed by haemarthrosis (36.4%), GIS bleedings (18.1%) and iliopsoas bleedings (4.5%). Prophylaxy was applied to nine patients (five patients with FVII, two patients with fibrinogen and one each with FV and FX deficiency)., Conclusions: The characteristics of clinical presentations, first bleeding attacks, bleeding prevalence and severe bleedings as well as prophylactic approaches are discussed in this article.

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

The aim of the study is to assess the relationship between T2* magnetic resonance imaging (MRI) values and age, serum ferritin level, left ventricular ejection fraction (LVEF), splenectomy status, and to identify appropriate modifications to chelation therapy based on T2* MRI results of children with thalassaemia major. Sixty-four patients with thalassaemia major (37 girls/27 boys) older than 8 years of age were enrolled in the study. Based on the first T2* MRI, the patients' myocardial iron depositions were classified into three groups: T2* MRI <10 ms (high risk group), T2* MRI 10-20 ms (medium-risk group) and T2* MRI >20 ms (low-risk group). There was no significant relationship between T2* MRI value and ages, serum ferritin levels and splenectomy status of thalassaemia major patients. The mean LVEFs were 60, 75, and 72.5 % in the high-, medium-, and low-risk groups, respectively (P = 0.006). The mean cardiac iron concentrations calculated from the T2* MRI values were 4.96 ± 1.93, 1.65 ± 0.37, and 0.81 ± 0.27 mg/g in the high-, medium-, and low-risk groups, respectively. Chelation therapies were re-designed in 24 (37.5 %) patients according to cardiac risk as assessed by cardiac T2* MRI. In conclusion, until recently, T2* MRI has been employed to demonstrate cardiac siderosis without a direct relationship with the markers used in follow-up of patients with thalassaemia. However, modifications of chelation therapies could reliably be planned according to severity of iron load displayed by T2* MRI.

Congenital rare factor deficiencies may present in infancy by life-threatening bleedings or may not show any symptoms until adulthood. It is reported more commonly in countries having consanguineous marriages. Data regarding surgical interventions of rare congenital factor deficiencies are based on case reports and records of guidelines. There are no well documented and separately prepared directories related to pre-surgical and prophylactic approaches of surgical interventions of these deficiencies. Our retrospective study consisted of 171 rare factor deficiencies that were followed up in our clinic, and of whom 61 had 88 surgical interventions between 1990 and 2012. Of these patients, 45 were having factor VII deficiency, and factor V, X, XI, XIII and fibrinogen deficiencies were present in five, four, three, two and two patients, respectively. In 23 patients, factor coagulant activities were under 5% (37.7%), in 15 it was between 5 and 30% (24.6%), and in 23 between 30 and 50% (37.7%). Twenty-eight were symptomatic and 33 were asymptomatic. Information of 51 (83.6%) male and 10 (16.4%) female patients with an age range of 5-25 years (13 ± 5.27), whose age at presentation ranged between 3 weeks and 18 years (7 ± 4.66), were retrieved from patient records and from the records contained in the data-processing environment introduced in 2005. The rate of familial consanguinity was 49.2%. Of the surgical interventions, 24 (27.3%) were major, 24 (27.3%) were minor and 40 (45.4%) were circumcision. We used fresh frozen plasma in 32, recombinant factor (rF)VIIa in 20, prothrombin complex concentrate in five and fibrinogen in three patients during surgical interventions. In 18 patients, antifibrinolytic agents were also used. In 27 patients, surgical interventions were applied without any replacement therapy. No additional doses were required after surgical prophylaxis doses. Thrombotic events were not observed. Antibody occurrence was not detected in these patients. In our study, we evaluated preparation for surgical procedures, factor replacement therapy before surgical intervention and postoperative follow-up in patients with rare coagulation factor deficiency.

Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.

The aim of the study was to evaluate cardiac function and early cardiac dysfunction of patients followed as thalassemia major. In this study, the authors compared 100 patients, diagnosed as thalassemia major with mean age 11.84 ± 4.35, with 60 healthy control subjects at the same age between 2008 and 2011. Early diagnosis of iron overload that may occur after repeated transfusions is important in this patient group. To detect early iron accumulation, the authors compared ferritin with the echo findings, the 24-hour Holter, and cardiac magnetic resonance imaging (MRI) T2* values in the patients of same age and sex, treated with chelators, without heart failure, nonsplenectomized, and do not differ in the presence of hepatitis C. Ferritin levels, left ventricular systolic functions (ejection fraction [EF], shortening fraction [SF]), left ventricular measurements, left ventricular diastolic functions, T2* image on cardiac magnetic resonance, heart rate variables in 24 hours, and Holter rhythm were evaluated to show the early failure of cardiac functions. In this study the authors confirmed that iron-related cardiac toxicity damages electrical activity earlier than myocardial contractility. Left ventricular diastolic diameter (LVDd), left ventricular mass (LVM), and LV systolic diameter (LVDs) levels were significantly higher in the patient group with ectopia. Patients with ectopia are the ones in whom LVM and LVDd are increased. In thalassemia major patients with ectopia, LF/HF ratio was markedly increased, QTc dispersion was clearly found higher in patients with ectopia rather than nonectopic patients. The standard deviation all normal RR interval series (SDNN) was found clearly lower in thalassemia major group with ectopia than control group because it is assumed that increase in cardiac sympathetic neuronal activity is related to exposure to chronic diastolic and systolic failure.

The present study was designed to evaluate the significance of echocardiography versus cardiac troponin I levels in early detection of anthracycline dependent cardiotoxicity in acute lymphoblastic leukemia (ALL) patients. A total of 276 pediatric ALL patients were included in the study prospectively along 3 phases of data collection lasted from 2002 to 2009; including phase I (March 2002 to February 2003; n = 25; 53.3% females), phase II (September 2003 to April 2004; n = 35; 57.1% females), and phase III (January 2005 to June 2009; n = 216; 52.7% females) with respect to cumulative anthracycline doses applied. Anthracycline was administered in accordance with berlin-Franfurt-Munich (BFM)-2000 protocol in doses of 30 to 350 mg/m(2) (in the first phase) and 30 to 240 mg/m(2) (in the following phases). Evaluation of cardiotoxicity was performed via echocardiography and measurement of cardiac troponin I levels. Patients in each phase were homogenous in terms of gender and age. Diastolic dysfunction determined via reduction E/A ratio below the cutoff value was demonstrated to deteriorate earlier than systolic functions and alteration in cardiac enzymes. Being similar between dose groups, cTnI levels were shown to rise in the presence of congestive heart failure. In conclusion, anthracycline cardiotoxicity appears to be detected in an earlier stage by using diastolic parameters compared to systolic parameters and cardiac enzymes.

The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.

Among several newly identified oncogenes, dek and af4 are attractive targets for researchers interested with leukemia. In this study quantitative Real-Time RT-PCR technique was used to define alterations in expression of dek and af4 genes associated with acute promyelocytic leukaemia (APL) t (15; 17). RNA samples obtained from bone marrow aspirates of fourteen APL patients, cDNA portions were labelled with Syber Green 1 dye and LightCycler analysis have been performed. Expression changes in patients were found not significant in comparison to healthy donors for af4 (P = 0.192) and dek (P = 0.0895). We suggest that af4 gene may have a role in leukomogenesis restricted to lymphoblastic lineage; also further studies must carry on with a larger series of patients in order to understand the relationship between the dek gene and APL. Our study was the first attempt for analysing dek and af4 genes in APL t (15; 17) patients by quantitative Real-Time RT-PCR. This rapid and sensitive method could be used to screen these genes in different types of leukaemia.