Evaluation of Renal Function Disorder With Urinary Neutrophil Gelatinase–associated Lipocalin Level in Patients With β-Thalassemia Major Background and Aim: Neutrophil gelatinase–associated lipocalin (NGAL) is found in the granules of human neutrophils, with many diverse functions. Expression of NGAL is induced under various pathophysiological conditions, for example, infection, inflammation, kidney injury, cardiovascular disease, burn injury, and intoxication, and it has an important antiapoptotic and anti-inflammatory role. Patients and Methods: A total of 37 patients with thalassemia disease β-thalassemia major (24 male and 13 female individuals) and 37 healthy controls (17 male and 20 female) were enrolled in this study. All patients were regularly transfused, and all of them were using oral chelator, deferasirox. Results: NGAL and cystatin C levels were significantly higher in the case group than in the control group. Conclusion: In patients with β-thalassemia major, renal damage can occur owing to regular blood transfusion. Urinary NGAL levels in these patients may be considered as a marker for early renal injury.

Evaluation of Bone Mineral Density in Children With Hemophilia: An Observational Case-Control Study Objectives: The objectives of this study were to study bone mineral content (BMC), bone mineral density (BMD), vitamin D level, and bone turnover markers in children with hemophilia and compare it with their normal counterparts. Design: This was an observational case-control study. Setting: This study was conducted in our tertiary care institute during the period spanning from September 2016 to June 2018. Materials and Methods: A total of 38 children with hemophilia 2 to 18 years of age and 38 age-matched and sex-matched healthy controls were included. Children with symptomatic hypocalcemia and those receiving drugs affecting BMC and BMD were excluded. Dual-energy x-ray absorptiometry was performed to estimate BMC and BMD. 25-Hydroxyvitamin D [25(OH)D], intact parathormone, osteocalcin, calcium, phosphate and alkaline phosphatase, and spot urine pyrilinks-D/creatinine ratio were estimated in them. Results: BMC and BMD in cases was lower than that in controls (P<0.05). Prevalence of low BMC was seen in 22 (58%) and low BMD in 8 (21%) of cases. All controls had normal BMC and BMD for age. The prevalence of low vitamin D level (<20 ng/mL) was seen in 36 (95%) among cases and in 25 (65%) among controls (P<0.001). Serum phosphorus was lower, and serum alkaline phosphatase was higher in cases than in controls (P<0.05). Conclusion: BMC, BMD, and vitamin D in hemophiliacs were lower than in the general population.

The Cutoff of Ferritin for Evaluation of Hypothyroidism in Patients With Thalassemia Background: Thalassemia major is a genetic disease with a recessive autosomal pattern of inheritance that occurs as a result of disorder in hemoglobin synthesis. Researchers aimed to investigate the cutoff of ferritin for the development of hypothyroidism in patients with thalassemia major. Materials and Methods: This was a retrospective analytic cross-sectional study that was conducted on the medical records of patients with thalassemia major. Overt hypothyroidism was defined as thyroid stimulating hormone (TSH) level of >6.5 mIU/L and T4 level of < 4.2 ng/dL and subclinical hypothyroidism was defined as TSH level of >6.5 mIU/L and T4 level of >4.2 ng/dL. Data were gathered by a form including age, sex, weight, height, body mass index, thyroid test results, and the mean of last 3 consecutive hemoglobin and ferritin levels. Results: In this study, 67 patients were evaluated. The mean age of the participants was 15.37±3.73 years. The frequency of subclinical hypothyroidism was 10.4%, and no cases of clinical hypothyroidism were noted as well as secondary hypothyroidism. Although there was a significant linear correlation between mean ferritin level and TSH (P=0.008), no significant correlation was noted between levels of ferritin and T4 levels. As ferritin was significantly correlated with TSH, the results showed that the mean serum level of ferritin in β-thalassemia major patients with hypothyroidism was higher than that in β-thalassemia major patients with normal thyroid status (P=0.013). The cutoff point for ferritin was 1953 ng/mL (sensitivity=85.7%, specificity=60%). Conclusion: It seems that considering the development of hypothyroidism by reaching the ferritin cutoff point, intensification of the iron chelation regimen along with a shorter interval for laboratory endocrine examinations can be recommended.

Pediatric Stroke: A Single-Center Experience The aim of this study was to evaluate the clinical characteristics, risk factors, treatment, and outcomes of pediatric stroke cases. A total of 118 patients diagnosed with arterial ischemic stroke (AIS), hemorrhagic stroke, and sinovenous thrombosis (SVT) between January 2000 and December 2011 were included. Neonatal cases were excluded. Demographic and clinical findings were retrospectively examined from medical records. We identified 118 patients with stroke. The age of the patients ranged from 1 to 215 months (17.92 y), with a mean age of 5.19±5.25 years. AIS accounted for the majority of cases (n=69, 58.5%), and the major etiology was cardiac disease (17%). Hemorrhagic stroke accounted for 19.5% (n=23) of the cases, and late hemorrhagic disease of the newborn was the major etiology (43%, n=10). SVT accounted for 22% (n=26) of the cases, and the major etiology was otitis media-mastoiditis (27%, n=7). Hemiplegia and headache were the most frequent symptoms for AIS and SVT, respectively. Stroke is rare in children compared with adults; however, it is detected more frequently with better imaging techniques and increased awareness. We found that children with AIS presented more commonly with hemiplegia and children with SVT with headache and strabismus. We did not find an association between thrombophilia and stroke.

A Phase 2, International, Multicenter, Open-label Clinical Trial of Subcutaneous Tbo-Filgrastim in Pediatric Patients With Solid Tumors Undergoing Myelosuppressive Chemotherapy This phase 2, multicenter, open-label trial investigated the safety and tolerability of tbo-filgrastim in pediatric patients receiving myelosuppressive chemotherapy. In total, 50 patients 1 month to below 16 years of age with solid tumors without bone marrow involvement were stratified into 3 age groups (2 infants, 30 children, 18 adolescents) and prophylactically administered tbo-filgrastim 5 µg/kg body weight once daily subcutaneously. The administration started after the last chemotherapy treatment in week 1 of the first cycle and continued until the expected neutrophil nadir had passed, and the neutrophil count had recovered to 2.0×109/L. The primary endpoint was safety and tolerability of tbo-filgrastim; secondary endpoints included efficacy. The mean (SD) number of doses administered was 9.2 (2.83) in children and 7.3 (1.88) in adolescents. Serious treatment-emergent adverse events were reported in 24% of patients; the most common were febrile neutropenia (FN) (12%), anemia (8%), and thrombocytopenia (8%). Nine patients (18%) experienced mild treatment-related treatment-emergent adverse events; the most common were musculoskeletal and connective tissue disorders (8%). No deaths or withdrawals occurred. The incidence of severe neutropenia (SN) was 52% and the mean (SD) duration of SN was 1.8 (2.21) days; FN incidence was 26%. A daily dose of tbo-filgrastim 5 μg/kg body weight administered to pediatric patients demonstrated a safety profile consistent with the safety profile in adult patients. The incidence of FN was on the lower end of the range reported in the literature and the SN results provide supportive data on the efficacy of tbo-filgrastim in pediatric patients.

Differentiated Thyroid Cancer in the Pediatric/Adolescent Population: Evolution of Treatment Differentiated thyroid cancer (DTC) is the most common cancer in adolescents and young adults. In 2015, the American Thyroid Association published guidelines for management of pediatric DTC. We report our institutional experience and highlight changing practices and new opportunities. A retrospective analysis of all patients diagnosed with DTC from 2001 to 2016 was performed. Among 59 eligible patients, 31 (53%), 15 (25%), and 13 (22%) had low-risk, intermediate-risk, and high-risk disease, respectively. Half (15/31) of low-risk and all intermediate-risk/high-risk patients received radioactive iodine (I-131) ablation. For low-risk patients, average I-131 dose decreased from 80 to 42.05 mCi, and the percentage of patients who received I-131 decreased over time. Eleven of 16 patients with tumor genomic data were found to have somatic targetable (n=6) or germline (n=5) mutations. Persistent/recurrent disease was only present in high-risk (n=8) and intermediate-risk (n=1) patients. Two patients with iodine-refractory disease received trametinib to enhance radioiodine uptake. All patients were alive at follow-up (median, 5 y; range, 1 to 15 y). Coincident with the recent American Thyroid Association guidelines, the use of I-131 in low-risk patients has decreased over time in our practice. Tumor sequencing and cancer genetic evaluation may help redefine opportunities for treatment of high-risk patients and family counseling.

Steroid-induced Bradycardia During Induction Chemotherapy in Children and Young Adults Diagnosed With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Systemic corticosteroids are widely used for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. Anecdotal case reports demonstrate bradycardia in patients receiving corticosteroids; however, a more in-depth analysis is lacking. This study aimed to describe the incidence, timing, and outcomes of bradycardia in children with ALL receiving corticosteroids during induction chemotherapy at our center from 2010 to 2016. A total of 153 children were included, with 150 (98%) demonstrating decreased heart rate following steroid administration with a median HR decrease of 23 beats per minute. Bradycardia ≤first percentile for age developed in 90 (59%) patients, with nadir occurring, on average, 7 doses into treatment, corresponding to 79 hours after initiation of therapy. No patient experienced adverse events related to bradycardia. Resolution of bradycardia at outpatient follow-up occurred in 62 of 71 (87%). Examination of nadir heart rate during subsequent hospitalizations in which steroids were not being administered did not demonstrate a significant incidence of bradycardia. Corticosteroid-induced bradycardia is common in children with ALL receiving induction chemotherapy. It was not associated with clinical adverse events and self-resolved without intervention. Therefore, further cardiac assessment may not be warranted in the presence of asymptomatic bradycardia suspected to be secondary to steroid administration.

Comparison of FDG PET/MRI and FDG PET/CT in Pediatric Oncology in Terms of Anatomic Correlation of FDG-positive Lesions The aims of our study were to compare F-18 fluorodeoxyglucose (FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) and PET/computed tomography (CT) in pediatric oncology patients in terms of anatomic correlation of FDG-positive lesions, and also to compare diffusion-weighted imaging (DWI) with PET to assess the correlation between apparent diffusion coefficient (ADC) values and standardized uptake value (SUV). Sequential PET/CT and PET/MRI images and/or whole-body DWI and ADC mapping in 34 pediatric patients were retrospectively analyzed. FDG-positive lesions were visually scored for CT, T1-weighted, T2-weighted, and DWI images separately in terms of anatomic correlation of FDG-avid lesions. Correlation analysis was performed for SUV parameters and ADC values. Among 47 FDG-positive lesions identified concurrently on PET/CT and PET/MRI, 37 were positive on CT and 46 were positive on at least one MRI sequence (P=0.012). Among 32 FDG-positive lesions for which DWI were available, 31 could be clearly depicted on DWI, resulting in significant difference compared with CT alone in the detection of FDG-positive lesions. No correlation was found between ADC and SUV. FDG PET/MRI exhibits better performance than PET/CT in terms of anatomic correlation of FDG-avid lesions. Therefore, PET/MRI may be more advantageous than PET/CT, not only due to reduced ionizing radiation dose but also for a better depiction of FDG-avid lesions in pediatric PET imaging.

Information and Training Needs of Pediatric Oncologists in Complementary and Integrative Medicine: A Cross-Sectional Study More than one third of all German pediatric patients with cancer use complementary and integrative medicine (CIM). Parents want to discuss the topic of CIM with their pediatric oncologists (POs); however, POs mostly do not feel confident discussing these topics. POs report openness to receiving further information and training, but CIM training opportunities in medical education seem rare. We investigated POs’ information and training needs and preference patterns regarding CIM training content with a paper-based or online survey. A total of 101 POs from Germany completed the survey. Only 11.4% agreed to being sufficiently informed of CIM. The participants stated needing further CIM information very often (8.6%), often (38.7%), or occasionally (44.1%). They considered an overview of CIM therapies and information about relaxation methods, herbal remedies, and acupuncture for cancer-related symptoms such as lack of appetite, nausea, or vomiting as most important in CIM training material, and also the topics of adverse effects and summary of evidence. Finally, POs reported on clinical situations in which a need for further information on CIM emerged. The results of our study indicate that there is a need for a structured training that offers knowledge and skills on the subject of patient counseling on CIM in pediatric oncology.

Complement Mediated Hemolytic Anemia Secondary to Plasmodium ovale Infection in a Child No abstract available