Can biomarkers predict myocardial iron overload in children with thalassemia major?

AIM: Beta-thalassemia major requires regular blood transfusions throughout life, which in turn leads to iron accumulation in the body. While cardiac T2* MRI is the gold standard in determining cardiac iron accumulation, it is not always feasible, which has led to the search for new biomarkers. Herein, the value of growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide in predicting cardiac iron accumulation is investigated in asymptomatic children with beta-thalassemia major. MATERIALS AND METHOD: Forty-one patients aged 11-21 years and 41 age-, gender-, body mass index-matched healthy controls were included. Serum growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were compared between the patients and controls. Additionally, the relations of these biomarkers with cardiac and liver T2 * MRI were investigated in the patients. RESULTS: In the patients, growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were higher than healthy controls (p < 0.001, p = 0.025, p < 0.001, respectively). There were no significant correlations of growth differentiation factor-15 and N-terminal pro-B-type natriuretic peptide levels with both cardiac and liver T2 * MRI measurements. While there was no significant correlation of serum galectin-3 with cardiac T2 * MRI measurements, a negative correlation was found with liver T2 * MRI measurements (p = 0.040, rho = -0.325). CONCLUSION: All three biomarkers investigated in this study failed to predict myocardial iron accumulation in asymptomatic children with beta-thalassemia major. However, a weak relation between serum galectin-3 level and hepatic iron accumulation was demonstrated.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Evaluation of left ventricular function and myocardial deformation in children with beta-thalassemia major by real-time three-dimensional (four-dimensional) and speckle tracking echocardiography.

AIM: This study aimed to evaluate the role of real-time three-dimensional (four-dimensional) and speckle tracking echocardiography for early detection of left ventricular systolic dysfunction and also for the relationship between myocardial deformation parameters and myocardial iron load which is measured by cardiac magnetic resonance relaxation time T2* values in asymptomatic children with beta-thalassemia major. MATERIAL AND METHODS: This multicenter cross-sectional study included 40 patients (mean age 15.4 ± 2.9, 42.1% male) and 40 healthy children whose age, gender, and body mass index-matched with patients. Each participant underwent conventional echocardiography and tissue Doppler imaging. Left ventricular ejection fraction; global longitudinal, circumferential, radial strains; twist; and torsion were measured by real-time three-dimensional and speckle tracking echocardiography. Cardiac magnetic resonance imaging T2* was measured in patients. RESULTS: Left ventricular global longitudinal, circumferential, and radial strains were decreased despite preserved global ventricular function in patients compared to healthy children (p = p = .029, p = p < .001, p = .003, respectively). There were no statistically significant differences between patients with T2* ≥ 20 ms and patients with T2* < 20 ms for all echocardiographic parameters. Also, there were no significant correlations between all echocardiographic parameters and T2* values in all patients, those with T2* ≥ 20 ms, and T2* < 20 ms. CONCLUSION: We found that even in asymptomatic children with beta-thalassemia major, left ventricular longitudinal, circumferential and, radial functions were impaired by real-time three-dimensional (four-dimensional) and speckle tracking echocardiography. This novel echocardiographic method might be an important tool for detecting subclinical left ventricular systolic dysfunction irrespective of T2* values.

The time to diagnosis and survival in children with solid tumors and lymphoma: results from a single center in Turkey.

The longer diagnostic intervals in low- and middle-income countries have been proposed among the possible causes of poorer outcomes in children with cancer. In this single-center study from Turkey, the diagnostic intervals and survival status of 138 children with solid tumors and lymphoma (excluding leukemia) were prospectively evaluated. The median total interval (from the beginning of the first cancer-related symptom to the first day of the cancer-specific therapy), the median patient interval (the time interval from the notification of the first cancer-related symptom to the first admission to a healthcare facility), and the median physician interval (the time interval between the first healthcare admission to the first pediatric oncology visit) were 65, 26, and 24 days, respectively. The estimated 5-year overall survival and event-free survival rates were 80.7% and 69.1%, respectively. The longer time intervals were correlated with age, paternal education, localization, and tumor type. Interestingly, none of the time parameters were found to be associated with survival on regression analysis. In conclusion, the diagnostic delay in children with cancer is multifactorial, and the patient- and disease-related factors are as important as the time intervals on survival.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1951903.

Ophthalmologic findings and complications before and after hematopoietic stem cell transplantation: single-center study.

PURPOSE: Different and various system complications and late effects may occur after hematopoietic stem cell transplantation (HSCT). It was aimed to obtain information about the frequency of ophthalmologic complications and their relationship with treatment. METHODS: This retrospective study includes 104 children who underwent HSCT between February 2019 and June 2020 at the Pediatric Bone Marrow Transplant Unit. Patients' ages, genders, diagnosis, transplant types, chemotherapy regimens, transplantation details, conditioning regimens, supportive cares, graft versus host disease (GvHD) prophylaxis, infection episodes, and ophthalmologic findings were evaluated. RESULTS: Of the 104 patients included in the study, 38 (36.5%) were female and 66 (63.5%) were male. Average age ± SD was 8.7 ± 4.91. Considering the diagnoses, the majority of the patients were acute lymphoblastic leukemia (46 patients-44%). Myeloablative regimen was used in 93 (89%) of the patients, and reduced intensity conditioning (RIC) was used in 11 patients (10%). While total body irradiation was applied in 16 (15%) patients, one patient was received cranial radiotherapy. Cyclosporine was used in 96 (92%) patients. CMV reactivation was detected in 54 (51%) of the patients. CMV retinitis was not seen. Ocular pathology was detected in 20 (19%) patients before HSCT and in 12 (11%) patients after HSCT. The most common pathology was dry eye. CONCLUSION: Routine ophthalmologic examinations are important in terms of early diagnosis. In addition, GvHD and CMV prophylaxis is important because of reducing the risk of ocular complications after HSCT.

The association of angiopoietin-like peptide 4 levels with obesity and hepatosteatosis in adolescents.

INTRODUCTION: Angiopoietin-like peptide 4 (ANGPTL-4) is an adipocytokine that regulates plasma lipoprotein levels by inhibiting the lipoprotein lipase enzyme. Changes in lipid profile can be seen in obese adolescents. Nonalcoholic fatty liver disease may also be a complication of obesity. Based on this information, in this study we aimed to evaluate the relationship between serum ANGPTL-4 levels and obesity and hepatosteatosis in adolescents. MATERIALS AND METHODS: A total of 85 volunteer adolescents, 55 of them were obese and 30 of them were normal weight, were included in our study. The adolescents having body mass index (BMI) 95% percentile and over according to age and sex was defined as obese. Thirty patients with grade 2-3 hepatosteatosis in abdominal ultrasound (USG) were included in 'obese adolescents with hepatosteatosis' subgroup and 25 obese cases with no hepatosteatosis in the USG were included in the 'obese adolescents without hepatosteatosis' group. Thirty patients with no hepatosteatosis in the abdominal USG and having BMI in normal percentiles according to their age and sex constituted the 'healthy control adolescents' group. Serum ANGPTL-4 levels were measured by Enzyme Linked Immunosorbent Assay. Laboratory tests, gender, age and BMI levels were compared statistically between groups. Correlations between ANGPTL-4 and other laboratory parameters were examined statistically in obese adolescent group. RESULTS: The BMI, ANGPTL-4, HbA1c, AST, ALT, total cholesterol, triglyceride, LDL-cholesterol, HOMA-IR and insulin levels of the obese adolescent group were found to be significantly higher than the healthy control group (p < 0.05). We found no statistically significant difference in BMI, ANGPTL-4, triglyceride, insulin and HOMA-IR levels among obese adolescents with or without hepatosteatosis (p > 0.05). In all obese adolescent groups and in obese adolescent group with hepatosteatosis; there was no statistically significant relationship between ANGPTL-4 and other variables (p > 0.05). CONCLUSIONS: We found that the levels of ANGPTL-4 increases in obesity in adolescents. However, our results make it difficult to establish a relationship between hepatosteatosis and ANGPTL-4. Targeting ANGPTL-4 may be beneficial for the pathogenesis and associated complications of obesity.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM).

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.

Association of depression and social anxiety symptom scores with disease characteristics in pediatric patients with chronic immune thrombocytopenia: a cross-sectional study.

Patients with ITP have been reported to experience higher levels of depression and anxiety than their healthy counterparts. The limited research conducted on this subject in the pediatric age group has demonstrated that patients have psychosocial difficulties, and their quality of life is adversely affected. The correlation of depressive symptoms with disease characteristics of cITP has never been investigated. This was a cross-sectional study in patients being treated for cITP. Communication with participants was done during routine outpatient visits or by telephone or e-mail, and a survey about demographics and the Children's Depression Inventory (CDI) and the Social Anxiety Scale for Children-Revised (SAS-CR) was administered prospectively. A total of 56 children with cITP were recruited. The mean CDI score was 17 (SD: ± 9.44). Approximately half of the patients had higher CDI scores than healthy Turkish children. Older age, time since diagnosis, a number of hospitalizations (both total and within the last year) were positively correlated with CDI scores. There was no significant correlation between SAS-CR scores and disease characteristics. Depressive symptom scores were higher in children with cITP compared with healthy children in this study. Psychological needs may be overlooked in the medical management of children with cITP.

Assessing Psychological Disorders in Turkish Adolescents with Transfusion-Dependent Thalassemia.

We investigated depression and anxiety levels and related psychological disorders in adolescents with transfusion-dependent thalassemia (TDT) in this study. The study was conducted in two pediatric hematology outpatient clinics and included adolescents with TDT (14.8 ± 2.4 years, n = 40) in the study and compared them with the healthy age-matched control group (14.3 ± 2.3 years, n = 62). The Turkish version of the Revised Child Anxiety and Depression Scale (RCADS) was used to determine depression, anxiety, and related psychologic disorders (obsession, panic disorder, social phobia). Depression, anxiety, obsession, panic disorder, and social phobia scores were significantly higher in the patient group compared with the control (all p < 0.05). Ferritin levels were positively correlated with total depression, general anxiety, separation anxiety, and social phobia scores, but transfusion frequency and young age were the confounding factors. Patients in early adolescence and those who require more frequent blood transfusions are at higher risk of developing psychological disorders; routine screening for mood disorders should be warranted. Serum ferritin level may be a good warning indicator for early recognition of psychologic disorders in TDT patients.

Children's only profession: Playing with toys.

The concepts of games and toys have a very important role in children's lives. It contributes to the development of cognitive, motor, psychosocial, emotional, and linguistic skills. It also plays a key role in raising self-confident, creative, and happy children. Therefore, attention should be paid to the concepts of games and toys, which are so important for the child to be a part of society as a healthy individual at every stage of his development. On the other hand, providing playgrounds where children can play comfortably and safely are essential in reducing the risk of accidents related to toys. All health-care components, especially pediatricians and family physicians, should take an active role in ensuring that these play processes, which are the most beautiful parts of childhood, are healthy and safe.

Helicobacter pylori infection in Turkish children with gastrointestinal symptoms and evaluation of serology.

Helicobacter pylori infection is a common etiopathogenetic factor in children with gastrointestinal symptoms in the developing world. Although serology offers an easy noninvasive method of diagnosis, its sensitivity and specificity are reported to be low among children. In this prospective study, we investigated the frequency and endoscopical and morphological findings of H. pylori infection in 180 Turkish children who underwent upper gastrointestinal endoscopy either for peptic symptoms or on a routine basis and in asymptomatic pediatric patients who underwent endoscopy for other reasons, and then evaluated the diagnostic accuracy of serology in our population. Overall H. pylori infection was diagnosed in 77 of the 180 patients (42.7%) by histology and urease test. The sensitivity of H. pylori specific IgG antibody assay by ELISA was determined to be 100%, while the specificity was 98%, the positive predictive value 97.4%, the negative predictive value 100%. Frequency of H. pylori infection is high in Turkish pediatric patients without gastrointestinal symptoms as well as in children with gastrointestinal complaints. H. pylori specific antibody assay is a noninvasive and sensitive method for the diagnosis of H. pylori infection in the Turkish pediatric population.

Evaluation of PAX5 gene in the early stages of leukemic B cells in the childhood B cell acute lymphoblastic leukemia.

B-lineage acute lymphoblastic leukemia (B-ALL) is a common subtype of acute leukemia in children. PAX5 plays a central role in B-cell development and differentiation. In this study, we analyzed PAX5 expression levels, transactivation domain mutations/deletions in B-ALL patients (n=115) and healthy controls (n=10). Relative PAX5 mRNA levels were significantly increased in B-ALL patients (p<0.0001). PAX5 expression was also evaluated in three different B-ALL subgroups (pro B, Common B and Pre B ALL) and showed stage specific expression levels. Pro B (p=0.04) and pre B (p=0.04) patients showed significantly high PAX5 mRNA levels compared to stage specific controls. At least one deletion of exons 7-8 or 9 has been identified in the 41% of the patients. CD34 positivity in patients and presence of large deletions (Δ7/8/9) showed a significant correlation (p=0.05). None of our patients showed PAX5 point mutations, but two previously identified SNPs (rs3780135 and rs35469494) were detected. Our results support that PAX5 is a critical factor in B-ALL development and aberrant PAX5 expression especially at early stages may leads to leukemic transformation.

The efficacy of magnetic resonance imaging and x-ray in the evaluation of response to radiosynovectomy in patients with hemophilic arthropathy.

OBJECTIVE: We aimed to assess the role of Magnetic Resonance Imaging (MRI) and X-Ray in the evaluation of response to radiosynovectomy (RS) in patients with hemophilic arthropathy. MATERIAL AND METHODS: Eleven patients who suffered from hemophilic arthropathy with a mean age of 11.7 (range between 7-15) were included in this study. 148-185 MBq Yttrium 90 silicate (Y-90) was administered intraarticularly to ten knee joints and one patient was treated with intraarticular 74 MBq Rhenium 186 (Re-186) injection into his ankle. Before radiosynovectomy, plain anteroposterior and lateral X-rays of the target joints were obtained by standard technique. The follow-up MRI and X-ray studies of the patients were done 6 months after RS. Pettersson hemophilic arthropathy scales were utilized to stage the condition of the joints on plain X-ray and classification of the investigated joints on MRI were done according to Denver score. The clinical assessment of the efficacy of the RS was made with the comparison of the average bleedings before and after the intervention. RESULTS: During the 6-month follow-up period after RS, an improvement in number of hemarthrosis 75% or greater compared with the prior six months occurred in six joints (54.5%). The Pettersson scores worsened in 1/11 (9%), remained unchanged in 9/11 (81.8%), and improved in 1/11 (9%) joints. At the 6-month follow-up, the MRI score worsened in one (9%) and was unchanged in 10/11 joints (90.9%). CONCLUSION: MRI is a more sensitive tool than plain radiography for evaluating and follow-up of joint disease in persons with hemophilia, but both methods don't show correlation with the therapeutic response Conflict of interest:None declared.

Hereditary spherocytosis with immunoglobulin A nephropathy.

Hereditary spherocytosis is a familial hemolytic anemia. Immunoglobulin A (IgA) nephropathy associated with hereditary spherocytosis has not been reported in children. Here, we report a case of a 17-year-old boy with IgA nephropathy and hereditary spherocytosis. The patient was diagnosed with hereditary spherocytosis at the age of 12 years and splenectomy was done at the age of 15 years. Later, the patient presented with macroscopic hematuria and proteinuria. Kidney biopsy of the boy was consistent with IgA nephropathy. Treatment with angiotensin-converting enzyme inhibitor was started. The patient became free of proteinuria after the 6th month of therapy.

A double-blind, crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy.

BACKGROUND: Granisetron is a safe and effective prophylaxis for nausea and vomiting associated with moderate to highly emetogenic chemotherapy. Few trials have been conducted to determine the optimal effective dose of granisetron in children with cancer. The objective of this report was to compare two doses of granisetron in patients with optic pathway tumors receiving moderately emetogenic doses of carboplatin. PATIENTS AND METHODS: In this double-blind, crossover, randomized study, antiemetic efficacy and tolerability of two dose levels (10 and 40 microg/kg) of granisetron in the prevention of acute and delayed nausea/emesis were compared in children and young adults. A total of 18 patients (13 boys) aged 1-23 years (median 7.7 years) treated with a moderately emetogenic dose of carboplatin were randomly assigned to receive either 10 or 40 microg/kg of slow granisetron intravenous (i.v.) infusions at alternating cycles of chemotherapy in a blinded fashion until the end of the study period or until their chemotherapy regimen ended. In this way, the patients acted as their own controls. RESULTS: Patients in the granisetron 10 and 40 microg/kg groups received 104 and 121 cycles of chemotherapy, respectively. There was no significant difference in antiemetic efficacy in terms of nausea and emesis between the dose groups in the first 5 days of chemotherapy. The treatment was well tolerated. CONCLUSION: We conclude that granisetron 10 and 40 microg/kg have comparable efficacy in controlling carboplatin-induced acute and delayed nausea/emesis and is well tolerated in children and young adults.