HbA1c or fructosamine on evaluating glucose intolerance in children with beta- thalassemia.

BACKGROUND: Beta-thalassemia major (ß-TM) patients are more likely to experience blood glucose intolerance and to date; the blood markers that could evaluate this are debatable. So, this study aimed to assess the roles of glycated hemoglobin A1c (HbA1c) and fructosamine in evaluating glucose intolerance in children with ß-TM and figuring out role of insulin resistance in these patients. METHODS: One hundred children diagnosed with ß-TM and 100 age and sex-matched controls were enrolled. Fasting plasma glucose (FPG), 2-h post-prandial blood glucose (2-h PG), HbA1c, fructosamine, fasting insulin level (FINS), insulin resistance index (HOMA-IR), and insulin sensitivity index (HOMA-IS) were evaluated. RESULTS: FPG and 2-h PG revealed glucose intolerance in 51 patients (51%), 19 of them had diabetes mellitus. HbA1c, fructosamine, FINS, and HOMA-IR showed a high statistically significant increase in patients compared to controls, (P < 0.001). Results revealed fructosamine was more specific in detecting prediabetes state and more sensitive in identifying diabetes mellitus in our patients when compared to HbA1c. CONCLUSIONS: Despite controversies on HbA1c in children with ß-TM, it is still valuable in glucose intolerance detection. Fructosamine showed more sensitivity and specificity. Furthermore, insulin resistance was prevalent in children with ß-TM highlighting the necessity of regular glycemic state evaluation. IMPACT: Glucose intolerance is a common complication in beta thalassemia patients. Conflicting data was reported about the role of HbA1c and fructosamine in evaluating glucose intolerance in thalassemic patients. Fructosamine does not yet have a threshold that may be used to distinguish between patients who have diabetes mellitus and those who do not. Fructosamine was more specific in detecting blood glucose intolerance compared to HbA1c and was more sensitive for diagnosing diabetes mellitus. Insulin resistance was common in patients with beta-thalassemia and often present before the onset of overt diabetes.

Expression of B-cell activating factor in pediatric patients with immune thrombocytopenia: a single institutional series and review of literature.

B-cell-activating factor (BAFF) is a crucial cytokine supporting survival and differentiation of B cells. Dysregulation of BAFF is involved in the pathogenesis of B-cell related autoimmune diseases including immune thrombocytopenia (ITP). The aim of this study was to evaluate the significance of BAFF expression in pediatric ITP patients. Eighty pediatric patients with ITP are subdivided in three groups. Group I included (32 patients) diagnosed with acute ITP less than 3 months, group II (48 patients) diagnosed with persistent ITP (from 3 to 12 months) and chronic ITP (more than 12 months) and group III 20 healthy controls. Complete blood picture, autoimmune profile, antiplatelet antibodies, coagulation profile, bone marrow examination, and RT-PCR were performed to detect the expression for BAF for all participants in this study. BAFF expression levels significantly increased in cases rather than in controls. BAFF Expression Value significantly increased in groups I & II (3.10 ± 1.99&3.29 ± 2.58) compared to controls (0.83 ± 0.45) as p < .001 for both. On the other hand, groups I & II were comparable in BAFF Expression Value (p = .470). BAFF expression increased in ITP patients, implying a function in the disease's pathogenesis.

Endothelial nitric oxide synthase gene polymorphism (786T/C) in childhood acute lymphoblastic leukemia survivors.

OBJECTIVES: To detect eNOS gene polymorphism and its relation to cardiovascular complications in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: CBC, renal and liver function tests, lipid profile, Carotid artery Intima Media Thickness (CIMT), and Brachial artery Intima Media Thickness (BIMT). eNOS gene polymorphism was done in 40 childhood ALL survivors and 40 controls. RESULTS: There was no significant difference between survivors and control groups regarding 786 T/C polymorphism. There was a significant increase in serum cholesterol, TGs, LDL, VLDL, and HbA1c in the TC and CC group more than in the TT group, while there was a significant decrease in serum HDL in the TC and CC group more than in the TT group. There was no significant difference as regards echocardiography findings between different polymorphisms of 786 T/C, but there was a significant difference between 786 T/C groups with regard to the carotid and brachial arteries intima media thickness (IMT) measurements being significantly higher in the TC and CC group more than in the TT group. CONCLUSION: Carotid and brachial arteries intima media thickness measurements were higher in the survivors when compared to healthy controls. eNOS gene polymorphism may play a role in modifying or developing CVD in pediatric ALL survivors.

Effect of cyclic pamidronate administration on osteoporosis in children with ß-thalassemia major: a single-center study.

BACKGROUND: Osteopenia and osteoporosis represent a prominent cause of morbidity in children with thalassemia. Multiple factors are responsible for the pathogenesis of bone loss in thalassemia, including diabetes, hypothyroidism, parathyroid gland dysfunction, accelerated hemopoiesis, direct iron toxicity of osteoblasts, iron chelators, and deficiencies of growth hormone or insulin growth factors. PURPOSE: To assess the effect of pamidronate administration on ß-thalassemia major-induced osteoporosis in children. METHODS: This study assessed the effects of different treatments (calcium and vitamin D versus calcium, vitamin D, and pamidronate) on patients with ß-thalassemia major and osteoporosis. Bone mineral density (BMD) and z scores were measured at baseline and after 1 year of treatment using dual-energy x-ray absorptiometry. RESULTS: The mean baseline BMD values of the lumbar spine were 0.71±0.07 (g/cm²) and 0.74±0.07 (g/cm²), respectively, while those at the end of the study were 0.81±0.07 (g/cm²) (P<0.001) and 0.78±0.07 (g/cm²) (P>0.05), respectively. The mean baseline z scores of the lumbar spine were -3.53±0.55 and -3.17±0.61, while those after treatment were -2.1±0.32 (P=0.001) and -3.11±0.67 (P>0.05), respectively. The baseline alkaline phosphatase levels were 351.5±86.07 µg/dL and 357.6±89.7 µg/dL, while those after treatment were 220.4± 59.26.07 µg/dL (P<0.001) and 320.3±83.99 µg/dL (P>0.05), respectively. CONCLUSION: Pamidronate administration effectively increased the BMD and z scores of children with ß-thalassemia major. Pamidronate had a favorable safety profile with no related serious adverse events during the study period.

Comparing oral iron bisglycinate chelate, lactoferrin, lactoferrin with iron and iron polymaltose complex in the treatment of children with iron deficiency anemia.

OBJECTIVES: Iron amino acid chelates have been developed to be used as food fortificants and therapeutic agents in the treatment of iron deficiency anemia. PURPOSE: To compare the efficacy of Oral iron bisglycinate chelate (FeBC), lactoferrin (LF), lactoferrin with iron and iron polymaltose complex (IPC) in treatment of iron deficiency anemia (IDA). METHODS: a comparative study was conducted on 120 children with IDA, they attended to outpatient clinic at Menoufia University Hospitals within a period from April to November 2019. All subjects were classified into FeBC Group (30 children received iron bisglycinate), LF Group (30 children received lactoferrin 100 mg), LF with iron Group (30 children received 30% iron saturated lactoferrin) and IPC Group (30 children received iron polymaltose complex with elemental iron of6 mg/kg/day). Serum iron, serum ferritin, transferrin saturation was investigated. RESULTS: After treatment serum iron, serum ferritin and transferrin saturation improved in FeBC group than LF group, in LF with iron group than LF group, and in IPC group than LF group. Serum ferritin improved in LF with iron group than IPC group. Side effects of drugs were higher in FeBC group than LF group, and higher in LF with iron group than FeBC group. CONCLUSIONS: Adding lactoferrin to iron helps increasing iron stores more than using iron alone in treatment of iron deficiency anemia. Lactoferrin is less effective than lactoferrin with iron, iron bisglycinate chelate and iron polymaltose complex in treatment of iron deficiency anemia.

The role of recombinant Human erythropoietin in neonatal anemia.

AIM: To estimate the blood level of Erythropoietin(EPO) in neonates with anemia of prematurity (APO) and in late hypo-regenerative anemia and to clarify role of EPO in correction of anemia and reducing the number of blood transfusions. METHODS: This study was carried out on 60 neonates divided into; group I (30 preterm neonates) with AOP received EPO (250 IU/kg/dose subcutaneously 3 times weekly for 4 weeks), compared to group II (30 neonates) with AOP treated only with blood transfusion. CBC parameters and transfusion requirements were followed during therapy. Serum level of EPO was measured by ELISA technique. RESULTS: By the end of the 4th week of therapy, there was significant increase in group I post r-Hu EPO compared to group II regarding reticulocyte counts (P < 0.001) leading to rise of the Hb (P < 0.001), Hct levels (P < 0.001) with subsequent reduction in the overall number of blood transfusions (P < 0.001). CONCLUSION: EPO therapy in conjunction with iron, vitamin E and folic acid, stimulated erythropoiesis and significantly reduced the need for blood transfusion in AOP.

IL-10 polymorphisms and T-cell subsets could affect the clinical presentation and outcome of childhood immune thrombocytopenia in Egyptian population.

The aim is to study IL-10 polymorphisms and IL-10 level and assess their relation to T-cell subsets in childhood immune thrombocytopenia (ITP). In all, 40 (25 acute, 15 chronic) ITP child patients were investigated at time of presentation, compared to 15 healthy, age- and gender-matched controls and followed up for 1 year to determine chronic cases. Studying the effect of IL-10 promoter polymorphism was done by PCR-RFLP, IL-10 level was determined by ELISA, natural killer cells and T-cell subsets were evaluated by flow cytometry. Subjects with IL-10 promoter (1082 AA and 592 AA) genotypes had lower IL-10 levels and had lower CD4%, higher CD8%, lower CD4/CD8 ratio and lower T-reg%. IL-10 polymorphisms had no effect on NK%. IL-10 serum levels and IL-10 promoter polymorphic genotype frequencies are not different between ITP cases and controls; however, in ITP patients, IL-10 promoter (1082 AA and 592 AA) genotypes and associated lower CD4, higher CD8, lower CD4/CD8 ratio is associated with more severe thrombocytopenia at presentation and had a poorer response to first-line treatment. Patients with lower T-reg cells had a higher tendency to develop chronic ITP. IL-10 level and polymorphisms as well as disturbed T-cell subsets percentages are demonstrable effectors of immune dysfunction in ITP and can affect the presentation and outcome of childhood ITP.

Value of Soluble Transferrin Receptors and sTfR/log Ferritin in the Diagnosis of Iron Deficiency Accompanied by Acute Infection.

There are many causes of anemia; the most common of these are acute and chronic infections, iron deficiency, or both. Identifying the cause is a very important step in management of anemia. So, we evaluated the usefulness of soluble transferrin receptor (sTfR) and of the sTfR/log ferritin in the diagnosis of iron deficiency anemia accompanied by acute infection. This study was conducted on 131 children aged 2-11 years old from those who attended the pediatric outpatient clinics in Menoufia university hospital. Hematological indices, iron balance and sTfR were evaluated and the sTfR/log F was calculated for each examined child. From the examined children four groups were distinguished: Group I (control): included 34 healthy children with normal iron status (66.7% males, age 4.2 ± 1.2). Group II (IDA): included 38 children diagnosed as iron deficiency anemia (47.4% males, age 4.9 ± 1.6). Group III (IDA + infection): included 26 children with infectious disease (upper respiratory tract infection, otitis media, pneumonia, stomatitis, and urinary tract infection) and anemia meeting criteria of IDA (50% males, age 4.2 ± 0.7). Group IV (anemia + infection): included 33 children with infectious anemia without iron deficiency (56.2% males, age 5.06 ± 1.4). It was proved that sTfR and sTfR/log Ferritin were significantly higher in children with anemia due to iron deficiency, and in those with infection + iron deficiency, versus those with infectious anemia or in healthy children. The use of sTfR and sTfR/log ferritin improves the diagnosis of IDA in pediatric patients, especially in the presence of coexisting acute infection.

Beneficial effect of melatonin in the treatment of neonatal sepsis.

OBJECTIVE: To study the effect of melatonin as an adjuvant therapy in the treatment of neonatal sepsis. METHODS: This study is a prospective nonrandomized nonblind case-control study and was carried on 40 neonates with neonatal sepsis diagnosed by both clinical and laboratory criteria. They were enrolled from the Neonatal Intensive Care Unit, Menoufia University Hospitals. These cases were selected during the study period from November 2015 to May 2016 and were divided into two groups: intervention group (number 20 neonates) received melatonin 20 mg as single dose and antibiotics and control group (number 20 neonates) received antibiotics only and then both groups followed by physical examination, complete blood count (CBC), and high sensitive C-reactive protein (hs-CRP) to evaluate the improvement in both groups. RESULTS: Before melatonin administration, there was no significant difference between intervention group and control group with regard to clinical condition, hs-CRP, and other serum parameters. After 24 and 72 hours of melatonin administration, both groups improved with regard to clinical condition, hs-CRP, and serum parameters with significant improvement in intervention group than control group. CONCLUSION: Melatonin could be used in the treatment of neonatal sepsis in both preterm and full-term neonates beside the conventional treatment.

Erythroferrone and iron status parameters levels in pediatric patients with iron deficiency anemia.

OBJECTIVES: To investigate the link between serum erythroferrone (ERFE) levels and iron status parameters in pediatric patients with iron deficiency anemia. METHODS: The study consisted of 66 children (36 with iron deficiency anemia and 30 healthy age- and gender-matched controls) who were investigated for serum levels of iron, total iron-binding capacity (TIBC) using automated chemistry analyzer, serum ferritin using electrochemiluminescence immunoassay and ERFE by specific enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Serum erythroferrone levels in iron deficiency anemia patients (191.55 ± 83.74 pg/mL) were significantly higher than those in control group (42.22 ± 16.55 pg/mL) (P < .001). In iron deficiency anemia patients, serum erythroferrone concentrations correlated negatively with hemoglobin concentration (r = -.39; P = .01), serum iron (r = -.63; P < .001), transferrin saturation (r = -.66; P < .001), and serum ferritin (r = -.46; P = .004) while positive correlation was observed between serum erythroferrone concentrations and TIBC (r = .62; P < .001) CONCLUSION: The newly identified erythroferrone hormone may act as physiological hepcidin suppressor in cases with iron deficiency anemia, and so it may serve as a specific promising target of therapy in such cases.

A randomized multicenter study: safety and efficacy of mini-pool intravenous immunoglobulin versus standard immunoglobulin in children aged 1-18 years with immune thrombocytopenia.

BACKGROUND: Because there is a global shortage of intravenous immunoglobulin, there is a need for new products to fill the gap. STUDY DESIGN AND METHODS: This was a multicenter, open-label study investigating the safety and efficacy of a newly developed mini-pool intravenous immunoglobulin G for children with immune thrombocytopenia. Seventy-two patients ages 1 to 18 years with newly diagnosed (<1 month) immune thrombocytopenia who had platelet counts from 5 to 20 × 109 /L with no serious bleeding were recruited from four centers in Egypt. Eligible patients were randomized into three groups 1:1:1. Group A (n = 24) received blood group-specific mini-pool intravenous immunoglobulin in a dose equivalent to immunoglobulin 1 g/kg over 6 to 8 hours, Group B (n = 24) received standard intravenous immunoglobulin (approximately 1g/kg) as a single dose, and Group C (n = 24) did not receive any platelet-enhancing therapy. Parents signed informed consent. RESULTS: Of the patients who received mini-pool intravenous immunoglobulin, 14 achieved a complete response (CR) (58.8%), and four had a response (16.6%). Of the patients who received intravenous immunoglobulin G, 16 achieved a complete response (66.6%), and four had a response (16.6%). In Group C, eight patients achieved a complete response (33.3%), and four had a response (16.6%). The median time to response was 8, 9, and 21 days in Group A, B, and C, respectively, which was significantly higher in Group C than Groups A and B (p < 0.001). Patients in Groups A and B reported 16 adverse drug reactions. CONCLUSION: Mini-pool intravenous immunoglobulin G was well tolerated, presented no safety issues, and was effective in the treatment of immune thrombocytopenia, with efficacy comparable to that of the standard intravenous immunoglobulin G group, and it was significantly more effective than no treatment.

Assessment of Obesity and Hepatic Late Adverse Effects in the Egyptian Survivors of Pediatric Acute Lymphoblastic Leukemia: a Single Center Study.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates reaching 80% emphasizes the necessity to determine treatment-related long-term effects. The aim of this study is to estimate the prevalence of overweight, obesity, and hepatic late adverse effects in a cohort of ALL survivors treated at the Hematology and Oncology Unit, Pediatrics Department, Menoufia University, Egypt. METHODS: In this case-control study, height, weight, and body mass index (BMI) were assessed for 35 pediatric ALL survivors and 35 healthy children. These parameters were plotted on the growth and WHO standard deviation charts for both males and females. Overweight and obesity were defined by BMI > 85th and 95th percentile respectively. Laboratory investigations were done in the form of iron profile, liver enzymes, total and direct bilirubin levels, serum urea &creatinine and detection of hepatitis C virus antibodies by ELISA. RESULTS: The weight and BMI were significantly greater in the survivors than controls (P value =0.002 and 0.039 respectively). ALT, total & direct bilirubin, serum ferritin and transferrin saturation were considerably higher in the survivors than the controls (P value = 0.03, 0.036, 0.044, 0.006 and 0.03 respectively). Ten (28.6%) of survivors had hepatitis C antibodies with none (0%) of controls (P value =0.02). CONCLUSIONS: Pediatric ALL survivors are at increased risk of overweight/obesity, hepatic dysfunction in the form of elevated liver enzymes, bilirubin levels, and C viral hepatitis. Screening of those survivors for such complications should be considered.

Serum Neutrophil Gelatinase-Associated Lipocalin: A Diagnostic Marker in Pediatric Sepsis.

OBJECTIVES: Sepsis is a life-threatening condition that arises when the response of the body to infection injures its own tissues and organs. The early prediction of sepsis by current clinical and laboratory methods remains inadequate. Serum neutrophil gelatinase-associated lipocalin level is increased in sepsis irrespective of renal dysfunction. Therefore, we aimed to correlate the serum neutrophil gelatinase-associated lipocalin value determined at admission with clinical progression and severity of disease in critically ill children and to declare its role as a potential diagnostic and prognostic marker for sepsis in critically ill children in the emergency department. DESIGN: A prospective cohort study. SETTING: The study carried out at the PICU of Menoufia University Hospital. PATIENTS: We serially enrolled 120 critically ill children admitted to the PICU at 2 fixed days per week in addition to 40 healthy children served as controls. INTERVENTIONS: Clinical examination was performed including calculation of the Pediatric Risk of Mortality and Pediatric Index of Mortality 2. Serum neutrophil gelatinase-associated lipocalin measurement was performed for patients at admission and for the controls. Patients were followed up for 30 days. The discriminatory power of neutrophil gelatinase- associated lipocalin was determined using the receiver-operating characteristic and other predictive likelihood values. MEASUREMENTS AND MAIN RESULTS: Serum neutrophil gelatinase-associated lipocalin level was significantly higher among the total patient cohort and those with sepsis than among the controls (p < 0.001), also in patients with systemic inflammatory response syndrome without sepsis and patients without systemic inflammatory response syndrome (p = 0.04 and <0.001). Furthermore, plasma level of neutrophil gelatinase-associated lipocalin was significantly elevated in nonsurvivors compared with survivors (p < 0. 001). Receiver-operating characteristic curve analysis exhibited an area under the curve of 0.84 for neutrophil gelatinase-associated lipocalin for diagnosis of sepsis, whereas C-reactive protein had an area under the curve of 0.79. Regarding the prognosis, neutrophil gelatinase-associated lipocalin had an area under the curve of 0.74 for prediction of mortality, whereas the area under the curve for Pediatric Risk of Mortality, Pediatric Index of Mortality 2, and C-reactive protein were 0.59, 0.58, and 0.62, respectively. CONCLUSION: Overall, the data support the view that measurement at admission, serum neutrophil gelatinase-associated lipocalin results in substantial added value for early diagnosis and prognostication of sepsis in critically sick children.

HFE gene mutation and iron overload in Egyptian pediatric acute lymphoblastic leukemia survivors: a single-center study.

BACKGROUND: Hereditary hemochromatosis gene (HFE) mutations have a role in iron overload in pediatric acute lymphoblastic leukemia (ALL) survivors. We aimed to evaluate the genotype frequency and allelic distribution of the two HFE gene mutations (C282Y and H63D) in a sample of Egyptian pediatric ALL survivors and to detect the impact of these two mutations on their iron profile. PATIENTS AND METHODS: This study was performed on 35 ALL survivors during their follow-up visits to the Hematology and Oncology Unit, Pediatric Department, Menoufia University Hospitals. Thirty-five healthy children of matched age and sex were chosen as controls. After completing treatment course, ALL survivors were screened for the prevalence of these two mutations by polymerase chain reaction-restriction fragment length polymorphism. Serum ferritin levels were measured by an enzyme-linked immunosorbent assay technique (ELISA). RESULTS: C282Y mutation cannot be detected in any of the 35 survivors or the 35 controls. The H63D heterozygous state (CG) was detected in 28.6% of the survivors group and in 20% of controls, while the H63D homozygous (GG) state was detected in 17.1% of survivors. No compound heterozygosity (C282Y/H63D) was detected at both groups with high G allele frequency (31.4%) in survivors more than controls (10%). There were significant higher levels of iron parameters in homozygote survivors than heterozygotes and the controls. CONCLUSION: H63D mutation aggravates the iron overload status in pediatric ALL survivors.

P-Glycoprotein Activity in Steroid-Responsive vs. Steroid-Resistant Nephrotic Syndrome.

OBJECTIVES: To explore the expression of P-glycoprotein (P-gp) in the peripheral blood nucleated cells (PBNCs) of children with nephrotic syndrome in relation to their clinical response to glucocorticoid treatment. METHODS: Thirty-six children with nephrotic syndrome (20 cases of steroid-responsive and 16 cases of steroid-resistant) were examined. All the participants were subjected to complete history taking, thorough clinical examination, laboratory investigations (24-h urinary protein, serum albumin, complete blood count with differential white blood cell count, serum cholesterol, serum urea, serum creatinine) and functional assay of P-gp using FACS Calibur flowcytometry. P-gp assay was done in both groups during remission. RESULTS: P-gp activity was significantly higher in steroid-resistant than steroid-sensitive cases. CONCLUSIONS: P-gp can be used as a predictor of outcome, as a part of laboratory evaluation of the cases before starting steroid therapy, so as to determine whether to use alternative line of therapy or use one of the P-gp inhibitors with steroid therapy.

Effect of Phototherapy on CD4, CD8 and Natural Killer Cells of Full Term Neonates with Indirect Hyperbilirubinemia.

Phototherapy is generally considered a very safe and well-tolerated treatment for hyperbilirubinaemia. However, clinical users should be aware of the unwanted effects of using phototherapy. Affection of neonatal immune system due to phototherapy has been reported. This study aimed to evaluate the effect of phototherapy on level of CD4+, CD8+ and natural killer (NK) (CD16+ & CD65+) lymphocytes subsets in neonates. The number of these lymphocytes was measured 72 hrs after phototherapy exposure in 30 full term neonates with indirect hyperbilirubinemia and compared to those of 25 healthy controls using flow cytometry. Results showed non-significant changes of the tested lymphocyte subsets after 72 hrs exposure to phototherapy. In conclusion, phototherapy has no significant effect on the level of circulating CD4+, CD8+ and NK lymphocytes.