L-carnitine decreases myocardial injury in children undergoing open-heart surgery: A randomized controlled trial.

Myocardial injury in open-heart surgery is related to several factors including ischemia-reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\kg\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group.   Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.   Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients. What is Known: • Myocardial injury in open-heart surgery is related to several factors including ischemia-reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. • L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery. What is New: • L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group. • L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.

Predictive value of red cell distribution width in children with pulmonary arterial hypertension associated with CHD.

BACKGROUND: Pulmonary arterial hypertension, a common consequence of untreated CHD, is associated with a significant morbidity and mortality. Recent researches have demonstrated that patients with clinically severe cardiovascular illnesses, including pulmonary hypertension, have a greater mortality risk when their red cell distribution width is high. This work aimed to assess the predictive value of red cell distribution width in children with pulmonary arterial hypertension-CHD and to correlate red cell distribution width with various clinical and echocardiographic data. SUBJECTS AND METHODS: Sixty patients with CHD associated with pulmonary arterial hypertension were enrolled as the patient group. Another 60 patients with CHD and no pulmonary arterial hypertension, matched for age and sex, were enrolled as the control group. Electrocardiography and echocardiographic evaluation were performed for all included children. Red cell distribution width as part of the complete blood count was also performed using a Coulter® LH 700 series haematology analyzer. RESULTS: The red cell distribution width was significantly higher in the pulmonary arterial hypertension-CHD group than in the CHD-only group (P < 0.05). There was a significant positive correlation between the red cell distribution width and mean pulmonary artery pressure. Red cell distribution width was an independent predictor of mortality in children with pulmonary arterial hypertension-CHD. The best red cell distribution width cut-off for predicting mortality in children with pulmonary arterial hypertension-CHD was ≥ 17.6%. CONCLUSION: Red cell distribution width was significantly higher in children with pulmonary arterial hypertension-CHD than in those without pulmonary arterial hypertension. Moreover, red cell distribution width could be a cheap easy predictive marker for mortality in children with pulmonary arterial hypertension-CHD.

Risk of atrial fibrillation development in adolescent patients with inflammatory bowel disease.

There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). Inflammatory bowel diseases (IBD), namely (Crohn's disease (CD) and ulcerative colitis (UC), are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. Atrial electromechanical delay (EMD) has been known as an early marker of AF. The objective of this study was to evaluate the atrial electromechanical properties in children and adolescents with IBD during remission. One hundred IBD patients aged 12-17 years (50 with CD and 50 with UC) in remission state and 100 healthy controls were recruited for the study. Atrial electromechanical properties were measured using transthoracic echocardiography, tissue Doppler imaging, and simultaneous surface ECG recording. Interatrial EMD, left intra-atrial, and right intra-atrial EMD were calculated. IBD patients in remission state have significantly prolonged left and right intra-atrial EMD and interatrial EMD compared to healthy controls (P = 0.03, P = 0.02, and P = 0.01 respectively). No statistical difference was observed between CD and UC in terms of inter- and intra-atrial EMDs.  Conclusion: Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD. What is Known: • There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). • Inflammatory bowel diseases are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. • Atrial electromechanical delay (EMD) has been reported as an early marker of AF. What is New: • Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. • Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD.

Myocardial function using two dimension speckle-tracking echocardiography in children with celiac disease.

The prevalence of cardiac complications linked to celiac disease (CD) is on expanding. This study aimed to evaluate the cardiac function in children with CD using two dimensional speckle tracking echocardiography (2D-STE) to detect early myocardial dysfunction, if any. This cross-sectional study included 40 children with CD as the patient group and 40 healthy age- and sex-matched children served as the control group. High sensitive troponin T (Hs-troponin T), anti-tissue transglutaminase immunoglobulin A (tTG-IgA), hemoglobin, ferritin, albumin, and vitamin D levels were measured in all participants. Conventional, tissue Doppler imaging (TDI), and 2D-STE were performed for all included children. Conventional echocardiographic parameters showed no significant difference between the two groups. Left ventricular global longitudinal strain (LV GLS) obtained by 2D-STE was substantially lower in children with CD than the control group; however, myocardial performance index (MPI) obtained by TDI was significantly higher in children with CD. Hs-troponin T levels were comparable in both groups. LV GLS was positively correlated with hemoglobin, ferritin, and albumin level, but it was inversely correlated with the duration of the disease and anti tTG-IgA.    Conclusion: 2D-STE can detect subclinical early cardiac dysfunction in children with CD and this cardiac injury correlated to the duration and severity of the disease and some nutritional deficiency in these children. What is Known: • The prevalence of cardiac complications linked to celiac disease (CD) is on expanding. • Only one study evaluated cardiac function in children with CD using two dimensional speckle tracking echocardiography (2D-STE). What is New: • Our study found that 2D-STE can detect early subclinical cardiac dysfunction in children with CD. Cardiac injury in theses children correlated to the duration and severity of the disease, hemglobin, ferritin, and albumin levels.

Lipid profile after omega-3 supplementation in neonates with intrauterine growth retardation: a randomized controlled trial.

BACKGROUND: Neonates with intrauterine growth restriction (IUGR) have a high lipid profile that predisposes them to cardiovascular disease later in life. We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR. METHODS: This clinical trial was conducted on 70 full-term neonates with IUGR. Neonates were randomly divided into two equal groups; the treatment group: received omega 3 supplement (40 mg/kg/day) for 2 weeks after the establishment of full feeding, and the control group, who were followed up to full feeding without any supplementation. Serum leptin level, total cholesterol (TC), high-density lipoprotein (HDL), triglycerides (TG), low-density lipoprotein (LDL), and anthropometric measurement were evaluated at admission and after 2 weeks of omega 3 supplementation in both groups. RESULTS: After treatment, HDL significantly increased, unlike TC, TG, LDL, LDL, and serum leptin levels, which significantly decreased in the treatment group compared to the control group after treatment. Interestingly, weight, length, and ponderal index greatly increased in omega 3-treated neonates compared to the control group. CONCLUSION: Omega 3 supplementations lowered serum leptin level, TG, TC, LDL, and VLDL but increased HDL and growth in neonates with IUGR. CLINICAL TRIAL REGISTRATION: The study was registered at clinicaltrials.gov (NCT05242107). IMPACT: Neonates with intrauterine growth retardation (IUGR) were reported to have a high lipid profile that predisposes them to cardiovascular disease later in life. Leptin is a hormone that adjusts dietary intake and body mass and has a significant role in fetal development. Omega 3 is known to be essential for neonatal growth and brain development. We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR. We found that omega 3 supplementations lowered serum leptin level and serum lipid profile but increased high density lipoprotein and growth in neonates with IUGR.

Baseline characteristics and analysis of predictors of the Outcome of septic pulmonary embolism in children: a retrospective observational study.

BACKGROUND: Septic pulmonary embolism is a rare disease in children. We aimed to assess the clinical, microbiological, and radiological characteristics and outcomes of pediatric septic pulmonary embolism (SPE) and to identify any predictive factors for in-hospital mortality in patients with this unusual disease to enhance prognosis and treatment. METHODS: A retrospective study to search the electronic medical records of children admitted to the pediatric pulmonology unit, Tanta University hospital with the diagnosis of SPE between January 2015 and June 2022. RESULTS: Seventeen pediatric patients were identified; ten males and seven females with a mean age of 9.4 ± 5.2 years. The most common presenting complaints were fever and shortness of breath (n = 17) followed by chest pain (n = 9), pallor (n = 5), limb swelling (n = 4), and back pain (n = 1). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common causative pathogen in nine patients. The most common extra-pulmonary septic foci were septic arthritis in five patients (29.4%), septic thrombophlebitis in four patients (23.5%), and infective endocarditis in two patients (11.8%). All patients exhibited wedge-shaped peripheral lesions and feeding vessel sign in CT chest, whereas bilateral diffuse lesions, nodular lesions, and cavitation were present in 94.1% of patients, pleural effusion was identified in 58.8% of patients, and pneumothorax was detected in 41.2% of patients. Fifteen patients improved and survived (88.2%), while two patients died (11.8%). CONCLUSION: Early diagnosis of SPE with vigorous early therapy is critical for a better outcome, including appropriate antibiotics and timely surgical interference to eradicate extra-pulmonary septic foci.

Citicoline in hypoxic ischemic encephalopathy in neonates: a randomized controlled trial.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the major complications that can lead to death or disability in neonates. We assessed the effect of citicoline as a neuroprotector in neonates with moderate and severe HIE. METHODS: This clinical trial was carried on 80 neonates with moderate to severe HIE who were not candidates for therapeutic cooling. They were subdivided randomly into two groups; citicoline treatment group which included 40 neonates who received citicoline 10 mg / kg /12 h IV for 4 weeks plus other supportive measures and the control group which included 40 neonates who were managed with placebo and the same supportive measures. All patients were evaluated for duration of mechanical ventilation (MV), need for inotropes, seizures (type, frequency, and duration), and duration of NICU. Cranial ultrasounds and brain magnetic resonance image (MRI) were performed for all included neonates after 4 weeks of treatment. Follow- ups of all neonates for the neurodevelopmental outcomes were done at 3, 6, 9, and 12 months. RESULTS: There was a significant reduction in the number of neonates having seizures after discharge in the citicoline-treated group (2 neonates) compared to the control group (11 neonates). Cranial ultrasound and MRI findings at 4 weeks were significantly better in the treatment group compared to the control group. Moreover, neurodevelopmental outcome showed significant improvement at 9 and 12 months in the citicoline treated neonates compared to the control group. There was statistically significant reduction in the duration of seizures, NICU stay, inotrope use, and MV in the treatment group compared to the control group. Citicoline was well tolerated with no remarkable side effects. CONCLUSION: Citicoline could be a promising neuroprotector drug in neonates with HIE. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT03949049). Registered at 14 May 2019, https://clinicaltrials.gov/ct2/show/NCT03949049.

Serum-soluble suppression of tumourigenicity-2 as a biomarker in children with congestive heart failure.

BACKGROUND: We aimed to evaluate serum soluble suppression of tumorigenicity-2 in children with congestive heart failure, to assess the diagnostic and prognostic values of soluble suppression of tumorigenicity-2 in these patients, and to correlate its levels with various clinical and echocardiographic data. METHODS: We included 60 children with congestive heart failure as the patient group. Sixty healthy children of matched age and sex served as the control group. Patients were evaluated clinically and by echocardiography. Serum level of suppression of tumorigenicity-2 was measured for patients at admission. All patients were followed up for death or readmission for a period of one year. RESULTS: Soluble suppression of tumorigenicity-2 was significantly higher in children with congestive heart failure as compared to the control group. Soluble suppression of tumorigenicity-2 was significantly increased in patients with higher severity of congestive heart failure. There was a significant increase in soluble suppression of tumorigenicity-2 in patients with bad prognosis compared to those with good prognosis. There was a significant positive correlation between soluble suppression of tumorigenicity-2 and respiratory rate, heart rate, and clinical stage of congenital heart failure, while there was a significant negative correlation between soluble suppression of tumorigenicity-2 and left ventricular systolic and diastolic function. The best cut-off of soluble suppression of tumorigenicity-2 to diagnose congestive heart failure was > 3.6 with 87% sensitivity and 79% specificity. The cut-off point of soluble suppression of tumorigenicity-2 to diagnose congestive heart failure in children was ≥ 31.56 ng/ml, with 95% sensitivity and 91.37% specificity. Moreover, the cut-off point of soluble suppression of tumorigenicity-2 to predict bad prognosis in children with congestive heart failure was ≥ 255.5 ng/ml, with 92% sensitivity and 89.0% specificity. CONCLUSION: Soluble suppression of tumorigenicity-2 is a good diagnostic and predictive biomarker in children with congestive heart failure.

Neutrophil-to-lymphocyte ratio as a predictive and prognostic marker in children with dilated cardiomyopathy.

OBJECTIVES: We aimed to evaluate neutrophil-to-lymphocyte ratio in children with acute heart failure due to dilated cardiomyopathy, to assess the predictive and prognostic values of neutrophil-to-lymphocyte ratio, and to correlate its levels with brain natriuretic peptide and other various data in these patients. METHOD: We included 50 children with acute heart failure due to dilated cardiomyopathy as the patient group. Fifty healthy children of matched age and sex served as the control group. Patients were evaluated clinically and by echocardiography. A complete blood count with differentiation to evaluate neutrophil-to-lymphocyte ratio was done, and the serum level of brain natriuretic peptide was also measured. All patients were followed up for death or readmission for a period of one year. RESULTS: Neutrophil-to-lymphocyte ratio was significantly higher in patient group as compared to the control group. Neutrophil-to-lymphocyte ratio was significantly increased in patients with higher severity of heart failure. There was a significant increase in neutrophil-to-lymphocyte ratio in patients with bad prognoses compared to those with good prognoses. There was a significant positive correlation between neutrophil-to-lymphocyte ratio and both brain natriuretic peptide and clinical stage of heart failure while there was a significant negative correlation between neutrophil-to-lymphocyte ratio and left ventricular systolic function. The best cut-off of neutrophil-to-lymphocyte ratio to predict adverse outcomes in children with dilated cardiomyopathy was >3.6 with 87% sensitivity and 79% specificity. The cut-off of neutrophil-to-lymphocyte ratio to predict patients who will not respond to conventional treatment was ≥3.85 with 85% sensitivity and 100% specificity. CONCLUSION: Neutrophil-to-lymphocyte ratio is a cheap good predictive and prognostic biomarker in children with dilated cardiomyopathy.

lncRNA GAS5 and RUNX1 Genes in Children With Primary Immune Thrombocytopenia.

We aimed to evaluate the expression levels and the prognostic value of growth arrest specific 5 (GAS5) and runt-related transcription factor 1 (RUNX1) genes in children with ITP. This prospective cohort study included 100 patients with newly diagnosed ITP (patient group) and 100 healthy children of matched age and sex (control group). We evaluated the expression levels of both GAS5 and RUNX1 genes at the time of diagnosis before the introduction of treatment. GAS5 was under-expressed, while RUNX1 was over-expressed among the newly diagnosed ITP children compared with the control group. Patients with GAS5 levels >0.50 had a significantly faster recovery compared with patients with levels≤0.50 while patients with levels of RUNX1≤2.6 had a significantly faster recovery compared with patients with levels >2.6. The best cut-off values of GAS5 and RUNX1 to predict complete recovery of ITP were ˃0.40 and ˂3.18, respectively, yielding a sensitivity of 76.47% and 79.41%, respectively. The best cut-off values of GAS5 and RUNX1 expression that predict chronic ITP were ˂0.17 and ˃4.1, respectively, yielding sensitivity of 88.89% and 77.78%, respectively. GAS5 and RUNX1 could be useful markers in children with primary ITP to predict disease course.

Acute lymphoblastic leukemia in children and SALL4 and BMI-1 gene expression.

BACKGROUND: Sal-like protein 4 transcription factor (SALL4) and B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene were reported to cause treatment failure and relapse in several malignancies. We aimed to evaluate the prognostic value of SALL4 and BMI-1 in children with acute lymphoblastic leukemia (ALL). METHODS: This prospective cohort study was carried out on 60 children with ALL as the patient group and 60 age- and sex-matched children as the control group. We evaluated the expression pattern of both SALL4 and BMI-1 genes in the peripheral blood using real-time reverse transcriptase-polymerase chain reaction in children with ALL at initial diagnosis before chemotherapy. We followed up with the patient group for 2 years for relapse or death. RESULTS: Both SALL4 and BMI-1 were overexpressed in ALL children compared to the control group. Moreover, the expression of SALL4 and BMI-1 in patients with relapse was significantly higher than those with complete remission. The best cut-off of SALL4 and BMI-1 to predict relapse were >2.21 and 0.55 yielding sensitivity of 92.3% and 84.6%, respectively. Patients with overexpression of SALL4 and BMI-1 had significantly shorter overall and disease-free survival. CONCLUSIONS: SALL4 and BMI-1 could be useful prognostic markers in children with ALL to predict relapse.

Effects of adherence to the Mediterranean diet in children and adolescents with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder in children and adults, which increased over the past twenty years. The Mediterranean diet is a well-known diet full of antioxidants and anti-inflammatory ingredients. AIM: To evaluate the safety, tolerability, and effects of adherence to the Mediterranean diet on disease patterns in children and adolescents with IBS. METHODS: This prospective, cross-sectional case-controlled study included 100 consecutive IBS patients diagnosed according to Rome IV criteria, aged 12-18 years. Patients were subdivided into two groups (50 patients each); Group I received a Mediterranean diet, and Group II on their regular diet for six months. Besides IBS scores (IBS-SSS, IBS-QoL, and total score), different clinical and laboratory parameters were evaluated at the start and end of the study. RESULTS: The Mediterranean diet was safe and well-tolerated in IBS patients. IBS children and adolescents with good adherence to the Mediterranean diet (KIDMED Score ≥ 8 points); group I showed significant improvement in IBS scores. IBS-SSS in the Mediterranean diet group was 237.2 ± 65 at the beginning of the study and decreased to 163.2 ± 33.8 at the end of the study (P < 0.001). It did not show a significant improvement in the group with a regular diet (248.3 ± 71.1 at the beginning of the study compared to 228.5 ± 54.3 at the study end with P < 0.05). The mean IBS-SSS in the Mediterranean diet group significantly improved compared with the group with a regular diet. Mean IBS-QoL in group I improved from 57.3 ± 12.9 at the start of the study to 72.4 ± 11.2 at the study end (P < 0.001) and significantly improved when compared to its level in group II at the study end (59.2 ± 12.7 with P < 0.001), while group II showed no significant improvement in IBS-QoL at the study end when compared to the beginning of the study (59.2 ± 11.7 with P >0.05). The mean total IBS score in group I became 28.8 ± 11.2 at the end of our study compared to 24.1 ± 10.4 at the start (P < 0.05) and significantly improved when compared to its level in group II at the end of the study (22.1 ± 12.5 with P < 0.05), while in group II, non-significant improvement in the total score at the end of our study compared to its mean level at the start of the study (22.8 ± 13.5 with P > 0.05). CONCLUSION: The Mediterranean diet was safe and associated with significant improvement in IBS scores in children and adolescent patients with IBS.

Study of Serum Ferritin, Zinc, and Copper Levels in Children With Helicobacter pylori Gastritis and the Effect of the Treatment.

OBJECTIVES: This study aimed to assess serum iron, zinc, and copper in symptomatic children with Helicobacter pylori infection, to correlate their serum levels with the degree of gastritis, and to evaluate the effect of H. pylori treatment on their levels. METHODS: This study was carried out on 70 children with upper gastrointestinal tract symptoms. H. pylori infection was diagnosed by the H. pylori antigen test in the stool and histopathologic findings during upper gastrointestinal endoscopy. Patients were divided into 2 groups; H. pylori -positive and H. pylori -negative groups. Hemoglobin, serum ferritin, transferrin (sTfR), zinc, and copper were assessed in all included children. RESULTS: The hemoglobin level, serum ferritin, and zinc were significantly lower in H. pylori -positive patients compared to H. pylori -negative patients. However, the serum copper level was comparable between the 2 groups. After treatment, the hemoglobin level, serum ferritin, and serum zinc significantly increased in H. pylori -positive patients, especially in those who responded to treatment compared to their levels before treatment. There was a significant negative correlation between the severity of histopathologic abnormalities and hemoglobin level, serum ferritin, and zinc levels, but a significant positive relation with sTfR concentrations in H. pylori -positive patients. CONCLUSIONS: H. pylori -infected children had low serum ferritin and zinc levels but high sTfR level with no effect on serum copper levels. After treatment, hemoglobin, serum ferritin, and zinc levels significantly improved in H. pylori -positive patients. Gastric histologic findings correlated significantly with hemoglobin, serum ferritin, zinc, and sTfR levels.

Lactoferrin for iron-deficiency anemia in children with inflammatory bowel disease: a clinical trial.

BACKGROUND: Iron-deficiency anemia (IDA) is common in children with inflammatory bowel disease (IBD); however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. We compared the effect of lactoferrin versus oral ferrous sulfate for the treatment of IDA in children with IBD. METHODS: Ninety-two IBD children with IDA were included but only 80 children completed the study and they were randomized into two groups: ferrous sulfate group (n = 40) who received ferrous sulfate 6 mg/kg/day for 3 months and lactoferrin group (n = 40) who received lactoferrin 100 mg/day for 3 months. Complete blood count, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TS), serum ferritin, interleukin-6 (IL-6), and hepcidin 25 were measured before and after the treatment. RESULTS: Hemoglobin (Hb), mean corpuscular volume, serum iron, TS, and serum ferritin significantly increased, while TIBC decreased significantly after the administration of either ferrous sulfate or lactoferrin compared to their baseline data. In addition, lactoferrin significantly increased Hb, serum iron, TS, and serum ferritin compared to ferrous sulfate. Moreover, lactoferrin significantly decreased IL-6 and hepcidin levels. CONCLUSION: Lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA. CLINICAL TRIAL REGISTRATION: The study was registered at www.pactr.org (PACTR202002763901803). IMPACT: Iron-deficiency anemia (IDA) in children with inflammatory bowel disease (IBD) is treated with oral iron therapy; however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. To the best of our knowledge, our study was the first in pediatrics that compared the effect of lactoferrin versus oral ferrous sulfate as an iron supplement for the treatment of IDA in children with IBD. We found that lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA.

Predictive Value of Plasma Copeptin Level in Children with Acute Heart Failure.

We investigated the ability of copeptin level to predict adverse outcome in pediatric heart failure (HF) and correlated copeptin level with various clinical and echocardiographic data. This cohort study was carried out on forty children with clinical picture of acute HF as the patient group and forty healthy children of matched age and sex as the control group. Echocardiographic examination and plasma copeptin level were performed for all included children at admission. Patients were followed up for 6 months for mortality or readmission. Plasma copeptin level was significantly higher in the patient group (16.2 ± 5) pmol/L compared to the control group (4.1 ± 2.3) pmol/L, P ˂0.001. Moreover, copeptin level was positively correlated with Ross classification, being the highest in patients with class IV (19.6 ± 3.9) pmol/L compared to those with class III (15.2 ± 4) pmol/L and class II (10.4 ± 1.5) pmol/L. Copeptin levels were significantly higher in patients with bad prognosis (21.2 ± 4.1) pmol/L compared to those with good prognosis (14.5 ± 4.1) pmol/L, P ˂0.001. Copeptin level had a significant positive correlation with age, heart rate, respiratory rate, and ROSS classification. On the contrary, copeptin level had a significant negative correlation with left ventricular fraction shortening and diastolic function. Copeptin at cut-off value of ≥ 19.5 pmol/L yielded a sensitivity of 75% and a specificity of 93% to predict adverse outcome in children with HF. Plasma copeptin level has a good prognostic value to predict adverse outcome in pediatric heart failure. Moreover, copeptin correlate well with the severity of pediatric HF.

Insulin resistance, leptin and adiponectin in lean and hypothyroid children and adolescents with obesity.

BACKGROUND: Obesity usually complicates hypothyroidism. Adipokines like leptin and adiponectin secreted by adipose tissue modulate insulin resistance (IR), appetite, and obesity. The association between adipokines, IR, and thyroid hormone has not been sufficiently studied in children. We investigated leptin and adiponectin as well as IR and their association with thyroid hormone in both lean and hypothyroid children and adolescents with obesity. METHODS: The study included 30 lean hypothyroid, 30 hypothyroid children and adolescents with obesity, and 30 healthy lean children as the control group. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), fasting blood glucose, fasting insulin, homeostatic model assessment method of insulin resistance (HOMA-IR), leptin, and adiponectin levels were estimated in all participants. RESULTS: Fasting insulin, HOMA-IR, and leptin levels were significantly elevated in hypothyroid children compared to the control group; more in hypothyroid children with obesity. In contrast, adiponectin levels were significantly lower in the hypothyroid children with obesity compared to the lean hypothyroid children and controls. HOMA-IR was positively correlated to TSH and BMI but inversely correlated with fT3 and fT4 in hypothyroid children. There was no correlation between IR and either leptin or adiponectin levels. Leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity. CONCLUSION: Insulin resistance and leptin levels are increased in hypothyroid children and adolescents; more in those with obesity. IR is not related to leptin and adiponectin levels, however, leptin and adiponectin levels correlate well with BMI in hypothyroid children and adolescents with obesity. IMPACT: Insulin resistance (IR) and leptin levels increase in hypothyroid children and adolescent; more with obesity. IR is not related to leptin and adiponectin levels, however leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity.

Adherence to the Mediterranean Diet Improved Clinical Scores and Inflammatory Markers in Children with Active Inflammatory Bowel Disease: A Randomized Trial.

Objective: The Mediterranean diet (MD) is a well-known style of diet that is full of antioxidants and may have anti-inflammatory effects. We evaluated the safety, tolerability, and effects of adherence to MD on disease activity and inflammatory markers in children and adolescents with active inflammatory bowel disease (IBD). Methods: This prospective, randomized study included 100 IBD patients aged twelve to eighteen years with mild to moderate disease activity (PCDAI score 10-45 or PUCAI 10-64). The included patients were divided into two groups of 50 patients each. Group I (26 patients with active CD and 24 patients with active UC) received MD with good adherence over 12 weeks with a KIDMED 8-point score, and group II (28 patients with active CD and 22 patients with active UC) received their usual diet with a KIDMED score ≤7 points. Patients in both groups received treatment similar for IBD activity. Results: Clinical remission was achieved in most of the patients after 12 weeks of treatment. Patients in the first group (adhering to an MD) showed a significant decrease in both clinical scores (PCDAI and PUCAI) and most inflammatory markers (CRP, calprotectin, TNF-α, IL17., IL 12 and IL13) compared to patients in their normal group, with earlier improvement in both PCDAI and CRP. Conclusion: Adherence to the MD improves clinical scores and inflammatory markers in children and adolescents with mild-moderate active IBD.

Platelet Activation Markers in Children with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease.

The study aimed to evaluate mean platelet volume (MPV), platelet distribution width (PDW), and platecrit in children with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), to assess the predictive value of these platelet activation markers for adverse outcomes, and to correlate their levels with various data in these patients. This prospective cohort study included 60 children with PAH-CHD as group I and 60 children with CHD and no PAH as group II. Another 60 healthy children of matched age and sex served as the control group. All included children were evaluated by echocardiography. MPV, PDW, and platecrit were also measured using an automated blood counter. All patients were followed up for death or readmission for 6 months. MPV, PDW, and platecrit were significantly higher in group I compared to group II and the control group and they correlated well with increasing severity of PAH. MPV, PDW, and platecrit positively correlated with right ventricular diameter and mean pulmonary artery pressure, however they correlated negatively with right ventricular systolic and diastolic function. The best cut-off of platelet activation markers levels to predict poor prognosis in group I was > 11.2 FL with 75% sensitivity and 96.6% specificity for MPV, > 12.7 FL with 75% sensitivity and 61.5% specificity for PDW, and > 0.505% with 75% sensitivity and 93.2% specificity for platecrit. MPV, PDW, and platecrit were elevated in children with PAH-CHD and found to be good predictive markers for poor prognosis in these children.

BAFF rs9514828 gene polymorphism and the risk of the development of inhibitors in children with severe haemophilia A.

INTRODUCTION: Haemophilia A (HA) is an x-linked recessive disease due to deficiency of coagulation factor VIII (FVIII). The development of neutralizing antibodies (inhibitors) against infused FVIII is a major concern. B cell activating factor (BAFF) has been implicated in several autoimmune diseases. AIM: We aimed to evaluate the possible association of BAFF rs9514828 gene polymorphism and the risk of the development of FVIII inhibitor in children with severe HA. METHODS: This cohort study was carried out on 100 newly diagnosed boys with severe HA who were never treated before with FVIII concentrate. Assessment of serum levels of BAFF and BAFF rs9514828 genotyping at first diagnosis was performed and the patients were followed up for the completion of a total of 50 exposure days or the development of inhibitors whichever occurred first. The patients were divided as positive or negative according to the presence or absence of inhibitors. RESULTS: The risk allele for BAFF rs9514828 (T) was significantly more frequent in the inhibitor positive patients than the inhibitor negative patients (P = .003). In addition, CT+TT genotypes were associated with increased risk of FVIII inhibitor development. Receiver operating characteristics (ROC) analysis showed that BAFF levels could predict the development of FVIII inhibitors at a cut-off value of ≥ .92 with a sensitivity of 85.9% and a specificity of 80.2%. CONCLUSION: BAFF rs9514828 gene polymorphism could be independent risk factor and elevated BAFF levels might be useful prognostic marker for the development of FVIII inhibitor in newly diagnosed children with severe HA.

Vitamin D and nonalcoholic fatty liver disease in children: a randomized controlled clinical trial.

Vitamin D is reported to have anti-inflammatory and insulin-sensitizing effects, yet vitamin D effects on hepatic fat content in children with nonalcoholic fatty liver disease (NAFLD) are not studied sufficiently. We aimed to evaluate the role of vitamin D supplementation on the hepatic fat content and NAFLD progression in children. This randomized controlled clinical trial was performed on 109 children with biopsy-proven NAFLD; only 100 patients completed the study. Patients were randomly assigned into two groups: the treatment group who received 2000 IU/day vitamin D for 6 months and the control group who received a placebo. Anthropometric measurements, vitamin D levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting blood glucose (FBG), fasting blood insulin level (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), and serum calcium level were measured at the beginning and the end of the study. Liver biopsy was taken before and at the end of the study for all included children. There was a significant improvement of the hepatic steatosis and lobular inflammation by liver biopsy in the treatment group after treatment. However, there was no significant effect on the hepatocyte ballooning or hepatic fibrosis. There were significant decrease of AST, ALT, TG, LDL, FBG, FBI, and HOMA-IR and significant increase of vitamin D levels and HDL in the treatment group compared to the placebo group (P < 0.05).Conclusion: Vitamin D supplementation was found to be beneficial in the treatment of NAFLD in children.Trial registration: www.pactr.org , PACTR201710002634203. What is Known: • Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in pediatrics. • Several studies reported a negative association between low serum vitamin D level and grades of NAFLD. What is New: • Vitamin D supplementation has significantly decreased hepatic steatosis and lobular inflammation and improved the grades of NAFLD in children, confirmed by liver biopsy, but no effect on hepatocyte ballooning or fibrosis was observed. • Adjuvant vitamin D supplementation is recommended in children with NAFLD.