Correlation of Asymmetric Dimethyl Arginine Level to Sickle Retinopathy in Children With Sickle Cell Disease.

Asymmetric dimethyl arginine (ADMA) is a competitive inhibitor of nitric oxide synthetase especially in L-arginine deficiency, which is the case in sickle cell disease (SCD). we aimed to assess the level of ADMA in children with sickle retinopathy and to correlate it to the degree of retinopathy. In this cross-sectional study 40 children with SCD were included, 20 of them with sickle cell retinopathy (SCR) (group I), 20 with normal fundus examination (group II), and another 20 healthy children served as controls (group III). We measured ADMA level by ELISA and performed fundus examination. Seventeen of the 20 children included in group I had Grade I retinopathy (85%), 2 children had Grade II retinopathy (10%), and 1 child had Grade III retinopathy (5%). ADMA was significantly higher in SCD than controls ( P -value <0.001), and it was even higher in patients with SCR compared those without retinopathy ( P -value <0.002), and there was positive linear correlation between ADMA and the grade of retinopathy. The type of retinopathy detect in the studied patients was the nonproliferative type. In conclusion, ADMA is elevated in children with SCD, and its level is even higher in those who develop SCR.

Prognostic value of detection of CD99+ , CD45- cells in peripheral blood by flow cytometry in children with Ewing sarcoma.

BACKGROUND: Early detection of metastasis and recurrence of Ewing sarcoma (ES) is important for early management. This work aimed to detect CD99+ , CD45- cells in peripheral blood by flow cytometry (FC) before and during chemotherapy and evaluate their prognostic significance. PROCEDURE: This prospective cohort study was carried out on 60 children newly diagnosed with ES at Children Cancer Hospital-Egypt 57357 and 40 healthy children control group. Detection of CD99+ , CD45- cells in peripheral blood was accomplished by FC at baseline before treatment and after five cycles of chemotherapy. Samples were classified as positive if they had more than the upper limit of cells observed in the control cases. Correlation between FC results and relapse and overall survival (OS) after one year was performed. RESULTS: Median percentage of CD99+ , CD45- cells was significantly increased in patients compared with controls (0.002% vs 0%, respectively, P < 0.001). Post-cycle 5 CD99+ , CD45- cells were increased in 12 patients, of them 11 patients' disease had either relapsed or progressed. Post-cycle 5 CD99+ ; CD45- cells had a 73.3% sensitivity and 97.8% specificity for predicting relapse or progression, whereas baseline only had 6.7% sensitivity and 77.8% specificity. The hazard ratio for mortality in the post-cycle 5 positive group was 18.4 [95% confidence interval (1.86 to 181.46)] times that of the negative group. One year OS was 91.67%. CONCLUSION: Post-cycle 5 CD99+ , CD45- cells in peripheral blood by FC is a strong predictor for relapse, progression, and mortality whereas baseline is a poor predictor in newly diagnosed patients with ES.

Assessment of plasmablast cells in immune thrombocytopenic purpura in children.

Primary immune thrombocytopenic purpura (ITP) is an autoimmune disorder with platelet destruction due to B- and T-cell dysregulation and antiplatelet autoantibodies production. Flow cytometry can be used to further characterize the B- and T-cell compartments involved in platelet destruction. This case-control study was to enumerate plasmablast cells in pediatric ITP patients and to correlate their levels with disease course. This study included 30 ITP patients and 10 controls. Identification and enumeration of Plasmablast were done by multicolor flow cytometry using specific antibody panels (CD19, CD27 & CD38) and sequential gating using FACSCanto flow cytometer and FlowJo software. We found that lymphocytes subpopulation in ITP patients and controls revealed increase in frequency of CD19 (B lymphocytes) in acute, persistent, and chronic ITP patients in comparison with controls (p < 0.001, 0.023, 0.001) respectively. Plasmablast cells could play a role in the pathogenesis of ITP and might guide therapy in ITP patients in the future.

Intracranial hemorrhage in primary immune thrombocytopenia (ITP): 20 years' experience in pediatrics.

Incidence of intracranial hemorrhage (ICH) among children with primary immune thrombocytopenia (ITP) varies among different studies. We published data during the period of 1997-2007 of ICH in children with primary ITP, addressing risk factors and outcome. The aim of this study is to assess changes in incidence, risk factors, and outcome of ICH in children with ITP from last decade and to report the overall 20 years' experience. We compared 2008-2018 with the decade before it. Data of children with ITP and ICH during study period and ITP control cases were analyzed. Neurosurgical intervention and outcome were also reported. A total of 4340 children with primary ITP were evaluated. Twenty-five (0.63%) ICH events were reported over 2 decades. Head trauma, hematuria, and platelet counts < 10 × 109/L were the risk factors mostly associated with ICH. Overall mortality was 24%, and a further 28% had neurologic sequelae. Neurosurgical intervention was done in 12% of cases with good outcome.Conclusion: Persistent platelet counts < 10 × 109/L were a significant risk factor for ICH in both time periods, while head trauma and hematuria were more reported in the period of 2008-2018 as significant risk factors for ICH. Outcome was comparable in both periods. What is Known: • ICH is a rare complication of ITP; however, early recognition of risk factors and aggressive treatment might lead to complete recovery without sequalae. Platelet counts less than < 10 × 109/L are the main risk factor for ICH. Few studies reported other significant risk factors. What is New: • Hematuria and head trauma are significant risk factors for ICH in ITP, in addition to having a persistently low platelet count < 10 × 109/L. (more than 90 days in chronic ITP, 45 days in persistent and 21 days in acute ITP) • Combined treatment with IVIG and HDMP followed by platelet transfusion was associated with complete recovery without sequelae in almost 50% of patients.

Premature atherosclerosis in children with beta-thalassemia major: New diagnostic marker.

BACKGROUND: Early vascular alteration, atherosclerosis and coronary artery disease have emerged as important cardiovascular complications among beta-thalassemia major (B-TM) patients. The aims of the current study were to assess the prevalence of premature atherosclerosis among our B-TM patients, and to investigate the diagnostic value of serum Osteoprotegerin assay as an early biomarker for atherosclerosis. METHODS: This cross-sectional study was conducted at Hematology unit - Pediatric Department, Zagazig University Children Hospital- Egypt in the period from March 2014 to March 2015. A total of 115 children were enrolled in the current study; as sixty-five (65) children with beta thalassemia major aged 5-18 years, on regular blood transfusion regimen represented the patient group. While fifty (50) healthy children, with comparable age and gender, were assigned as control group. All participants were subjected to history taking, thorough clinical examination and laboratory investigations including; complete blood count, liver and kidney function tests, C- reactive protein, lipid profile, serum ferritin and serum Osteoprotegerin (OPG) assay. Also, carotid artery intima media thickness (CAIMT) was performed by duplex ultrasound for patients and controls. RESULTS: Our B-TM patients were transfusion-dependent for as long as 8.5 ± 3.8 years with significantly higher serum ferritin levels (2490 ± 1579 ng/dl vs 83 ± 32 ng/dl, p = 0.001), C-reactive protein (5.7 ± 5.7 vs 0.9 ± 0.9), liver enzymes and bilirubin when compared to controls. Significantly higher serum triglyceride (128 ± 20 vs 101 ± 7 mg/dL, p = 0.009) and atherogenic index of plasma (0.45 ± 0.12 vs 0.22 ± 0.04, p = 0.001) were recorded in patients than comparisons. On the contrary, total serum cholesterol (116 ± 16 vs 143 ± 5, p < 0.001), low density lipoprotein-cholesterol (LDL-C) (44 ± 9 vs 73 ± 6, p < 0.001) and high density lipoprotein cholesterol (HDL-C) (39 ± 2 vs 61 ± 5, p < 0.001), were significantly lowered in patients versus normal peers. Carotid arteries intima media thickness (CAIMT) of both side were significantly increased for patients (Rt 0.62 ± 0.2 vs. 0.29 ± 0.07 mm, p = 0.001 & Lt 0.66 ± 0.17 vs 0.29 ± 0.05 mm, p = 0.001) when compared with healthy controls, and showed positive correlation with, serum triglyceride, atherogenic index of plasma, and serum Osteoprotegerin levels. ELISA assay of serum Osteoprotegerin (OPG) revealed significantly higher levels for thalassemia patients than matched healthy controls (427 ± 102 vs. 324 ± 126 pg/ml, p = 0.02). Of particular interest is the obvious positive correlation between OPG levels and CAIMT of both sides (Rt r 0.54, p = 0.001 &Lt r 0.479, p = 0.001) and also with serum triglycerides (r 0.374, p = 0.03). CONCLUSIONS: Subclinical atherosclerosis started prematurely in children with beta- thalassemia. Carotid artery intima media thickness represented a simple, accurate and non-invasivemodality for early detection ofatherosclerosis. It was correlated well with serum Osteoprotegerin; this finding highlighted the possible validity of OPG assay as an early predictor of atherosclerosis in thalassemia children.