Amira A.M. Adly

Early predictors of myocardial disease in children and adolescents with type 1 diabetes mellitus

Background: The spectrum of diabetic heart disease involves a progression from normal heart to preclinical left ventricular diastolic and systolic dysfunction followed by overt echocardiographic evidence of left ventricular (LV) dysfunction and finally symptomatic heart failure.

Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis

OBJECTIVE Triggering receptor expressed on myeloid cells-1 (TREM-1) is an important receptor involved in the innate inflammatory response and sepsis. We assessed soluble TREM-1 (sTREM-1) in 112 septic neonates (63 culture-positive and 49 culture-negative) and 40 healthy controls as a potential early diagnostic and prognostic marker for neonatal sepsis (NS). METHODS Studied neonates were evaluated for early- or late-onset sepsis using clinical and laboratory indicators upon admission. sTREM-1 was measured on initial sepsis evaluation and at 48h after antibiotic therapy. For ethical reasons, cord blood samples were collected from control neonates and only samples from neonates that proved to be healthy by clinical examination and laboratory analysis were further analyzed for sTREM-1. RESULTS Baseline sTREM-1 levels were significantly elevated in culture-proven (1461.1±523pg/mL) and culture-negative sepsis (1194±485pg/mL) compared to controls (162.2±61pg/mL) with no significant difference between both septic groups. Culture-positive or negative septic preterm neonates had significantly higher sTREM-1 compared to full term neonates. sTREM-1 was significantly higher in neonates with early sepsis than late sepsis and was associated with high mortality. sTREM-1 was significantly decreased 48h after antibiotic therapy compared to baseline or levels in neonates with persistently positive cultures. sTREM-1 was positively correlated to white blood cells (WBCs), absolute neutrophil count, immature/total neutrophil (I/T) ratio, C-reactive protein (hs-CRP) and sepsis score while negatively correlated to gestational age and weight. hs-CRP and sepsis score were independently related to sTREM-1 in multiregression analysis. sTREM-1 cutoff value of 310pg/mL could be diagnostic for NS with 100% sensitivity and specificity (AUC, 1.0 and 95% confidence interval [CI], 0.696-1.015) while the cutoff value 1100pg/mL was predictive of survival with 100% sensitivity and 97% specificity (AUC, 0.978 and 95% CI, 0.853-1.13). However, hs-CRP cutoff 13.5mg/L could be diagnostic for NS with a sensitivity of 76% and specificity of 72% (AUC, 0.762 and 95% CI, 0.612-0.925) and levels were not related to survival as no significant difference was found between dead and alive septic neonates. CONCLUSIONS Elevated sTREM-1 could be considered an early marker for NS that reflects sepsis severity and poor prognosis.

Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

Heart disease is the leading cause of mortality and morbidity in β‐thalassemia major (β‐TM). Aggregability of abnormal red cells and membrane‐derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young β‐TM patients compared with 40 age‐ and sex‐matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b+) and ErMPs (glycophorin A+) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 μg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non‐compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D‐dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

N-Terminal Natriuretic Peptide and Ventilation-Perfusion Lung Scan in Sickle Cell Disease and Thalassemia Patients with Pulmonary Hypertension

The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 β-thalassemia major (β-TM) and 15 β-thalassemia intermedia (β-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 ± 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, β-TI and β-TM patients, respectively. Pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. Pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators.

Subclinical atherosclerosis in young beta-thalassemia major patients.

Subclinical atherosclerosis in young β-thalassemia major (β-TM) patients and its risk factors including dyslipidemia compared to type 1 diabetic patients were assessed. Ninety subjects were included and divided into three groups: group I comprised 30 β-TM patients with a mean age of 18.4 ± 6.18 years; group II comprised of 30 type 1 diabetic patients with a mean age of 19.23 ± 4.25 years, and 30 healthy subjects served as controls in group III. Fasting lipid profiles, hemoglobin (Hb) electrophoresis, serum ferritin and high resolution ultrasound for the measurement of carotid artery intima media thickness (CIMT) were done. Serum triglycerides, total cholesterol, apoprotein A (ApoA), and CIMT were significantly elevated, while high density lipoproteins (HDL) were significantly lowered in thalassemic and diabetic patients compared to controls. In thalassemic patients, CIMT was positively correlated with age, Hb F, ferritin and cholesterol levels. Atherogenic lipid profiles in young thalassemic patients with increased CIMT highlights their importance as prognostic factors for vascular risk stratification.

Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young β-thalassemia intermedia patients.

To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in β‐thalassemia intermedia (TI) patients compared with single HU therapy.

Soluble CD40L in children and adolescents with type 1 diabetes: relation to microvascular complications and glycemic control.

CD40‐soluble CD40 ligand (sCD40L) interactions might constitute an important mediator for vascular inflammation that initiates diabetic microangiopathy. Little is known about the relation between sCD40L and glycemic control. Therefore, this study aimed to evaluate sCD40L levels in patients with type 1 diabetes and its relation to microvascular complications and metabolic control. Sixty patients with type 1 diabetes were compared with 30 healthy control subjects. Detailed medical history, thorough clinical examination, and laboratory assessment of high‐sensitivity C‐reactive protein, glycemic control, and the presence of microvascular complications were performed. Measurement of serum sCD40L levels was done using enzyme‐linked immunosorbent assay. Patients were divided into two groups according to the presence of microvascular complications. Serum sCD40L levels were significantly elevated in patients with type 1 diabetes in both groups compared with healthy controls (p < 0.001). Patients with microvascular complications had higher serum sCD40L concentrations than non‐complicated cases (median, 13 000 vs. 450 pg/mL; p < 0.001). Serum sCD40L cutoff value of 530 pg/mL was able to differentiate complicated from non‐complicated cases (p < 0.001). Patients with microalbuminuria or peripheral neuropathy showed higher levels of sCD40L when compared with patients without these complications (p < 0.05). Serum sCD40L levels were positively correlated with hemoglobin A1c and urinary albumin excretion (p < 0.001). We suggest that serum sCD40L levels are elevated in type 1 diabetes, particularly in patients with microvascular complications and a significant correlation with glycemic control exists. Therefore, measurement of serum sCD40L levels in poorly controlled patients would help to identify those at high risk of developing microvascular complications.

Serum and Urinary Nitrites and Nitrates and Doppler Sonography in Detection of Early Diabetic Complications

Objective: to evaluate serum and urinary nitrite and nitrate concentrations as an index of nitric oxide (NO) production in type1diabetes mellitus (T1DM) and to investigate the possible alteration and correlation with intra renal Doppler resistive indexes (RIs). Design: The study included 90 children and adolescent with T1DM divided into 2 groups: Group 1: included 45 prepubertal type1 diabetics who were defined as Tanner stage1. Their age ranged between 8-14 years. Group 2: included 45 pubertal type diabetics who were defined as Tanner stages 2-5. Their ages ranged between 15-19 years. They were compared to 45 age and sex matched healthy controls. Clinical examination was done. Laboratory investigations included; post-prandial blood glucose (PPBG), glycosylated heamoglobin (HbA1C), Fundus examination, urinary microalbumin and measurement of serum and urinary nitrite and nitrate levels. Doppler ultrasonographic registration of intrarenal RIs were performed. Results: Compared to controls, both diabetic groups had significantly increased concentrations of serum (P=0.001) and urinary NO (P=0.008).Doppler RIs values were significantly elevated in both diabetic groups compared to controls (P<0.001).A significant positive correlation was found between serum and urinary NO levels (P<0.001). Serum NO was positively correlated with Doppler RIs (P=0.002), HbA1c (P=0.012), PPBG (P=0.000) and diabetes duration (P=0.004). Doppler RIs were positively correlated with mean HbA1c (P=0.025), PPBG (P=0.001) and diabetes duration (P=0.000). Conclusion: In type 1 diabetes chronic hyperglycemia may act through a mechanism that involves increased NO production or action and contributes to generating intrarenal hemodynamic abnormalities which could be detectable by Doppler ultrasonography even before overt clinical nephropathy. Further follow up studies are needed to document the usefulness of Doppler ultrasound in detection of preclinical nephropathy.

Clinicopathological and radiological study of Egyptian β-thalassemia intermedia and β-thalassemia major patients: relation to complications and response to therapy.

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian β-thalassemia intermedia (β-TI) patients were compared with 70 β-thalassemia major (β-TM) patients. β-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, β-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in β-TM patients compared with β-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for β-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between β-TI and β-TM. We provide evidence that calls for the use of HU in β-TI patients.

A longitudinal prospective study of bleeding diathesis in Egyptian pediatric patients: single-center experience.

Keeping an updated registry of bleeding disorders is crucial for planning care and documenting prevalence. We aimed to assess the prevalence of various bleeding disorders including rare inherited coagulation and platelet disorders concerning their clinico-epidemiological, diagnostic data and bleeding manifestations severity. Patients suffering from manifestations of bleeding or coagulation disorders presented to Hematology Clinic during 16 years were included and prospectively followed up. Demographics, clinical characteristics, complete blood count, bleeding, prothrombin and activated partial thromboplastin times, platelet aggregation tests and bone marrow aspiration were recorded. Overall 687 patients with bleeding disorders from total 2949 patients were identified. Inherited coagulation defects were found in 27.2%; hemophilia A (70.6%), hemophilia B (13.9%), factor I deficiency (2.3%), factor V deficiency (1.6%), factor X deficiency (4.2%), factor VII deficiency (2.6%), factor XIII deficiency (1.1%), combined factor deficiency (2.1%) and unclassified coagulation disorders in 1.6% of studied patients. Overall 72.7% had diagnosed with platelet disorders; immune thrombocytopenia was the commonest (74.8%), and inherited conditions represent (25.2%) in the following order: Glanzmans thrombasthenia (11.2%), von Willebrand disease (6.6%), Bernard–Soulier syndrome (1%) and Chediak Higashi in 0.4% and unclassified in 6%. Median age of diagnosis of coagulation and platelet disorders were 33 and 72 months. Presenting symptoms of coagulation disorders were: 25.1% post circumcision bleeding, 22.5% ecchymosis, 20.9% hemoarthrosis and 15% epistaxis. Symptoms of rare coagulation disorders were postcircumcision bleeding (20%), bleeding umbilical stump (20%), epistaxis (12%), hemoarthrosis (8%) and hematomas (4%). Presenting symptoms in rare inherited platelet disorders were purpura, ecchymosis, epistaxis and bleeding gums, respectively. Analysis of the clinico-epidemiological data of patients with bleeding disorders is a useful tool for monitoring and improving their quality of care.