CMV, B and C hepatitis among multi-transfused hereditary hemolytic Anemia children: an updated Egyptian experience.

BACKGROUND AND OBJECTIVES: Regular blood transfusion has improved the overall survival and quality of life for patients with hereditary hemolytic anemias. Nevertheless, it carries a real risk of acquisition of blood-borne virus infections, especially viral hepatitis. The purpose of the current study is to present an Egyptian update on blood-borne hepatitis C & B viruses (HCV & HBV) and cytomegalovirus (CMV) among multi-transfused Egyptian children with hereditary hemolytic anemias, especially after implementation of national preventive programs in Egypt. PATIENTS AND METHODS: All pediatric patients with hereditary hemolytic anemias who have regular follow-up and received frequent blood transfusion at the Pediatric Hematology Units, Menuofia and Zagazig Universities Hospitals, Egypt, during the study period, were recruited. They were tested for hepatitis B surface antigen (HBVsAg), hepatitis C antibody (HCVab), and CMV immunoglobulin M (IgM) serology. Those with positive results were confirmed by real-time polymerase chain reaction (PCR). RESULTS: Four hundred and seventy-seven hereditary hemolytic anemia patients fulfilled the study inclusion criteria. Their ages ranged from 2 to 18 years, 54.9% of them were males. Seroprevalence of HCVab and CMV-IgM were (14.7% & 6.7% respectively) and they were confirmed by PCR. None of the studied cases were HBVsAg positive. Seropositivity for HCV was significantly associated with older age of the patients, higher transfusion frequency, longer disease duration, and higher mean serum ferritin. CONCLUSION: HCV followed by CMV infections still represent a significant problem for patients with hereditary hemolytic anemias. Nationwide plans should be taken to ensure meticulous and highly sensitive methods of blood screening before transfusion. On the other hand, it seems that HBV compulsory vaccination had succeeded to eliminate HBV infection.

Factor VIII inhibitor development in Egyptian hemophilia patients: does intron 22 inversion mutation play a role?

BACKGROUND: Hemophilia A (HA) is an X-linked recessive bleeding disorder characterized by qualitative and quantitative deficiency of factor VIII (FVIII). The development of inhibitor antibodies against FVIII is the most challenging complication of treatment. Mutations in the FVIII gene is one of the genetic factors that leads to development of FVIII inhibitors especially intron 22 inversion (Inv22). OBJECTIVES: This study was carried out to assess the frequency of Inv22 of FVIII gene in Egyptian patients with hemophilia A and its role as a risk factor for developing inhibitors. PATIENTS AND METHODS: Seventy-two patients with severe HA and 48 patients with moderate HA were enrolled in the current study. All patients were treated on demand with either plasma-derived factor VIII or recombinant factor VIII concentrates. Genotyping of FVIII Inv22 was performed by LD-PCR while the presence and magnitude of inhibitor activity in blood was determined by the Bethesda assay. RESULTS: Around 23% of all hemophilia cases had positive Inv22. Intron 22 inversion mutation was detected in 6 and 33% of patients with moderate and severe HA respectively. Twenty-one cases (18%) of all hemophilic patients developed inhibitors. Thirty-7% of patients with Inv22 had inhibitor in their blood, almost all, but one, had severe HA. The risk of an inhibitor development during replacement therapy was four folds higher among Inv22 positive cases as compared with mutation negative peers (OR 4.3, 95% CI 1.6-11.9, P = 0.003). CONCLUSIONS: The prevalence of Inv22 of F VIII in Egyptian hemophiliacs is nearly like that of other population. This mutation was more frequently detected among severe hemophilic patients as compared with moderately affected peers. The presence of Inv22 mutation significantly predispose to FVIII inhibitor development.

Intrafamilial Transmission of Hepatitis C Virus Among Families of Infected Pediatric Oncology Patients.

BACKGROUND: Hepatitis C virus (HCV) is the most commonly encountered blood transmittable hepatitis among cancer patients. Several studies have reported clustering of HCV infections in families or household contacts of infected cases. Data about the epidemiologic aspects of intrafamilial transmission from pediatric cancer patients are scarce and still debated. We aimed to identify the magnitude of horizontal intrafamilial transmission of HCV from infected pediatric oncology patients; its prevalence, risk factors and possible routes of transmission. METHODS: One hundred fifty-seven (86 HCV positive, 71 HCV negative) pediatric oncology patients who received treatment and follow-up at Zagazig university Hospital-Egypt and their household family contacts (751) were enrolled in this cross-sectional case-control study. Blood samples were collected from 450 relatives of HCV infected cases (group 1) and 301 household contacts of HCV-negative cases (group 2) for analysis of HCV antibodies and HCV RNA to confirm positivity. Family contacts of HCV-infected cases were interviewed, and close-ended questionnaire was completed for each participant to determine risk factors and possible routes of HCV intrafamilial transmission. RESULTS: Significantly higher HCV prevalence and chronicity rates were documented among relatives of HCV-infected cases as compared with contacts of HCV-negative cases (12.6% and 10.6% for group 1 vs. 7% and 5.3% for group 2, respectively). Risk factors of infection were calculated by univariate and logistic regression analysis among contacts of HCV-infected cases. Female caregivers, particularly mother (OR 5.1, 95% CI: 2-13.5), contact with index cases blood, either directly without using personal protective equipment (OR 7.8, 95% CI: 2.9-23.8) or indirectly through common use of sharps (razors, scissors) (OR 8.9, 95% CI: 3.5-20.5) and nail clippers (OR 2.1, 95% CI: 1.1-5.4) and giving care to infected cases (OR 2.9, 95% CI: 1.3-16.6) represented the real predictors of intrafamilial HCV infection. CONCLUSIONS: Intrafamilial transmission of HCV from infected children to their relatives does occur. Parenteral route is the only documented way of transmission either directly or indirectly.

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.

MicroRNA-21 as a novel biomarker in diagnosis and response to therapy in asthmatic children.

BACKGROUND: The underlying molecular mechanisms leading to asthma remain largely unclear. MicroRNAs (miRNAs) are short noncoding RNAs exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. However, the role of miRNAs, specifically microRNA-21 (miRNA- 21), in the regulation of allergic airway inflammation is not well defined. Our aim was to investigate the serum miRNA- 21 expression levels as potential biomarker in childhood asthma [with, without inhaled corticosteroid (ICS) therapy, and steroid resistant (SR)]; and their possible contributions in disease status, its molecular target interleukin-12 (IL-12) p35, and response to therapy. MATERIALS AND METHODS: This study included 175 children; 95 were asthmatic patients subdivided into 3 groups [40 asthmatic children without ICS, 40 steroid sensitive (SS) asthma children and 15 steroid resistant (SR) asthma children] and 80 were healthy children as healthy controls. The miRNA-21 expressions levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) in all children. Serum IL-12p35 and total IgE levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression levels of miRNA-21 were significantly higher in the asthmatic children than in control group (P<0.001); with significantly higher levels in asthmatic patients without ICS or in SR patients compared to SS children (P<0.001). On contrast, serum IL-12p35 levels were significantly decreased in asthmatic patients without ICS therapy or in SR asthma patients as compared to SS patients (P<0.001). Our data revealed that serum miRNA-21 expression levels was significant negatively correlated with serum IL-12p35 levels and FEV1, while it was positively correlated with both sputum and blood eosinophils. Importantly, serum miRNA-21 had a predictive value in differentiating SS from SR patients, with an AUC value of 0.99, specificity of 86.7%, sensitivity of 97.5% and P<0.001. CONCLUSION: This study suggested that serum miRNA-21 is stable and detectable in serum of asthmatic children, which could promise potential biomarker in diagnosis as well as in response to therapy of asthma.

High-intensity light-emitting diode vs fluorescent tubes for intensive phototherapy in neonates.

BACKGROUND: Special blue fluorescent tubes are recommended by the American Academy of Pediatrics (AAP) as the most effective light source for lowering serum bilirubin. A high-intensity light-emitting diode ('super LED') could render intensive phototherapy more effective than the above conventional methods. This study compared the efficacy and safety of a high-intensity light-emitting diode bed vs conventional intensive phototherapy with triple fluorescent tube units as a rescue treatment for severe unconjugated neonatal hyperbilirubinaemia. METHOD: This was a randomised, prospective trial. Two hundred jaundiced neonates ≥ 35 weeks gestation who met the criteria for intensive phototherapy as per AAP guidelines were randomly assigned to be treated either with triple fluorescent tube units (group 1, n = 100) or a super LED bed (group 2, n = 100). The outcome was the avoidance of exchange transfusion by successful control of hyperbilirubinaemia. RESULTS: Statistically significant higher success rates of intensive phototherapy were achieved among neonates treated with super LED (group 2) than in those treated conventionally (group 1) (87% vs 64%, P = 0.003). Significantly higher 'bilirubin decline' rates were reported in both haemolytic and non-haemolytic subgroups treated with the super LED bed compared with a similar sub-population in the conventionally treated group. Comparable numbers of neonates in both groups developed rebound jaundice (8% vs 10% of groups 1 and 2, respectively). Side-effects were mild in both groups, but higher rates of hyperthermia (12% vs 0%, P = 0.03), dehydration (8% vs 2%, P = 0.26) and skin rash (39% vs 1%, P = 0.002) were reported in the fluorescent tubes-treated group compared with the LED group. CONCLUSIONS: Super LED is a safe rescue treatment for severe neonatal hyperbilirubinaemia, and its implementation may reduce the need for exchange transfusion.

Reducing ventilator-associated pneumonia in neonatal intensive care unit using "VAP prevention Bundle": a cohort study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a serious health care-associated infection, resulting in high morbidity and mortality. It also prolongs hospital stay and drives up hospital costs. Measures employed in preventing ventilator-associated pneumonia in developing countries are rarely reported. In this study we tried to assess the efficacy of our designed "VAP prevention bundle" in reducing VAP rate in our neonatal intensive care unit (NICU). METHOD: This prospective before-and-after study was conducted at university hospital NICU, all neonates who had mechanical ventilation for ≥ 48 h were eligible. VAP rates were evaluated before (phase-I) and after (phase-II) full implementation of comprehensive preventive measures specifically designed by our infection control team. RESULTS: Of 143 mechanically ventilated neonates, 73 patients developed VAP (51%) throughout the study period (2500 mechanical ventilation days). The rate of VAP was significantly reduced from 67.8% (42/62) corresponding to 36.4 VAP episodes/1000 mechanical ventilation days (MV days) in phase-I to 38.2% (31/81) corresponding to 23 VAP/1000 MV days (RR 0.565, 95% confidence interval 0.408-0.782, p = 0.0006) after VAP prevention bundle implementation (phase-II). Parallel significant reduction in MV days/case were documented in post-intervention period (21.50 ± 7.6 days in phase-I versus 10.36 ± 5.2 days in phase-II, p = 0.000). There were a trend toward reduction in NICU length of stay (23.9 ± 10.3 versus 22.8 ± 9.6 days, p = 0.56) and overall mortality (25% versus 17.3%, p = 0.215) between the two phases but didn't reach statistical significance. The commonest micro-organisms isolated throughout the study were gram-negative bacteria (63/66, 95.5%) particularly Klebsilla pneumonia (55/66, 83.4%). CONCLUSION: Implementation of multifaceted infection control bundle resulted in reduction of VAP rate, length of stay in our NICU.

Nutritional Status in Children with Un-Operated Congenital Heart Disease: An Egyptian Center Experience.

BACKGROUND: Malnutrition is a common cause of morbidity and mortality in children with congenital heart disease (CHD). This study aimed to identify prevalence and predictors of malnutrition in Egyptian children with symptomatic CHD. METHODS: This case-control study included 100 children with symptomatic CHD (76 acyanotic and 24 cyanotic) and 100 healthy children matched for age and sex as a control group. Clinical Evaluation and Laboratory Assessment of Nutritional Status were documented. Anthropometric measurements were recorded and Z scores for weight for age (WAZ), weight for height (WHZ), and height for age (HAZ) have been calculated. Malnutrition was defined as weight, height, and weight/height Z score ≤-2. RESULTS: The overall prevalence of malnutrition was 84.0% in patients with CHD and 20% in controls. Severe malnutrition was diagnosed in 71.4% of cases. All anthropometric measurements and levels of biochemical markers of nutritional state were significantly lower in the patients group compared to controls. In patients with acyanotic CHD, stunting was proportionately higher (57.89%) than in cyanotic CHD, while wasting was predominant (45.83%) in the latter. Malnutrition correlated significantly with low hemoglobin level, low arterial oxygen saturation, heart failure, pulmonary hypertension, and poor dietary history. CONCLUSION: Malnutrition is a very common problem in children with symptomatic CHD and predicted by the presence of low hemoglobin level, low arterial oxygen saturation, heart failure, poor dietary history, and pulmonary hypertension.

Cadmium status among pediatric cancer patients in Egypt.

Cadmium (Cd) is a toxic, nonessential, and bio-accumulating heavy metal widely used in industry. Several studies have suggested a positive association between Cd exposure and risks of several cancers. However, data from general population, especially children are sparse.In the current cross-sectional case-control study, we aimed to assess the association between Cd exposure, as expressed by Cd body status (blood, urine, scalp hair, and nails) and cancer among Egyptian children. Three hundred and fifty pediatric cancer cases aged 3 to 14-years old were enrolled in our study. Their body Cd levels were evaluated using Atomic Absorption Spectrophometer and were compared with Cd levels of 350 healthy children.Significantly higher Cd levels (blood, urine, scalp hair, and nails) were documented in cancer cases when compared with control (P < 0.001). Such difference was still detected when comparing each malignant type separately, with controls. Tobacco smoke exposure, rural residence, and low socioeconomic status were reported more frequently among cases than comparisons.Positive association between Cd exposure and pediatric malignancy may be present.

NT-proBNP as early marker of subclinical late cardiotoxicity after doxorubicin therapy and mediastinal irradiation in childhood cancer survivors.

BACKGROUND: Childhood cancer survivors treated with anthracyclines and mediastinal irradiation are at risk for late onset cardiotoxicity. AIMS OF THE STUDY: To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) as early predictors of late onset cardiotoxicity in asymptomatic survivors of childhood cancer treated with doxorubicin with or without mediastinal irradiation. METHODS: A cross-sectional study on 58 asymptomatic survivors of childhood cancer who received doxorubicin in their treatment protocols and 32 asymptomatic Hodgkin's lymphoma survivors who received anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and conventional echocardiography were determined. RESULTS: Thirty percent of survivors had abnormal NT-proBNP levels. It was significantly related to age at diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI detected myocardial affection in 20% more than conventional echocardiography. Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy. CONCLUSIONS: TDI could detect early cardiac dysfunction even in those with normal conventional echocardiography. Measurement of NT-proBNP represents an interesting strategy for detecting subclinical cardiotoxicity. We recommend prospective and multicenter studies to validate the role of NT-proBNP as an early marker for late onset doxorubicin-induced cardiotoxicity.

Childhood temporal lobe epilepsy: correlation between electroencephalography and magnetic resonance spectroscopy: a case-control study.

BACKGROUND: The diagnosis of epilepsy should be made as early as possible to give a child the best chance for treatment success and also to decrease complications such as learning difficulties and social and behavioral problems. In this study, we aimed to assess the ability of magnetic resonance spectroscopy (MRS) in detecting the lateralization side in patients with Temporal lobe epilepsy (TLE) in correlation with EEG and MRI findings. METHODS: This was a case-control study including 40 patients diagnosed (clinically and by EEG) as having temporal lobe epilepsy aged 8 to 14 years (mean, 10.4 years) and 20 healthy children with comparable age and gender as the control group. All patients were subjected to clinical examination, interictal electroencephalography and magnetic resonance imaging (MRI). Proton magnetic resonance spectroscopic examination (MRS) was performed to the patients and the controls. RESULTS: According to the findings of electroencephalography, our patients were classified to three groups: Group 1 included 20 patients with unitemporal (lateralized) epileptic focus, group 2 included 12 patients with bitemporal (non-lateralized) epileptic focus and group 3 included 8 patients with normal electroencephalography. Magnetic resonance spectroscopy could lateralize the epileptic focus in 19 patients in group 1, nine patients in group2 and five patients in group 3 with overall lateralization of (82.5%), while electroencephalography was able to lateralize the focus in (50%) of patients and magnetic resonance imaging detected lateralization of mesial temporal sclerosis in (57.5%) of patients. CONCLUSION: Magnetic resonance spectroscopy is a promising tool in evaluating patients with epilepsy and offers increased sensitivity to detect temporal pathology that is not obvious on structural MRI imaging.

Hodgkin lymphoma in childhood: clinicopathological features and therapy outcome at 2 centers from a developing country.

Hodgkin lymphoma (HL) accounts for 5% to 6% of all childhood cancer. It displays characteristic epidemiological, clinical, and pathological features according to various geographic areas. We aimed to assess the epidemiological aspects, clinicopathological features, and treatment outcome of pediatric HL treated at 2 Egyptian centers: Zagazig University Pediatric Oncology Unit and Benha Special Hospital Pediatric Oncology Unit. We carried a cross-sectional retrospective study by reviewing medical records for all patients admitted with the diagnosis of HL over 8 years in 2 oncology units during the period from January 2004 to January 2012. Age of the patients at presentation ranged from 3 to 14 years (median 6 years) and male: female ratio 1.7:1. Lymphadenopathy was the most common presentation (96.6%). Mixed cellularity subtype was dominant (50.8%), followed by nodular sclerosis (28.9%), lymphocyte-rich (18.6%) with lymphocyte depletion being the least dominant (1.7%). More than half of patients (55.9 %) had advanced disease (Ann Arbor stage III/IV disease). The duration of follow-up ranged from 5 to 87 months (mean 39.8 ±â€Š24.1 months). The 5-year overall survival and event-free survival for patients were 96.6% and 84.7% respectively. In Egypt, HL occurs in young age group, with a higher incidence of mixed cellularity subtype and advanced disease. None of the clinical, epidemiological, or pathological characteristics had a significant association with the overall survival. The outcomes of HL in our 2 centers were satisfactory approaching the international percentage.

Reducing Ventilator-Associated Pneumonia in Neonatal Intensive Care Unit Using "VAP Prevention Bundle"

Background and study aim : Ventilator-associated pneumonia (VAP) is a serious health care- associated infection, resulting in high morbidity and mortality. It also prolongs hospital stay and drives up hospital costs. Measures employed for preventing ventilator-associated pneumonia in developing countries are scarcely reported. The aim of the current work is to assess the efficacy of our designed "VAP prevention bundle" in reducing VAP rates in the neonatal intensive care unit (NICU). Patients and Methods: This prospective before-and-after study was conducted at Zagazig university hospital NICU; all neonates who had mechanical ventilation during the period from January 2013 to March 2014 for ≥48 hours were eligible after parental consent. VAP rates were evaluated before (phase-I) and after (phase-II) full implementation of the comprehensive preventive measures specifically designed by our infection control team. Results: Out of 143 mechanically ventilated neonates, 73 patients developed VAP (51%) throughout the study period (2500 mechanical ventilation days). The rate of VAP was significantly reduced from 67.8% (42/62) corresponding to 36.4 VAP episodes/1000 mechanical ventilation days (MV days) in phase-I to 38.2% (31/81) corresponding to 23 VAP/1000 MV days (RR 0.565, 95% confidence interval 0.408- 0.782, p= 0.0006) after VAP prevention bundle implementation (phase-II). Parallel significant reduction in MV days/case were documented in the post-intervention period (21.50±7.6 days in phase-I versus 10.36 ± 5.2 days in phase-II, p= 0.000). There were trends toward reduction in NICU length of stay (23.9±10.3 versus 22.8±9.6 days, p=0.56) and overall mortality (25% versus 17.3%, p=0.215) between the two phases which didn't reach statistical significance. The commonest micro-organisms isolated throughout the study were gram-negative bacteria (63/66, 95.5%) particularly Klebsilla pneumonia (55/66, 83.4%). Conclusion: The implementation of our multifaceted infection control bundle has resulted in a significant reduction of VAP rates, length of stay and hospital cost in our NICU. These rates are still far behind the internationally acknowledged ones