Psychosocial and mental profile of children with sickle cell disease and their caregivers.

Sickle cell disease (SCD), a chronic debilitating disorder that may negatively affect health-related quality-of-life (HRQoL). In this observational, case-control study, we aim to assess the prevalence of impaired psychosocial profile and poor HRQoL among SCD patients and their caregivers as well as to determine the association of such impairment with parameters of disease severity. Sixty-five children and adolescents with SCD and 65 age- and sex-matched healthy controls and their caregivers were recruited. Demographic and clinical characteristics were collected, and a thorough clinical and psychiatric assessments and HR QoL were conducted. Recruited children and adolescents with SCD were 34 (52.3%) boys and 31 (47.7%) girls, and their mean age was 11.40 ± 3.55. Most of them (n = 44, 67.7%) had sickle HbSß+, and vaso-occlusive crises were the most common causes for hospital admission (n = 24, 36.9%). Children with SCD and their caregivers had depression and anxiety symptoms scores higher than reported in the control group. Children with SCD had significantly less self-esteem and less QoL scores with the least scores were in the communication domain. This adverse psychological profile was significantly negatively correlated with the age of the child, duration of illness, number and duration of hospitalizations, disease severity score, and occurrence of complications. We conclude that HRQoL of children suffering from SCD, and their caregivers are adversely affected necessitating implementation of interventions which focus on reducing depressive symptoms, enhancing self-esteem and QoL.

Efficacy and safety of early-start deferiprone in infants and young children with transfusion-dependent beta thalassemia: Evidence for iron shuttling to transferrin in a randomized, double-blind, placebo-controlled, clinical trial (START).

Children with transfusion-dependent thalassemia (TDT) require regular blood transfusions that, without iron-chelation therapy, lead to iron-overload toxicities. Current practice delays chelation therapy (late-start) until reaching iron overload (serum ferritin ≥1000 µg/L) to minimize risks of iron-depletion. Deferiprone's distinct pharmacological properties, including iron-shuttling to transferrin, may reduce risks of iron depletion during mild-to-moderate iron loads and iron overload/toxicity in children with TDT. The early-start deferiprone (START) study evaluated the efficacy/safety of early-start deferiprone in infants/young children with TDT. Sixty-four infants/children recently diagnosed with beta-thalassemia and serum ferritin (SF) between 200 and 600 µg/L were randomly assigned 1:1 to receive deferiprone or placebo for 12 months or until reaching SF-threshold (≥1000 µg/L at two consecutive visits). Deferiprone was initiated at 25 mg/kg/day and increased to 50 mg/kg/day; some recipients' dosages increased to 75 mg/kg/day based on iron levels. The primary endpoint was the proportion of patients ≥SF-threshold by month 12. Monthly transferrin saturation (TSAT) assessment evaluated iron-shuttling. At baseline, there was no significant difference in mean age (deferiprone: 3.03 years, placebo: 2.63 years), SF (deferiprone: 513.8 µg/L, placebo: 451.7 µg/L), or TSAT (deferiprone: 47.98%, placebo: 43.43%) between groups. At month 12, there was no significant difference in growth or adverse event (AE) rates between groups. No deferiprone-treated patients were iron-depleted. At month 12, 66% of patients receiving deferiprone remained below SF threshold versus 39% of placebo (p = .045). Deferiprone-treated patients showed higher TSAT levels and reached ≥60% TSAT threshold faster. Early-start deferiprone was well-tolerated, not associated with iron depletion, and efficacious in reducing iron overload in infants/children with TDT. TSAT results provide the first clinical evidence of deferiprone shuttling iron to transferrin.

Sleep disordered breathing and its relation to stroke and pulmonary hypertension in children with sickle cell disease: a single-center cross-sectional study.

Sleep disordered breathing (SDB) is a common underdiagnosed sequela of sickle cell disease (SCD) that has been linked to the frequency of vaso-occlusive crises. To determine the frequency of SDB in children with SCD and its association to SCD-related complications, thirty children and adolescents with SCD at their steady state underwent clinical, laboratory, and radiological assessment using transcranial duplex (TCD) and echo assessment of tricuspid regurge velocity (TRV). All participants had an overnight polysomnography after completing the modified STOP-Bang questionnaire. The mean age of the studied cohort was 10.2 years, with male: female ratio 1.7:1. Six children (20%) had high-risk for obstructive sleep apnea (OSA), while nine (30%) were at intermediate risk. Sleep apnea defined as apnea (AHI) > 1 event/hour was found among 18/30 (60%) subjects (14 males and 4 females). Children with AHI > 5 (moderate to severe OSA) had significantly higher TRV (p = 0.007) and left MCA flow velocity (p = 0.049) when compared to those with AHI < 5. Children with AHI > 5 were at higher risk of OSA according to the modified STOP-Bang questionnaire (p = 0.02). AHI positively correlated with TRV (r = 0.53, p = 0.003), right MCA flow velocity (r = 0.45, p = 0.013), and left MCA flow velocity (r = 0.55, p = 0.002), and negatively correlated to BMI-SDS (r = - 0.48, p = 0.008). The high frequency of OSA in the studied cohort with SCD and its association with increasing risk of PH and TCD changes highlights the importance of early detection and management of OSA in children with SCD.

Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years.

Long-term safety and efficacy data on the iron chelator deferiprone in sickle cell disease (SCD) and other anemias are limited. FIRST-EXT was a 2-year extension study of FIRST (Ferriprox in Patients With Iron Overload in Sickle Cell Disease Trial), a 1-year, randomized noninferiority study of deferiprone vs deferoxamine in these populations. Patients who entered FIRST-EXT continued to receive, or were switched to, deferiprone. Altogether, 134 patients were enrolled in FIRST-EXT (mean age: 16.2 years), with mean (SD) exposure to deferiprone of 2.1 (0.8) years over the 2 studies. The primary end point was safety. Secondary end points were change in liver iron concentration (LIC), cardiac T2∗, serum ferritin (SF), and the proportion of responders (≥20% improvement in efficacy measure). The most common adverse events considered at least possibly related to deferiprone were neutropenia (9.0%) and abdominal pain (7.5%). LIC (mg/g dry weight) decreased over time, with mean (SD) changes from baseline at each time point (year 1, -2.64 [4.64]; year 2, -3.91 [6.38]; year 3, -6.64 [7.72], all P < .0001). Mean SF levels (µg/L) decreased significantly after year 2 (-771, P = .0008) and year 3 (-1016, P = .0420). Responder rates for LIC and SF increased each year (LIC: year 1, 46.5%; year 2, 57.1%; year 3, 66.1%; SF: year 1, 35.2%; year 2, 55.2%; year 3, 70.9%). Cardiac T2∗ remained normal in all patients. In conclusion, long-term therapy with deferiprone was not associated with new safety concerns and led to continued and progressive reduction in iron load in individuals with SCD or other anemias. The trial was registered at www.clinicaltrials.gov as #NCT02443545.

Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study.

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. AIM: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. METHODS: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. RESULTS: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. CONCLUSION: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.

High Risk of HBV Infection Among Vaccinated Polytransfused Children With Malignancy.

AIM OF THE STUDY: The national Egyptian hepatitis B virus (HBV) vaccination program coverage of all infants started in 1992. The study aimed to assess immunity against HBV and occurrence of HBV breakthrough infections in vaccinated polytransfused children with malignancies. PATIENTS AND METHODS: Eighty-nine polytransfused children with malignancies were recruited; 37 were on chemotherapy (male:female 20:17; mean age 7.7±4.0 y), and there were 52 naive patients (male:female 31:21; mean age 7.6±3.2 y). In addition, 162 age-matched and sex-matched healthy controls were recruited. Patients' sera were tested for quantitative anti-hepatitis B surface (HBs) (enzyme-linked immunoassays technique), hepatitis B surface antigen (HBsAg), total anti-hepatitis B core, and HBV-DNA (nested polymerase chain reaction for surface, core, and x-regions). RESULTS: There was a significant lower percentage of having protective anti-HBs (10 to 100 IU/L) level among those receiving chemotherapy (13.5%) than those without (44.2%) and controls (32.1%). Twenty-one (67.7%) of those on chemotherapy were HBsAg positive compared with 10 (32.2%) of those without. Overall, 46 patients were HBV-DNA positive; 38 were c-region positive, 5 were s-region positive, 2 positive for the c-region and the s-region, and 1 tested positive for the c-region and the x-region. Of 46 patients, 20 were also positive for HBsAg (overt infection), while 26 had occult HBV infection (HBsAg-negative). Anti-HBs ≥10 IU/L co-existed among 45% of patients with overt infection and in 50% of those with occult infection. There was nonsignificant impact of receiving chemotherapy on the level of HBV-DNA. CONCLUSIONS: Vaccinated children with malignancies, especially those under chemotherapy, are at a significant risk of HBV infection. The co-existence of anti-HBs with HBsAg and/or HBV-DNA may represent a possible residual transfusion-transmission risk with mutant HBV strains.

COVID-19 in Children With Cancer: A Single Low-Middle Income Center Experience.

BACKGROUND: Coronavirus disease-2019 (COVID-19) could be associated with morbidity and mortality in immunocompromised children. OBJECTIVE: The objective of this study was to measure the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among hospitalized children with cancer and to detect the associated clinical manifestations and outcomes. METHODOLOGY: A prospective noninterventional study including all hospitalized children with cancer conducted between mid-April and mid-June 2020 in Ain Shams University Hospital, Egypt. Clinical, laboratory, and radiologic data were collected. SARS-CoV-2 infection was diagnosed by reverse transcription polymerase chain reaction tests in nasopharyngeal swabs. RESULTS: Fifteen of 61 hospitalized children with cancer were diagnosed with SARS-CoV-2. Their mean age was 8.3±3.5 years. Initially, 10 (66.7%) were asymptomatic and 5 (33.3%) were symptomatic with fever and/or cough. Baseline laboratory tests other than SARS-CoV-2 reverse transcription polymerase chain reaction were not diagnostic; the mean absolute lymphocyte count was 8.7±2.4×109/L. C-reactive protein was mildly elevated in most of the patients. Imaging was performed in 10 (66.7%) patients with significant radiologic findings detected in 4 (40%) patients. Treatment was mainly supportive with antibiotics as per the febrile neutropenia protocol and local Children Hospital guidance for management of COVID-19 in children. CONCLUSIONS: Pediatric cancer patients with COVID-19 were mainly asymptomatic or with mild symptoms. A high index of suspicion and regular screening with nasopharyngeal swab in asymptomatic hospitalized cancer patients is recommended.

Micro-elimination of hepatitis C through testing of Egyptian pregnant women presenting at delivery: implications for screening policies.

OBJECTIVES: Despite the high burden of hepatitis C virus (HCV) infection in Egypt, screening of pregnant women is not yet universal, making national and global elimination unlikely. This study assessed the proportion of pregnant women who were screened for HCV infection at delivery, the prevalence and risk factors for HCV infection, the associated adverse neonatal outcomes, and the real-life linkage to care of infected women and follow-up of their infants' HCV status and timing of testing. METHODS: Data were collected from medical records of a retrospective cohort of all pregnant women who were admitted to a university hospital in Cairo for delivery between January and June 2018 (n = 6734). HCV antibody- and RNA-positive women and their infants were prospectively followed-up by phone interviews till September 2019. RESULTS: 2177 (32.3%) pregnant women were screened for HCV infection. 19 (0.9%) tested HCV antibody- and RNA-positive. Being ≥ 30 years old (ORa 3.6, 95% CI: 1.4-9.2; P = 0.009), history of abortion (ORa 3.5, 95% CI: 1.2-10.3; P = 0.022) and blood transfusion (ORa 29.1, 95% CI: 9.6-88.4; P < 0.001) were independent risk factors for infection. Adverse neonatal outcomes did not vary significantly among HCV antibody-positive and antibody-negative women. Only 13 (68.4%) HCV antibody- and RNA-positive women started treatment with direct-acting antivirals (DAAs) post-breastfeeding (two completed the treatment course and were cured). Four (21.1%) did not start treatment, and two (10.5%) were lost to follow-up. All infants of the 13 HCV antibody- and RNA-positive women who started DAA therapy tested HCV RNA-negative within their first year of life. CONCLUSION: Extending screening services to all pregnant women and better linkage to care are essential for the national elimination of HCV infection.

OBJECTIFS: Malgré la charge élevée de l'infection par le virus de l'hépatite C (VHC) en Egypte, le dépistage des femmes enceintes n'est pas encore universel, ce qui rend peu probable l'élimination nationale et mondiale. Cette étude a évalué la proportion de femmes enceintes qui ont été dépistées pour l'infection par le VHC à l'accouchement, la prévalence et les facteurs de risque d'infection par le VHC, les résultats néonatals indésirables associés et le ralliement réel avec les soins aux femmes infectées et le suivi du statut VHC de leurs nourrissons et le calendrier des tests. MÉTHODES: Les données ont été collectées à partir des dossiers médicaux d'une cohorte rétrospective de toutes les femmes enceintes admises dans un hôpital universitaire du Caire pour un accouchement entre janvier et juin 2018 (n = 6734). Les femmes testées positives pour les anticorps et l'ARN du VHC et leurs nourrissons ont fait l'objet d'un suivi prospectif par des entretiens téléphoniques jusqu'en septembre 2019. RÉSULTATS: 2.155 (32,3%) femmes enceintes ont été dépistées pour l'infection au VHC. 19 (0,9%) ont été testées positives pour les anticorps et l'ARN du VHC. Avoir ≥30 ans (ORa: 3,6 ; IC95%: 1,4-9,2; p = 0,009), les antécédents d'avortement (ORa : 3,5 ; IC 95%: 1,2-10,3; p = 0,022) et la transfusion sanguine (ORa: 29,1 ; IC95%: 9,6-88,4; p <0,001) étaient des facteurs de risque indépendants d'infection. Les résultats néonatals défavorables ne variaient pas de manière significative entre les femmes positives et négatives aux anticorps anti-VHC. Seules 13 (68,4%) femmes positives pour les anticorps et l'ARN du VHC ont commencé un traitement avec des antiviraux à action directe (AAD) après l'allaitement (deux ont terminé le traitement et ont été guéries). Quatre (21,1%) n'ont pas commencé le traitement et deux (10,5%) ont été perdus de vue. Tous les nourrissons des 13 femmes positives pour l'anticorps et l'ARN du VHC qui ont commencé un traitement par AAD ont été testés négatifs pour l'ARN du VHC au cours de leur première année de vie. CONCLUSION: L'extension des services de dépistage à toutes les femmes enceintes et un meilleur lien avec les soins sont essentiels pour l'élimination nationale de l'infection par le VHC.

The Adverse Impact of Thalassemia Major on Adolescents' Oral Health-related Quality of Life.

BACKGROUND: Adolescents with beta-thalassemia major (ßTM) had unfavorable quality of life (QOL). OBJECTIVES: To assess oral health status of adolescents with ßTM and its impact on their oral health-related QOL (OHRQoL). SUBJECTS AND METHODS: Forty adolescents with ßTM were recruited and compared with 40 age-matched and sex-matched healthy adolescents. Intraoral examination including dental caries assessment, oral hygiene index simplified (OHI-S), and Angle classification were performed. OHRQoL questionnaires were filled-out using child perception questionnaire-short form16. RESULTS: Although the majority of adolescents with ßTM had dental problems and convinced by their need for dental treatment, nearly half of them never brushed their teeth nor visited dental office. Patients showed higher frequency of class II malocclusion (P=0.017) and higher percentage of poor simplified debris index (DI-S) and OHI-S grade (P=0.008, 0.037, respectively). The median of DI-S and OHI-S were significantly higher in adolescents with ßTM (P=0.009, 0.037, respectively). Adolescents with ßTM had worse emotional well-being total score (P=0.049) than controls. Patients with poor oral hygiene had the worse total OHRQoL score (P=0.03). The total OHRQoL score showed significant positive correlation with oral hygiene; DI-S, calculus index-S, and OHI-S (P=0.028, 0.038, and 0.045, respectively). CONCLUSION: ßTM had a negative impact on the emotional well-being aspect.

Body Composition in Egyptian Children With Transfusion-dependent Thalassemia: The Impact of Nutrition and Metabolic Profile.

BACKGROUND: Growth failure is a common complication in children with beta-thalassemia major (ß-TM) that has persisted despite major treatment advances. It could stem from malnutrition, especially in those who live in poor countries and who have inadequate nutrient intake. AIM: The aim of this study was to assess the influence of nutrition on growth, total body composition, and metabolic profile in Egyptian children with ß-TM. SUBJECTS AND METHODS: This cross-sectional study included 200 children with ß-TM and 50 age-matched and sex-matched healthy children. All subjects underwent full clinical assessment, which included assessment of growth and total body composition using anthropometric measurements (weight, height, mid-arm circumference, skinfold thickness, and body mass index) and bioelectric impedance analysis device (TANITA SC330). Nutritional assessment was performed using 24-hour dietary recall. Fasting serum insulin, C-peptide, and fasting serum lipid profile (high-density lipoprotein, low-density lipoprotein, cholesterol, and triglyceride) were measured. RESULTS: Children with ß-TM had a significantly lower mean value of the daily consumption of the studied nutrient elements including kilocalories, protein, carbohydrate, calcium, and phosphorus (P<0.001). ß-TM had a negative impact on anthropometric measures; the mean of all measurements recorded in children with ß-TM was significantly lower than that in the control group (P<0.001). Children with ß-TM had a significant abnormality in lipid profile, with higher triglyceride levels and lower cholesterol, low-density lipoprotein, and high-density lipoprotein than controls. They had significantly lower serum insulin and C-peptide. Age, sex, serum ferritin, and caloric intake have a significant impact on body composition in children with ß-TM. CONCLUSION: Regular assessment of nutrition is crucial for the health of children with ß-TM.

Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer.

BACKGROUND: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. AIM: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. MATERIALS AND METHODS: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks' treatment with oral ion and were followed up with complete blood count and iron profile. RESULTS: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. CONCLUSIONS: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.

Angiopoietin-2 as a Marker of Retinopathy in Children and Adolescents With Sickle Cell Disease: Relation to Subclinical Atherosclerosis.

OBJECTIVES: Angiopoietin-2 (Ang-2) is a multifaceted cytokine that functions in both angiogenesis and inflammation. A proangiogenic state has been found in adults with sickle cell disease (SCD), mainly because of elevated Ang-2 levels. We determined Ang-2 level in 40 children and adolescents with SCD compared with 40 healthy controls and assessed its relation to retinopathy as well as carotid intimamedia thickness (CIMT). METHODS: Hematologic profile, serum ferritin, and serum Ang-2 were measured. CIMT was assessed using high-resolution ultrasound. Fundus examination was performed followed by fundus fluorescein angiography. Optical coherence tomography angiography (OCTA) was used to find small vascular changes not clinically manifested. RESULTS: Ang-2 levels and CIMT were significantly higher in SCD patients compared with controls. The incidence of nonproliferative retinopathy was 45%. SCD patients with retinopathy were older in age with a history of sickling crisis of >3 attacks per year and had a higher incidence of sickle cell anemia than sickle ß-thalassemia. Ang-2 cutoff value 9000 pg/mL could significantly detect the presence of retinopathy among SCD patients with 100% sensitivity and specificity. Serum Ang-2 levels were positively correlated with HbS and CIMT. Logistic regression analysis revealed that Ang-2 and HbS significantly contribute to retinopathy among patients with SCD. CONCLUSIONS: Elevated Ang-2 highlights the role of angiogenesis in the pathophysiology of SCD and may be considered a promising marker for screening of patients at risk of sickle retinopathy and vascular dysfunction.

Surfactant protein D as a marker for pulmonary complications in pediatric patients with sickle cell disease: Relation to lung function tests.

BACKGROUND: Surfactant protein D (SP-D) is considered a candidate biomarker for lung integrity and for disease progression. AIM: We determined the level of SP-D in children and adolescents with SCD and assessed its possible relation to pulmonary complications and lung function. METHODS: Serum SP-D levels were assessed in 50 SCD patients compared with 30 healthy controls. High-resolution computerized tomography (HRCT) of the chest was done. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1 ), FEV1 /FVC% and forced expiratory flow rate during 25-75% of expiration (FEF25-75%) were determined. RESULTS: SP-D was significantly higher in SCD patients than controls, particularly patients with sickle cell anemia than those with sickle ß-thalassemia. SP-D levels were significantly associated with increasing severity of interstitial lung disease. The highest SP-D levels were observed among patients with restrictive lung disease followed by mixed type then obstructive lung disease. SP-D was positively correlated to HbS and serum ferritin while negatively correlated to duration of hydroxyurea treatment and parameters of pulmonary functions. ROC curve analysis revealed that SP-D cutoff value 720 ng/mL could significantly detect the presence of abnormal pulmonary function among SCD patients with 82% sensitivity and 88% specificity. Logistic regression analysis showed that SP-D is an independent factor related to abnormal pulmonary function in SCD. CONCLUSIONS: SP-D may be a promising biomarker for screening of SCD patients for risk of later pulmonary complications.

Negative Impact of Prolonged Antibiotics or Persistent Diarrhea on Vitamin K1 Levels in 2-24 Weeks aged Egyptian Infants.

BACKGROUND: To evaluate the hazard of prolonged antibiotic therapy and/or persistent diarrhea on vitamin K1 (VK1) level and bleeding profile in infants (2-24 weeks). METHODS: A one-year case-control study, conducted at Ain Shams University, Egypt. 338 infants (2-24 weeks) were recruited and divided into 3 groups (1:1:3 ratios); group A (n=67) patients who received antibiotics for ≥10 days, group B (n=67) who had persistent diarrhea ≥ 14 days and group C (n=204) age- and gender- matched infants who had not either received antibiotics nor had diarrhea. All subjected to clinical assessment, bleeding history and had their complete blood count (CBC), PT and PTT, liver transaminases and VK1 level assayed. RESULTS: There was a significant increase in frequency of VKDB (vitamin K deficiency bleeding) and abnormal bleeding profile in cases than control group. There was significant negative correlation between VK1 level and duration of diarrhea, length of antibiotics used and bleeding profile. Antibiotic usage has hazardous effect on VK1 level in those with diarrhea; more patients were receiving antibiotic in those with persistent diarrhea and VKDB (N=55) than those with persistent diarrhea and normal VK1 (N=12). The longer duration of antibiotic therapy the lower level of VK1. Combining cephalosporin/penicillin therapy and/or diarrhea, in particular, had an impact on VK1 level. CONCLUSION: VKDB, a preventable cause of life-threatening hemorrhage, is still a major health problem in Egyptian infants, where persistent diarrhea and misuse of antibiotics are prevalent, necessitate a booster dose of VK in those high risk infants.

Influence of thiopurine methyltransferase gene polymorphism on Egyptian children with acute lymphoblastic leukaemia.

Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period. Thirty-two patients were on maintenance and another 32 completed their chemotherapy. Seventy healthy age-matched and sex-matched children served as controls. They were subjected to clinical assessment, haematological panel investigations and TPMT gene polymorphism for G238C, G460A and A719G alleles assessment using PCRfollowed byRFLP analysis.Although none of the studied patients had themutantTPMTvariant alleles,myelosuppression toxicity in the form of different degree of neutropenia was detected in all patients. As a result of myelosuppression toxicity, most of the patients needed 6-MP dose modification either once (53.1%), twice (15.6%), or ≥ thrice (25.1%) during their maintenance course and 96.9% of the patients required to stop 6-MP for less than a week (62.5%), up to 2 weeks (28.1%), or > 2 weeks (6.3%). Patients also developed infection who mostly (71%) needed hospitalization. None of the studied G238C, G460A and A719G TPMT variant alleles were detected. Infections and febrile neutropenia were common causes of 6-PM dose modification and interruption.

Endothelial monocyte activating polypeptide II in children and adolescents with type 1 diabetes mellitus: Relation to micro-vascular complications.

OBJECTIVES: Endothelial monocyte-activating polypeptide II (EMAP II) is a multifunctional polypeptide with proinflammatory and antiangiogenic activity. Hyperglycemia and dyslipidemia appears to be significant factors contributing to increased EMAP-II levels. We determined serum EMAP II in children and adolescents with type 1 diabetes as a potential marker for micro-vascular complications and assessed its relation to inflammation and glycemic control. METHODS: Eighty children and adolescents with type 1 diabetes were divided into 2 groups according to the presence of micro-vascular complications and compared with 40 healthy controls. High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c) and EMAP II levels were assessed. RESULTS: Serum EMAP II levels were significantly increased in patients with micro-vascular complications (1539 ± 321.5 pg/mL) and those without complications (843.6 ± 212.6 pg/mL) compared with healthy controls (153.3 ± 28.3 pg/mL; p<0.001). EMAP II was increased in patients with microalbuminuria than normoalbuminuric group (p<0.001). Significant positive correlations were found between EMAP II levels and body mass index, fasting blood glucose, HbA1c, serum creatinine, triglycerides, total cholesterol, urinary albumin creatinine ratio (UACR) and hs-CRP (p<0.05). A cutoff value of EMAP II at 1075 pg/mL could differentiate diabetic patients with and without micro-vascular complications with a sensitivity of 93% and specificity of 82%. CONCLUSIONS: We suggest that EMAP II is elevated in type 1 diabetic patients, particularly those with micro-vascular complications. EMAP II levels are related to inflammation, glycemic control, albuminuria level of patients and the risk of micro-vascular complications.

One-Year Prospective Study of Community Acquired Influenza and Parainfluenza Viral Infections in Hospitalized Egyptian Children with Malignancy: Single Center Experience.

BACKGROUND: Respiratory viruses are widespread in the community and easily transmitted to immunocompromised patients. AIMS: Assess the prevalence of community-acquired respiratory viral infections among children with cancer presenting with clinical picture suggestive of lower respiratory tract infections (LRTIs), and evaluate its risk factors and prognosis. METHODS: Over a year, 90 hospitalized children with malignancy and LRTIs recruited, subjected to clinical assessment, investigated through hematology panel, blood culture, chest x-ray, CT chest and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses, and respiratory syncytial virus (RSV), and prospectively followed up for the clinical outcome. RESULTS: Viral pathogens were identified in 34 patients (37.7%), with a seasonal peak from April to May. The most frequently detected virus was influenza virus [type A (16 cases; 47%), type B (4 cases; 12%)] followed by parainfluenza virus [PIV1 (9 cases; 26%), PIV3 (3 cases; 15%)], and none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed infections [bacterial/viral and bacterial/fungal] in 13, and 36 cases had unidentified etiology. The majority of patients with influenza and parainfluenza infections had hematological malignancy, presented with fever, and had mild self-limited respiratory illness. Five patients with mixed viral and bacterial infection had severe symptoms necessitating ICU admission. Six patients died from infection-related sequelae; two had mixed PIV and Staphylococcal infections. CONCLUSIONS: Community acquired influenza and parainfluenza infections are common in pediatrics patients with malignancy, either as isolated or mixed viral/bacterial infections. Clinical suspicion is essential as hematological and radiological manifestations are nonspecific. Rapid diagnosis and management are mandatory to improve patients' outcome.

Early Predictors of Renal Dysfunction in Egyptian Patients with ß-Thalassemia Major and Intermedia.

BACKGROUND: Better survival of thalassemia patients allowed previously unrecognized renal complications to emerge. OBJECTIVES: Assess prevalence and early predictors of renal dysfunction in young ß-thalassemia major (ß-TM) and intermedia (ß-TI) patients. SUBJECTS: 66 ß-TM (group I), 26 ß-TI (group II) Egyptian patients and 40 healthy controls. METHODS: Clinical assessment and laboratory data including kidney and liver function tests, such as serum ferritin, serum bicarbonate, plasma osmolality and urinary total proteins, microalbuminuria (MAU), N-acetyl-ß-D-glucosaminidase (NAG), retinol binding protein (RBP), α-1 microglobulin, bicarbonate, osmolality, creatinine clearance (CrCl), % fractional excretion of bicarbonate (% FE-HCO3). RESULTS: The prevalent renal abnormality was proteinuria (71%), followed by increased urinary level of RBP (69.4%), NAG (58.1%), α-1 microglobulin (54.8%) and microalbuminuria (29%) and also decreased urinary osmolality (58.1%). CrCl was a better assessment of renal function and significantly lowered in thalassemia patients. Tubular dysfunctions were more significant in splenectomized ß-TM patients who showed more elevation of NAG and α-1 microglobulin and lower urinary osmolality. NAG, RBP and α-1 microglobulin were negatively correlated with CrCl and positively correlated with serum ferritin and urinary total protein. Z-score analysis for identifying patients with renal dysfunction proved superiority of urine total protein and RBP. Comparative statistics of different frequencies revealed significant difference between the urinary total protein and both MAU and % FE-HCO3. CONCLUSION: Asymptomatic renal dysfunctions are prevalent in young ß-TM and ß-TI patients that necessitate regular screening. Urinary total protein and RBP may be cost-effective for early detection.

Psychiatric morbidity in Egyptian children with acute lymphoblastic leukemia and their care providers.

AIM OF THE STUDY: To evaluate the psychological morbidity of acute lymphoblastic leukemia (ALL) on children and their parents at different stages of illness and to assess the crucial contribution of the psychologist in the pediatric oncology team. METHODS: We recruited 103 children with ALL and their 96 parents, and divided them into five groups according to disease phase: diagnosis, initial remission, active treatment, survival and relapsing. We compared these to 22 healthy controls and their parents. Patients and controls were subjected to clinical assessments, the symptoms checklist of the International Classification of Disease ICD (ICD-10), and the Wechsler Intelligence Scale for Children The parents of patients and controls underwent a general health questionnaire, the ICD-10 symptoms checklist, rating scales for anxiety and depression, post-traumatic stress disorder (PTSD) assessment scale, and the physical cognitive affective social economic ego problems (PCASEE) questionnaire for quality of life (QOL) rating. RESULTS: Psychiatric morbidity was evident in nearly 60% of leukemic children and their parents and was significantly increased in comparison to controls. Children mostly suffered from adjustment and oppositional defiant disorders. The most common discriminators between patient groups were conduct and attention problems being lowest in newly diagnosed patients, and social aggression being lowest in patients in remission. The three parameters were highest in relapsed patients whose parents mostly had adjustment and depressive disorders. Risk factors for child psychopathology were older age, female gender, and parental psychopathology. Mothers and parents with lower education and professional level were found to be vulnerable. Performance and total intelligence quotient (IQ) were significantly lower in leukemic children, and these were most pronounced in the survivor group. Risk factors for cognitive dysfunction were younger age, longer chemotherapy duration, and lower parental education level. CONCLUSION: Most patients and their caregivers suffered from significant psychiatric morbidity, highlighting the need for routine screening to improve psychological outcomes in such cases.