Safety and efficacy of L-Glutamine in reducing the frequency of acute complications among patients with sickle cell disease: A randomized controlled study.

To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.

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.

Endothelin-1 gene polymorphism (G8002A) and endothelial monocyte-activating polypeptide II: Role in vascular dysfunction in pediatric patients with ß-thalassemia major.

BACKGROUND: Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, stimulates production of reactive oxygen species. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide. AIM: To assess ET-1 gene polymorphism (G8002A) in pediatric patients with ß-thalassemia major (ß-TM) as a potential genetic marker for vascular dysfunction and its possible relation to EMAP II, oxidative stress and vascular complications. METHODS: ß-TM patients (n = 95) without symptomatic cardiac or renal disease were compared with 95 healthy controls. Markers of hemolysis, serum ferritin, urinary albumin-to-creatinine ratio, serum EMAP II, malondialdehyde (MDA) and antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase and catalase were measured. ET-1 gene polymorphism (G8002A) was determined using polymerase chain reaction­restriction fragment length polymorphism. RESULTS: ß-TM patients had significantly higher EMAP II than healthy controls. EMAP II was significantly higher among patients with cardiac disease, pulmonary hypertension (PH) risk, nephropathy, poor compliance to therapy and ferritin ≥ 2500 µg/L. There were significant correlations between EMAP II and transfusion index, LDH, ferritin and oxidative stress markers. The AA genotype of ET-1 gene polymorphism (G8002A) was significantly higher among ß-TM patients than controls. The number of patients with cardiac disease, PH risk or nephropathy was significantly higher among AA genotype compared with GG and GA genotypes. Lactate dehydrogenase (LDH), serum ferritin, EMAP II, MDA, SOD and GPx were significantly higher in AA genotype. CONCLUSION: ET-1 gene polymorphism (G8002A) could be a possible genetic marker for prediction of increased susceptibility to cardiopulmonary and renal complications among pediatric patients with ß-TM.

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.

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.

The implementation of automated red blood cell exchange (erythrocytapheresis) as a treatment modality in sickle cell disease patients: Single center experience.

BACKGROUND: Improvements of health infrastructure, preventive care and clinical management is important to reduce the morbidity and mortality of sickle cell disease (SCD). OBJECTIVE: This prospective, investigator-initiated non-randomized open-label intervention, single centre study describes the implementation of the automated erythrocytapheresis in low-middle income country as a treatment modality for SCD patients to improve the standard of care and highlights its benefits and challenges. METHODOLOGY: Eligible patients with SCD who had overt stroke, abnormal/conditional transcranial doppler (TCD), or other indications were subjected to regular automated erythrocytapheresis program. RESULTS: From 18th Dec 2017 till 17th Dec 2022, 21 subjects were enrolled; seventeen (80.9 %) were Egyptian and four (19.1 %) were non-Egyptian (three Sudanese and one Nigerian). Totalling 133 sessions had been performed mainly in working hours with fluctuating frequency per month. All sessions maintained isovolumic status and were performed using central venous access. The target HbS concentration was set from the start; the mean final FCR % fraction was 51, most of the session (n = 78, 58.7 %) were able to achieve target FCR. The majority of session pass smoothly with no adverse event (n = 81, 60.9 %), except for certain challenges as shortage of the required blood (n = 38), hypotension (n = 2), hypocalcaemia (n = 2). CONCLUSION: Automated erythrocytapheresis is safe and effective modality for management of patients with sickle cell disease.

Evaluation of the effect of eltrombopag therapy on the platelet collagen receptor glycoprotein VI (GPVI) expression and soluble GPVI levels in young patients with immune thrombocytopenia.

BACKGROUND: Platelet glycoprotein VI (GPVI) receptor is essential for platelet adhesion and aggregation. Eltrombopag is as an effective treatment for chronic immune thrombocytopenia (ITP); yet, its effect on platelet function is not fully characterized. AIM: This prospective study investigated the effect of eltrombopag therapy on platelet function through assessment of GPVI receptor expression and soluble GPVI levels among pediatric patients with persistent or chronic ITP. METHODS: Thirty-six children and adolescents with persistent or chronic ITP were divided equally into two groups either to receive eltrombopag therapy or the standard of care. All patients were followed-up for 12 months with assessment of bleeding score and complete blood count (CBC). Evaluation of GPVI expression using flow cytometry and measurement of its soluble form by ELISA was done at baseline and at 6 months. RESULTS: ITP patients on eltrombopag had significantly lower bleeding score after 6 months of therapy while the quality of life has significantly improved. Platelet count was significantly increased throughout the study. GPVI expression by flow cytometry and soluble GPVI levels were significantly increased after eltrombopag therapy. After 12 months, ITP patients on eltrombopag were able to maintain a good quality of life and low bleeding score. CONCLUSION: Our data suggest that eltrombopag, through its effect on the GPVI receptor expression and its soluble form, might reduce bleeding manifestations and improve the quality of life of chronic and persistent ITP children independent of its effect on the platelet count.

Ledipasvir-sofosbuvir in Adolescents With Chronic Hepatitis C and Hematological Malignancies Undergoing Chemotherapy.

OBJECTIVES: In children with hematological malignancies, chronic hepatitis C virus (HCV) infection has been associated with more rapid liver disease progression and higher risk of malignancy relapse due to chemotherapy interruption. We evaluated the safety and efficacy of ledipasvir-sofosbuvir for 12weeks in these patients. METHODS: In a phase 2, open-label study, at one site in Egypt, patients ages 12-<18years with chronic HCV genotype 1 or 4 infection undergoing maintenance chemotherapy for hematological malignancies received ledipasvir-sofosbuvir (90 mg/400 mg) once daily for 12weeks. The efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12). Safety was assessed by the incidence of adverse events and clinical and laboratory data, including HCV flares defined as alanine aminotransferase >3-fold increase from Day 1 and HCV RNA elevation >1 × log10 from Day 1. RESULTS: Of the 19 adolescents enrolled and treated, median age was 14 years (range 12-17), 84% (16/19) were male, and all had HCV genotype 4 and were HCV treatment naive. All patients completed treatment and achieved SVR12 (19/19, 100%, 95% confidence interval, 82-100). Common adverse events were pyrexia (5/19, 26%), diarrhea (4/19, 21%), and headache (4/19, 21%). Three patients experienced serious adverse events of pneumonia (two patients), and osteoarthritis and diarrhea (one patient); none were considered related to study drug. No patient experienced HCV flares. CONCLUSIONS: Ledipasvir-sofosbuvir was well-tolerated and efficacious in adolescents with chronic HCV genotype 4 and leukemia undergoing maintenance chemotherapy. These data support the use of this interferon and ribavirin-free regimen in adolescents with hematological malignancies.

Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study.

No specific antiviral drugs have been approved for the treatment of COVID-19. This study aimed to evaluate the efficacy of favipiravir in treatment of COVID-19. This was a multicenter randomized controlled study including 96 patients with COVID- 19 who were randomly assigned into a chloroquine (CQ) group and a favipiravir group. None of the patients in the favipiravir group needed mechanical ventilation (p = 0.129). One patient (2.3%) in the favipiravir group and two patients (4.2%) in the CQ group died (p = 1.00). Favipiravir is a promising drug for COVID-19 that decreases the hospital stay and the need for mechanical ventilation.ClinicalTrials.gov Identifier NCT04351295.

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.

Hidden brain iron content in sickle cell disease: impact on neurocognitive functions.

Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment. We aim to quantitatively measure cerebral tissue R2* to investigate the brain iron deposition in children and young adults with SCD in comparison to beta thalassemia major (BTM) and healthy controls and evaluate its impact on neurocognitive functions in patients with SCD. Thirty-two SCD, fifteen BTM, and eleven controls were recruited. Multi-echo fast-gradient echo sequence brain MRI was performed, and brain R2* values of both caudate and thalamic regions were calculated. SCD patients were examined for the neurocognitive functions. SCD had high iron overload 0.30 ± 0.12 mg/kg/day. 68.9% of SCD had under-threshold IQ, 12.5% had moderate to severe anxiety, and 60.8% had depression. There were no differences between SCD, BTM, and controls in brain MRI except that left thalamus R2* higher in BTM than both SCD and controls (p = 0.032). Mean right caudate R2* was higher in female than male (p = 0.044). No significant association between brain R2* and LIC or heart R2* values in SCD. Left caudate R2* directly correlate with age and HbS%, and negatively correlate with HbA% while right thalamus R2* negatively correlate with transfusion index and among SCD patients.Conclusion: Neurocognitive dysfunction in SCD could not be explained solely by brain iron overload. What is Known: • Children with sickle cell disease are at great risk of brain damage due to their irregularly shaped red blood cells that can interrupt blood flow to the brain. • There are a number of factors that have negative brain effects that result in learning difficulties, and this not only due to increase brain iron content. What is New: • Assessment of quantitative brain iron content using MRI R2* in children and young adults with SCD in comparison to beta thalassemia major and healthy controls. • Impact of brain iron content on neurocognitive functions of children and young adults with SCD.

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.

Angiotensinogen M235T Gene Polymorphism is a Genetic Determinant of Cerebrovascular and Cardiopulmonary Morbidity in Adolescents with Sickle Cell Disease.

BACKGROUND: Cerebrovascular stroke is a common critical complication of sickle cell disease (SCD). Angiotensinogen (AGT) M235T gene polymorphism is associated with risk of ischemic stroke and cardiovascular disease. AIM: We investigated the potential association between angiotensinogen M235T gene polymorphism and susceptibility to cerebrovascular and cardiopulmonary complications in adolescents with SCD. METHODS: Forty-six patients with SCD in steady state were studied stressing on history of stroke, hydroxyurea/chelation therapy, hematological profile, and echocardiographic findings. Polymerase chain reaction-based restriction fragment length polymorphism analysis was used to detect AGT M235T gene polymorphism. Fifty sex- and age-matched healthy controls were enrolled for assessment of M235T gene polymorphism pattern. RESULTS: The distribution of AGT M235T gene polymorphism was similar between SCD patients and healthy controls. The frequency of T allele of AGT M235T gene polymorphism (TT and MT genotypes) was significantly higher among patients with history of manifest stroke (P < .001). Patients with TT and MT genotypes had higher incidence of cardiopulmonary complications (P = .041) as well as higher percentage of HbS (P < .001) and lower hemoglobin level (P = .008) compared with those with MM genotype. Serum ferritin, liver iron concentration, and cardiac T2* were not related to T alleles or genotypes. Logistic regression analysis revealed that M235T genotype was a significant independent factor related to the occurrence of stroke among patients with SCD (Odds Ratio 14.05, 95% confidence interval 3.82-28.91; P = .001). CONCLUSION: AGT M235T gene polymorphism may represent a genetic modifier to vascular morbidities in Egyptian patients with SCD.

Neuropilin-1/CD304 Expression by Flow Cytometry in Pediatric Precursor B-Acute Lymphoblastic Leukemia: A Minimal Residual Disease and Potential Prognostic Marker.

Flow cytometry (FCM) is used for quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) through discriminating leukemic B-lymphoblasts from normal B-cell precursor counterparts "hematogones." Neuropilin-1 (NRP-1)/CD304 is a vascular endothelial growth factor receptor implicated in the progression of hematological malignancies. We evaluated NRP-1/CD304 as MRD and prognostic marker in pediatric precursor B-ALL using FCM. Seventy children with precursor B-ALL and 40 control children were enrolled. CD304 percentage and fluorescence intensity were significantly higher in precursor B-ALL at diagnosis compared with controls. In total, 28 of 70 (40%) precursor B-ALL patients at diagnosis were CD304 (group A), whereas 42/70 (60%) patients were CD304 (group B). Group A showed higher incidence of lymphadenopathy and TEL-AML1 fusion gene than group B. CD304 was reevaluated in group A patients at day 28 postinduction chemotherapy which revealed 12/28 (42.9%) patients with persistent CD304 expression (MRD; group A1) and 16/28 (57.1%) patients who turned CD304 (MRD; group A2). At diagnosis, group A1 showed lower incidence of TEL-AML1 fusion gene and higher risk stratification than group A2. NRP-1/CD304 expression by FCM is efficient in discriminating leukemic B-lymphoblasts from hematogones, a stable leukemia-associated phenotype for MRD monitoring, and a putative poor prognostic marker in pediatric precursor B-ALL.