Interleukin-1 Receptor Antagonist Gene Polymorphisms in Egyptian Children and Adolescents With Primary Immune Thrombocytopenia: Association With Disease Susceptibility, Response to Therapy, and Outcome.

Immune thrombocytopenia (ITP) is one of the most common hematologic disorders with poorly predictable clinical course and outcome. We studied the distribution of interleukin 1 receptor antagonist (IL-1Ra) gene polymorphism (intron-2) among children and adolescents with ITP and correlated IL-1Ra gene polymorphism to disease susceptibility, response to therapy, and outcome. Sixty children with ITP (mean age: 9.2±4.5 y) and 100 healthy controls (mean age: 8.83±4.05 y) were enrolled. The frequencies of the allele A2 and genotype A1A2 were significantly higher in patients compared with controls ( P <0.0001, P =0.0008, respectively). Allele A2 conferred 3.1 times increased relative risk for disease development. Allele A2 and genotypes A1A2 and A2A2 were significantly more frequent among remitted patients ( P =0.028 and 0.024, respectively). There was no significant difference between different genotypes and alleles regarding bleeding score ( P >0.05). Patients with polymorphic allele A2 (A1A2/A2A2) showed significantly better response to steroids than those with homozygous wild allele A1 ( P =0.028). IL-1Ra polymorphism might contribute to the susceptibility to ITP in Egyptian children. The presence of A2 polymorphic allele of IL-1Ra gene was found to be associated with better disease outcome and response to steroids than those with homozygous wild allele.

Treatment outcomes for childhood acute lymphoblastic leukemia in low-middle income country before minimal residual disease risk stratification.

BACKGROUND: Outcome of childhood acute lymphoblastic leukemia (ALL) in low- and middle-income countries is lagging in many aspects including diagnosis, risk stratification, access to treatment and supportive care. OBJECTIVE: to report the outcome of childhood ALL at Ain Shams University Children's Hospitals with the use of risk-based protocols before the implementation of minimal residual disease technology and to evaluate the use of double delayed intensification (DDI) in standard risk patients. METHODS: Two hundred and twenty patients with ALL diagnosed between January 2005 and December 2014 were included in the study. Patients were treated according to a modified CCG 1991 and 1961 for standard and high risk respectively. Patients were stratified into three risk groups: standard risk (SR), high-risk standard arm (HR-SA), and high-risk augmented arm (HR-AA). RESULTS: Among the whole cohort, the 10-year event-free survival (EFS) and overall survival (OS) were 78.1% and 84.3% respectively. Patients with Pre-B immunophenotype (IPT) had significantly better outcome than T-cell IPT (EFS 82.0% versus 58.6%, p < 0.001; OS 86.9% versus 69%, p = 0.003 for Pre-B and T-cell respectively). Among the SR group, patients treated with single delayed intensification (SDI) had comparable EFS and OS rates when compared to patients treated with DDI with EFS 82.4% versus 87.5%, p = 0.825 and OS 88.2% versus 93.5%, p = 0.638 for SDI and DDI groups, respectively. CONCLUSION: The use of risk-based protocol with simple laboratory techniques resulted in acceptable survival outcome in resource limited settings. The use of double delayed intensification showed no survival advantage in patients with standard risk.

Analysis of Causes of Hospitalization Among Children with Sickle Cell Disease in a Group of Private Hospitals in Jeddah, Saudi Arabia.

PURPOSE: Sickle cell anemia (SCA) is a chronic hematologic condition that requires frequent hospitalization representing a significant economic burden on the health services. The aim of this study was to explore the causes and underlying factors of hospitalization among children with SCA, as well as the factors affecting their length of hospital stay. PATIENTS AND METHODS: This retrospective study included children and adolescents less than 16 years old who were admitted in a group of private hospitals in Jeddah, Saudi Arabia, during the period from January 2018 to December 2019. RESULTS: A total of 94 patients were included in this study, 59.6% were males, with a mean age 7.29 ± 3.82 years. The majority of the patients (91.5%) had sickle cell disease. The most common cause of hospital admission was vaso-occlusive crises (VOC) (64.9%) followed by infection (24.5%), acute chest syndrome (ACS) (18.1%), and acute hemolytic crisis (12.8%). We found no significant difference between gender and different causes of admissions (p > 0.05). While in relation to age group, limb pain and back pain were found to be significantly more frequent among children ≥ 7 years old (p = 0.03,0.04), while infections were significantly more frequent among children < 7 years old (p = 0.003). We analyzed the length of hospital stay and different factors, and we found that the mean length of hospital stay was significantly higher among children who were admitted with infections (p = 0.01) and ACS (p < 0.001) and among children who are non-compliant on hydroxyurea (p = 0.04). CONCLUSION: The most common cause of hospitalization among children with SCD in Jeddah, Saudi Arabia, was VOC followed by infection, ACS and acute anemia. The length of hospital stay was more prolonged among children with infection and ACS, as well as children who were non-compliant to hydroxyurea.

Analysis of the most common causes of blood donor deferral in northern Jeddah: a single-center study.

PURPOSE: We aimed to conduct a retrospective study in order to statistically analyze the commonest causes for blood donor rejection in northern Jeddah, Kingdom of Saudi Arabia according to the American Association of Blood Banks. This will help in developing better strategies to minimize the loss of treasured blood donors. SUBJECTS AND METHODS: A sample of 500 rejected donors was randomly selected from a single blood bank between October 2016 to May 2017. The evaluation of blood donors was according to the personal history questionnaire and a medical examination done before the blood donation proceeded. RESULTS: The causes of deferral were categorized into three main categories: personal factors, medical examination and medical history. The most common personal cause of deferral was lack of sleep (29 [5.80%]); however, the most common medical examination cause of deferral was low blood pressure (68 [13.60%]). Concerning the medical history, the commonest cause was cupping (58 [11.6%]). CONCLUSION: Low blood pressure (13.6%), cupping (11.6%) and less hours of sleep in the night prior to donation (5.8%) were the major causes of rejection in this study. Similarities and variations between the commonest causes of blood donor rejection may be due to the differences and similarities in the geographic area and in the cultural, educational and socioeconomic factors.

Serum Sclerostin Level and Bone Mineral Density in Pediatric Hemophilic Arthropathy.

OBJECTIVE: To assess serum sclerostin levels in relation to severity of arthropathy and bone mineral density (BMD) in children with hemophilic arthropathy. METHODS: This cross-sectional study included 40 male children suffering from Hemophilia A, and 10 matched healthy controls. Assessment of factor VIII deficiency degree, frequency of bleeding, type of treatment, body mass index (BMI), disease severity using the Hemophilia Joint Health Score (HJHS) and lumbar spine (LS) Z score for bone mineral density (BMD) using dual-energy X-ray absorbiometry was done. Serum sclerostin levels were measured for all patients and controls. RESULTS: Significant difference of serum sclerostin levels between the patient and control groups with Mean ± SD (0.09 ± 0.07 ng/ml) and (0.04 ± 0.01 ng/ml) (P value = 0.028) respectively was found. Significant positive correlations between serum sclerostin levels and the patients' age, and HJHS (P value <0.05) were found, while it had negative correlation with DEXA Z score, not reaching a significant value. LS-BMD-Z score levels ranged from (-4.5 to 1.2), with 15 patients with low BMD Z score (less than -2) representing 37.5% of total patients. CONCLUSIONS: Serum sclerostin levels are elevated in hemophilic children denoting bone metabolism affection and correlates with increased age, and HJHS. Increased levels of serum sclerostin may identify hemophilic patients at high risk for developing osteoporosis.

Renal Abnormalities Among Egyptian Children With Hemophilia A Using Renal Scintigraphy: Relation to Risk Factors and Disease Severity.

Many risk factors may contribute to renal disease in patients with hemophilia A. AIM: We aimed to evaluate functional and structural renal abnormalities among a group of Egyptian children with severe and moderate hemophilia A using technetium-99m diethylene triamine pentaacetic acid (99mTc-DTPA) and technetium-99 m dimercaptusuccinic acid (99mTc-DMSA) scan. We also aimed to determine the relation between these abnormalities and different risk factors and disease severity. PATIENTS AND METHODS: Forty male patients, 16 with severe and 24 with moderate hemophilia A, were enrolled in this study. Their mean age was 10.2 ± 4.3 years (range, 5-17 years). Full history taking, clinical examination, laboratory, and radionuclide investigations including serum creatinine, blood urea nitrogen (BUN), urine analysis, creatinine clearance, 24-hour urinary protein, 99mTc-DTPA scan, and 99mTc-DMSA scan were performed to all enrolled patients. RESULTS: Serum creatinine and BUN were normal in all patients, and corrected creatinine clearance was diminished in 2 patients. However, 99mTc-DTPA results yielded 19 (47.5%) patients with diminished glomerular filtration rate (GFR). Moreover, it showed that 14 (35%) had obstructive uropathy, 15 (37.5%) had obstructive nephropathy, while 11 (27.5%) patients showed normal scan. One patient had atrophy of 1 kidney on 99mTc-DMSA scan. Among our cohort, 5 (12.5%) patients were hypertensive. Microscopic hematuria was detected in 14 (35%) patients while 72.5% had proteinuria. We found an association between hematuria and hypertension with diminished GFR. CONCLUSION: Despite normal kidney functions (serum creatinine and BUN), we found a high rate of diminished GFR and obstructive uropathy and nephropathy as detected by 99mTc-DTPA scan among children with hemophilia A.

Study of alpha hemoglobin stabilizing protein expression in patients with ß thalassemia and sickle cell anemia and its impact on clinical severity.

UNLABELLED: The α hemoglobin stabilizing protein (AHSP) binds α-Hb and prevents its precipitation limiting free α-Hb toxicities. Our aim was to study AHSP expression in ß thalassemia syndromes in relation to their clinical severity and to compare it with its level in sickle cell anemia. We compared patients with ß-thalassemia (n=37) (ß-thalassemia major (BTM) (n=19) and ß-thalassemia intermedia (BTI) (n=18)) with 12 patients with sickle cell anemia as regards clinical severity, age at presentation, transfusion dependency, mean pre-transfusion hemoglobin level, use of hydroxyurea and AHSP expression by real time quantitative PCR. Median (and IQR) AHSP expression was significantly higher in patients with sickle cell anemia 2275 (3898) compared to thalassemia 283 (718), P=0.001, with no significant difference between BTM and BTI (P=0.346). It was also significantly higher in non-transfusion dependent patients with ß thalassemia (NTDT) compared to transfusion dependent ones (P=0.019), and in patients on hydroxyurea therapy (P<0.001). However, there was no significant difference in its level according to clinical severity score (P=0.946) or splenectomy status (P=0.145). CONCLUSION: AHSP expression was higher in patients with sickle cell anemia versus thalassemia, with no significant difference between BTM and BTI. Expression was higher in patients with NTDT and on hydroxyurea therapy.

Group A beta-hemolytic streptococcal pharyngitis and carriage rate among Egyptian children: a case-control study.

BACKGROUND: Improper prescription of antibiotics for treatment of acute pharyngitis predisposes to emergence of a carrier state and antibiotic-resistant strains of group A streptococci (GAS). We sought to identify the frequency and antimicrobial susceptibility patterns of group A streptococci among Egyptian children with acute pharyngitis compared with asymptomatic children. DESIGN AND SETTING: Case-control study conducted from September 2013 to August 2014 at a pediatric outpatient clinic in Egypt. PATIENTS AND METHODS: Throat swabs were collected from children with acute pharyngitis and from asymptomatic children. We evaluated the accuracy of McIsaac scores and the rapid antigen detection test (RADT) for diagnosis of GAS pharyngitis with throat culture as a reference test. Antimicrobial susceptibility testing of GAS isolates was done by the disc diffusion method. RESULTS: Of 142 children with acute pharyngitis (cases) and 300 asymptomatic children (controls) (age range, 4-16 years), GAS pharyngitis was diagnosed in 60/142 children (42.2%); 48/300 (16%) were found to be carriers. All GAS isolates in the case group were sensitive to penicillin; however, an MIC90 (0.12 micro g/mL) for penicillin is high and an alarming sign. The resistance rate to macrolides was 70% with the cMLSB phenotype in 65.1%. The sensitivities and specificities were 78.3% and 73.2% for McIsaac score of >=4 and 81.1% and 93.9% for RADT, respectively. GAS isolates in the control group were 100% sensitive to penicillin, while 12.5% and 37.5% were resistant to macrolides and tetracycline, respectively. CONCLUSION: An increased MIC90 for GAS isolates to penicillin is an alarming sign. A high frequency of resistance to macrolides was also observed.

Ovarian function in female survivors of childhood malignancies.

BACKGROUND: Chemotherapy-induced infertility is a common side effect observed in women of fertile age after treatment for malignant disease. OBJECTIVES: to study gonadal function and fertility in female survivors of childhood malignancies. PATIENTS AND METHODS: Study included 30 female cancer survivors and 30 age-matched healthy females as a control group. Data collected regarding; type of malignancy, age at diagnosis, duration on and off treatment, treatment received (radiation or chemotherapeutic regimens), sexual, menstrual, pregnancy, and fertility histories were also recorded. Laboratory investigations included; T4, thyroid stimulating hormone (TSH), leutinizing hormone (LH), follicular stimulating hormone (FSH), and anti-Mullerian hormone (AMH). Pelviabdominal ultrasound was done to estimate the mean ovarian volume. RESULTS: Among patients; 80% had normal menarche and 6 (20%) had delayed menarche (P > .05). There was higher LH and FSH levels and lower AMH levels in patients (P < .05) with no significant difference in thyroid function tests (P > .05). Lower mean ovarian volume was observed among female survivors (6.32 ± 2.31 cm(3)) (P = .041). There was a higher FSH and LH levels among female survivors of solid tumors compared to those with hematological tumors (P = .05 and .04 respectively). There was a significant positive correlation between FSH level and patients' age at start of malignancy (r = 0.65, P = .014), age of menarche (r = 0.74, P = .036), and duration of treatment (r = 0.54, P = .025).There was a significant negative correlation between age of menarche and AMH level (r = -0.61, P = .03). CONCLUSION: Female survivors of childhood malignancies had reduced ovarian reserve and reduced mean ovarian volume, especially those with older age, older age of menarche, and longer treatment duration.