Role of interleukin 4 (IL4) and interleukin 6 (IL6) in the pathogenesis and prognosis of childhood primary immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the breakdown of immune tolerance. Impairment of the cellular immunity is primarily evaluated by the levels of the cytokines which can help in predicting the course of ITP. We aimed to assess the levels of IL4 and IL6 in children with ITP and evaluate their role in the pathogenesis and prognosis of this disease. A prospective cohort study was carried on 60 children (15 patients with newly diagnosed ITP, 15 patients with persistent ITP, 15 patients with chronic ITP and 15 healthy children as a control group). Serum IL-4 and serum IL-6 were measured using Human IL-4 and IL-6 ELISA kit in patients and controls. Patients with newly diagnosed and persistent ITP had significantly higher levels of IL4 and IL6 compared to patients with chronic ITP and healthy controls (p < 0.001). The mean serum level of IL4 was 762.0, 741.0, 364.6 and 436.8 pg/ml, and the mean serum level of IL6 was 178.5, 164.4, 57.9 and 88.4 pg/ml for patients with newly diagnosed, persistent, chronic ITP and healthy controls respectively. Serum IL-4 was significantly higher in patients who achieved remission than those who did not improve on first line therapy. CONCLUSION: Serum IL-4 and IL-6 may have a role in the pathogenesis of primary ITP. IL-4 seems to be a good predictor to treatment response. WHAT IS KNOWN: • There is a delicate balance of specific cytokine levels in immune thrombocytopenia, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. changes in IL-4 and IL-6 might be involved in the pathogenesis of newly diagnosed ITP in both paediatric and adult patients. • We conducted this research study to measure the serum level of IL-4 and IL-6, in newly diagnosed, persistent and chronic ITP patients and study their relation to disease pathogenesis as well as patient's outcome. WHAT IS NEW: • We found that IL4 seems to be a good predictor to treatment response and it was a very interesting observation in our study, and to the best of our knowledge, there is no published data about this finding.

Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor-1 and osteonecrosis risk in childhood acute lymphoblastic leukemia.

BACKGROUND: Osteonecrosis (ON) is one of the major therapy-related complications in childhood acute lymphoblastic leukemia (ALL). The purpose of the current study is to assess the frequency of ON in children with ALL and to detect whether polymorphisms in vitamin D receptor gene (VDR) and plasminogen activator inhibitor-1 (PAI-1) gene can affect the risk of ON. PATIENTS AND METHODS: Nighty-six ALL children were enrolled. Serum 25-hydroxyvitamin D 25(OH)D levels were performed in addition to the detection of polymorphisms in PAI-1and VDR genes by polymerase chain reaction. RESULTS: Ten out of 96 patients had ON (four males and six females aged above 10 years) and had an insufficient level of 25(OH)D. Fifty-two percent of patients had PAI-1 GG genotype while 48% had PAI-1 GA genotype. PAI-1 polymorphism was detected in 60% of all ON cases. The frequencies of VDR genotypes were CT (56.3%), CC (39.6%), and TT (4.2%). Osteonecrosis was found in eight patients with CC genotype and in two patients with CT genotype. CONCLUSION: Osteonecrosis can develop early during the therapy of ALL. Older age and insufficient level of 25(OH)D were considered important risk factor for the development of osteonecrosis. PAT-1 and VDR gene polymorphism may be a genetic risk factor in its pathogenesis.

Assessment of cystatin C in pediatric sickle cell disease and ß-thalassemia as a marker of subclinical cardiovascular dysfunction: a case-control study.

Cardiovascular complications represent the main determinant of survival in patients with hemoglobinopathies. Serum cystatin C is a well-known marker of nephropathy in sickle cell disease (SCD) and ß-thalassemia patients that has recently emerged as a strong predictor of cardiovascular dysfunction in patients with and without kidney disease. We performed a case control study to determine the role of cystatin C as a predictor of subclinical cardiovascular dysfunction in SCD and ß-thalassemia patients. We enrolled 40 SCD patients with a mean age of 12.4 years, 40 ß-thalassemia patients with a mean age of 11.4 years and 40 age and sex-matched controls. We assessed hematological profile, serum ferritin, urinary albumin-creatinine ratio (UACR), serum cystatin C, echocardiography and carotid intima media thickness (CIMT). UACR, cystatin C and CIMT were higher in SCD and ß-thalassemia patients compared to controls (p < .001). Significantly higher cystatin C levels were observed in SCD and ß-thalassemia patients with nephropathy or left ventricular systolic dysfunction (shortening fraction <30%, or ejection fraction <55%; p < .001). Moreover, SCD patients with pulmonary hypertension had significantly higher cystatin C levels. Cystatin C levels were positively correlated with CIMT in SCD (p = .02) and ß-thalassemia patients (p < .001) while negatively correlated with ejection fraction and shortening fraction (p < .001). The cutoff values of cystatin C ≥ 16.03 and ≥ 13.2 (ng/mL) could detect subclinical cardiac dysfunction risk among SCD and ß-thalassemia patients respectively. Cystatin C appears to be a promising marker for subclinical cardiovascular dysfunction in SCD and ß-thalassemia patients.

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.

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.

Diarrhea in neutropenic children with cancer: An Egyptian center experience, with emphasis on neutropenic enterocolitis.

BACKGROUND: Diarrhea is a frequent complication in children with cancer who received intensive chemotheraputic regimens. It may be caused by several factors, neutropenic enterocolitis (NE) being the most serious. AIM: To study diarrhea in neutropenic cancer patients in the pediatric age group, with its underlying etiologies and risk factors, especially the bacterial causes, with special concern on NE. MATERIALS AND METHODS: This study was carried out at the Pediatric Hematology and Oncology Units, Zagazig University Hospitals, Egypt, from January 2009 to September 2010. All children with malignant diseases who are ≤12 years of age were included. Patients who were neutropenic (<500/ mm(3)) on admission or who became neutropenic during their stay in the hospital were monitored regularly (daily) for diarrhea. Neutropenic cancer patients with diarrhea were grouped into two groups: Group 1, with NE, and group 2, with neutropenic diarrhea rather than NE. On the first day of diarrhea, patients were subjected to complete blood count, blood cultures, stool microscopy and culture. Abdominal ultrasonography was carried out within 3 days of diarrhea. RESULTS: A total of 200 children ≤12 years old, suffering from different malignancies, with a total of 180 neutropenic episodes were followed. Diarrhea was observed in 100 episodes (55.5%). NE constituted 16% of these diarrheal episodes. All patients with NE had significantly more severe neutropenia, and this was of longer duration than the other group. All patients with NE were febrile, with 100% positive blood culture. Stool analysis diagnosed giardiasis in 4.8% of the non-NE patients and in none of the NE patients, while stool culture was positive in 75% of the NE patients compared with 40.5% of the other group. CONCLUSIONS: Diarrhea is a common complication in neutropenic cancer children. Gram negative bacteria and Candida are the most incriminated pathogens. Duration and severity of neutropenia carry a great risk for the development of NE.