Thyroid hemodynamic alterations in Egyptian patients with sickle cell disease: relation to disease severity, total body iron and thyroid function.

Background: Intraparenchymal thyroid Doppler measurements might be considered a useful index of the thyroid status as well as micro-circulation elsewhere in the body among sickle cell disease (SCD) patients. The authors aim to evaluate the intra-thyroidal hemodynamic changes and thyroidal volume in SCD patients and its relation to the disease severity, and thyroid functions tests as well as iron overload state. Methods: Sixty SCD patients, randomly recruited from the regular attendants of the Pediatric Hematology Clinic, Ain Shams University, Cairo, Egypt, were studied focusing on the disease duration, the transfusion history, the recorded Hydroxyurea, and chelation therapies and the vaso-occlusive crises history. Thyroid Doppler ultrasonography [Thyroid volume, Resistance index (RI) and pulsatility index (PI)] was performed and liver & cardiac MRI were assessed. Results: Thirteen (21.7%) of the SCD patients had hypothyroidism by thyroid function tests. SCD patients had significantly higher RI and PI values and a lower thyroid volume compared to the control group. No significant correlations were found between the thyroid functions tests and the thyroid Doppler parameters; a negative correlation of the disease duration to the thyroid volume and a positive one to RI & PI values were found. The mean serum ferritin did not significantly correlate to the thyroid Doppler indices nor did Liver and cardiac MRI results. Conclusion: The authors demonstrated an increased intra-thyroidal RI & PI and a decreased thyroid volume among SCD patients which might be related to impaired thyroidal microcirculation and vasculopathy rather than iron overload.

Vascular dysfunction in patients with young ß-thalassemia: relation to cardiovascular complications and subclinical atherosclerosis.

We aimed to study the endothelial dysfunction among children and adolescents with transfusion-dependent ß-thalassemia using von Willebrand factor antigen (VWF:Ag) and flow cytometric analysis of circulating CD144(+) endothelial microparticles (EMPs) and endothelial progenitor cells (CD34(+)VEGFR2(+)) and assess their relation to iron overload, erythropoietin and chelation therapy as well as echocardiographic parameters and carotid intima-media thickness. The VWF:Ag, EMPs, and CD34(+)VEGFR2(+) cells were significantly higher among patients with ß-thalassemia than controls (P < .001). The type of chelation and patients' compliance did not influence the results. No significant correlations were found between the studied vascular markers. Patients with evident heart disease had higher VWF: Ag, EMPs, and CD34(+)VEGFR2(+) cells than those without. Carotid intima-media thickness was increased among patients but not correlated with vascular markers. We suggest that procoagulant EMPs and VWF: Ag are involved in cardiovascular complications in patients with young ß-thalassemia. CD34(+)VEGFR2(+) cells were further increased in response to tissue injury contributing to reendothelialization and neovascularization.

BIRC6/Apollon gene expression in childhood acute leukemia: impact on therapeutic response and prognosis.

OBJECTIVE: Although BIRC6/Apollon seems to play a critical role as an antiapoptotic regulator, its clinical relevance in acute leukemia remains largely elusive. Therefore, we aimed to investigate BIRC6 gene expression in childhood acute leukemia in relation to clinicopathological characteristics at presentation, therapeutic response, and prognosis. METHODS: BIRC6 expression level was assessed in 75 children with acute leukemia; 30 patients with acute myeloblastic leukemia (AML) and 45 patients with acute lymphoblastic leukemia (ALL) using real-time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The median level of BIRC6 expression did not differ significantly between AML and ALL patients. BIRC6 expression level was higher in patients with AML and ALL with extramedullary involvement, white blood cell (WBC) count ≥ 10 × 10(9) /L, and unfavorable cytogenetics at diagnosis. BIRC6 gene expression was higher in patients with unfavorable response to therapy at day 14, those who developed relapse or died in both leukemic groups. The best cutoff value of BIRC6 to predict therapeutic response and disease outcome was determined. AML and ALL patients with BIRC6 overexpression had significantly shorter overall and disease free survivals. CONCLUSIONS: This is the first report to study BIRC6 gene in pediatric ALL. Our results suggested that BIRC6 gene expression could be considered as an adverse risk factor in childhood acute leukemia and, hence, could be used to guide therapeutic regimens.