OBJECTIVE -To study the prevalence of and risk factors for abnormal glucose tolerance in transfusion-dependent ␤-thalassemic patients.RESEARCH DESIGN AND METHODS -A total of 89 transfusion-dependent ␤-thalassemic patients were interviewed. Diabetes was previously diagnosed in 14 of them. In the remaining 75 patients, 68 participated in an oral glucose tolerance test. Potential risk factors were identified using the independent t test, 2 test, and Fisher's exact test. Logistic regression analysis was used to select the independent risk factors that best predicted abnormal glucose tolerance. A two-tailed P value of Ͻ0.05 was considered to be statistically significant.RESULTS -The prevalence of impaired glucose tolerance was 8.5% (7 of 82) and that of diabetes was 19.5% (16 of 82). Presentation with diabetic ketoacidosis was 31.1% (5 of 16). The risk factors for abnormal glucose tolerance found in transfusion-dependent ␤-thalassemic patients were serum ferritin concentration and hepatitis C infection.

Worldwide, thalassemia is the most commonly inherited hemolytic anemia, and it is most prevalent in Asia and the Middle East. Iron overload represents a significant problem in patients with transfusion-dependent beta-thalassemia. Chelation therapy with deferoxamine has traditionally been the standard therapeutic option but its usage is tempered by suboptimal patient compliance due to the discomfort and demands associated with the administration regimen. Therefore, a great deal of attention has been focused on the development of oral chelating agents. Deferiprone, even though available for nearly two decades in Asia with recent encouraging data on cardiac iron removal and long-term efficacy, has serious adverse effects including agranulocytosis and neutropenia which has impeded it from routine clinical practice. A novel oral chelator; deferasirox is effective throughout a 24 h dosing period and both preclinical and clinical data indicate that it successfully removes both hepatic and cardiac iron. In Asia, optimal management of severe thalassemia patients and the availability and access to oral iron chelators still presents a major challenge in many countries. In this regard, the development and implementation of consensus guidelines for management of Asian patients with transfusion-dependent thalassemia will be a major step towards improving and maintaining the continuity of patient care.

The incidence and clinical spectrum of severe bacterial infection were studied in 89 patients with thalassemia major that was diagnosed between January 1971 and March 2002. There were 20 patients with 24 episodes of severe bacterial infection, resulting in an incidence of 1.6 infections per 100 patient-years. The clinical spectrum included liver abscess (6 cases), septicemia (6 cases), soft-tissue infection (2 cases), osteomyelitis (2 cases), corneal ulcer (1 case), enteritis (1 case), and abscesses of the lung, kidney, intra-abdominal region, retropharynx, gums, and buttocks (1 case each). The leading causal microorganisms were gram-negative bacilli, especially Klebsiella pneumoniae (10 of 20 isolates). Other responsible pathogens were Pseudomonas aeruginosa (2/20), Vibrio vulnificus (2/20), Acinetobacter baumanii (1/20), Streptococcus intermidius (1/20), Yersinia enterocolitica (1/20), Staphylococcus aureus (1/20), Escherichia coli (1/20), and Salmonella species (1/20). Splenectomy and delays in the start of iron-chelating therapy were 2 independent risk factors.

In patients with thalassemia major, genetic differences may influence their susceptibility to hypogonadotropic hypogonadism, possibly as a result of differences in the amounts of blood transfused and/or their vulnerability to free radical damage. The hematologic phenotype is a main determinant of the severity of thalassemia major; hence, it may influence the need for and frequency of blood transfusion and the patient's iron-overload status.

Aberrant expression of the simple mucin-type carbohydrate antigens such as T, Tn, sialyl-T and sialyl-Tn is associated with poor prognosis in several cancers. b1,3-N-acetylglucosaminyltransferase-3 (B3GNT3), a member of the b3GlcNAcT family, is responsible for forming extended core 1 (T antigen) oligosaccharides. The role of B3GNT3, which is expressed in various tissues including human fetal brain, in regulating neuroblastoma (NB) formation and cell behaviors remains unclear. Here, we showed that increased B3GNT3 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as a favorable Shimada's subset of pathology. Univariate and multivariate analyses revealed that positive B3GNT3 expression in tumor tissues predicted a favorable prognosis in NB patients independent of other prognostic markers. B3GNT3 overexpression suppresses T antigen formation and malignant phenotypes including migration and invasion of SK-N-SH cells, whereas B3GNT3 knockdown enhances these phenotypes of SK-N-SH cells. Moreover, B3GNT3 expression decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt and ERK1 ⁄ 2. We conclude that B3GNT3 predicts a favorable cancer behavior of NB and suppresses malignant phenotypes by modulating mucin-type O-glycosylation and signaling in NB cells. (Cancer Sci 2013; 104: 1600-1608 N euroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for 8-10% of all pediatric malignancies. This tumor arises from primordial neuroepithelial cells of the neural crest.(1,2) The behavior of NB is markedly heterogeneous, ranging from spontaneous differentiation or regression into ganglioneuroblastoma (GNB) or ganglioneuroma with a favorable prognosis to highly undifferentiated tumors with a rapid progression and very poor outcomes.(3) Metastasis, a NB staging factor, is found in 50-60% of all NB cases, and advanced NB typically metastasize to distant lymph nodes, bone marrow, bone, liver or other organs. Although the overall prognosis for NB patients has improved remarkably with recent advances in therapies, the long-term survival of patients with high-risk NB remains poor despite intensive multimodal therapy.(1,2) Thus, finding new prognostic factors is required to further understand NB pathogenesis and to tailor therapies for improving treatment outcomes of patients with unfavorable NB.Glycosylation is one of the most important processes in posttranslational modification of proteins. It is commonly found that oligosaccharide structures of glycoproteins are changed during malignant transformations.(4) Because the sugar chains of glycoproteins are essential for maintaining ordered intercellular interactions among differentiated cells in multicellular organisms, alterations in the sugar chains constitute the molecular basis of abnormal intercellular behaviors in tumor cells, such as invasion into the surrounding tissues and metastasis. (5) There are two major types of protein glycosylation in mam...