Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes

Many patients with bone marrow failure syndromes need frequent transfusions of red blood cells, and most of them eventually suffer from organ dysfunction induced by excessively accumulated iron. The only way to treat transfusion-induced iron overload is iron chelating therapy. However, most patients have not been treated effectively because daily/continuous administration of deferoxamine is difficult for outpatients. Recently, a novel oral iron chelator, deferasirox, has been developed, and introduction of the drug may help many patients benefit from iron chelation therapy. In this review, we will discuss the current status of iron overload in transfusion-dependent patients, and the development of Japanese guidelines for the treatment of iron overload in Japan, which were established by the National Research Group on Idiopathic Bone Marrow Failure Syndromes in Japan

Iron chelation therapy in the myelodysplastic syndromes and aplastic anemia: a review of experience in South Korea

Emerging clinical data indicate that transfusion-dependent patients with bone marrow-failure syndromes (BMFS) are at risk of the consequences of iron overload, including progressive damage to hepatic, endocrine, and cardiac organs. Despite the availability of deferoxamine (DFO) in Korea since 1998, data from patients with myelodysplastic syndromes, aplastic anemia, and other BMFS show significant iron overload and damage to the heart and liver. The recent introduction of deferasirox, a once-daily, oral iron chelator, may improve the availability of iron chelation therapy to iron-overloaded patients, and improve compliance in patients who may otherwise find adherence to the DFO regimen difficult

Body iron metabolism and pathophysiology of iron overload

Iron is an essential metal for the body, while excess iron accumulation causes organ dysfunction through the production of reactive oxygen species. There is a sophisticated balance of body iron metabolism of storage and transport, which is regulated by several factors including the newly identified peptide hepcidin. As there is no passive excretory mechanism of iron, iron is easily accumulated when exogenous iron is loaded by hereditary factors, repeated transfusions, and other diseased conditions. The free irons, non-transferrin-bound iron, and labile plasma iron in the circulation, and the labile iron pool within the cells, are responsible for iron toxicity. The characteristic features of advanced iron overload are failure of vital organs such as liver and heart in addition to endocrine dysfunctions. For the estimation of body iron, there are direct and indirect methods available. Serum ferritin is the most convenient and widely available modality, even though its specificity is sometimes problematic. Recently, new physical detection methods using magnetic resonance imaging and superconducting quantum interference devices have become available to estimate iron concentration in liver and myocardium. The widely used application of iron chelators with high compliance will resolve the problems of organ dysfunction by excess iron and improve patient outcomes

Postoperative Lateral Ligamentous Laxity Diminishes with Time After TKA in the Varus Knee

For successful TKA, good soft tissue balance is one of the most important factors; however, it is unknown whether the coronal balance immediately after surgery is maintained with time. We hypothesized, if neutral mechanical alignment was achieved at the time of TKA, some degree of lateral ligamentous laxity could be accepted and the laxity would diminish with time. To confirm this hypothesis, we posed two scientific questions: (1) Does the coronal ligament balance measured immediately after TKA change with time? (2) Does the degree of preoperative varus alignment correlate with the lateral or medial ligamentous laxity observed after TKA? We measured coronal lateral or medial ligamentous laxity in 71 knees with varus deformities immediately after surgery and at 3, 6, and 12 months thereafter. The mean mechanical axis was 15.9° varus preoperatively and 0.4° varus postoperatively. The mean medial ligamentous laxity was relatively constant postoperatively from immediately after surgery to 12 months. However, the mean lateral ligamentous laxity was as much as 8.6° immediately after surgery and decreased to 5.1° at 3 months. The lateral ligamentous laxity immediately after surgery correlated with the preoperative varus mechanical axis. Our data show residual lateral ligamentous laxity observed in preoperative varus deformity may be corrected spontaneously after TKA