NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan.

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.

Dietary supplementation of 25-hydroxycholecalciferol improves livability in broiler breeder hens.

The study aimed to examine the effects of 25-hydroxycholecalciferol (25-OH-D3) on reproductive performance and livability in broiler breeder hens. Hens at age of 26 wk were continued on restricted rations (R) or allowed ad libitum feeding (Ad) to 60 wk of age. Ad-feed intake greatly impaired egg production and hens' livability. The survival rate in both R- and Ad-hens was improved (86.7 vs.78.9% and 48.2 vs.29.1%, respectively) as was egg production in R-hens (P < 0.05) by inclusion of 69 µg 25-OH-D3/kg feedin the basal diet. Sudden death (SD) was the cause of hen mortality; hens died earlier with heavier BW and greater absolute and relative abdominal fat weights than surviving hens. Interestingly, feed intake of SD hens became less than that of surviving hens after 37 and 42 wk in Ad- and R-groups, respectively, and led to a progressive decline in SD hen BW with a ratio (relative to surviving hens of the same age) equaled 1 around 34 to 38 wk in Ad-groups and 52 to 53 wk in R-groups. Supplementation of 25-OH-D3 ameliorated untoward changes of heart and respiratory rate of Ad-survivors after 29 wk (P < 0.05), but had no significant effects on SD AD-hens. In contrast to the surviving counterparts, all SD hens experienced persistently higher respiratory rates in conjunction with declining heart rates (P < 0.05), suggesting compromised cardiac function as the cause of SD, in which hens increased heart and respiratory rate for more blood and oxygen supply to meet the need for rapid BW gain and/or adiposity in response to Ad-feed intake or due to genetically better feed efficiency even under R-feed intake. As the cardiorespiratory derangements advanced, compromised cardiac function ultimately led to heart failure and sudden death despite spontaneous reductions in feed intake and BW loss in all SD hens. Provision of 69 µg 25-OH-D3/kg feed is an effective and practical method to improve livability in broiler breeder hens.

Superwarfarin intoxication: hematuria is a major clinical manifestation.

Since superwarfarin is popular and readily available in stores, it may cause intoxication or overexposure, which can result in coagulopathy or abnormal bleeding in humans and, thus, is an important public health problem. We report our clinical experience with superwarfarin intoxication. Nine patients, including eight patients who had histories of ingesting superwarfarin, were studied. Of the patients, hematuria occurred in eight. Laboratory tests among the nine patients showed extremely prolonged prothrombin times and activated partial thromboplastin times, which could be corrected to normal by mixing 1:1 with normal pooled plasma; they also had very low functional levels of factor II, VII, IX, X, and proteins C and S, but normal functional levels of factors V, VIII, fibrinogen, and anti-thrombin III. Large doses of vitamin K1 were needed for 3 months or more to treat and correct the coagulopathy among the patients. The majority of the patients presented with gross hematuria, suggesting that hematuria is probably a major clinical manifestation of superwarfarin intoxication. Prolonged use of large doses of vitamin K1 is needed for the treatment of superwarfarin intoxication.

Hyperhomocysteinemia, deep vein thrombosis and vitamin B12 deficiency in a metformin-treated diabetic patient.

Vitamin B12 deficiency may be induced by long-term use of metformin, which may in turn lead to hyperhomocysteinemia. Thus, hyperhomocysteinemia may increase the risk of vascular thrombosis in diabetic patients, when metformin is used and a homozygous methylenetetrahydrofolate reductase (MTHFR) C677T mutation is present. We report a 65-year-old Taiwanese diabetic woman who was treated with metformin for 6 years and who had suffered from swelling of the left lower extremity for 3 months. Ascending venography confirmed the diagnosis of proximal deep vein thrombosis, while hyperhomocysteinemia, megaloblastic anemia caused by vitamin B12 deficiency, and a homozygous C677T mutation of the MTHFR gene were also found. She had no identifiable venous thrombotic risk factors other than hyperhomocysteinemia, which seemed to be caused by both MTHFR C677T homozygous mutation and vitamin B12 deficiency. With the substitution of insulin injection for metformin, short-term supplement of vitamin B12, and anticoagulant therapy for the deep vein thrombosis, her anemia and hyperhomocysteinemia recovered rapidly. The deep vein thrombosis also responded well. Our findings highly suggested the role of metformin in causing vitamin B12 deficiency, which may serve as an additional risk factor for venous thrombosis in diabetic patients. Our report also highlights the need to check vitamin B12 levels during metformin treatment.