[Safety of warfarin therapy in children with coronary aneurysm due to Kawasaki disease].

Objective: To investigate the safety of warfarin for Kawasaki disease (KD) with coronary artery aneurysm (CAA) and its prognosis. Methods: Twenty one children with KD complicated with giant CAA, multiple CAA in one coronary artery or thrombosis in coronary artery were enrolled in this prospective study. Warfarin was used to control the goal international normalized ratio (INR) ranging from 2.0 to 3.0. The CAA diameter, number, location and thrombus in coronary artery were recorded at the beginning of treatment, 1, 2, 3, 4 weeks and 2, 3, 6, 12 months after treatment, as well as the influence on INR, electrocaroliogram, creatine kinase-MB (CK-MB), troponin I. Standardized warfarin bleeding risk training and management was implemented. Children were divided into implementation group and non-implementation group according to the status of actual implementation of their parents. The incidence of bleeding events was compared between the two groups. Comparisons between groups were performed using a Rank sum test and a Fisher exact test. Results: In the 21 patients (15 males and 6 females), the age of onset ranged from 2 months to 6 years. There were 4 cases with grade Ⅱ, 7 cases with grade Ⅲ, 7 cases with grade Ⅳ and 3 cases with grade Ⅴ according to the severity of coronary arterial lesions before treatment. The time of clinical detection of thrombus in 10 children with thrombosis ranged from the fourth day to the fourth month. The dose distribution of warfarin was 0.06-0.10 mg/(kg·d), and the INR was 1.80-2.59. Among the 10 cases with thrombus, 8 cases had disappearance of thrombi and 2 cases with grade Ⅴ had thrombus organization to different degree. After treatment, the coronary artery ectasia of the 4 cases with grade Ⅱ all returned to normal. Among the 7 cases with grade Ⅲ, 3 cases of coronary artery aneurysms returned to normal, and 4 cases did not change. Among the 7 cases with grade Ⅳ , 5 cases of coronary artery aneurysms shrank to grade Ⅲ, and 2 cases remained unchanged. Three cases with grade Ⅴ lesions had no changes in aneurysm. Neither new thrombus nor new CAA was detected during the treatment. There was no significant change in electrocardiogram before and after treatment. No statistically significant difference was found regarding the troponin I (0.07 (0-3.01) vs. 0.04 (0-0.29) µg/L, Z=0.932, P>0.05) and CK-MB (20.6 (11.2-58.2) vs. 29.0 (16.7-47.0) U/L, Z=1.906, P>0.05) before and after treatment. The incidence of bleeding events in the implementation group was significantly lower than that in the non-implementation group (2/15 vs. 4/6, Fisher=5.689, P=0.031). Conclusions: The application of goal INR of 2.0-3.0 and adjustment of warfarin dose according to the severity of CAA combined with standardized and strict warfarin bleeding risk training and management, can increase the safety of warfarin therapy in children with KD, improve the prognosis of coronary artery lesions, promote the dissolution of thrombi, prevent new thrombosis, and effectively reduce the incidence of bleeding complication.

Prognostic significance of Cbx4 expression and its beneficial effect for transarterial chemoembolization in hepatocellular carcinoma.

Our recent investigations showed that polycomb chromobox 4 (Cbx4) promotes angiogenesis and metastasis of hepatocellular carcinoma (HCC) through its sumoylating action on hypoxia-inducible factor-1α protein. Here, we attempt to identify the prognostic significances of Cbx4 by a retrospective analyses in 727 cases of HCC patients with and without postoperative transarterial chemoembolization (TACE) or transarterial embolization (TAE). Binary logistic regression tests indicated that Cbx4 is correlated with histological grading, tumor-node-metastasis stage, microvessel density, distant metastasis and hematogenous metastasis of HCC. By univariate and multivariate analyses, we show that Cbx4 is an independent prognostic factor of HCC, and both TAE and TACE treatments have no effects on the overall survival in HCC patients with low Cbx4 expression. More intriguingly, TACE prolongs, while TAE shortens, the overall survival of HCC patients with high Cbx4 expression, indicating that Cbx4 is a good biomarker on decision-making to perform postoperative TACE in HCC patients. Moreover, Cbx4 overexpression enhances while Cbx4 silencing antagonizes doxorubicin-induced cell death of HCC cell lines. In conclusion, Cbx4 is an independent prognostic factor for HCC patients, and the patients with high Cbx4 expression should receive postoperative TACE treatment to improve their survival.