Retrospective analysis of infliximab in the treatment of Kawasaki disease / 中华儿科杂志

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.

Histone acetylation and expression of acetylation-related enzymes in children with tetralogy of Fallot / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to investigate the role of histone acetylation and acetylation-related enzymes in the pathogenesis of TOF.</p><p><b>METHODS</b>Myocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed.</p><p><b>RESULTS</b>Compared with the control group, the TOF group showed significantly increased acetylation of H3K9 (P=0.0165) and significantly decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group (P=0.025; P=0.017), and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01).</p><p><b>CONCLUSIONS</b>Upregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.</p>