Effects of immunoglobulin plus prednisolone in reducing coronary artery lesions in patients with Kawasaki disease: study protocol for a phase III multicenter, open-label, blinded-endpoints randomized controlled trial.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis of unclear etiology that mainly affects infants and young children. Strategies to reduce the incidence and severity of coronary artery lesions (CALs), the determinant factor in the long-term prognosis of KD, are currently a focus of studies on KD. Corticosteroids, preferred in the treatment of the majority of vasculitides, are controversial in the treatment of acute KD. In this trial, we will evaluate whether the addition of prednisolone to standard intravenous immunoglobulin (IVIG) plus aspirin therapy can reduce the occurrence of CAL in Chinese patients with KD. METHODS: This is a multicenter, prospective, open-label, randomized controlled trial, which is expected to be conducted in more than 20 hospitals in China and aims to assess the efficacy and safety of IVIG + prednisolone treatment versus standard treatment. Patients with KD who fulfill the inclusion and exclusion criteria will be recruited and randomized (1:1) to receive either a large dose of IVIG (2 g/kg over 12-24 h with a maximum dose of 60 g) + aspirin 30 mg/kg/d or IVIG (2 g/kg over 12-24 h) + aspirin 30 mg/kg/d + prednisolone (2 mg/kg/d with a maximum dose of 60 mg tapered over 15 days after normalization of C-reactive protein concentration). The primary outcome will be the occurrence of CAL at 1 month of illness. The follow-up duration for each participant will be set as 1 year. Patients and treating physicians will be unmasked to group allocation. DISCUSSION: This will be the first multicenter randomized controlled trial to evaluate the efficacy of IVIG + aspirin + prednisolone in Chinese pediatric patients with KD, which may provide high-level evidence for improving the initial treatment for acute KD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04078568 . Registered on 16 August 2018.

Giant bilateral axillary artery aneurysms with left complete obstructive thrombus in intravenous immunoglobulin-sensitive Kawasaki disease: a case report.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis that predominantly affects medium-sized arteries. In addition to well-known coronary artery aneurysms (CAAs), peripheral systemic artery aneurysms (SAAs) have also been sporadically reported. In the literatures, SAAs occurred mainly in untreated, intravenous immunoglobin (IVIG)-resistant, or severe refractory KD, and thrombotic events in SAAs were rarely reported. CASE PRESENTATION: A 10-month-old boy with a history of KD was referred to our hospital for suspected pseudoaneurysm of the axillary arteries. Four months prior to presentation, he had persistent fever, conjunctival congestion, and rash. On the 10th day of fever echocardiogram showed biliteral CAAs. He was then diagnosed with KD and given IVIG 2 g/kg and aspirin at a local hospital. His fever and symptoms soon subsided and he was discharged with low dose aspirin and dipyridamole. One month prior to presentation, his parents incidentally palpated swellings in his bilateral axillae. On admission, physical examination revealed a pulsatile swelling in his right axilla and a non-pulsatile swelling in the left with impalpable left brachial and radial pulses, cooler and less active left upper limb than the right one. While the pulses of other three limbs were normal. Ultrasound examination revealed giant bilateral axillary artery aneurysms (AAAs) with massive thrombus in the left. Angiography confirmed giant bilateral AAAs with left AAAs completely occluded and fine collateral vessels connecting to the distal brachial artery, in addition to giant bilateral multiple CAAs without stenoses. The patient was given intravenous prostaglandin for 10 days to allow for formation of collateral circulation, as well as aspirin, low molecular weight heparin (which was switched to warfarin before discharge) and metoprolol. At discharge, the temperature and movement of his left upper limb improved significantly. On follow-up at 7 months, his left upper limb further improved and was similar to the right with no occurrence of cardiovascular events. The images of CAAs and AAAs on echocardiogram and computerized tomography remained the same. CONCLUSIONS: This case highlights the importance of evaluating peripheral SAAs in KD patients with CAAs, even if their course of treatment appears smooth. For both large non-aortic SAAs and CAAs in KD patients, antithrombotic therapy is of utmost importance.

[Histone acetylation and expression of acetylation-related enzymes in children with tetralogy of Fallot].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.