Ling Sun

A meta-analysis on the effect of corticosteroid therapy in Kawasaki disease.

The current recommended therapy for Kawasaki disease (KD) is the combination of intravenous immunoglobulin (IVIG) and aspirin. However, the role of corticosteroid therapy in KD remains controversial. Using meta-analysis, this study aimed to investigate the efficacy of corticosteroid therapy in KD by comparing it with standard IVIG and aspirin therapy. We included all related randomized and quasi-randomized controlled trials by searching Medline, the Cochrane Central Register of Controlled Trials, EMBASE, Pub Med, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the Japanese database (Japan Science and Technology) as well as hand searches of selected references. Data collection and meta-analysis were performed to evaluate the effect of corticosteroids. Our search yielded 11 studies; 7 of which evaluated the effect of corticosteroid for primary therapy in KD, and 4 investigated the effect of corticosteroid therapy in IVIG-resistant patients. Meta-analysis of these studies revealed a significant reduction in the rates of initial treatment failure among patients who received corticosteroid therapy in combination with IVIG compared to IVIG alone (odds ratio (OR)u2009=u20090.50; 95% CI, 0.32~0.79; pu2009=u20090.003). Furthermore, the use of corticosteroids reduced the duration of fever and the time required for C-reactive protein to return to normal. Our data did not show any significant increase in the incidence of coronary artery lesions or coronary aneurysms (ORu2009=u20090.67; 95% CI, 0.35~1.28; pu2009=u20090.23) in the corticosteroid group. Conclusion. Corticosteroid combined with IVIG in primary treatment or as treatment of IVIG-resistant patients improved clinical course without increasing coronary artery lesions in children with acute KD.

Estimation of birth population-based perinatal-neonatal mortality and preterm rate in China from a regional survey in 2010

Abstract Objective: To estimate birth population-based perinatal-neonatal mortality and preterm rate in China from a regional survey in 2010. Study design: Data of total births in 2010 obtained from 151 level I–III hospitals in Huai’an, Jiangsu, were prospectively collected and analyzed. Results: From 61u2009227 birth registries (including 60u2009986 live births and 241 stillbirths), we derive a birth rate of 11.3‰ (of 5.4 million regional population), a male-to-female ratio of 116:100 and valid data from 60u2009615 newborns. Mean birth weight (BW) was 3441u2009±u2009491u2009g with 13.6% macrosomia. Low BW was 2.8% (1691/60u2009372) with 8.83% mortality. Preterm rate was 3.72% (2239/60u2009264) with 7.61% mortality. Cesarean section rate was 52.9% (31u2009964/60u2009445), multiple pregnancy 1.8% (1088/60u2009567) and birth defects 6.7‰ (411/61u2009227). There were 97.4% healthy newborns and 2.2% (1298) requiring hospitalized after birth. The perinatal mortality was 7.7‰ (471/61u2009227, including 241 stillbirths, 230 early neonatal deaths). The neonatal mortality was 4.4‰ (269/60u2009986). The main causes of neonatal death were birth asphyxia (24.5%), respiratory diseases (21.5%), prematurity related organ dysfunction (18.5%) and congenital anomalies (7.7%), whereas incidence of congenital heart disease and respiratory distress syndrome was 8.6‰ and 6.1‰, respectively. Conclusions: This regional birth population-based data file contains low perinatal-neonatal mortality rates, associated with low proportion of LBW and preterm births, and incidences of major neonatal disease, by which we estimate, in a nationwide perspective, in 16 million annual births, preterm births should be around 800u2009000, perinatal and neonatal mortality may be 128u2009000–144u2009000 and 80u2009000–96u2009000, respectively, along with 100u2009000 respiratory distress syndrome.

A high-fat maternal diet decreases adiponectin receptor-1 expression in offspring

Abstract In early life, over-nutrition may increase the risk of insulin resistance in the adult stage. Adiponectin and its receptor may play a key role in this process. This study aimed to identify the effect of a high-fat (HF) maternal diet on metabolic parameters and muscle adiponectin signaling in young adult offspring. We found that offspring born to dams fed HF chow (HF; 31% of calories from fat) had elevated body and adipose tissue weight and higher serum glucose levels after glucose challenge at three weeks (W3) and eight weeks (W8) of age. Offspring exposed to a HF diet also had higher serum adiponectin levels at W3 compared to controls. However, adiponectin levels were significantly decreased compared to controls by W8. Adiponectin receptor 1u2009mRNA expression in skeletal muscle was decreased in the HF group at W3 and W8, and there was no difference between the two groups in adiponectin receptor 2 expression. Furthermore, glucose transporter 4u2009mRNA and protein expression was decreased in the skeletal muscle of the HF group at W3 and W8. Our results suggest that a HF maternal diet decreases adiponectin receptor 1 expression in the offspring, which could contribute to reduced sensitivity to adiponectin and to adverse nutritional programing outcomes.

Understanding the pathogenesis of Kawasaki disease by network and pathway analysis.

Kawasaki disease (KD) is a complex disease, leading to the damage of multisystems. The pathogen that triggers this sophisticated disease is still unknown since it was first reported in 1967. To increase our knowledge on the effects of genes in KD, we extracted statistically significant genes so far associated with this mysterious illness from candidate gene studies and genome-wide association studies. These genes contributed to susceptibility to KD, coronary artery lesions, resistance to initial IVIG treatment, incomplete KD, and so on. Gene ontology category and pathways were analyzed for relationships among these statistically significant genes. These genes were represented in a variety of functional categories, including immune response, inflammatory response, and cellular calcium ion homeostasis. They were mainly enriched in the pathway of immune response. We further highlighted the compelling immune pathway of NF-AT signal and leukocyte interactions combined with another transcription factor NF-κB in the pathogenesis of KD. STRING analysis, a network analysis focusing on protein interactions, validated close contact between these genes and implied the importance of this pathway. This data will contribute to understanding pathogenesis of KD.

Correlation between brachial artery flow-mediated dilation and endothelial microparticle levels for identifying endothelial dysfunction in children with Kawasaki disease

Background:We investigated vascular endothelial dysfunction by sonographic features of flow-mediated dilation (FMD) and circulating endothelial microparticles (EMPs) in Kawasaki disease (KD).Methods:Twenty-eight patients with KD were prospectively grouped according to stage of disease: acute, subacute, and convalescent. In addition, 28 healthy children and 28 febrile children were selected as controls. And cases in the convalescent phase were divided into two subgroups: coronary artery lesion (CAL) and no coronary lesion (NCAL). CD144+/CD42b−, CD62E+, and CD105+ EMPs were measured by flow cytometry; FMD was obtained by sonography.Results:There were significant differences in FMD among the five groups. When compared with healthy controls, there were significantly greater numbers of CD144+/CD42b−, CD62E+, and CD105+ EMPs and a higher proportion of CD62E+ EMPs in KD patients. The proportions and numbers of CD144+/CD42b−, CD62E+, and CD105+ EMPs in KD patients were not statistically different than in febrile controls. There were no significant differences in FMD and EMPs between the CAL and NCAL subgroups. There were significantly negative correlations between the values of FMD and EMPs in the three phases of KD.Conclusion:The increased levels of EMPs have significant correlation with decreased values of FMD, both of which may reflect endothelial dysfunction in child KD.

Evaluation of left ventricular systolic strain in children with Kawasaki disease.

The current study aimed to assess left ventricular (LV) longitudinal systolic strains in children with KD using two-dimensional speckle-tracking imaging and to analyze the relationship of LV myocardial deformation to coronary lesions and laboratory markers. The study enrolled 101 children with acute KD. An additional 50 age- and gender-matched normal children were enrolled as control subjects. During different phases of KD, echocardiograms were recorded for 61 children. Two-dimensional strain analysis software was used to track myocardial movement and obtain the strain from each LV segment. The LV longitudinal systolic strain decreased significantly in children with acute KD but increased immediately after intravenous immunoglobulin therapy. At 6–8xa0weeks after the onset of KD, all LV strains had recovered to normal. The LV systolic strain was not associated with coronary dilation in either acute or convalescent KD. In acute KD, aspartate transaminase, alanine transaminase, erythrocyte sedimentation rate, C-reactive protein (CRP), and hemoglobin (Hb) were found to be associated with coronary dilation, whereas LV systolic strains were found to be correlated with elevated CRP and decreased Hb. Speckle-tracking imaging of LV systolic strain was simple and accurate in evaluating LV function during different phases of KD. No association between LV dysfunction and coronary dilation was observed, but a relationship with CRP and Hb was found. Further studies are recommended to validate the current study results and explore further how these findings can improve clinical practice.

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an East China population

The objectives of the study were to find the risk factors associated with intravenous immunoglobulin (IVIG) resistance and generate a prediction scoring system of IVIG resistance in patients with Kawasaki disease (KD). We retrospectively reviewed the clinical records of KD patients between January 2006 and December 2014. Multivariate logistic regression was performed to identify the risk factors of IVIG non-responders. The independent risk factors were used to construct a new scoring system and compared with Kobayashi and Egami scoring systems. Multivariate logistic regression analysis identified age <6xa0months, rash, edema of extremities, % neutrophils, and serum albumin as independent risk factors for IVIG non-responders. We assigned one point for rash, edema of extremities, and % neutrophils ≥80xa0%. Two points were assigned for age <6xa0months and serum albumin <35xa0g/L. Using a cutoff point of three or more, we identified the IVIG non-responders with 71.4xa0% sensitivity and 76.0xa0% specificity. The new scoring system had a relatively better performance than Kobayashi and Egami scoring systems in the KD patients in East China. Clinical pediatricians must pay more attention to these high-risk patients, and use of additional therapies early in the course of their illness is necessary.

Histopathological and Ultrastructural Examinations of Rabbit Coronary Artery Vasculitis Caused by Bovine Serum Albumin: An Animal Model of Kawasaki Disease

Abstract Objective: To observe the histopathological and ultrastructural features of coronary artery vasculitis in rabbits caused by repeated intravenous injections of bovine serum albumin (BSA), mimicking Kawasaki disease. Materials and Methods: Twenty weanling rabbits were randomly and equally divided into treatment groups for BSA or normal saline (NS), and administered the respective treatment by intravenous injection once every 12 days for two cycles. Six weeks after the first treatment, rabbits underwent coronary angiography and coronary arteries were removed within 1u2009h. Histopathological examination was performed by light, scanning electron, and transmission electron microscopy. Results: Coronary arteriography revealed that 3 rabbits (3/10) in the BSA group had various levels of dilation and narrowing of the left coronary arteries, while histological examination showed that 10 rabbits (10/10) had infiltration of the coronary arteries by inflammatory cells. Incomplete endothelium, breakage of elastic fiber, and intimal thickening were also observed in 8 rabbits (8/10) from the BSA group. Ultrastructurally, in 3 rabbits (3/10) in the BSA group, leukocyte migration, shedding of endothelial microparticles from the plasma membranes, incomplete endothelium, abscission of endothelial cells, breakage of the internal elastic lamina (IEL), degeneration of smooth muscle cells in the medial membrane, and swollen mitochondria were detected. By contrast, the IEL of the NS control group was continuous and of uniform thickness. Conclusion: This rabbit model of coronary arteritis displayed histopathological and ultrastructural features similar to those of Kawasaki disease in humans. Breakage of the IEL, a key factor in aneurysm formation, was observed in the coronary arteries. Therefore weanling rabbits may serve as an experimental model for immune complex vasculitis involving coronary arteries that mimics Kawasaki disease.

Changes in Profiles of Kawasaki Disease Noted over Time in Suzhou, China

Objectives: The purpose of the present study was to explore the changes in epidemiological, clinical and laboratory characteristics of Kawasaki disease (KD) over a 12-year period in this area. Methods: The medical records of KD patients hospitalized in the Children’s Hospital of Soochow University from January 2006 to December 2017 were retrospectively reviewed and analyzed. To elucidate the changes more clearly in these years, we divided all patients into three groups according to the time of admission, 5-year time intervals apart. Results: We found the number of KD had increased in recent years, although the age compositions had some variances. The male-to-female ratio peaked in patients aged 6–11 months and then decreased with ages. Incidence rates of clinical characteristics were almost the same except for cervical lymphadenopathy. Significant differences were noted in percentage of neutrophils, albumin, C-reactive protein, erythrocyte sedimentation rate (ESR) and platelets. However, only ESR and platelets were significantly different after adjusting the days of disease onset. A trend showing a shorter fever duration before intravenous immunoglobulin treatment was also noted. Conclusions: The number of KD was increasing annually. Our results were indicative of a possibly changed etiology of the disease. However, further large-scale long-term surveillance is warranted.

Evaluation of right ventricular myocardial strains by speckle tracking echocardiography after percutaneous device closure of atrial septal defects in children

The aim of this study was to clarify the influence of the ASD closure by occluder device on right ventricular acute and long‐term changes in longitudinal systolic strains, by evaluating right ventricular wall deformation in children using speckle tracking echocardiography (STE).