Haitao Lv

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.

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.

Role of the PTEN/PI3K/VEGF pathway in the development of Kawasaki disease

Kawasaki disease (KD) is a disease of unknown etiology and the leading cause of childhood acquired heart disease. In this study, the significance of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/vascular endothelial growth factor (VEGF) pathway in the development of KD was investigated in a rabbit model. Rabbits were divided into the control group, which received saline injection, and the experimental group, which was treated with bovine serum albumin to induce arthritis and KD. After 1, 7 and 30 days the animals were sacrificed, and the white blood cell count, serum VEGF, and serum creatine kinase (CK) levels were measured. The coronary artery was examined histologically as well as immunohistochemically for PTEN and PI3K. After the induction of arthritis, coronary artery of the rabbits showed endothelial cell swelling, osteoporosis, necrosis and inflammatory cell infiltration. PTEN expression in these rabbits increased with the increasing number of modeling days. The expression of PI3K showed a decreasing trend. The number of white blood cells in rabbits after KD modeling were significantly higher than those in the controls. One day and 7 days after modeling the serum VEGF level in KD rabbits was significantly higher than that in the control group after 1 and 7 days followed by a decrease by 30 days. There was no significant change in serum CK on the day after the modeling, and the serum CK level was significantly higher after 7 and 30 days. In conclusion, the expression of PTEN/PI3K was altered at different stages of KD. PTEN expression gradually increased with the disease progression, while the expression of PI3K gradually decreased. Serum markers indicated that the PTEN/PI3K/VEGF signaling pathway is important in the vascular injury in KD.

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).

Coronary artery aneurysm regression after Kawasaki disease and associated risk factors: a 3-year follow-up study in East China

Kawasaki disease (KD) is the leading cause of acquired heart disease due to its complicated coronary artery lesions. Up to now, few studies were focused on the status of persistent coronary artery aneurysms (CAA) in KD patients. The present study was designed to identify the coronary artery outcomes and seek the risk factors associated with the regression of CAA in KD patients. One hundred and twenty KD patients with CAA hospitalized in Children’s Hospital of Soochow University from Jan 2008 to Dec 2013 were prospectively studied by a 3-year follow-up. Data regarding demographic, clinical, laboratory, and echocardiographic characteristics were documented and further analyzed. It was estimated that 39.2% of the patients had complete regression of CAA within 4xa0weeks, 59.2% within 8xa0weeks, and 70.0% within 16xa0weeks. No fatal cardiac events occurred. We found patients who aged ≤u20091xa0year, received initial intravenous immunoglobulin (IVIG) treatment after the 10th day of illness, and IVIG non-responders were associated with the regression of persistent CAA. The relative risks were 1.55, 1.87, and 1.88, respectively. Age, initial IVIG treatment, and IVIG response were risk factors of persistent CAA, and more attention should be paid on these patients.