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Background: Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAL. Although most of the current studies have shown a certain correlation between CAL and IVIG resistance, the conclusions are not completely consistent. Thus, we performed this meta-analysis to evaluate the association between IVIG resistance and CAL in KD., Methods: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through April 21, 2020 were searched to detect relevant studies. Data analysis was performed with STATA 15.1., Results: A total of 53 relevant studies were eligible to this analysis, including 30312 KD patients, of which 4750 were IVIG resistance and 25562 were responders. There was a significant difference found between IVIG resistance and IVIG response groups in the incidence of CAL (P < 0.001, odds ratio (OR), 3.89; 95% confidence interval (CI) (3.18, 4.75)). The heterogeneity test results showed that the I2 value was 74.8%. The meta-regression analysis showed that the study regions might be the sources of heterogeneity. The subgroup analysis suggested that the incidence of CAL in the IVIG resistance group was still higher than that in the IVIG response group under different regions, IVIG resistance diagnostic criteria, CAL diagnostic criteria, and study types. Meanwhile, the sensitivity analysis did not find any significant impact from every single study., Conclusions: This is the first meta-analysis to reveal the incidence of CAL was associated with IVIG resistance in KD patients. Further well-designed studies with uniform criteria are needed to evaluate the incidence of CAL in IVIG resistant patients., Competing Interests: The authors have declared that no competing interests exist.

Background: There is no golden standard for the diagnosis of Kawasaki disease (KD), the most common cause of acquired heart disease in children in many countries. In recent years, many studies have focused on the relationship between microRNAs (miRNAs) and KD. Thus, we perform this meta-analysis to understand the role of circulating miRNAs as a biomarker to detect KD., Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through March 10, 2019. Meta-disc 1.4 and STATA 15.1 (Stata Corporation, College Station, TX) were used to conduct the meta-analysis., Results: Six eligible articles were included in this meta-analysis. The overall performance of total mixed miRNAs detection was: pooled sensitivity, 0.7 (95% confidence interval, 0.66-0.74); pooled specificity, 0.87 (95% confidence interval, 0.83-0.90); and area under the summary receiver operating characteristic curves value (SROC), 0.8302. The meta-regression analysis indicated that the specimen types, the composition of the control group, and types of the reference miRNA were not responsible for the existing heterogeneities. The subgroup analysis showed that SROC of the plasma group (0.8890) was more significant than the serum group (0.7204), and SROC of the non-healthy control group (0.9622) was more significant than the healthy control group (0.8096)., Conclusions: : This is the first meta-analysis show that miRNAs may be used as novel biomarkers for detecting KD, especially for distinguishing KD from other febrile diseases. More studies are needed in the future to clarify the association between KD and miRNAs., Prospero Registration Number: CRD42019129976., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is currently the most common acquired heart disease in children in many countries. Nevertheless, there is no single useful marker existing for predicting CAL of KD. Recently, many reports have noted that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be utilized as a biomarker to predict CAL. Thus, we perform a meta-analysis to ascertain the diagnostic value of NT-proBNP in detecting CAL of KD in the acute phase. PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure were searched to detect relevant publications. Finally, eight eligible studies were included. The overall diagnostic sensitivity and specificity were 0.84 (95% confidence interval [CI]: 0.78-0.89) and 0.71 (95% CI: 0.68-0.75), respectively. The area under the summary receiver operating characteristic curves value (SROC) curve was 0.8582 ± 0.0531. Moreover, the overall sensitivity and specificity across five studies adopted the threshold of approximately 900 ng/L were 0.82 (95% CI: 0.73-0.89) and 0.72 (95% CI: 0.68-0.76), respectively. SROC was 0.8868 ± 0.0486. This meta-analysis would be the first one to describe the role of NT-proBNP in detecting CAL of KD. We register this study with PROSPERO (CRD42019130083).

Background: In recent years, many studies focused on the association between the neutrophil-to-lymphocyte ratio (NLR) and the risk of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (rKD), with inconsistent results. Therefore, we aimed to investigate the role of NLR as a biomarker in detecting rKD., Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through May 18th, 2019. Meta-disc 1.4 and STATA 15.1 were used to perform this metaanalysis in a fixed/random-effect model., Results: A total of 7 relevant studies were eligible to analyze pooled accuracy. The overall performance of NLR detection was: pooled sensitivity, 0.66 (95% confidence interval [CI], 0.63 - 0.70); pooled specificity, 0.71 (95%CI, 0.69 - 0.73); and area under the summary receiver operating characteristic curves value (SROC), 0.7956. The meta-regression analysis showed that the type of samples was the sources of heterogeneity. The subgroup analysis suggested that NLR detection after the initial treatment of IVIG had the largest area under curve of SROC in all the subgroups: pooled sensitivity, 0.58 (95%CI, 0.53 - 0.63); pooled specificity, 0.77 (95%CI, 0.75 - 0.79); and SROC, 0.8440., Conclusions: This is the first meta-analysis demonstrated that NLR might be a biomarker for detecting rKD, especially NLR value after the initial treatment of IVIG. More well-designed researches need to be done to launch the application of NLR for predicting rKD in the clinic.

Kawasaki disease (KD) is a systemic febrile, inflammatory vascular disease of unknown etiology. The coronary artery abnormality (CAA) caused by KD has become the most commonly acquired heart disease in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAA. Thrombocytosis is common during the course of KD, but changes in and significances of platelet function and parameters are unclear. In this study, we enrolled 120 patients, including 40 patients with KD, 40 febrile controls, and 40 afebrile controls. The platelet function was assessed using the platelet function analyzer (PFA)-200. Platelet parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet hematocrit (PCT) were measured. In the febrile period, the PDW and MPV were lower in KD patients (P < 0.05). The platelet function did not change significantly during the febrile period of KD but weakened in the defervescence phase. No significant differences between the CAA and normal groups, and between IVIG resistance and response groups. The diagnostic cutoff value of the PDW level for predicting KD was 10.85 fL with a sensitivity of 55% and a specificity of 77.5% (area under curve (AUC) = 0.690, 95% confidence interval (CI): 0.574-0.806, P < 0.01). Besides, the MPV level was 9.55 fL with sensitivity of 75% and specificity of 70% (AUC = 0.733, 95%CI: 0.620-0.846, P < 0.001). This is the first longitudinal study of platelet function changes in KD patients using PFA-200. Besides, lower PDW and MPV may be available markers for early diagnosis of KD.

Background: Kawasaki disease (KD) is now the leading cause of acquired heart disease in children in developed countries. Intravenous immunoglobulin (IVIG) and aspirin were considered as the standard initial treatment of KD for decades. However, the optimal dose of aspirin has remained controversial. In recent years, many studies compared the efficacy of low-dose with high-dose aspirin in the acute phase of KD, but the results have not always been consistent. Therefore, we performed this meta-analysis to evaluate the efficacy of low-dose aspirin compared with high-dose for the initial treatment of KD., Methods: Studies related to aspirin therapy for KD were selected from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Google scholar through Mar 25th, 2019. Data were analyzed using STATA Version 15.1. Additionally, publication bias and sensitivity analysis were also performed by STATA version 15.1., Results: Six studies were included in our analysis of the rate of coronary artery lesion (CAL), five reports for IVIG-resistant KD (rKD), and four for the duration of fever and hospitalization. However, no significant differences were found between low-dose and high-dose aspirin groups in the incidence of CAL (risk ratio (RR), 0.85; 95%CI (0.63, 1.14); P = 0.28), the risk of rKD (RR, 1.39; 95%CI (1.00, 1.93); P = 0.05), and duration of fever and hospitalization (the mean standard deviation (SMD), 0.03; 95%CI (-0.16, 0.22); P = 0.78)., Conclusion: Low-dose aspirin (3-5 mg·kg-1·d-1) may be as effective as the use of high-dose aspirin (≥30 mg·kg-1·d-1) for the initial treatment of KD. Further well-designed randomized clinical trials are needed to evaluate the efficacy of low-dose aspirin for the initial treatment of KD., Competing Interests: The authors have declared that no competing interests exist.