UNASSIGNED: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries.
UNASSIGNED: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified.
UNASSIGNED: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions.
UNASSIGNED: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Coronary artery lesions (CALs) are serious complications of KD that can result in stenosis and thrombosis, but the specific underlying pathogenic mechanisms have not been elucidated. Therefore, exploring biomarkers to help predict early CALs is urgently needed for clinical treatment.
METHODS: Patients were recruited from three independent cohorts. In the discovery cohort, Data-Independent Acquisition Mass Spectrometry (DIA-MS) was performed to screen plasma proteins from healthy controls (HCs), KD patients prior to intravenous immunoglobulin (IVIG) treatment, and KD patients post-IVIG treatment. KD patients were further divided into KD patients without CALs (nCAL) and with CALs (CALs) groups. Bioinformatic analysis was carried out for the differentially expressed proteins (DEPs) and hub proteins. Candidate proteins were quantified by enzyme-linked immunosorbent assay (ELISA) in the validation cohort 1 and 2. Furthermore, candida albicans cell wall extract (CAWS)-induced KD vasculitis mice and cell models were established to investigate the expression of biomarkers identified in the aforementioned clinical cohort.
RESULTS: According to the quantitative proteomics analysis, SERPINE1 was significantly increased in KD patients with CALs. Receiver operating characteristic curves (ROC) revealed that plasma SERPINE1 exhibited greater ability in predicting CALs (AUC = 0.824, P < 0.0001). After IVIG treatment, the concentrations of SERPINE1 in the nCALs group significantly decreased. However, the concentration of SERPINE1 remained persistently elevated in the CALs group. Moreover, the expression of SERPINE1 was significantly upregulated in the heart tissue of KD mice, KD plasma, or tumor necrosis factor-α (TNF-α)-stimulated human coronary artery endothelial cells (HCAECs).
CONCLUSIONS: Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients.

UNASSIGNED: The paper was to investigate the clinical relevance of oxidative stress (OS) and inflammation-associated targets in coronary artery lesions (CALs) associated with Kawasaki disease (KD).
UNASSIGNED: The clinical data from 455 sufferers diagnosed with KD between February 2021 and June 2023 were gathered and divided into two groups: CAL and NCAL. The regression analysis was conducted to search for independent covariates for CALs related to OS and inflammation. The predictive nomogram was structured according to these risk factors. The properties of the model were estimated using calibration and receiver operating characteristic curves.
UNASSIGNED: The levels of CRP, IL-6, PLT count, ESR, ox-HDL, MDA, and PLR were more elevated in CAL patients with KD; interestingly, HDL and superoxide dismutase (SOD) were low in the CAL group. Ascension of CRP, IL-6, ESR, ox-HDL, MDA, and PLR, and diminution of HDL and SOD were considered independent risk factors. The nomogram constructed using these factors demonstrated a satisfactory calibration degree and discriminatory power, with an area under the curve of 0.812. In the verification set, the area under the curve was found to be 0.799.
UNASSIGNED: The model was established according to 8 OS and inflammation-associated risk factors bound up with CALs in KD sufferers. It may be a usable approach for early diagnosis of CALs in KD.

Pediatric patients with coronary artery lesions (CALs) after Kawasaki disease (KD) may be complicated with myocardial ischemia. Although previous studies in adults have proven the diagnostic value of 99mTc-MIBI myocardial perfusion imaging (MPI) for ischemic heart disease, its feasibility and accuracy in this pediatric population remain uncertain. In this retrospective study, we collected data of 177 pediatric patients (Age range: 6 months to 14 years) who had undergone MPI and coronary artery angiography (CAG) between July 2019 and February 2023. Using the positive result of CAG as the reference standard of myocardial ischemia, we compared the results of 99mTc-MIBI MPI with other non-invasive examinations, including cardiac magnetic resonance imaging (CMRI), echocardiogram, and comprehensive electrocardiogram-related examinations. All patients finished adenosine triphosphate stress MPI without major side effects. The sensitivity of MPI was 79.17%, which was greater than CMRI and echocardiogram (P < 0.05). The negative predictive value and the accuracy of MPI were 89.9% and 71.75%, indicating the advantages over others. Composite monitoring strategy of MPI and CMRI effectively improved the diagnostic performance (P < 0.001). In 4 cases diagnosed with myocardial ischemia by \"MPI + CMRI,\" despite the absence of significant stenosis, multiple giant coronary artery aneurysms (GCAA) were all observed in CAG. 99mTc-MIBI MPI is the preferred non-invasive examination for detecting myocardial ischemia in pediatric patients with CAL after KD. When combined with CMRI, it can enhance diagnostic accuracy. Multiple GCAAs without stenosis may be an isolated risk factor of myocardial ischemia.

UNASSIGNED: Kawasaki Disease (KD) is a pediatric vasculitic disorder characterized by systemic small vasculitis, notably coronary arteritis, with unclear pathogenesis. This explorative case-control study investigated the association between folic acid (FA), vitamin D3 (VD3), and vitamin B12 (VB12) levels and the different types of Kawasaki Disease, as well as the incidence of coronary artery lesions (CALs).
UNASSIGNED: In this explorative case control study, 365 KD children admitted to our hospital from January 1, 2022 to June 30, 2023 were included as the KD group. Simultaneously, 365 healthy children who received physical examination during the same period were included as the control group. The KD group was divided into typical KD group and incomplete KD group (IKD group), CALs group and non-CALS group, and IVIG sensitive group and IVIG resistant group. The children with CALs were divided into small tumor group, medium tumor group and large tumor group. Serum levels of FA, VB12, and VD3 were compared across all groups.
UNASSIGNED: Serum levels of FA and VD3 were significantly decreased in both the KD and CALs groups (p < 0.05), and both factors were identified as independent risk factors for KD and CALs. Similarly, reduced serum VD3 levels were observed in the IKD and IVIG-resistant groups (p < 0.05), with VD3 also being an independent risk factor for both IKD and IVIG resistance. Additionally, lower serum FA levels were noted in the group with large aneurysms (p < 0.05), establishing FA as an independent risk factor for aneurysm size.
UNASSIGNED: Serum levels of folic FA and vitamin VD3 were significantly reduced in children with KD. Furthermore, these reductions were more pronounced in children with IKD and CALs. This pattern suggests that lower FA and VD3 levels may increase the risk of more severe coronary lesions in KD patients. Therefore, monitoring these biomarkers could provide valuable insights for early clinical diagnosis and intervention.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD).
METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis.
RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients.
CONCLUSIONS: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

UNASSIGNED: Coronary artery lesion (CAL) is a common yet serious complication in children with Kawasaki disease. The aim of the present study was to evaluate the influencing factors of CAL in children with Kawasaki disease, to provide reference for the clinical treatment and care of children with Kawasaki disease.
UNASSIGNED: A retrospective cohort study.
UNASSIGNED: Children with Kawasaki disease treated in a tertiary hospital in China between 1 January 2021 and 31 December 2022 were selected. The characteristics and clinical data of children with Kawasaki disease were analyzed. Spearman\'s correlation analysis was conducted to evaluate the relationship between CAL and the characteristics of children with Kawasaki disease. A logistic regression analysis was used to analyze the influencing factors of CAL in children with Kawasaki disease.
UNASSIGNED: In total, 185 children with Kawasaki disease were included; the incidence of CAL in children with Kawasaki disease was 18.38%. Pearson\'s correlation analysis showed that gender (r = 0.504), age (r = 0.611), duration of fever ≥10 days (r = 0.579), hemoglobin (Hb) (r = 0.623), and C-reactive protein (CRP) (r = 0.558) were all correlated with the CAL in children with Kawasaki disease (all p < 0.05). Logistic regression analyses showed that male [odds ratio (OR) = 2.543, 95% confidence interval (CI): 1.801-3.077, p = 0.040], age ≤2 years (OR = 3.002, 95% CI: 2.744-3.641, p = 0.012), duration of fever ≥10 days (OR = 2.089, 95% CI: 1.624-2.515, p = 0.028), Hb ≤105 g/L (OR = 1.914, 95% CI: 1.431-2.406, p = 0.013), and CRP ≥100 mg/L (OR = 2.168, 95% CI: 1.893-2.531, p = 0.035) were the risk factors of CAL in children with Kawasaki disease (all p < 0.05).
UNASSIGNED: The incidence of CAL in children with Kawasaki disease is high and there are many related risk factors. Clinical medical workers should take early warning and carry out interventions and nursing care according to these risk factors to improve the prognosis of children with Kawasaki disease.

OBJECTIVE: Kawasaki syndrome (KS) is an acute vasculitis that affects children < 5 years of age and leads to coronary artery lesions (CAL) in about 20-25% of untreated cases. Machine learning (ML) is a branch of artificial intelligence (AI) that integrates complex data sets on a large scale and uses huge data to predict future events. The purpose of the present study was to use ML to present the model for early risk assessment of CAL in children with KS by different algorithms.
METHODS: A total of 158 children were enrolled from Women and Children\'s Hospital, Qingdao University, and divided into 70-30% as the training sets and the test sets for modeling and validation studies. There are several classifiers are constructed for models including the random forest (RF), the logistic regression (LR), and the eXtreme Gradient Boosting (XGBoost). Data preprocessing is analyzed before applying the classifiers to modeling. To avoid the problem of overfitting, the 5-fold cross validation method was used throughout all the data.
RESULTS: The area under the curve (AUC) of the RF model was 0.925 according to the validation of the test set. The average accuracy was 0.930 (95% CI, 0.905 to 0.956). The AUC of the LG model was 0.888 and the average accuracy was 0.893 (95% CI, 0,837 to 0.950). The AUC of the XGBoost model was 0.879 and the average accuracy was 0.935 (95% CI, 0.891 to 0.980).
CONCLUSIONS: The RF algorithm was used in the present study to construct a prediction model for CAL effectively, with an accuracy of 0.930 and AUC of 0.925. The novel model established by ML may help guide clinicians in the initial decision to make a more aggressive initial anti-inflammatory therapy. Due to the limitations of external validation and regional population characteristics, additional research is required to initiate a further application in the clinic.

Coronary artery lesions (CALs) are the most common complications of Kawasaki disease (KD) and play a crucial role in determining the prognosis of the disease. Consequently, the early identification of children with KD who are at risk of developing coronary artery damage is vitally important. We sought to investigate the relationship between the Systemic Immune-Inflammation Index (SII) and CALs in patients with KD and to assess its predictive value. We carried out a retrospective review and analysis of medical records for KD patients treated at the First Affiliated Hospital of Anhui Medical University between January 2017 and January 2023. We utilized single-variable tests, binary logistic regression analysis, ROC curve analysis, restricted cubic spline tests, and curve fitting to evaluate the association between SII and CALs. In our study, 364 patients were included, with 63 (17.3%) presenting with CALs at the time of admission. The binary logistic regression analysis indicated that SII was a significant risk factor for CALs at admission, evident in both unadjusted and models adjusted for confounders. The ROC curve analysis revealed an AUC (Area Under the Curve) value of 0.789 (95%CI 0.723-0.855, P < 0.001) for SII\'s predictive ability regarding CALs at admission. A consistent positive linear relationship between SII and the risk of CALs at admission was observed in both the raw and adjusted models. Our research findings suggest that SII serves as a risk factor for CALs and can be used as an auxiliary laboratory biomarker for predicting CALs.

The purpose of this study is to analyze the early clinical features of coronary artery lesion (CAL) in Kawasaki disease (KD), evaluate systemic inflammation indicators, and enhance early recognition of CAL in the acute phase of KD. A total of 314 children with KD were divided into those with CAL (CAL group) and without CAL (NCAL group) using echocardiographic results, and their clinical data were retrospectively analyzed. For KD patients, male, children aged 3 to 9 years, and those with fever longer than 6 days before intravenous immunoglobulin (IVIG) use were more likely to have CAL. There were significant differences in sex, age, and fever time (P < .05). Moreover, some laboratory indicator test results revealed there was a significant difference between N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and interleukin-6 (IL-6), and the CAL (P < .05). This study has certain guiding significance for early clinical evaluation.