BackgroundAlbumin (ALB) level is closely associated with the occurrence of intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). The association between ALB level and CALs progression, is critical to the prognosis of KD patients. But little is known about it. This study aims to investigate the effect of the ALB level on CALs progression in KD patients.MethodsA total of 3,479 KD patients from 1 January 2005 to 30 November 2020, in Wenzhou, China were recruited. A total of 319 KD patients who had CALs and ALB data, and finish the follow-up as requested were enrolled in this study. They were classified into the low ALB group and the normal ALB group, divided by 30 g/L. CALs outcomes were classified into two categories according to the CALs changes from the time that CALs were detected within 48 h before or after IVIG treatment to 1 month after disease onset: progressed and no progressed. Multiple logistic regression models were used to assess the independent effect of ALB level on CALs progression among KD patients. Stratified analysis was performed to verify the ALB level on CALs progression among patients in different subgroups.ResultsHigher proportion of IVIG resistance (P < 0.001), receiving non-standard therapy (P < 0.001), and receiving delayed IVIG treatment (P = 0.020) were detected in patients with lower ALB level. Patients with lower ALB level had higher C-reactive protein (CRP) level (P = 0.097) and white blood cell count (WBC) (P = 0.036). After adjustment for confounders, patients with lower ALB level had higher odds of CALs progression; the adjusted odds ratio (OR) was 3.89 (95% CI: 1.68, 9.02). Similar results were found using stratification analysis and sensitivity analysis. Male gender and age over 36 months, as covariates in multiple logistic regression models, were also associated with CALs progression.ConclusionLow ALB level is identified as an independent risk factor for CALs progression in KD patients. Male gender and age over 36 months are also proved to be risk factors for CALs progression. Further investments are required to explore its mechanisms.

BackgroundKawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology. After the pandemic of coronavirus disease 2019 (COVID-19), some children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showed clinical symptoms similar to KD, indicating a close relationship between KD and SARS-CoV-2. Therefore, we designed this retrospective study to analyze the characteristics of KD patients before and after the COVID-19 pandemic.MethodsWe retrospectively collected demographic and laboratory data of KD patients in Yuying Children's Hospital of Wenzhou Medical University from 1 January 2015 to 31 December 2020. Yuying Children's Hospital of Wenzhou Medical University is located in eastern China and is the largest pediatric heart disease center in the region, which includes a population of nearly 10 million. We studied the characteristics of KD patients and analyzed the changes in these characteristics before and after the emergence of SARS-CoV-2 in this area.ResultsThe analysis revealed the following novel features: (1) Under the influence of the COVID-19 pandemic, the onset age of Kawasaki disease became younger. (2) After the occurrence of COVID-19, the hospitalization days of KD patients were shorter than before the pandemic. (3) After the occurrence of COVID-19, the albumin of KD patients was higher than before the pandemic. (4) The COVID-19 pandemic did not have a significant effect on the incidence of coronary artery lesions (CALs) in Kawasaki disease.ConclusionAfter the COVID-19 outbreak, the characteristics of KD patients showed a younger trend of age, shorter hospitalization days and higher levels of albumin, but the incidence of CALs did not change significantly.

Background Kawasaki disease (KD) is a kind of vasculitis with unidentified etiology. Given that the current diagnosis and therapeutic strategy of KD are mainly dependent on clinical experiences, further research to explore its pathological mechanisms is warranted. Methods Enzyme linked immunosorbent assay (ELISA) was used to measure the serum levels of SIGIRR, TLR4 and caspase-8. Western blotting was applied to determine protein levels, and flow cytometry was utilized to analyze cell apoptosis. Hematoxylin eosin (HE) staining and TUNEL staining were respectively used to observe coronary artery inflammation and DNA fragmentation. Results In this study, we found the level of SIGIRR was downregulated in KD serum and KD serum-treated endothelial cells. However, the level of caspase-8 was increased in serum from KD patients compared with healthy control (HC). Therefore, we hypothesized that SIGIRR-caspase-8 signaling may play an essential role in KD pathophysiology. In vitro experiments demonstrated that endothelial cell apoptosis in the setting of KD was associated with caspase-8 activation, and SIGIRR overexpression alleviated endothelial cell apoptosis via inhibiting caspase-8 activation. These findings were also recapitulated in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. Conclusion Our data suggest that endothelial cell apoptosis mediated by SIGIRR-caspase-8 signaling plays a crucial role in coronary endothelial damage, providing potential targets to treat KD.

Background: Kawasaki disease (KD) is a kind of vasculitis with unidentified etiology. Given that the current diagnosis and therapeutic strategy of KD are mainly dependent on clinical experiences, further research to explore its pathological mechanisms is warranted. Methods: Enzyme linked immunosorbent assay (ELISA) was used to measure the serum levels of SIGIRR, TLR4 and caspase-8. Western blotting was applied to determine protein levels, and flow cytometry was utilized to analyze cell apoptosis. Hematoxylin eosin (HE) staining and TUNEL staining were respectively used to observe coronary artery inflammation and DNA fragmentation. Results: in this study, we found the level of SIGIRR was downregulated in KD serum and KD serum-treated endothelial cells. However, the level of caspase-8 was increased in serum from KD patients compared with healthy control (HC). Therefore, we hypothesized that SIGIRR-caspase-8 signaling may play an essential role in KD pathophysiology. In vitro experiments demonstrated that endothelial cell apoptosis in the setting of KD was associated with caspase-8 activation, and SIGIRR overexpression alleviated endothelial cell apoptosis via inhibiting caspase-8 activation. These findings were also recapitulated in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. Conclusion: our data suggest that endothelial cell apoptosis mediated by SIGIRR-caspase-8 signaling plays a crucial role in coronary endothelial damage, providing potential targets to treat KD.

Background: The etiology of liver injury in children with Kawasaki disease(KD) is not yet clear.It is common for children who are responded to intravenous gamma globulin (IVIG) therapy to develop liver injury after IVIG treatment. This research is to explore related factors of liver injury after IVIG treatment in children with KD who responded retrospectively to IVIG.Methods: A total of 806 children with KD were included in this analysis. The clinical characteristics, laboratory findings, and drug use before IVIG were collected. Difference analysis, ROC curve analysis and logistic regression analysis were performed to obtain possible risk factors for liver injury after IVIG treatment.Results: Among the clinical symptoms of the two groups of children, children with lymphadenopathy had a lower risk of developing liver injury after IVIG treatment(p=0.040),while there were no significant differences in other symptoms. Among laboratory indicators, the liver injury group had higher levels of platelet(PLT),eosinophil(EO) and brain natriuretic peptide(BNP) levels and lower hemoglobin(HB),erythrocyte sedimentation rate(ESR) and prothrombin time(PT) levels before IVIG treatment (p<0.05).There were no significant difference in c-reactive protein(CRP) and Procalcitonin(PCT)(p>0.05).The use of antibiotics, dipyridamole and aspirin doses between two groups had statistically significant differences(p>0.05).Further ROC curve analysis of aspirin dose found the optimal cut-off point of aspirin was 34.7 mg/(k*d)(the 95% CI: 0.504-0.601,p=0.026).The logistic regression analysis showed high-dose aspirin (≥34.7mg/(kg*d))was a risk factor for liver damage after IVIG treatment in KD children. Further multivariate regression analysis prompted that the use of antibiotics and higher doses of aspirin(≥34.7mg/(kg*d))in the acute phase were independent risk factors for liver injury after IVIG treatment in children with KD(Antibiotic use: OR=2.195,95%CI:1.206-3.994,p=0.01;Aspirin use: OR=1.526,95%CI:1.083-2.151,p=0.016).Conclusions: For KD children with normal liver function in the acute phase, the younger the age of KD onset, the smaller the weight, the absence of lymphadenopathy, and more elevated PLT,EO, BNP, reduced HB,ESR and PT in acute stage, the more likely to develop liver injury after treatment. There was no significant correlation between the degree of systemic inflammation(levels of CRP and PCT)in the acute phase and liver damage after IVIG treatment. The use of antibiotics and high-dose aspirin in the acute phase may be the risk factors for liver function damage after IVIG treatment in KD children.