No abstract

The role of aspirin in the treatment of the acute phase of KD should be questioned as a definite benefit has not been shown in our study. Further prospective studies incorporating large multicentre samples of patients are needed to confirm this finding.

Background. Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study. Methods. We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers. Results. A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness ( n = 77 ). Group 2 was defined with days 5-7 ( n = 817 ), group 3 with days 8-10 ( n = 249 ), group 4 with days >10 ( n = 138 ). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences ( p < 0.05 ). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 ( p < 0.05 ) and group 2 ( p < 0.05 ) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance ( p > 0.05 ). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs. Conclusions. IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800).

Background: This study aims to identify some biomarkers for monitoring the recovery of lung injury in severe COVID-19 patients from stabilized stage toward convalescence.Methods: We enrolled participants who diagnosed with severe COVID-19 (n = 28) and health volunteers (n = 25) from Taikang Tongji (Wuhan) Hospital. The patients were in a stabilized stage and had a course of 48.1±12.8 days. We followed these patients for 90 days. The blood routine, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, TNF-α, IFN-α, IFN-γ), type II alveolar epithelium injury indicators (Surfactant protein A (SP-A), Krebs von den Lungen-6 (KL-6)) and chest CT were tested on the 1, 30, 60, and 90 days after enrollment. Results: In stabilized stage, the parameters of blood routine and some cytokines (IL-1β, IL-2, IL-4, IL-12p70, TNF-α) had bounced back to normal (p>0.05). Some cytokines (IL-5, IL-6, IL-10, IL-17A, IFN-α, IFN-γ) and type II alveolar epithelium injury indicators (SP-A and KL-6) were still higher than normal (p<0.05). During the stabilized stage to convalescence, in spite of the variation of monocyte count, monocyte/lymphocyte ratio, IL-5, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α, SP-A and KL-6 were downward trend (p<0.05), only KL-6 level (p<0.05) could simultaneously reflect the lung injury volume which be measured by CT. Conclusions: Our preliminary data indicated that KL-6 could be an effective prognostic biomarker for monitoring the recovery of lung function in patients with severe COVID-19 from stabilized stage toward convalescence.

Background. Kawasaki disease (KD) is a systemic vasculitis of unknown etiology in children. Coronary artery abnormalities are the most common complications of KD. Recent evidence showed that genetic polymorphisms may lead to susceptibility to KD. Genetic variants in platelet glycoprotein have been reported to be associated with coronary artery disease. The aim of the present study is to investigate the correlation between the role of platelet glycoprotein and coronary artery aneurysms in KD patients. Methods. We did a case-control study that enrolled 818 KD patients and 1401 healthy children with the same age and sex from January 2013 to December 2016. Analysis of single-nucleotide polymorphism (rs1126643) of the platelet glycoprotein Ia/IIa C807T was performed by multiplex polymerase chain reactions in this study. Results. A significant difference in the genotype distribution between KD cases and controls was observed for the glycoprotein Ia/IIa C807T (rs1126643) polymorphism ( p = 0.026 ). Compared with the healthy children, the rs1126643T allele carriers had odds ratio (OR) of 0.63 for developing KD (TT vs. CC: adjusted OR = 0.62, 95% confidence interval (CI) = 0.43–0.88, p = 0.0078 ; TT vs. CT/CC: adjusted OR = 0.63, 95% CI = 0.44–0.889, p = 0.0093 ). Furthermore, we also found that children less than 60 months of age and female patients with rs1126643 T allele carriers had an adjusted OR of 0.66 (95% CI = 0.46–0.95) for noncoronary artery aneurysm patients ( p = 0.0242 ). Single-nucleotide polymorphism rs1126643 TT seems to represent a protective factor against KD in coronary artery aneurysm formation in multivariate analysis. Conclusions. The platelet glycoprotein Ia/IIa T allele carriers may have a protective effect on the risk of coronary artery aneurysms of KD patients, especially in females and children aged less than 60 months. These results may provide evidence for platelet glycoprotein Ia/IIa gene polymorphisms in the pathogenesis of KD patients.

Background. Between 10 and 20% of Kawasaki disease (KD) patients are resistant to treatment with initial intravenous immunoglobulin (IVIG) and have a high risk of developing coronary artery lesions. Some studies have been conducted to identify predictive factors. However, the results are controversial. This study aims to identify the risk factors for IVIG-resistant KD patients in a Chinese population. Methods. We performed a retrospective analysis of medical records of consecutive KD patients from two medical centers in South China from January 2015 to December 2017. A total of 1281 KD patients were eligible for inclusion in this study and maintained follow-up for over 12 months. The KD patients were divided into two groups based on IVIG response. Clinical characteristics and laboratory variables were compared between the two groups. Multivariate logistic regression analysis was performed to identify the risk factors of IVIG resistance in KD patients. Results. Of the 1281 KD patients, 141 (11.0%) cases who were IVIG resistant to adjunctive therapies for primary treatment were classified as group 1. The remaining patients were in group 2 (n = 1140), classified as the control group. There was a significant difference in male to female ratio and the length of hospital stay between the two groups ( P < 0.05 ). Group 1 had a higher white blood cell count ( P = 0.01 ) and C-reactive protein level ( P < 0.01 ) before IVIG treatment than in group 2. Group 1 had a significantly higher white blood cell count and percentage of neutrophils after the IVIG infusion than in group 2 ( P < 0.001 ). In addition, the mean values of C-reactive protein level and neutrophil percentage before and after treatment difference comparison were significantly different. Multivariate analysis showed that patients presenting with coronary artery lesions in the acute phase and a C-reactive protein level >100 mg/L at diagnosis were associated with IVIG resistance in KD. During the 12-month follow-up period, group 1 had an obviously higher incidence of coronary artery lesions than group 2, and the difference between the groups was statistically significant ( P < 0.001 ). Conclusions. Patients presenting with coronary artery lesions in the acute phase and elevated C-reactive protein levels before IVIG treatment might be a useful and important value for predicting IVIG resistance in KD. Risk assessment based on coronary artery lesions and C-reactive protein levels prior to the treatment may improve the outcome of IVIG resistance.

Background Kawasaki disease (KD) is a systemic vasculitis, and the formation of coronary artery lesions(CAL) is its most common sequela. Both genetic and environmental factors are considered to be important factors of in KD. Integrin α2 (ITGA2) is a transmembrane receptor that is associated with susceptibility to several diseases, but its relevance to KD with CAL is unclear. Methods We genotyped ITGA2 rs1126643 in 785 KD patients with the CAL and no-CAL(NCAL) (300 patients with CAL, and 485 age- and sex-matched patients with NCAL). OR (95% CI) and adjusted OR (95% CI) were used to evaluate the intensity of the association. Results We found a significantly increased risk of KD with CAL associated with ITGA2 rs1126643 genotypes (CT vs CC: adjusted OR = 1.57, 95% CI = 1.16–2.12, P = 0.0032; CT/TT vs CC: adjusted OR = 1.49, 95% CI = 1.12–2.00, P = 0.0068; T vs C: adjusted OR = 1.66, 95% CI = 1.16–2.51, P = 0.0165). Moreover, we found that carriers of the CT/TT genotype had a significant risk of KD with coronary artery lesion susceptibility for children ≤60 months of age, and the CT/TT genotype was significantly associated with an increased risk of SCAL formation and MCAL formation when compared with the CC genotype. Conclusion ITGA2 rs1126643 was associated with increased susceptibility and severity of CAL in KD.

Objective To investigate the clinical manifestations, laboratory data and coronary artery lesions of refractory Kawasaki disease, and to follow up the patients in the near to medium term. Methods Patients with refractory KD admitted to Guangzhou Women and Children's Medical Center between January 1, 2016 and December 31, 2020 were collected and their clinical data were retrospectively analyzed. Results A total of 42 patients were diagnosed with refractory KD, including 31 (73.81%) and 11 (26.19%) were male and female, respectively, with a median age of 26.7±19.3 (2-99) months. The average time, from onset to diagnosis and IVIG use, was 5.8±0.9 (4-12 ) days, while the fever lasted for 14.8±4.0 (8-34) days. A total of 29 patients exhibited coronary artery disease complications. All patients exhibited persistent or recurrent fever after two doses of IVIG therapy. A total of 41 patients were given a methylprednisolone regimen for up to three consecutive days as follows, while one patient continued to receive IVIG. The diameter of coronary arteries returned to normal 10 patients during the follow-up period, patients with medium and huge tumors exhibited shrunken diameter of coronary arteries, although they were not completely normal. Follow-up observations are still ongoing. Conclusion There is no unified diagnostic criteria and treatment plan for children with refractory KD. For patients that still experience fever after two IVIG treatments, clinicians need to consider the possibility of this type of KD. Development of an effective treatment plan is imperative to shortening fever time and prevention of progressive aggravation of coronary artery disease. Longer follow-up observation is also needed for this group of patients with coronary artery outcomes.