Relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin resistance in Kawasaki disease.

BACKGROUND: This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. METHODS: We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. RESULTS: The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P < 0.05). Additionally, the age of patients with uveitis involvement was lower than those without involvement. No significant relationships existed between ESR, AST, or ALT values and uveitis (P > 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. CONCLUSION: Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.

Single center clinical analysis of macrophage activation syndrome complicating juvenile rheumatic diseases.

BACKGROUND: Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis. METHODS: Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference. RESULTS: Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred. CONCLUSIONS: Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.

The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

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. CONCLUSION: 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.

Exploring viral infections' role in Kawasaki disease onset: A study during the COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, known viral diseases declined in all ages. By using the current situation as a natural experiment, this study aimed to evaluate whether the change in the incidence of Kawasaki disease (KD) during the COVID-19 pandemic varies with age and whether a specific infectious disease mediates the occurrence of KD. Monthly number of KD patients were extracted from the nationwide inpatient database. Segmented regression analysis was conducted on the interrupted time series data. Additionally, causal mediation analysis was performed to examine the role of viral infections in the changes in the number of KD patients. After the first emergency declaration for COVID-19 in Japan, there was an immediate decrease in the number of KD patients per 100 000 population aged between 6 months and 4 years (immediate change = -2.66; 95% confidence interval [CI]: -5.16 to -0.16) and aged 5-15 years (immediate change = -0.26; 95% CI: -0.49 to -0.04). However, no immediate change was observed in patients under 6 months of age. In the causal mediation analysis for each viral infection, it was found that the decrease in the number of patients with KD was mediated by changes in the number of patients with pharyngoconjunctival fever and infectious gastroenteritis. The current results suggest that viral infections may be one of the etiological agents for KD, while they may not be the main cause in early infancy. Specifically, we found that adenovirus infection and gastroenteritis was closely related to the onset of KD in some areas of Japan.

[Predictive indicators and risk model construction for coronary artery lesions in Kawasaki disease children over 5 years old]. / 5å²ä»¥ä¸Šå·å´Žç— å„¿ç«¥åˆå¹¶å† çŠ¶åŠ¨è„‰ç— å˜çš„é¢„æµ‹æŒ‡æ ‡ä¸Žé£Žé™©æ¨¡åž‹æž„å»º.

OBJECTIVES: To study predictive indicators for coronary artery lesions (CAL) and construct a risk prediction model for CAL in Kawasaki disease (KD) children over 5 years old. METHODS: A retrospective analysis of KD children over 5 years old at Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2018 to January 2023 was conducted. Among them, 47 cases were complicated with CAL, and 178 cases were not. Multivariate logistic regression analysis was used to explore predictive indicators for CAL in KD children over 5 years old and construct a risk prediction model. The receiver operating characteristic curve was used to evaluate the effectiveness of the prediction model. Finally, the Framingham risk scoring method was used to quantify the predictive indicators, calculate the contribution of each indicator to the prediction of CAL in KD children over 5 years old, and construct a risk prediction scoring model. RESULTS: The multivariate logistic regression analysis showed that the duration of fever before the initial intravenous immunoglobulin (IVIG) treatment (OR=1.374, 95%CI: 1.117-1.689), levels of hypersensitive C-reactive protein (hs-CRP; OR=1.008, 95%CI: 1.001-1.015), and serum ferritin levels (OR=1.002, 95%CI: 1.001-1.003) were predictive indicators for CAL in KD children over 5 years old. The optimal cutoff values for predicting CAL were: duration of fever before initial IVIG treatment of 6.5 days (AUC=0.654, 95%CI: 0.565-0.744), hs-CRP of 110.50 mg/L (AUC=0.686, 95%CI: 0.597-0.774), and ferritin of 313.62 mg/L (AUC=0.724, 95%CI: 0.642-0.805). According to the Framingham risk scoring method, the low, medium, and high-risk states of CAL occurrence were defined as probabilities of <10%, 10%-20%, and >20%, respectively, with corresponding scores of 0-4 points, 5-6 points, and ≥7 points. CONCLUSIONS: In KD children over 5 years old, those with a longer duration of fever before initial IVIG treatment, higher levels of hs-CRP, or elevated serum ferritin levels are more likely to develop CAL.

Knowledge framework of intravenous immunoglobulin resistance in the field of Kawasaki disease: A bibliometric analysis (1997-2023).

BACKGROUND: Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made tremendous progress in recent years, but intravenous immunoglobulin (IVIG) resistance remains a major dilemma. Bibliometric analysis had not been used previously to summarize and analyze publications related to IVIG resistance in KD. This study aimed to provide an overview of the knowledge framework and research hotspots in this field through bibliometrics, and provide references for future basic and clinical research. METHODS: Through bibliometric analysis of relevant literature published on the Web of Science Core Collection (WoSCC) database between 1997 and 2023, we investigated the cooccurrence and collaboration relationships among countries, institutions, journals, and authors and summarized key research topics and hotspots. RESULTS: Following screening, a total of 364 publications were downloaded, comprising 328 articles and 36 reviews. The number of articles on IVIG resistance increased year on year and the top three most productive countries were China, Japan, and the United States. Frontiers in Pediatrics had the most published articles, and the Journal of Pediatrics had the most citations. IVIG resistance had been studied by 1889 authors, of whom Kuo Ho Chang had published the most papers. CONCLUSION: Research in the field was focused on risk factors, therapy (atorvastatin, tumor necrosis factor-alpha inhibitors), pathogenesis (gene expression), and similar diseases (multisystem inflammatory syndrome in children, MIS-C). "Treatment," "risk factor," and "prediction" were important keywords, providing a valuable reference for scholars studying this field. We suggest that, in the future, more active international collaborations are carried out to study the pathogenesis of IVIG insensitivity, using high-throughput sequencing technology. We also recommend that machine learning techniques are applied to explore the predictive variables of IVIG resistance.

[Kawasaki disease versus Multisystem Inflammatory Syndrome COVID-19 with Kawasaki disease phenotype. Single-center experience]. / Enfermedad de Kawasaki versus Síndrome Inflamatorio Multisistémico COVID 19 con fenotipo enfermedad de Kawasaki. Experiencia de un centro.

In pediatrics, a process called Pediatric Inflammatory Multisystem Syndrome (PIMS) associated with recent infection by SARS-CoV-2 virus has been observed. One of its variants presents similarities with Kawasaki disease (KD). OBJECTIVE: to compare the clinical presentation, laboratory testing, and evolution of KD with PIMS Kawasaki phenotype (PIMS-KD) in patients hospitalized before the pandemic, compared with the pandemic period. PATIENTS AND METHOD: Cross-sectional study in two groups of patients at the Hospital Exequiel González Cortés: typical KD (group 1) and PIMS-KD (group 2). Data on demographic, clinical, and biochemical details were collected, as well as echocardiogram, treatment, and evolution records. IgG and IgM serology for SARS-CoV-2 was performed in both groups. RESULTS: In the KD group and the PIMS-KD group, 20 and 33 patients were analyzed, respectively. There were differences in age, days of fever, count of leukocytes, lymphocytes, and platelets, erythrocyte sedimentation rate (ESR), and hospital stay. In 25% of the KD group, there were alterations in the echocardiogram and, in the PIMS-K group, all patients received corticosteroids and 25 patients received intravenous immunoglobulin (IVIG). In both groups, a favorable clinical evolution was observed, characterized by the absence of complications and mortality. CONCLUSIONS: Based on the data obtained in our study, the importance of the epidemiological link is emphasized as an essential factor in differentiating between both pathologies, highlighting the need to consider factors such as age, duration of fever, count of leukocytes, lymphocytes, and platelets, and degree of cardiac involvement, for a differential evaluation between patients with PIMS-KD versus KD.

Development of an immunoinflammatory indicator-related dynamic nomogram based on machine learning for the prediction of intravenous immunoglobulin-resistant Kawasaki disease patients.

BACKGROUND: Approximately 10-20% of Kawasaki disease (KD) patients suffer from intravenous immunoglobulin (IVIG) resistance, placing them at higher risk of developing coronary artery aneurysms. Therefore, we aimed to construct an IVIG resistance prediction tool for children with KD in Shanghai, China. METHODS: Retrospective analysis was conducted on data from 1271 patients diagnosed with KD and the patients were randomly divided into a training set and a validation set in a 2:1 ratio. Machine learning algorithms were employed to identify important predictors associated with IVIG resistance and to build a predictive model. The best-performing model was used to construct a dynamic nomogram. Moreover, receiver operating characteristic curves, calibration plots, and decision-curve analysis were utilized to measure the discriminatory power, accuracy, and clinical utility of the nomogram. RESULTS: Six variables were identified as important predictors, including C-reactive protein, neutrophil ratio, procalcitonin, CD3 ratio, CD19 count, and IgM level. A dynamic nomogram constructed with these factors was available at https://hktk.shinyapps.io/dynnomapp/. The nomogram demonstrated good diagnostic performance in the training and validation sets (area under the receiver operating characteristic curve = 0.816 and 0.800, respectively). Moreover, the calibration curves and decision curves analysis indicated that the nomogram showed good consistency between predicted and actual outcomes and had good clinical benefits. CONCLUSION: A web-based dynamic nomogram for IVIG resistance was constructed with good predictive performance, which can be used as a practical approach for early screening to assist physicians in personalizing the treatment of KD patients in Shanghai.

Investigating the comparative effect of vitamin D level with the type of complications in Henoch Schönlein purpura and Kawasaki disease.

INTRODUCTION AND OBJECTIVES: Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. MATERIALS AND METHODS: The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients' electronic file, and then they were analyzed after collecting information of the patients. RESULTS: In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P=0.02), hematuria (P=0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P<0.001) were significant. DISCUSSION AND CONCLUSIONS: The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients.

C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10-20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. METHODS: Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. RESULTS: Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58-0.72), specificity as 0.71 (95% CI 0.57-0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66-0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35-3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35-0.69), and the diagnostic odds ratio was 5 (95% CI 2-10). CONCLUSION: CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

Association between maternal heavy metal exposure and Kawasaki Disease, the Japan Environment and Children's Study (JECS).

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting young children, with an unclear etiology. We investigated the link between maternal heavy metal exposure and KD incidence in children using the Japan Environment and Children's Study, a large-scale nationwide prospective cohort with approximately 100,000 mother-child pairs. Maternal blood samples collected during the second/third trimester were analyzed for heavy metals [mercury (Hg), cadmium (Cd), lead (Pb), selenium (Se), manganese (Mn)], divided into four quartiles based on concentration levels. KD incidence within the first year of life was tracked via questionnaire. Among 85,378 mother-child pairs, 316 children (0.37%) under one year were diagnosed with KD. Compared with the lowest concentration group (Q1), the highest (Q4) showed odds ratios (95% confidence interval) for Hg, 1.29 (0.82-2.03); Cd, 0.99 (0.63-1.58); Pb, 0.84 (0.52-1.34); Se, 1.17 (0.70-1.94); Mn, 0.70 (0.44-1.11), indicating no concentration-dependent increase. Sensitivity analyses with logarithmic transformation and extended outcomes up to age 3 yielded similar results. No significant association was found between maternal heavy metal levels and KD incidence, suggesting that heavy metal exposure does not increase KD risk.

Kawasaki disease in Kenya and review of the African literature.

BACKGROUND: Kawasaki disease has been described across the globe, although publications from Africa are limited. To our knowledge, there are no publications on Kawasaki disease from Kenya, which triggered this report. METHODS: A retrospective cross-sectional study was undertaken to identify in-patients with a discharge diagnosis of Kawasaki disease, over 2 different 5-year periods, at two pediatric hospitals in Nairobi, Kenya. We reviewed the medical records of all patients and report their clinical findings, diagnostic workup and treatment. In addition, we undertook a detailed review of the literature. RESULTS: Twenty-three patients with Kawasaki disease were identified, of those 12 (52.2%) had incomplete disease. The mean age was 2.3 years (SD+/-2.2) (range 0.3-10.3) with a male to female ratio of 1:1. The mean duration of fever at diagnosis was 8.3 days (SD+/-4.7) (range 2-20). Oral changes were the most common clinical feature and conjunctivitis the least common. Thrombocytosis at diagnosis was seen in 52% (12/23). Twenty-one patients (91.3%) were treated with intravenous immunoglobulin and all except 1 received aspirin. Baseline echocardiograms were performed in 95.7% (22/23) and found to be abnormal in 3 (13.6%). Follow-up data was limited. Our literature review identified 79 publications with documented cases of Kawasaki disease in children from 22 countries across the African continent with a total of 1115 patients including those from this report. Only 153 reported cases, or 13.7%, are from sub-Saharan Africa. CONCLUSIONS: This is the first publication on Kawasaki disease from Kenya and one of the largest reports from sub-Saharan Africa. It is the first to have a complete review of the number of published cases from the African continent. Challenges in the diagnosis and management of Kawasaki disease in many African countries include disease awareness, infectious confounders, access and cost of intravenous immunoglobulin, access to pediatric echocardiography and follow-up. Increasing awareness and health care resources are important for improving outcomes of Kawasaki disease in Africa.

Convergence and divergence in Kawasaki disease and multisystem inflammatory syndrome in children: results from the COVASAKI survey.

OBJECTIVES: To compare Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS-C) in children. METHODS: Prospective collection of demographics, clinical and treatment data. Assessment of type 1 interferon (IFN) score, CXCL9, CXCL10, Interleukin (IL)18, IFNγ, IL6, IL1b at disease onset and at recovery. RESULTS: 87 patients (43 KD, 44 MIS-C) were included. Age was higher in MIS-C compared to KD group (mean 31±23 vs. 94±50 months, p<0.001). Extremities abnormalities (p=0.027), mucosal involvement (p<0.001), irritability (p<0.001), gallbladder hydrops (p=0.01) and lymphadenopathy (p=0.07) were more often recorded in KD. Neurological findings (p=0.002), gastrointestinal symptoms (p=0.013), respiratory involvement (p=0.019) and splenomegaly (p=0.026) were more frequently observed in MIS-C. Cardiac manifestations were higher in MIS-C (p<0.001), although coronary aneurisms were more frequent in KD (p=0.012). In the MIS-C group, the multiple linear regression analysis revealed that a higher IFN score at onset was related to myocardial disfunction (p<0.001), lymphadenopathy (p=<0.001) and need of ventilation (p=0.024). Both CXCL9 and CXCL10 were related to myocardial disfunction (p<0.001 and p=0.029). IL18 was positively associated to PICU admission (0.030) and ventilation (p=004) and negatively associated to lymphadenopathy (0.004). IFNγ values were related to neurological involvement and lymphadenopathy (p<0.001), IL1b to hearth involvement (0.006). A negative correlation has been observed between IL6 values, heart involvement (p=0.013) and PICU admission (p<0.001). CONCLUSIONS: The demographic and clinical differences between KD e MIS-C cohorts confirm previous reported data. The assessment of biomarkers levels at MIS-C onset could be useful to predict a more severe disease course and the development of cardiac complications.

The effect of vitamin D status on the occurrence of Kawasaki Disease: a meta-analysis.

AIM: The relationship between vitamin D status and Kawasaki Disease (KD), as well as coronary artery lesion (CAL), has yet to be established. METHODS: A meta-analysis was conducted to assess the correlation between vitamin D status and KD, as well as the impact of vitamin D status on the progression of KD into CAL. RESULTS: The meta-analysis revealed a consistent and significant association between serum 25(OH)D level and the occurrence KD (studies N = 22; z = -3.51, P < 0.001). Patients with KD had markedly lower levels of vitamin D than healthy controls (SMD: -1.30 ng/mL, 95%CI: -2.05 to -0.55 ng/mL). CONCLUSION: The study provided evidence supporting a significant association between lower serum vitamin D levels and the occurrence of KD, particularly within the Chinese population. However, the findings did not suggest a direct impact of vitamin D on the development of CAL in KD patients.

Semaphorin 7A promotes endothelial permeability and inflammation via plexin C1 and integrin ß1 in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions. METHODS: Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1ß, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran. RESULTS: The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin ß1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin ß1-dependent manner, while both plexin C1 and integrin ß1 contributed to Sema7A-induced HCAEC hyperpermeability. CONCLUSIONS: Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin ß1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.

Investigating the comparative effect of vitamin D level with the type of complications in Henoch Schönlein purpura and Kawasaki disease / Investigación del efecto comparativo del nivel de vitamina D con el tipo de complicaciones en la púrpura de Henoch-Schönlein y la enfermedad de Kawasaki

Introduction and objectives: Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. Materials and methods: The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients’ electronic file, and then they were analyzed after collecting information of the patients. Results: In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P=0.02), hematuria (P=0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P<0.001) were significant. Discussion and conclusions: The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients.(AU)

Introducción y objetivos: La púrpura de Henoch-Schönlein (HSP) y la enfermedad de Kawasaki (EK) son dos patologías inflamatorias principales entre las vasculitis infantiles. Teniendo en cuenta los efectos antiinflamatorios de la 25-hidroxivitamina D3, decidimos investigar la asociación del nivel sérico de esta con el tipo y la gravedad de dichas afecciones. Materiales y métodos: El presente estudio se realizó como una cohorte histórica de 254 niños afectados con vasculitis por EK y HSP. Los datos requeridos se extrajeron mediante un cuestionario elaborado por un investigador del expediente electrónico de los pacientes y se analizaron después de recopilar la información de los usuarios. Resultados: En el grupo HSP, 54 y 46% de los participantes eran niños y niñas, respectivamente. De manera similar, en el grupo KD, los varones se vieron más afectados. El nivel comparativo de 25-hidroxivitamina D3 en pacientes con HSP con y sin afectación renal (p = 0,02), hematuria (p = 0,14), y en dos grupos con y sin enfermedad cardiaca, y en dos con y sin dilatación de la arteria coronaria en usuarios con EK (p < 0,001) fueron significativos. Discusión y conclusiones: Los hallazgos mostraron que los niveles insuficientes de vitamina D se asociaron significativamente con la exacerbación de las complicaciones de ambas enfermedades, por lo que parece que la deficiencia de vitamina D puede ser un factor predictivo eficaz de la gravedad en pacientes con HSP y EK.(AU

Knowledge, attitudes, and practices towards Kawasaki disease from caregivers of children with Kawasaki disease: a cross-sectional study.

PURPOSE: To examine the knowledge, attitudes, and practices (KAP) of caregivers of children with Kawasaki disease toward Kawasaki disease. METHODS: This cross-sectional study was conducted at four hospitals in China from March 2023 to June 2023. The KAP scores were evaluated using a self-designed questionnaire (Cronbach's α = 0.840; KMO = 0.7381). Correlations between dimension scores were evaluated by Pearson correlation analysis. A structural equation model (SEM) was used to examine the relationships among factors. RESULTS: Of 643 surveyed, 49.50% were male caregivers. The mean knowledge, attitude, and practice scores were 7.12 ± 2.34 (possible range, 0-11), 29.23 ± 5.67 (possible range, 12-60), and 21.57 ± 5.34 (possible range, 6-30). Knowledge correlated with attitude (r = 0.172, P < 0.001) and practice (r = 0.280, P < 0.001). Attitude was significantly related to practice (r = 0.598, P < 0.001). SEM showed knowledge had a positive effect on attitudes (ß = 0.581, P < 0.001) and practices (ß = 0.786, P < 0.001). In addition, attitudes also positively affected practices (ß = 0.554, P < 0.001). Occupation type (ß = 0.598, P = 0.025) and monthly per capita income (ß=-0.750, P = 0.020) had different effects on attitudes, while monthly per capita income also had negative effects on practices (ß=-0.410, P = 0.021). CONCLUSION: Caregivers of children with Kawasaki disease have moderate knowledge and unfavorable attitudes but proactive practices toward this disease. The results could help design an educational intervention to improve KAP, which could translate into better patient management and outcomes. TRIAL REGISTRATION: Not applicable.

Combination of S100A12/TLR2 signaling molecules and clinical indicators in a new predictive model for IVIG-resistant Kawasaki disease.

Although intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) presents with persistent inflammatory stimulation of the blood vessels and an increased risk of coronary artery dilatation. However, the pathogenesis of this disease is unclear, with no established biomarkers to predict its occurrence. This study intends to explore the utility of S100A12/TLR2-related signaling molecules and clinical indicators in the predictive modeling of IVIG-resistant KD. The subjects were classified according to IVIG treatment response: 206 patients in an IVIG-sensitive KD group and 49 in an IVIG-resistant KD group. Real-time PCR was used to measure the expression of S100A12, TLR2, MYD88, and NF-κB in peripheral blood mononuclear cells of patients, while collecting demographic characteristics, clinical manifestations, and laboratory test results of KD children. Multi-factor binary logistic regression analysis identified procalcitonin (PCT) level (≥ 0.845 ng/mL), Na level (≤ 136.55 mmol/L), and the relative expression level of S100A12 (≥ 10.224) as independent risk factors for IVIG-resistant KD and developed a new scoring model with good predictive ability to predict the occurrence of IVIG-resistant KD.

Adverse Events Following COVID-19 Vaccination in Adolescents: Insights From Pharmacovigilance Study of VigiBase.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. METHODS: In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization's global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12-17 years, ICSRs following any vaccines on adolescents aged 12-17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. RESULTS: Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents; myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05-27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89-9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72-1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44-0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59-2.09) were not significantly higher following COVID-19 vaccination. CONCLUSION: In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

Involvement of IL-17 A/IL-17 Receptor A with Neutrophil Recruitment and the Severity of Coronary Arteritis in Kawasaki Disease.

PURPOSE: To assess the role of the interleukin (IL)-17 A/IL-17 receptor A (IL-17RA) in Kawasaki disease (KD)-related coronary arteritis (CA). METHODS: In human study, the plasma levels of IL-17 A and coronary arteries were concurrently examined in acute KD patients. In vitro responses of human coronary endothelial cells to plasma stimulation were investigated with and without IL-17RA neutralization. A murine model of Lactobacillus casei cell-wall extract (LCWE)-induced CA using wild-type Balb/c and Il17ra-deficient mice were also inspected. RESULTS: The plasma levels of IL-17 A were significantly higher in KD patients before intravenous immunoglobulin therapy, especially in those with coronary artery lesion. The pre-IVIG IL-17 A levels positively correlated with maximal z scores of coronary diameters and plasma-induced endothelial mRNA levels of chemokine (C-X-C motif) ligand-1, IL-8, and IL-17RA. IL-17RA blockade significantly reduced such endothelial upregulations of aforementioned three genes and inducible nitric oxide synthase, and neutrophil transmigration. IL-17RA expression was enhanced on peripheral blood mononuclear cells in pre-IVIG KD patients, and in the aortic rings and spleens of the LCWE-stimulated mice. LCWE-induced CA composed of dual-positive Ly6G- and IL-17 A-stained infiltrates. Il17ra-deficient mice showed reduced CA severity with the fewer number of neutrophils and lower early inducible nitric oxide synthase and chemokine (C-X-C motif) ligand-1 mRNA expressions than Il17ra+/+ littermates, and absent IL-17RA upregulation at aortic roots. CONCLUSION: IL-17 A/IL-17RA axis may play a role in mediating aortic neutrophil chemoattraction, thus contributory to the severity of CA in both humans and mice. These findings may help to develop a new therapeutic strategy toward ameliorating KD-related CA.