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1.
J Nippon Med Sch ; 91(3): 285-295, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38972741

RESUMO

BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFß receptors. Measurement of the inflammatory cytokines IL-1ß, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.


Assuntos
Benzimidazóis , Compostos de Bifenilo , Candida albicans , Modelos Animais de Doenças , Síndrome de Linfonodos Mucocutâneos , Tetrazóis , Animais , Benzimidazóis/farmacologia , Benzimidazóis/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Tetrazóis/farmacologia , Tetrazóis/administração & dosagem , Candida albicans/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Camundongos Endogâmicos DBA , Solubilidade , Água , Vasculite/tratamento farmacológico , Masculino , Camundongos , Citocinas/metabolismo , Interleucina-6/metabolismo
2.
J Nippon Med Sch ; 91(3): 277-284, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38972740

RESUMO

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.


Assuntos
Amônia , Circulação Coronária , Síndrome de Linfonodos Mucocutâneos , Imagem de Perfusão do Miocárdio , Radioisótopos de Nitrogênio , Tomografia por Emissão de Pósitrons , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Masculino , Feminino , Amônia/sangue , Tomografia por Emissão de Pósitrons/métodos , Criança , Pré-Escolar , Imagem de Perfusão do Miocárdio/métodos , Oclusão Coronária/etiologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/fisiopatologia , Aneurisma Coronário/etiologia , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/fisiopatologia , Adolescente , Lactente , Hemodinâmica
3.
Sci Rep ; 14(1): 15671, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977728

RESUMO

The study aims to explore the central genes that Kawasaki disease (KD) and Obesity (OB) may jointly contribute to coronary artery disease. Investigating single-cell datasets (GSE168732 and GSE163830) from a comprehensive gene expression database, we identified characteristic immune cell subpopulations in KD and OB. B cells emerged as the common immune cell characteristic subgroup in both conditions. Subsequently, we analyzed RNA sequencing datasets (GSE18606 and GSE87493) to identify genes associated with B-cell subpopulations in KD and OB. Lastly, a genome-wide association study and Mendelian randomization were conducted to substantiate the causal impact of these core genes on myocardial infarction. Quantitative real-time PCR (qRT-PCR) to validate the expression levels of hub genes in KD and OB. The overlapping characteristic genes of B cell clusters in both KD and OB yielded 70 shared characteristic genes. PPI analysis led to the discovery of eleven key genes that significantly contribute to the crosstalk. Employing receiver operating characteristic analysis, we evaluated the specificity and sensitivity of these core genes and scored them using Cytoscape software. The inverse variance weighting analysis suggested an association between TNFRSF17 and myocardial infarction risk, with an odds ratio of 0.9995 (95% CI = 0.9990-1.0000, p = 0.049). By employing a single-cell combined transcriptome data analysis, we successfully pinpointed central genes associated with both KD and OB. The implications of these findings extend to shedding light on the increased risk of coronary artery disease resulting from the co-occurrence of OB and KD.


Assuntos
Linfócitos B , Estudo de Associação Genômica Ampla , Síndrome de Linfonodos Mucocutâneos , Obesidade Infantil , Transcriptoma , Síndrome de Linfonodos Mucocutâneos/genética , Humanos , Obesidade Infantil/genética , Linfócitos B/metabolismo , Linfócitos B/imunologia , Criança , Perfilação da Expressão Gênica , Masculino , Feminino , Análise da Randomização Mendeliana , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/etiologia , Pré-Escolar , Infarto do Miocárdio/genética , Análise de Célula Única
4.
Sci Rep ; 14(1): 15232, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956281

RESUMO

Intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) was associated with coronary artery lesions. Neutrophil percentage-to-albumin ratio (NPAR) is an index of mortality in several inflammatory diseases. This study focused on the association of NPAR with IVIG- resistance in KD. Clinical and laboratory data of 438 children with KD before IVIG treatment were retrospectively analyzed. Notably, high NPAR was associated with older age, high WBC, NP, ALT, total bilirubin and CRP, as well as with high the incidence of IVIG-resistance, and with low hemoglobin (Hb), PLT, ALB and sodium levels. NPAR (OR: 2.366, 95% CI: 1.46-3.897, p = 0.001) and Hb (OR: 0.967, 95% CI: 0.944-0.989, p = 0.004) were independent risk factors for IVIG-resistance. NPAR showed linear relation with IVIG-resistance (p for nonlinear = 0.711) and the nonlinear correlation was found between IVIG-resistance and Hb (p for nonlinear = 0.002). The predictive performance of NPAR was superior to Beijing model (z = 2.193, p = 0.028), and not inferior to Chongqing model (z = 0.983, p = 0.326) and the combination of NPAR and Hb (z = 1.912, p = 0.056). These findings revealed that NPAR is a reliable predictor of IVIG-resistance.


Assuntos
Biomarcadores , Resistência a Medicamentos , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Neutrófilos , Humanos , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Pré-Escolar , Lactente , Biomarcadores/sangue , Estudos Retrospectivos , Criança , Albuminas/metabolismo
5.
Cytokine ; 180: 156667, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38857561

RESUMO

BACKGROUND: Kawasaki disease (KD) is a vasculitis of unknown etiology in children aged under 5 years. Coronary arterial aneurysm (CAA) is the major complication of KD. It is no longer though to be a self-limiting disease because its cardiovascular sequelae might persist into adulthood. NLRP3 is a key protein of the NLRP3 inflammasome that participates in sterile inflammatory disease. This study investigated the serum levels of NLRP3 in patients with KD at different stages to explore the relationships between serum NLRP3 and clinical parameters. METHODS: A total of 247 children enrolled in this study. There were 123 patients in the acute stage of KD, and 93 healthy children made up the healthy control (HC) group. Among the acute KD patients, 52 had coronary arterial aneurysm (KD-CAA) and 71 did not (KD-NCAA). 36 patient samples were collected after IVIG and aspirin treatment. Additionally, 29 patients were in the cardiovascular sequelae stage. Enzyme-linked immunosorbent assay was used to measure serum NLRP3 levels in all subjects. RESULTS: Serum NLRP3 was elevated in the KD group and was even higher in the KD-CAA subgroup than in the KD-NCAA subgroup of acute-stage patients. Serum NLRP3 declined when the patients were treated with IVIG and aspirin, but during the convalescent (coronary sequelae) stage, serum NLRP3 re-increased. Serum NLRP3 was higher in the ≥ 6-mm-coronary-arterial-diameter group than that the < 6-mm-diameter group. The ROC curve of serum NLRP3 indicated its utility in the prediction of both KD and KD-CAA. CONCLUSIONS: NLRP3 may be involved in the development of KD and CAA in children with KD. Targeting NLRP3 might mitigate CAA, thereby reducing the risk of cardiovascular events in adulthood.


Assuntos
Biomarcadores , Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/complicações , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Masculino , Feminino , Aneurisma Coronário/sangue , Aneurisma Coronário/etiologia , Pré-Escolar , Biomarcadores/sangue , Lactente , Criança , Aspirina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico
6.
BMC Public Health ; 24(1): 1591, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872194

RESUMO

BACKGROUND: Kawasaki disease (KD) is the most important acquired heart disease in children. This study investigated annual incidence, seasonality, secular trend and the correlation of KD incidence with viral activity in Taiwan. METHODS: Through the national health insurance database, we identified KD during 2001-2020. The viral activity was obtained from nationwide surveillance database. We analyzed KD age-specific annual incidence, secular trends, seasonality and the correlation between KD incidence and common enteric or respiratory viral activity. RESULTS: The KD incidence of subjects younger than 18 years significantly increased from 2001 to 2020 (11.78 and 22.40 per 100,000 person-years, respectively), and substantially decreased with age. Infants younger than 1 year presented the highest KD annual incidence at 105.82 to 164.34 per 100,000 person-years from 2001 to 2020. For all KD patients, the most frequently occurring season was summer followed by autumn. The KD incidence of infants younger than 1 year had significantly positive correlation with enteric (r = 0.14) and respiratory (r = 0.18) viral activity. CONCLUSIONS: This study demonstrates the increasing trend of KD annual incidence and seasonality (more in summer and autumn) in Taiwan. The activity of common respiratory and enteric viruses was significantly correlated with KD incidence in infants.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Estações do Ano , Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Taiwan/epidemiologia , Lactente , Incidência , Pré-Escolar , Masculino , Feminino , Criança , Adolescente , Recém-Nascido , Vigilância da População
7.
Front Immunol ; 15: 1400046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887295

RESUMO

Background: Kawasaki disease shock syndrome (KDSS) is a critical manifestation of Kawasaki disease (KD). In recent years, a logistic regression prediction model has been widely used to predict the occurrence probability of various diseases. This study aimed to investigate the clinical characteristics of children with KD and develop and validate an individualized logistic regression model for predicting KDSS among children with KD. Methods: The clinical data of children diagnosed with KDSS and hospitalized between January 2021 and December 2023 were retrospectively analyzed. The best predictors were selected by logistic regression and lasso regression analyses. A logistic regression model was built of the training set (n = 162) to predict the occurrence of KDSS. The model prediction was further performed by logistic regression. A receiver operating characteristic curve was used to evaluate the performance of the logistic regression model. We built a nomogram model by visualizing the calibration curve using a 1000 bootstrap resampling program. The model was validated using an independent validation set (n = 68). Results: In the univariate analysis, among the 24 variables that differed significantly between the KDSS and KD groups, further logistic and Lasso regression analyses found that five variables were independently related to KDSS: rash, brain natriuretic peptide, serum Na, serum P, and aspartate aminotransferase. A logistic regression model was established of the training set (area under the receiver operating characteristic curve, 0.979; sensitivity=96.2%; specificity=97.2%). The calibration curve showed good consistency between the predicted values of the logistic regression model and the actual observed values in the training and validation sets. Conclusion: Here we established a feasible and highly accurate logistic regression model to predict the occurrence of KDSS, which will enable its early identification.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/sangue , Masculino , Feminino , Pré-Escolar , Lactente , Estudos Retrospectivos , Modelos Logísticos , Criança , Choque/etiologia , Choque/diagnóstico , Curva ROC , Nomogramas , Prognóstico , Biomarcadores/sangue
9.
Pediatr Allergy Immunol ; 35(6): e14176, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899598

RESUMO

BACKGROUND: It has been suggested that allergic diseases may increase after Kawasaki disease (KD). We aimed to analyze the temporal patterns of allergic disease incidence after KD. METHODS: A nationwide population-based matched cohort study was conducted using data from the Korean National Health Insurance claims database. Patients aged <5 years diagnosed with KD and their 1:3 propensity score-matched controls were included. Three cohorts were established: Cohort A, patients with allergies; Cohort B, patients without allergies; and Cohort C, patients without allergies, but excluding patients with birth history and underlying medical conditions. Cumulative incidence rates (%) and associated hospital visits for allergic rhinitis, atopic dermatitis, urticaria, and asthma were compared between the cases and controls during the 6-year follow-up period. RESULTS: The study population comprised 8678 patients diagnosed with KD and 26,034 controls. In Cohort A, although initially, there were intergroup differences in the number of hospital visits for certain allergic diseases, these differences were inconsistent and varied depending on the type of allergic disease. Over time, the differences narrowed, and by the sixth year, the gap had decreased significantly. In Cohorts B and C, the initial incidence rates of the four allergic diseases and associated hospital visits were lower in patients with KD as compared to controls. However, with a faster rate of increase, the incidence rates and number of hospital visits eventually surpassed those of the controls. CONCLUSIONS: The pattern of delayed increase in cumulative incidence rates and hospital visits for allergic diseases after KD suggests the possibility of a shared genetic or immunologic susceptibility between KD and allergic diseases, which becomes evident over time, rather than a direct influence of KD resulting in allergic diseases.


Assuntos
Hipersensibilidade , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Masculino , Feminino , Pré-Escolar , Incidência , República da Coreia/epidemiologia , Lactente , Hipersensibilidade/epidemiologia , Estudos de Coortes , Seguimentos , Dermatite Atópica/epidemiologia
10.
Clin Drug Investig ; 44(6): 425-437, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38869717

RESUMO

BACKGROUND AND OBJECTIVE: Intravenous immunoglobulin (IVIG) is a prominent therapeutic agent for Kawasaki disease (KD) that significantly reduces the incidence of coronary artery anomalies. Various methodologies, including machine learning, have been employed to develop IVIG non-responder prediction models; however, their validation and reproducibility remain unverified. This study aimed to develop a predictive scoring system for identifying IVIG nonresponders and rigorously test the accuracy and reliability of this system. METHODS: The study included an exposure group of 228 IVIG non-responders and a control group of 997 IVIG responders. Subsequently, a predictive machine learning model was constructed. The Shizuoka score, including variables such as the "initial treatment date" (cutoff: < 4 days), sodium level (cutoff: < 133 mEq/L), total bilirubin level (cutoff: ≥ 0.5 mg/dL), and neutrophil-to-lymphocyte ratio (cutoff: ≥ 2.6), was established. Patients meeting two or more of these criteria were grouped as high-risk IVIG non-responders. Using the Shizuoka score to stratify IVIG responders, propensity score matching was used to analyze 85 patients each for IVIG and IVIG-added prednisolone treatment in the high-risk group. In the IVIG plus prednisolone group, the IVIG non-responder count significantly decreased (p < 0.001), with an odds ratio of 0.192 (95% confidence interval 0.078-0.441). CONCLUSIONS: Intravenous immunoglobulin non-responders were predicted using machine learning models and validated using propensity score matching. The initiation of initial IVIG-added prednisolone treatment in the high-risk group identified by the Shizuoka score, crafted using machine learning models, appears useful for predicting IVIG non-responders.


Assuntos
Imunoglobulinas Intravenosas , Aprendizado de Máquina , Síndrome de Linfonodos Mucocutâneos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Pré-Escolar , Lactente , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem , Criança , Estudos Retrospectivos
11.
Cell Commun Signal ; 22(1): 328, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872145

RESUMO

BACKGROUND: Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. METHODS: We measured mtDNA and 2'3'-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. RESULTS: KD patient serum exhibited increased mtDNA and 2'3'-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. CONCLUSION: These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.


Assuntos
DNA Mitocondrial , Inflamação , Proteínas de Membrana , Poro de Transição de Permeabilidade Mitocondrial , Síndrome de Linfonodos Mucocutâneos , Nucleotidiltransferases , Transdução de Sinais , Síndrome de Linfonodos Mucocutâneos/metabolismo , Síndrome de Linfonodos Mucocutâneos/patologia , Síndrome de Linfonodos Mucocutâneos/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Humanos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Inflamação/patologia , Inflamação/metabolismo , Inflamação/genética , Animais , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Masculino , Camundongos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Feminino , Doença Aguda , Camundongos Endogâmicos C57BL , Pré-Escolar
12.
BMC Pediatr ; 24(1): 415, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926640

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age. Muscular weakness is a rare manifestation of KD, and only 11 pediatric patients with KD combined with muscular weakness have been reported, of which evidence of myositis was found in 2/3 of the patients, and 1/3 could not be explained by myositis, the mechanism of which is still unclear. Cases of KD combined with bladder retention are even more rare, and there has been only 1 case report of KD combined with bladder retention in a child with no previous underlying disease. CASE PRESENTATION: We report a 22-month-old Asian child with incomplete Kawasaki disease (IKD) who initially presented with fever and progressive muscular weakness in the lower extremities, followed by the bladder and bowel retention abnormalities and rapid onset of heart failure, respiratory failure and shock. The child developed coronary artery ectasia (CAA) without the main clinical features of KD such as rash, conjunctival congestion, desquamation of the extremity endings, orofacial changes and enlarged lymph nodes in the neck. Creatine kinase and electromyography were normal. Temperature gradually normalized and muscle strength recovered slightly after intravenous immunoglobulin. The child could be helped to walk after 1 week of aspirin combined with steroid therapy. CONCLUSIONS: We present the case of a 22-month-old child with IKD. The child began with progressive muscular weakness in the extremities, followed by the bladder and bowel retention abnormalities, and rapidly developed heart failure, respiratory failure, and shock. Despite early failure to detect the disease, the child recovered rapidly and had a favorable prognosis. KD comorbidities with muscular weakness as the main manifestation are uncommon. This is the first case report of IKD combined with both muscular weakness and bladder and bowel retention, which may provide clinicians with diagnostic and therapeutic ideas, as well as a basis for future exploration of the mechanisms of KD combined with muscular weakness or bladder and bowel retention abnormalities.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Debilidade Muscular , Retenção Urinária , Humanos , Lactente , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Debilidade Muscular/etiologia , Retenção Urinária/etiologia
13.
J Med Virol ; 96(5): e29660, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727136

RESUMO

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.


Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/virologia , COVID-19/epidemiologia , COVID-19/complicações , Pré-Escolar , Japão/epidemiologia , Lactente , Criança , Adolescente , Incidência , Masculino , Feminino , Viroses/epidemiologia , Viroses/complicações , SARS-CoV-2/patogenicidade
14.
J Int Med Res ; 52(5): 3000605241252115, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38713460

RESUMO

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.


Assuntos
Doença da Artéria Coronariana , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/imunologia , Pré-Escolar , Estudos Retrospectivos , Lactente , LDL-Colesterol/sangue , Resistência a Medicamentos , Lipídeos/sangue , Criança , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Fatores de Risco , Apolipoproteínas B/sangue , Prognóstico
15.
Clin Immunol ; 264: 110237, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723855

RESUMO

Multisystem inflammatory syndrome in children (MIS-C) shares several clinical and immunological features with Kawasaki Disease (KD) and pediatric hyperinflammation, but the immuno-phenotypic overlap among these clinical mimics is still incompletely understood. Here we analyzed serum samples from treatment-naïve patients with MIS-C (n = 31) and KD (n = 11), pediatric hyperinflammation (n = 13) and healthy controls (HC, n = 10) by proximity extension assay (PEA) to profile 184 blood biomarkers. Collectively, immunophenotypic overlap between MIS-C and hyperinflammation exceeds overlap with KD. Overexpression of IL-17A in MIS-C and KD could best separate these conditions from hyperinflammatory conditions, while those were hallmarked by overabundance of adenosin deaminase and IL-18. Depletion in serum TNF-related subfamily member 9 (TNFRSF9) and apoptosis inducing ligand (TRAIL) linked with cardiovascular manifestations and myocarditis in MIS-C. Altogether, our analysis highlights important differences in molecular marker signatures also across different MIS-C and KD cohorts and suggests several previously unidentified molecular associations in context of cardiovascular inflammation.


Assuntos
Biomarcadores , Síndrome de Linfonodos Mucocutâneos , Proteômica , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Biomarcadores/sangue , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/imunologia , Masculino , Feminino , Proteômica/métodos , Criança , Pré-Escolar , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Inflamação/sangue , Lactente , Interleucina-17/sangue , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Interleucina-18/sangue , Adenosina Desaminase/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/imunologia
16.
Andes Pediatr ; 95(2): 174-182, 2024 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-38801365

RESUMO

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.


Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Fenótipo , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/complicações , COVID-19/complicações , COVID-19/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Masculino , Feminino , Estudos Transversais , Pré-Escolar , Criança , Lactente , Diagnóstico Diferencial , Ecocardiografia , Imunoglobulinas Intravenosas/uso terapêutico
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(5): 461-468, 2024 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-38802905

RESUMO

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.


Assuntos
Proteína C-Reativa , Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Masculino , Pré-Escolar , Feminino , Estudos Retrospectivos , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/sangue , Modelos Logísticos , Proteína C-Reativa/análise , Criança , Fatores de Risco , Imunoglobulinas Intravenosas/uso terapêutico , Ferritinas/sangue
18.
Int Immunopharmacol ; 134: 112194, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703570

RESUMO

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.


Assuntos
Resistência a Medicamentos , Imunoglobulinas Intravenosas , Aprendizado de Máquina , Síndrome de Linfonodos Mucocutâneos , Nomogramas , Humanos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Lactente , China , Criança , Proteína C-Reativa/análise
19.
Immun Inflamm Dis ; 12(5): e1277, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38775687

RESUMO

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.


Assuntos
Bibliometria , Resistência a Medicamentos , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/farmacologia , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/epidemiologia
20.
Pediatr Rheumatol Online J ; 22(1): 50, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693550

RESUMO

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.


Assuntos
Resistência a Medicamentos , Ecocardiografia , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Estudos Transversais , Ecocardiografia/métodos , Pré-Escolar , Lactente , Criança , Uveíte/etiologia , Uveíte/epidemiologia , Conjuntivite/etiologia , Conjuntivite/epidemiologia , Incidência , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Sedimentação Sanguínea , Contagem de Leucócitos , Fatores Imunológicos/uso terapêutico , Contagem de Plaquetas
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