24 research outputs found
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Author Correction: Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers.
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Seasonality of Kawasaki disease: a global perspective
Background: Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Methods: Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. Results: A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Conclusion: Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics
Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network
Objetivos: Describir la presentación clínica, el manejo y los resultados de la enfermedad de Kawasaki (EK) en Latinoamérica y evaluar los indicadores pronósticos tempranos de aneurisma de la arteria coronaria (AAC). Diseño del estudio: Se realizó un estudio observacional basado en el registro de la EK en 64 centros pediátricos participantes de 19 países latinoamericanos de forma retrospectiva entre el 1 de enero de 2009 y el 31 de diciembre de 2013, y de forma prospectiva desde el 1 de junio de 2014 hasta el 31 de mayo de 2017. Se recopilaron datos demográficos, clínicos y de laboratorio iniciales. Se utilizó una regresión logística que incorporaba factores clínicos y la puntuación z máxima de la arteria coronaria en la presentación inicial (entre 10 días antes y 5 días después de la inmunoglobulina intravenosa [IGIV]) para desarrollar un modelo pronóstico de AAC durante el seguimiento (>5 días después de la IGIV). Resultados: De 1853 pacientes con EK, el ingreso tardío (>10 días tras el inicio de la fiebre) se produjo en el 16%, el 25% tuvo EK incompleta y el 11% fue resistente a la IGIV. Entre los 671 sujetos con puntuación z de la arteria coronaria notificada durante el seguimiento (mediana: 79 días; IQR: 36, 186), el 21% presentaba AAC, incluido un 4% con aneurismas gigantes. Un modelo pronóstico simple que utilizaba sólo una puntuación z de la arteria coronaria máxima ≥2,5 en la presentación inicial fue óptimo para predecir la AAC durante el seguimiento (área bajo la curva: 0,84; IC del 95%: 0,80, 0,88). Conclusiones: De nuestra población latinoamericana, la puntuación z de la arteria coronaria ≥2,5 en la presentación inicial fue el factor pronóstico más importante que precedió a la AAC durante el seguimiento. Estos resultados resaltan la importancia de la ecocardiografía temprana durante la presentación inicial de la EK. © 2023 Los autoresObjectives: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). Study design: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). Results: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). Conclusion: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD. © 2023 The Author(s
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SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C.
BACKGROUND: Recent infection with SARS‑CoV‑2 in children has been associated with multisystem inflammatory syndrome in children (MIS-C). SARS‑CoV‑2 has undergone different mutations. Few publications exist about specific variants and their correlation with the severity of MIS-C. METHODS: This was a single-center, retrospective study including all patients admitted with MIS-C at Rady Childrens Hospital-San Diego between May 2020 and March 2022. Local epidemiologic data, including viral genomic information, were obtained from public records. Demographics, clinical presentation, laboratory values, and outcomes were obtained from electronic medical records. RESULTS: The analysis included 104 pediatric patients. Four MIS-C waves were identified. Circulating variants in San Diego during the first wave included clades 20A to C. During the second wave, there were variants from clades 20A to C, 20G, 21C (Epsilon), 20I (Alpha), and 20J (Gamma). The third wave had Delta strains (clades 21A, 21I, and 21J), and the fourth had Omicron variants (clades 21K, 21L, and 22C). MIS-C presented with similar symptoms and laboratory findings across all waves. More patients were admitted to the pediatric intensive care unit (PICU) (74%) and required inotropic support (63%) during the second wave. None of the patients required mechanical circulatory support, and only two required invasive ventilatory support. There was no mortality. CONCLUSIONS: The various strains of SARS-CoV-2 triggered MIS-C with differing severities, with the second wave having a more severe clinical course. Whether the differences in disease severity across variants were due to changes in the virus or other factors remains unknown
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Infliximab for intensification of primary therapy for patients with Kawasaki disease and coronary artery aneurysms at diagnosis
ObjectiveChildren with Kawasaki disease (KD) and an initial echocardiogram that demonstrates coronary artery aneurysms (CAAs, Z score ≥2.5) are at high risk for severe cardiovascular complications. We sought to determine if primary adjunctive infliximab treatment at a dose of either 5 or 10 mg/kg, compared with intravenous immunoglobulin (IVIG) alone, is associated with a greater likelihood of CAA regression in patients with KD with CAA at the time of diagnosis.Design and settingSingle-centre observational study.PatientsChildren with acute KD and Z score ≥2.5 at baseline.InterventionsPrimary adjunctive infliximab (5 or 10 mg/kg) within 48 hours of initiating IVIG 2 g/kg.Main outcome measuresIncidence of CAA regression to Zmax <2 within 2 months of disease onset.ResultsOf the 168 patients with KD, 111 received IVIG alone and 57 received primary adjunctive infliximab therapy: 39 received 5 mg/kg and 18 received 10 mg/kg. Incidence of CAA regression to Zmax <2 within 2 months was statistically significant at 52%, 62% and 83% in the IVIG alone, IVIG+infliximab 5 mg/kg and IVIG+infliximab 10 mg/kg, respectively. The multivariable logistic regression model adjusting for age, sex, baseline Zmax and bilateral CAA at baseline showed that IVIG plus 10 mg/kg infliximab was significantly associated with a greater likelihood of CAA regression (adjusted OR: 4.45, 95% CI 1.17 to 16.89, p=0.028) compared with IVIG alone. The difference between IVIG+infliximab 5 mg/kg and IVIG alone was not significant.ConclusionsPrimary adjunctive high-dose 10 mg/kg infliximab treatment was associated with a greater likelihood of CAA regression in patients with CAA at the time of diagnosis
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Temporal Clusters of Kawasaki Disease Cases Share Distinct Phenotypes That Suggest Response to Diverse Triggers.
ObjectiveTo test the hypothesis that cases of Kawasaki disease within a temporal cluster have a similar pattern of host response that is distinct from cases of Kawasaki disease in different observed clusters and randomly constructed clusters.Study designWe designed a case-control study to analyze 47 clusters derived from 1332 patients with Kawasaki disease over a 17-year period (2002-2019) from a single clinical site and compared the cluster characteristics with those of 2 control groups of synthetic Kawasaki disease clusters. We defined a "true" Kawasaki disease cluster as at least 5 patients within a 7-day moving window. The observed and synthetic Kawasaki disease clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, rotated empirical orthogonal function analysis.ResultsIn a univariate analysis, the median values for age, coronary artery z-score, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and age-adjusted hemoglobin for several of the true Kawasaki disease clusters exceeded the 95th percentile for the 2 synthetic clusters. REOF analyses revealed distinct patterns of demographic and clinical measures within clusters.ConclusionsCases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features and levels of inflammation than would be expected by chance. These observations suggest that different triggers and/or different intensities of exposures result in clusters of cases of Kawasaki disease that share a similar response pattern. Analyzing cases within clusters or cases who share demographic and clinical features may lead to new insights into the etiology of Kawasaki disease
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Intravenous immunoglobulin resistance in Kawasaki disease patients: prediction using clinical data
BackgroundAbout 10-20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features.MethodsData were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z-score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation.ResultsFive machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706-0.72] in the Korean cohort and 0.696 [IQR: 0.609-0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z-score, KD clinical signs, or both did not considerably improve the median AUC in either cohort.ConclusionsUsing commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility.ImpactWe demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful
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Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers.
Kawasaki Disease (KD) is the most common cause of pediatric acquired heart disease, but its etiology remains unknown. We examined 1164 cases of KD treated at a regional children's hospital in San Diego over a period of 15 years and uncovered novel structure to disease incidence. KD cases showed a well-defined seasonal variability, but also clustered temporally at much shorter time scales (days to weeks), and spatiotemporally on time scales of up to 10 days and spatial scales of 10-100 km. Temporal clusters of KD cases were associated with strongly significant regional-scale air temperature anomalies and consistent larger-scale atmospheric circulation patterns. Gene expression analysis further revealed a natural partitioning of KD patients into distinct groups based on their gene expression pattern, and that the different groups were associated with certain clinical characteristics that also exhibit temporal autocorrelation. Our data suggest that one or more environmental triggers exist, and that episodic exposures are modulated at least in part by regional weather conditions. We propose that characterization of the environmental factors that trigger KD in genetically susceptible children should focus on aerosols inhaled by patients who share common disease characteristics
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Subgroups of children with Kawasaki disease: a data-driven cluster analysis.
BACKGROUND: Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups. METHODS: We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Childrens Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022. Patients were grouped by hierarchical clustering on principal components with k-means parcellation based on 14 variables, including age at onset, ten laboratory test results, day of illness at the first intravenous immunoglobulin infusion, and normalised echocardiographic measures of coronary artery diameters at diagnosis. We also analysed the seasonality and Kawasaki disease incidence from 2002 to 2019 by subgroup. To explore the biological underpinnings of identified subgroups, we did differential abundance analysis on proteomic data of 6481 proteins from 32 patients with Kawasaki disease and 24 healthy children, using linear regression models that controlled for age and sex. FINDINGS: Among 1016 patients with complete data in the final analysis, four subgroups were identified with distinct clinical features: (1) hepatobiliary involvement with elevated alanine transaminase, gamma-glutamyl transferase, and total bilirubin levels, lowest coronary artery aneurysm but highest intravenous immunoglobulin resistance rates (n=157); (2) highest band neutrophil count and Kawasaki disease shock rate (n=231); (3) cervical lymphadenopathy with high markers of inflammation (erythrocyte sedimentation rate, C-reactive protein, white blood cell, and platelet counts) and lowest age-adjusted haemoglobin Z scores (n=315); and (4) young age at onset with highest coronary artery aneurysm but lowest intravenous immunoglobulin resistance rates (n=313). The subgroups had distinct seasonal and incidence trajectories. In addition, the subgroups shared 211 differential abundance proteins while many proteins were unique to a subgroup. INTERPRETATION: Our data-driven analysis provides insight into the heterogeneity of Kawasaki disease, and supports the existence of distinct subgroups with important implications for clinical management and research design and interpretation. FUNDING: US National Institutes of Health and the Irving and Francine Suknow Foundation