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Background: Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. Case presentation: In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child's thrombus has dissolved, and the myocardial ischemia has resolved. Conclusions: This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course. [ABSTRACT FROM AUTHOR]

Previous research has indicated a negative correlation between exclusive breastfeeding and the incidence of Kawasaki disease (KD). However, the validation of this discovery through meta-analytical studies has been lacking. Furthermore, uncertainties persist regarding whether breastfeeding reduces the risk of coronary artery lesions (CAL) or resistance to intravenous immunoglobulin (IVIG). A systematic exploration of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ClinicalTrials.gov databases was conducted to identify longitudinal or randomized controlled trials investigating the efficacy of breastfeeding in preventing KD. The primary focus was on the incidence of KD, with secondary emphasis placed on the incidence of CAL and IVIG resistance. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. Of the 179 potentially eligible studies identified, five (n = 1,982,634) were included. The analysis revealed a significantly lower risk of KD (expressed as odds ratio, with 95% confidence intervals and p-values) in comparisons between exclusive breastfeeding and formula feeding (0.62, 0.43−0.91, p = 0.014), exclusive breastfeeding/partial breastfeeding and formula feeding (0.66, 0.46− 0.96, p = 0.03), and exclusive breastfeeding and partial breastfeeding/formula feeding (0.81, 0.74− 0.90, p < 0.01). However, no significant difference was observed in the risk of developing KD when comparing partial breastfeeding to formula feeding exclusively. Regarding secondary outcomes, no statistically significant difference was found in the risk of CAL or IVIG resistance across any comparison formats. Our study suggests that breastfeeding correlated with a reduced risk of KD but not with a reduced risk of CAL or IVIG resistance. These findings advocate for the implementation of breastfeeding policies in clinical practice. [ABSTRACT FROM AUTHOR]

Approximately 10–20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion. This retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests. There were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events. We concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients. [ABSTRACT FROM AUTHOR]

We aimed to explore simple and effective clinical parameters or combinations to predict coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease (KD). This retrospective cohort study included pediatric patients with KD from January, 2013 to December, 2022. Multiple demographic and clinical data were collected, collated, and calculated from the medical records. Then they were divided into the coronary artery dilation and aneurysm formation group or the non-coronary artery dilation and aneurysm formation group. Lymphocyte-C-reactive protein ratio (LCR) was transformed into its natural logarithm and expressed as lnLCR. A total of 64 pediatric patients with KD were enrolled in this cohort study after 1:3 propensity score matching (PSM). For each unit increase in lnLCR, the possibility of coronary artery dilation and aneurysm formation decreased to 0.419 times the original value. The areas under the receiver operating characteristic (ROC) curves of lnLCR combined with albumin (ALB), ALB, and lnLCR to classify pediatric patients with KD into the coronary artery dilation and aneurysm formation group were 0.781, 0.692, and 0.743, respectively. LCR combined with ALB upon admission is a promising predictor of coronary artery dilation and aneurysm formation in pediatric patients with KD. [ABSTRACT FROM AUTHOR]

Background: Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression. Methods: We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment. We included a novel 3-transcript signature for childhood tuberculosis, and four published signatures which differentiate bacterial infection, viral infection, or Kawasaki disease from other febrile illnesses. Signature performance was assessed using receiver operating characteristic curve statistics. We also explored conceptual frameworks for multiclass diagnostic signatures, including additional transcripts found to be significantly differentially expressed in previous studies. Relaxed, regularised logistic regression models were used to derive two novel multiclass signatures: a mixed One-vs-All model (MOVA), running multiple binomial models in parallel, and a full-multiclass model. In-sample performance of these models was compared using radar-plots and confusion matrix statistics. Results: Samples from 91 children were included in the study: 23 bacterial infections (DB), 20 viral infections (DV), 14 Kawasaki disease (KD), 18 tuberculosis disease (TB), and 16 healthy controls. The five signatures tested demonstrated cross-platform performance similar to their primary discovery-validation cohorts. The signatures could differentiate: KD from other diseases with area under ROC curve (AUC) of 0.897 [95% confidence interval: 0.822–0.972]; DB from DV with AUC of 0.825 [0.691–0.959] (signature-1) and 0.867 [0.753–0.982] (signature-2); TB from other diseases with AUC of 0.882 [0.787–0.977] (novel signature); TB from healthy children with AUC of 0.910 [0.808–1.000]. Application of signatures outside of their designed context reduced performance. In-sample error rates for the multiclass models were 13.3% for the MOVA model and 0.0% for the full-multiclass model. The MOVA model misclassified DB cases most frequently (18.7%) and TB cases least (2.7%). Conclusions: Our study demonstrates the feasibility of NanoString technology for cross-platform validation of multiple transcriptomic signatures in parallel. This external cohort validated performance of all five signatures, including a novel sparse TB signature. Two exploratory multi-class models showed high potential accuracy across four distinct diagnostic groups. [ABSTRACT FROM AUTHOR]

Objective: The level of mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells had been identified to be involved in several immune and cardiovascular diseases. Thus, the aim of this study is to evaluate the levels of mtDNA-CN in Kawasaki disease (KD) and to construct a nomogram prediction for coronary artery lesions in children with KD. Methods: One hundred and forty-four children with KD diagnosed from March 2020 to March 2022 were involved in the study. The clinical features and laboratory test parameters of these children were assessed between the KD and normal groups. Univariable and multivariable analyses were performed sequentially to identify the essential risk factors. Subsequently, a nomogram prediction was constructed. Results: A total of 274 children were included in the analysis. Of these, 144 (52.6%) represented the KD group. Peripheral blood DNA mtDNA qPCR showed that the-log value of mtDNA-CN in the KD group (6.67 ± 0.34) was significantly higher than that in the healthy group (6.40 ± 0.18) (P<0.001). The area under the ROC curve for mtDNA-CN in distinguishing KD was 0.757. MtDNA-CN (OR = 13.203, P = 0.009, 95% CI 1.888-92.305), RBC (OR = 5.135, P = 0.014, 95% CI 1.394-18.919), and PA (OR = 0.959, P = 0.014, 95% CI 0.927-0.991) were identified as independent risk factors for coronary artery dilation in children with KD. Finally, the nomogram predictive was established based on the results of multivariable analysis, demonstrating the satisfied prediction and calibration values. Conclusion: The results of this study revealed that mtDNA-CN could be used as a biomarker in predicting the development of KD. Furthermore, the higher the mtDNA-CN was significantly associated with coronary artery dilation in KD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. Methods: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. Results: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. Conclusion: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD. [ABSTRACT FROM AUTHOR]

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions. [ABSTRACT FROM AUTHOR]

Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = −0.72, FDP: r = −0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin. [ABSTRACT FROM AUTHOR]

Background: Kawasaki Disease (KD) involves arterial inflammation, primarily affecting the coronary arteries and leading to coronary artery lesions. Recent advancements in understanding the immunomodulatory roles of vitamin D have prompted investigations into the potential correlation between serum vitamin D levels and the risk of coronary artery lesions (CAL) in KD. This review aims to explore this association. Methods: A systematic search utilizing relevant keywords related to Kawasaki disease and coronary artery lesions was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). The quality of the incorporated studies was assessed utilizing the Newcastle-Ottawa Scale. The study protocol is registered in PROSPERO under the registry code CRD42024493204. Results: In a review of five studies involving 442 KD patients and 594 healthy controls, KD patients generally had lower serum vitamin D levels compared to controls, with mixed findings on the association with coronary artery lesions and IVIG resistance. While three studies supported lower vitamin D in KD, one showed no significant difference. Regarding CAL, one study found lower vitamin D, another found higher levels associated with CAL, and two found no significant difference. Conclusions: Overall, the evidence is inconclusive, but there's a trend suggesting potential benefits of sufficient vitamin D levels in Kawasaki disease rather than evidence refuting any association with clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries. Methods: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified. Results: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions Conclusion: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis assesses the effectiveness of no or low-dose versus high-dose aspirin on the incidence of coronary artery aneurysms (CAAs), intravenous immunoglobulin (IVIG) resistance, hospital stay length, and fever duration during the acute phase of Kawasaki disease. Our review adheres to the Preferred Reporting Items for Systematic Reviews guidelines. The PubMed and Google Scholar databases were comprehensively searched to identify relevant studies in the literature, including observational studies and randomized controlled trials (RCTs). The primary outcome was the incidence of CAAs. The secondary outcomes were the hospital stay length, fever duration, and IVIG resistance. The risk of bias was assessed using the Newcastle–Ottawa scale for cohort studies and Cochrane's Risk of Bias Tool for RCTs. The data were analyzed using the Review Manager software. Twelve studies with a total of 68,495 participants met the inclusion criteria. The incidences of CAAs (odds ratio [OR] = 0.93; 95% confidence interval [CI] = 0.64–1.34) and IVIG resistance (OR = 1.46; 95% CI = 1.00–2.12) did not differ significantly between no or low-dose versus high-dose aspirin in treating acute KD. Moreover, the fever durations (mean difference [MD] = 3.55 h; 95% CI = −7.99–15.10) and hospital stay lengths (MD = −0.54 days; 95% CI = −2.50–1.41) were similar in the no and low-dose aspirin group compared to the high-dose aspirin group. Our review indicates that there are no significant differences in the incidences of CAA and IVIG resistance, fever durations, and hospital stay lengths between no or low-dose versus high-dose aspirin in treating the acute phase of KD. [ABSTRACT FROM AUTHOR]

Background: Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease is associated with coronary artery lesion development. Purpose: This study aimed to explore the factors associated with IVIG-resistance and construct and validate an interpretable machine learning (ML) prediction model in clinical practice. Methods: Between December 2014 and November 2022, 602 patients were screened and risk factors for IVIGresistance investigated. Five ML models are used to establish an optimal prediction model. The SHapley Additive exPlanations (SHAP) method was used to interpret the ML model. Results: Na+, hemoglobin (Hb), C-reactive protein (CRP), and globulin were independent risk factors for IVIGresistance.Anonlinear relationship was identified between globulin level and IVIG-resistance. The XGBoost model exhibited excellent performance, with an area under the receiver operating characteristic curve of 0.821, accuracy of 0.748, sensitivity of 0.889, and specificity of 0.683 in the testing set. The XGBoost model was interpreted globally and locally using the SHAP method. Conclusion: Na+, Hb, CRP, and globulin levels were independently associated with IVIG-resistance. Our findings demonstrate that ML models can reliably predict IVIG-resistance. Moreover, use of the SHAP method to interpret the established XGBoost model's findings would provide evidence of IVIG-resistance and guide the individualized treatment ofKawasaki disease. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is frequently associated with thrombo inflammation, which can predispose to developing of life-threatening conditions in children such as the multisystem inflammatory syndrome (MIS-C) and Kawasaki disease. Because of the consistent overlap in pathogenesis and symptoms, identifying laboratory tests that may aid in the differential diagnosis of these pathologies becomes crucial. We performed an electronic search in PubMed, Web of Science and Scopus, without date or language restrictions, to identify all possible studies reporting D-dimer values in separate cohorts of children with MIS-C or Kawasaki disease. Three multicenter cohort studies were included in our analysis, totaling 487 patients (270 with MIS-C and 217 with Kawasaki disease). In this meta-analysis, significantly higher D-dimer values were found in MIS-C compared to Kawasaki disease in all three studies, yielding an SMD of 1.5 (95 % CI, 1.3–1.7) mg/L. Thus, very high D-dimer values early in the course of disease should raise the clinical suspicion of MIS-C rather than Kawasaki disease. Further studies should be planned to identify harmonized D-dimer diagnostic thresholds that may help discriminate these conditions. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels, which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as the disease progresses, with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated with KD, but also evaluates the possibility of using circulating endothelial injury biomarkers, such as circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tools for KD: a "liquid biopsy" approach. The challenges of translating liquid biopsies to use in KD and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostic tools is promising, and we hope this will be translated to clinical applications in the near future. [ABSTRACT FROM AUTHOR]

Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease. We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes. Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14–4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14–4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents. In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan. [Display omitted] • Cesarean section delivery disrupts microbiota and immune regulation but its association with Kawasaki disease is uncertain. • This study examined the association between Cesarean section and Kawasaki disease in 15,796 mother-infant pairs in Taiwan. • Cesarean section increased Kawasaki disease risk, while it was not associated with the risk of negative control outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Vaccinations are essential in minimizing the effects of global health crises including COVID-19 pandemic. This study investigates the potential association between COVID-19 vaccination and the occurrence of medium vessel vasculitis. Methods: Several databases were utilized to conduct a comprehensive literature review. The studies were carefully evaluated to ensure their quality and eliminate any potential bias. Results: After reviewing 935 search results and removing duplicates, we selected 10 case reports. We discovered that medium vessel vasculitis may occur after COVID-19 vaccination, typically appearing around 16.2 days after vaccination. The patients in the study had a median age of 43.5 years and were predominantly males (80%). Additionally, half of the cases were reported after the second dose of vaccination. Conclusions: Vaccination-associated vasculitis is a rare yet possible complication of COVID-19 vaccination and lacks a clear treatment protocol. [ABSTRACT FROM AUTHOR]

Aims/Background Kawasaki disease is an acute inflammatory condition primarily affecting the young children. It can lead to coronary artery abnormalities, which can worsen the prognosis. Early diagnosis of coronary disease is crucial for the effective treatment and the prognosis evaluation. To explore the clinical significance of ultrasound examination characteristics, peripheral blood red cell distribution width, and changes in N-terminal pro-brain natriuretic peptide levels for the early detect coronary artery abnormality in children with Kawasaki disease. Methods The case-control study was conducted. 85 Kawasaki disease patients diagnosed in our hospital from January 2020 to December 2023 were selected as the Kawasaki disease group. 100 healthy children who received physical examination in the Department of Child Healthcare during the same period were selected as control group. The cardiac ultrasound indicators, erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, N-terminal pro-brain natriuretic peptide of two groups were compared. The Kawasaki disease group was further divided into the coronary artery lesion group and the non-coronary artery lesion group based on whether coronary artery lesions occurred in the Kawasaki disease patients. The differences of above indicators were compared. Results The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of the Kawasaki disease group were all higher than those of the control group (p < 0.05). There was no significant difference in left ventricular ejection fraction between Kawasaki disease group and control group (p > 0.05). The erythrocyte sedimentation rate, C-reactive protein, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease group were all higher than those of control group (p < 0.05). The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions (p < 0.05). The left ventricular ejection fraction of Kawasaki disease patients with coronary artery lesions was lower than that of Kawasaki disease patients without coronary artery lesions (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions, and the differences were statistically significant (p < 0.05). After treatment, the left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions significantly decreased (p < 0.05), and the left ventricular ejection fraction significantly increased (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with or without coronary artery lesions significantly decreased after treatment compared with before treatment in the same group (p < 0.05). Conclusion Kawasaki disease patients with coronary artery lesions exhibit significantly increased coronary artery vessel diameter, as well as elevated red cell distribution width and N-terminal pro-brain natriuretic peptide concentration. The combined use of ultrasound combined with red cell distribution width and N-terminal pro-brain natriuretic peptide examination can assist in determining whether Kawasaki disease patients have coronary artery lesions and assessing the clinical treatment effect. [ABSTRACT FROM AUTHOR]

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Introduction: Multisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings. In this study, the clinical findings, organ involvements, similarities, and differences in laboratory and imaging of the children with MIS-C and KD at the time of admission will be revealed in detail, and the treatment methods and follow-up results will be revealed. Material and method: Our study was a single-center study and included pediatric patients who were treated with a diagnosis of MIS-C between March 2020 and July 2023 in the pediatric cardiology, pediatric emergency, pediatric infection, and pediatric intensive care clinics at Celal Bayar University and who were treated with a diagnosis of KD (complete/incomplete) between January 2015 and July 2023. MIS-C diagnosis was made according to the Turkish Ministry of Health COVID-19 guidelines. Sociodemographic characteristics, clinical, laboratory, and echocardiography findings, treatments given, and clinical course of all patients included in the study were evaluated. Results: The median age was 30 months (7–84) in KD and 96 months (6-204) in MIS-C, and it was significantly higher in the MIS-C group (p = 0.000). Symptom duration was significantly longer in the MIS-C group (p = 0.000). In terms of clinical features, gastrointestinal syndrome findings (nausea, vomiting, abdominal pain) and respiratory findings (dyspnea) were significantly higher in the MIS-C group (p = 0.007, p = 0.000, p = 0.002, respectively). Regarding cardiovascular system involvement, coronary involvement was significantly higher in the KD group. However, valvular involvement, left ventricular systolic dysfunction, and pericardial effusion were significantly higher in the MIS-C group (p = 0.000, p = 0.001, p = 0.003, p = 0.023, respectively). In terms of laboratory findings, white blood cell count was higher in KD (p = 0.000), absolute lymphocyte count, platelet level, blood sodium, and albumin levels were lower in MIS-C group (p = 0.000, p = 0.000, p = 0.000, p = 0.000, p = 0.003, respectively), ferritin and troponin levels were significantly higher in MIS-C group. These results were statistically significant (p = 0.000, p = 0.000, respectively). D-dimer and fibrinogen levels were high in both groups, and no significant statistical difference was detected between the two groups. There was no significant difference between the two groups regarding the length of hospitalization and mortality, but steroid use was significantly higher in the MIS-C group (p = 0.000). Conclusion: In conclusion, this study has demonstrated the similarities and differences between MIS-C and KD regarding clinical findings, organ involvement, and laboratory and imaging results. The results of our study have important implications in terms of contributing to the data in the existing literature on these two diseases and for the correct diagnosis and better management of pediatric patients presenting with these disorders. What is known: Multisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings. What is new: Although MIS-C and KD have many similarities, their symptoms, disease processes, possible complications, and treatment regimens may differ. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the predictive value of systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV) in predicting intravenous immunoglobulin (IVIG) resistance in children diagnosed with Kawasaki disease (KD). Methods: The clinical data of pediatric patients diagnosed with Kawasaki disease and admitted to our hospital between January 2006 and December 2022 were retrospectively analyzed. Results: In total, 771 children diagnosed with KD were included in this study, 86 (11.2%) of whom were diagnosed with IVIG resistance. The correlation between SII, SIRI, PIV and IVIG resistance was evaluated using univariate testing, binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. Our study found that the SII, SIRI, and PIV were independent risk factors (p=0.001, p<0.001, and p=0.02, respectively). The area under the ROC curve (AUC) values of the SII, SIRI, and PIV were 0.626 (95% confidence interval (CI): 0.553-0.698, p<0.001), 0.571 (95% CI: 0.500-0.642, p=0.032), and 0.568 (95% CI: 0.495-0.641, p=0.040), respectively, and the cutoff values were 2209.66, 3.77, and 1387.825, respectively. Conclusion: The SII, SIRI, and PIV have potential value in predicting IVIG resistance in patients with KD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of electrocardiogram QT interval dispersion (QTd) combined with 25-hydroxyvitamin D [25-(OH) D], growth differentiation factor-15 (GDF-15) and pentraxin 3 (PTX3) in the evaluation of coronary artery lesions (CAL) in children with Kawasaki disease. Methods: 180 children with Kawasaki disease admitted to our hospital from June 2018 to June 2023 were selected, and patients were divided into CAL group (36 cases) and non-CAL group (144 cases) according to whether CAL occurred. All children received electrocardiogram examination to obtain QTd and corrected QT dispersion (QTcd), and serum 25-(OH)D, GDF-15 and PTX3 levels were detected. The factors affecting the occurrence of CAL in children with Kawasaki disease were analyzed by multivariate Logistic regression analysis, and a Log P model of multi-index combined application was constructed. The predictive value of QTd, 25-(OH)D, GDF-15 and PTX3 for CAL in children with Kawasaki disease were analyzed by receiver operating characteristic (ROC) curve. Results: The levels of QTd, QTcd, GDF-15 and PTX3 in CAL group were higher than those in non-CAL group (P<0.05), and the level of 25-(OH)D was lower than that in non-CAL group(P<0.05). Treatment non-response, high QTd, high QTcd, high GDF-15, and high PTX3 were risk factors for CAL in children with Kawasaki disease (P<0.05), and high 25-(OH)D was a protective factor (P<0.05). The Log P models of multi-index combined application were constructed as follows: A: electrocardiogram parameter model: Ln (P/1-P)=0.512 ×QTd+0.596 QTcd; B: serum 3 index model: Ln (P/1-P)=0.712×GDF-15+0.626×PTX3-0.609×25- (OH)D; C: 5-factor joint application model (above A+B model): Ln (P/1-P)=0.512×QTd+0.596 QTcd+0.712×GDF-15+0.626×PTX3-0.609×25-(OH)D. ROC analysis showed that, models A, B and C had certain predictive efficacy for CAL in children with Kawasaki disease, and their ROC-AUC (0.95CI) were 0.709 (0.490~0.921), 0.787 (0.579~0.966) and 0.835 (0.699~0.955) respectively. C combined application model has the highest prediction efficiency. Conclusion: The QTd increase, QTcd increased, GDF-15 increase, PTX3 increase, and 25-(OH)D decrease in children with Kawasaki disease with CAL, the combined detection of the above indicators has a high predictive efficiency for the occurrence of CAL in children with Kawasaki disease. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD. Methods: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram. Results: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages. Conclusion: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Kawasaki disease (KD) is an acute febrile illness of childhood that can lead to coronary artery aneurysms (CAAs) and myocardial infarction. Intravenous immunoglobulin reduces the prevalence of CAA when given to patients with KD within 10 days of fever onset. Children with KD may undergo evaluation for other diagnoses before treatment, particularly those with incomplete KD criteria. If KD outcomes are improved with early treatment, a delay in treatment while evaluating for other causes might place these patients at risk. Methods We performed a retrospective cohort study of children treated for KD within the first 10 days of illness at our KD center from 2014 to 2021 to determine the prevalence of CAA by day of treatment. Results A total of 290 patients met the study criteria. No statistically significant difference was found in the odds of developing a maximum z score ≥2.5 for each day of delayed treatment within 10 days of fever onset (adjusted odds ratio, 0.87; 95% CI,.72–1.05; P =.13). Subgroup analyses by age, sex, and year of treatment did not reveal a significant association between treatment day and maximum z score ≥2.5, although the number of patients <6 months of age was small. Conclusions Our study supports current recommendations. We found similar odds of developing adverse coronary outcomes regardless of treatment day within 10 days from fever onset. [ABSTRACT FROM AUTHOR]

This study aimed to describe the characteristics of multisystemic inflammatory syndrome associated with COVID-19 (MIS-C) in the first three years of the pandemic in children in a pediatric hospital in Peru. We conducted an observational, descriptive study with data from 73 patients and described the clinical and laboratory characteristics, treatment and complications according to the wave of the pandemic and whether they had shock. The median age was 6 years, gastrointestinal and mucocutaneous manifestations were frequent in the three waves. Kawasaki disease-like phenotype was present in 34 (46.6%) patients and 21 (28.8%) patients developed shock. The most commonly used treatment was immunoglobulin (95.9%), followed by acetylsalicylic acid (94.5%) and corticosteroid (86.3%). Five (7%) patients had coronary aneurysm and 17 (23.3%) were admitted to the intensive care unit (ICU). Patients with shock had greater laboratorial alteration and need for mechanical ventilation. In conclusion, MIS-C has decreased in the first three years of the pandemic, possibly due to COVID-19 vaccination in children. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease is an acute immune vasculitis, which is more common in children under 5 years old. Kawasaki disease mainly affects the cardiovascular system, especially the coronary arteries. Once coronary artery damage occurs, it can significantly impact the patient’s prognosis. Therefore, in some countries and regions, Kawasaki disease has become a common acquired heart disease. Methods: First, univariate analysis was conducted on each predictive factor. Then, Least Absolute Shrinkage and Selection Operator and random forest algorithms were used to screen all predictive factors, and the prediction model was evaluated using receiver operating characteristic curve, calibration curve, and Decision Curve Analysis. Results: This study, based on data from 228 Kawasaki disease patients, utilized a random forest model to identify four predictive factors: white blood cell count, creatine kinase isoenzyme MB, albumin, and neutrophil count. These factors were used to construct a prediction model, which achieved an area under the curve of 0.743. Conclusions: We developed a forest plot based on white blood cell count, creatine kinase isoenzyme MB, albumin, and neutrophil count to effectively predict the occurrence of coronary artery lesions in Kawasaki disease. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a syndrome primarily affecting young children, typically under the age of five, and is characterized by the development of acute vasculitis. Through extensive research conducted on both murine and human subjects, it has been demonstrated that heightened levels of reactive oxygen species (ROS) play a pivotal role in the development of KD, especial coronary artery lesions (CALs). Hydrogen gas exhibits potent antioxidant properties that effectively regulate ROS production and the inflammatory response. Methods: We used Lactobacillus casei cell wall extract (LCWE)-induced vasculitis in mice as an animal model of KD and treated the mice with hydrogen gas inhalation. Results: We observed significant dilatation and higher Z scores in the left coronary artery (LCA) in D21 and D28 in mice after LCWE treatment compared to the control group (p < 0.001) and a significant resolution of LCA diameters (p < 0.01) and Z scores (p < 0.01) after treatment with inhaled hydrogen gas. We further demonstrated that serum IL-6 expression was higher in mice after LCWE treatment (p < 0.01) and IL-6 significantly decreased after inhaled hydrogen gas therapy (p < 0.001). Conclusion: According to our literature review, this is the first report where hydrogen gas inhalation has been demonstrated to be effective for the treatment of coronary artery dilatation in a KD murine model. [ABSTRACT FROM AUTHOR]

We conducted an autopsy on a 3‐month‐old boy in whom Kawasaki disease (KD) was strongly suspected based on the autopsy findings. The infant had a fever and was brought to a nearby clinic, where he was prescribed antipyretics and kept under observation. However, 15 days after onset of the fever, he suddenly died in bed. He exhibited no obvious redness of the lips, tongue, or conjunctiva. Membranous desquamation was present on his distal fingers. Vasculitis was observed in the coronary arteries, renal artery, splenic artery, and pulmonary vein. In addition, coronary artery aneurysms were present in the right coronary artery and left anterior descending artery. Thrombotic occlusion was observed in one aneurysm in the right coronary artery, resulting in acute myocardial infarction. The coronary artery wall showed infiltration of numerous macrophages and neutrophils. This case was classified as incomplete KD because the coronary artery aneurysm could not be demonstrated before death and was only recognized at autopsy. Pathologists and forensic scientists need to be aware that there are cases in which KD goes undiagnosed and untreated, leading to coronary artery aneurysm formation and sudden death. [ABSTRACT FROM AUTHOR]

Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute systemic vasculitis involving small and medium-sized vessels. It can be complicated by varying degrees of cardiac damage, especially coronary artery disease. The disease mainly occurs in children aged < 5 years, with rarer cases in older children and adults. Intravenous immunoglobulin combined with aspirin is the widely accepted treatment regimen in the acute phase, but the dosage recommended by the American Heart Association guidelines is not suitable for heavier children. This article reports the successful management of an overweight 14-year-old child with Kawasaki disease. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a systemic inflammatory disease characterized by vasculitis. In South Korea, some pediatric doctors empirically prescribe steroids to control febrile pediatric patients. This study aimed to evaluate the clinical characteristics of patients with KD after steroid exposure. This was a single-center, retrospective, observational study. This study included patients (aged ≤15 years) between January 2020 and July 2022. We compared two groups, one group exposed to steroids and the other group who were not, using the Student's t-test or analysis of variance; otherwise, the Mann–Whitney U test or Kruskal–Wallis test was conducted. Statistical significance was set at p < 0.05. In total, 190 patients with KD were enrolled; of these, 64 (33.7 %) had a history of steroid exposure, and 126 (66.3 %) had no history of steroid exposure. In the steroid exposure group, prolonged fever duration (6.72 ± 1.72 versus 5.61 ± 1.19, p-value = <0.001), a lower proportion of complete KD (29.69 % vs. 88.10 %, p-value = <0.001), and a significantly lower level of C-reactive protein were observed. However, no significant correlations were observed between the Transthoracic Echocardiography (TTE) results (coronary artery aneurysm, existence of pericardial effusion) and prognostic factors (days of hospitalization, the number of intravenous immunoglobulin administrations, and Kobayashi score) between the two groups. Patients with KD and previous steroid exposure may exhibit an incomplete KD phenotype with prolonged fever. Although previous steroid exposure does not affect the prognosis of KD, including coronary artery aneurysms, it may mask the classic features of KD, resulting in a delayed diagnosis. [ABSTRACT FROM AUTHOR]

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The hypercoagulable state in Kawasaki disease (KD) may lead to complex cardiovascular sequelae. We present the case of a 2-month-old infant with complete KD complicated by giant coronary artery aneurysms, coronary sinus thrombosis, and post-myocardial infarction syndrome (Dressler syndrome), resulting in 2 distinct episodes of pericardial effusion. (Level of Difficulty: Intermediate.).

Yihua Jin,1,&ast; Zhimin Geng,1,2,&ast; Kun Lin,1 Xinyu Gu,1 Xiwei Feng,1 Songling Fu,1 Wei Wang,1 Chunhong Xie,1 Yujia Wang,1 Fangqi Gong1 1Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Pediatric Cardiovascular Diseases Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangqi Gong; Yujia Wang, Email gongfangqi@zju.edu.cn; wangyujia@zju.edu.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM.Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD.Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD.Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.Keywords: Kawasaki disease, monocyte subsets, L-Selectin, coronary artery lesions

Background: Approximately 10–20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion. Methods: This retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests. Results: There were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events. Conclusion: We concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients.

Background: Previous research has indicated a negative correlation between exclusive breastfeeding and the incidence of Kawasaki disease (KD). However, the validation of this discovery through meta-analytical studies has been lacking. Furthermore, uncertainties persist regarding whether breastfeeding reduces the risk of coronary artery lesions (CAL) or resistance to intravenous immunoglobulin (IVIG). Methods: A systematic exploration of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ClinicalTrials.gov databases was conducted to identify longitudinal or randomized controlled trials investigating the efficacy of breastfeeding in preventing KD. The primary focus was on the incidence of KD, with secondary emphasis placed on the incidence of CAL and IVIG resistance. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. Results: Of the 179 potentially eligible studies identified, five (n = 1,982,634) were included. The analysis revealed a significantly lower risk of KD (expressed as odds ratio, with 95% confidence intervals and p-values) in comparisons between exclusive breastfeeding and formula feeding (0.62, 0.43−0.91, p = 0.014), exclusive breastfeeding/partial breastfeeding and formula feeding (0.66, 0.46− 0.96, p = 0.03), and exclusive breastfeeding and partial breastfeeding/formula feeding (0.81, 0.74− 0.90, p

Abstract Background Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. Case presentation In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child’s thrombus has dissolved, and the myocardial ischemia has resolved. Conclusions This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Abstract Background Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression. Methods We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment. We included a novel 3-transcript signature for childhood tuberculosis, and four published signatures which differentiate bacterial infection, viral infection, or Kawasaki disease from other febrile illnesses. Signature performance was assessed using receiver operating characteristic curve statistics. We also explored conceptual frameworks for multiclass diagnostic signatures, including additional transcripts found to be significantly differentially expressed in previous studies. Relaxed, regularised logistic regression models were used to derive two novel multiclass signatures: a mixed One-vs-All model (MOVA), running multiple binomial models in parallel, and a full-multiclass model. In-sample performance of these models was compared using radar-plots and confusion matrix statistics. Results Samples from 91 children were included in the study: 23 bacterial infections (DB), 20 viral infections (DV), 14 Kawasaki disease (KD), 18 tuberculosis disease (TB), and 16 healthy controls. The five signatures tested demonstrated cross-platform performance similar to their primary discovery-validation cohorts. The signatures could differentiate: KD from other diseases with area under ROC curve (AUC) of 0.897 [95% confidence interval: 0.822–0.972]; DB from DV with AUC of 0.825 [0.691–0.959] (signature-1) and 0.867 [0.753–0.982] (signature-2); TB from other diseases with AUC of 0.882 [0.787–0.977] (novel signature); TB from healthy children with AUC of 0.910 [0.808–1.000]. Application of signatures outside of their designed context reduced performance. In-sample error rates for the multiclass models were 13.3% for the MOVA model and 0.0% for the full-multiclass model. The MOVA model misclassified DB cases most frequently (18.7%) and TB cases least (2.7%). Conclusions Our study demonstrates the feasibility of NanoString technology for cross-platform validation of multiple transcriptomic signatures in parallel. This external cohort validated performance of all five signatures, including a novel sparse TB signature. Two exploratory multi-class models showed high potential accuracy across four distinct diagnostic groups.

Abstract Objective This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. Methods A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. Results In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. Conclusion Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

Abstract Background Kawasaki Disease (KD) involves arterial inflammation, primarily affecting the coronary arteries and leading to coronary artery lesions. Recent advancements in understanding the immunomodulatory roles of vitamin D have prompted investigations into the potential correlation between serum vitamin D levels and the risk of coronary artery lesions (CAL) in KD. This review aims to explore this association. Methods A systematic search utilizing relevant keywords related to Kawasaki disease and coronary artery lesions was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). The quality of the incorporated studies was assessed utilizing the Newcastle-Ottawa Scale. The study protocol is registered in PROSPERO under the registry code CRD42024493204. Results In a review of five studies involving 442 KD patients and 594 healthy controls, KD patients generally had lower serum vitamin D levels compared to controls, with mixed findings on the association with coronary artery lesions and IVIG resistance. While three studies supported lower vitamin D in KD, one showed no significant difference. Regarding CAL, one study found lower vitamin D, another found higher levels associated with CAL, and two found no significant difference. Conclusions Overall, the evidence is inconclusive, but there’s a trend suggesting potential benefits of sufficient vitamin D levels in Kawasaki disease rather than evidence refuting any association with clinical outcomes.