Pediatric heart transplantation is limited by donor avail-ability with those needing transplantation often requiring prolonged mechanical circulatory support.

The treatment of intravenous immunoglobulin-resistant Kawasaki disease (IVIGRKD) is still controversial, and few studies investigate using glucocorticoids (GCs) alone as rescue therapy for Kawasaki Disease (KD) patients. This study aimed to investigate the efficacy of using GCs alone as rescue therapy in IVIGRKD patients and to further explore the appropriate GCs dosage. We enrolled 210 IVIGRKD diagnosed in our hospital and conducted a cohort analysis. Patients were divided into the intravenous immunoglobulin (IVIG) group, IVIG + GCs group, and the GCs group. The GCs group was further divided into GCs A group(10-15 mg/kg/d) and GCs B group(1-4 mg/kg/d). Clinical outcomes and changes in coronary arteries after the treatment during a one-year period were observed. Propensity-score matching and logistic regression analyses were used to make the comparison. After propensity-score matching, the therapeutic response rate in the GCs group was significantly higher than that in the IVIG group (91.1% vs. 69.6%, P = 0.004). And there was no significant difference between the IVIG group and IVIG + GCs group and between the GCs group and IVIG + GCs group. We further compared various doses of GCs (10–15 mg/kg/d and 1–4 mg/kg/d) and didn’t find a significant difference. After logistic regression analysis, it was found that the therapeutic response rate in the GCs group was significantly higher than in the IVIG group (P = 0.001, OR = 2.24, 95% CI 1.37–3.67). Additionally, the therapeutic response rate was significantly higher in the IVIG + GCs group than in the IVIG group (P = 0.01, OR = 4.73, 95% CI: 1.40-16.02). However, there was no significant difference between the GCs and IVIG + GCs groups. Different doses of GCs (10–15 mg/kg/d and 1–4 mg/kg/d) were also not significantly correlated with the treatment efficiency. There was no significant difference in preventing coronary artery lesions (CALs) between different groups. Single-GCs therapy is a viable option for patients who do not respond to IVIG, and a dosage of 1–4 mg/kg/d of GCs demonstrated comparable efficacy to higher-dose regimens and may represent an effective treatment option for IVIGRKD patients.

Patients infected with SARS-CoV-2 may experience acute and long-term immune disorders. Immunological factors are thought to play an important role in Kawasaki disease. To analyze the impact of COVID-19 infection on Kawasaki disease, this study retrospectively analyzed 161 children with Kawasaki disease onset during the COVID-19 pandemic. The proportion of IVIG-Resistant individuals and the rate of corticosteroid use in the 1-7 weeks from COVID-19 infection to Kawasaki disease onset were higher than that of the noninfected group, even after excluding suspected cases of multiple system inflammatory syndrome. Compared to the noninfected group, the level of CD4 was lower, and the levels of CD3-CD16+CD56+, complement C4, TNF-alpha, and IFN-gamma were higher in the 1-7 weeks after COVID-19 infection. In conclusion, the risk of IVIG resistance was significantly increased in children with Kawasaki disease onset 1-7 weeks after COVID-19 infection, which may be related to the long-term impact of COVID-19 on immunity.

Purpose:To evaluate the diagnostic and predictive value of a 12-cytokine panel for Kawasaki disease (KD) and intravenous immunoglobulin (IVIG) resistance. Patients and Methods:A retrospective case-control study was conducted using clinical data from children diagnosed with KD at Children's Hospital, Zhejiang University School of Medicine, between December 1, 2023, and March 30, 2025. Demographic characteristics, laboratory findings, and echocardiographic results were collected. KD patients were compared with febrile controls without KD. Differences in sex, age, 12-cytokine profile, complete blood count, C-reactive protein level, and erythrocyte sedimentation rate were analyzed. Additionally, cytokine levels were compared between IVIG-resistant and IVIG-responsive KD patients to assess their predictive value for IVIG resistance. Results:A total of 686 KD patients and 101 febrile non-KD controls were enrolled. Compared with controls, KD patients were significantly younger and presented higher levels of IFN-α, IL-10, IL-1β, IL-2, IL-4, IL-5, IL-6, and IL-8, as well as elevated neutrophil counts and white blood cell counts. Logistic regression analysis identified age (in months), IL-10, IL-5, and the absolute neutrophil count as independent predictors of KD diagnosis. Among the KD patients, 80 were IVIG resistant. Compared with IVIG-responsive patients, IVIG-resistant patients presented significantly higher levels of IFN-γ, IL-10, IL-17, IL-2, IL-5, IL-6, and IL-8 but lower levels of IFN-α. Logistic regression revealed that IL-10 and IL-8 were independent predictors of IVIG resistance. When the concentration of IL-10 exceeded 14.70 pg/mL, the sensitivity and specificity for predicting IVIG resistance were 0.675 and 0.748, respectively. Similarly, when the concentration of IL-8 exceeded 23.55 pg/mL, the sensitivity and specificity were 0.725 and 0.658, respectively. Conclusion:The 12-cytokine panel has potential as a diagnostic and predictive tool for KD. Elevated IL-10 and IL-5 levels are independent predictors of KD diagnosis, whereas elevated IL-10 and IL-8 levels are independent predictors of IVIG resistance. These findings support the clinical utility of cytokine profiling in KD management.

Kawasaki disease (KD) is one of the most challenging diseases that is defined as an acute vasculitis that affects the coronary arteries primarily in children. It causes complications if left untreated at early stages, ultimately leading to death. Corticosteroids have been recognized to treat and cause great impact on the patients with KD. Glucocorticoid is one of the main corticosteroids that are being used to treat KD and cutaneous wounds. However, ineffectiveness of a few glucocorticoids can limit the efficacy of this treatment. This study particularly aimed to elucidate the impact of glucocorticoids on cutaneous wounds in KD. To perform the meta-analysis, a comprehensive literature survey was conducted to unveil the studies and research conducted on Kawasaki patients that revealed different glucocorticoids in the form of specific interventions influencing KD. The literature was searched using numerous keywords, screened and data was extracted to perform the meta-analysis and then it was conducted using the metabin function of R package meta. A total of 2000 patients from both intervention and control groups were employed to carry out the meta-analysis to analyse and evaluate the impact of glucocorticoids on curing KD and cutaneous wounds in patients. The results disclosed that glucocorticoids along with other steroids, mainly IVIG (intravenous immunoglobulin), was an effective intervention to patients suffering from Kawasaki. The results depicted significant outcomes with the values (risk ratio [RR]: 1.08, 95% confidence interval [CI]: 0.58-2.00, p < 0.01) and enlightened the fact that adopting different glucocorticoids may significantly improve the efficacy of skin lesions along with KD. Hence, interventions of glucocorticoids must be utilized in the clinical practice to reduce the incidence of skin wounds and adverse effects caused due to KD.

Purpose: 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.

BackgroundCoronary 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 presentationIn 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.ConclusionsThis 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.

J-tip guide wire entrapment within the heart is a serious and dangerous complication that is rarely mentioned. We present a case in which the J-tip guide wire was entrapped in the right atrium during tunneled cuffed venous catheterization. We were unable to remove the guide wire using previously reported methods and concluded with surgery. Owing to the special structure of the guide wire itself, a safe removal process needs to be discussed. Patient consent for publication was obtained prior to the submission of the manuscript.

Objectives: By using GWAS(genome-wide association studies) and linkage disequilibrium analysis to investigate the susceptibility genes of KD(Kawasaki disease), previous studies have identified that the CaN(calcineurin)-NFAT(the nuclear factor of activated T cell) signal pathway were significantly associated with susceptibility to KD. However, little is known about the molecular basis of the CaN/NFAT pathway involved in KD. Therefore, in our study we investigate the role of Ca2+/CaN/NFAT signaling pathway in macrophages in vitro and in vivo on coronary artery lesions induced by LCWE (Lactobacillus casei cell wall extract). Methods and results: We observed that LCWE could increase the expression of NFAT1 and NFAT2 in macrophages in vitro, and also enhance the transcriptional activity of NFAT by promoting the nucleus translocation. Similarly, in LCWE-induced mice model, the expression of NFAT1 and NFAT2 and associated proinflammatory factors were increased significantly. In addition, by knocking down or overexpressing NFAT1 or NFAT2 in macrophages, the results indicated that NFAT signaling pathway mediated LCWE-induced immune responses in macrophages and regulated the synthesis of IL(interleukin)-6, IL-1(i and TNF(tumor necrosis factor)-& alpha; in LCWE-induced macro-phage activation. As well, we found that this process could be suppressed by CaN inhibitor CsA(cyclosporinA). Conclusions: Therefore, the CaN/NFAT signaling pathway mediated LCWE-induced immune responses in mac-rophages, and also participated in the LCWE-induced CALs(coronary artery lesions). And also the inhibitory effect of CsA in LCWE-induced cell model towards a strategy to modulate the CaN/NFAT pathway during the acute course of KD might be helpful in alleviate KD-induced CALs.

Kawasaki disease can be combined with liver injury. As a mainstay treatment for Kawasaki disease, aspirin may cause liver injury. This study aimed to compare the safety and effectiveness of clopidogrel versus aspirin in Kawasaki disease with mild-to-moderate liver injury. This study retrospectively analysed 166 children with Kawasaki disease combined with mild-to-moderate liver injury. The children treated with clopidogrel were less likely to have aggravated liver injury than those treated with aspirin (n = 2/100 vs. n = 13/66, P < 0.001). The initial alanine aminotransferase value of the clopidogrel group was higher (131.5 [98.5, 167.5] vs. 96 [72, 133], P < 0.001), while the time of alanine aminotransferase recovery to normal was similar (5 [4, 7] vs. 4 [3, 7], P = 0.179). No significant fever differences observed between groups: 7.5 [6, 9] for aspirin vs. 7 [6, 8] for clopidogrel group, P = 0.064. The probability of nonresponse to intravenous immunoglobulin (n = 29/100 vs. n = 30/66, P = 0.030) and the days of hospitalization (n = 6 [4, 9] vs. n = 7 [5, 10], P = 0.007) in the clopidogrel group were less than those in the aspirin group. In conclusion, the application of clopidogrel is potentially superior to aspirin in Kawasaki disease combined with mild-to-moderate liver injury.

1 病例资料 例 1:男,10 岁 10 月,因"咳嗽伴咯血 2d"入院. 患儿2d内无明显诱因下出现单声咳嗽伴咯血5 次,咯血量累计约1000 mL. 最多单次咯血量约 500 mL,为鲜红色伴血凝块,当地医院予垂体后叶素治疗后略好转,遂至浙江大学医学院附属儿童医院(我院)就诊. 患儿的既往史及家族史无特殊. 入院体格检查:神志清楚,口唇苍白,咽充血,呼吸略促,未见明显三凹征,两肺呼吸音粗,右肺闻及少许粗湿啰音.

BACKGROUND:Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome with some clinical manifestations similar to Kawasaki disease (KD), which is difficult to distinguish. OBJECTIVE:The study aimed to characterize the demographic characteristics, clinical characteristics, laboratory features, cardiac complications, and treatment of MIS-C compared with KD. STUDY DESIGN:Studies were selected by searching the PubMed, EMBASE and so on before February 28, 2022. Statistical analyses were performed using Review Manager 5.4 software and STATA 14.0. RESULTS:Fourteen studies with 2928 participants were included. MIS-C patients tended to be older and there was no significant difference in the sex ratio. In terms of clinical characteristics, MIS-C patients were more frequently represented with respiratory, gastrointestinal symptoms and shock. At the same time, they had a lower incidence of conjunctivitis than KD patients. MIS-C patients had lower lymphocyte counts, platelet (PLT) counts, erythrocyte sedimentation rates (ESRs), alanine transaminase (ALT), and albumin levels and had higher levels of aspartate transaminase (AST), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin, C-reactive protein (CRP), D-dimer, fibrinogen, ferritin, and creatinine. MIS-C patients had a higher incidence of left ventricle (LV) dysfunction, valvular regurgitation, pericardial effusion, myocarditis, and pericarditis. The incidence of coronary artery lesion (CAL) was lower in MIS-C patients [OR (95% CI): 0.52 (0.29, 0.93), p =0.03], while it was similar in the acute period. MIS-C patients had higher utilization of glucocorticoids (GCs) and lower utilization of intravenous immune globulin (IVIG). CONCLUSIONS:There were specific differences between MIS-C and KD, which might assist clinicians with the accurate recognition of MIS-C and further mechanistic research.

Purpose Macrophages-mediated inflammation is linked with endothelial damage of Kawasaki disease (KD). KCa3.1, a calcium-activated potassium channel, modulates inflammation of macrophages. However, little is known about the role of KCa3.1 in inflammation by macrophages involved in KD. Hence, this study is aimed to explore the potential role of KCa3.1 in regulating inflammatory response by macrophages and subsequent vascular injury in an in vitro model of KD. Methods RAW264.7 cells were stimulated with Lactobacillus casei cell wall extract (LCWE) with or without TRAM-34 or PDTC or AG490. Subsequently, mouse coronary artery endothelial cells (MCAECs) were incubated with RAW264.7 cells-conditioned medium to mimic local inflammatory lesions in KD. CCKi8 assay was used to evaluate cell viability. The mRNA levels of inflammatory mediators were detected by qRT-PCR. Expressions of KCa3.1, MCAECs injury-associated molecules, proteins involved in signal pathways of nuclear factor-κB (NF-κB), signal transducers and activators of transcription (STAT) 3 and p38 were evaluated by Western blot. Results Our study showed that LCWE increased KCa3.1 protein level in RAW264.7 macrophages and KCa3.1 inhibition by TRAM-34 notably suppressed the expression of pro-inflammatory molecules in LCWE-treated macrophages via blocking the activation of NF-κB and STAT3 pathways. Besides, the inflammation and damage of MCAECs were attenuated in the TRAM-34-treated group compared with the KD model group. This vascular protective role was dependent on the down-regulation of NF-κB and STAT3 signal pathways, which was confirmed by using inhibitors of NF-κB and STAT3. Conclusion This study demonstrates that KCa3.1 blockade of macrophages suppresses inflammatory reaction leading to mouse coronary artery endothelial cell injury in a cell model of KD by hampering the activation of NF-κB and STAT3 signaling pathway. These findings imply that KCa3.1 may be a potential therapeutic target for KD.

BACKGROUND:Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of the body's innate immune system; however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. We aim to comprehensively delineate monocyte heterogeneity in healthy and KD infants and to reveal the underlying mechanism for KD.METHODS:Peripheral monocytes were enriched from peripheral blood samples of two healthy infants and two KD infants. scRNA-seq was performed to acquire the transcriptomic atlas of monocytes. Bio-information analysis was utilized to identify monocyte subsets and explore their functions and differentiation states. SELL+CD14+CD16- monocytes were validated using flow cytometry.RESULTS:Three monocyte subsets were identified in healthy infants, including CD14+CD16- monocytes, CD14+CD16+ monocytes, and CD14LowCD16+ monocytes. Cell trajectory analysis revealed that the three monocyte subsets represent a linear differentiation, and possess different biological functions. Furthermore, SELL+CD14+CD16- monocytes, which were poorly differentiated and relating to neutrophil activation, were found to be expanded in KD.CONCLUSION:Our findings provide a valuable resource for deciphering the monocyte heterogeneity in healthy infants and uncover the altered monocyte subsets in KD patients, suggesting potential biomarkers for KD diagnosis and treatment.

INTRODUCTION:Kawasaki disease (KD) is an acute febrile systemic vasculitis, but the etiology remains unknown. We studied serum levels of CD147, DcR3, and IL33 in different stages of KD to explore the value of CD147, DcR3, and IL33 in the pathophysiology of KD.METHODS:We measured serum levels of CD147, DcR3, and IL33 by enzyme-linked immunosorbent assay (ELISA) at different stages with 71 KD patients and 66 healthy control children. We apply for network tools GeneMANIA and Cytoscape APP to analyze the functions of these pro-inflammatory factors at the gene and protein level.RESULTS:Serum levels of CD147, DcR3, and IL33 were significantly increased in KD patients before IVIG treatment. Serum levels of CD147, DcR3, and IL33 gradually decreased over time after the treatment of IVIG. Eight cases were IVIG non-responders, while nine KD patients got CALs, but they did not overlap. And there were no statistical differences between group IVIG responders and IVIG non-responders or between groups without CALs and with CALs. We explored the functions of CD147, DcR3, and IL33 from GeneMANIA and Cytoscape APP and found these third pro-inflammatory factors were coexpressed, physical interactions, genetic interactions with other KD-related factors.CONCLUSION:CD147, DcR3, and IL33 are involved in the pathophysiology of KD, which provides novel evidence for diagnosing and treating KD with their inhibitors.

室间隔完整型肺动脉闭锁(pulmonary atresia with intact ventricular septum,PA/IVS)是一种少见的复杂紫绀型先天性心脏病,约占先天性心脏病的1％～3％[1].PA/IVS的病理解剖包括肺动脉瓣的完全梗阻、右心室及三尖瓣不同程度的发育不良、伴或不伴冠状动脉畸形.如果早期没有进行外科干预, PA/IVS的病死率极高,患儿出生后2周内病死率为50％,6个月内病死率约为85％.PA/IVS多数需分期手术,但由于其病理解剖的多样性和复杂性,初期治疗方法各异.初期手术依据患儿右心室发育程度以及有无右心室依赖性冠状动脉循环(right ventricle dependent coronary circulation,RVDCC)等,采用右心室减压术和/或体肺分流术如改良Blalock-Taussig分流术或动脉导管支架置入术[2].浙江大学医学院附属儿童医院采用经皮球囊肺动脉瓣打孔扩张术对6例PA/IVS患儿进行右心室减压,并根据患儿循环状态同期处理动脉导管,治疗效果满意,现报道如下.

Abstract Background The calcineurin and nuclear factor of activated T-cells (CaN-NFAT) signaling pathway had been found to be associated with Kawasaki disease (KD) susceptibility and coronary artery aneurysm formation as a contributor. To evaluate serum calcineurin (CaN) and nuclear factor of activated T-cells 1(NFAT1) levels in patients with Kawasaki disease (KD). Methods Serum levels of CaN and NFAT1 were measured by enzyme-linked immunosorbent assay method in 66 healthy children and 74 KD patients at acute, afebrile and subacute stage. Results The serum levels of CaN and NFAT1 increased significantly in the acute stage, and decreased progressively in the afebrile and subacute stage, along with the reduction of C-reactive protein, white blood cells and neutrophil counts. And in the acute stage, the afebrile stage and the subacute stage, the expression of CaN and NFAT1 was upregulated significantly in KD patients compared to that in the healthy control. After the IVIG treatment, the serum levels of CaN and NFAT1 declined significantly in IVIG responders. However, the CaN and NTAT1 levels in the IVIG non-responders declined slowly. And in the afebrile stage, the NFAT1 levels were lower in KD patients with coronary artery lesions (CALs) (268.82 ± 11.96 ng/ml) than those without CALs (285.84 ± 25.13 ng/ml). However, the serum levels of CaN in KD patients with CALs had no significant difference with those in KD patients without CALs. Conclusions The specific regulation of CaN and NFAT1 serum levels in the course of KD was suggested that both of them were related in the development of KD.

Ca 2+ /nuclear factor of activated T-cells (Ca 2+ /NFAT) signaling pathway may play a crucial role in the pathogenesis of Kawasaki disease (KD). We investigated the poorly understood Ca 2+ /NFAT regulation of coronary artery endothelial cells and consequent dysfunction in KD pathogenesis. Human coronary artery endothelial cells (HCAECs) stimulated with sera from patients with KD, compared with sera from healthy children, exhibited significant increases in proliferation and angiogenesis, higher levels of NFATc1 and NFATc3 and some inflammatory molecules, and increased nuclear translocation of NFATc1 and NFATc3. HCAECs stimulated with sera from patients with KD treated with cyclosporine A (CsA) showed decreased proliferation, angiogenesis, NFATc1 and inflammatory molecules levels as compared with results for untreated HCAECs. In conclusion, our data reveal that KD sera activate the Ca 2+ /NFAT in HCAECs, leading to dysfunction and inflammation of endothelial cells. CsA has cytoprotective effects by ameliorating endothelial cell homeostasis via Ca 2+ /NFAT.

Although intravenous immunoglobulin (IVIG) can effectively treat Kawasaki disease (KD), 10–20% of KD patients show no beneficial clinical response. Developing reliable criteria to discriminate non-responders is important for early planning of appropriate regimens. To predict the non-responders before IVIG treatment, gene expression dataset of 110 responders and 61 non-responders was obtained from Gene Expression Omnibus. After weighted gene co-expression network analysis, we found that modules positively correlated with the non-responders were mainly associated with myeloid cell activation. Transcripts up-regulated in the non-responders, IL1R2, GK, HK3, C5orf32, CXCL16, NAMPT and EMILIN2, were proven to play key roles via interaction with other transcripts in co-expression network. The crucial transcripts may affect the clinical response to IVIG treatment in acute KD. And these transcripts may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of the non-responders.

To clarify the independent risk factors and construct a scoring system for Kawasaki disease (KD) with coronary artery lesions (CAL) at acute and subacute stages.