Risk Of Coronary Artery Aneurysms Research Articles

Consensus Committee of experts on Kawasaki Disease and Chinese Journal of Contemporary Pediatrics – the expert consensuses on intravenous immunoglobulin, aspirin, and glucocorticoid

Introduction and aim. Kawasaki disease (KD) is an acute vasculitis with unknown etiology, usually occurring in chil dren under 5 years old. This article will summarize the three consensuses formulated in China about KD. Material and methods. English databases for consensus search include UpToDate, BMJ Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed, etc.; Chinese databases in clude China Biomedical Literature Service, China Knowledge Network, Wanfang database, etc. All literature searches ended on February 28, 2022. Analysis of the literature. KD is a common acquired heart disease in children and can lead to severe complications such as coronary injury. However, intravenous immunoglobulin (IVIG) combined with oral aspirin (Asp) is currently recognized as the most effective treatment in KD acute stage and the first-line treatment to prevent cardiovascular complications. Glucocorticoid (GC) is mainly used for KD patients with a high risk of coronary artery aneurysm (CAA), no immunoglobulin response, and confirmed CAA. There are already consensus guidelines on diagnosing and treat ing KD in different countries. This article summarizes the relevant expert consensus on aspirin, glucocorticoids and IVIG for the treatment of Kawasaki disease in China. Conclusion. Still, there are inconsistent opinions in the literature on the mechanism, optimal timing, and dosage of medication for KD.

Risk factors and scores for prediction of coronary artery aneurysms in Kawasaki disease: a European monocentric study

BackgroundJapanese Kawasaki disease (KD) risk scores cannot be adopted in non-Japanese patients. In North American populations a baseline coronary artery Z-score > 2 and the Son score are associated with coronary artery aneurysms (CAAs) at 4 and 8 weeks from disease onset. In European populations, the Kawanet and Kawanet-echo scores are associated with intravenous immunoglobulin resistance. This study aims to evaluate the association between KD risk scores and baseline coronary artery Z-scores with CAAs at one, two, and six months in a European population.MethodsHistorical cohort study of all the children diagnosed with KD in a tertiary care hospital in Milan, Italy, between 1st January 2015 and 31st May 2021. Univariate and multivariate (adjusting for age and corticosteroid therapy) logistic regression analyses were used to study the association between the risk scores, a baseline Z-score ≥ 2 and ≥ 2.5 with CAAs.ResultsEighty-nine patients were diagnosed with KD at our Centre, and 12 were excluded based on the exclusion criteria. We included 77 patients, 51 (66%) males, and 26 (34%) females, with a median age at presentation of 27 months (IQR 13–46). A baseline Z-score ≥ 2 was correlated with CAAs at one and two-month follow-ups (odds ratio (OR) 10, 95% confidence interval (CI) 2–72, and OR 18, CI 3-357) but not at six-month follow-up. The Son score showed an association with one and two-month follow-up CAAs (OR 3, CI 1.3-7, and OR 3, CI 1.3-8) but not with a six-month follow-up.ConclusionsPatients with a baseline Z-score ≥ 2 are at higher risk for CAAs in the long term. The Son score should be tested in larger European samples. Further studies should keep the observational periods longer than 8 weeks from KD onset.

Childhood rheumatic diseases: bites not only the joint, but also the heart.

Cardiovascular involvement in juvenile rheumatic diseases is the primary manifestation in paediatric vasculitis and a major organ manifestation in paediatric connective tissue diseases. Though coronary vasculitis is the prototypical manifestation of Kawasaki disease, it can also be seen in patients with polyarteritis nodosa. Pericarditis is the most common manifestation seen in juvenile rheumatic diseases like systemic onset JIA, and lupus. Cardiac tamponade, valvular insufficiency, aortic root dilatation and arrhythmias are seen rarely. Cardiac involvement is often recognized late in children. The development of cardiac disease in juvenile systemic sclerosis is associated with a poor outcome. In long term, childhood onset of rheumatic diseases predisposes to diastolic dysfunction and premature atherosclerosis during adulthood. Key Points • Pericarditis is the most common cardiac manifestation in SLE and can lead to tamponade. • Conduction defects are common in juvenile mixed connective tissue disease and systemic sclerosis. • Pulmonary hypertension is a significant contributor to mortality in juvenile systemic sclerosis. • In Kawasaki disease, early treatment can reduce risk of coronary artery aneurysms.

Abstract 480: IL-33 Promotes Cardiovascular Lesions Development In A Mouse Model Of Kawasaki Disease

Kawasaki Disease (KD), a pediatric acute febrile illness and systemic vasculitis, is the leading cause of acquired heart diseases in children. Coronary artery aneurysms (CAAs) occur in up to 25% of untreated children, which is reduced to 5% with intravenous immunoglobulin (IVIG) treatment. However, up to 20% of KD patients are refractory to IVIG and at higher risk of CAAs, highlighting the need to characterize the mechanisms mediating KD vasculitis to develop more efficient therapies. IL-33 is released upon inflammation and tissue damage and exerts its effects by binding to its receptor ST2 ( IL1RL1 ). Levels of IL-33 are elevated in KD patients during the acute phase. However, how IL-33 contributes to the development of KD cardiovascular lesions remains unknown. Using the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, we observed increased Il33 mRNA expression in hearts and abdominal aortas aneurysms of LCWE-injected mice. While ST2 was detected by immunofluorescence in the abdominal aortas of both control and LCWE-injected mice, IL-33 was mainly detected in tissues from LCWE-injected mice. Single-cell RNA-sequencing of abdominal aortas from LCWE-injected mice indicated that Il33 transcripts were expressed primarily by fibroblasts, endothelial cells, B cells, and vascular smooth muscle cells. In contrast, Il1rl1 was highly expressed by tissue infiltrating regulatory T cells, macrophages, eosinophils, and neutrophils. Blocking IL-33 with either anti-IL-33 or using Il33 -/- mice significantly attenuated LCWE-induced KD vasculitis. Our results indicate that IL-33 participates in LCWE-induced KD vasculitis in mice and could therapeutically be targeted to inhibit KD cardiovascular lesions.

IL-33 promotes cardiovascular lesions development in a mouse model of Kawasaki Disease

Abstract Kawasaki Disease (KD), a pediatric acute febrile illness and systemic vasculitis, is the leading cause of acquired heart diseases in children. Coronary artery aneurysms (CAAs) occur in up to 25% of untreated children, which is reduced to 5% with intravenous immunoglobulin (IVIG) treatment. However, up to 20% of KD patients are refractory to IVIG and at higher risk of CAAs, highlighting the need to characterize the mechanisms mediating KD vasculitis to develop more efficient therapies. IL-33 is released upon inflammation and tissue damage and exerts its effects by binding to its receptor ST2 (IL1RL1). Levels of IL-33 are elevated in KD patients during the acute phase. However, how IL-33 contributes to the development of KD cardiovascular lesions remains unknown. Using the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, we observed increased Il33 mRNA expression in hearts and abdominal aortas aneurysms of LCWE-injected mice. While ST2 was detected by immunofluorescence in the abdominal aortas of both control and LCWE-injected mice, IL-33 was mainly detected in tissues from LCWE-injected mice. Single-cell RNA-sequencing of abdominal aortas from LCWE-injected mice indicated that Il33 transcripts were expressed primarily by fibroblasts, endothelial cells, B cells, and vascular smooth muscle cells. In contrast, Il1rl1 was highly expressed by tissue infiltrating regulatory T cells, macrophages, eosinophils, and neutrophils. Blocking IL-33 with either anti-IL-33 antibody or using Il33 −/−mice significantly attenuated LCWE-induced KD vasculitis. Our results indicate that IL-33 promotes LCWE-induced KD vasculitis in mice and could therapeutically be targeted to inhibit KD cardiovascular lesions.

Coronary Artery Involvement in Kawasaki Disease-Echocardiographic Evaluation of Cases in a Tertiary Care Hospital

Background: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease. Cardiovascular manifestations can be prominent in the acute phase of the illness. Echocardiography is useful in recognizing these cardiac manifestations. We carried out a retrospective study by analyzing the data of Kawasaki disease patients in a tertiary care hospital. Methods: The prevalence of coronary artery dilatation and clinical outcome were documented. Clinical, laboratory, and echocardiographic findings were obtained at baseline and 1 week, 6 weeks after initial therapy with intravenous immunoglobulin in addition to high doses of Aspirin which reduces the risk of coronary artery aneurysm. Results: One hundred and forty-nine patients with mean age 3± 2 years old, 60% males with Kawasaki disease were included. One hundred and thirty-two patients had coronary involvement (left main coronary artery 36.37 %, left anterior descending artery 28.03%, right main coronary artery 24.25%, circumflex branch in 11.37%). Administration of intravenous immunoglobulin (IVIG) and aspirin has greatly reduced the incidence of coronary lesions in affected children. The initial cardiac findings developed over first few weeks of illness resolved in most of the cases in the subsequent echocardiogram studies after IVIG. The mean duration to normalization of abnormal echocardiography findings is 6±3 months. Conclusion: Coronary artery involvement is seen in most of children with Kawasaki disease. Intravenous gamma globulin and aspirin has been reported to reduce the likelihood of development of giant coronary artery aneurysms and appears to have a direct beneficial effect on abnormalities in cardiac function associated with the acute phase of Kawasaki disease. Cardiovasc j 2023; 15(2): 144-150

Epidemiological Profile and Management of Kawasaki Syndrome at Rabat Children’s Hospital: A retrospective study from Morocco

Kawasaki disease (KD) is a common pediatric vasculitis with a risk of coronary artery aneurysm. In this report, we review some particularities of KD disease, especially coronary involvement, and highlight its aspects during the COVID-19 epidemic which saw the emergence of a syndrome named multisystem inflammatory syndrome in children (MIS-C). Because of its many similarities with KD, MIS-C is often referred to as Kawasaki-like disease (KLD) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).We report on a retrospective study on the different epidemiological, clinical, and evolutionary aspects of KD and the coronary involvement resulting from this disease before and after the pandemic. The study is based on the echocardiography records of the P4 Department at Rabat Children’s Hospital, from January 2002 to December 2021. A total of 379 patients were diagnosed with KD during that period. This includes 47 cases that were reported during the first year of the COVID-19 epidemic in Morocco (March 2020). Echocardiography results for our series show that cardiac complications wererelatively more frequent among KD patients during the COVID-19 period, perhaps because they were relatively older (67 months on average) than classic KD patients (37 months on average). However, all patients had a favorable outcome after treatment with a combination of intravenous immunoglobulin (IVIG) and aspirin. The few patients who did not respond to standard treatment received corticosteroids, and no mortality occurred. We conclude that as far as cardiac complications,KD, KLD, and MIS-C are the same core disease that is triggered under different conditions for different age groups.The emergence of the Sars-Cov-2 virus changed the epidemiologic profile of KD but not its treatment. Insights from this study would help in the decision to initiate targeted immunotherapy quickly and reduce the risk factors associated with KD.

Identifying Kawasaki Disease With a Low Coronary Artery Aneurysm Risk.

Kawasaki disease (KD) patients with a high risk of coronary artery aneurysm (CAA) development are well characterized and targeted for intensified primary intravenous immunoglobulin (IVIG) treatment. However, the characteristics of KD patients with a low CAA risk are less well-known. The present study was a secondary analysis of Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki disease (Post RAISE), a multicenter, prospective cohort study of KD patients in Japan. The target of the analysis was patients with a Kobayashi score <5 who were predicted to respond to IVIG. The incidence of CAA during the acute phase, the primary outcome, was assessed based on all echocardiographic evaluations performed between week 1 (days 5-9) and month 1 (days 20-50) after the start of primary treatment. Multivariable logistic regression was used to identify the independent risk factors of CAA during the acute phase, based on which a decision tree was created to identify a subpopulation of patients with KD with a low CAA risk. Multivariate analysis found that a baseline maximum Z score >2.5, age <12 months at fever onset, nonresponsiveness to IVIG, low neutrophils, high platelets and high C-reactive protein were independent predictors of CAA during the acute phase. The decision tree created by using these risk factors identified 679 KD patients who had a low incidence of CAA during the acute phase (4.1%) and no medium or large CAA. The present study identified a KD subpopulation with a low CAA risk comprising around a quarter of the entire Post RAISE cohort.

Effect of Beta Blockers on the Hemodynamics and Thrombotic Risk of Coronary Artery Aneurysms in Kawasaki Disease.

This study aims to simulate beta blockers' (BB) effects on coronary artery aneurysms' (CAA) hemodynamics and thrombotic risk in Kawasaki disease (KD). BB are recommended in cases of large aneurysms due to their anti-ischemic effect. Coronary blood flow (CBF) was simulated in KD patient-specific CAA models using computational fluid dynamics. Hemodynamic indices that correlate with thrombotic risk were calculated following two possible responses to BB: (1) preserved coronary flow (third BB generation) and (2) reduction in coronary flow (first and second BBgenerations) at reduced heart rate. Following CBF reduction scenario, mean TAWSS and HOLMES significantly decreased compared to normal conditions, leading to a potential increase in thrombotic risk. Preserved CBF at lower heart rates, mimicking the response to vasodilating BBs, does not significantly affect local CAA hemodynamicscompared with baseline, while achieving the desired anti-ischemic effects. Different BB generations lead to different hemodynamic responses in CAA.

Cardiovascular Complications in Patients with Kawasaki Disease in a Tertiary Care Hospital in West Bengal, Eastern IndiaA Prospective Clinical Study

ABSTRACT Introduction: Kawasaki Disease (KD) is an acute self-limiting systemic vasculitis involving medium and small-sized arteries. It may soon replace rheumatic fever to become the most common cause of acquired heart disease in Indian children. Coronary Artery Aneurysm (CAA) which can develop in 15-25% of untreated children remains the most dreaded complication of KD. Predicting the risk of CAA and taking timely measures can help in reducing the fatality of the condition. Aim: To study the spectrum of cardiovascular complications in patients with KD and also to assess associated risk factors for developing CAA in the patients under study. Materials and Methods: This prospective clinical study was carried out in the Paediatric Medicine Ward, Burdwan Medical College and Hospital, West Bengal, Eastern India, from 1st January, 2020 to 31st May, 2021. Total 52 children diagnosed with KD, aged between one month to 12 years, were included and followed-up for six months. Data regarding demographic variables, duration of fever, Intravenous Immunoglobulin (IVIG) resistance, hepatomegaly, neutrophilia, thrombocytopenia, haematocrit, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), hepatic transaminases (alanine transaminase, aspartate amino-transferase), hyponatremia, hypoalbuminemia, and N-terminal-brain natriuretic peptide (NT-proBNP) were collected. Univariate and multivariate regression analyses were done using these variables for assessment of risk factors. Results: In the present study, out of 52 children, 28 (53.85%) were males and 24 (46.15%) were females with mean age of 3.74±2.55 years. Cardiovascular complications were observed in 27 (51.92%) patients, of whom 19 (35.54%) had CAA. Duration of fever ≥10 days, IVIG resistance, thrombocytopenia, low hematocrit, Alanine Transaminase (ALT) ≥100 U/L, hypoalbuminemia, and raised NT-proBNP were proven to be significant risk factors for development of CAA on univariate analysis. Thrombocytopenia and raised NT-proBNP came across as significant on binary logistic regression analysis. Conclusion: In this study, one or more types of cardiovascular abnormalities were present in 51.92% cases. Seven risk factors were identified to be significant in development of CAA on univariate analysis and among them two were proven significant in binary logistic regression.

Association between Rab31/rs9965664 polymorphism and immunoglobulin therapy resistance in patients with Kawasaki disease.

Kawasaki disease (KD) is an acute febrile systemic vasculitis affecting infants and young children. A high dose of intravenous immunoglobulin (IVIG) is the first-line strategy for patients with KD to reduce persistent inflammation and the risk of coronary artery aneurysm (CAA) formation. Unfortunately, 10-20% of the patients showed no response to the treatment and were defined as resistant to IVIG. Rab31 has been reported to regulate innate immunity in several human diseases. However, whether single nucleotide polymorphism (SNP) in Rab31 gene could predispose to IVIG therapy response in KD was uncovered. Rab31/rs9965664 polymorphism was genotyped in 1,024 Chinese patients with KD through TaqMan assay. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between Rab31/rs9965664 polymorphism and IVIG therapeutic effects. Our results showed that Rab31/rs9965664 AA/GA genotype was significantly associated with an increased risk of IVIG resistance compared to GG genotype (GA vs. GG: p = 0.0249; AA vs. GG: p = 0.0016; AA/GA vs. GG: p = 0.0039; and AA vs. GG/GA: p = 0.0072). Moreover, the KD individuals carrying the rs9965664 A allele displayed lower Rab31 protein levels, and the expression level of Rab31 in the IVIG-resistant group was decreased significantly when compared to that observed in the response group. A mechanical study demonstrated that Rab31 modulated IVIG response through NLRP3 and p38 pathways. These results suggested that Rab31/rs9965664 polymorphism might be associated with an increased risk of IVIG resistance in southern Chinese patients with KD. The possible mechanism is that Rab31 regulates the NLRP3 pathway negatively to inhibit IVIG response.

The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population.

BackgroundKawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported.MethodsA total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance.ResultsBoth of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06–3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10–2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62–4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37–3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22–2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24–2.27, p = 0.0008).ConclusionOur findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.

Diagnosis delay is associated with heart failure severity in multisystem inflammatory syndrome in children

Diagnosis delay leads to an increased risk of coronary artery aneurysms in Kawasaki disease. In multisystem inflammatory syndrome in children (MIS-C), diagnosis delay could worsen heart failure. This study aims to test the hypothesis that a long time to diagnosis is associated with heart failure severity in MIS-C. A retrospective single-center observational study was conducted between May 2020 and April 2022. Children with a MIS-C diagnosis meeting WHO criteria were included. A long time to diagnosis was defined as 6 days or more. Outcomes were assessed on severity of heart failure, including peak NT-proBNP, minimal left ventricular ejection fraction (LVEF) and need for inotropes (dobutamine, milrinone, adrenaline). Thirty-two children were included in the study. One child was excluded due to previous vaccination against COVID-19. The median age [1st–3rd interquartile range] was 8 [5–10] years old. The median time to diagnosis was 5.3 [4.0–6.3] days. Children with a long time to diagnosis ( n = 13), compared with those with a short time to diagnosis ( n = 18), had a higher peak NT-proBNP (22304 [13859–47889] ng/L versus 5555 [2384–10227] ng/L, respectively, P < 0.001), lower LVEF (40 [30–50] % versus 45 [45-55,5] %, respectively, P = 0.02), and were more often treated with inotropes (8 children (57%) versus 0 child (0%) respectively, P < 0.001). Diagnosis delay is associated with heart failure severity in MIS-C. Early diagnosis and treatment are crucial to avoid the use of inotropes and limit morbidity.

Exploring the relationship between pyroptosis, infiltrating immune cells and Kawasaki disease with resistance to intravenous immunoglobulin (IVIG) via bioinformatic analysis

BackgroundKawasaki disease (KD) is a kind of vasculitis predominantly afflicting children younger than five. Although intravenous immunoglobulin (IVIG) has been regarded as the first-line therapy, there are some children unresponsive to it, resulting in higher risk of coronary artery aneurysms (CAA), the most severe complication of KD. Pyroptosis is an inflammatory apoptosis, which resembles the traits of IVIG-resistance. Therefore, our research aims to find relationships between KD with IVIG-resistance and pyroptosis, and provide the underlying mechanisms of IVIG-resistance. MethodsThe transcriptome data of three datasets were downloaded from Gene Expression Omnibus (GEO) database. CIBERSORTx and WGCNA were combined to identify the coexpression gene network correlated with the up-regulated immune cells in KD, using differentially expressed genes (DEGs) overlapped in GSE68004 and GSE73461. The key genes in hub module were intersected with pyroptosis-related genes (PRGs). Then KD patients were divided into subgroups according to the expression of remaining genes, along with the construction of risk score (RS) based on the least absolute shrinkage and selection operator (LASSO) regression analysis. Besides, we explored the clinical value of RS between IVIG-responsive and -resistant KD patients in GSE16797. In addition, the biological pathways between subgroups were evaluated using Gene Set Variation Analysis (GSVA). ResultsA total of 4246 DEGs and three immune cells, including Monocytes, M0 macrophage, and neutrophils, were analyzed with P < 0.05 between KD and healthy controls (HCs). The lightcyan module was the hub module based on WGCNA, and only NLRC4, CASP1, CASP4, GSDMD, IL1B and PYCARD in the hub module were overlapped with PRGs. Then KD patients in GSE68004 were stratified into two clusters on the basis of the expression levels of six genes. RS was built with five out of six genes (exclude PYCARD) according to the LASSO analysis, which could differentiate C1 from C2, IVIG-responsive from -resistant KD patients. Besides, the high-risk group (C1) tended to be with increased levels of inflammation, immune responses and infiltration of neutrophils according to the analysis of GSVA and CIBERSORTx. ConclusionWe built a pyroptosis-related RS to evaluate the degree of pyroptosis and infiltrating immune cells in subgroups of KD, and associated it with the responsiveness to IVIG, which might help us to further understand the pathological process during IVIG-nonresponse.

CircRNA-3302 promotes endothelial-to-mesenchymal transition via sponging miR-135b-5p to enhance KIT expression in Kawasaki disease

Endothelial-to-mesenchymal transition (EndMT) is implicated in myofibroblast-like cell-mediated damage to coronary artery wall of Kawasaki disease (KD) patients, which subsequently increases the risk of coronary artery aneurysm. Many circular RNAs (circRNAs) have been reported to be associated with cardiovascular diseases. However, the roles and underlying molecular mechanism of circRNAs in KD-associated EndMT remains indefinite. In this research, we screened out circRNA-3302 from human umbilical vein endothelial cells (HUVECs) treated by sera from healthy controls (HCs) or KD patients via circRNA sequencing (circRNA-seq). In addition, circRNA-3302 upregulation was verified in endothelial cells stimulated by KD serum and pathological KD mice modeled with Candida albicans cell wall extracts (CAWS). Moreover, in vitro experiments demonstrated that overexpression of circRNA-3302 could markedly induce EndMT, and silencing of circRNA-3302 significantly alleviated KD serum-mediated EndMT. To further explore the molecular mechanisms of circRNA-3302 inducing EndMT, RNA sequencing (RNA-seq), a dual-luciferase reporter system, nuclear and extra-nuclear RNA isolation, RT-qPCR and Western blot analyses and so on, were utilized. Our data demonstrated that circRNA-3302 contributed to the KD-associated EndMT via sponging miR-135b-5p to enhance KIT expression. Collectively, our results imply that circRNA-3302 plays an important role in KD-associated EndMT, providing new insights into minimizing the risks of developing coronary artery aneurysms.

Pediatric expert consensus on the application of glucocorticoids in Kawasaki disease.

Kawasaki disease (KD) is one of the common acquired heart diseases in under-5-year-old children and is an acute self-limiting vasculitis. After nearly 60 years of research, intravenous immunoglobulin combined with oral aspirin has become the first-line treatment for preventing coronary artery aneurysm in the acute stage of KD. However, glucocorticoid (GC), infliximab, and other immunosuppressants are options for the treatment of KD patients with a high risk of coronary artery aneurysm, no response to intravenous immunoglobulin and a confirmed diagnosis of coronary artery aneurysm. At present, there are still controversies over the use of GC in the treatment of KD. With reference to the latest research findings of KD treatment in China and overseas, this consensus invited domestic pediatric experts to fully discuss and put forward recommendations on the indications, dosage, and usage of GC in the first-line and second-line treatment of KD.

Association study of miR-149, miR-196a2, and miR-499a polymorphisms with coronary artery aneurysm of Kawasaki disease in southern Chinese population.

BackgroundAccumulating evidence suggests that several microRNA (miRNA) polymorphisms are closely associated with disease susceptibility or progression, such as in Kawasaki disease (KD). Our previous studies revealed the association of miR‐149 rs2292832 T>C and miR‐196a2 rs11614913 C>T polymorphisms with KD susceptibility. The present study further focused on the relationship between three miRNA polymorphisms (miR‐149 rs2292832 T>C, miR‐196a2 rs11614913 C>T and miR‐499a rs3746444 A>G) and the risk of coronary artery aneurysm (CAA) in southern Chinese KD patients.MethodsWe evaluated 318 KD patients with CAAs and 784 patients without CAAs. TaqMan assays were used to estimate genotyping and analyze the relationship between miRNA polymorphisms (miR‐149 rs2292832 T>C, miR‐196a2 rs11614913 C>T and miR‐499a rs3746444 A>G) and risk associations of CAA by odds ratios (ORs) and 95% confidence intervals (CIs).ResultsWe found that the miR‐149 rs2292832 TC/CC genotype increased the CAA risk (adjusted OR = 1.53, 95% CI = 1.15–2.03, p = 0.003 for TC, adjusted OR = 1.63, 95% CI = 1.08–2.47, p = 0.021 for CC), whereas the miR‐499a rs3746444 AG genotype decreased the CAA risk in KD patients (adjusted OR = 0.33, 95% CI = 0.25–0.45 p ≤ 0.001). Moreover, patients carrying two or three of these single nucleotide polymorphism (SNP) genotypes (rs2292832 TC/CC and rs11614913 TT and rs3746444 AA) had a higher risk for CAA than those who harbored only zero or one of these SNP genotypes.ConclusionsOur results demonstrated that the miR‐149 rs2292832 T>C polymorphism increased the risk of CAA in KD patients and that the miR‐499a rs3746444 A>G polymorphism decreased the risk of CAA in KD patients. Further studies with larger sample sizes and different centers are needed to confirm the findings of the present study.

Treatment and Coronary Artery Aneurysm Formation in Kawasaki Disease: A Per-Day Risk Analysis

To assess whether 'treatment day' is a significant predicting factor in Kawasaki disease and imposes a risk for coronary artery aneurysms (CAAs) in a per-day analysis. CAA formation can be reduced from 25% to 10% when treated with intravenous immunoglobulin (IVIG). Patient data from (n=1016) a single center were collected for an observational cohort study. After exclusions, we retrospectively analyzed 776 patients in total. A multivariate analysis was performed with treatment day as a continuous variable (n=691). Patients were categorized as no enlargement, small CAA, medium CAA, and giant CAA. Late treatment per-day was a significant predicting factor for the development of larger CAAs. ORs for medium and giant CAAs per delayed day were 1.1 (95% CI 1.1-1.2) P<.05 and 1.2 (95% CI 1.1-1.2) P<.05, respectively. We showed that every day of delay in treatment of patients with Kawasaki disease inherently carries a risk of medium and giant aneurysm formation. There was no cut-off point for treatment day that could mark a safe zone.

Kawasaki disease in a five-month-old infant

Introduction: Kawasaki disease, an acute self-limited vasculitis of small and medium arteries of unknown etiology, is the leading cause of heart disease in children in most developed countries. If untreated, it can lead to coronary artery dilatation and aneurysm, placing patients at risk for coronary thrombosis, myocardial infarction, or sudden death. Case Report: A previously healthy five-month-old boy presented with a history of respiratory symptoms and fever, being admitted for respiratory syncytial virus bronchiolitis. He maintained fever for five days associated with progressive clinical worsening and sequential development of conjunctival injection, cracked lips, swelling of hands and feet, and polymorphous rash of the limbs. Diagnostic procedures showed increased levels of inflammatory markers, hyponatremia, hypoalbuminemia, sterile pyuria, and aseptic meningitis. Despite an initial normal echocardiogram, Kawasaki disease was suspected and the boy started intravenous immunoglobulin on the fifth day. On the seventh day, echocardiogram showed signs of pancarditis and mild coronary artery ectasia and acetylsalicylic acid was started. The boy was discharged, but eight days later echocardiogram revealed major and diffuse coronary artery ectasia in a follow-up consultation and he was readmitted to start corticosteroid therapy. After five months, the boy displayed normalization of cardiac changes, without further complications. Comments: Kawasaki disease below six months of age is rare and associated with a high risk of coronary artery aneurysm. It is important to recognize the clinical and laboratory criteria associated with this entity and start early treatment, avoiding cardiac complications.

Impact of Platelet Glycoprotein Ia/IIa C807T Gene Polymorphisms on Coronary Artery Aneurysms of KD Patients

Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology in children. Coronary artery abnormalities are the most common complications of KD. Recent evidence showed that genetic polymorphisms may lead to susceptibility to KD. Genetic variants in platelet glycoprotein have been reported to be associated with coronary artery disease. The aim of the present study is to investigate the correlation between the role of platelet glycoprotein and coronary artery aneurysms in KD patients. Methods We did a case-control study that enrolled 818 KD patients and 1401 healthy children with the same age and sex from January 2013 to December 2016. Analysis of single-nucleotide polymorphism (rs1126643) of the platelet glycoprotein Ia/IIa C807T was performed by multiplex polymerase chain reactions in this study. Results A significant difference in the genotype distribution between KD cases and controls was observed for the glycoprotein Ia/IIa C807T (rs1126643) polymorphism (p=0.026). Compared with the healthy children, the rs1126643T allele carriers had odds ratio (OR) of 0.63 for developing KD (TT vs. CC: adjusted OR = 0.62, 95% confidence interval (CI) = 0.43–0.88,p=0.0078; TT vs. CT/CC: adjusted OR = 0.63, 95% CI = 0.44–0.889,p=0.0093). Furthermore, we also found that children less than 60 months of age and female patients with rs1126643 T allele carriers had an adjusted OR of 0.66 (95% CI = 0.46–0.95) for noncoronary artery aneurysm patients (p=0.0242). Single-nucleotide polymorphism rs1126643 TT seems to represent a protective factor against KD in coronary artery aneurysm formation in multivariate analysis. Conclusions The platelet glycoprotein Ia/IIa T allele carriers may have a protective effect on the risk of coronary artery aneurysms of KD patients, especially in females and children aged less than 60 months. These results may provide evidence for platelet glycoprotein Ia/IIa gene polymorphisms in the pathogenesis of KD patients.