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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]

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]

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]

Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients' electronic file, and then they were analyzed after collecting information of the patients. In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P = 0.02), hematuria (P = 0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P < 0.001) were significant. The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients. [ABSTRACT FROM AUTHOR]

A 34-year-old man with a history of Kawasaki disease had been experiencing chest pain at rest since middle school. Multidetector-row computed tomography showed no aneurysm formation; however, the right coronary artery had an anomalous origin with moderate stenosis. Invasive coronary angiography revealed moderate right coronary artery stenosis with a fractional flow reserve of 0.97. Finally, with a positive acetylcholine provocation test and elevated index of microvascular resistance, the patient was diagnosed with microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries. This is the first reported case of both microvascular and epicardial vasospastic angina after Kawasaki disease. In patients with a history of Kawasaki disease, even those without cardiac sequelae, coronary endothelial and microvascular dysfunctions should be taken into consideration. We report the first case of both microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries after Kawasaki disease. Coronary endothelial and microvascular dysfunctions should be taken into consideration in patients with a history of Kawasaki disease, even those without cardiac sequelae. [ABSTRACT FROM AUTHOR]

To investigate whether two brands of intravenous immunoglobulin (IVIG) from the same manufacturer lead to varied effects when administered to patients with Kawasaki disease. (KD) Clinical characteristics, laboratory data, IVIG response, and coronary arteries change were analyzed between two groups. We included 158 KD cases. The mean age at KD diagnosis was 23 ± 1.39 (range, 2–95) months. In the first IVIG course, 18 (11.4 %) patients were unresponsive. TBSF (brand T) and Privigen (brand P) were administered to 94 and 64 patients, respectively. The brand P group had a significantly longer fever (P < 0.001) and hospitalization (P = 0.007) durations after the therapy and a higher number of IVIG unresponsiveness (P = 0.016) than the brand T group. In the multivariate logistic regression analysis, a high Formosa score (≥3, Odds ratio [OR], 4.939; 95 % confidence interval [CI], 1.199–20.337; P = 0.027), high levels of CRP (≥12 mg/L, OR: 4.257,95 % CI,1.265–14.322; P = 0.019), and treatment with brand P (OR, 3.621; 95 % CI, 1.029–12.677; P = 0.045) were independent risk factors for IVIG unresponsiveness. Compared with brand T, brand P prolonged the fever and hospitalization durations after IVIG treatment and increased the proportion of IVIG treatment unresponsiveness, but it did not infer the coronary arteries sequelae. [ABSTRACT FROM AUTHOR]

La maladie de Kawasaki (MK) est la vascularite la plus fréquente chez l'enfant de moins de 5 ans. Elle constitue une urgence diagnostique et thérapeutique. Sa gravité est liée à l'atteinte coronarienne qui survient chez 3–5 % des patients traités. Le défi de cette maladie est de deux types : (1) sa reconnaissance rapide, (2) la réduction de l'incidence des anévrismes coronariens (AC). Nous reprenons dans cette revue la prise en charge thérapeutique de cette maladie et notamment l'adjonction dans le cas de MK sévère d'un traitement adjuvant par corticothérapie qui semble réduire l'incidence des AC notamment dans les populations asiatiques. D'autres traitements (anti-TNF, anti-IL-1, ciclosporine) peuvent également apporter un bénéfice, mais les données sont à ce jour limitées et ne permettent pas leur indication en 1re intention mais seulement en cas de MK réfractaires après une ou deux doses d'IgIV. Kawasaki disease (KD) is the most common vasculitis in children under 5 years of age. It is a diagnostic and therapeutic emergency. Its severity is related to its coronary involvement, which occurs in 3–5 % of patients treated. The challenge of this disease is twofold: (1) its rapid recognition, (2) the reduction of the incidence of coronary aneurysm (CA). In this review, we discuss the therapeutic management of this disease and in particular the addition of adjuvant corticosteroid therapy in severe KD, which seems to reduce the incidence of CA, particularly in Asian populations. Other treatments (anti-TNF, anti-IL-1, ciclosporin) may also be of benefit, but the data are scarce and do not allow their indication as first-line treatment but only in cases of refractory MK after one or two doses of IVIG. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute pediatric vasculitis that predominantly affects children under the age of 5 years. To date, genome-wide association studies (GWAS) have identified several KD susceptibility genes (e.g., BLK, CD40, FCGR2A, BCL2L11 , and IGHV), which are mainly involved in B cell immunity. In this study, we aimed to identify additional KD susceptibility genes mainly involved in B cell development and functions by analyzing our previous GWAS data and conducting a replication study using new sample. Initially, we selected 30 single nucleotide polymorphisms (SNPs) in B-cell-related genes that were significantly (P < 0.01) associated with KD in our previous GWAS analysis of 247 KD cases with complete type and 1,000 healthy controls. Replication study was performed by genotyping the new 837 KD case samples with Fluidigm system and comparing them with 3,553 control genotypes. Among the 30 candidate SNPs, two were significantly associated with KD (P < 0.001) in the replication study. An even greater association between these SNPs and KD was observed in the combined analysis of GWAS and replication samples: odds ratio (OR) = 1.97 (P = 8.61 × 10−6) for rs2270699 (nonsynonymous SNP: c.10588C > T, p.Arg3530Trp) in the heparan sulfate proteoglycan 2 (HSPG2) gene and OR = 1.28 (P = 1.34 × 10−6) for rs3130992 (intronic SNP) in both the corneodesmosin (CDSN) and psoriasis susceptibility 1 candidate 1 (PSORS1C1) genes. These results suggest that the B-cell-related genes, HSPG2 and CDSN or PSORS1C1 , play a role in the development of KD. [ABSTRACT FROM AUTHOR]

/Purpose : Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes. This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019–2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups. BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2–3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2–3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2–3 months in children with incomplete KD. BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2–3 months. [ABSTRACT FROM AUTHOR]

Although the etiology of Kawasaki disease (KD) remains unknown, the most common view is that an infectious agent triggers the activation of the inflammatory cascade in predisposed children. The coronavirus disease 2019 (COVID-19) pandemic has led to the establishment of infection control measures, which reduced the overall incidence of respiratory infections; however, a resurgence of respiratory syncytial virus (RSV) infection occurred in the summer of 2021. This study aimed to examine the relationship between respiratory pathogens and KD during the COVID-19 pandemic and the RSV epidemic in Japan between 2020 and 2021. We retrospectively reviewed the medical charts of pediatric patients with KD or respiratory tract infection (RTI) admitted to National Hospital Organization Okayama Medical Center between December 1, 2020, and August 31, 2021. All patients with KD and RTI underwent multiplex polymerase chain reaction testing upon admission. We classified patients with KD into the three subgroups—pathogen-negative, single pathogen-positive, and multi-pathogen-positive—and compared their laboratory data and clinical features. This study enrolled 48 patients with KD and 269 with RTI. Rhinovirus and enterovirus were the most prevalent pathogens in both patients with KD and RTI (13 [27.1%] and 132 patients [49.1%], respectively). The clinical characteristics of the pathogen-negative KD group and the pathogen-positive KD group at diagnosis were similar; however, the pathogen-negative group tended to receive additional treatment, such as multiple courses of intravenous immunoglobulin, intravenous methylprednisolone, infliximab, cyclosporine A, and plasmapheresis, more frequently. The number of patients with KD remained stable when RTI was not prevalent but increased following the surge in RTI with RSV. An epidemic of respiratory infections led to an increase in the incidence of KD. Patients with respiratory pathogen-negative KD could have greater recalcitrance to intravenous immunoglobulin than those with respiratory pathogen-positive KD. [ABSTRACT FROM AUTHOR]

This article compares two important pathophysiological states, Kawasaki disease, and multisystem inflammatory syndrome, in children associated with COVID-19 (MIS-C). Both occur predominantly in children, have a temporal association with an infectious agent, and are associated with immune-system alteration and systemic inflammation under certain circumstances. The two share common pathophysiology, including enhancement of interleukin-1 neutrophils, activation of the inflammasome, pyroptosis, or NETosis. Moreover, the clinical presentation of the diseases overlaps. However, they are indeed two separate diseases, proven by the differences in the epidemiological and etiological aspects and the pathophysiological processes involved in the development and frequency of some clinical signs. This article highlights potentially exciting areas that have not yet been studied in detail, which could help better understand the development of these diseases. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute vasculitis with a particular tropism for the coronary arteries. KD mainly affects male children between 6 months and 5 years of age. The diagnosis is clinical, based on the international American Heart Association criteria. It should be systematically considered in children with a fever, either of 5 days or more, or of 3 days if all other criteria are present. It is important to note that most children present with marked irritability and may have digestive signs. Although the biological inflammatory response is not specific, it is of great value for the diagnosis. Because of the difficulty of recognising incomplete or atypical forms of KD, and the need for urgent treatment, the child should be referred to a paediatric hospital as soon as the diagnosis is suspected. In the event of signs of heart failure (pallor, tachycardia, polypnea, sweating, hepatomegaly, unstable blood pressure), medical transfer to an intensive care unit (ICU) is essential. The standard treatment is an infusion of IVIG combined with aspirin (before 10 days of fever, and for a minimum of 6 weeks), which reduces the risk of coronary aneurysms. In case of coronary involvement, antiplatelet therapy can be maintained for life. In case of a giant aneurysm, anticoagulant treatment is added to the antiplatelet agent. The prognosis of KD is generally good and most children recover without sequelae. The prognosis in children with initial coronary involvement depends on the progression of the cardiac anomalies, which are monitored during careful specialised cardiological follow-up. [ABSTRACT FROM AUTHOR]

Nailfold capillaroscopy has been used as a non-invasive diagnostic method for microvasculature evaluation in various rheumatological disorders. The present study aimed to determine the utility of nailfold capillaroscopy in the diagnosis of Kawasaki Disease (KD). In this case–control study nailfold capillaroscopy was performed in 31 patients with KD and 30 healthy controls. All nailfold images were evaluated for capillary distribution and capillary morphology such as enlargement, tortuosity, and dilatation of the capillaries. Abnormal capillaroscopic diameter was identified in 21 patients from the KD group and 4 patients in the control group. The most common abnormality in capillary diameter was irregular dilatation in 11 (35.4%) KD patients and in 4 people (13.3%) in the control group. Distortions of the normal capillary architecture was commonly seen in the KD group (n = 8). A positive correlation was observed between coronary involvement and abnormal capillaroscopic results (r =.65, P <.03). The sensitivity and specificity of capillaroscopy for the diagnosis of KD were 84.0% (95%CI: 63.9–95.5%) and 72.2% (95%CI: 54.8–85.8%), respectively. The PPV and NPV of capillaroscopy for KD were 67.7% (95%CI: 48.6–83.3) and 86.7% (95% CI: 69.3–96.2), respectively. Capillary alterations are more common in KD patients compared to control group. Thus, nailfold capillaroscopy can be useful in detecting these alterations. Capillaroscopy is a sensitive test for detecting capillary alternations in KD patients. It could be used as a feasible diagnostic modality for evaluating microvascular damage in KD. [ABSTRACT FROM AUTHOR]

• Del-1 is an extracellular glycoprotein which is known to play a role in regulation of inflammation. • Antibodies to Del-1 are implicated to have a role in multisystem inflammatory conditions such as Kawasaki disease. • There is an increased autoimmune response to Del-1 in Kawasaki disease, although it is comparable to other febrile illnesses. • Lower levels of autoantibodies against Del-1 correlate to the presence of coronary aneurysms in children with Kawasaki disease. • Del-1 autoantibody levels could be used to predict the presence of coronary aneurysms if developed into a point of care test. Kawasaki disease (KD), a rare multisystem inflammatory condition that predominantly affects children under six years of age, is the leading cause of childhood-acquired heart disease in developed countries. The pathogenesis is unknown, but studies support that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to Del-1 (also known as EDIL3) in children with KD. Del-1 is an extracellular matrix protein that is expressed both in macrophages and vascular endothelium. Del-1 has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against DEL-1 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not overall higher in children with KD. Elevation in Post-IVIG samples in comparison to pre-IVIG and convalescent samples supports the commonality of anti-Del-1 antibodies. Autoantibodies were notably lower in children with KD who had coronary Z score elevations in comparison to those who did not. [ABSTRACT FROM AUTHOR]

Three patients, aged 2 years 0 months, 2 years 2 months, and 6 years 1 month at the time of plain old balloon angioplasty (POBA), developed an aneurysm in the left anterior descending coronary branch after suffering from Kawasaki disease. POBA was subsequently performed due to 99 % stenosis proximal to the aneurysm. There was no restenosis within a few years after percutaneous coronary intervention, and there was no evidence of ischemia, although 75 % restenosis occurred in two patients after 7 years. Although calcified lesions are more likely to occur 6 years after the onset of Kawasaki disease, none of the patients in this study had calcified lesions within 4 years of Kawasaki disease onset, and good results were obtained with POBA alone. POBA can be safely performed in children and is an effective treatment for improving myocardial ischemia if calcification has not progressed. Plain old balloon angioplasty (POBA) can be performed effectively and safely for Kawasaki disease coronary artery stenosis in early childhood if calcification is minimal, with little restenosis for at least several years. POBA is a useful tool in the treatment of coronary artery stenosis in early childhood. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is the leading cause of acquired heart disease. The cardiac clinical features seen with KD require diagnosis and treatment within 10 days of symptoms to decrease the risk of complications. This case report examines the complexity of prolonged fever in a pediatric patient with a positive test for severe acute respiratory coronavirus 2 and meets the KD criteria. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the differences in the clinical characteristics of Kawasaki disease between older and younger children.Study Design: This retrospective study examined 405 children with Kawasaki disease admitted to Showa University Northern Yokohama Hospital between 2015 and 2019.Results: Eligible patients were classified into the older (≥3.0 years of age, n = 169) and younger (<3.0 years of age, n = 236) groups. Skin rash was found in significantly fewer cases (112 [66.3%] vs 229 [97.0%], P < .001 in the younger group). Cervical lymphadenopathy was more common in older children (153 [90.5%] vs 165 [69.9%], P < .001) and in incomplete Kawasaki disease (3 or 4 findings) (34 [20.1%] vs 25 [10.6%], P = .0078). The diagnosis was more delayed in older children (median: 5.0 days vs 4.0 days, P = .003) than the younger group. Additionally, fever nonresponsive to a single intravenous immunoglobulin was more common, and the duration of fever was significantly longer in the older group (48 [28.4%] vs 47 [19.9%], P = .0479).Conclusions: Kawasaki disease should be suspected in children aged >3.0 years with cervical lymphadenopathy and fever, despite the absence of skin rash. Additionally, incomplete Kawasaki disease, fever unresolved by a single intravenous immunoglobulin infusion, and the tendency to delay treatment initiation are more common in children aged >3.0 years. [ABSTRACT FROM AUTHOR]

Coronary thrombosis is a common cardiovascular complication of Kawasaki disease (KD), which seriously affects the long-term therapeutic effect of KD. The purpose was to determine the incidence and timing of coronary thrombosis and to identify risk factors for coronary thrombosis in KD with giant coronary artery aneurysm (GCAA). A total of 94 consecutive KD patients with GCAA from Children's Hospital Affiliated to Chongqing Medical University were enrolled retrospectively. The cumulative incidence of coronary thrombosis in KD patients with GCAA was 59 % (n = 54). Coronary thrombosis mainly occurred in the acute phase (n = 41/54, 76 %), with a median time of 16 days after onset. Cox regression analysis was used to identify risk factors for coronary thrombosis. Cox regression analysis indicated that male (hazard ratios, 1.87; 95 % CI, 1.01–3.44; P = 0.43), left anterior descending artery (LAD) involvement (hazard ratios, 3.75; 95 % CI, 1.85–7.39; P < 0.001), coronary absolute diameter ≥ 8 mm (hazard ratios, 2.93; 95 % CI, 1.36–6.29; P = 0.006) constituted a higher risk of coronary thrombosis after adjusting for confounders. Kaplan-Meier method showed the cumulative incidence for coronary thrombosis in KD patients with GCAA was 79 %, 92 %, and 88 % in male, LAD involvement, coronary absolute diameter > 8 mm, respectively. Male, LAD involvement, and coronary absolute diameter ≥ 8 mm were associated with a high incidence of coronary thrombosis. Based on the analysis of the incidence, time and risk factors of coronary thrombosis in different periods, this study may provide an essential reference for thromboprophylaxis management of KD with GCAA. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a kind of pediatric vasculitis, whose pathogenesis has not been elucidated until now. Many scholars believe that KD is one type of infectious diseases in the susceptible groups. However, no recognized pathogens are confirmed. Human cytomegalovirus (HCMV) is a ubiquitous human herpes virus, which can infect varieties of cells including endothelial cells. Studies reported that the viral protein pUL135 is very important for virus replication, reactivation and immune escape. Therefore, we hypothesize that HCMV pUL135 may have a pathogenic effect on KD. We first determined pUL135 levels in the serum from KD patients. Next, we examined the effects and mechanisms of pUL135 on endothelial cell proliferation and migration. Finally, we assessed the effect of pUL135 on cardiac inflammation in a KD murine model. Data showed that pUL135 level was significantly increased in the serum from KD patients compared with the healthy and fever controls. And pUL135 expression in endothelial cells remarkably inhibited cell proliferation, migration and tube formation. Moreover, expression of pUL135 obviously affected actin cytoskeleton. Mechanism investigation substantiated that pUL135 mediated endothelial cell dysfunction via regulating CD2AP. Ultimately, we found that HCMV pUL135 aggravated coronary arteritis in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. Our findings imply that HCMV pUL135-mediated endothelial dysfunction plays an important role in exacerbating coronary artery injury in KD conditions. • HCMV pUL135 aggravated coronary arteritis in the KD mouse model. • HCMV pUL135 inhibited endothelial cell proliferation and migration. • HCMV pUL135 exerted its function via CD2AP. • Our new findings suggest that circulating HCMV pUL135 may be a sensitive predictor for coronary artery injury in KD patients. [ABSTRACT FROM AUTHOR]

Background: Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants (DOAC) in children.Objectives: The investigators aimed to obtain safety and efficacy data for edoxaban in children.Methods: We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years old with cardiac disease (ENNOBLE-ATE). Patients were randomized 2:1 to age- and weight-based oral edoxaban once-daily versus SOC for 3 months (main study period), stratified by cardiac diagnosis Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis.Results: The modified intention to treat cohort included 167 children. One patient per group experienced a non-major CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51/109) with edoxaban and 41.4% (24/58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, one CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2/33 KD patients with coronary artery thromboses and/or myocardial infarctions).Conclusion: Edoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. [ABSTRACT FROM AUTHOR]

Les vascularites primitives de l'enfant sont des maladies inflammatoires rares touchant les vaisseaux sanguins et pouvant se compliquer d'ischémie, voire de nécrose de certains organes. Elles constituent un véritable défi diagnostique et thérapeutique pour les pédiatres. À l'échelle mondiale, les vascularites les plus fréquentes de l'enfant sont la vascularite à IgA et la maladie de Kawasaki, mais dont les complications peuvent être sévères. Les autres vascularites de l'enfant, telles que la péri-artérite noueuse, l'artérite de Takayasu, les vascularites à ANCA, ou encore la maladie de Behçet, sont rares mais potentiellement graves. L'examen clinique minutieux et complet est une des clés du diagnostic. En effet, la précocité de la prise en charge thérapeutique est essentielle car le pronostic vital peut être engagé et le risque de séquelles à long terme conséquent. Un certain nombre de diagnostics différentiels doivent être évoqués, notamment en cas de début précoce avant l'âge de 1 an. Cet article propose un état des lieux des différentes vascularites de l'enfant et une démarche diagnostique clinique et paraclinique pour guider le clinicien. Primary childhood vasculitis are a real diagnostic and therapeutic challenge for pediatricians. Some vasculitis are quite common, while others are much rarer compared to adults. Worldwide, the most common vasculitis in children are IgA vasculitis and Kawasaki disease, which are usually self-limited although children may develop severe complications. Other vasculitis in children, such as polyarteritis nodosa, Takayasu arteritis, ANCA vasculitis, and Behçet disease, are rare but may be life-threatening. A careful clinical examination is a key for diagnosis. Indeed, early treatment is essential, regarding the high risk of long-term damages. Differential diagnosis must be considered, especially in the case of early onset, before the age of 1 year. This article provides an overview of vasculitis main features in children, and may help the clinician to an early diagnosis. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a medium vessel vasculitis and is the most common cause of acquired heart disease in childhood. If left untreated, KD leads to coronary artery aneurysms in 15–25% of patients and the mortality rate in the UK is currently 0.4%. As such, KD is an important preventable cause of heart disease in the young. The aetiology of KD remains unknown, but most likely it represents an aberrant inflammatory host response to one or more as yet unidentified immunological trigger(s) in genetically predisposed individuals. The purpose of this article is not to provide an exhaustive review of KD. Rather we provide practical guidance to the clinical approach to refractory KD. Only brief background on the pathogenesis and epidemiology of KD, and emerging newer clinical trials is provided, to place our clinical approach in context. [ABSTRACT FROM AUTHOR]

• Involvement of immunosuppressive receptors in the pathogenesis of Kawasaki disease. • Peripheral CD4+ and CD8+ T cells differ in their expression between patients and controls. • The expression of peripheral neutrophils differed between patients and controls. • Peripheral neutrophils in subgroups of patients with complications differ in their expression. • New potential biomarkers for Kawasaki disease and coronary artery aneurysms were discovered. To elucidate the relationship between leukocyte-associated Ig-like receptor-1 (LAIR-1) and the pathogenesis of Kawasaki disease (KD) and coronary artery aneurysms(CAA). The study cohort comprises children who were diagnosed with KD and were categorized into two groups: KD patients with CAA (KD-CAA) and KD without CAA (KD-NCAA), with healthy children serving as control group (HC). LAIR-1 on leukocytes was examined via flow cytometry, while serum LAIR-1 (sLAIR-1) was quantified using ELISA. IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-α, IFN-γ and TNF-α were examined by Immunofluorescence assay. sLAIR-1 levels were elevated in the KD and KD-CAA groups compared with those in the HC and KD-NCAA groups (P < 0.05). sLAIR-1 exhibited an area under the curve value of 0.858 for predicting KD (P < 0.001) and 0.628 for predicting CAA (P = 0.055, borderline significance). LAIR-1 was increased on the neutrophils in KD group, whereas it was lower in KD-CAA than that in KD-NCAA, and decreased in KD after IVIG treatment. In contrast, LAIR-1 was reduced on CD4+ and CD8+ T lymphocyte in KD group, and increased in KD after IVIG treatment (all P < 0.05). LAIR-1 on neutrophils showed a positive correlation with IL-5, while on CD4+ T cells, it was negatively correlated with IL-2, IL-6, IL-10, IFN-γ, and IL-8. On CD8+ T cells, LAIR-1 was negatively correlated with IL-2 and IFN-γ. sLAIR-1 may serve as a potential biomarker for KD and CAAs, while LAIR-1 might be implicated in KD pathogenesis and CAA. [ABSTRACT FROM AUTHOR]

• KD is a vasculitis that mainly affects children under 5 years of age. • Etiopathogenesis is still not clear, but it is thought to be a complex interplay of genetic factors, infections and immunity. • Cardiac complications are rare, but thrombosis of the coronary artery may occur, causing vascular occlusion and subsequent myocardial ischemia. • Cases of association of KD with lymphoma have not been still reported. Coronary artery vasculitis is a rare pathological condition and is often a manifestation of systemic vasculitis, such as Polyarteritis Nodosa, Kawasaki Disease, Takayasu Arteritis, and Giant Cell Arteritis, with Kawasaki Disease being the most common cause in children. We present the autopsy case of a 6-year-old boy with classic Hodgkin lymphoma who died of sudden cardiac death due to thrombosis caused by vasculitis, which exclusively affected the coronary arteries and was suggestive of Kawasaki Disease. To further investigate the histological features of Kawasaki Disease across all age groups, we conducted a literature review using the search terms "Kawasaki AND vasculitis AND histopathology" and "Kawasaki vasculitis histopathology" in Scopus, Google Scholar, and PubMed, covering the period from 1967 to 2023. The inclusion criteria were as follows: coronary histology (inflammation and/or aneurysm and/or thrombosis), postmortem studies, English language, free articles, all age groups, case reports, and case series. [Display omitted] [ABSTRACT FROM AUTHOR]

• DIA-MS based proteomics was conducted using plasma samples to investigate novel biomarkers in KD patients associated with CALs. • Candidate biomarkers were validated with an independent set of samples via ELISA. • Plasma SERPINE1 was identified as a new potential predictive biomarker for CALs in KD patients. • SERPINE1 was also upregulated in the heart tissues of CAWS-induced KD mice and KD plasma, or TNF-α-stimulated HCAECs. Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Coronary artery lesions (CALs) are serious complications of KD that can result in stenosis and thrombosis, but the specific underlying pathogenic mechanisms have not been elucidated. Therefore, exploring biomarkers to help predict early CALs is urgently needed for clinical treatment. Patients were recruited from three independent cohorts. In the discovery cohort, Data-Independent Acquisition Mass Spectrometry (DIA-MS) was performed to screen plasma proteins from healthy controls (HCs), KD patients prior to intravenous immunoglobulin (IVIG) treatment, and KD patients post-IVIG treatment. KD patients were further divided into KD patients without CALs (nCAL) and with CALs (CALs) groups. Bioinformatic analysis was carried out for the differentially expressed proteins (DEPs) and hub proteins. Candidate proteins were quantified by enzyme-linked immunosorbent assay (ELISA) in the validation cohort 1 and 2. Furthermore, candida albicans cell wall extract (CAWS)-induced KD vasculitis mice and cell models were established to investigate the expression of biomarkers identified in the aforementioned clinical cohort. According to the quantitative proteomics analysis, SERPINE1 was significantly increased in KD patients with CALs. Receiver operating characteristic curves (ROC) revealed that plasma SERPINE1 exhibited greater ability in predicting CALs (AUC = 0.824, P < 0.0001). After IVIG treatment, the concentrations of SERPINE1 in the nCALs group significantly decreased. However, the concentration of SERPINE1 remained persistently elevated in the CALs group. Moreover, the expression of SERPINE1 was significantly upregulated in the heart tissue of KD mice, KD plasma, or tumor necrosis factor-α (TNF-α)-stimulated human coronary artery endothelial cells (HCAECs). Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients. [ABSTRACT FROM AUTHOR]

• Syk is involved in the development of the CAWS vasculitis. • Syk inhibitors suppress the development of CAWS vasculitis. • Low dose-CAWS evokes vasculitis that is smaller and less frequent than of high dose. The activation of innate immunity may be involved in the development of Candida albicans -induced murine vasculitis, which resembles Kawasaki disease (KD) vasculitis. This study aimed to histologically clarify the time course of the development of vasculitis in this model in detail and to estimate the potential role of spleen tyrosine kinase (Syk) inhibitors in KD vasculitis. DBA/2 male mice were intraperitoneally injected with a vasculitis-inducing substance and treated with a Syk inhibitor (R788 or GS-9973). Systemic vasculitis, especially in the aortic annulus area, was histologically evaluated. Regarding lesions in the aortic annulus area, some mice in the untreated control group already showed initiation of vasculitis 1 day after the final injection of a vasculitis-inducing substance. The vasculitis expanded over time. Inflammation occurred more frequently at the aortic root than at the coronary artery. The distribution of inflammatory cells was limited to the intima, intima plus adventitia, or all layers. In the Syk inhibitor-treated groups, only one mouse had vasculitis at all observation periods. The severity and area of the vasculitis were reduced by both Syk inhibitors. Candida albicans -induced murine vasculitis may occur within 1 day after the injection of a vasculitis-inducing substance. Additionally, Syk inhibitors suppress murine vasculitis. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) patients are at risk of developing the serious complication of coronary artery dilation (CAD). To diagnose CAD caused by KD, various Z -Score formulas are used worldwide. This paper aims to evaluate the differences and inclusiveness among the six most commonly used Z -Score formulas in diagnosing CAD in Suzhou, China. Additionally, the study seeks to compare the differences in CAD diagnosis among different high-risk factor groups. By doing so, this research provides a valuable reference for accurately diagnosing CAD in KD patients. This paper presents a retrospective analysis of 1509 patients diagnosed with KD at the Children's Hospital of Soochow University between January 2018 and December 2020. We collected the patients' clinical and echocardiographic data and used six Z -Score formulas (Kobayashi et al., de Zorzi et al., Kurotobi et al., McCrindle et al., Olivieri et al., and Dallaire et al.) to diagnose the degree of CAD in different segments. We then compared the diagnostic differences and inclusiveness of these formulas, especially the diagnostic differences in medium to giant CAA. To achieve this, we divided the patients into groups based on their age (≤12 months, 13–30 months, and > 30 months) and fever duration (≤5 days, 6–7 days, 8–9 days, and ≥ 10 days). Using the McNemar test and the Kappa test, we compared the differences and the consistencies of CDA diagnosis among the six Z -Score formulas. Moreover, we used the Friedman test and Chi-square segmentation formula to compare the differences in age and number of fever duration between groups and to compare each Z -Score formula pair within the group. Except for the LMCA segment, where there were no statistically significant differences between de Zorzi formula and McCrindle formula, the Z -score formulas showed statistically significant differences in the degree of CAD diagnosis across all other segments. Inclusiveness assessment revealed that Kobayashi formula and Dallaire formula showed significantly higher rates of dilatation (6.58% and 5.32%), or of small aneurysms (6.52% and 4.52%) compared to other formulas (1.0%–1.73%). Medium aneurysms were also more likely to be identified with Kobayashi and Dallaire formulas (0.8% and 0.8%) compared to the remaining formulas (0.13–0.40%). There are significant differences in the diagnoses of medium to giant CAA made by these six formulas in LAD and RCA. The longer the duration of fever and the younger the age, the higher the diagnosis rates of CAD and CAA. There were no statistically significant differences between de Zorzi formula and McCrindle formula, de Zorzi formula and Oliveri formula, and Kurotobi formula and Dallaire formula within the four groups based on the duration of fever. Similarly, there were no statistically significant differences between Kobayashi formula and Dallaire formula, and between de Zorzi formula and Oliveri formula in the age groups of ≤12 months and 13–30 months. There are diagnostic differences among these six Z -score formulas, considering the aforementioned statistics. Kobayashi formula and Dallaire formula are more inclusive, and less likely to under-diagnose significant CAD. They perform evenly for dilatation only, for small aneurysms and the median size aneurysms, and that is for segments of LMCA, LAD and RCA. In addition, McCrindle formula joins the "inclusive" pack for LAD and RCA in the matter of CAD. The younger the age of the patients and the longer the duration of fever, the higher the diagnosis rates of CAD and CAA. Furthermore, the younger the age of the patients and the shorter the duration of fever, the greater the differences between the various formulas. • The 6 Z-Score formulas show diagnostic differences. • We compared the diagnostic differences among 6 Z-Score formulas regarding medium to giant CAA. • Younger children with shorter fever have greater differences in 6 Z-Score formulas. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The cause remains unknown; however, epidemiologic and demographic data support a single preceding infectious agent may lead to KD. A variety of pathophysiologic responses have been proposed, including direct invasion of the coronary arteries, a superantigen response, and a post-infectious autoimmune phenomenon. A role for B cell responses during KD are supported by numerous findings including B cell specific markers identified in genome wide association studies. We have recently published data showing children with KD have similar plasmablast (PB) responses to children with infections. Since during other infections, cells expressing antibodies against the preceding infection are enriched in PBs, we sought to explore the specific antibodies encoded by PBs during KD. In one child we see a massive expansion in IGHV4–34 utilizing antibodies, which has been associated with autoimmunity in the past. We further explored this expansion of IGHV4–34 utilization during the peripheral PB rise with next generation sequencing (NGS) analysis and utilizing newer techniques of chromium chip single cell separation (10x Genomics®). We also utilized peptide array screening to attempt to identify an antigen to the most prolific clones. [Display omitted] • Clonal expansion of near germline use of IGHV4-34 plasmablasts in a child with KD. • Expansion and class switching of IGHV4-34 clones consistent with foreign antigen targeting. • Child lacked clinical signs of typical autoimmunity associated with IGHV4-34. • IGHV4-34 monoclonal antibody representing most common clonal expansion showed no specific linear antigen targeting. [ABSTRACT FROM AUTHOR]

Kawasaki syndrome (KS) is a systemic vasculitis of unknown etiology that affects medium and small blood vessels. The aim of our study is to analyze coronary artery lesions in children with KS and their risk factors. All children under the age of 15 years-old presenting KS and admitted in the pediatric department of three university hospital (Sahloul hospital, and Farhat Hached hospital of Sousse, Ibn El Jazzar hospital of Kairoun) from January 2000 to December 2018 were included. Sixty-five patients were included in our study. The mean age at diagnosis was of 29.9 months [2-120 months] and the sex ratio was of 1.7. Echocardiography was performed in all patients. It showed coronary dilation in 37% of patients with coronary artery diameter of 4.2 mm on average [3.2-7mm]. The coronary aneurysm was small in 19 cases and medium in 5 cases. No giant aneurysm has been identified. In univariate analysis, the predictors of coronary artery lesions were male sex, atypical form, fever duration more than 10 days, hepatic cytolysis, thrombocytosis and anemia. In multivariate analysis, only the last four parameters were the predictive factors of the coronary artery involvement. Several risk factors can be used to determine which children are predisposed to develop coronary dilations. In case of patient with risk factors, intravenous immunoglobulins should be initiated early to avoid these serious complications. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a form of systemic vasculitis that primarily affects children under the age of 5 years old. Antibiotics are often prescribed for KD patients even before a diagnosis is made due to their prolonged fever and elevated inflammatory markers. Therefore, the purpose of this study was to investigate the impact of antibiotics usage on the disease outcome of KD. We carried out a retrospective chart review of children between 2005 and 2017 for initial immunoglobulin (IVIG) treatment of KD. KD children with initial IVIG treatment more than 10 days after the onset of symptoms were excluded. In total, 280 children were eligible for this study, among which 209 had been treated with antibiotic(s) and 71 had not been. The IVIG resistance rates were 5.6% (4/71), 8.9% (10/112), and 21.6% (21/97) in non-users, single-drug users, and multiple-drug users, respectively (r = 0.205, p = 0.003). The IVIG resistance rate of the multiple antibiotics drug users in KD patients was significantly higher than the other two groups. Furthermore, the likelihood of IVIG resistance was found to increase with elevated C-reactive protein (CRP) values (1.010/unit, p < 0.001) but not with total white blood cell (WBC) count (p = 0.466). The probability of IVIG resistance increases with elevated CRP values and the use of multiple IV antibiotics, thus indicating that physicians should be prudent in administering multiple IV antibiotics when treating assumed infections in KD children. [ABSTRACT FROM AUTHOR]

Background/purpose: The association between dysregulated innate immune responses seen in Kawasaki disease (KD) with predisposition to Kawasaki-like multisystem inflammatory syndrome in children (MIS-C) remains unclear. We aimed to compare the innate immunity transcriptome signature between COVID-19 and KD, and to analyze the interactions of these molecules with genes known to predispose to KD.Methods: Transcriptome datasets of COVID-19 and KD cohorts (E-MTAB-9357, GSE-63881, GSE-68004) were downloaded from ArrayExpress for innate immune response analyses. Network analysis was used to determine enriched pathways of interactions.Results: Upregulations of IRAK4, IFI16, STING, STAT3, PYCARD, CASP1, IFNAR1 and CD14 genes were observed in blood cells of acute SARS-CoV-2 infections with moderate severity. In the same patient group, increased expressions of TLR2, TLR7, IRF3, and CD36 were also noted in blood drawn a few days after COVID-19 diagnosis. Elevated blood PYCARD level was associated with severe COVID-19 in adults. Similar gene expression signature except differences in TLR8, NLRP3, STING and IRF3 levels was detected in KD samples. Network analysis on innate immune genes and genes associated with KD susceptibility identified enriched pathways of interactions. Furthermore, higher expression levels of KD susceptibility genes HLA-DOB, PELI1 and FCGR2A correlated with COVID-19 of different severities.Conclusion: Our findings suggest that most enriched innate immune response pathways were shared between transcriptomes of KD and COVID-19 with moderate severity. Genetic polymorphisms associated with innate immune dysregulation and KD susceptibility, together with variants in STING and STAT3, might predict COVID-19 severity and potentially susceptibility to COVID-19 related MIS-C. [ABSTRACT FROM AUTHOR]

The case of a 14-year-old girl with acute myocardial infarction due to coronary artery aneurysms (CAAs) of unknown origin, which resembled coronary artery lesions caused by Kawasaki disease, is reported. She was transferred to our hospital due to chest pain with ST-T elevation. She had no history of Kawasaki disease. On the first admission, she was misdiagnosed with acute myocarditis. Then, 54 days later, she experienced chest pain with exertional dyspnea. Her electrocardiogram showed negative T waves in the chest leads. A CAA of the left coronary artery was suspected on two-dimensional echocardiography. Coronary angiograms showed 90% stenosis and multiple CAAs of the left anterior descending artery and the bifurcation of the left coronary artery. Both the right coronary artery and left circumflex artery were occluded. A left ventriculogram showed dyskinesis and an aneurysm at the apex. She underwent triple-vessel coronary artery bypass grafting, and her symptoms improved. In addition, an intracranial aneurysm was also found on cerebral angiography. There were no specific laboratory findings other than SS-A antibodies. It was suspected that the weakness of the vessels was related to the disease. It may have been a different disease that was never previously detected, but her CAAs were Kawasaki-like CAAs. < Learning objective: A timely precise diagnosis of acute myocardial infarction is unlikely to be made in children because they are rare. The present patient was initially misdiagnosed as having acute myocarditis, because the coronary arteries could not be detected by two-dimensional echocardiography. Either computed tomographic angiography or magnetic resonance angiography is recommended in patients with ST-T abnormalities on the electrocardiogram if it is difficult to identify the coronary arteries. In this case, the patient had a rare coronary artery disease in which the cause of the coronary artery aneurysms was unknown. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is a newly recognized condition affecting children with recent infection or exposure to coronavirus disease 2019 (COVID-19). MIS-C has symptoms that affect multiple organs systems, with some clinical features resembling Kawasaki disease (KD) and toxic shock syndrome (TSS).Objective Of the Review: Our goal was to review the current literature and describe the evaluation and treatment algorithms for children suspected of having MIS-C who present to the emergency department.Discussion: MIS-C has a wide clinical spectrum and diagnosis is based on a combination of both clinical and laboratory findings. The exact mechanism of immune dysregulation of MIS-C is not well understood. Physical findings may evolve and do not necessarily appear at the same time. Gastrointestinal, cardiac, inflammatory, and coagulopathy manifestations and dysfunction are seen frequently in MIS-C.Conclusions: The diagnosis of MIS-C is based on clinical presentation and specific laboratory findings. In the emergency setting, a high level of suspicion for MIS-C is required in patients exposed to COVID-19. Early diagnosis and prompt initiation of therapy offer the best chance for optimal outcomes. [ABSTRACT FROM AUTHOR]

We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years. [ABSTRACT FROM AUTHOR]

American Heart Association (AHA) guidelines for management of Kawasaki disease (KD) rely on coronary artery (CA) z-scores from echocardiograms. Compared with echocardiography, cardiac CT (CCT) offers better visualization of distal segments and evaluation for thrombosis and stenosis. Despite increasing use of CCT in KD, CA z-scores for CCT are not available and measurement concordance between imaging modalities is a critical knowledge gap. We retrospectively reviewed KD patients with CA aneurysms who had concurrent echocardiography and CCT between 2016 and 2020. Patients were included if they had history of CA z-scores of ≥3 on echocardiography during their clinical course. Agreement between CCT and echocardiography was assessed using Bland-Altman analysis. Paired CCT and echocardiography studies were available in 18 patients (21 studies). The largest CA aneurysms were large/giant (z-score ≥10) in 14 studies, medium (z-score ≥5, <10) in 3 studies, and small (z score ≥2.5, <5) in 2 studies. Intra- and inter-observer reliability for CCT measurements were high for all CA segments (ICC 99.7% and 98.6%). For the LMCA, proximal LAD and proximal and distal RCA there was high correlation between echocardiogram and CCT absolute measurements with wider variation between modalities for the distal LAD and circumflex. Overall, CCT measurements tended to be smaller than echocardiogram measurements, and led to a lower AHA z-score risk classification in 24% of studies. CCT and echocardiography have high agreement for absolute measurements of proximal CA segments, but more measurement discrepancy exists for distal CA segments with bias toward lower dimensions on CCT. [ABSTRACT FROM AUTHOR]

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Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) with coronary artery aneurysms (complex KD) presents relentless challenges for families. Psychosocial experiences and needs were explored. A descriptive, exploratory study of adolescents and parents using a needs survey and psychosocial instruments (anxiety, depression, and functional impairment). Fifty-one parents and 38 adolescents participated. Predominant interests were for information sheets, newsletters, Web sites, and phone applications. Gaps in disease-specific knowledge and awareness of coronary artery aneurysms between parents and adolescents were identified. Psychosocial concerns for adolescents included symptoms of anxiety (22%), depression (13%), and functional impairment (22%). Multivariable analyses indicated higher depression scores associated with longer travel distance from specialists (p =.04). Parent-reported social concerns for their adolescent were associated with higher anxiety (p =.005) and functional impairment (p =.005). Written commentary complemented the findings. Care protocols require psychosocial assessment/referral and the use of virtual platforms. The groundwork was laid for developing patient and family-centered strategies. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a form of self-limiting vasculitis that causes coronary artery abnormalities in children. Although clinical trials of monoclonal antibodies and anti-cytokine biologics that block cytokine cascades have been conducted, the studies have revealed contradictory results. To examine the effectiveness of treatment with monoclonal antibodies and anti-cytokine biologics for KD patients, we conducted this systematic review and meta-analysis. Relevant randomized controlled trials (RCTs) and observational studies (e.g., cohort studies, case-control studies, case-series, and case-reports) were included to summarize available evidence, both qualitatively and quantitatively. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ICUSHI were used for systematic research. Meta-analysis of the included studies was conducted using fixed-effect or random-effects models, depending on the degree of between-study heterogeneity. We assessed coronary artery and treatment outcomes of the interventions. The certainty of evidence and risk of bias were assessed using the GRADE and Cochrane risk of bias tool. The protocol of this review is registered with PROSPERO (CRD42016033079). Results: Of all searched studies, 183 studies were qualitatively analyzed. We finally included four randomized controlled trials with 456 patients in quantitative syntheses. Monoclonal antibodies and anti-cytokine biologics did not reduce the frequency of CAA (risk ratio [RR], 0.93; 95% confidence interval [95%CI], 0.65 to 1.32, low certainty of evidence), compared with the conventional treatment with IVIG. However, the frequency of treatment resistance (RR, 0.60; 95%CI, 0.38 to 0.95, moderate certainty of evidence) was reduced by the antibodies. We found no statistical differences in either "any adverse event" (RR, 0.92; 95%CI, 0.80 to 1.06, low certainty of evidence) or "adverse events attributable to the administration of the medication" (RR, 1.10; 95%CI, 0.72 to 1.69, low certainty of evidence) between the two groups. Conclusions: Although monoclonal antibodies and anti-cytokine biologics were not effective in reducing the frequency of CAA in KD patients, the frequency of treatment resistance might be reduced by those agents compared with conventional IVIG therapy alone. [Display omitted] [ABSTRACT FROM AUTHOR]

• The optimal timing of vaccination after IVIG therapy is unclear. • Vaccination 6 months after IVIG therapy produced a low serological response. • However, booster vaccination at 12 months achieved acquired immunity. Due to the presence of maternal passive antibodies, the measles vaccine is ineffective if administered before age 12–15 months. The optimal timing for administering a live attenuated vaccine (LAV) after intravenous immunoglobulin therapy (IVIG) for Kawasaki disease (KD) has not been fully investigated. The recommended interval between vaccination and IVIG therapy for KD differs by country. The present study aimed to evaluate efficacy of LAV six months after IVIG therapy for KD in Japan. The present, single-arm, prospective, interventional study included patients aged 6 months or older with no medical history of measles, rubella, varicella or mumps or vaccinations against these diseases. The subjects received these vaccinations for the first time at six months after IVIG therapy. Virus-specific IgG levels for each virus measured by EIA was examined at nine months after IVIG therapy. If the results were negative, the subjects received a booster vaccination at 12 months after IVIG therapy. The primary outcome was the prevalence of positivity for antibodies after the initial and booster vaccinations. The present study enrolled 32 subjects, 31% of whom were female, with an average age of 10.8 (standard deviation 2.8) months at IVIG therapy. At six months after IVIG therapy, 9% and 6% of the subjects were seropositive for measles and varicella titers, respectively, but were seronegative for the mumps and rubella titers. The seroconversion rate for measles, mumps, rubella, and varicella after the initial vaccination was 88%, 6%, 78%, and 16%, respectively. The seroconversion rate after a booster vaccination was 100% for measles and rubella, 97% for mumps, and 77% for varicella. The seroconversion rate was low for LAV at six months after a single dose of IVIG for KD, but seroconversion was achievable with a booster vaccination at 12 months. Clinical Trial Registration: UMIN-CTR, UMIN000007174, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000008452. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) incidence is increasing in Ontario. Cardiovascular sequelae following KD are well-described. However, there are limited data on non-cardiovascular outcomes. To determine the risk of hearing loss, anxiety, developmental disorders, intellectual disabilities and attention-deficit/hyperactivity disorder (ADHD) among KD survivors vs. non-exposed children. We included all Ontario children (≤18 yr) surviving hospitalization with a KD diagnosis between 1995 and 2018, using population-based health administrative databases. We excluded children with prior KD diagnoses and non-residents. KD cases were matched with 100 non-exposed children by age, sex and year. Follow-up continued until death or March 2019. We calculated the prevalence, incidence and adjusted hazard ratios (aHR [95%CI]) of outcomes between 0–1 yr, 1–5 yr, 5–10 yr and >10 yr follow-up. Among 4597 KD survivors, 364 (7.9%) were diagnosed with hearing loss, 1213 (26.4%) anxiety disorders, 398 (8.7%) developmental disorders, 51 (1.1%) intellectual disability and 21 (0.5%) ADHD, during median 11 year follow-up. Compared to 459,700 non-exposed children, KD survivors were not at increased risk of hearing loss after adjustment for potential confounders. KD survivors were at increased risk of anxiety disorders between 0–1 yr (aHR 1.75 [1.46–2.10]), 1–5 yr (aHR 1.13 [1.01–1.28]), 5–10 yr (aHR 1.14 [1.03–1.28]) and >10 yr (aHR 1.11 [1.02–1.22]); developmental disorders between 0–1 yr (aHR 1.49 [1.28–1.74]) and 1–5 yr (aHR 1.19 [1.02–1.40]); intellectual disabilities >10 yr (aHR 2.36 [1.36–4.10]); and ADHD >10 yr (aHR 2.01 [1.14–3.57]). KD survivors are at increased risk of being diagnosed with anxiety disorders sooner, being diagnosed with developmental disorders between 0 and 5 yr and being diagnosed with intellectual disabilities or ADHD >10 yr after KD diagnosis. This may justify enhanced developmental and audiological surveillance of KD survivors. [ABSTRACT FROM AUTHOR]

Aim: To describe the contemporary experience of Kawasaki Disease (KD) in a tertiary paediatric hospital.Methods: This was a retrospective analysis of admissions with suspected/confirmed KD to John Hunter Children's Hospital from 1 January 2015 to 31 December 2016, with follow-up. Patients were stratified into classical, incomplete, unlikely and uncertain KD cohorts based on the 2004 American Heart Association (AHA) guidelines.Results: Forty (40) patients had 45 admissions with suspected KD. Twenty-four (24) patients (60%) had complete and incomplete KD. Twenty-nine per cent (29%) (7/24) were not diagnosed at presentation. Thirty per cent (30%) (12/40) were incompletely assessed according to the AHA pathway. Seventy-one per cent (71%) of KD patients (17/24) were treated with aspirin and intravenous immunoglobulin. The incidence was 22-26 per 100,000 in children less than 5 years during the study period, higher compared to prior data.Conclusion: The diagnosis of KD remains challenging, with some children not diagnosed at the time of initial presentation. The increase in KD incidence is hypothesis generating and requires further investigation. [ABSTRACT FROM AUTHOR]

• A useful dynamic nomogram was developed for predicting IVIG resistance in Kawasaki disease patients in Shanghai. • The dynamic nomogram was built based on immunoinflammatory markers detected on patient admission. • Machine learning algorithms were used to screen predictors to build a predictive model. • The nomogram combining six immunoinflammatory markers reliably predicted IVIG-resistant KD. • It is worthwhile to explore the in-depth mechanisms of CD3, CD19, and IgM in the nomogram which are rarely researched in other studies. Approximately 10–20% of Kawasaki disease (KD) patients suffer from intravenous immunoglobulin (IVIG) resistance, placing them at higher risk of developing coronary artery aneurysms. Therefore, we aimed to construct an IVIG resistance prediction tool for children with KD in Shanghai, China. Retrospective analysis was conducted on data from 1271 patients diagnosed with KD and the patients were randomly divided into a training set and a validation set in a 2:1 ratio. Machine learning algorithms were employed to identify important predictors associated with IVIG resistance and to build a predictive model. The best-performing model was used to construct a dynamic nomogram. Moreover, receiver operating characteristic curves, calibration plots, and decision-curve analysis were utilized to measure the discriminatory power, accuracy, and clinical utility of the nomogram. Six variables were identified as important predictors, including C-reactive protein, neutrophil ratio, procalcitonin, CD3 ratio, CD19 count, and IgM level. A dynamic nomogram constructed with these factors was available at https://hktk.shinyapps.io/dynnomapp/. The nomogram demonstrated good diagnostic performance in the training and validation sets (area under the receiver operating characteristic curve = 0.816 and 0.800, respectively). Moreover, the calibration curves and decision curves analysis indicated that the nomogram showed good consistency between predicted and actual outcomes and had good clinical benefits. A web-based dynamic nomogram for IVIG resistance was constructed with good predictive performance, which can be used as a practical approach for early screening to assist physicians in personalizing the treatment of KD patients in Shanghai. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD), an acute exanthematous febrile pediatric illness involving systemic non-specific inflammatory reactions in small- and medium-sized arteries, poses a significant risk of coronary artery and myocardial inflammatory injury. Developing new KD treatments with improved safety and fewer side-effects is highly desirable. Forsythoside B (FTS-B), extracted from the Forsythia suspensa plant, exerts anti-inflammatory activity by inhibiting NF-κB, which is regulated by SIRT1, the reduced expression of which is strongly associated with cardiovascular disease. However, it has yet to be established whether FTS-B influences KD-related inflammatory damage. In this study, we investigated the effects of FTS-B on inflammation in cellular and murine models of KD. Our findings revealed that KD is associated with cardiac dysfunction and inflammatory injury to myocardial and human coronary artery endothelial cells (HCAECs), resulting in a pyroptosis-feedback loop. Both cellular and KD models were characterized by reduced SIRT1 expression and increased NF-κB p65 expression. Contrastingly, the rates of pyroptosis in both murine model myocardial tissues and HCAECs were significantly alleviated in response to FTS-B treatment. Also in both models, we detected an increase of SIRT1 expression and a decrease in the expression of p65. Further examination of the protective mechanism of FTS-B using the SIRT1-specific inhibitor, EX 527, revealed that this inhibitor blocked the palliative effects of FTS-B on inflammatory injury-induced pyroptosis. These results highlight the potential utility of the SIRT1–NF-κB–p65 pathway as a therapeutic target for KD treatment and demonstrate that FTS-B can alleviate KD-induced cardiac and HCAEC inflammatory injury via inhibition of pyroptosis. • Kawasaki disease (KD)-induced coronary inflammation and cardiac injury causes pyroptosis. • FTS-B alleviates HCAEC inflammatory injury and KD mice coronary artery inflammation and cardiac injury. • FTS-B exerts anti-inflammatory activity by inhibiting NF-κB. • FTS-B alleviates cardiac injury via SIRT1 activation and pyroptosis inhibition. [ABSTRACT FROM AUTHOR]

• Most UK meningococcal B vaccination is co-administered in the national immunisation programme. • Seizures, febrile seizures, Kawasaki disease are uncommon after this vaccination. • A small increased risk of seizures and febrile seizures was found post-vaccination. • It is unclear if this increased risk is due to one, other or a vaccine combination. The study investigated the safety of 4-component meningococcal serogroup B vaccination (4CMenB) in routine care. 4CMenB exposure and seizures, febrile seizures and Kawasaki disease were identified from The Health Improvement Network (THIN) database of UK electronic primary healthcare records, 2015–2018. A self-controlled case series analysis was completed. Anaphylaxis, Guillain-Barré syndrome and acute disseminated encephalomyelitis were secondary outcomes. A total of 107,231 children aged 1–18 months received ≥1 doses of 4CMenB vaccination. Most 4CMenB exposure (93%) was on the same day as other vaccines within a complete national immunisation program stage. With day 0 as day of vaccination, 43 seizures occurred in days 0–6 after 239,505 doses, and 23 febrile seizures occurred in days 0–6, and 4 Kawasaki disease cases in days 1–28 after 194,929 4CMenB doses. Adjusted incidence rate ratios including all 4CMenB exposures were 1.43 (95%CI: 1.02–2.02) for seizures and 1.72 (95%CI: 1.08–2.75) for febrile seizures. There were insufficient cases to model Kawasaki disease, and no cases of the secondary outcomes in risk periods when they may be associated with the vaccination. This study shows few cases of the outcomes after vaccination including 4CMenB with an increased risk of seizures and febrile seizures. It is not possible to attribute the finding to one specific vaccination as the majority of 4CMenB was given with other vaccinations. Trial registration: NA. [ABSTRACT FROM AUTHOR]