The purpose of this study is to determine whether adding intravenous methylprednisolone pulse (IVMP) to primary adjunctive prednisolone with intravenous immunoglobulin (IVIG) improves treatment resistance and coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) with a high risk of treatment resistance. This multicenter, prospective, observational study was conducted at 28 hospitals in Japan from October 2016 to June 2020. For patients predicted to be resistant to treatment based on a Kobayashi score ≥ 5 and total bilirubin ≥ 1.0 mg/dL, each hospital independently decided to add IVMP followed by prednisolone, prednisolone alone, or nothing to the primary IVIG therapy. In total, 2856 consecutive KD patients were enrolled; of these, 399 (14.0%) were predicted to be treatment resistant. Patients who were resistant to the primary treatment and required additional treatment comprised 59%, 20%, and 26% of the IVIG-alone group, IVIG-plus-prednisolone group, and IVIG-plus-IVMP group, respectively (P < .0001). The CAA incidence (Z score ≥ 2.5) at month 1 was similar among the treatment groups (6.7%, 4.8%, and 7.3%, respectively; P = .66). CAA occurred more frequently in patients who needed third- or later-line therapy.Conclusions: Primary adjunctive corticosteroid therapy improved the treatment response and suppressed inflammation. However, the study found no benefit of adding IVMP to prednisolone therapy. Patients receiving IVIG alone achieved coronary outcomes comparable to those of patients receiving primary adjunctive corticosteroid therapy although they were more likely to require additional rescue treatment. KD inflammation should be resolved no later than the third line of additional treatment to reduce the risk of CAA.Trial registration: University Hospital Medical Information Network Clinical Trials Registry in Japan ( https://www.umin.ac.jp/ctr/index.htm ) under code UMIN000024937.

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

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

OBJECTIVE: To determine the long-term outcomes among a cohort of patients with Kawasaki disease (KD) and a history of giant coronary artery aneurysms (CAAs) at a single US center.
METHODS: Medical records for all patients with KD and giant CAAs at a pediatric academic institution were reviewed. Primary outcomes included major adverse cardiovascular events (MACE) and normalization of CA luminal diameter, using Kaplan-Meier analyses.
RESULTS: There were 60 patients with KD and giant CAAs identified between 1989 and 2023. The majority of patients were male (71.7%) with a median age at diagnosis of 0.9 years (range, 0.2-13.3 years). Patients were followed for a median of 11 years, up to 34.5 years. MACE occurred in 13 patients (21.7%) at a median of 1.4 years (range, 0.04-22.6 years) after KD diagnosis. The 10-, 20-, and 30-year MACE-free rates were 75%, 75%, and 60%. Patients with maximal CA z scores of ≥20 or bilateral CAA were more likely to have MACE. During follow-up, 26.7% of CAA regressed to a normal luminal diameter at a median of 3.6 years (range, 0.6-12.0 years). The 10-, 20- and 30-year likelihood of CA regression to normal luminal diameter was 36%, 46%, and 46%.
CONCLUSIONS: Over 30 years, MACE occurred in nearly 22% of patients, more often in those with bilateral CAA or CA z scores of ≥20. Despite regression to a normal luminal diameter in >25% of CAAs, patients with a history of KD-associated giant CAA require ongoing surveillance for cardiac complications, even years after the initial disease.

UNASSIGNED: Kawasaki disease (KD) is a paediatric multi-system vasculitis. Mainly, the coronary arteries become affected due to acute inflammation and formation of coronary artery aneurysms (CAAs) may occur. As the size of the CAA increases, so does the risk of clinical complications and serious cardiac outcomes. These patients may experience life-threatening thrombotic coronary artery occlusion and myocardial ischaemia unless antiplatelet and anticoagulation therapy is not initiated in a timely manner.1.
UNASSIGNED: This case report presents a 12-year-old patient with KD who developed CAAs in two coronary arteries despite initial administration of intravenous immunoglobulins and acetylsalicylic acid, followed by extensive thrombosis of both coronary arteries, although antithrombotic therapy was started after the diagnosis of CAAs.
UNASSIGNED: Our case is notable because of the severity of the clinical manifestation despite the administration of antiplatelet agents and anticoagulants. It could be speculated that the development of coronary thrombosis in this case might be strongly correlated with the late initiation of oral anticoagulation. The high-quality images of the affected coronary arteries in such a young patient could be of educational value.

Multisystem inflammatory syndrome in adults (MIS-A) is a systemic inflammatory disease associated with COVID-19 and follows coronary artery aneurysms similar to Kawasaki disease. In many cases, it is improved by treatments such as high-dose steroids or intravenous immunoglobulin (IVIg). However, the role of untreated coronary artery aneurysms leading to future stenosis remains unknown. Untreated MIS-A may potentially lead to the formation of coronary aneurysms. In cases of COVID-19 where young adults present with angina-like symptoms, an evaluation for angina is considered. Herein, we report a case of a 27-year-old female who developed unstable angina with coronary artery aneurysms six months after COVID-19 infection. She required surgery for unstable angina, which resulted in an improvement in chest pain. Coronary artery lesions are considered to be related to MIS-A, and treatment was conducted in accordance with that for Kawasaki disease. Currently, the pathological differences and prognosis between MIS-A and Kawasaki disease remain unclear, but the elucidation of the conditions is warranted in the future.

Acute acalculous cholecystitis (AAC) is an inflammatory disease of the gallbladder in the absence of gallstones. AAC has been linked to various systemic illnesses including Kawasaki disease (KD). We report a case of a five-year-old male brought to the emergency department (ED) with a history of fever and vomiting for four days. He was admitted as a case of KD. Then, we discovered that he had AAC, which was well managed by intravenous immunoglobulin (IVIG) as the fever subsided, C-reactive protein (CRP) decreased, and repeated abdominal ultrasound showed a decrease in gallbladder thickness without any evidence of coronary artery aneurysms.

UNASSIGNED: Coronary artery dilation (CAD) had rarely been described as a cardiac complication of febrile disease other than Kawasaki disease (KD). There are rare cases complicated by CAD reported in patients with Mycoplasma pneumoniae (MP) infection.
UNASSIGNED: A 6-year-old boy with severe Mycoplasma pneumoniae pneumonia (MPP) was transferred to our hospital due to significant respiratory distress on the 11th day from disease onset. Nadroparin, levofloxacin, and methylprednisolone followed by oral prednisone were aggressively prescribed. His clinical condition gradually achieved remission, and the drugs were withdrawn on the 27th day. Regrettably, the recurrent fever attacked him again in the absence of infection-toxic manifestations. Necrotizing pneumonia (NP) was found on chest CT. And echocardiography revealed right CAD (diameter, 3.40mm; z-score, 3.8), however, his clinical and laboratory findings did not meet the diagnostic criteria of KD. CAD was proposed to result from MP infection, and aspirin was prescribed. Encouragingly, the CAD regressed one week later (diameter, 2.50mm; z-score, 1.4). Additionally, the child defervesced seven days after the initiation of prednisone and Nadroparin treatment. The patient was ultimately discharged home on the 50th day. During follow-up, the child was uneventful with normal echocardiography and fully resolved chest CT lung lesions.
UNASSIGNED: CAD can develop in patients with severe MP infection. Pediatricians should be alert to the possibility of CAD in patients with severe MP infection and recognize that CAD might also develop in febrile disease rather than KD.

BACKGROUND: Coronary status at one month after Kawasaki disease (KD) onset had a great significance. The present study aimed to establish a prediction model for coronary artery aneurysms (CAA) at one month in children with KD.
METHODS: Patients with a diagnosis of KD between May 2017 and Dec 2018 were enrolled as the development cohort to build a prediction model. The model was validated by internal and external validation. Patients between Jan 2019 and Dec 2019 were enrolled as the validation cohort. The adaptive least absolute shrinkage and selection operator (LASSO) was used to select the possible predictors. Receiving operating characteristic curve (ROC), calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. The performance of the Son score was also assessed.
RESULTS: LASSO regression demonstrated that age, sex, and CALs in the acute stage were predictors for CAA at one month. The area under the ROC (AUC) was 0.946 (95% confidence interval: 0.911-0.980) with a sensitivity of 92.5% and a specificity of 90.5%. The calibration curve and the DCA showed a favorable diagnostic performance. The internal and external validation proved the reliability of the prediction model. The AUC of our model and the Son score were 0.941 and 0.860, respectively (P < 0.001).
CONCLUSIONS: Our prediction model for CAA at one month after disease onset in KD had an excellent predictive utility.

BACKGROUND: Direct oral anticoagulants have the potential to improve care in children requiring chronic anticoagulation. Edoxaban has favourable pharmacokinetics that could benefit younger patients but data on long-term safety and efficacy for specific paediatric indications are lacking.
OBJECTIVE: We present a single-centre experience using edoxaban in children who require chronic anticoagulation for large coronary artery aneurysms secondary to Kawasaki disease.
METHODS: Weight-based dosing of once-daily oral edoxaban was offered as alternative to standard anticoagulation for patients aged 1-18 years. Chart review was performed for a median follow-up period of 49 months on edoxaban. Steady-state pharmacokinetics and pharmacodynamics of edoxaban were also explored.
RESULTS: Sixteen patients on chronic therapy with edoxaban were included. No major bleeding events were reported. Two patients experienced coronary artery thrombosis after 23 and 38 months on edoxaban, 7 and 11 years after diagnosed with Kawasaki disease, respectively. This predicts 70% event-free rate at 12 years from diagnosis. Area under the curve estimates over the dosing interval of 24 hours were similar to those reported in adults.
CONCLUSIONS: Edoxaban use is feasible and well-tolerated for long-term use in paediatric population. We suggest appropriate exposure using weight-based once-daily dosing strategy that may be comparable to standard-of-care anticoagulation in prevention of coronary artery thrombosis. Larger studies are needed to evaluate long-term safety and efficacy of edoxaban in this population.