Mycoplasma pneumoniae-induced Kawasaki disease via PINK1/Parkin-mediated mitophagy.

Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that primarily affects children. The objective of this study was to explore the function and underlying mechanism of mitophagy in Mycoplasma pneumoniae (MP)-induced KD. To create MP-induced KD models, Human coronary endothelial cells (HCAECs) and DBA/2 mice were employed and treated with Mp-Lipid-associated membrane proteins （LAMPs）. Lactate dehydrogenase (LDH) levels were tested to determine cellular damage or death. The inflammatory cytokines tumor necrosis factor (TNF)--α and interleukin (IL)-6 were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. RT-qPCR and Western blotting were used to determine the expression of Intercellular Adhesion Molecule(ICAM)-1, vascular cell adhesion molecule (VCAM)-1, inducible nitric oxide synthase(iNOS), LC3, p62, PINK1(a mitochondrial serine/threonine-protein kinase), and PARKIN(a cytosolic E3-ubiquitin ligase). The adenosine triphosphate （ATP）, reactive oxygen species （ROS）, and mitochondrial membrane potential（MMP） levels were measured to determine mitochondrial function. Mitophagy was investigated using immunofluorescence and a mitophagy detection test. Autophagosome and mitochondrial morphology were examined using transmission electron microscopy. To identify inflammatory cell infiltration, hematoxylin and eosin staining was utilized. Mp-LAMPs increased the levels of TNF-α, IL-6, ICAM-1, VCAM-1, and iNOS in an HCAEC cell model, along with LDH release. After Mp-LAMPs exposure, there was a rise in LC3 and a reduction in p62. Meanwhile, the expression of PINK1 and Parkin was increased. Cyclosporin A dramatically increased ATP synthesis and MMP in HCAEC cells treated with Mp-LAMPs, while suppressing ROS generation, demonstrating excessive mitophagy-related mitochondrial dysfunction. Additionally, neither body weight nor artery tissue were affected due to PINK1 and Parkin suppression Cyclosporin A in Mp-LAMPs-treated mice. These findings indicated that PINK1/Parkin-mediated mitophagy inhibition may be a therapeutic target for MP-induced KD.

Methylprednisolone pulse and prednisolone for intensification of primary treatment in Kawasaki disease patients at high risk of treatment resistance: a multicenter prospective cohort study.

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.

Novel predictors of intravenous immunoglobulin resistance in patients with Kawasaki disease: a retrospective study.

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

The incidence of periungual desquamation and thrombocytosis in Kawasaki disease and the importance of systematic observation in the subacute phase.

Background: Periungual desquamation and thrombocytosis are characteristic of the subacute phase of Kawasaki disease (KD). However, accurate observations of periungual desquamation and thrombocytosis are lacking. Methods: This retrospective study included patients with acute-phase KD who received treatment at seven affiliated university hospitals in Korea between 2015 and 2017. Data were extracted from an anonymized registry established by the Korean Society of Kawasaki Disease. We investigated whether the findings of patients observed according to a set protocol until the subacute stage (group I) were different from those of patients observed without the use of a protocol (group II). Results: A total of 879 patients with KD were included in the analysis. Periungual desquamation was observed in 85% and 12.7% of patients in groups I and II, respectively. Thrombocytosis was observed in 76.7% and 44.7% of patients in groups I and II, respectively. Furthermore, compared to the initial test, the platelet counts of patients increased 100% and 67.9% in group I and II, respectively. When incomplete KD was defined only by the main symptoms during the acute stage and the diagnostic criterion of periungual desquamation during the subacute stage was excluded, the significant difference in the incidence of incomplete KD between groups I and II was no longer apparent. Conclusion: Performing regular and detailed observations has resulted in a higher incidence of periungual desquamation and thrombocytosis during the subacute phase of KD than those reported in recent studies. This indicates that until now, we have been neglecting the observation of symptoms and signs during the subacute phase. Regular monitoring during this period can also aid in differentiating suspected cases of KD and facilitate appropriate follow-up of complications.

The Effectiveness of No or Low-Dose versus High-Dose Aspirin in Treating Acute Kawasaki Disease: A Systematic Review and Meta-Analysis.

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

Etiology and prognosis of non-Kawasaki disease induced coronary aneurysms in children: a retrospective case series study.

While Kawasaki disease (KD) induced coronary artery aneurysms (KD CAAs) in children are well studied, the features and prognosis of non-KD induced CAAs (non-KD CAAs) in the pediatric population are poorly documented. This case series study is to analyze the etiology and prognosis of non-KD CAAs in children and compare the characteristics of non-KD CAAs and KD CAAs. Non-KD CAA and KD CAA cases at our department from January 2022 to December 2023 were retrospectively collected. Etiologies and prognosis of non-KD CAAs were analyzed. Furthermore, demographic data, biochemical parameters and outcomes between children with Non-KD CAAs and children with KD CAAs were comparatively studied. Fifteen children with non-KD CAAs with a median age of 6 years and 117 children with KD CAAs with a median age of 2.0 years (p = 0.022) were included in this study. The causes of non-KD CAAs include: unknown etiologies (2 cases), coronary artery structural abnormalities (4), Takayasu arteritis (2), virus infection (2), cardiomyopathy (2), aplastic anemia with agranulocytosis (1), ANCA-associated vasculitis (1), and mucopolysaccharidosis (1). In the non-KD CAA group, there were a total of 19 CAAs with 3 being giant, 5 medium, and 11 small; 4 patients had complete CAA regression; an infant with a fistula between the right coronary artery and the coronary sinus complicated with cardiac enlargement died of heart failure. The KD group had significantly higher levels of CRP, white cells counts and ESR with zero mortality. Non-KD CAA cases had a significantly lower regression rate than KD-CAA cases (26.7% vs 66.7%, p = 0.004), and the probability of CAA regression in non-KD patients was 0.341 of that in KD patients (p = 0.006, OR = 0.341, 95% CI: 0.179-0.647). CONCLUSIONS: Various etiologies for Non-KD CAAs are identified. Patients with Non-KD CAAs were observed to have lower inflammatory indexes but poorer recovery than patients with KD CAAs. Therapeutic strategies different than those for KD may be needed for non-KD CAAs. WHAT IS KNOWN: • Coronary artery aneurysm (CAA) in children is most commonly induced by Kawasaki disease (KD CAA), with a 50 ~ 70% regression rate in 1 to 2 years. • CAA induced by diseases other than KD (non-KD CAA) in children is rare and its prognosis remains largely unknown. WHAT IS NEW: • Most non-KD CAA cases are caused by coronary artery structural malformations. • Non-KD CAA in children has poorer prognosis and lower regression rate compared with KD CAA. • In addition to guideline directed anti-platelet and anti-coagulant therapies, treatments targeting the causal factor are necessary for non-KD CAA.

Retropharyngeal and parapharyngeal infections in children: A retrospective analysis.

OBJECTIVES: To describe presentations, management and outcomes of retropharyngeal and parapharyngeal infections in children presenting to a tertiary care pediatric emergency department. METHODS: A retrospective chart review of children with deep neck infections such as retropharyngeal or parapharyngeal infection from January 2008 to December 2018 was conducted at a pediatric hospital. RESULTS: There were 176 retropharyngeal, 18 parapharyngeal and 6 with both retropharyngeal and parapharyngeal infections treated during the 10-year study period. Males were 60% of the cohort and the mean age was 4.3 (SD: 3.2) years. No significant differences in age or sex ratio or presentations were seen in children with retropharyngeal infections compared with parapharyngeal infections. All received parenteral antibiotics; 42% (84/200) of children underwent surgery and four of them had more than one surgical drainage. Age <12 months and the diagnosis of parapharyngeal infections were associated with significantly higher rates of surgical treatment. Children under 12 months of age were sicker at presentation and had a high complication rate of 23% compared with 1% in the older children (p = 0.002). Seven children had co-existence of Kawasaki disease with deep neck infections. CONCLUSIONS: Early diagnosis of retropharyngeal and parapharyngeal infections especially in infants under a year of age is important as they are more likely to have complications and need surgical management. Most paediatric patients with retropharyngeal and parapharyngeal infections have a phlegmon or very small abscesses and are treated non-operatively with parenteral antibiotics.

Ileocecal Intussusception in the Era of Coronavirus Disease 2019 (COVID-19) Infection and Multisystem Inflammatory Syndrome in Children (MIS-C): A Case Report and Literature Review.

Ileocecal intussusception (ICI) is the most common abdominal emergency and cause of intestinal obstruction in young children, carrying a high risk of mortality and morbidity. Enteric viral infectious and inflammatory syndromes are known triggers for intussusception (ileoileal and ileocolic) by causing mesenteric lymphoid hyperplasia that may act as a leading point allowing the bowel to invaginate into itself. Gastrointestinal (GI) symptoms are common in children with coronavirus disease 2019 (COVID-19) infection, with a subset of patients solely having GI complaints at the time of presentation.  COVID-19 as a trigger for intussusception in children has been hypothesized and suggested in multiple cases reported to date, both during the acute phase of illness and as a part of multisystem inflammatory syndrome in children (MIS-C). We present a seven-month-old male who developed ICI and became a diagnostic dilemma due to viral co-infections and the gradual emergence of MIS-C during the hospital stay. We are describing this presentation in an attempt to expand the understanding of the implications of COVID-19 and MIS-C in this young and unique age group.

Human cytomegalovirus pUL135 protein affects endothelial cell function via CD2AP in Kawasaki disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our findings imply that HCMV pUL135-mediated endothelial dysfunction plays an important role in exacerbating coronary artery injury in KD conditions.

Long COVID Definition, Symptoms, Risk Factors, Epidemiology and Autoimmunity: A Narrative Review.

The virus called SARS-CoV-2 emerged in 2019 and quickly spread worldwide, causing COVID-19. It has greatly impacted on everyday life, healthcare systems, and the global economy. In order to save as many lives as possible, precautions such as social distancing, quarantine, and testing policies were implemented, and effective vaccines were developed. A growing amount of data collected worldwide allowed the characterization of this new disease, which turned out to be more complex than other common respiratory tract infections. An increasing number of convalescents presented with a variety of nonspecific symptoms emerging after the acute infection. This possible new global health problem was identified and labelled as long COVID. Since then, a great effort has been made by clinicians and the scientific community to understand the underlying mechanisms and to develop preventive measures and effective treatment. The role of autoimmunity induced by SARS-CoV-2 infection in the development of long COVID is discussed in this review. We aim to deliver a description of several conditions with an autoimmune background observed in COVID-19 convalescents, including Guillain-Barré syndrome, antiphospholipid syndrome and related thrombosis, and Kawasaki disease highlighting a relationship between SARS-CoV-2 infection and the development of autoimmunity. However, further studies are required to determine its true clinical significance.

Candesartan Attenuates Vasculitis in a Mouse Model of Kawasaki Disease Induced by Candida albicans Water-Soluble Fraction.

BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFß receptors. Measurement of the inflammatory cytokines IL-1ß, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

Evaluation of Coronary Circulation by 13N-Ammonia Myocardial Perfusion Positron Emission Tomography in Patients with Right Coronary Artery Occlusion Due to Kawasaki Disease.

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.

Myocardial perfusion impairment in children with Kawasaki disease: assessment with cardiac magnetic resonance first-pass perfusion.

Background: Kawasaki disease (KD) potentially increases the risk of myocardial ischemia. This study aimed to semi-quantitatively evaluate myocardial perfusion impairment using cardiac magnetic resonance (CMR) first-pass perfusion in children with KD and explore the association between coronary artery (CA) dilation and myocardial perfusion. Methods: From December 2018 to July 2021, 77 patients with KD (48 male, 5.71±2.80 years) and 37 age- and sex-matched normal controls (20 male, 6.19±3.32 years) who underwent CMR in West China Second University Hospital were enrolled in this cross-sectional study with prospective data collection. A total of 30 of these patients completed the follow-up CMR, with a median interval of 13 months. Myocardial perfusion parameters including perfusion index (PI) and maximum signal intensity (Max SI) were obtained through rest first-pass perfusion. The internal diameter of the CA was assessed via coronary magnetic resonance angiography (CMRA) to calculate the coronary Z score. The global and regional myocardial parameters among the subgroups were compared. Statistical analysis included one-way analysis of variance (ANOVA), Pearson's correlation, and multivariate linear regression. Results: The global Max SI and regional Max SI of all segments in patients with and without CA dilation decreased compared with those in controls (P=0.19 and P<0.001, respectively). The global PI of patients with CA dilation and regional PI in segments subtended by dilated CA were lower than that of controls (P=0.002 and P<0.001, respectively) and were negatively correlated with the Z score (global: r=-0.576; regional: r=-0.351, both P<0.001). Multivariate analysis revealed that the Z score was negatively associated with global PI in KD (ß=-0.409, P=0.02, model R2=0.170). The global Max SI of patients with and without CA dilation during the follow-up CMR decreased compared with that of the first CMR (42.18±9.84 vs. 34.48±8.24, P=0.02; 44.82±7.13 vs. 36.61±7.67, P=0.03, respectively). Conclusions: CMR myocardial first-pass perfusion imaging can semi-quantitatively evaluate impaired myocardial perfusion in KD patients. Not only patients with CA dilation and segments subtended by dilated CA but also those without CA dilation and segments subtended by non-dilated CA developed myocardial perfusion impairment, the severity of myocardial perfusion impairment is associated with the degree of CA dilation.

Identification of a mimotope of a complex gp41 Human Immunodeficiency VIrus epitope related to a non-structural protein of Hepacivirus previously implicated in Kawasaki disease.

Background: We have previously isolated a highly mutated VH1-02 antibody termed group C 76-Q13-6F5 (6F5) that targets a conformational epitope on gp41. 6F5 has the capacity to mediate Ab dependent cell cytotoxicity (ADCC). When the VH1-02 group C 76 antibodies variable chain sequence was reverted to germline (76Canc), this still retained ADCC activity. Due to this ability for the 76Canc germline antibody to functionally target this epitope, we sought to identify a protein target for vaccine development. Methods: Initially, we interrogated peptide targeting by screening a microarray containing 29,127 linear peptides. Western blot and ELISAs were used to confirm binding and explore human serum targeting. Autoimmune targeting was further interrogated on a yeast-displayed human protein microarray. Results: 76Canc specifically recognized a number of acidic peptides. Meme analysis identified a peptide sequence similar to a non-structural protein of Hepacivirus previously implicated in Kawasaki disease (KD). Binding was confirmed to top peptides, including the Hepacivirus-related and KD-related peptide. On serum competitions studies using samples from children with KD compared to controls, targeting of this epitope showed no specific correlation to having KD. Human protein autoantigen screening was also reassuring. Conclusions: This study identifies a peptide that can mimic the gp41 epitope targeted by 76C group antibodies (i.e. a mimotope). We show little risk of autoimmune targeting including any inflammation similar to KD, implying non-specific targeting of this peptide during KD. Development of such peptides as the basis for vaccination should proceed cautiously.

Treatment intensification in Kawasaki disease - current perspectives.

INTRODUCTION: Intravenous immunoglobulin is the standard of care in Kawasaki disease. However, a subset of patients exhibits resistance to intravenous immunoglobulin treatment, even when Kawasaki disease is promptly diagnosed and managed. While intravenous immunoglobulin reduces the occurrence of coronary artery abnormalities from 15-25% to 3-5%, it does not entirely eliminate the risk. Besides, management guidelines for non-coronary complications of Kawasaki disease, for instance, myocarditis, remain speculative. AREAS COVERED: Recent literature suggests that a subset of patients with Kawasaki disease may benefit from treatment intensification with drugs, such as corticosteroids, infliximab, anakinra, and/or ciclosporin. In this manuscript, we have reviewed recent advances in the management of Kawasaki disease, especially with regard to preemptive intensification of therapy in children at high risk of cardiac complications. A comprehensive search was made using Web of Science, Scopus, and PubMed databases to gather English articles published from 1967 to 2023 on the treatment of Kawasaki disease. We incorporated the following words in the search strategy: 'Kawasaki disease,' 'intravenous immunoglobulin/IVIg,' 'intravenous immunoglobulin/IVIg-resistant Kawasaki disease,' 'treatment intensification,' or 'primary intensification of treatment/therapy.' EXPERT OPINION: The 'high-risk' group in Kawasaki disease needs to be identified with early intensification of primary therapy for better coronary and myocardial outcomes.

Research perspective in the clinical management of Kawasaki disease.

This study examines research perspective in the clinical diagnosis, treatment, and prevention of cardiovascular complications in Kawasaki Disease (KD). Starting with an overview of the disease, it introduces KD's clinical manifestations, etiology, epidemiological features, and its impact on the cardiovascular system. Subsequently, the study discusses in detail the diagnostic methods, pathological mechanisms, and treatment strategies for KD, including foundational and emerging approaches such as high-dose intravenous immunoglobulin and aspirin therapy, biologic therapy, and corticosteroid pulse therapy. Additionally, it outlines strategies for preventing cardiovascular complications, including early risk assessment and long-term management. The study also explores the intersection of the COVID-19 pandemic with an increase in KD-like symptoms, emphasizing the need for further studies on the association between SARS-CoV-2 and KD. Lastly, it explores future research directions to enhance understanding of KD and improve patient outcomes and quality of life. This study provides valuable insights into the comprehensive treatment and management of KD and highlights avenues for future research.

Plasma proteomic profiling reveals that SERPINE1 is a potential biomarker associated with coronary artery lesions in Kawasaki disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients.

Guideline for the diagnosis and treatment of incomplete Kawasaki disease in children in China.

BACKGROUND: Kawasaki disease (KD) is a pyretic ailment predominantly observed in children aged below 5 years. There is currently a dearth of precise markers for timely identification of incomplete Kawasaki disease (IKD). It is imperative to develop updated, comprehensive, and evidence-based guidelines to effectively direct clinical practice. METHODS: The guideline development group comprised individuals with diverse expertise in both content and methodology and carried out an extensive exploration of the following digital repositories: CNKI, VIP, Wanfang Data, UpToDate, BMJ, Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed. The entire period from the establishment of these databases until January 1, 2024 was covered. To evaluate IKD, systematic reviews and randomised controlled trials were assessed using the risk of prejudice instrument specified in the Cochrane Handbook, along with the evidence robustness framework established by the GRADE group. The recommendations were formulated based on the findings, considering the evidence strength. After several iterations of expert consensus, the relevant professional committees in China endorsed the ultimate guideline. RESULTS: These guidelines address clinical questions regarding the classification and definition of KD, diagnosis of IKD, treatment during the acute phase of IKD, and follow-up of IKD. CONCLUSIONS: To provide healthcare professionals with guidance and decision-making bases for the diagnosis and treatment of IKD in China, 13 recommendations were formulated based on expert consensus and evidence of best practices.

B-cell hub genes play a cardiovascular pathogenic role of in childhood obesity and Kawasaki disease as revealed by transcriptomics-based analyses.

The study aims to explore the central genes that Kawasaki disease (KD) and Obesity (OB) may jointly contribute to coronary artery disease. Investigating single-cell datasets (GSE168732 and GSE163830) from a comprehensive gene expression database, we identified characteristic immune cell subpopulations in KD and OB. B cells emerged as the common immune cell characteristic subgroup in both conditions. Subsequently, we analyzed RNA sequencing datasets (GSE18606 and GSE87493) to identify genes associated with B-cell subpopulations in KD and OB. Lastly, a genome-wide association study and Mendelian randomization were conducted to substantiate the causal impact of these core genes on myocardial infarction. Quantitative real-time PCR (qRT-PCR) to validate the expression levels of hub genes in KD and OB. The overlapping characteristic genes of B cell clusters in both KD and OB yielded 70 shared characteristic genes. PPI analysis led to the discovery of eleven key genes that significantly contribute to the crosstalk. Employing receiver operating characteristic analysis, we evaluated the specificity and sensitivity of these core genes and scored them using Cytoscape software. The inverse variance weighting analysis suggested an association between TNFRSF17 and myocardial infarction risk, with an odds ratio of 0.9995 (95% CI = 0.9990-1.0000, p = 0.049). By employing a single-cell combined transcriptome data analysis, we successfully pinpointed central genes associated with both KD and OB. The implications of these findings extend to shedding light on the increased risk of coronary artery disease resulting from the co-occurrence of OB and KD.