Progression prediction of coronary artery lesions by echocardiography-based ultrasomics analysis in Kawasaki disease.

BACKGROUND: Echocardiography-based ultrasomics analysis aids Kawasaki disease (KD) diagnosis but its role in predicting coronary artery lesions (CALs) progression remains unknown. We aimed to develop and validate a predictive model combining echocardiogram-based ultrasomics with clinical parameters for CALs progression in KD. METHODS: Total 371 KD patients with CALs at baseline were enrolled from a retrospective cohort (cohort 1, n = 316) and a prospective cohort (cohort 2, n = 55). CALs progression was defined by increased Z scores in any coronary artery branch at the 1-month follow-up. Patients in cohort 1 were split randomly into training and validation set 1 at the ratio of 6:4, while cohort 2 comprised validation set 2. Clinical parameters and ultrasomics features at baseline were analyzed and selected for models construction. Model performance was evaluated by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) and decision curve analysis (DCA) in the training and two validation sets. RESULTS: At the 1-month follow-ups, 65 patients presented with CALs progression. Three clinical parameters and six ultrasomics features were selected to construct the model. The clinical-ultrasomics model exhibited a good predictive capability in the training, validation set 1 and set 2, achieving AUROCs of 0.83 (95% CI, 0.75-0.90), 0.84 (95% CI, 0.74-0.94), and 0.73 (95% CI, 0.40-0.86), respectively. Moreover, the AUPRC values and DCA of three model demonstrated that the clinical-ultrasomics model consistently outperformed both the clinical model and the ultrasomics model across all three sets, including the training set and the two validation sets. CONCLUSIONS: Our study demonstrated the effective predictive capacity of a prediction model combining echocardiogram-based ultrasomics features and clinical parameters in predicting CALs progression in KD.

Coronary thrombosis and myocardial ischemia in Kawasaki disease: a case report.

BACKGROUND: Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. CASE PRESENTATION: In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child's thrombus has dissolved, and the myocardial ischemia has resolved. CONCLUSIONS: This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Incidence of Kawasaki disease among children in Chandigarh, India during 2015-2019: a trend analysis.

Background: Only limited information exists regarding the epidemiology of Kawasaki disease (KD) in low-income and middle-income countries. The present study provides the incidence of KD during 2015-2019 in Chandigarh, north India. Our centre follows the largest KD cohort in India. Methods: Children with KD at Chandigarh diagnosed during January 2015-December 2019 were enrolled in the study. Annual incidence rates were determined using decadal growth rates of the National Census 2011. We computed the incidence of KD in children aged <5, and <15 years. We also undertook linear trend analysis using our incidence data from 1994 to 2019. Findings: During 2015-2019, 83 patients (66 males, 17 females) were diagnosed with KD in Chandigarh. Incidence rates during these 5 years were 5.64, 9.25, 9.11, 9.87, and 9.72/100,000 in children aged <5 years, and 2.65, 4.44, 3.86, 5.07, 4.74/100,000 in children aged <15 years. The median age at diagnosis was 48 months (range: 12 days to 15 years). Compared to previous data (2009-2014), there was a 53.1% increase in annual incidence of KD in children aged <5 years, and a 53.7% increase in children aged <15 years. Coronary artery abnormalities during acute phase were noted in 16.9%, and in 7.2% of patients at 6 weeks of follow-up. The trend analysis indicated a monthly rise of 0.002 cases per 100,000 children aged <5 years, and 0.0165 cases per 100,000 children aged <15 years. Interpretation: The incidence of KD has continued to show an upward trend in Chandigarh over the period 2015-2019. This may indicate a true rise in the occurrence of KD or may reflect better disease ascertainment as a result of greater awareness about KD amongst healthcare professionals. Funding: None.

Whole-exome sequencing reveals Kawasaki disease susceptibility genes and their association with coronary artery lesion.

Objective: This study aimed to explore Kawasaki disease (KD) susceptibility genes and their complications like coronary artery lesions (CAL) using whole exome sequencing (WES). Methods: Between April 1, 2021, and December 31, 2022, our study included 55 pediatric patients diagnosed KD at our center, alongside a cohort of healthy children who sought medical care at our institution during the same timeframe. We extracted peripheral blood DNA from all participants and employed the advanced high-throughput Illumina Next-Generation Sequencing technology for comprehensive analysis. Through bioinformatics evaluation, we identified potential susceptibility genes. Moreover, from the 55 KD patients, we selected 15 for the CAL group and 40 for the non-CAL group. We aimed to investigate whether there were significant differences in the allele frequencies of the targeted susceptibility genes between these subgroups, to explore the risk alleles associated with the development of CAL in KD. Results: HLA-DRB1 rs17882084 and IL6ST rs781455079 genotypes and alleles differed significantly between KD and non-KD (P < 0.05). No differences existed for IL17RC rs143781415 and VEGFB rs776229557 (P > 0.05). No differences in HLA-DRB1 rs17882084, IL6ST rs781455079, and VEGFB rs776229557 genotypes existed between CAL and non-CAL groups (P > 0.05). However, the IL17RC rs143781415 genotype differed significantly between them (P < 0.05). Conclusions: HLA-DRB1 rs17882084 and IL6ST rs781455079 genotypes may be potential KD susceptibility gene candidates. Specifically, HLA-DRB1 rs17882084 GA genotype and A allele, and IL6ST rs781455079 TC genotype and C allele may increase KD risk. Additionally, the IL17RC rs143781415 genotype may increase CAL risk in KD patients.

Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy.

INTRODUCTION: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. METHODS: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). RESULTS: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. CONCLUSION: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.

A large thrombus within a giant coronary artery aneurysm in a child with Kawasaki disease: A case report.

Kawasaki disease (KD) is an acute systemic vasculitis that preferentially involves coronary arteries in young children, and predominantly affects young children. Cardiovascular lesions are the most severe complications of this disease. Even though giant aneurysms are rare, they can complicate thrombus formation, leading to myocardial ischemia, myocardial infarction, and even cardiac death. Later in life, it can lead to steno-occlusive lesions. Follow-up led to coronary artery stenosis. In this article, we report a case of a pediatric patient with KD who presented with a large thrombus within a giant coronary aneurysm as a consequence of delayed treatment with intravenous immunoglobulin (IVIG) and IVIG resistance, which contributed to the formation of coronary artery lesions. Transthoracic echocardiography is a valuable tool for detecting coronary artery abnormalities; however, computed tomography coronary angiography is valuable for precisely delineating coronary anatomy and complications. It is important to maintain a slightly higher international normalized ratio to decrease the risk of thrombosis in coronary artery aneurysms.

Expansion of a Novel Subset of L-Selectin+ Classical Monocytes in Kawasaki Disease.

Purpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM. Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD. Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD. Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.

Multisystem Inflammatory Syndrome of the Adults (MIS-A) - The undercover threat for young adults. A systematic review and meta-analysis of medical cases.

Background: COVID-19 related syndromes are not yet well described and understood. Multisystem inflammatory syndrome of the adults (MIS-A) is a recently characterized syndrome affecting multiple organs of young adults, causing serious complications, even shock and death. Objectives: To determine the clinical characteristics, course, and complications of MIS-A in a systematic way and summarize currently used treatments. Methods: Literature search in March 2023 in PubMed and Scopus databases. Case reports and case-series that fulfilled the CDC criteria for MIS-A were eligible for inclusion. Results: A total of 71 patients from 60 reports were included. 66% of the patients were male and the mean age of the synthetic cohort was 32.9 years old. The majority (70.4%) of the enrolled cases had no significant medical history. MIS-A was diagnosed after a median of 4 weeks period. All but two patients presented with cardiac symptoms, while the most common secondary diagnostic criterion was abdominal pain, vomiting or diarrhea followed by shock or hypotension. Heart failure therapy and immunomodulation were used as therapeutic options. Although more than half of the cohort was admitted to the Intensive Care Unit (ICU) (n=39) only 4 deaths were reported. Conclusion: MIS-A can affect patients independently of age, sex, and co-morbidity status, resulting in serious complications, often including severe cardiac disease, shock, acute kidney injury and sometimes death. It can occur immediately after SARS-CoV-2 acute infection until two months later, usually manifesting four weeks after acute disease.

DDIAS Regulation of STAT3/CCL2 Promotes Macrophage Polarization to M1 type in Kawasaki Disease.

OBJECTIVE: To investigate the molecular mechanism by which DNA damage induced apoptosis suppressor (DDIAS) regulates STAT3/CCL2 to enhance macrophage polarization to M1 type in Kawasaki disease (KD). METHODS: A KD vascular model was established by culturing human coronary artery endothelial cells (HCAECs) in vitro. Small interfering RNA of DDIAS (si-DDIAS) was transfected into the KD cell model. The human macrophage cell line THP-1 was induced into M1 macrophages using phorbol myristate acetate (PMA) and lipopolysaccharide (LPS) and co-cultured with the endothelial cells using the HCAECs medium. Western blot analysis was utilized to assess cellular DDIAS, p-STAT3, STAT3, and CCL2 protein expression. MTT was utilized to detect cell proliferation. ELISA was utilized to assess the expression levels of TNF-α, IL-4, IL-6, IL-8 and CCL2 in cell supernatants. Flow cytometry was utilized to examine cell apoptosis and the expression of M1 macrophage surface marker CD86. RESULTS: The expression level of DDIAS was elevated in the KD group compared to the Control group. Serum inhibition of HCAEC proliferation in the KD group was concentration-dependent and pro-inflammatory cytokines were substantially elevated, while the anti-inflammatory cytokines were substantially reduced (P<0.05). Compared to the si-NC group, cell proliferation was considerably enhanced; pro-inflammatory cytokines were substantially reduced; anti-inflammatory cytokines were substantially elevated, and the expression of p-STAT3 and CCL2 was lowered in the si-DDIAS group (P<0.05). The percentage of M1 macrophages was substantially elevated in the THP-1+LPS group compared to the THP-1 group (P<0.05). Compared to the THP-1+LPS+si-NC group, macrophage CCL2 expression was decreased in the THP-1+LPS+si-DDIAS group; the percentage of M1 macrophages was substantially lowered (P<0.05); and the levels of pro-inflammatory cytokines and CCL2 in the cell supernatant were substantially reduced. Incubation of macrophages with STAT3 agonist reversed these changes, which were exacerbated by the addition of neutralizing antibody CCL2. CONCLUSIONS: Downregulation of DDIAS inhibits macrophage polarization toward the M1 type through inhibition of the STAT3/CCL2 signaling pathway and can ameliorate vascular injury and inflammation in KD coronary arteries.

Nail pitting in an infant with Kawasaki disease-A novel clinical finding.

A variety of nail changes have been described in children with Kawasaki disease during the convalescent phase. These include Beau's lines, leukonychia, and orange-brown chromonychia. However, nail pitting is distinctly unusual in KD. We report one such case.

Regression effect of renin-angiotensin-aldosterone system inhibitors on Kawasaki disease patients with coronary artery aneurysm: a prospective, observational study.

PURPOSE: This study is to investigate whether angiotensin type 1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis) can regress coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD). METHODS: This multicenter, prospective, observational study was conducted at 53 institutions throughout Japan. We enrolled patients who were diagnosed with KD after January 2015 and had a medium or large CAA (maximum luminal diameter ≥ 4 mm or z score ≥ + 5) 30 days or later after KD onset. RESULTS: Of the 209 patients, 47 (22%) were taking ARBs/ ACEis. Compared with those in the non-ARB/ACEi group, the baseline CAA diameter was significantly greater (6.7 mm vs. 5.5 mm, p < 0.01), and bilateral CAA (70% vs. 59%, p = 0.01) and giant CAA (32% vs. 20%, p = 0.08) were more frequently observed in the ARB/ACEi group. Although the overall regression rates did not differ between the groups (67% vs. 65%), the regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group (36% vs. 23%). Multivariate Cox regression analysis after adjustment for other clinical variables suggested that ARBs/ACEis may be a factor in CAA regression (hazard ratio [HR]: 1.5, 95% confidence interval [CI]: 0.91-2.46). CONCLUSIONS: Although ARBs/ ACEis were used more frequently in patients with severe CAA, these patients had similar CAA regression rates to patients not taking ARBs/ACEis. ARBs/ACEis may be beneficial agents aimed at inducing CAA regression in KD patients. WHAT IS KNOWN: • Large CAAs are less likely to regress and are always at risk of life-threatening cardiac events. • Moderate CAA, age less than 1 year, and female sex have been reported to be factors that promote the regression of CAA. WHAT IS NEW: • Although ARBs/ACEis were used more frequently in patients with severe CAA, these patients had a similar rate of CAA regression to patients who did not take ARBs/ACEis. • The regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group.

Effectiveness of Initial Corticosteroid Treatment in Kawasaki Disease Children Suspected to be IVIG Resistant.

This retrospective study assessed the efficacy of initial treatment with intravenous immunoglobulin (IVIG), aspirin, and corticosteroids in Kawasaki disease (KD) patients at risk for IVIG resistance. Data from pediatric patients with KD between January 2010 and December 2019 were divided into the IVIG-sensitive and IVIG-resistant groups based on treatment response. Risk factors for IVIG resistance were identified through univariate analysis. Outcomes included comparison of fever resolution time, hospital stay, and coronary artery lesion (CALs) incidence at multiple intervals post-treatment. An observational group (January 2020 to December 2022) was given additional methylprednisolone if they exhibited three or more IVIG resistance risk factors. The IVIG-resistant group had a higher proportion of males and significantly elevated inflammatory markers (CRP, ESR, PCT) and TBIL, NT-proBNP compared to the IVIG-sensitive group (all p < 0.05), while showing lower levels of albumin, ARR (AST/ALT ratio), and serum sodium (all p < 0.05). Both the IVIG-sensitive and observational groups had significantly shorter fever resolution times and hospital stays than the IVIG-resistant group (all p < 0.05). CALs incidence was consistently higher in the IVIG-resistant group across all follow-up periods (all p < 0.05), with significant differences observed between the observational group and IVIG-resistant group at 1-month, 3-month, and 6-month post-treatment (all p < 0.05). Notably, prior to treatment, the observational group had a higher CALs incidence compared to the IVIG-sensitive group (all p < 0.05). In children with KD who exhibit ≥ 3 risk factors for IVIG non-response, initial treatment with IVIG, aspirin, and glucocorticoids can effectively reduce fever duration, hospitalization duration, and incidence of CALs and is considered safe.

Redundant role of PAD2 and PAD4 in the development of cardiovascular lesions in a mouse model of Kawasaki Disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. While circulating neutrophils are increased and activated during acute KD, it is unclear whether neutrophils and neutrophil extracellular traps (NETs) contribute to the pathogenesis of KD. Peptidylarginine deiminase 4 (PAD4), an enzyme involved in protein citrullination and essential for NETs formation, is implicated in the pathogenesis of various diseases. Here, we used the Lactobacillus casei cell wall extract (LCWE)-induced mouse model of KD vasculitis to determine the contribution of PAD4 in KD vasculitis. We found that the pan-PADs inhibitor, Cl-amidine, significantly reduced LCWE-induced cardiovascular lesions, but neutrophil-specific Padi4 KO mice did not impact development of KD vasculitis. While in vitro treatment of macrophages, which highly express Padi4, with Cl-amidine inhibited IL-1ßsecretion, macrophage-specific Padi4 KO mice did not reduce the lesions. Padi4-/- mice also developed KD vasculitis, AFM30a, a PAD2 inhibitor, significantly reduced KD vasculitis in Padi4-/- mice, indicating a compensatory role of PAD2 in PAD4 deficiency. We also identified several citrullinated proteins in macrophages with constitutively active NLRP3 inflammasome that were inhibited by Cl-amidine treatment, suggesting that protein citrullination participates in NLRP3 inflammasome activation. These data indicate a dispensable role for PAD4-dependent NETs formation, and a redundant role of PAD2 and PAD4 in this murine KD vasculitis. The cardioprotective effects of Cl-amidine to reduce the severity of murine KD vasculitis is not limited to PAD4 inhibition and may include decreased citrullination in the inflammasome pathway.

The value of CT coronary angiography for a comprehensive assessment of left circumflex artery in Kawasaki disease: 9 years of experience from a tertiary center.

Background: Transthoracic echocardiography (TTE) has traditionally been the primary method for coronary imaging in children with Kawasaki disease (KD). We aimed to evaluate coronary artery lesions (CALs) of the left circumflex artery (LCx) in KD on computed tomography coronary angiography (CTCA). Methods: Over a 9-year period (November 2013-December 2022), 225 children with KD underwent radiation-optimized CTCA on a 128-slice dual-source platform. TTE was performed on the same day, or a day prior or after CTCA. Findings: On CTCA, LCx CALs were seen in 41/225 (18.2%) patients. However, TTE detected CALs in only one third of these patients [15/41 (36.6%)]. CTCA showed 47 LCx CALs in 41 patients-aneurysms in 39 patients (40 fusiform, 2 saccular; 7 giant aneurysms), stenoses in 3, and thrombosis in 2. Thromboses and stenoses were both missed on TTE. Proximal LCx aneurysms were seen in 39 patients-of these, 12 had distal extension. Six patients had distal LCx aneurysms without proximal involvement and 2 non-contiguous multiple aneurysms. Four (9.75%) patients had isolated LCx involvement. Based on CTCA findings, treatment protocols had to be modified in 3/41 (7.3%) patients. Interpretation: This study highlights anatomical findings of LCx involvement in KD. Isolated LCx CALs were noted in 4/41 (9.75%) patients. TTE alone proved inadequate for LCx assessment in children with KD. With abnormalities detected in 18.2% of cases, including those missed by TTE, CTCA emerges as an essential imaging modality. The findings have implications for treatment planning and follow-up strategies in children with KD. Funding: None.

Single-cell RNA sequencing: an emerging tool revealing dysregulated innate and adaptive immune response at single cell level in Kawasaki disease.

INTRODUCTION: Kawasaki disease [KD] is a systemic disorder characterized by acute febrile illness due to widespread medium-vessel vasculitis, mainly affecting children. Despite the ongoing advanced research into the disease pathophysiology and molecular mechanisms, the exact etiopathogenesis of KD is still an enigma. Recently, single-cell RNA sequencing [scRNA-seq], has been utilized to elucidate the pathophysiology of KD at a resolution higher than that of previous methods. AREA COVERED: In the present article, we re-emphasize the pivotal role of this high-resolution technique, scRNA-seq, in the characterization of immune cell transcriptomic profile and signaling/response pathways in KD and explore the diagnostic, prognostic, and therapeutic potential of this new technique in KD. Using combinations of the search phrases 'KD, scRNA-seq, CAA, childhood vasculitis' a literature search was carried out on Scopus, Google Scholar, and PubMed until the beginning of 2024. EXPERT OPINION: scRNA-seq presents a transformative tool for dissecting KD at the cellular level. By revealing rare cell populations, gene expression alterations, and disease-specific pathways, scRNA-seq aids in understanding the intricacies of KD pathogenesis. This review will provide new insights into pathogenesis of KD and the field of applications of scRNA-seq in personalized therapeutics for KD in the future.

Identification of novel mitophagy-related biomarkers for Kawasaki disease by integrated bioinformatics and machine-learning algorithms.

Background: Kawasaki disease (KD) is a systemic vasculitis primarily affecting the coronary arteries in children. Despite growing attention to its symptoms and pathogenesis, the exact mechanisms of KD remain unclear. Mitophagy plays a critical role in inflammation regulation, however, its significance in KD has only been minimally explored. This study sought to identify crucial mitophagy-related biomarkers and their mechanisms in KD, focusing on their association with immune cells in peripheral blood. Methods: This research used four datasets from the Gene Expression Omnibus (GEO) database that were categorized as the merged and validation datasets. Screening for differentially expressed mitophagy-related genes (DE-MRGs) was conducted, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A weighted gene co-expression network analysis (WGCNA) identified the hub module, while machine-learning algorithms [random forest-recursive feature elimination (RF-RFE) and support vector machine-recursive feature elimination (SVM-RFE)] pinpointed the hub genes. Receiver operating characteristic (ROC) curves were generated for these genes. Additionally, the CIBERSORT algorithm was used to assess the infiltration of 22 immune cell types to explore their correlations with hub genes. Interactions between transcription factors (TFs), genes, and Gene-microRNAs (miRNAs) of hub genes were mapped using the NetworkAnalyst platform. The expression difference of the hub genes was validated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: Initially, 306 DE-MRGs were identified between the KD patients and healthy controls. The enrichment analysis linked these MRGs to autophagy, mitochondrial function, and inflammation. The WGCNA revealed a hub module of 47 KD-associated DE-MRGs. The machine-learning algorithms identified cytoskeleton-associated protein 4 (CKAP4) and serine-arginine protein kinase 1 (SRPK1) as critical hub genes. In the merged dataset, the area under the curve (AUC) values for CKAP4 and SRPK1 were 0.933 [95% confidence interval (CI): 0.901 to 0.964] and 0.936 (95% CI: 0.906 to 0.966), respectively, indicating high diagnostic potential. The validation dataset results corroborated these findings with AUC values of 0.872 (95% CI: 0.741 to 1.000) for CKAP4 and 0.878 (95% CI: 0.750 to 1.000) for SRPK1. The CIBERSORT analysis connected CKAP4 and SRPK1 with specific immune cells, including activated cluster of differentiation 4 (CD4) memory T cells. TFs such as MAZ, SAP30, PHF8, KDM5B, miRNAs like hsa-mir-7-5p play essential roles in regulating these hub genes. The qRT-PCR results confirmed the differential expression of these genes between the KD patients and healthy controls. Conclusions: CKAP4 and SRPK1 emerged as promising diagnostic biomarkers for KD. These genes potentially influence the progression of KD through mitophagy regulation.

Multisystem inflammatory syndrome in neonates associated with pneumothorax: Case report.

The coronavirus disease 2019 (COVID-19) pandemic that was spread worldwide since 2019 and showed a highly contagious character affecting the lifestyle of people worldwide causing symptoms that are not limited to the respiratory system only but had multi-systemic effects that may progress to severe complications that roughly affect people's health. A newly recognized SARS-CoV-2-associated syndrome called pediatric multisystem inflammatory syndrome has been described worldwide. Initially, it was reported as hyper-inflammatory shock and "Kawasaki-like" symptoms with fever and conjunctivitis, a similar syndrome is also reported in neonates and called Multisystem Inflammatory Syndrome of neonates (MIS-N). In this paper, we presented a case of a newborn baby girl born by caesarian section affected by multisystem inflammatory syndrome of neonates presenting with respiratory distress on her third day of life, then she developed bilateral pneumothorax and pneumomediastinum respectively that required intubation, which highlights that the recognition of pneumothorax and pneumomediastinum as potential presentations of immunoglobulin G (IgG) positive MIS-N in newborns remains crucial.

Ferulic acid suppresses the inflammation and apoptosis in Kawasaki disease through activating the AMPK/mTOR/NF-κB pathway.

Background: Kawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including anti-inflammatory, anti-apoptosis, and anti-fibrosis, and so on. So far, the protective effects of FA on KD have not been explored. Methods: In this study, we established Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model and the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model to investigate the anti-inflammatory and anti-apoptosis effects of FA on KD, and try to elucidate the underlying mechanism. Results: Our in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. In addition, Our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC). The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition. Conclusion: In conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future.