Development Of Coronary Artery Lesions Research Articles

Establishment and validation of a nomogram for predicting intravenous immunoglobulin resistance and coronary artery lesion involvement in Kawasaki disease: a retrospective study.

We aimed to develop a useful nomogram for early identification of Kawasaki disease (KD) children at a high risk of intravenous immunoglobulin (IVIG) resistance and coronary artery lesion (CAL) complications to improve KD management. Clinical data from 400 patients treated at our hospital between January 1, 2016, and December 31, 2023, were collected. Lasso regression was utilized to screen risk factors for IVIG resistance and CAL involvement. Subsequently, a Logistic regression model incorporating parameters screened by Lasso regression was established and visualized as a nomogram. The discrimination, calibration, clinical applicability, and universality of the model were evaluated using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and internal validation. NEU%, HDL-C, and MHR were identified as predictors of IVIG resistance by Lasso regression, with C-index of the Logistic model being 0.886 for the training set and 0.855 for the validation set. For predicting CAL development, sex, fever date before the first IVIG administration, KD type, and the level of HDL-C and MHR were the optimal variables, yielding C-index of 0.915 and 0.866 for the training and validation set, respectively. Calibration curves for both validation sets performed well, indicating strong predictive abilities of the models. We established a nomogram for predicting IVIG resistance that incorporates NEU%, HDL-C, and MHR and a second nomogram for CAL complications incorporating sex, fever date, KD type, and the level of HDL-C and MHR in KD patients, based on the Lasso-Logistic regression model. These nomograms were of guiding significance for screening KD children at high risk of developing IVIG resistance and CAL complications, thereby improving prognosis. Key Points • Two nomograms were established to predict IVIG resistance and CAL complications in KD patients, based on the Lasso-Logistic regression model.

Unravel the Enigma of Kawasaki Disease: Groping in the Dark

Kawasaki disease is one of the leading causes of acquired cardiac disease in childhood especially in Asian countries. Research efforts are extensive and focus on finding the molecular origin of Kawasaki disease. Kawasaki disease shows initially typical symptoms followed by coronary artery lesions in a few percentage of cases. Some patients develop coronary artery lesions, some do not. Research focus on finding biomarkers to predict the development of coronary artery lesions in a child with Kawasaki disease. Kawasaki-like features of the disease are known like MIS-C or Kawasaki-like syndrome, not clearly showing the classical clinical picture of Kawasaki disease. From that point, Kawasaki is not Kawasaki. This manuscript attempts to unravel the molecular and immunological enigma of a rare pediatric disease with to date, unknown etiology.

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

This study aimed to explore Kawasaki disease (KD) susceptibility genes and their complications like coronary artery lesions (CAL) using whole exome sequencing (WES). 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. 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). 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.

A novel scoring system based on sIL-2R for predicting IVIG resistance in Chinese children with KD

ObjectiveThis study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance.MethodsA retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data.ResultsIn our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model.ConclusionOur newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

Construction and validation of predictive models for intravenous immunoglobulin-resistant Kawasaki disease using an interpretable machine learning approach.

Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease is associated with coronary artery lesion development. This study aimed to explore the factors associated with IVIG-resistance and construct and validate an interpretable machine learning (ML) prediction model in clinical practice. Between December 2014 and November 2022, 602 patients were screened and risk factors for IVIG-resistance investigated. Five ML models are used to establish an optimal prediction model. The SHapley Additive exPlanations (SHAP) method was used to interpret the ML model. Na+, hemoglobin (Hb), C-reactive protein (CRP), and globulin were independent risk factors for IVIG-resistance. A nonlinear relationship was identified between globulin level and IVIG-resistance. The XGBoost model exhibited excellent performance, with an area under the receiver operating characteristic curve of 0.821, accuracy of 0.748, sensitivity of 0.889, and specificity of 0.683 in the testing set. The XGBoost model was interpreted globally and locally using the SHAP method. Na+, Hb, CRP, and globulin levels were independently associated with IVIG-resistance. Our findings demonstrate that ML models can reliably predict IVIG-resistance. Moreover, use of the SHAP method to interpret the established XGBoost model's findings would provide evidence of IVIG-resistance and guide the individualized treatment of Kawasaki disease.

The effect of vitamin D status on the occurrence of Kawasaki Disease: a meta-analysis.

The relationship between vitamin D status and Kawasaki Disease (KD), as well as coronary artery lesion (CAL), has yet to be established. A meta-analysis was conducted to assess the correlation between vitamin D status and KD, as well as the impact of vitamin D status on the progression of KD into CAL. The meta-analysis revealed a consistent and significant association between serum 25(OH)D level and the occurrence KD (studies N = 22; z = -3.51, P < 0.001). Patients with KD had markedly lower levels of vitamin D than healthy controls (SMD: -1.30ng/mL, 95%CI: -2.05 to -0.55ng/mL). The study provided evidence supporting a significant association between lower serum vitamin D levels and the occurrence of KD, particularly within the Chinese population. However, the findings did not suggest a direct impact of vitamin D on the development of CAL in KD patients.

Single-Cell Transcriptome Reveals Potential Mechanisms for Coronary Artery Lesions in Kawasaki Disease.

Coronary artery lesions (CALs) are the most common and major complication of Kawasaki disease (KD) in developed countries. However, the underlying immunologic mechanisms of CAL development in KD remain unclear. Here, we conducted single-cell transcriptome analyses of 212 210 peripheral blood mononuclear cells collected from a cross-sectional cohort of 16 children, including 4 patients with KD with CALs, 5 patients with KD without CALs, 4 healthy controls, and 3 febrile controls. KD altered the proportion of peripheral blood mononuclear cells, including an increasing trend in inflammatory cells (megakaryocytes and monocytes) and a decreasing trend in lymphocytes (eg, CD4+ T, CD8+ T, mucosal-associated invariant T, natural killer, and γδ T cells), highlighting the potential presence of lymphopenia phenomenon in KD. Our data indicated the presence of inflammatory cytokine storm in patients with KD with CALs, caused by systemic upregulation of TNFSF13B (tumor necrosis factor superfamily member 13b), CXCL16 (C-X-C motif chemokine ligand 16), TNFSF10 (tumor necrosis factor superfamily member 10), and IL1RN (interleukin 1 receptor antagonist), mainly produced by monocytes (especially for the Mono_CD14-CD16 cluster) and megakaryocytes. We also found that myeloid cells of patients with KD, particularly in those with CALs, might play a role in vascular injury (eg, increased MMP [matrix metalloproteinase] 9, MMP17, and MMP25) and immune cell recruitment. The immune landscape of patients with KD with CALs was featured by lower exhaustion levels in natural killer cells, a high cytotoxic state in the CD8_Pro cluster, and activation of the complement system in monocytes. Additionally, the activation of B cells was more pronounced in the early stage of KD. Collectively, this study provides a comprehensive understanding of the roles of various immune cells and inflammatory cytokine storms in the development of CALs in KD and offers a valuable resource for identifying novel therapeutic targets for patients with KD with CALs.

Coronary artery lesions in Takayasu arteritis.

Takayasu arteritis (TAK) is a granulomatous inflammation of vessels of large diameter, mainly affecting the aorta and its proximal branches, which is more common in young women. The incidence of coronary artery disease in TAK is unknown and not sufficiently studied. A literature review was performed for the period 2003 to 2023 using a search of the PubMed and Scopus scientific databases. We used the following key words to search the academic journal databases: "Takayasu arteritis", "coronary angiography", "myocardial revascularization", "coronary artery disease", "angina pectoris", and "myocardial infarction". The analysis of studies showed that coronary artery lesions (CAL) in TAK are not uncommon, being identified particularly in children and young individuals. Pathology of the coronary arteries increases the morbidity and mortality of TAK patients. In TAK, the ostia and proximal segments of the coronary arteries are more frequently affected, presenting as stenosis or occlusion with the development of stable coronary artery disease, unstable coronary artery disease, acute myocardial infarction, and sudden death. The diagnosis of TAK and coronary artery pathology is often complicated due to nonspecific manifestations and frequently the absence of symptoms. The treatment of patients with TAK with CAL is challenging and requires both pharmacological therapy and interventional or surgical methods of myocardial revascularization. Takayasu arteritis is a more prevalent cause of CAL development, especially in young patients, than previously believed, and cardiovascular death due to CAL is not rare. Early diagnosis of TAK with CAL, particularly occlusion or hemodynamically significant stenosis, and the prompt initiation of appropriate treatment prevent dangerous complications, reduce mortality, and improve prognosis.

Association of recent antibiotic exposure and coronary artery lesions in Kawasaki disease: nationwide study.

To investigate the relationship between recent antibiotic exposure and the development of coronary artery lesions (CALs) during the clinical course of Kawasaki disease (KD). Data were obtained from the 25th nationwide epidemiological survey of KD conducted in Japan from 2017 to 2018. Baseline characteristics and clinical course were compared between Antibiotics (+) and Antibiotics (-) groups. Nationwide survey of KD in Japan. KD patients were enrolled by response to a questionnaire sent to physicians working in pediatrics at hospitals with >100 beds. Antibiotic exposure within one week before the first hospital visit as KD patients. The relationship between recent antibiotic exposure and the development of coronary artery lesions (CALs). Out of 28,265 KD patients, 12,918 (45.7%) received antibiotics. In KD patients who received antibiotics in the week before KD diagnosis, the frequency of coronary artery lesions (CALs) at each phase were significantly higher compared to those who did not receive antibiotics. In further analysis using propensity score matching, recent antibiotic exposure and the initial IVIG resistance were associated with CALs at the acute and the sequelae phase. After adjusting for the status of initial IVIG resistance, recent antibiotic exposure remained associated with CALs during the acute phase (adjusted OR 1.29, 95%CI 1.16, 1.43) and the sequelae phase (1.26, 95%CI 1.04, 1.52). These observations suggest that recent antibiotic exposure might be associated with higher frequency of CAL development in KD patients, possibly by altering the gut microbiota and diminishing beneficial bacteria.

Nomogram for predicting coronary artery lesions in patients with Kawasaki disease.

Coronary artery lesions are the most important complications of Kawasaki disease. Approximately 25-30% of untreated patients develop coronary artery disease, which can lead to long-term cardiovascular sequelae. The aim of this study is to evaluate the risk factors for coronary artery lesions in Kawasaki disease and to construct a nomogram for predicting the likelihood of developing such lesions. Data from 599 patients between January 2012 and June 2020 were reviewed retrospectively. Patients were randomly assigned to the training set (n = 450) and the validation set (n = 149). A comparison of clinical features and laboratory data was performed, followed by multivariate logistic regression analysis to identify independent risk factors and develop the nomogram. The predictive efficiency of the nomogram was evaluated using the calibration curve, area under the receiver operating characteristic curve (AUC), C-index, and decision curve analysis (DCA). Intravenous immunoglobulin (IVIG) resistance, delayed IVIG treatment, C-reactive protein, and neutrophil/lymphocyte ratio were identified as independent risk factors for the development of coronary artery lesions. The nomogram was constructed based on these four variables. The calibration curve of the nomogram showed a high degree of agreement between the predicted probability and the actual probability. The AUC of the nomogram in the training and validation set was 0.790 and 0.711, respectively. In addition, DCA revealed that the nomogram provided a significant net benefit, further supporting its clinical utility. The constructed nomogram demonstrates a strong and reliable performance in predicting coronary artery lesions, which enables clinicians to make timely and tailored clinical decisions.

The role of red blood cell distribution width in predicting coronary artery lesions in pediatric patients with kawasaki disease.

Recent studies have shown that red blood cell distribution width (RDW) has emerged as a novel predictor of cardiovascular diseases. We aim to investigate the association between RDW and the risk of coronary artery lesions (CALs) in pediatric patients with Kawasaki disease (KD). KD patients were classified as the CALs group (patients with CALs) and non-CALs group (patients without CALs). Differences among the groups were analyzed by Mann-Whitney U-test and Chi-square analysis. The independent risk factors of CALs were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the optimal cut-off value. The red blood cell distribution width (RDW) and C-reactive protein were significantly higher in the CALs group than those in the non-CALs group (p < 0.01). Multivariate logistic regression analysis revealed that RDW (OR = 5.2, 95% CI, 4.064 to 6.654) was independent risk factors of CALs in KD patients (p < 0.01). The subgroup analysis also confirmed that the high level of RDW was an independent risk factor for the development of CALs in patients with complete and incomplete KD. The ROC analysis showed the optimal cut-off value of RDW for predicting CALs was >13.86%, with a sensitivity of 75.79% and specificity of 92.81% (AUC = 0.869, 95% CI = 0.844-0.892; p < 0.0001). RDW is an independent predictor with high sensitivity and specificity to predict CALs in KD patients. The elevation in RDW level (>13.86%) may be used as novel biomarkers for early predicting CALs in KD patients during the acute phase.

Tenascin-C predicts IVIG non-responsiveness and coronary artery lesions in kawasaki disease in a Chinese cohort.

To assess the predictive value of tenascin-C (TN-C) for intravenous immunoglobulin (IVIG) non-responsiveness and coronary artery lesions (CALs) development at the acute stage of Kawasaki disease, and to build novel scoring systems for identifying IVIG non-responsiveness and CALs. A total of 261 patients in acute-stage Kawasaki disease were included. Serum samples before IVIG initiation were collected and TN-C expression levels were measured using an enzyme-linked immunosorbent assay. In addition to TN-C, another fifteen clinical and laboratory parameters collected before treatment were compared between IVIG responsive and non-responsive groups, and between groups with and without CALs. Multiple logistic regression analyses were performed to construct new scoring systems for the prediction of IVIG non-responsiveness and CALs development. IVIG non-responsive group (n = 51) had significantly higher TN-C level compared to IVIG responsive group (n = 210) (15.44 vs. 12.38 IU/L, P < 0.001). A novel scoring system composed of TN-C, total bilirubin, serum sodium and albumin was established to predict IVIG non-responsiveness. Patients with a total score ≥ 2 points were classified as high-risk cases. With the sensitivity of 78.4% and specificity of 73.8%, the efficiency of our scoring system for predicting IVIG non-responsiveness was comparable to the Kobayashi system. Consistently, the group developing CALs at the acute stage (n = 42) had significantly higher TN-C level compared to the group without CALs (n = 219) (19.76 vs. 12.10 IU/L, P < 0.001). A new scoring system showed that patients with elevated TN-C, platelet count ≥ 450 × 109/L, and delayed initial infusion of IVIG had a higher risk of developing CALs. Individuals with a total score ≥ 3 points were classified as high-risk cases. The sensitivity and specificity of the novel simple system for predicting CALs development were 83.3% and 74.0%, respectively, yielding a better efficiency than the Harada score. Elevated TN-C appeared to be an independent risk factor for both IVIG non-responsiveness and CALs in Chinese children with KD. Our scoring systems containing TN-C is simple and efficient in the early identification of high-risk KD cases that could benefit from more individualized medications.

Abstract 9361: Interleukin-33 System as Potential Biomarker and Therapeutic Target in Kawasaki Disease

Introduction: Kawasaki disease (KD) is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions (CALs) during childhood. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as DAMPs. Hypothesis: IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Methods: Serum levels of soluble ST2 (sST2) in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). Results: Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries (87.2 [18.4-224.0] ng/mL vs. 31.7 [8,8-290.3] ng/mL, p = 0.017). In vitro , IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein–1 in HCAECs in a time- and concentration-dependent manner. Notably, compared to isoconcentration of tumor necrosis factor-α (TNF-α), IL-33 significantly increased IL-6 production; 10 ng/mL of IL-33 increased the production of IL-6 by 13-fold compared with that by TNF-α (9.1 ng/mL vs. 0.7 ng/mL, p &lt; 0.05). Moreover, IL-1β increases IL-33 production by HCASMCs in a concentration-dependent manner. Conclusions: The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD.

Interleukin-33/ST2 Axis as Potential Biomarker and Therapeutic Target in Kawasaki Disease.

Kawasaki disease (KD) is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions (CALs) during childhood. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as a DAMP. We studied whether IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Serum levels of soluble ST2 (sST2) in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells (HCAECs). Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries. In vitro, IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein-1 in HCAECs in a time- and concentration-dependent manner. Moreover, IL-33 induced significantly greater production of IL-6 and IL-8 in HCAECs compared to the condition stimulated with isoconcentration of tumor necrosis factor-α. The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD.

Association of miR-181c/d gene locus rs8108402 C/T polymorphism with susceptibility to Kawasaki disease in Chinese children.

BackgroundKawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. The rs8108402 C/T single nucleotide polymorphism (SNP) is located in the promoter region of miR-181-c/d gene and the intron of Nanos3 gene. The miR-181 family contributes to the pathogenesis of cardiovascular and inflammatory disorders, while Nanos3 is involved in DNA transcription regulation and cell proliferation. However, no studies have examined the association between miR-181c/d and Nanos3 polymorphisms and the susceptibility and progression of KD.ObjectiveThe purpose of our study is to examine the association of miR-181c/miR-181d/Nanos3 gene locus rs8108402 C/T polymorphism with KD susceptibility, intravenous immunoglobulin (IVIG) responsiveness, and the development of coronary artery lesions (CAL).MethodsPeripheral blood specimens from 100 children with KD and 100 healthy children were collected. The polymorphism of rs8108402 C/T was detected using polymerase chain reaction-sequencing-based typing technique.ResultsThere were statistically significant differences in C and T allele frequency distributions between the KD group and healthy controls for the polymorphic site rs8108402 C/T (P = 0.002). The distribution of the genotypes CC, CT, and TT also presented statistical significant difference between the KD and control groups (P = 0.003). Compared to the rs8108402 C allele, the T allele was associated with increased KD susceptibility (OR = 2.080, 95% CI = 1.317∼3.283). However, there were no significant associations discovered between the rs8108402 C/T polymorphism and CAL formation or IVIG unresponsiveness in the study.ConclusionSNP rs8108402 C/T located in the miR-181c/d promoter and Nanos3 intronic region is associated with susceptibility to Kawasaki disease but not with the development of coronary artery lesions or IVIG unresponsiveness in Chinese children.

Association of Genetic Polymorphisms in Kawasaki Disease with the Response to Intravenous Immunoglobulin Therapy.

Kawasaki disease (KD) is an acute febrile and systemic vasculitis disease mainly affecting children < 5years old. Although the first case of KD was reported in 1967 and despite extensive research on KD since then, the cause of the disease remains largely unknown. The most common complications of KD are coronary artery lesions (CAL), which significantly increase the risk of coronary heart disease. The standard treatment for KD is high-dose intravenous immunoglobulin (IVIG) plus aspirin within 10days from symptoms' appearance, which has been shown to decrease the incidence of CAL to 5-7%. Despite the benefits of IVIG, about 25% of the patients treated with IVIG develop resistance or are unresponsive to the therapy, which represents an important risk factor for CAL development. The cause of IVIG unresponsiveness has not been fully elucidated. However, the role of gene polymorphisms in IVIG response has been suggested. Herein, we comprehensively review genetic polymorphisms in KD that have been associated with IVIG resistance/unresponsiveness and further discuss available models to predict IVIG unresponsiveness.Kindly check and confirm inserted city in affiliation [1] is correctly identified.confirm.

Breastfeeding has no protective effects on the development of coronary artery lesions in Kawasaki disease: a retrospective cohort study

BackgroundKawasaki disease (KD) is a self-limiting vasculitis with an unknown etiology. It has been reported that breastfeeding has a potential protective effect on KD development. However, whether breastfeeding has an effect on the development of coronary artery lesions (CALs) remains unclear.MethodsWe retrospectively reviewed the medical records of patients with the main diagnosis of KD hospitalized in our hospital from May 2017 to November 2018. Standardized telephone interviews were carried out to obtain feeding practices before KD was onset.ResultsTwo hundred and ninety-three (51.6%) were exclusively breastfed, 223 (39.3%) were partially breastfed and 52 (9.2%) were formula fed. There were no significant differences in the characteristics regarding age, gender, incomplete KD, intravenous immunoglobulin (IVIG) resistance, and the laboratory variables among the three groups. With formula feeding as a reference, patients exclusively breastfed and partially breastfed seemed to have a higher incidence of CALs, even after adjusting confounders, but were not statistically significant. After grouping patients who were older than six months into formula feeding, partial breastfeeding for < 2 months, partial breastfeeding for ≥ 2 and < 4 months, partial breastfeeding for ≥ 4 and < 6 months and exclusively breastfeeding based on the length of breastfeeding, the results remained the same (P > 0.05).ConclusionsBreastfeeding has no protective effect on the development of CALs in KD.

Combination of fecal calprotectin and initial coronary dimensions to predict coronary artery lesions persistence in Kawasaki disease

Kawasaki Disease (KD) is systemic vasculitis involving medium-sized vessels in children. The aim of our study is to determine if fecal calprotectin (FC) could be useful in predicting the development or persistence of coronary artery lesions (CALs) in KD. We conducted a prospective monocentric study including all consecutive diagnoses of. Clinical, laboratory, echocardiographic data were recorded during the acute and subacute phase, including FC. Correlations among laboratory values, FC, clinical manifestations, IVIG-responsiveness and CALs development were investigated. We enrolled 26 children (76.9% boys; median age 34.5 months). The combination of FC > 250 microg/g and z-score > 2 during the acute phase was associated with the persistence of CALs (p = 0.022). A z-score > 2 alone during the acute phase was not related to CALs during the subacute stage (p > 0.05). A neutrophil percentage > 70% and WBC > 15,000/mmc during the acute phase significantly correlated with the presence of CALs during the subacute phase (p = 0.008). C-reactive protein (CRP) > 13 mg/dL at KD onset was significantly associated with the presence of CALs during the acute (p = 0.017) and subacute phase (p = 0.001). The combination of FC > 250 microg/g and a z-score > 2 during the acute phase of KD may be used as a predictor of CALs persistence. It can be useful especially in children with an initial CRP < 13 mg/dl.

CD36 is Associated With the Development of Coronary Artery Lesions in Patients With Kawasaki Disease.

Kawasaki disease (KD) is an autoimmune-like vasculitis of childhood involving the coronary arteries. Macrophages require scavenger receptors such as CD36 to effectively clear cellular debris and induce self-tolerance. In this study, we hypothesized that CD36 plays an important role in the immunopathogenesis of KD, by aiding in the clearance of plasma mitochondrial DNA, and by amplifying the immune response by activating the inflammasome pathway via AIM2. Fifty-two healthy controls, 52 febrile controls, and 102 KD patients were recruited for RT-PCR of target mRNA expression and plasma mitochondrial DNA. Blood samples were obtained 24 hours prior and 21 days after the administration of intravenous immunoglobulin (IVIG) therapy. Patients with acute KD had higher plasma levels of cell-free mitochondrial DNA (ND1, ND4, and COX1), and higher mRNA expressions of CD36 and AIM2 when compared to both healthy and febrile controls. A greater decrease in both CD36 and AIM2 mRNA expression after IVIG therapy was associated with the development of coronary artery lesions. Coronary artery lesions were associated with a larger decrease of CD36 expression following IVIG therapy, which may indicate that prolonged expression of the scavenger receptor may have a protective effect against the development of coronary artery lesions in KD.

Sivelestat's effect on Candida albicans water-soluble fraction-induced vasculitis.

We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water-soluble fraction-induced vasculitis. Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water-soluble fraction-induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM-1) positive areas, ICAM-1 and tumor necrosis factor-α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood. The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH-treated mice. The NE- and ICAM-1-positive regions, and the mRNA expression of ICAM-1 and tumor necrosis factor-α were lower in the SSH-treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH-treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH-treated mice. Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE-inhibitory effect, SSH sites of action may also include monocytes.