BACKGROUND:We aimed to explore predictive measures for intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD). METHODS:Patients diagnosed with KD were enrolled in this study. Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups. Independent predictors of IVIG resistance were analyzed, and a predictive model for KD children with IVIG resistance was constructed. RESULTS:A total of 277 children with KD, 180 boys and 97 girls, aged 2-128 (median 23) months, were enrolled in the study. Compared with the IVIG-responsive group, the IVIG-resistant group had higher levels of the peripheral neutrophil count, mean platelet volume, mean platelet volume-to-lymphocyte ratio and C-reactive protein, and total serum bilirubin, but lower levels of peripheral lymphocyte count, serum albumin and serum prealbumin. Age (in months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis. A logistic regression model and a scoring system were set up, where cut-off values of - 0.46 and 6.5 points yielded sensitivities of 83.9% and 77.4%, and specificities of 74.8% and 61.0%, respectively. The areas under the curve (AUC) were 0.808 in the logistic regression model, and 0.750 in the scoring system. CONCLUSION:Our model for predicting IVIG-resistant children with KD, involving age (months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment, is helpful for clinical prediction of children with IVIG-resistant KD.

BACKGROUND:Kawasaki disease (KD) is an acute febrile illness of unknown etiology and predictors for intravenous immunoglobulin (IVIG) resistance have been widely explored in recent decades. Neutrophil to lymphocyte platelet ratio (NLPR) was reported to be associated with the outcomes in many diseases. However, its relationship with IVIG resistance has not be explored. METHODS:The medical data of patients diagnosed with KD in Children's Hospital of Soochow University between January 2019 and December 2020 were retrospectively reviewed and analyzed. Patients were trisected into three groups based on NLPR. Logistics regression was used to analyze the association between NLPR and IVIG resistance. Restricted cubic spine was used to exhibit the relationship. Sensitivity analysis and subgroup analysis were also carried out. RESULTS:A total of 803 patients were included in the present study (61.8% males; median age: 24 months). IVIG resistance occurred in 74 (9.2%) patients. Multivariable-adjusted analyses revealed higher NLPR (odds ratio [95% confidence interval]: 1.12 [1.00-1.24]) was an independent predictor of IVIG resistance, which was strengthened by sensitivity analyses. The association of NLPR and IVIG resistance was not modified by age, sex, CALs, or days of IVIG initiation ≤ 4. CONCLUSION:NLPR may be a valuable prognostic marker in KD patients with IVIG resistance.

OBJECTIVE:We aimed to develop a nomogram to predict risk of resistance to intravenous immunoglobulin (IVIG) in children with Kawasaki disease in eastern China. METHODS:We retrospectively analysed the data of children with Kawasaki disease who received IVIG during hospitalisation at Soochow University Affiliated Children's Hospital. IVIG resistance was defined as recrudescent or persistent fever ≥36 h after the end of the IVIG infusion. Baseline variables were analysed using least absolute shrinkage and selection operator (LASSO) to identify the predictors of IVIG resistance, which were then used to construct a predictive nomogram. Calibration curve and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the model. The predictive nomogram was validated on test sets of external data and prospective data. RESULTS:Between January 2015 and December 2020, 1293 Kawasaki disease patients were hospitalized in Soochow University Affiliated Children's Hospital. Among them, 72 (5.57%) showed IVIG resistance. LASSO identified haemoglobin, percentage of neutrophils, C-reactive protein level, platelet count, serum albumin, serum sodium, serum alkaline phosphatase, coronary artery damage, and complete Kawasaki disease as risk factors for IVIG resistance. The nomogram constructed using these factors showed satisfactory discriminatory power (AUC, 0.75), and sensitivity (0.74) and specificity (0.64). In the external data and prospective data, the AUC was 0.66 and 0.83, respectively, the sensitivity was 0.86 and 1, respectively, and the specificity was 0.49 and 0.60, respectively. CONCLUSIONS:The predictive nomogram constructed using nine factors associated with IVIG resistance in children with Kawasaki disease could be a useful tool for identifying patients likely to show IVIG resistance. This nomogram may help reduce the risk of coronary artery lesions.Key MessagesNone of the IVIG resistance scoring systems has shown consistently good performance in previous studies. Tools to predict the risk of IVIG resistance in eastern China are lacking.In our series, haemoglobin level, percentage of neutrophils, platelet count, coronary artery damage, incomplete Kawasaki disease, and CRP, serum albumin, serum sodium, and serum alkaline phosphatase levels were risk factors of IVIG resistance in hospitalized children in the eastern China cities of Suzhou and Fuzhou.We propose an easy-to-use nomogram to predict the risk factors of IVIG resistance in hospitalized children.

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.

BACKGROUND:Kawasaki disease (KD) causes coronary artery lesions (CAL) and is the leading cause of acquired heart disease in children. The aim of this study is to evaluate the risk factors and set-up a scoring system for predicting CAL of KD. METHODS:We retrospectively reviewed a total of 478 patients diagnosed with KD. We compared age, gender, laboratory data, and treatment response in two groups and developed a scoring system for predicting CAL. RESULTS:During the study period, 365 of these patients had complete medical records of coronary surveys by echocardiography. Anemia, hypoalbuminemia, C reactive protein (CRP), alanine aminotransferase, neutrophil count, and neutrophil/lymphocyte ratio (NLR) showed significant differences with CAL formation. We determined the cut-off value using a receiver-operating-characteristic (ROC) curve, and following multivariate logistic regression analysis, four independent risk factors demonstrated a significant difference with CAL formation, including CRP > 103 mg/L, NLR > 3.5, male gender, and intravenous immunoglobulin (IVIG) resistance. We established a score system based on the above evaluation, for which a ROC curve was performed, and a total score of ≥ 2 points showed a sensitivity of 60.8% and a specificity of 70.6%, with an area under the ROC curve of 0.696. CONCLUSIONS:Identifying children at risk is important in order to prevent CAL from developing. Four independent risk factors that can predict CAL formation were CRP > 103 mg/L, NLR > 3.5, male gender, and IVIG resistance. This first report incorporated NLR into score systems to predict CAL reinforces previously well-known risk factors for the CAL formation among KD patients.

Background:Early identification and treatment are paramount for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Unfortunately, there is no single crucial biomarker to identify these patients in a timely manner, which makes KD the most common cause of acquired heart disease in children in developed countries. Recently, many studies have focused on the association between serum ferritin (SF), IVIG resistance, and CALs in KD. We thus performed a systematic review and meta-analysis to ascertain the diagnostic and prognostic values of SF in predicting IVIG resistance and CALs in KD in the acute phase. Methods:The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were extracted from the data to evaluate the SF levels in KD. The hazard ratios (HRs) of related risk factors and their corresponding 95% confidence intervals (CIs) were applied to compute the pooled assessments of the outcomes. Results:A total of 11 eligible articles were included in this meta-analysis, including twenty studies for diagnosis and five studies for prognosis. In terms of diagnostic values, SF could identify KD patients in the overall studies with a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.76 (95% CI: 0.69-0.82), 0.82 (95% CI: 0.76-0.88), 4.33 (95% CI: 3.07-6.11), 0.29 (95% CI: 0.22-0.38), 15.0 (95% CI: 9.00-25.00), and 0.86 (95% CI: 0.83-0.89), respectively. In studies comparing KD patients and controls, there were a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.79 (95% CI: 0.72-0.84), 0.84 (95% CI: 0.79-0.91), 4.61 (95% CI: 3.27-6.51), 0.26 (95% CI: 0.20-0.34), 20.82 (95% CI: 11.83-36.64), and 0.89 (95% CI: 0.86-0.91), respectively. For the prognostic values, we found poor survival outcomes based on KD patients (HR = 1.31, 95% CI: 1.07-1.59, = 0.008). Conclusion:Our meta-analysis suggests that SF may be used as a workable and critical biomarker for the diagnosis and prognosis of IVIG resistance and CALs in patients with KD. We also propose that maintaining the dynamic balance between iron, SF, and ferroptosis will be an important therapeutic strategy to reduce the morbidity of CALs. Systematic review registration:[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022279157].

Several studies explored the associations of pre-albumin (PA)/albumin (ALB) and ALB-combined indicators (prognostic nutrition index [PNI], albumin-to-globulin ratio [AGR], bilirubin-to-albumin [BAR], and C-reactive protein/albumin ratio [CAR]) with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD) patients. However, the results were controversial. A meta-analysis was conducted to reconfirm their associations and predictive performance. Databases of PubMed, EMBASE, and the Cochrane library were searched. The pooled standardized mean difference (SMD) or odds ratios (ORs) assessed the association, while the pooled area under the receiver operating characteristic curve (AUC) evaluated the predictive power. Ninety-four studies were included. Overall and subgroup meta-analyses demonstrated lower ALB and higher CAR were associated with IVIG resistance (ALB: SMD = -0.61; OR = 0.83; CAR: SMD = 1.47; OR = 1.69) and CALs (ALB: SMD = -0.56; OR = 0.92; CAR: SMD = 0.52). PNI was reduced in IVIG-resistant (SMD = -0.82) and coronary artery aneurysm (SMD = -0.18) patients in subgroup analysis and high PNI predicted the decreased risk of CALs in overall analysis (OR = 0.82). ALB, CAR, and PNI were a good or fair biomarker for differentiating IVIG-resistant (CALs) from IVIG-sensitive (non-CALs) patients (AUC > 0.6 or > 0.7). PA (SMD = -0.72) and BAR (SMD = 1.10) were differential in IVIG-resistant, but not in CAL patients compared with controls. AGR was not associated with CALs ( > 0.05). In conclusion, ALB, CAR, PNI, PA, and BAR may represent promising biomarkers for the prediction of IVIG resistance and CALs in KD patients.

OBJECTIVE:To study the changes of plasma prealbumin (PA) and C-reactive protein (CRP) in children with Kawasaki disease, and to explore the importance of integral analysis of plasma PA and CRP in predicting the severity of coronary artery lesions in Kawasaki Disease. METHODS:In a retrorespective study, 108 children with Kawasaki disease admitted in our hospital were enrolled. The statistical methods included t test, Chi-square test, and ROC curve analysis. The changes of plasma PA and CRP during the disease were studied. Also, the usefulness of comprehensive analysis of PA and CRP in predicting the severity of coronary artery lesions was also evaluated. RESULTS:During the acute phase of Kawasaki disease, the plasma PA level was decreased distinctly, while the CRP level increased significantly. Among the 55 cases whose plasma PA level was <80 mg/L, setting CRP=76.5 mg/L as the cutoff value, the occurrence of coronary artery dilations for those with CRP level<76.5 mg/L was significantly higher than those with CRP level >76.5 mg/L (P<0.05). CONCLUSION:Plasma PA and CRP changed greatly during the process of Kawasaki disease. And it may be of importance in predicting the severity of coronary artery lesions, by using integrated plasma PA and CRP.

BACKGROUND:Early identification of intravenous immunoglobulin (IVIG) resistance contributes to better management of Kawasaki disease (KD). This study aims to establish an effective prediction model for IVIG resistance in the Chinese population. METHODS:A total of 658 eligible patients diagnosed with KD were enrolled in this study, with 461 in the training cohort and 197 in the validation cohort. The demographic characteristics and potential risk factors were compared between IVIG-responsive and resistant groups. Predictors were selected by the Akaike information criterion. The nomogram's performance was evaluated by calibration curve, decision curve analysis, and operating characteristic curve. RESULTS:White blood cell counts (WBC), neutrophil-lymphocyte ratio (N/L ratio), hematocrit (HCT), albumin (ALB), total bilirubin (TBIL), lactate dehydrogenase (LDH), and creatinine (Cr) were detected as predictors of IVIG resistance. A predictive nomogram incorporating these predictors was constructed using the training cohort. The calibration curve and decision curve analysis showed good discrimination and calibration of the proposed nomogram in both training and validation sets, and the area under the receiver operating characteristic curve (AUROC) in both sets was 75.8% and 74.2%, respectively. CONCLUSION:This study identified WBC, N/L ratio, HCT, ALB, TBIL, LDH, and Cr as predictors for IVIG resistance in patients with KD. The proposed novel nomogram with a high level of accuracy and reliability may benefit clinical decision-making upon treatment initiation.

Intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) was associated with coronary artery lesions. Neutrophil percentage-to-albumin ratio (NPAR) is an index of mortality in several inflammatory diseases. This study focused on the association of NPAR with IVIG- resistance in KD. Clinical and laboratory data of 438 children with KD before IVIG treatment were retrospectively analyzed. Notably, high NPAR was associated with older age, high WBC, NP, ALT, total bilirubin and CRP, as well as with high the incidence of IVIG-resistance, and with low hemoglobin (Hb), PLT, ALB and sodium levels. NPAR (OR: 2.366, 95% CI: 1.46-3.897, p = 0.001) and Hb (OR: 0.967, 95% CI: 0.944-0.989, p = 0.004) were independent risk factors for IVIG-resistance. NPAR showed linear relation with IVIG-resistance (p for nonlinear = 0.711) and the nonlinear correlation was found between IVIG-resistance and Hb (p for nonlinear = 0.002). The predictive performance of NPAR was superior to Beijing model (z = 2.193, p = 0.028), and not inferior to Chongqing model (z = 0.983, p = 0.326) and the combination of NPAR and Hb (z = 1.912, p = 0.056). These findings revealed that NPAR is a reliable predictor of IVIG-resistance.

C-reactive protein (CRP) to albumin ratio (CRP/Alb) has emerged as a novel marker of inflammation, but few studies have evaluated the role of CRP/Alb ratio in Kawasaki disease (KD). Coronary artery lesions (CAL) in children with KD is a major acquired heart disease. We aimed to assess the association between CRP/Alb ratio and CAL formation in children with KD. This retrospective study enrolled children diagnosed with KD and divided them into two groups, KD with CAL and KD without CAL. We compared the difference in gender, age, laboratory data, intravenous immunoglobulin (IVIG) resistance rate, and incidence of CAL between the two groups. Multivariable logistic regression analysis was used to assess the independent risk factors of CAL. We adopted receiver operating characteristic (ROC) curve analysis to determine the predictive ability of CRP/Alb ratio in predicting CAL. In total, 410 KD patients were reviewed, with 143 in the KD with CAL group and 267 in the KD without CAL group. KD children with CAL had a higher CRP/Alb ratio than those without CAL (3.14 ± 3.17 vs. 2.12 ± 2.04, < 0.001). Multivariable logistic regression analysis demonstrated that male gender (OR = 3.222, < 0.001), incomplete KD (OR = 1.968, = 0.031), greater platelet count (OR = 1.004, < 0.001), higher CRP (OR = 0.982, = 0.048), and higher CRP/Alb ratio (OR = 1.994, = 0.016) were all independent risk factors for predicting CAL. KD children with a high CRP/Alb ratio (≥2.94) had a higher incidence rate of CAL and IVIG resistance than those with a low CRP/Alb ratio (<2.94) (49.6 vs. 28.7%, < 0.001 and 11.6 vs. 3.5%, = 0.001, respectively). This report is the first to show the role of CRP/Alb ratio in KD children. CRP/Alb ratio can serve as a novel predicting marker for CAL formation and IVIG resistance in KD.

Kawasaki disease (KD) is the common acute, self-limiting vasculitis in children, often affecting coronary arteries, which may lead to coronary artery dilation, stenosis, or in severe cases, myocardial infarction. This study aimed to identify new approaches for reducing or preventing coronary artery lesions (CAL) in KD patients by analyzing specific serological markers across various paediatric groups. Clinical data were collected from 100 children diagnosed with Kawasaki disease (KD) admitted at First Affiliated Hospital of Hebei North University between May 2023 and June 2024. These children were divided into two groups based on coronary artery injury status: Occurrence group (n = 31) and Non-occurrence group (n = 69). Additionally, data from 100 children with acute upper respiratory tract infections (URTI) and 100 healthy children who underwent routine physical examination during the same period (Healthy group) were included for comparison. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), D-dimer (D-D), albumin (ALB), and T-cell subsets were measured and compared across groups to evaluate their clinical utility in diagnosing coronary artery damage in KD. NT-proBNP and D-D levels were highest in KD children with coronary artery injury and lowest in the healthy group, while ALB levels were lowest in KD children with coronary artery injury and highest in the healthy group, with statistically significant differences ( < 0.001). Analysis of T-cell subsets revealed that cluster of differentiation (CD)3, CD4, and CD4/CD8 levels were highest in the Healthy group, while CD8 levels were highest in the Occurrence group, with statistically significant differences ( < 0.001). The combined diagnostic model demonstrated an area under the curve (AUC) value of 0.885 (95% CI: 0.829-0.941), showing higher specificity and AUC value compared to each marker individually. The combination of serum NT-proBNP, D-D, ALB, and T-cell subsets offers valuable predictive insights for coronary artery damage in KD children and may serve as an auxiliary diagnostic tool.

OBJECTIVE:To investigate the association between the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT ratio, AAR) and intravenous immunoglobulin (IVIG) resistance, coronary artery lesions (CAL), and coronary artery aneurysms (CAA) in children with Kawasaki disease (KD). DESIGN:We retrospectively studied 2678 children with KD and divided them into two groups: a low-AAR group and a high-AAR group with a median AAR of 1.13 as the cut-off point. The differences in laboratory data, clinical manifestations, and coronary artery damage rates were compared between the two groups. RESULTS:The incidence of CAL was higher in the low-AAR group than in the high-AAR group at 2 and 3-4 weeks after illness onset ( < 0.001, respectively). The IVIG resistance rate was significantly higher in the low-AAR group than in the high-AAR group (29.94% vs 21.71%, < 0.001). The levels of C-reactive protein, erythrocyte sedimentation rate, white blood cell count, bilirubin, fibrinogen, thrombin time, D-dimer, and brain natriuretic peptide were also significantly higher in the low-AAR group compared with the high-AAR group. The levels of albumin and IgG were significantly lower in the low-AAR group compared with those of the high-AAR group. The proportion of typical KD cases in the low-AAR group was significantly higher than that in the high-AAR group. Low-AAR correlated with the risk of coronary artery damage and IVIG resistance. CONCLUSION:Children with KD who had low-AAR value were more likely to develop coronary artery damage and IVIG resistance. Low AAR is a risk factor for CAL, CAA, and IVIG resistance in KD.

Coronary artery lesions (CALs) are the most common complications of Kawasaki disease (KD) and play a crucial role in determining the prognosis of the disease. Consequently, the early identification of children with KD who are at risk of developing coronary artery damage is vitally important. We sought to investigate the relationship between the Systemic Immune-Inflammation Index (SII) and CALs in patients with KD and to assess its predictive value. We carried out a retrospective review and analysis of medical records for KD patients treated at the First Affiliated Hospital of Anhui Medical University between January 2017 and January 2023. We utilized single-variable tests, binary logistic regression analysis, ROC curve analysis, restricted cubic spline tests, and curve fitting to evaluate the association between SII and CALs. In our study, 364 patients were included, with 63 (17.3%) presenting with CALs at the time of admission. The binary logistic regression analysis indicated that SII was a significant risk factor for CALs at admission, evident in both unadjusted and models adjusted for confounders. The ROC curve analysis revealed an AUC (Area Under the Curve) value of 0.789 (95%CI 0.723-0.855, P < 0.001) for SII's predictive ability regarding CALs at admission. A consistent positive linear relationship between SII and the risk of CALs at admission was observed in both the raw and adjusted models. Our research findings suggest that SII serves as a risk factor for CALs and can be used as an auxiliary laboratory biomarker for predicting CALs.