Low- versus high-concentration intravenous immunoglobulin for children with Kawasaki disease in the acute phase

Abstract Purpose: Few studies have compared the effects of low-concentration (5%) and high-concentration (10%) intravenous immunoglobulin (IVIG) preparations for patients with Kawasaki disease (KD) in the acute phase. The purpose of this study was to compare outcomes between low- and high-concentration IVIG preparations in children with KD, using a national inpatient database in Japan.Method: We used the Diagnostic Procedure Combination database to identify patients with KD treated with IVIG from April 2012 to March 2020. We identified those receiving high- and low-concentration IVIG preparations as an initial treatment. The outcomes included the proportions of patients with coronary artery abnormalities (CAAs) and IVIG resistance, length of stay, and medical costs. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results.Result: We identified 48,046 patients with KD and created 4:1 propensity score-matched pairs between the low- and high-concentration IVIG groups. There was a significant difference in the percentage with IVIG resistance between the two groups (20.6% vs 24.1%; risk difference, 3.5% [95% confidence interval, 2.3-4.7]; p < 0.001). However, there was no significant difference in CAAs (1.6% vs 1.6%; risk difference, 0.013% [95% confidence interval, −0.34 to 0.37]; p = 0.953). The instrumental variable analyses showed similar results.Conclusions: The proportion of CAAs did not differ significantly between those receiving low- and high-concentration IVIG. To confirm the results of this study, prospective studies adjusting for duration of IVIG administration and duration of observation are needed.

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Abstract 12698: Sodium-containing versus Sodium-trace Preparations of Ivig for Children With Kawasaki Disease in Acute Phase

Circulation ◽

10.1161/circ.142.suppl_3.12698 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Takanori Suzuki ◽

Nobuaki Michihata ◽

Tetsushi Yoshikawa ◽

Kazuyoshi Saito ◽

Kiyohide Fushimi ◽

...

Keyword(s):

Kawasaki Disease ◽

Length Of Stay ◽

Propensity Score ◽

Acute Phase ◽

Medical Cost ◽

Instrumental Variable ◽

Systemic Vasculitis ◽

Developed Countries ◽

Recommended Treatment ◽

Ivig Resistance

Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). Hyponatremia in patients with KD in the acute phase is known to be associated with IVIG resistance and coronary artery abnormalities (CAA). There are two types of IVIG, sodium-containing (high Na) and sodium-trace (low Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low Na IVIG preparations in KD children using a national inpatient database in Japan. Methods: We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low Na preparations of IVIG as an initial treatment. Outcomes included proportion of CAA, IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. Results: We identified 47,292 patients with KD and created 23646 propensity score-matched pairs between the high and low Na IVIG groups. There were significant differences in proportions of CAA (2.5% vs. 2.9%; p=0.016) and IVIG resistance (23.8% vs. 24.9%; p=0.006) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analyses confirmed that high Na IVIG was significantly associated with lower proportion of CAA compared with low Na IVIG (odds ratio, 1.69; p<0.001). Conclusions: The present study suggests that high Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study.

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Malattia di Kawasaki: quale dose di immunoglobuline nei bambini grandi?

Medico e Bambino pagine elettr ◽

10.53126/mebxxiii231 ◽

2020 ◽

Vol 23 (9) ◽

pp. 231-233

Author(s):

Lorenzo Mambelli ◽

Alessandra Iacono ◽

Giovanna Rametta ◽

Federico Marchetti

Keyword(s):

Retrospective Study ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Treatment Effects ◽

Ivig Treatment ◽

Japanese Children ◽

Ivig Resistance ◽

Coronary Aneurysms ◽

Significant Difference ◽

Randomised Controlled

In a retrospective study conducted on a population of Japanese children with a weight ≥ 25 kg and with Kawasaki disease, no significant difference has been observed for the onset of coronary aneurysms, intravenous immunoglobulin (IVIg) resistance, duration of the hospitalisation and adverse treatment effects among the groups treated with 2 g/kg and 1 g/kg doses of IVIg. New randomised controlled studies are desirable to check the most appropriate IVIg dose for old children, also considering the cortisone treatment in association with the IVIg treatment firstly.

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Sodium-Containing Versus Sodium-Trace Preparations of IVIG for Children With Kawasaki Disease in The Acute Phase

10.21203/rs.3.rs-213815/v1 ◽

2021 ◽

Author(s):

Takanori Suzuki ◽

Nobuaki Michihata ◽

Shotaro Aso ◽

Tetsushi Yoshikawa ◽

Kazuyoshi Saito ◽

...

Keyword(s):

Kawasaki Disease ◽

Length Of Stay ◽

Propensity Score ◽

Medical Cost ◽

Instrumental Variable ◽

Propensity Score Analysis ◽

Systemic Vasculitis ◽

Developed Countries ◽

Instrumental Variable Analysis ◽

Ivig Resistance

Abstract Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high Na) and sodium-trace (low Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low Na IVIG preparations in KD children using a national inpatient database in Japan.Methods: We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results.Results: We identified 42345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p=0.031) and IVIG resistance (17% vs. 18%; p=0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.Conclusions: The present study suggests that high Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study.

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Is there an association between intravenous immunoglobulin resistance and coronary artery lesion in Kawasaki disease?—Current evidence based on a meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0248812 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248812

Author(s):

Xiaolan Zheng ◽

Jinhui Li ◽

Peng Yue ◽

Lei Liu ◽

Jiawen Li ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Diagnostic Criteria ◽

Meta Analysis ◽

Coronary Artery Lesion ◽

Current Evidence ◽

Cochrane Central Register ◽

Ivig Resistance ◽

Significant Difference

Background Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAL. Although most of the current studies have shown a certain correlation between CAL and IVIG resistance, the conclusions are not completely consistent. Thus, we performed this meta-analysis to evaluate the association between IVIG resistance and CAL in KD. Methods PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through April 21, 2020 were searched to detect relevant studies. Data analysis was performed with STATA 15.1. Results A total of 53 relevant studies were eligible to this analysis, including 30312 KD patients, of which 4750 were IVIG resistance and 25562 were responders. There was a significant difference found between IVIG resistance and IVIG response groups in the incidence of CAL (P < 0.001, odds ratio (OR), 3.89; 95% confidence interval (CI) (3.18, 4.75)). The heterogeneity test results showed that the I2 value was 74.8%. The meta-regression analysis showed that the study regions might be the sources of heterogeneity. The subgroup analysis suggested that the incidence of CAL in the IVIG resistance group was still higher than that in the IVIG response group under different regions, IVIG resistance diagnostic criteria, CAL diagnostic criteria, and study types. Meanwhile, the sensitivity analysis did not find any significant impact from every single study. Conclusions This is the first meta-analysis to reveal the incidence of CAL was associated with IVIG resistance in KD patients. Further well-designed studies with uniform criteria are needed to evaluate the incidence of CAL in IVIG resistant patients.

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Abstract 16564: Analysis of the Mechanisms of Intravenous Immunoglobulin-Resistant Kawasaki Disease Using iPS Cell Technology

Circulation ◽

10.1161/circ.130.suppl_2.16564 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Kazuyuki Ikeda ◽

Tomonaga Ameku ◽

Yui Nomiya ◽

Masahiro Nakamura ◽

Satoshi Matsui ◽

...

Keyword(s):

Gene Expression ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Expression Profiles ◽

Systemic Vasculitis ◽

Dermal Fibroblasts ◽

Gene Set Enrichment Analysis ◽

Recurrent Fever ◽

Ips Cell ◽

Ivig Resistance

Introduction: Kawasaki disease (KD) is a systemic vasculitis of unknown origin. Although the treatment of intravenous immunoglobulin (IVIG) significantly resolves inflammation, 10-20% of KD patients have persistent or recurrent fever after the administration of IVIG, and IVIG-resistant patients have a particularly high risk of developing coronary artery abnormalities. Hypothesis: The mechanisms of IVIG-resistant KD have been analyzed using the patients’ leukocyte samples. However, vascular endothelial cells (ECs), closely related to the vasculitis of KD, have not been examined in the previous reports. We propose a hypothesis that ECs are mainly involved in the etiology of IVIG-resistance. Methods: The purpose of this study is to establish new in vitro disease models of vasculitis using induced pluripotent stem cell (iPSC) technology, and clarify the mechanisms of IVIG-resistance in KD. Dermal fibroblasts or T cells from 2 IVIG-resistant and 2 IVIG-responsive KD patients were reprogrammed by episomal vectors encoding Oct3/4, Sox2, Klf4, L-Myc, LIN28, and p53 shRNA. The iPSC lines were then differentiated into ECs by using a previously-reported differentiation method, and the EC samples were subjected to the microarray analyses. Results: The KD patient-derived iPSCs could be differentiated into ECs. The gene expression profiles were compared between iPS-derived ECs (iPS-ECs) generated from IVIG-resistant and IVIG-responsive KD patients. We found that 107 genes were at least two fold up-regulated and 101 genes were at least two fold down-regulated in iPS-ECs from IVIG-resistant KD patients compared with those from IVIG-responsive patients. The Principle Component Analysis (PCA) was performed, but the gene expression levels showed no significant differences between the groups. The Gene Set Enrichment Analysis (GSEA) revealed that the gene sets related to IL-6, NRAS (a member of the RAS oncogene family) and breast cancer were up-regulated in iPS-ECs from IVIG-resistant KD patients. Conclusions: Taking into account that the concentration of IL-6 has been reported to be elevated in acute phase of IVIG-resistant KD, our results suggest that the up-regulation of IL-6 related genes in ECs might be involved in the pathogenesis of IVIG-resistant KD.

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Abstract O.07: The Clinical Risk Factors of Intravenous Immunoglobulin Resistance and Coronary Artery Lesion of Kawasaki Disease: Retrospective Analysis of 602 Cases

Circulation ◽

10.1161/circ.131.suppl_2.o07 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

lijian xie ◽

Cuizhen Zhou ◽

Renjian Wang ◽

Tingting Xiao ◽

Jie Shen ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Coronary Artery ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Clinical Evidence ◽

Clinical Risk Factors ◽

Ivig Treatment ◽

Ivig Resistance ◽

Sensitive Group

Introduction: The incidence of Kawasaki disease (KD) in China is increasing for years. The current coronary artery lesion (CAL) incidence is 5-10% in KD with intravenous immunoglobulin (IVIG) treatment. And the 10-20% KD patients still exhibit IVIG resistance. However, little clinical evidence on the occurrence of either CAL or IVIG resistance for big KD sample study in China during the past decade. Objective: In order to find clinical risk factors of CAL and IVIG resistance of KD in China. Methods: We retrospectively analyzed the clinical manifestations, laboratory results, treatment and complications of cardiac vascular of 602 KD cases from 2007 to 2012 admitted at Shanghai Children’s Hospital. The SAS 9.2 edition was used for statistical analysis. The mean ± standard deviation or the median were used for measurements. Case numbers and percentages were used for the count number. The t-test and the Mann-Whitney test were both used for mean comparisons. Single factor and multi-factor logistic regression analyses were used to analyze the risk factors. Results: 1. The KD gender male to female ratio was 1.85: 1. The KD median age was 2.0 years old (one month to 11.7 years old). 20.1% cases (121 of 602) exhibited CAL. There was no difference of CAL incidence between the gender (p=0.09). 2. The incidence of bright red cracked lips (p=0.001), peeling of the skin of the toes (p=0.021) and perianal skin peeling (p=0.031) are less in group with CAL. 3. Among the 602 cases, there were 525 cases that were sensitive to IVIG therapy. 100 of those cases had CAL with an incidence of 19.1%. Among the 26 IVIG resistance cases, there were 9 cases with CAL with an incidence of 34.6%, which was higher than the IVIG sensitive group (p=0.05). 4. ESR (p=0.014), CRP (p=0.017), PLT (p=0.003) and Hb (p=0.032) were much higher in the IVIG resistance group than the IVIG sensitive group, even though the IVIG resistance group started the IVIG treatment earlier (p=0.003). 5. Logistic regression analysis was conducted to show that GPT≥80IU/L was the independent risk factor of IVIG resistance, risk ratio was 2.945 (p=0.012) . Conclusion: This research suggests that risk factors of clinical evidence for IVIG resistance and CAL in KD.

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Abstract 54: The Correlation Between IgE And The Level Of Interleukin-21 In Kawasaki Disease

Circulation ◽

10.1161/circ.131.suppl_2.54 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

Hae-Yong Lee

Keyword(s):

Kawasaki Disease ◽

Serum Level ◽

Acute Phase ◽

Immunoglobulin E ◽

Significant Difference ◽

History Of ◽

Interleukin 21 ◽

Christian Hospital ◽

Age Range ◽

Chemiluminescent Method

Purpose: It has been reported that serum level of immunoglobulin E (IgE) is increased in patients with Kawasaki disease (KD) after acute phase. However the exact mechanism of increasing IgE is yet to be revealed. We investigated whether the interleukin-21 (IL-21) could be related with the high IgE in KD. Instead of IL-4, IL-21 was focused in this study because it has been reported that its level is increased in various autoimmune vasculitis. Methods: From June 2008 to June 2010, 49 patients with KD admitted in Wonju Severance Christian Hospital and 13 controls with high fever due to unknown infection who had no history of KD were included in this study. The sera from patients and controls were collected and checked in terms of immunoglobulin E (Chemiluminescent method, Siemens, Munich, Germany) and IL-21 (ELISA, eBioscience, San Diego, USA). Results: The median age of patients with KD was 3 years of age (range: 0.4-10) and that of controls was 7 years of age (range: 1-12). The group of patients with KD was composed of 39 complete KD and 10 incomplete KD. Among patients with KD, 10 patients had coronary arterial dilatation (CAD) and 39 patients had no coronary complications. The median value of IL-21 in patients with KD was significantly increased as 466 pg/mL (range: 0-1544) while that value in controls was <62.5 pg/mL (range: 0- 825 pg/mL) ( P < 0.01). We could not find the significant correlation between the serum level of IgE and that of IL-21 in patients with KD (Spearman R=0.2, P = 0.08) though 30% of patients with KD showed increased IgE more than 100 IU/mL. In addition, our data showed no significant difference between CAD group and non CAD group in terms of serum IL-21. Conclusion: Our data showed firstly that IL-21 is increased in patients with KD. There was no significant correlation between high IgE and the level of IL-21.

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Effect of Early Intravenous Immunoglobulin Therapy in Kawasaki Disease: A Systematic Review and Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2020.593435 ◽

2020 ◽

Vol 8 ◽

Author(s):

Fan Yan ◽

Huayong Zhang ◽

Ruihua Xiong ◽

Xingfeng Cheng ◽

Yang Chen ◽

...

Keyword(s):

Systematic Review ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Meta Analysis ◽

The United States ◽

Cochrane Library ◽

Ivig Treatment ◽

Intravenous Immunoglobulin Therapy ◽

Increased Risk ◽

Significant Difference

Background: In the latest 2017 American Heart Association guidelines for Kawasaki disease (KD), there are no recommendations regarding the early administration of intravenous immunoglobulin (IVIG). Therefore, the purpose of this systematic review and meta-analysis was to investigate the effects of early IVIG therapy on KD.Methods: We searched databases including the PubMed, Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2019.Results: Fourteen studies involving a total of 70,396 patients were included. Early treatment with IVIG can lead to an increased risk of IVIG unresponsiveness [OR 2.24; 95% CI (1.76, 2.84); P = 0.000]. In contrast to the studies performed in Japan [OR 1.27; 95% CI (0.98, 1.64); P = 0.074] that found no significant difference in coronary artery lesions (CAL) development, studies conducted in China [OR 0.73; 95% CI (0.66, 0.80); P = 0.000] and the United States [OR 0.50; 95% CI (0.38, 0.66); P = 0.000] showed a reduced risk in the occurrence of CAL with early IVIG treatment.Conclusions: At present, the evidence does not support the treatment with IVIG in the early stage of the onset of KD. But, early IVIG treatment could be a protective factor against the development of CAL, which needs to be further clarified.

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The Effects of Including Aerobic Exercise in the Treatment Protocol of Concussions: A Systemic Review and Meta-analysis

International Journal of Kinesiology and Sports Science ◽

10.7575/aiac.ijkss.v.7n.4p.33 ◽

2019 ◽

Vol 7 (4) ◽

pp. 33

Author(s):

Sofie De Wandel ◽

Tracey Sulak ◽

Darryn S. Willoughby

Keyword(s):

Physical Activity ◽

Confidence Interval ◽

Aerobic Exercise ◽

Children And Adolescents ◽

Effect Size ◽

Meta Analysis ◽

Risk Difference ◽

Systemic Review ◽

Significant Difference ◽

The Mean

Background of Study: More research studies are being completed advocating for the use of exercise as an intervention and form of treatment for concussions. However, exercise can include many forms of physical activity, intensities, and durations. This systemic review and meta-analysis focused on the use of aerobic exercise, such as cycling or walking, as an intervention and form of treatment for children and young adults suffering from a concussion. Objective: The purpose of this systematic review and meta-analysis was to determine if the addition of aerobic exercise to an individual concussion treatment makes a significant difference when compared to treatments using flexibility as a form of physical activity or traditional methods of treatment following guidelines from the 2016 Berlin Consensus Statement on Concussion in Sport. Method: The search conducted for articles generated 472 studies. Out of these, 5 studies were selected based from the inclusion criteria. Results: Aerobic exercise was shown to significantly decrease the absolute risk difference for the development of prolonged post-concussion symptoms in children and adolescents with concussions when compared to those who reported no physical activity. The mean risk difference for the independent variable (IV) was -0.12 with a 95% confidence interval was reported to be -0.17 to -0.07 and an effect size of Z = 4.94 (P < 0.00001). Aerobic exercise was also shown to have an effect on the change in post-concussion symptom scale scores. The mean IV difference was 8.7 with a 95% confidence interval of 2.05 to 14.35 and an effect size of Z=3.02 (p=0.003). Conclusion: In conclusion, while there is evidence that aerobic exercise is beneficial for children and adolescents with a concussion, more studies need to be completed focusing on this age group and the effects of aerobic exercise on concussion recovery.

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Predictive Value of Albumin-Bilirubin Grade For Intravenous Immunoglobulin Resistance In A Large Cohort Of Patients With Kawasaki Disease: A Prospective Study

10.21203/rs.3.rs-476187/v1 ◽

2021 ◽

Author(s):

Yu Yan ◽

Lina Qiao ◽

Shuran Shao ◽

Nanjun Zhang ◽

Mei Wu ◽

...

Keyword(s):

Risk Factor ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Predictive Value ◽

Independent Risk Factor ◽

Laboratory Data ◽

Multivariate Logistic Regression Analysis ◽

Predictive Ability ◽

Ivig Infusion ◽

Ivig Resistance

Abstract Background: Intravenous immunoglobulin (IVIG) resistance, which defined that Kawasaki disease (KD) patients have recrudescence fever more than 36 hours after IVIG infusion, and its prediction is one of the primary clinical issues and study hotspots in KD. This study aimed to prospectively investigated the value of albumin-bilirubin grade (ALBI) in predicting IVIG resistance in KD, and assessed whether ALBI has more predictive value or accuracy than either ALB or TBil alone in predicting IVIG resistance.Methods: A total of 823 patients with KD were prospectively enrolled. The clinical and laboratory data were compared between IVIG-response group (n=708) and IVIG-resistance group (n=115). Multivariate logistic regression analysis was performed to identify the independent risk factors of IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of ALBI, ALB, and TBil in predicting IVIG resistance. Results: ALBI was significantly higher in patients with IVIG resistance and was identified as an independent risk factor for IVIG resistance in KD. The parameter of ALBI ≥ –2.57 (AUC: 0.705, 95%CI: 0.672–0.736), ALB ≤ 33.0g/L (AUC: 0.659, 95%CI: 0.626–0.692), and TBil ≥16.0μmol/L (AUC: 0.626, 95%CI: 0.592–0.659), produced a sensitivity, specificity, PPV, and NPV of 0.617, 0.657, 0.226, 0.914, and 0.651; 0.374, 0.850, 0.289, 0.893, and 0.783; 0.269, 0.941, 0.425, 0.888, and 0.847, respectively.Conclusion: A higher ALBI was an independent risk factor for IVIG resistance. It yielded better predictive ability than ALB and TBil alone for initial IVIG resistance.

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