Predictive Value of Serum Lipid for Intravenous Immunoglobulin Resistance and Coronary Artery Lesion in Kawasaki Disease

Shao, Shuran; Zhou, Kaiyu; Liu, Xiaoliang; Liu, Lei; Wu, Mei; Deng, Yuxin; Duan, Hongyu; Li, Yifei; Hua, Yimin; Wang, Chuan

doi:10.1210/clinem/dgab230

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…Our machine learning nding seems to be consistent with a previous nding showing that levels of serum total cholesterol decreased in the acute phase of KD patients due to abnormal lipid metabolism [31]. In particular, recent report by Shao et al [32] revealed that serum total cholesterol level before the initial IVIG treatment was signi cantly lower in the cases of IVIG resistance in a single-center prospective cohort study. Although the underlying mechanism for association between dyslipidemia and the severity of systemic in ammation in KD remains unclear, a recent study by Zhang et al [33] revealed that dyslipidemia during acute phase of KD was associated with aberrant levels of adipokines including adiponectin, omentin-1, and chemerin.…”

Section: Discussionsupporting

confidence: 92%

“…Although the underlying mechanism for association between dyslipidemia and the severity of systemic in ammation in KD remains unclear, a recent study by Zhang et al [33] revealed that dyslipidemia during acute phase of KD was associated with aberrant levels of adipokines including adiponectin, omentin-1, and chemerin. In the above study by Shao et al 32 , alterations in the other lipid proteins were also associated with IVIG resistance: a higher level of triglyceride and lower levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A. Thus, although the lipid pro le was not fully evaluated in the present study, dyslipidemia due to systemic in ammation in the acute phase of KD patients may be a rational explanation for the usefulness of serum total cholesterol level as one of predictors for IVIG resistance in the Yamanashi score.…”

Section: Discussionmentioning

confidence: 90%

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A Simple Scoring Model Based on Machine Learning Predicts Intravenous Immunoglobulin Resistance in Kawasaki Disease

Sunaga

Watanabe

Katsumata

et al. 2022

Preprint

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In Kawasaki disease (KD), accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial to reduce a risk for developing coronary artery lesions. To establish a simple and accurate scoring model predicting IVIG resistance, we conducted a retrospective cohort study of 996 KD patients that were diagnosed at 11 facilities for 10 years, in which 108 cases (23.5%) were resistant to initial IVIG treatment. We performed machine learning with random forest model using 30 clinical variables at diagnosis in 796 and 200 cases for training and test datasets, respectively. Random forest model accurately predicted IVIG resistance (AUC; 0.75, sensitivity; 0.54, specificity; 0.80). Next, using top five influential features (days of illness at initial therapy, serum levels of C-reactive protein, sodium, total bilirubin, and total cholesterol) in the random forest model, we designed a simple scoring system. In spite of its simplicity, the scoring system predicted IVIG resistance (AUC; 0.73, sensitivity; 0.55, specificity; 0.83) as accurately as the random forest model itself. Moreover, accuracy of our scoring system with five clinical features was almost identical to that of Gunma score with seven clinical features (AUC; 0.73, sensitivity; 0.53, specificity; 0.83), a well-known logistic regression scoring model, and superior to that of two widely used scores (Kurume score; 0.67, 0.46 and 0.76, respectively, and Osaka score; 0.69, 0.33 and 0.84, respectively). Conclusions: Our simple scoring system based on the findings in machine learning, as well as machine learning itself, seems to be useful to accurately predict IVIG resistance in KD patients.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

A Simple Scoring Model Based on Machine Learning Predicts Intravenous Immunoglobulin Resistance in Kawasaki Disease

Sunaga

Watanabe

Katsumata

et al. 2022

Preprint

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“…Interestingly, enhanced NETosis has been implicated in Kawasaki disease (KD) ( 49 ), as has disordered lipid metabolism, specifically low HDL-c and HDL particles ( 50 ). Furthermore, lower apoAI levels were recently associated with resistance to intravenous immunoglobulin therapy and worse coronary artery lesions in a prospective cohort study of KD ( 51 ). KD, beyond clinical parallels with MIS-C, has long been suggested to occur following an elusive infectious trigger.…”

Section: Discussionmentioning

confidence: 99%

Changes in HDL cholesterol, particles, and function associate with pediatric COVID-19 severity

Mietus‐Snyder

Suslovic

Delaney

et al. 2022

Front. Cardiovasc. Med.

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BackgroundMyriad roles for high-density lipoprotein (HDL) beyond atheroprotection include immunologic functions implicated in the severity of coronavirus disease-2019 (COVID-19) in adults. We explored whether there is an association between HDL and COVID-19 severity in youth.MethodsA pediatric cohort (N = 102), who tested positive for COVID-19 across a range of disease manifestations from mild or no symptoms, to acute severe symptoms, to the multisystem inflammatory syndrome of children (MIS-C) was identified. Clinical data were collected from the medical record and reserve plasma aliquots were assessed for lipoproteins by NMR spectroscopy and assayed for HDL functional cholesterol efflux capacity (CEC). Findings were compared by COVID-19 status and symptom severity. Lipoprotein, NMR spectroscopy and CEC data were compared with 30 outpatient COVID negative children.ResultsDecreasing HDL cholesterol (HDL-c), apolipoprotein AI (ApoA-I), total, large and small HDL particles and HDL CEC showed a strong and direct linear dose-response relationship with increasing severity of COVID-19 symptoms. Youth with mild or no symptoms closely resembled the uninfected. An atypical lipoprotein that arises in the presence of severe hepatic inflammation, lipoprotein Z (LP-Z), was absent in COVID-19 negative controls but identified more often in youth with the most severe infections and the lowest HDL parameters. The relationship between HDL CEC and symptom severity and ApoA-I remained significant in a multiply adjusted model that also incorporated age, race/ethnicity, the presence of LP-Z and of GlycA, a composite biomarker reflecting multiple acute phase proteins.ConclusionHDL parameters, especially HDL function, may help identify youth at risk of more severe consequences of COVID-19 and other novel infectious pathogens.

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“…For example, hepatosplenomegaly is very rare in patients with KD but can be seen in patients with refractory KD [ 29 ]. Dyslipidemia, including hypertriglyceridemia, also occurs more frequently in refractory KD than in KD [ 30 ]. Second, the lack of awareness of the possible co-occurrence of KD and MAS is a more fundamental reason than others [ 12 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Under-Recognized Macrophage Activation Syndrome in Refractory Kawasaki Disease: A Wolf in Sheep’s Clothing

et al. 2022

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Recognition of macrophage activation syndrome (MAS) in patients with refractory Kawasaki disease (KD) can be challenging. This study aimed to investigate the incidence of MAS in patients with refractory KD and to compare the characteristics of refractory KD and MAS. Medical records of 468 patients diagnosed with KD from January 2010 to December 2019 were retrospectively reviewed. Of the 468 KD patients, 63 were enrolled in the study as a refractory KD group (n = 59) and an MAS group (n = 4). The incidence of MAS was 0.8% (4/468) in patients with KD and 6.3% (4/63) in patients with refractory KD. Compared to the refractory KD group, the MAS group had higher frequencies of incomplete KD, hepatosplenomegaly, third-line treatment, and MAS screening, and showed lower levels of albumin. No significant differences were found in other clinical and laboratory findings. In addition to four patients with MAS, five patients with refractory KD who received third-line treatment showed severe systemic inflammation and organ dysfunction, but only one in five patients underwent MAS screening, including ferritin levels. In conclusion, given the relatively high incidence of MAS in children with refractory KD and the similar phenotype between refractory KD and MAS, we propose that MAS screening should be included in routine laboratory tests for refractory KD.

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Predictive Value of Serum Lipid for Intravenous Immunoglobulin Resistance and Coronary Artery Lesion in Kawasaki Disease

Cited by 11 publications

References 45 publications

A Simple Scoring Model Based on Machine Learning Predicts Intravenous Immunoglobulin Resistance in Kawasaki Disease

A Simple Scoring Model Based on Machine Learning Predicts Intravenous Immunoglobulin Resistance in Kawasaki Disease

Changes in HDL cholesterol, particles, and function associate with pediatric COVID-19 severity

Under-Recognized Macrophage Activation Syndrome in Refractory Kawasaki Disease: A Wolf in Sheep’s Clothing

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