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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Risk factors and an early predictive model for Kawasaki disease shock syndrome in Chinese children.

BACKGROUND: Kawasaki disease shock syndrome (KDSS), though rare, has increased risk for cardiovascular complications. Early diagnosis is crucial to improve the prognosis of KDSS patients. Our study aimed to identify risk factors and construct a predictive model for KDSS. METHODS: This case-control study was conducted from June, 2015 to July, 2023 in two children's hospitals in China. Children initially diagnosed with KDSS and children with Kawasaki disease (KD) without shock were matched at a ratio of 1:4 by using the propensity score method. Laboratory results obtained prior to shock syndrome and treatment with intravenous immunoglobulin were recorded to predict the onset of KDSS. Univariable logistic regression and forward stepwise logistic regression were used to select significant and independent risk factors associated with KDSS. RESULTS: After matching by age and gender, 73 KDSS and 292 KD patients without shock formed the development dataset; 40 KDSS and 160 KD patients without shock formed the validation dataset. Interleukin-10 (IL-10) > reference value, platelet counts (PLT) < 260 × 109/L, C-reactive protein (CRP) > 80 mg/ml, procalcitonin (PCT) > 1ng/ml, and albumin (Alb) < 35 g/L were independent risk factors for KDSS. The nomogram model including the above five indicators had area under the curves (AUCs) of 0.91(95% CI: 0.87-0.94) and 0.90 (95% CI: 0.71-0.86) in the development and validation datasets, with a specificity and sensitivity of 80% and 86%, 66% and 77%, respectively. Calibration curves showed good predictive accuracy of the nomogram. Decision curve analyses revealed the predictive model has application value. CONCLUSIONS: This study identified IL-10, PLT, CRP, PCT and Alb as risk factors for KDSS. The nomogram model can effectively predict the occurrence of KDSS in Chinese children. It will facilitate pediatricians in early diagnosis, which is essential to the prevention of cardiovascular complications.

Development of a nomogram model to predict malignant vasovagal syncope in Chinese children.

Objective: Vasovagal syncope (VVS) is the commonest form of syncope, and malignant VVS draws substantial attention due to its life-threatening cardiac asystolic risk. This study aimed to explore the predictive role of a wide panel of clinical indicators for malignant VVS in children, and further to develop a nomogram model. Methods: This is a retrospective case-control study. VVS is diagnosed based on head-up tilt test (HUTT). STATA software (version 14.0) was used for statistical analysis, and effect sizes are expressed as odds ratio (OR) and 95% confidence interval (CI). Results: Total 370 children with VVS were analyzed, and of them 16 children had malignant VVS. Sixteen malignant VVS and 64 non-malignant VVS were matched on age and sex by a 1:4 propensity scores matching method. Mean corpuscular hemoglobin (MCH) and standard deviation of average RR intervals milliseconds (SDANN) were significantly and independently associated with malignant VVS after adjusting for confounders, with OR reaching 1.437 (95% CI: 1.044 to 1.979; P = 0.026) and 1.035 (95% CI: 1.003 to 1.068; P = 0.029), respectively. Calibration and discrimination analyses revealed that the addition of MCH and SDANN can enhance model performance. Then, a nomogram to predict malignant VVS was developed using general characteristics and two above significant factors, and higher values in medical history, number of syncope, MCH and SDANN were associated with a greater risk of malignant VVS. Conclusion: MCH and SDANN were two promising factors for the development of malignant VVS, and modeling of significant factors in a nomogram can provide strong reference to aid clinical decision-making.

Development of prognostic nomogram model to predict syncope recurrence in children with vasovagal syncope.

Backgrounds: Vasovagal syncope (VVS) is a common form of syncope. In children with VVS, recurrent syncope or presyncope can affect the physical and mental health of both children and parents, which markedly impairs quality of life. Objectives: We aimed to identify factors at baseline that can predict the recurrence of syncope or presyncope over a 5-year follow-up period, and further to develop a prognostic nomogram model. Methods: This cohort is bidirectional in design. From July 2017 to August 2022, children with VVS were included and followed up every 3 to 6 months. Head-up Tilt Test (HUTT) was performed for diagnosing VVS. Data were analyzed using STATA software, and risk estimates are presented as hazard ratio (HR) and 95% confidence interval (CI). Results: Total 352 children with VVS who had complete information were included in this study. Median follow-up time was 22 months. Overall, supine mean arterial pressure (MAP-supine) in HUTT and baseline urine specific gravity (USG) were associated with the significant risk of syncope or presyncope recurrence (HR: 0.70 and 3.00, respectively; both P < 0.05). Calibration and discrimination analyses revealed that the addition of MAP-supine and USG can result in a better fit. A prognostic nomogram model based on significant factors annexed with five traditional promising factors was finally constructed, with strong discriminative and predictive abilities (C-index approaching 0.700, P < 0.05). Conclusions: Our findings indicated that MAP-supine and USG can independently predict the significant risk of syncope recurrence in children with VVS, and the prediction was more obvious in a nomogram model.