Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2021680?articleTools=true

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.

BACKGROUND
Red blood cell distribution width (RDW), a component of an electronic complete blood count, is a measure of heterogeneity in the size of circulating erythrocytes. In patients with symptomatic cardiovascular disease (CVD), RDW is associated with mortality. However, it has not been demonstrated that RDW is a predictor of mortality independent of nutritional deficiencies or in the general population.


METHODS
Red blood cell distribution width was measured in a national sample of 8175 community-dwelling adults 45 years or older who participated in the 1988-1994 National Health and Nutrition Examination Survey; mortality follow-up occurred through December 31, 2000. Deaths from all causes, CVD, cancer, and other causes were examined as a function of RDW.


RESULTS
Higher RDW values were strongly associated with an increased risk of death. Compared with the lowest quintile of RDW, the following were adjusted hazard ratios (HRs) for all-cause mortality (and 95% confidence intervals [CIs]): second quintile, HR, 1.1 (95% CI, 0.9-1.3); third quintile, HR, 1.2 (95% CI, 1.0-1.4); fourth quintile, HR, 1.4 (95% CI, 1.2-1.8); and fifth quintile, HR, 2.1 (95% CI, 1.7-2.6). For every 1% increment in RDW, all-cause mortality risk increased by 22% (HR, 1.22; 95% CI, 1.15-1.30; P < .001). Even when analyses were restricted to nonanemic participants or to those in the reference range of RDW (11%-15%) without iron, folate, or vitamin B(12) deficiency, RDW remained strongly associated with mortality. The prognostic effect of RDW was observed in both middle-aged and older adults for multiple causes of death.


CONCLUSION
Red blood cell distribution width is a widely available test that is a strong predictor of mortality in the general population of adults 45 years or older.

Red Blood Cell Distribution Width and the Risk of Death in Middle-aged and Older Adults.

Congenital heart disease is the most common birth defect, and because of major advances in medical and surgical management, there are now more adults living with congenital heart disease (CHD) than children. Until recently, the cause of the majority of CHD was unknown. Advances in genomic technologies have discovered the genetic causes of a significant fraction of CHD, while at the same time pointing to remarkable complexity in CHD genetics. This review will focus on the evidence for genetic causes underlying CHD and discuss data supporting both monogenic and complex genetic mechanisms underlying CHD. The discoveries from CHD genetic studies draw attention to biological pathways that simultaneously open the door to a better understanding of cardiac development and affect clinical care of patients with CHD. Finally, we address clinical genetic evaluation of patients and families affected by CHD.

Genetics and Genomics of Congenital Heart Disease.

Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”.

https://www.mdpi.com/2072-6643/5/11/4760/pdf

Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

Objective
To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs).

Methods
Serum Th1 and Th2 cytokines, including interferon-γ (IFNγ), tumor necrosis factor α (TNFα), interleukin-10 (IL-10), IL-6, IL-4, and IL-2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre-IVIG, at 3 days after temperature normalization following IVIG treatment [post-IVIG], and 1 month posttreatment).

Results
Levels of IL-6, IL-10, TNFα, and IFNγ were significantly increased in KD patients pre-IVIG. Post-IVIG, the levels of IL-6, IL-10, and IFNγ quickly decreased. The levels of TNFα decreased significantly after IVIG treatment in KD patients without CALs post-IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post-IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL-4, IL-6, IL-10, and IFNγ were significantly higher in KD patients with CALs than in those without CALs. The post-IVIG levels of IL-6 and IL-10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre-IVIG, an IL-10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNFα level 10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL-10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs.

Conclusion
Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.37815

Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease.

Macrophage activation syndrome in Kawasaki disease: more common than we thought?

To assess the predictors for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). A total of 560 KD patients were reviewed retrospectively, including 410 complete KD (cKD) and 150 incomplete KD (iKD) patients. The laboratory data were compared between the IVIG-resistant and IVIG-responsive groups, as well as between the coronary artery lesions (CALs+) and without coronary artery lesions (CALs-) groups. In the cKD patients, C-reactive protein (CRP) levels had a sensitivity of 65.52% and a specificity of 62.7% for predicting IVIG-resistance at a cutoff point of >100 mg/L. When albumin 1300 pg/ml. Interleukin-6 levels had a sensitivity of 76.19% and a specificity of 61.59% at a cutoff value of >45 pg/ml. Erythrocyte sedimentation rate (ESR) levels had a sensitivity of 53.26% and a specificity of 64.14% for predicting CALs at a cutoff point of >75 mm/h. In the iKD patients, the sensitivity and specificity for predicting IVIG-resistance were 80 and 54.1% when hemoglobin 70%, the sensitivity and specificity for predicting IVIG-resistance were 68 and 66.94%, respectively. ESR levels had a sensitivity of 70.83% and a specificity of 65.81% for predicting IVIG-resistance at a cutoff point of >80 mm/h. NT-proBNP levels had a sensitivity of 78.57% and a specificity of 56.67% for predicting IVIG-resistance at a cutoff point of >360 pg/ml. Interleukin-6 levels had a sensitivity of 70.59% and a specificity of 66.28% at a cutoff value of >25 pg/ml. Interleukin-10 levels had a sensitivity of 64.71% and a specificity of 74.42% for predicting IVIG-resistance at a cutoff value of >8 pg/ml. ESR levels had a sensitivity of 61.82% and a specificity of 65.12% for predicting CALs at a cutoff point of >75 mm/h. The white blood cell count, proportion of neutrophils, hemoglobin, CRP, ESR, albumin, NT-proBNP, interleukin-6 and 10 may be effective predictors for IVIG resistance and CALs in KD patients.

/pdf/predictors-for-intravenous-immunoglobulin-resistance-and-e0x3lw87fh.pdf

Predictors for intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease.

Background
Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme for folate metabolism in humans; it is encoded by the MTHFR gene. Several studies have assessed the association between MTHFR C677T polymorphism and the risk of congenital heart defects (CHDs), while the results were inconsistent.

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0058041&type=printable

MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29 case-control and TDT studies.

To investigate the differential expression of microRNA-150-5p (miR-150-5p) and early growth response 1 (EGR1) in myocardial fibrosis (MF) cells, and determine the effect between miR-150-5p and EGR1 on MF. Human MF cells were generated via Trypanosoma cruzi (T. cruzi) infection, a mouse model of MF was generated via angiotensin II. The expression levels of miR-150-5p and EGR1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The correlation between miR-150-5p and EGR1 was confirmed by a luciferase reporter assay. The viability, proliferation, and apoptotic rate were detected by cell counting kit-8 (CCK-8), colony-formation and flow cytometry assays. Hematoxylin-eosin (HE) staining and Masson staining visualized the degree of MF. Echocardiography was performed to obtain the levels of left ventricle fractional shortening (LVFS) and left ventricle ejection fraction (LVEF), computer algorithms and a videographics program were used to obtain the levels of left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and ±left ventricular dp/dt maximum (LV dp/dtmax). We found that the expression of miR-150-5p in MF cells was lower than normal cardiomyocytes, while the expression level of EGR1 in MF cells were higher than normal cardiomyocytes. Cell experiments demonstrated that EGR1 and miR-150-5p could influence the development of MF, and the expression of EGR1 in cardiomyocytes was regulated by miR-150-5p directly. Lastly, we confirmed that sh-Egr1 would decrease the severity of MF, while miR-150-5p antagomir could aggravate MF. Our results illustrate the mechanism of MF development, and provide a potential target for MF treatment.

https://www.tandfonline.com/doi/pdf/10.1080/15384101.2019.1617614

Songling Fu

Papers

Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease.

Macrophage activation syndrome in Kawasaki disease: more common than we thought?

Predictors for intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease.

MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29 case-control and TDT studies.

MiR-150-5p retards the progression of myocardial fibrosis by targeting EGR1