[Association between serum uric acid and subclinical cardiac damage in children with primary hypertension].

OBJECTIVE: To evaluate the condition of subclinical cardiac damage in children with primary hypertension and the association between serum uric acid and subclinical cardiac damage. METHODS: A retrospective analysis was performed on the medical data of 55 children who were hospitalized and diagnosed with primary hypertension in the Department of Cardiology, Children's Hospital of Soochow University from January 2015 to June 2020. Forty-five healthy children, matched for age and sex, were enrolled as the control group. The two groups were compared in terms of clinical features, laboratory examination, and parameters for left ventricular structure, systolic function, and diastolic function. The correlation of serum uric acid with the parameters for left ventricular structure, systolic function, and diastolic function in children with primary hypertension was analyzed. RESULTS: Compared with the control group, the hypertension group had significantly higher left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT) (P < 0.05). Among the children with primary hypertension, 20 (36%) had left ventricular hypertrophy. The hypertension group had significantly larger left atrial diameter and aortic root diameter than the control group (P < 0.05). The hypertension group had a significantly higher ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity than the control group (P < 0.05). The correlation analysis showed that in children with primary hypertension, serum uric acid was positively correlated with LVM (r=0.534, P < 0.01), left atrial diameter (r=0.459, P < 0.01), and aortic root diameter (r=0.361, P=0.010). After adjustment for blood pressure, serum uric acid was still positively correlated with the above parameters (P < 0.05). CONCLUSIONS: Children with primary hypertension may have subclinical cardiac damage such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial enlargement, and proximal aortic dilation. Elevated serum uric acid is significantly associated with cardiac damage in children with primary hypertension.

Ionic mechanisms underlying atrial electrical remodeling after a fontan-style operation in a canine model.

Atrial arrhythmia is an important cause of late death in patients after the Fontan-Style operation. However, the detailed electrophysiological characteristics of the post-Fontan atrium and its underlying mechanisms are largely unknown. In this study, we investigated electrophysiological characteristics and the ionic remodeling in the right atrium (RA) of a canine model after the Fontan operation. We performed the operation of RA to pulmonary artery connection to mimic the Fontan operation. We undertook hemodynamic measurements, cardiac electrophysiological studies, and ion current measurements. The expression of ionic channels was analyzed by PCR and western-blotting. Our Fontan model induced RA hypertension, enlarged the size of RA, and increased atrial fibrosis, representing the classic characteristic of Fontan patients. In the Fontan group, the atrial effective refractory period and the active potential duration were reduced, and the atrial tachycardia has been more often to be induced. The electrical conduction mapping showed that the Fontan group reduced the conduction velocity. The Fontan operation significantly down-regulated the expression of KCND3/Kv4.3, CACNA1C/Cav1.2 and SCN5A, but up-regulated the expression of KCNJ2/Kir2.1. Correspondingly, The Fontan operation reduced transient-outward (Ito) and L-type Ca2 (ICa,L) and INa currents, while increasing the inward-rectifier current (IK1). Thus, the net shortening of the action potential in the post-Fontan atrium is associated with the altered expression of ionic channels which disturbed the balance between inward and outward currents. Taken together, the Fontan operation induces the ionic remodeling, and thus altered electrophysiological characteristics of the right atrium, improving our understanding on the pathophysiology of atrial arrhythmias in Fontan patients.

Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic ß Cell Function in Obese Children.

OBJECTIVES: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic ß cell function. METHOD: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for ß-cell function [HOMA-ß]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. RESULTS: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-ß levels in obese children. CONCLUSIONS: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic ß cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to ß cell function in obese children.

Evaluation of right ventricular myocardial strains by speckle tracking echocardiography after percutaneous device closure of atrial septal defects in children.

OBJECTIVES: The aim of this study was to clarify the influence of the ASD closure by occluder device on right ventricular acute and long-term changes in longitudinal systolic strains, by evaluating right ventricular wall deformation in children using speckle tracking echocardiography (STE). METHODS AND MATERIALS: We enrolled 30 children with ASDs and 40 controls in our study. The Amplatzer atrial defect occluder was used to close the ASDs. Transthoracic echocardiographic examinations were performed at 3 points in time: the day before closure, 1 day after closure, and 3 months after closure. The dimensions of the right atrium (RA) and the right ventricle (RV) were measured in apical four-chamber view. RV segmental longitudinal systolic strains (SLSs) and global longitudinal systolic strain (GLS) were obtained by two-dimensional STE. RESULTS: Before ASD closure, the RV SLSs and GLS were significantly higher than those of the controls. At 1 day after closure, the diameters of RA and RV decreased. All the RV SLSs and GLS decreased accordingly and were lower than the control values. At 3 months after closure, the apical free wall strain, all segments of septal strains, and GLS increased significantly compared with the values obtained at 1 day after closure. The diameters of the RA and RV decreased further as well. There were no significant differences in the strains compared with the control values, except for the free wall basal strain. CONCLUSIONS: Transcatheter device closure of ASDs improves RV strain indices and RV function recover to normal over 3 months.

Evaluation of left ventricular systolic strain in children with Kawasaki disease.

The current study aimed to assess left ventricular (LV) longitudinal systolic strains in children with KD using two-dimensional speckle-tracking imaging and to analyze the relationship of LV myocardial deformation to coronary lesions and laboratory markers. The study enrolled 101 children with acute KD. An additional 50 age- and gender-matched normal children were enrolled as control subjects. During different phases of KD, echocardiograms were recorded for 61 children. Two-dimensional strain analysis software was used to track myocardial movement and obtain the strain from each LV segment. The LV longitudinal systolic strain decreased significantly in children with acute KD but increased immediately after intravenous immunoglobulin therapy. At 6-8 weeks after the onset of KD, all LV strains had recovered to normal. The LV systolic strain was not associated with coronary dilation in either acute or convalescent KD. In acute KD, aspartate transaminase, alanine transaminase, erythrocyte sedimentation rate, C-reactive protein (CRP), and hemoglobin (Hb) were found to be associated with coronary dilation, whereas LV systolic strains were found to be correlated with elevated CRP and decreased Hb. Speckle-tracking imaging of LV systolic strain was simple and accurate in evaluating LV function during different phases of KD. No association between LV dysfunction and coronary dilation was observed, but a relationship with CRP and Hb was found. Further studies are recommended to validate the current study results and explore further how these findings can improve clinical practice.

Phenazine-1-carboxylic acid production in a chromosomally non-scar triple-deleted mutant Pseudomonas aeruginosa using statistical experimental designs to optimize yield.

We constructed a non-scar triple-deleted mutant Pseudomonas aeruginosa to improve phenazine-1-carboxylic acid (PCA) yield and then optimized the culture conditions for PCA production. Using a non-scar deletion strategy, the 5'-untranslated region of the phz1 gene cluster and two genes, phzM and phzS, were knocked out of the P. aeruginosa strain M18 genome. The potential ability for high-yield PCA production in this triple-deleted mutant M18MSU1 was successfully realized by using statistical experimental designs. A 2(5-1) fractional factorial design was used to show that the three culture components of soybean meal, corn steep liquor and ethanol had the most significant effect on PCA production. Using a central composite design, the concentration of the three components was optimized. The maximum PCA production was predicted to be 4,725.1 mg/L. With the optimal medium containing soybean meal 74.25 g/L, corn steep liquor 13.01 g/L and ethanol 21.84 ml/L, a PCA production of 4,771.2 mg/L was obtained in the validation experiments, which was nearly twofold of that before optimization and tenfold of that in the wild-type strain. This non-scar triple-deleted mutant M18MSU1 may be a suitable strain for industrial production of this biologically synthesized fungicide due to its high PCA production, presumed safety, thermal adaptability and cost-effectiveness.

Prediction nomogram for coronary artery aneurysms at one month in Kawasaki disease.

BACKGROUND: Coronary status at one month after Kawasaki disease (KD) onset had a great significance. The present study aimed to establish a prediction model for coronary artery aneurysms (CAA) at one month in children with KD. METHODS: Patients with a diagnosis of KD between May 2017 and Dec 2018 were enrolled as the development cohort to build a prediction model. The model was validated by internal and external validation. Patients between Jan 2019 and Dec 2019 were enrolled as the validation cohort. The adaptive least absolute shrinkage and selection operator (LASSO) was used to select the possible predictors. Receiving operating characteristic curve (ROC), calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. The performance of the Son score was also assessed. RESULTS: LASSO regression demonstrated that age, sex, and CALs in the acute stage were predictors for CAA at one month. The area under the ROC (AUC) was 0.946 (95% confidence interval: 0.911-0.980) with a sensitivity of 92.5% and a specificity of 90.5%. The calibration curve and the DCA showed a favorable diagnostic performance. The internal and external validation proved the reliability of the prediction model. The AUC of our model and the Son score were 0.941 and 0.860, respectively (P < 0.001). CONCLUSION: Our prediction model for CAA at one month after disease onset in KD had an excellent predictive utility.

The prevalence of hypertension and elevated blood pressure and its correlation with overweight/obesity among students aged 6-17 years in Suzhou.

OBJECTIVES: Lifestyle changes have led to an increase in the prevalence of hypertension in Chinese children and adolescents. The aim of this study was to analyze the prevalence of hypertension and its association with overweight and obesity among students aged 6-17 years in Suzhou. This retrospective analysis included physical examination data of primary and junior high school students in Suzhou Industrial Park from 2016 to 2019. METHODS: Elevated blood pressure and hypertension were defined using blood pressure criteria appropriate for age, sex, and height percentile. Overweight and obesity were defined using the 2007 diagnostic criteria proposed by the World Health Organization for school-age children. Logistic regression analysis was used to evaluate the association between hypertension and overweight and obesity. RESULTS: A total of 128,113 students were included. The prevalence of elevated BP and hypertension was 9.92% and 13.56%, respectively. The incidence of high blood pressure was higher in boys than in girls and increased with an increase in body mass index (BMI). The prevalence of hypertension in obese boys and girls (27.07% and 27.49%, respectively) was 2.3-fold and 2.8-fold higher than that in normal-weight boys and girls (11.58% and 9.83%, respectively). CONCLUSIONS: Blood pressure was positively correlated with BMI, and the risk of high blood pressure due to overweight/obesity was 10.44%. Overweight and obesity significantly increased the risk of hypertension in students aged 6-17 years in Suzhou. Targeted weight-loss programs during childhood and adolescence may reduce the risk of hypertension in adulthood.

Effect of Fish Oil on Insulin Sensitivity in Children: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials.

OBJECTIVES: Fish oil has been shown to reduce the risk of metabolic disorders. However, the effects of fish oil intervention on glucose metabolism and insulin sensitivity are still controversial, especially in children. The current meta-analysis aimed to evaluate the effects of fish oil intervention on insulin sensitivity in children. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, ClinicalTrials.gov and China National Knowledge Infrastructure databases were searched up to August 2020 for relevant studies evaluating fish oil intake compared with placebo on insulin sensitivity indications (Homeostatic Model for Insulin Resistance). A fixed-effects model was used to calculate the pooled effect. RESULTS: A total of 13 studies with 1,132 participants (567 in placebo group and 565 in fish oil group) were included in the meta-analysis. Compared with the placebo group, fish oil intervention had beneficial effects on insulin sensitivity in the pooled analysis (weighted mean difference, -0.219; 95% confidence interval, -0.392 to -0.046; p=0.013). In subgroup analyses, when the fish oil intervention period was short-term (≤6 months), low dose (eicosapentaenoic acid + docosahexaenoic acid dose <1.5 g/day) and high ratio (eicosapentaenoic acid to docosahexaenoic acid ≥1), it could improve insulin sensitivity. No heterogeneity was found for the pooled and subgroup analyses. CONCLUSION: Fish oil intervention has a beneficial effect on insulin sensitivity in children.

Neutrophil to Lymphocyte Ratio Is Increased and Associated With Left Ventricular Diastolic Function in Newly Diagnosed Essential Hypertension Children.

Aim: Hypertension is associated with cardiac structural and functional changes, including left ventricular hypertrophy (LVH) and LV systolic dysfunction diastolic dysfunction. Neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory biomarker associated with cardiovascular diseases. The current study aimed to evaluate NLR in children with newly diagnosed essential hypertension and its relationship between blood pressure and cardiac changes. Methods and Subjects: Sixty-five children with newly diagnosed essential hypertension and 54 healthy children were included. Clinical characteristics, blood cell counts, and biochemical parameters were collected. LVH was assessed by calculation of LV mass index (LVMI), and LV systolic function was evaluated by measuring LV ejection fraction and fractional shortening. LV diastolic function was primarily assessed with E/E' ratio by Doppler and echocardiography. Results: The hypertension children had significantly higher LVMI and E/E' ratio than the controls, whereas there was no difference in LV systolic function between the two groups. The NLR was significantly higher in the hypertension group than the control group. Moreover, NLR was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in the hypertension group. Additionally, a significantly positive correlation between NLR and E/E' ratio was found in the hypertension group. However, NLR was not related to LVH and LV systolic function indicators in hypertension children. Conclusion: NLR is elevated in hypertension children, and it is associated positively with office blood pressure levels. Moreover, NLR may help assess LV diastolic function in hypertension children.

Decreased Flow-Mediated Dilatation in Children With Type 1 Diabetes: A Systematic Review and Meta-Analysis.

Type 1 diabetes (T1DM) is a strong risk factor for the development of cardiovascular disease. Flow-mediated dilatation (FMD) is an early noninvasive marker of endothelial function and it predicts future cardiovascular disease. However, the changes in FMD among T1DM children are still controversial. The present meta-analysis aimed to investigate whether FMD is impaired in children with T1DM. PubMed, EMBASE, Cochrane library, and Web of Science were searched for studies comparing FMD in children with T1DM and healthy controls. The Newcastle-Ottawa quality assessment scale for case-control studies was used to assess study quality. Data were pooled using a random effects models to obtain the weighted mean differences (WMD) in FMD and 95% CIs. Overall, 19 studies with 1245 patients and 872 healthy controls were included in this meta-analysis. Children with T1DM had significantly lower FMDs compared with healthy controls (WMD: -2.58; 95% CI: -3.36 to -1.81; P < .001). Meta-regression analysis revealed that low-density lipoprotein cholesterol levels impacted the observed difference in FMD between T1DM and healthy children. This meta-analysis showed that T1DM children have impaired endothelial function, which indicates they are at higher risk of developing cardiovascular disease in later life.

Serum CTRP3 Levels In Obese Children: A Potential Protective Adipokine Of Obesity, Insulin Sensitivity And Pancreatic ß Cell Function.

PURPOSE: CTRP3 is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The current study aimed to investigate the potential role of CTRP3 in obese children and explore its relationships with insulin sensitivity, pancreatic ß cell function, and obesity-related markers. PATIENTS AND METHODS: We studied the levels of serum CTRP3 in 48 obese and 36 normal weight pre-puberty children. The levels of blood pressure, lipids, glucose, and insulin were measured, and the values of HOMA-IR, HOMA-ß and insulinogenic index were calculated. The correlations of these measurements with CTRP3 levels were analyzed. RESULTS: In this study, we found that CTRP3 serum levels significantly decreased in obese children compared to controls, and insulin resistant obese subjects have lower CTRP3 levels in contrast with the non-insulin resistant obese subjects. Moreover, serum CTRP3 concentrations significantly decreased, while glucose and insulin concentrations significantly increased after a 3 hrs oral glucose tolerance test in obese children. Furthermore, Serum CTRP3 levels correlated negatively and significantly with BMI, triglycerides, systolic blood pressure, fasting insulin, glucose, HOMA-IR, HOMA-ß and insulinogenic index in obese children. CONCLUSION: In summary, serum CTRP3 levels significantly decreased in obese children, and negatively correlated with insulin resistance and pancreatic ß cell function indicators. Therefore, CTRP3 may play a protective role in the glucose homeostasis and tightly related to ß cell function as well as obesity-related markers in obese children.

Echocardiographic Prediction of Left Ventricular Dysfunction After Transcatheter Patent Ductus Arteriosus Closure in Children.

Objectives: To evaluate the change of left ventricular (LV) systolic function after transcatheter patent ductus arteriosus (PDA) closure in children, and to identify whether echocardiography parameters could be the predictors of LV dysfunction post-PDA closure if present. Methods: This study enrolled 191 pediatric PDA patients, and all of them underwent successful transcatheter PDA closure between January 2016 and December 2018. The patent ductus arteriosus diameter (PDAd), aortic root diameter (AOd), left atrial diameter (LAd), right ventricular outflow tract dimension (RVOT), LV end-diastolic dimension (LVEDD), and LV end-systolic dimension (LVESD) were all measured by echocardiography at pre-closure, post-closure (within 24 h after the procedure), and follow-up (3 months after the procedure). The ratio of PDAd to AOd (PDAd/AOd), the ratio of LAd to AOd (LAd/AOd), the left ventricular ejection fraction (LVEF), and the fractional shortening (FS) were calculated. Results: The LAd, LVESD, LVEDD, FS, and LVEF decreased significantly in the 24 h after closure, compared to pre-closure levels. However, all echocardiography parameters recovered to pre-closure levels at 3 months after PDA closure in all patients. Moreover, the pre-closure LAd, LVEF, PDAd/AOd, and LAd/AOd were higher in the patients with post-closure LV systolic dysfunction than in those without post-closure LV systolic dysfunction. Furthermore, the pre-closure LVEF, PDAd/AOd, and LAd/AOd were correlated with the post-closure LVEF, and pre-closure LVEF ≤ 66.5%, PDAd/AOd ≥ 0.28, and LAd/AOd ≥ 1.54 predict the post-closure LV systolic dysfunction. Conclusion: Transcatheter closure of PDA causes a significant deterioration in LV systolic function early after PDA closure, which recovered completely within 3 months of post-closure in children. Pre-closure LVEF, PDAd/AOd, and LAd/AOd can be the predictors of post-closure left ventricular systolic dysfunction.

Calcium-handling abnormalities underlying atrial arrhythmogenesis in a Fontan operation canine model.

BACKGROUND: Atrial tachyarrhythmia (AT) is a common complication in patients who have undergone a Fontan operation. In this study, we investigated whether abnormal Ca2+ handling contributes to the Fontan operation-related atrial arrhythmogenic substrate. METHODS: Mongrel dogs were randomly assigned to sham and Fontan groups. The Fontan operation model was developed by performing an atriopulmonary anastomosis. After 14 days, an electrophysiological study was performed to evaluate the AT vulnerability. Ca2+ handling properties were measured by loading atrial cardiomyocytes (CMs) with fura-2 AM. The L-type Ca2+ (ICa-L) and Na+-Ca2+ exchanger (INCX) currents of the CMs were recorded by the whole-cell patch-clamp technique. The key Ca2+ handling proteins expression was assessed by Western blotting. RESULTS: The AT inducibility was higher in the Fontan group than in the sham group (85.71 vs. 14.29%, P < 0.05). The Fontan operation resulted in decreased Ca2+ transient (CaT) amplitude and sarcoplasmic reticulum (SR) Ca2+ content, but in enhanced diastolic intracellular Ca2+ concentration and SR Ca2+ leak in the atrial CMs. The spontaneous CaT events, triggered ectopic activity and INCX density were increased, but ICa-L density was reduced in CMs from the Fontan atria (all P < 0.05). Additionally, the Fontan operation resulted in decreased SR Ca2+ ATPase expression and Cav1.2 expression, but in increased NCX1 and Ser2814-phosphorylated ryanodine receptor 2. The calmodulin-dependent protein kinase II expression and function were markedly enhanced in the Fontan atria. CONCLUSION: The Fontan operation caused atrial CM Ca2+ handling abnormalities that produced arrhythmogenic-triggered activity and increased vulnerability to AT in experimental Fontan dogs.

Clinical Experience of Transcatheter Closure for Residual Ventricular Septal Defect in Pediatric Patients.

BACKGROUND: Open cardiac surgery has traditionally been the gold standard for repair of ventricular septal defect (VSD). The inherent risks and complications associated with open surgery and the incidence of postoperative residual VSD are significant disadvantages of the open surgical approach. OBJECTIVE: To evaluate the methodology and efficacy of transcatheter closure of postoperative residual VSD in children. METHODS: Patients with postoperative VSD who underwent percutaneous device closure in the period from August 2010 and February 2014 in our center were analyzed retrospectively. Twelve children, including 8 males and 4 females, with mean age of 8.13 ± 5.39 years (range 0.67-17 years) and mean weight of 29.63 ± 20.86 kg (range 5.5-66 kg) were included in the study. RESULTS: Ten cases had residual shunts situated at the margin of the patches while the other two had residual shunts because of multiple muscular VSD. The mean VSD diameter was 3.84 ± 1.86 mm (range 2.3-8.7 mm). On cardiac catheterization, the reported mean pulmonary circulatory blood volume/systemic circulation volume (Qp/Qs) ratio was 1.86 ± 0.91 (range 1.1-4.25) and the mean pulmonary artery pressure was 25.92 ± 12.42 mm Hg (range 7-52 mm Hg). Successful transcatheter closure was obtained in all twelve patients with postsurgery residual VSD. Two cases with residual muscular VSD underwent retrograde catheterization via the femoral artery while one case with residual VSD located at the lower margin of the patch was accessed via the internal jugular vein. The mean procedure time was 81.25 ± 25.86 minutes (range 40-120 minutes). There was no evidence of residual VSD, and no instances of new-onset valvular regurgitation were reported, with the only two exceptions being patients who had multiple muscular VSDs where clinically insignificant residual shunts were detected. CONCLUSION: Our retrospective study highlights the potential safety and therapeutic efficacy of transcatheter approach for closing postoperative residual VSD in children. RECOMMENDATIONS: More robust studies with longer-term follow-up of outcomes are required to firmly establish the safety profile and respective indications for use of various occluder devices for treating different categories of residual VSD.