Hypertension crisis as the first symptom of renovascular hypertension in children.

BACKGROUND: Renovascular hypertension (RVH) is one of the main causes of hypertensive crisis (HTN-C). It is characterized by acute onset and severe disease, and early diagnosis and treatment are difficult. The objective was to describe the characteristics of RVH and factors associated with RVH leading to HTN-C in children. At present, there are few clinical studies on RVH in children with large cases in China. METHODS: This study retrospectively analyzed the clinical data of inpatient children with RVH. Patients were divided into non-hypertensive crisis (non-HTN-C) group, and HTN-C group according to the first symptoms and blood pressure. Further, HTN-C were classified as hypertensive urgency (HTN-U) or hypertensive emergency (HTN-E). RESULTS: Fifty-four pediatric cases (41 boys and 13 girls) were included. 83.3% of the RVH cases were ≥ 6 years old. Three cases were classified into the non-HTN-C group. Of the 51 HTN-C cases, 18 cases were grouped as HTN-U and 33 as HTN-E. The HTN-U group were mainly asymptomatic (50.0%, 9/18) while the HTN-E group mainly presented with neurological symptoms (72.7%, 24/33). The number of unknown etiology children was 32 (59.2%). The top three known etiologies were Takayasu's arteritis (50.0%, 11/22), congenital renal dysplasia (27.3%, 6/22) and fibromuscular dysplasia (13.6%, 3/22). As for the target organ damage of RVH, patients had a higher prevalence of left ventricular hypertrophy (71.4%, 35/49) and retinopathy (77.8%, 21/27). CONCLUSIONS: Most RVH patients with HTN-C as the first symptoms, especially for males over 6 years old, should be assessed for RVH even if they were asymptomatic. Most asymptomatic patients with RVH already had target organ damage, and symptomatic patients even developed life-threatening complications. As preventive measures, routine monitoring of BP during children's physical examinations is advised.

Predictors for Intravenous Immunoglobulin Resistance in Patients with Kawasaki Disease.

Background: Between 10 and 20% of Kawasaki disease (KD) patients are resistant to treatment with initial intravenous immunoglobulin (IVIG) and have a high risk of developing coronary artery lesions. Some studies have been conducted to identify predictive factors. However, the results are controversial. This study aims to identify the risk factors for IVIG-resistant KD patients in a Chinese population. Methods: We performed a retrospective analysis of medical records of consecutive KD patients from two medical centers in South China from January 2015 to December 2017. A total of 1281 KD patients were eligible for inclusion in this study and maintained follow-up for over 12 months. The KD patients were divided into two groups based on IVIG response. Clinical characteristics and laboratory variables were compared between the two groups. Multivariate logistic regression analysis was performed to identify the risk factors of IVIG resistance in KD patients. Results: Of the 1281 KD patients, 141 (11.0%) cases who were IVIG resistant to adjunctive therapies for primary treatment were classified as group 1. The remaining patients were in group 2 (n = 1140), classified as the control group. There was a significant difference in male to female ratio and the length of hospital stay between the two groups (P < 0.05). Group 1 had a higher white blood cell count (P=0.01) and C-reactive protein level (P < 0.01) before IVIG treatment than in group 2. Group 1 had a significantly higher white blood cell count and percentage of neutrophils after the IVIG infusion than in group 2 (P < 0.001). In addition, the mean values of C-reactive protein level and neutrophil percentage before and after treatment difference comparison were significantly different. Multivariate analysis showed that patients presenting with coronary artery lesions in the acute phase and a C-reactive protein level >100 mg/L at diagnosis were associated with IVIG resistance in KD. During the 12-month follow-up period, group 1 had an obviously higher incidence of coronary artery lesions than group 2, and the difference between the groups was statistically significant (P < 0.001). Conclusions: Patients presenting with coronary artery lesions in the acute phase and elevated C-reactive protein levels before IVIG treatment might be a useful and important value for predicting IVIG resistance in KD. Risk assessment based on coronary artery lesions and C-reactive protein levels prior to the treatment may improve the outcome of IVIG resistance.

Prediction of Immune Infiltration Diagnostic Gene Biomarkers in Kawasaki Disease.

Kawasaki disease (KD) is characterized by disorder of immune response with unknown etiology. Immune cells may be closely related to the onset of KD. The focus of this research was to evaluate the significance of the infiltration of immune cells for this disease and find possible diagnostic biomarkers for KD. The Gene Expression Omnibus database was utilized to retrieve two freely accessible gene expression patterns (GSE68004 and GSE18606 datasets) from human KD and control specimens. 114 KD, as well as 46 control specimens, were searched for obtaining differentially expressed genes (DEGs). Candidate biological markers were determined utilizing the support vector machine recursive feature elimination and the least absolute shrinkage and selection operator regression model analysis. To assess discriminating capacity, the area under the receiver operating characteristic curve (AUC) was computed. The GSE73461 dataset was utilized to observe the biomarkers' expression levels and diagnostic significance in KD (78 KD patients and 55 controls). CIBERSORT was employed to assess the composition profiles of the 22 subtypes of immune cell fraction in KD on the basis of combined cohorts. 37 genes were discovered. The DEGs identified were predominantly involved in arteriosclerotic cardiovascular disease, atherosclerosis, autoimmune disease of the urogenital tract, and bacterial infectious disease. Gene sets related to complement and coagulation cascades, Toll-like receptor signaling pathway, Fc gamma R-mediated phagocytosis, NOD-like receptor signaling pathway, and regulation of actin cytoskeleton underwent differential activation in KD as opposed to the controls. KD diagnostic biomarkers, including the alkaline phosphatase (ALPL), endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2 (EDEM2), and histone cluster 2 (HIST2H2BE), were discovered (AUC = 1.000) and verified utilizing the GSE73461 dataset (AUC = 1.000). Analyses of immune cell infiltration demonstrated that ALPL, EDEM2, and HIST2H2BE were linked to CD4 memory resting T cells, monocytes, M0 macrophages, CD8 T cells, neutrophils, and memory CD4 T cells. ALPL, EDEM2, and HIST2H2BE could be utilized as KD diagnostic indicators, and they can also deliver useful information for future research on the disease's incidence and molecular processes.

Duchenne Muscular Dystrophy With Low Acidic α-Glucosidase Activity: Two Case Reports and Literature Review.

Background: Pompe disease is usually considered in children with elevated creatine kinase (CK) levels and decreased acidic α-glucosidase (GAA) enzyme activity. However, there are exceptions, such as GAA pseudo deficiency alleles, which result in lower GAA enzyme activity but do not cause Pompe disease. Here, we report two cases presenting with high CK levels and low GAA activity who were ultimately diagnosed with Duchenne muscular dystrophy (DMD). Case Presentation: Case 1 patient was a 2-month-old boy who presented with an extremely high serum CK level (5,480∼11,880 U/L) and low GAA activity (2.72 nmol/1 h/mg). The whole-exome sequencing did not find the pathogenic GAA gene mutation, however, there was a DMD gene hemizygous variation (c. 7657C > T, p. Arg2553Ter) inherited from his mother, which was verified by the first-generation sequencing. Further genetic analysis of GAA identified two homozygous pseudo deficiency alleles (c.1726G > A, p. Gly576Ser and c.2065G > A, p. Glu689Lys), which were believed to induce the patient's low GAA activity. Therefore, the boy was diagnosed with DMD, although he had extremely low GAA activity. Case 2 patient was also a 2-month-old boy presenting with a significant increase in CK level (12,408∼24,828 U/L). His blood GAA activity (colorimetric method) was 9.02 nmol/1 h/mg. Similarly, his whole-exome sequencing did not find the pathogenic mutation of the GAA gene, but a DMD gene hemizygous variation (c.5571del, p. Lys1857AsnfsTer8), hence he was diagnosed with DMD as well. Regarding GAA activity, the case 2 patient was not as low as the case 1 patient, mainly because his two GAA pseudo deficiency alleles were heterozygous. Conclusion: Pompe disease is usually screened in infants with high CK levels. We should be aware that pseudo deficiency alleles can cause low GAA activities but not Pompe disease. Genetic tests would be helpful to distinguish cases with GAA pseudo deficiency alleles from patients with some muscular disorder diseases such as DMD.

Clinical Characteristics of Hospitalized Pediatric Patients With Hypertensive Crisis-A Retrospective, Single-Center Study in China.

Background: A hypertensive crisis is a medical emergency that causes acute damage to multiple organs. However, the etiology, clinical features, and prognosis of hypertensive crisis in Chinese children remain relatively unknown. The purpose of this study was to analyze the clinical characteristics of pediatric hypertensive crisis patients from a single center in China. Methods: We analyzed data from 70 children with hypertensive crisis between January, 2000, and January, 2022. The patients were divided into two groups: those diagnosed with a hypertensive emergency (n = 46) and those diagnosed with hypertensive urgency (n = 24). Baseline etiologies and risk factors were compared between the two groups. The following data were collected and analyzed: age, sex, weight, height, family history of hypertension, blood pressure, clinical manifestations of hypertensive crisis, underlying causes, biochemical indicators, and antihypertensive drugs. Results: The major symptoms of hypertensive crisis were headache (n = 31, 44.29%), followed by visual symptoms (n = 15, 21.43%), and dizziness (n = 13, 18.57%). Further analysis showed that the incidence of convulsions was significantly higher in patients with hypertensive emergency than those with hypertensive urgency (χ2 = 5.38, p = 0.02). The leading underlying causes were renal disease (n = 34, 48.57%), followed by vascular disease (n = 11, 15.71%), essential hypertension (n = 9, 12.86%), oncological disease (n = 9, 12.86%), central nervous system disease (n = 3, 4.29%), endocrine and metabolic diseases (n = 2, 2.86%), and other (one case with lead poisoning, one case with histiocytosis). End-organ damage occurred in 46 patients with hypertensive crisis, including retinal damage (n = 20, 43.48%), brain damage (n = 19, 41.30%), heart damage (n = 15, 32.61%), and renal damage (n = 3, 6.52%). Hypertensive crisis was most common among children aged 7-12 years. Among children aged 13-18 years, hypertensive urgency was more common than hypertensive emergency. The incidence of dyslipidemia, elevated serum creatinine, and elevated uric acid did not differ significantly between the two groups. Most patients with hypertensive crisis need combined antihypertensive therapy (n = 60, 85.71%). There were no cases of mortality. Conclusions: Hypertensive crisis is caused by secondary diseases, especially renal disease and vascular disease, in the majority of pediatric patients. Combination therapy with antihypertensive agents and treatment of secondary etiology results in a good prognosis.

Case Report: Talaromyces marneffei Infection in a Chinese Child With a Complex Heterozygous CARD9 Mutation.

Talaromyces marneffei (TM) infection is rarely seen in clinical practice, and its pathogenesis may be related to deficiency in antifungal immune function. Human caspase recruitment domain-containing protein 9 (CARD9) is a key molecule in fungal immune surveillance. There have been no previous case reports of TM infection in individuals with CARD9 gene mutations. Herein, we report the case of a 7-month-old Chinese boy who was admitted to our hospital with recurring cough and fever with a papular rash. A blood culture produced TM growth, which was confirmed by metagenomic next-generation sequencing. One of the patient's sisters had died of TM septicaemia at 9 months of age. Whole exome sequencing revealed that the patient had a complex heterozygous CARD9 gene mutation with a c.1118G>C p.R373P variation in exon 8 and a c.610C>T p.R204C variation in exon 4. Based on the culture results, voriconazole antifungal therapy was administered. On the third day of antifungal administration, his temperature dropped to within normal range, the rash gradually subsided, and the enlargement of his lymph nodes, liver, and spleen improved. Two months after discharge, he returned to the hospital for a follow-up examination. His general condition was good, and no specific abnormalities were detected. Oral voriconazole treatment was continued. Unexplained TM infection in HIV-negative individuals warrants investigation for immune deficiencies.

A Retrospective Cohort Study of Intravenous Immunoglobulin Therapy in the Acute Phase of Kawasaki Disease: The Earlier, the Better?

BACKGROUND: Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study. METHODS: We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers. RESULTS: A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness (n = 77). Group 2 was defined with days 5-7 (n = 817), group 3 with days 8-10 (n = 249), group 4 with days >10 (n = 138). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences (p < 0.05). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 (p < 0.05) and group 2 (p < 0.05) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance (p > 0.05). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs. CONCLUSIONS: IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800).

Sitosterolemia With Atherosclerosis in a Child: A Case Report.

Introduction: Sitosterolemia is a rare condition in children and is often misdiagnosed as familial hypercholesterolemia. Serious complications can result if not treated promptly and effectively. When pediatric patients are diagnosed with sitosterolemia, vascular, and cardiac studies are important to evaluate for the presence of atherosclerosis. Few cases of severe atherosclerotic heart disease in children with sitosterolemia have been reported, making this case worthy of presentation. Case Presentation: Here, we report a case of sitosterolemia in an 8-year-old child. The patient presented with severe hypercholesterolemia and xanthoma. He was diagnosed two and a half years prior with familial hypercholesterolemia because his father had elevated cholesterol levels. After conventional treatment, the patient was dissatisfied with lipid level control and visited our hospital for further management. Genetic tests of the patient and parents found mutations in intron 7 (NM 022436.2, c.904+1G>A) and intron 9 (NM 022436.2, C. 1324+1de1G) of ABCG5. The 7 intron mutation was from his mother, and the 9 intron mutation was from his father. The patient was diagnosed with sitosterolemia. Results: The child was treated with ezetimibe, a low plant sterol diet, and clopidogrel anticoagulant therapy. After 3 months of treatment, the blood lipid level was significantly lower. Conclusion: Genetic testing should be completed as soon as possible to avoid misdiagnosis in children with abnormally elevated hypercholesterolemia who have a family history of elevated cholesterol. In addition, clinicians should rule out great arterial lesions and be vigilant in evaluating patients for systemic arterial disease and atherosclerosis.

A Chromosomal Inversion of 46XX, inv (6) (p21.3p23) Connects to Congenital Heart Defects.

Congenital heart defects (CHDs) represent the most common human birth defects. Ventricular septal defect (VSD) is the most common subtype of CHDs. It has been shown that about 20-40% of VSDs are closely related to chromosomal aneuploidies or Mendelian diseases. In this study, we report a pedigree with VSD associated with a balanced paracentric inversion of chromosome 6, inv (6)(p21.3p23), a rarely reported CHD-associated chromosomal abnormality related to the fragile site at 6p23. We have found that the major clinical features of the proband include CHDs (ventricular septal defect, severe pulmonary hypertension, tricuspid regurgitation, and patent foramen ovale), severe pneumonia, and growth retardation. Our study reports a rare chromosomal abnormality connected to CHDs, which may represent a new genetic etiology for VSD.

Beta Blocker Therapy for Congenital Hepatic Arteriovenous Fistula in Two Neonates.

Introduction: Hepatic arteriovenous fistula (HAVF) is an abnormal communication between the hepatic arteries and hepatic veins. This condition is treated mainly using interventional closure and surgery. However, these procedures are associated with many postoperative complications and high mortality. Propranolol and other beta blockers have been used widely and effectively to treat infantile hemangiomas. However, no reports describe the use of these drugs to treat congenital HAVF. Case Description:Here, we present two cases in which beta blocker therapy was used to treat congenital HAVF in neonates. In both cases, antenatal examinations revealed cardiac enlargement and hepatic space-occupying lesions. After birth, both patients rapidly presented with respiratory distress, cyanosis, and heart failure. Echocardiography suggested enlargement of the right heart, widening of the pulmonary artery, and severe pulmonary arterial hypertension, and hepatic examinations revealed HAVF. Results:After admission, the patients were treated with dopamine, milinone, and furosemide for heart failure. However, their conditions worsened, as indicated by nod-like breathing and cyanosis. Endotracheal intubation and ventilator-assisted breathing and a small dose of oral propranolol (1 mg/kg/d) were initiated. The patients' conditions improved, as indicated by decreases in levels of the N-terminal pro-hormone BNP, and the ventilators were removed. The propranolol dose was increased gradually to 2 mg/kg/d. After 2 weeks of propranolol treatment, the neonate in case 2 developed bronchospasm, which improved after propranolol treatment ended and metoprolol treatment was initiated. Liver imaging performed 8-9 months after beta blocker therapy suggested the disappearance of the arteriovenous fistulae in case 2, and close to disappearing of the arteriovenous fistulae in case 1. Conclusion:Propranolol and metoprolol can effectively treat HAVF in infants, an observation consistent with that found in earlier studies that have shown beta blockers are a valid medical treatment option for infantile hemangioma. However, future studies should explore the underlying potential mechanism.

Amiodarone-Related Pure Red Cell Aplastic Anemia and Hypothyroidism in a Child With Total Anomalous Pulmonary Venous Connection.

Introduction: Amiodarone is an effective anti-arrhythmic drug, but there are many clinical side effects that limit its application. There are no case reports of amiodarone-related pure red cell aplastic anemia (PRCA). Case Presentation: Here, we present a case of amiodarone-related PRCA and hypothyroidism in a 7-month-old boy. The patient had a total anomalous pulmonary venous connection (the cardiac type) and had undergone cardiac surgery at the age of 2 months. Eleven days after the operation, atrial tachycardia was observed. Amiodarone was administered orally (15 mg/kg.d), following which the arrhythmia was under control. Subsequently, the patient was prescribed amiodarone (5 mg/kg.d) and discharged. Regular medical consultations were not conducted as required. At 7 months of age (5 months after the operation), the patient returned to the hospital for re-examination. The electrocardiogram showed intermittent sinus bradycardia, occasional junctional escape beats, hemoglobin 7.9 g/DL, and thyroid function-TSH 9.660 uIU/mL. Results: Amiodarone was discontinued. Thyroxine was administered orally. Subsequently, the heart rate improved and TSH returned to normal levels. Nutritional therapy was recommended based on a diagnosis of nutrition-related anemia. A re-visit at 9 months of age showed that the weight was 6 kg, but the routine blood test indicated that hemoglobin was 5.9 g/DL with positive cell anemia and low reticulocyte count. Bone marrow cytology examination suggested PRCA. The hemoglobin level was gradually restored after treatment with prednisone. Conclusion: The use of amiodarone in small infants and young children and its side effects should be carefully monitored. The potential mechanism of amiodarone-related PRCA needs further study.

Chronic Active Epstein-Barr Virus Infection With Systemic Vasculitis and Pulmonary Arterial Hypertension in a Child.

Introduction: A chronic active Epstein-Barr virus (EBV) infection (CAEBV), which is characterized by persistent "infectious mononucleosis-like" symptoms, can lead to cardiovascular complications, including coronary artery aneurysms. No published studies have reported an occurrence of chronic EB virus infection in conjunction with systemic vasculitis and pulmonary hypertension. Case Presentation: Herein, we present a case of a 9-year-old boy with CAEBV, associated with pulmonary arterial hypertension (PAH) and systemic vasculitis. Recurrent skin ulcers were a major early clinical manifestation in this case. The histopathological examination of a dermal biopsy sample from the lesions revealed vasculitis, and the in-situ hybridization test was positive for EBV-encoded small RNA. Results: The patient was administered immunosuppressants (prednisolone and cyclophosphamide) and targeted drugs (sildenafil and bosentan) to control the pulmonary pressure. This combination therapy decreased the systolic pulmonary arterial pressure to 40 mm Hg (on echocardiography), and the N-terminal pro b-type natriuretic peptide level also reduced to 62.3 pg/ml. After discontinuation of prednisone, the child developed shortness of breath, edema, and oliguria. He was again started on prednisone, with an addition of thalidomide. Sildenafil was replaced by riociguat, due to the side effect of penile erection. The patient is being followed up every 2 months at the clinic. The most recent follow-up visit was 2 weeks before this report was written, during which, the child was observed to have no rash, shortness of breath, edema, and other symptoms. Written informed consent was obtained from the parents for the publication of this case report. Conclusion: A CAEBV should be considered among the differential diagnoses while managing a pediatric patient with secondary PAH and systemic vasculitis. However, elucidation of its potential pathophysiological mechanisms requires further study.

Serum Chemerin Levels Correlate With Determinants of Metabolic Syndrome in Obese Children and Adolescents.

OBJECTIVES: This study aimed to investigate serum chemerin concentrations in obese children and adolescents and to investigate the associations of chemerin with body mass index (BMI), lipid levels, and insulin sensitivity. METHODS: Forty-eight obese and 40 nonobese Chinese children and adolescents were included in the study. BMI and levels of chemerin, lipids, glucose, and insulin were measured following an overnight fast. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and BMI standard deviation score (BMI-SDS) were determined for all participants. RESULTS: Serum chemerin levels were found to be significantly higher in obese children and adolescents than in control group members (94.83 ± 5.99 ng/mL vs 56.43 ± 4.16 ng/mL, P < .001). There were significant correlations between chemerin and age, BMI, BMI-SDS, total triglyceride (TG) levels, insulin levels, and HOMA-IR. After controlling for age, we found that chemerin levels were also significantly correlated with BMI-SDS (r =+ 0.284, P = .008) and HOMA-IR (r =+ 0.241, P = .034). In a stepwise multiple regression analysis, we observed only BMI-SDS to be an important determinant of chemerin level. CONCLUSIONS: In our sample of Chinese children and adolescents, chemerin levels were significantly higher in the obese group than in the control group. Chemerin levels were positively correlated with BMI-SDS and HOMA-IR and negatively correlated with age. We thus believe that further study is necessary to investigate the risk of metabolic abnormalities in young obese children and adolescents.

Pentoxifylline Prevents Driamycin-Induced Myocardial Fibrosis and Apoptosis in Rats.

Adriamycin (ADR) is a potent antineoplastic agent, but long-term treatment is limited by its cumulative, life-threatening cardiomyopathy. Recently, a few reports have shown that pentoxifylline (PTX) might produce cardioprotection in cardiac dysfunction. Here, we investigated the protective effects of PTX on ADR-induced cardiomyopathy in rats. Male rats were randomly assigned either to saline, ADR (adriamycin, 5 mg/kg/week), or A (adriamycin, 5 mg/kg/week) + PTX (pentoxifylline, 50 mg/kg/day) groups. After 3 weeks, these animals were sacrificed and the heart tissue was harvested for histological analysis and assessment of hepatocyte growth factor (HGF) and caspase-3 expression. Histopathological findings showed that PTX can alleviate myocardial damage caused by ADR. Cardiac fibrosis was significantly suppressed in the A+PTX group compared to that in the ADR group. The HGF gene expression was decreased significantly in the ADR group compared with the control group, but was increased in the A+PTX group. Caspase-3 was up-regulated in the ADR group, and down-regulated in the A+PTX group. These results show that treatment with PTX exerts a protective effect against ADR-induced myocardial fibrosis via regulation of HGF and caspase-3 gene expression. PTX may thus represent a useful new clinical tool for the treatment of ADR-induced cardiomyopathy.