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Coronavirus disease 2019 (COVID-19) has become a significant global public health problem. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes the disease, utilizes angiotensin-converting enzyme II (ACE2) as a major functional receptor to enter host cells. No study has systematically assessed ACE2 expression in multiple tissues in children. This study investigated ACE2 expression and ACE2 protein's histological distribution in various organs in paediatric patients (the small intestine, thymus, heart and lungs). Our study revealed that ACE2 was highly expressed in enterocytes of the small intestine and widely expressed in the myocardium of heart tissues. The most notable finding was the positive staining of ACE2 in the Hassall's corpuscles epithelial cells. Negligible ACE2 expression in the lung tissues may contribute to a lower risk of infection and fewer symptoms of pneumonia in children than in adults with COVID-19 infection. These findings provide initial evidence for understanding SARS-CoV-2 pathogenesis and prevention strategies in paediatric clinical practice, which should be applicable for all children worldwide.
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COVID-19 , SARS-CoV-2 , Adulto , Humanos , Niño , Enzima Convertidora de Angiotensina 2/genética , Corazón , Salud PúblicaRESUMEN
Several studies have investigated the efficacy and safety outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and heart failure (HF). Herein, this meta-analysis was aimed to compare the effect of NOACs with warfarin in this population. We systematically searched the PubMed database until December 2019 for studies that compared the effect of NOACs with warfarin in patients with AF and HF. Risk ratios (RRs) and 95% confidence intervals (CIs) were abstracted and then pooled using a random-effects model. A total of nine studies were included in this meta-analysis. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism (RR = 0.82 (95% CI, 0.73-0.92)), all-cause death (RR = 0.87 (95% CI, 0.80-0.94)), major bleeding (RR = 0.84; (95% CI, 0.74-0.97)), intracranial hemorrhage (RR = 0.50; 95% CI, 0.43-0.59), and hemorrhagic stroke (RR = 0.49 (95% CI, 0.38-0.63)). There were no differences in the risks of ischemic stroke (RR = 0.89 (95% CI, 0.75-1.04)) and gastrointestinal bleeding (RR = 1.11 (95% CI, 0.79-1.55)) in patients treated with NOACs versus warfarin. Compared with warfarin use, the use of NOACs had similar or lower risks of thromboembolic and bleeding events in patients with AF and HF.
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Fibrilación Atrial , Insuficiencia Cardíaca , Accidente Cerebrovascular , Administración Oral , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento , Warfarina/uso terapéuticoRESUMEN
Several studies have explored the use of NOACs compared with vitamin K antagonists (VKAs) in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF); and therefore, we aimed to compare the efficacy and safety outcomes of NOACs with VKAs in this population. We systematically searched the PubMed and Embase databases until August 5, 2019 for studies that compared the effect of NOACs with VKAs in patients with HCM and AF. The risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. A total of four observational studies were included in this meta-analysis. Overall, compared with VKAs use, the use of NOACs was associated with reduced risks of ischemic stroke (RR 0.49, 95% CI 0.34-0.69), all-cause death (RR 0.44, 95% CI 0.35-0.55), and intracranial hemorrhage (RR 0.43, 95% CI 0.24-0.77). There were no differences in the risks of stroke or systemic embolism, major or clinically relevant bleeding, and gastrointestinal bleeding in patients with NOACs versus VKAs. Re-analyses with a fixed-effects model produced the similar results as the main analyses. For the efficacy and safety outcomes, comparisons of NOACs versus warfarin produced the similar results as those of NOACs versus VKAs. Based on current data from observational studies, compared with VKAs, NOACs had similar or lower risks of thromboembolic and bleeding events in patients with HCM and AF.
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Fibrilación Atrial/tratamiento farmacológico , Cardiomiopatía Hipertrófica/epidemiología , Inhibidores del Factor Xa/administración & dosificación , Accidente Cerebrovascular/prevención & control , Tromboembolia/prevención & control , Administración Oral , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/mortalidad , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Tromboembolia/diagnóstico , Tromboembolia/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION AND IMPORTANCE: Partially anomalous pulmonary venous connection (PAPVC) is a rare congenital heart disease, often concomitant with atrial septal defects (ASDs). PAPVC usually tends to be treated by surgery, but the case we report will open up new perspectives for the interventional treatment of PAPVC present with ASD. CASE PRESENTATION: We present a case of a 2-year-old 11 kg boy transthoracic echocardiography showed secundum-type ASD. A supracardiac-PAPVC was accidentally detected during cardiac catheterization, and an abnormal pulmonary vein connection was detected with a vertical vein (VV) opening. Ultimately, ASD and VV were both occluded. CLINICAL DISCUSSION: Surgical therapy of PAPVC is the first line treatment of most centers in the world. However, the main complications after surgical repair of PAPVC raise our concerns, such as pulmonary stenosis, caval vein stenosis and sinus node dysfunction. Therefore, percutaneous closure of PAPVC can be an alternative method. This case of percutaneous interventional closure of ASD and supracardiac PAPVC through a vertical vein in the same surgery was first reported. Patients with ASD tend to have missed diagnoses of PAPVC. We can evaluate it by transesophageal echocardiography (TEE), cardiac magnetic resonance imaging (CMR) and computed tomography (CT). CONCLUSIONS: This case suggests that the effect of interventional therapy is quite reliable. For children with ASD, attention should be paid to the omission of the presence or absence of PAPVC before surgery. During interventional therapy, a guide wire rather than a catheter should be preferred to explore the atrial septum and pulmonary veins to avoid a missed diagnosis of PAPVC.
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FAT10 is a new member of the ubiquitin-like protein family with yet-to-be defined biological functions in the heart. Our objective was to determine the role of FAT10 in the heart. FAT10 is expressed in the normal human and murine hearts, as detected by qPCR and Western blotting. Expression of FAT10 is increased in the heart at the border zone of myocardial infarction and in cultured neonatal rat cardiac myocytes (NRCM) subjected to hypoxia/reoxygenation (H/R) stress. Lentiviral-mediated overexpression of FAT10 in NRCM reduced p53 (TP53) and its target miR-34a levels, while BCL2 level, a target of miR-34a, was increased and BAX level, a pro-apoptotic protein, was reduced. These changes were associated with reduced apoptosis, detected by FACS analysis of annexin-V expression and TUNEL assay, in response to H/R injury. Knock down of FAT10 by shRNA targeting had the opposite effects. Likewise, lentiviral mediated expression of miR-34a was associated with reduced BCL2 and increased BAX levels in NRCM and also reversed changes in BCL-2 and BAX levels observed upon over-expression of FAT10. Treatment of NRCM with proteasome inhibitor MG132 increased p53 and miR-34a levels and reduced BLC2/BAX ratio. These changes were not reversed upon over-expression of FAT10. Thus, FAT10 is upregulated in the heart and NRCM in response to H/R stress, which protects cardiac myocytes against apoptosis. The anti-apoptotic effects of FAT10 are associated with suppression of p53, probably through fatylation and proteasomal degradation, reduced miR-34a expression, and a shift in the BCL2/BAX proteins against apoptosis. Thus, FAT10 is a cardioprotective protein.
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Miocitos Cardíacos/metabolismo , Ubiquitinas/metabolismo , Animales , Apoptosis/genética , Apoptosis/fisiología , Células Cultivadas , Humanos , Masculino , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Miocardio/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitinas/genética , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The subject of the study is an 11-month old IVF baby girl with the typical clinical manifestation of malonyl coenzyme A decarboxylase deficiency, including developmental delay, limb weakness, cardiomyopathy, and excessive excretion of malonic acid and methylmalonic acid. Whole genome sequencing (WGS) revealed a novel heterozygous nonsense mutation (c.672delG, p.Trp224Ter) in the MLYCD gene of the proband and her father and a novel heterozygous deletion in 5'-UTR-exon1-intron1 of the MLYCD gene of the proband and her mother. The patient's cardiac function and limb weakness improved considerably after 3 months of a low-fat diet supplemented with L-carnitine. Furthermore, mapping of gene mutations and clinical manifestations was done by case collection.
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Introduction: To investigate the clinical characteristics and disease outcomes of a pedigree with compound heterozygous mutations in the SLC22A5 gene. Methods: Serum acylcarnitine profiles of patients were analyzed using tandem mass spectrometry. DNA samples isolated from patients and their first-degree relatives were subjected to high-throughput sequencing, and mutations were validated using Sanger sequencing. Results: The proband, a 4-month-old girl, presented with seizure episodes and mild cardiac hypertrophy and was diagnosed with primary carnitine deficiency (PCD), with carnitine levels of 5.165â mol/L. Her brother, a 6-year-and 4-month-old boy, was also diagnosed with PCD with serum-free carnitine levels of 1.014â mol/L (reference values 10-60â mol/L). Compound heterozygous mutations (c.760C > T [p.R254X] and c.825G > A [p.W275X]) were detected in the SLC22A5 gene in both patients and were inherited from the mother and father, respectively. Oral L-carnitine significantly improved or resolved the clinical symptoms. Conclusion: Children with compound mutations in SLC22A5 may present different clinical manifestations, particularly at different ages. Early clinical manifestations have a greater impact on the organs and may cause irreversible damage. PCD can cause epilepsy and dilated cardiomyopathy. Tandem mass spectrometry and high-throughput sequencing are recommended to confirm the diagnosis. Early L-carnitine supplementation can improve symptoms and reverse organ damage in some children. Tandem mass spectrometry should be used to screen for newborns with a family history of PCD.
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OBJECTIVES: Hypertension in children has attracted increasing attention. However, clinical-based studies investigating characteristics and secular trends of pediatric hypertension remain limited. This study aimed to investigate the clinical characteristics and secular trends of different types of hypertension among hospitalized children in China. METHODS: This retrospective analysis was based on medical records from nine tertiary children's hospitals in China during 2010â¼2020. A total of 5847 pediatric inpatients (aged <18âyears) with the diagnosis of hypertension were enrolled. Information on the clinical characteristics of each patient was obtained from their first admission records. RESULTS: During the past decade, secondary hypertension sustained to be the dominant type of hypertension in children, with the proportion increased from 51.2% during 2010â¼2015 to 59.8% during 2016â¼2020. The main causes of secondary hypertension were neurologic disorders in children aged 0â¼2âyears, which changed to renal diseases after 3âyears of age. Compared with primary hypertension, secondary hypertension was common in girls (43.1 vs. 23.3%) and children under 5âyears of age (32.2 vs. 2.1%). Moreover, over four-fifths of primary hypertensive individuals had obesity and obesity-related comorbidities, and the proportion of clusters of one or more comorbidities increased in the past decade (79.7 â 85.2%). CONCLUSION: Secondary hypertension sustained to be the dominant type of hypertension among children, especially in girls. Renal diseases were the most common causes of secondary hypertension in children, followed by rheumatic immune diseases. For primary hypertension, over four-fifths of inpatients had obesity and obesity-related diseases, and the proportion kept rising.
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Hipertensión , Obesidad , Femenino , Niño , Humanos , Preescolar , Estudios Retrospectivos , China/epidemiología , Hipertensión/epidemiología , Hipertensión EsencialRESUMEN
OBJECTIVES: To describe clinical and imaging characteristics of an isolated subclavian artery (ISA) in pediatric patients. BACKGROUND: ISA is a rare congenital aortic arch anomaly defined as a loss of connection between the subclavian artery and aorta. The clinical manifestations and complications of ISA in children are unclear. METHODS: This retrospective study included clinical and imaging data of ISA patients younger than 18 years whose data were recorded in the electronic radiology database during January 2006-August 2019. RESULTS: Of 102 enrolled patients, 59 had been diagnosed in the first year of life. The majority of the patients also had congenital heart diseases, of which tetralogy of Fallot was the most common. The vertebral artery and collateral branch of the descending aorta served as blood flow supplies in 94 and 8 patients with ISA, respectively, as confirmed using computed tomography or magnetic resonance imaging. However, the blood supply did not influence the development of ISA. Eleven patients exhibited mild or moderate stenosis of the ISA, although only two exhibited coldness or a blood pressure gradient in the upper extremities. These two symptomatic patients also presented with patent ductus arteriosus, and this association was significant (P = 0.008). CONCLUSION: ISA management is often determined based on symptoms and associated congenital heart diseases. The ISA is prone to stenosis in patients with ipsilateral patent ductus arteriosus. We recommend early surgical ligation or percutaneous closure of the ductus arteriosus in patients with ISA.