Prevalence of Bicuspid Aortic Valve in Turner Syndrome Patients Receiving Cardiac MRI and CT: A Meta-Analysis

Turner syndrome (TS) is a rare disorder affecting 25–50 in 100000 female newborns. Bicuspid aortic valve (BAV) is assumed to be the most common congenital heart defect (CHD) in TS. In literature, reported BAV prevalence in TS ranges between 14% and 34%. The specific BAV prevalence in TS is still unknown. The aim of this study was to give a more precise estimation of BAV prevalence in TS by conducting a meta-analysis of TS-studies, which detected BAV by either cardiac magnetic resonance imaging (MRI) or cardiac computed tomography (CT). We searched PubMed, Cochrane Library, and Web of Science databases to collect observational studies including the prevalence of BAV identified by cardiac MRI or cardiac CT in TS patients up to June 4th, 2021. After screening for inclusion, data extraction, and quality assessment by two independent reviewers, the meta-analysis was performed with R 4.1.1 software. Results are shown as proportion and weighted mean difference with 95% confidence intervals (95% CI). In total, 11 studies involving 1177 patients were included. Pooled data showed that the prevalence of BAV in TS patients was 23.7% (95% CI: 21.3% to 26.1%). No high heterogeneity was found between the included studies. The current meta-analysis reveals that BAV can be detected in 23.7% of TS patients receiving cardiac MRI or cardiac CT. Therefore, BAV can be considered as the most common CHD in TS. Compared to TTE, cardiac MRI and cardiac CT might represent superior imaging modalities in BAV assessment of adult TS patients

Energy Drinks and Their Acute Effects on Arterial Stiffness in Healthy Children and Teenagers: A Randomized Trial

Adolescents are the main consumer group of energy drinks (ED). Studies suggest that acute ED consumption is associated with increased peripheral blood pressure. Little is known of the ED-induced effects on arterial stiffness. Therefore, this study aimed to investigate the acute effects of ED consumption on arterial stiffness in healthy children and teenagers by conducting a prospective, randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants (n = 27, mean age = 14.53 years) consumed a body-weight-adjusted amount of an ED or a placebo on two consecutive days. Arterial stiffness was evaluated sonographically by two-dimensional speckle tracking of the common carotid artery (CCA) at baseline and up to four hours after beverage consumption. The ED intake led to a significantly decreased peak circumferential strain of the CCA (11.78 +/- 2.70% vs. 12.29 +/- 2.68%, p = 0.043) compared with the placebo. The results of this study indicate that the acute ED consumption might be associated with increased arterial stiffness in healthy children and teenagers. Minors, particularly those with increased cardiovascular morbidity, should be discouraged from ED consumption

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Physical Activity and Diet Quality: Effects on Cardiovascular Morbidity in Women with Turner Syndrome&mdash;Results from an Online Patient Survey

Turner syndrome (TS) is a rare chromosomal disease with increased cardiovascular morbidity and mortality. The aim of this study was to investigate the influence of physical activity and diet quality on cardiovascular morbidity in German TS women. An anonymous online questionnaire was established. The questionnaire was based on the 2020 WHO recommendations on physical activity and sedentary behaviour and included the 14-Item Mediterranean Diet Assessment Tool. In addition, TS patients were asked about existing cardiovascular conditions. In total, 83 TS women were included in the final analysis. The achievement of &lt;600 Metabolic Equivalent-minutes per week for recreational activities was significantly associated with the presence of arterial hypertension (p = 0.006). High adherence to the Mediterranean diet was achieved by only 20.5% of TS subjects and tended to be inversely associated with the presence of lipid metabolism disorders (p = 0.063). Only 37.3% of TS participants received nutritional counselling. Given the increased cardiovascular risk, specific counselling for lifestyle optimisation may play an important role in the management of TS. Further studies are required to evaluate the effects of regular aerobic physical training and different nutritional programs on cardiovascular morbidity in TS

Energy Drinks and Their Acute Effects on Heart Rhythm and Electrocardiographic Time Intervals in Healthy Children and Teenagers: A Randomized Trial

Beyond their effect on blood pressure, the effect of energy drinks on heart rate in children and teenagers has not been evaluated until now. Thus, this study aimed to investigate the acute cardiovascular effects of energy drinks in healthy children and teenagers. Twenty-six children and adolescents (mean age 14.49 years) received a commercially available energy drink (ED) and placebo on two consecutive days based on the maximum caffeine dosage as proposed by the European Food Safety Authority. Heart rhythm and electrocardiographic time intervals were assessed in a prospective, randomized, double-blind, placebo-controlled, crossover clinical study design. ED consumption resulted in a significantly increased number of supraventricular extrasystoles (SVES) compared to the placebo, whereas supraventricular tachycardia or malignant ventricular arrhythmias were not observed. The mean heart rate (HR) was significantly lower following consumption of EDs. In contrast, QTc intervals were not affected by EDs. Being the first of its kind, this trial demonstrates the cardiovascular and rhythmological effects of EDs in minors. Interestingly, EDs were associated with adverse effects on heart rhythm. Whether higher dosages or consumption in children with preexisting conditions may cause potentially harmful disorders was beyond the scope of this pilot study and remains to be determined in future trials. Trial Registration Number (DRKS-ID): DRKS00027580

Cardiovascular Care of Turner Syndrome Women in Germany: Where Do We Stand?&mdash;Results from an Online Patient Survey

Background: This study aimed to investigate whether the cardiovascular care of Turner Syndrome (TS) women in Germany is in accordance with the latest clinical practice guidelines established by the 2016 Cincinnati international TS meeting. Methods: An anonymous online questionnaire was created to ask TS subjects about existing cardiovascular conditions and cardiovascular care received. Depending on cardiovascular morbidity and type of medical care received, the fulfillment of the latest clinical practice guidelines for the care of TS women was assessed. Results: 120 TS patients were included in this study. The mean age of TS subjects was 36.79 years. Only 80% of subjects received annual blood pressure measurements within the TS cohort, and only 60% received cardiac imaging according to international clinical practice guidelines. More than 55% of TS women did not feel well informed about TS-specific cardiovascular risk factors by their treating physician. Conclusions: A potential lack of cardiovascular care might be present in TS women in Germany as the results of this online patient survey suggest. The cardiovascular care of TS patients, particularly cardiac imaging and patient education, needs to receive more attention

Energy Drinks Decrease Left Ventricular Efficiency in Healthy Children and Teenagers: A Randomized Trial

Background: Minors are considered the main consumer group of energy drinks (EDs). The aim of this study was to investigate the acute effects of ED consumption on left ventricular (LV) hemodynamics and efficiency in healthy children and teenagers. Methods: This study was a randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants consumed a weight-adjusted amount of an ED or a placebo on two consecutive days. LV hemodynamics and efficiency parameters were evaluated non-invasively by generating LV pressure&ndash;volume loops (PVLs) through simultaneous echocardiography and blood pressure measurement. Results: A total of 24 children and teenagers (14.90 &plusmn; 2.27 years, 13 male) were included in the present study. Conventional echocardiographic parameters of LV function did not show significant differences between both beverage groups. The non-invasive generation of LV PVLs revealed a significantly lower cardiac efficiency 240 min after the ED consumption compared to the placebo intake (140.72 (133.21&ndash;149.73) mmHg vs. 135.60 (124.78&ndash;140.33) mmHg, p &lt; 0.01). Conclusions: Acute ED consumption is associated with a significantly lower cardiac efficiency in healthy minors. The generation of non-invasive LV PVLs might be beneficial in the assessment of subtle changes in LV efficiency. Further studies need to investigate the influence of chronic ED consumption on LV function and morphology