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Echocardiography is the fundamental tool in the management of children with congenital heart disease (CHD), and cross-sectional echocardiography is still the main technique used for diagnosis and therapeutic planning. Recent advances in pediatric echocardiography include 3D echocardiography and functional imaging. The recent development of specific pediatric probes allows imaging of pediatric hearts with high temporal and spatial resolution. Lesions are often anatomically complex, and 3D echocardiography allows increased appreciation of complex spatial relationships and can thereby be valuable in understanding functional anatomy and planning interventions. Assessment of pediatric myocardial function can be difficult, with highly variable ventricular morphology. Assessment of right ventricular function and function of the single ventricle are current challenges in CHD. The introduction of myocardial tissue Doppler velocities and deformation imaging (strain and strain-rate quantification) facilitates the quantification of myocardial function independent of underlying morphology. These techniques offer new insights into the mechanics of CHD. [ABSTRACT FROM AUTHOR]

The global population is increasingly reliant on vaccines to maintain population health with billions of doses used annually in immunisation programmes. Substandard and falsified vaccines are becoming more prevalent, caused by both the degradation of authentic vaccines but also deliberately falsified vaccine products. These threaten public health, and the increase in vaccine falsification is now a major concern. There is currently no coordinated global infrastructure or screening methods to monitor vaccine supply chains. In this study, we developed and validated a matrix-assisted laser desorption/ionisation-mass spectrometry (MALDI-MS) workflow that used open-source machine learning and statistical analysis to distinguish authentic and falsified vaccines. We validated the method on two different MALDI-MS instruments used worldwide for clinical applications. Our results show that multivariate data modelling and diagnostic mass spectra can be used to distinguish authentic and falsified vaccines providing proof-of-concept that MALDI-MS can be used as a screening tool to monitor vaccine supply chains., (© 2024. The Author(s).)

This document has been developed to provide a guide for basic and advanced reporting in paediatric echocardiography. Furthermore, it aims to help clinicians in the interpretation of echocardiographic measurements and functional data for estimating the severity of disease in different paediatric age groups. The following topics will be reviewed and discussed in the present document: (i) the general principle in constructing a paediatric echocardiographic report, (ii) the basic elements to be included, and (iii) the potential and limitation of currently employed tools used for disease severity quantification during paediatric reporting. A guide for the interpretation of Z-scores will be provided. Use and interpretation of parameters employed for quantification of ventricular systolic function will be discussed. Difficulties in the adoption of adult parameters for the study of diastolic function and valve defects at different ages and pressure and loading conditions will be outlined, with pitfalls for the assessment listed. A guide for careful use of prediction scores for complex congenital heart disease will be provided. Examples of basic and advanced (disease-specific) formats for reporting in paediatric echocardiography will be provided. This document should serve as a comprehensive guide to (i) structure a comprehensive paediatric echocardiographic report; (ii) identify the basic morphological details, measures, and functional parameters to be included during echocardiographic reporting; and (iii) correctly interpret measurements and functional data for estimating disease severity., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: This study aimed to describe the natural history and predictors of all-cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM)., Methods and Results: This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18 years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS-LAH)]. One hundred forty-nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan-like syndrome, and 3 (2%) NS-LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36-80) mmHg, P = 0.004]. Over a median follow-up of 197.5 [inter-quartile range (IQR) 93.58-370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6-175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69-98.51], 90.42% (95% CI 84.04-94.33), and 84.12% (95% CI 75.42-89.94) at 1, 5, and 10 years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non-sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all-cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event., Conclusions: These findings highlight a distinct category of patients with Noonan-like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy-related HCM., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global 'Prevent, Detect and Respond' strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated., Aim: To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population., Methods: Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters., Results: Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis., Conclusion: Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further., Competing Interests: Declaration of Competing Interest Wolf CM: consultancy with Day One Biopharmaceuticals, Inc., BioMarin Pharmaceuticals, Adrenomed AG, and Pliant Therapeutics; ownership interest: Preventage Therapeutics. Zenker M: consultancy with Day One Biopharmaceuticals, Inc. and Novo Nordisk., (Copyright © 2023. Published by Elsevier B.V.)

Preventing, detecting, and responding to substandard and falsified vaccines is of critical importance for ensuring the safety, efficacy, and public trust in vaccines. This is of heightened importance in context of public health crisis, such as the COVID-19 pandemic, in which extreme world-wide shortages of vaccines provided a fertile ground for exploitation by falsifiers. Here, a proof-of-concept study explored the feasibility of using a handheld Spatially Offset Raman Spectroscopy (SORS) device to authenticate COVID-19 vaccines through rapid analysis of unopened vaccine vials. The results show that SORS can verify the chemical identity of dominant excipients non-invasively through vaccine vial walls. The ability of SORS to identify potentially falsified COVID-19 vaccines was demonstrated by measurement of surrogates for falsified vaccines contained in vaccine vials. In all cases studied, the SORS technique was able to differentiate between surrogate samples from the genuine COVISHIELD™ vaccine. The genuine vaccines tested included samples from six batches across two manufacturing sites to account for any potential variations between batches or manufacturing sites. Batch and manufacturing site variations were insignificant. In conjunction with existing security features, for example on labels and packaging, SORS provided an intrinsic molecular fingerprint of the dominant excipients of the vaccines. The technique could be extended to other COVID-19 and non-COVID-19 vaccines, as well as other liquid medicines. As handheld and portable SORS devices are commercially available and widely used for other purposes, such as airport security, they are rapidly deployable non-invasive screening tools for vaccine authentication., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pavel Matousek reports financial support was provided by Agilent Technologies. Pavel Matousek has patent #US20100053606 licensed to Agilent Technologies. Pavel Matousek also declares consultancy for Agilent Technologies, of which Robert Stokes is an employee., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years., Methods: A retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses., Results: Over the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management., Conclusions: Multidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base., Competing Interests: Declaration of Competing Interest MSZ declares honoraria for one lecture each for each of the three mentioned in the last 3 years: Norwegian Neurological Society; Copenhagen Neuropsychological Society, Rigshospitalet; and Cygnet Healthcare. None of the other authors report any conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Good communication is central to good healthcare. As a result of poor communication between parents and healthcare professionals (HCPs) in clinical settings, this study aimed to address this problem by developing a communication tool to empower parents and act as a prompt for HCPs to talk about the child's care and gather information at the point of admission to hospital about what is important to families, therefore supporting patient-centered communication. A design thinking process was used to develop a physical copy of Chloe's card and evaluate its use. Design thinking is a problem-solving approach, which uses an empathetic lens to integrate viewpoints of different stakeholders throughout the process of creating solutions. Design thinking involves five processes: (1) empathise-including a literature review and data synthesis, (2) define-by completing semi-structured interviews with parents about their experience of communication and HCPs perceptions of parent's experience of communication, (3) ideate-iterate the design of Chloe's card with parents and HCPs, (4) prototype-develop the design of Chloe's card, and (5) test-pilot test in clinical practice. Results from this initial study suggest that a small hand-held card, with emoticons and a place to write concerns, was acceptable to parents and feasible to use in clinical practice. Parents do not always feel heard by HCPs and a tool such as Chloe's card may help facilitate sharing of information about matters important to them and their child. However, some HCPs felt the need for a communication tool undermined their clinical skills. Feedback from HCP participants suggests that the idea of Chloe's card was acceptable and perceived as potentially being useful in clinical practice. Further work is required, as part of a larger study, to further refine this communication tool, identify those parents who would benefit most from Chloe's card, as well as to further refine the HCP process prior to implementing it into clinical settings. It was noted future iterations would benefit from a digital version linked with a child's electronic record, as well as multi-language versions and information for parents.

Introduction: To decrease psychological risk for content moderators, the study initiated the first steps of developing a robust employment screening tool, namely, the Cognitive Adaptability and Resiliency Employment Screener., Method: The study consisted of three phases with 4,839 total participants., Results: In Phase 1, a set of 76 items were developed and tested via exploratory factor analysis, yielding three factors (i.e., Psychological Perseverance & Agility, Rumination & Emotional Lingering, and Expressiveness & Sociability) and also reducing the scale to 68 items. In Phase 2 through confirmatory factor analysis, the three-factor structure showed good fit (CFI = 0.92, RMSEA = 0.05) and demonstrated sufficient overall reliability. In Phase 3, the convergent validity and divergent validity of the tool were established relative to constructs such as resilience, cognitive control and flexibility, emotion regulation, and optimism., Discussion: Altogether, the findings revealed that the scale demonstrated good psychometric properties that, pending future studies, may serve as a promising employment screener for content moderators., Competing Interests: WT, MaS, XH, PM, MiS, TB, and RG are/were employed by TaskUs Inc. KJ and ML are employed by TaskUs as consultants on an as-needed basis., (Copyright © 2023 Torralba, Savio, Huang, Manchanda, Steiger, Bharucha, López, Joyner and Guevara.)

Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome. Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up., Competing Interests: Competing interests: All authors have read and understood the BMJ policy on declaration of interests. No competing interests were declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: COVID-19 has caused significant worldwide morbidity and mortality. Congenital heart disease (CHD) is likely to increase vulnerability and understanding the predictors of adverse outcomes is key to optimising care., Objective: Ascertain the impact of COVID-19 on people with CHD and define risk factors for adverse outcomes., Methods: Multicentre UK study undertaken 1 March 2020-30 June 2021 during the COVID-19 pandemic. Data were collected on CHD diagnoses, clinical presentation and outcomes. Multivariable logistic regression with multiple imputation was performed to explore predictors of death and hospitalisation., Results: There were 405 reported cases (127 paediatric/278 adult). In children (age <16 years), there were 5 (3.9%) deaths. Adjusted ORs (AORs) for hospitalisation in children were significantly lower with each ascending year of age (OR 0.85, 95% CI 0.75 to 0.96 (p<0.01)). In adults, there were 24 (8.6%) deaths (19 with comorbidities) and 74 (26.6%) hospital admissions. AORs for death in adults were significantly increased with each year of age (OR 1.05, 95% CI 1.01 to 1.10 (p<0.01)) and with pulmonary arterial hypertension (PAH; OR 5.99, 95% CI 1.34 to 26.91 (p=0.02)). AORs for hospitalisation in adults were significantly higher with each additional year of age (OR 1.03, 95% CI 1.00 to 1.05 (p=0.04)), additional comorbidities (OR 3.23, 95% CI 1.31 to 7.97 (p=0.01)) and genetic disease (OR 2.87, 95% CI 1.04 to 7.94 (p=0.04))., Conclusions: Children were at low risk of death and hospitalisation secondary to COVID-19 even with severe CHD, but hospital admission rates were higher in younger children, independent of comorbidity. In adults, higher likelihood of death was associated with increasing age and PAH, and of hospitalisation with age, comorbidities and genetic disease. An individualised approach, based on age and comorbidities, should be taken to COVID-19 management in patients with CHD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Japanese encephalitis virus is a leading cause of neurological infection in the Asia-Pacific region with no means of detection in more remote areas. We aimed to test the hypothesis of a Japanese encephalitis (JE) protein signature in human cerebrospinal fluid (CSF) that could be harnessed in a rapid diagnostic test (RDT), contribute to understanding the host response and predict outcome during infection. Liquid chromatography and tandem mass spectrometry (LC-MS/MS), using extensive offline fractionation and tandem mass tag labeling (TMT), enabled comparison of the deep CSF proteome in JE vs other confirmed neurological infections (non-JE). Verification was performed using data-independent acquisition (DIA) LC-MS/MS. 5,070 proteins were identified, including 4,805 human proteins and 265 pathogen proteins. Feature selection and predictive modeling using TMT analysis of 147 patient samples enabled the development of a nine-protein JE diagnostic signature. This was tested using DIA analysis of an independent group of 16 patient samples, demonstrating 82% accuracy. Ultimately, validation in a larger group of patients and different locations could help refine the list to 2-3 proteins for an RDT. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034789 and 10.6019/PXD034789.

Tricuspid regurgitation (TR) is commonly seen in surgically palliated patients with hypoplastic left heart syndrome, and when significant, is associated with an increase in both morbidity and mortality. Tricuspid valve dysfunction appears to be the result of a combination of inherent structural malformations and the unique physiological circumstances resulting from right ventricular pressure and volume overload. Valve dysfunction evolves rapidly, and manifests early on in the surgical pathway. Whilst traditional echocardiographic imaging can identify anatomical defects and dysfunction resulting in varying degrees of regurgitation even at early stages, more sophisticated investigations such as 3D echocardiography, strain imaging and transesophageal 3DE might prove useful to better demonstrate the complex interactions between abnormal anatomy of the valve complex, ventricular function, mechanical synchrony, and TR. Recognition of specific mechanisms of TR can enhance patient-specific care by directing precise surgical interventions and by informing the best timing for intervention on the valve., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bharucha and Viola.)

Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation.