We present the case for subspecialisation in paediatric gastrointestinal and hepato-pancreatico-biliary radiology. We frame the discussion around a number of questions: What is different about the ...paediatric patient and paediatric gastrointestinal system? What does the radiologist need to do differently? And finally, what can be translated from these subspecialty areas into everyday practice? We cover conditions that the sub-specialist might encounter, focusing on entities such as inflammatory bowel disease and hepatic vascular anomalies. We also highlight novel imaging techniques that are a focus of research in the subspecialties, including contrast-enhanced ultrasound, MRI motility, magnetisation transfer factor, and magnetic resonance elastography.
Respiratory viral infections in the elderly Watson, Alastair; Wilkinson, Tom M. A.
Therapeutic Advances in Respiratory Disease,
2021, Letnik:
15
Book Review, Journal Article
Recenzirano
Odprti dostop
With the global over 60-year-old population predicted to more than double over the next 35 years, caring for this aging population has become a major global healthcare challenge. In 2016 there were ...over 1 million deaths in >70 year olds due to lower respiratory tract infections; 13–31% of these have been reported to be caused by viruses. Since then, there has been a global COVID-19 pandemic, which has caused over 2.3 million deaths so far; increased age has been shown to be the biggest risk factor for morbidity and mortality. Thus, the burden of respiratory viral infections in the elderly is becoming an increasing unmet clinical need. Particular challenges are faced due to the interplay of a variety of factors including complex multimorbidities, decreased physiological reserve and an aging immune system. Moreover, their atypical presentation of symptoms may lead to delayed necessary care, prescription of additional drugs and prolonged hospital stay. This leads to morbidity and mortality and further nosocomial spread. Clinicians currently have limited access to sensitive detection methods. Furthermore, a lack of effective antiviral treatments means there is little incentive to diagnose and record specific non-COVID-19 viral infections. To meet this unmet clinical need, it is first essential to fully understand the burden of respiratory viruses in the elderly. Doing this through prospective screening research studies for all respiratory viruses will help guide preventative policies and clinical trials for emerging therapeutics. The implementation of multiplex point-of-care diagnostics as a mainstay in all healthcare settings will be essential to understand the burden of respiratory viruses, diagnose patients and monitor outbreaks. The further development of novel targeted vaccinations as well as anti-viral therapeutics and new ways to augment the aging immune system is now also essential.
The reviews of this paper are available via the supplemental material section.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carries a substantial risk of severe and prolonged illness; treatment options are currently limited. We assessed the efficacy ...and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19.
We did a randomised, double-blind, placebo-controlled, phase 2 pilot trial at nine UK sites. Adults aged 18 years or older and admitted to hospital with COVID-19 symptoms, with a positive RT-PCR or point-of-care test, or both, were randomly assigned (1:1) to receive SNG001 (6 MIU) or placebo by inhalation via a mouthpiece daily for 14 days. The primary outcome was the change in clinical condition on the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention-to-treat population (all randomised patients who received at least one dose of the study drug). The OSCI is a 9-point scale, where 0 corresponds to no infection and 8 corresponds to death. Multiple analyses were done to identify the most suitable statistical method for future clinical trials. Safety was assessed by monitoring adverse events for 28 days. This trial is registered with Clinicaltrialsregister.eu (2020-001023-14) and ClinicalTrials.gov (NCT04385095); the pilot trial of inpatients with COVID-19 is now completed.
Between March 30 and May 30, 2020, 101 patients were randomly assigned to SNG001 (n=50) or placebo (n=51). 48 received SNG001 and 50 received placebo and were included in the intention-to-treat population. 66 (67%) patients required oxygen supplementation at baseline: 29 in the placebo group and 37 in the SNG001 group. Patients receiving SNG001 had greater odds of improvement on the OSCI scale (odds ratio 2·32 95% CI 1·07-5·04; p=0·033) on day 15 or 16 and were more likely than those receiving placebo to recover to an OSCI score of 1 (no limitation of activities) during treatment (hazard ratio 2·19 95% CI 1·03-4·69; p=0·043). SNG001 was well tolerated. The most frequently reported treatment-emergent adverse event was headache (seven 15% patients in the SNG001 group and five 10% in the placebo group). There were three deaths in the placebo group and none in the SNG001 group.
Patients who received SNG001 had greater odds of improvement and recovered more rapidly from SARS-CoV-2 infection than patients who received placebo, providing a strong rationale for further trials.
Synairgen Research.
Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality despite current treatment strategies which focus on smoking cessation, pulmonary rehabilitation, and ...symptomatic relief. A focus of COPD care is to encourage self-management, particularly during COVID-19, where much face-to-face care has been reduced or ceased. Digital health solutions may offer affordable and scalable solutions to support COPD patient education and self-management, such solutions could improve clinical outcomes and expand service reach for limited additional cost. However, optimal ways to deliver digital medicine are still in development, and there are a number of important considerations for clinicians, commissioners, and patients to ensure successful implementation of digitally augmented care. In this narrative review, we discuss advantages, pitfalls, and future prospects of digital healthcare, which offer a variety of tools including self-management plans, education videos, inhaler training videos, feedback to patients and healthcare professionals (HCPs), exacerbation monitoring, and pulmonary rehabilitation. We discuss the key issues with sustaining patient and HCP engagement and limiting attrition of use, interoperability with devices, integration into healthcare systems, and ensuring inclusivity and accessibility. We explore the essential areas of research beyond determining safety and efficacy to understand the acceptability of digital healthcare solutions to patients, clinicians, and healthcare systems, and hence ways to improve this and sustain engagement. Finally, we explore the regulatory challenges to ensure quality and engagement and effective integration into current healthcare systems and care pathways, while maintaining patients’ autonomy and privacy. Understanding and addressing these issues and successful incorporation of an acceptable, simple, scalable, affordable, and future-proof digital solution into healthcare systems could help remodel global chronic disease management and fractured healthcare systems to provide best patient care and optimisation of healthcare resources to meet the global burden and unmet clinical need of COPD.
Background
The SIOP‐Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis‐based treatment initiation, ...but only for a relatively small percentage of approximately 10% of non‐Wilms tumors (non‐WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics.
Purpose
To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors.
Study Type
Consensus process using a Delphi method.
Population
Not applicable.
Field Strength/Sequence
Abdominal MRI including T1‐ and T2‐weighted imaging, contrast‐enhanced MRI, and diffusion‐weighted imaging at 1.5 or 3 T.
Assessment
Twenty‐three radiologists from the SIOP‐RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5‐point Likert scales, ranking‐ and multiple choice questions.
Statistical Tests
The cut‐off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale.
Results
Consensus on specific characteristics mainly concerned the discrimination between WTs and non‐WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors.
Data Conclusion
Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts.
Level of Evidence: 3
Technical Efficacy Stage: 3
Plasma membrane-located transport proteins are key adaptations for obligate intracellular Microsporidia parasites, because they can use them to steal host metabolites the parasites need to grow and ...replicate. However, despite their importance, the functions and substrate specificities of most Microsporidia transporters are unknown. Here, we provide functional data for a family of transporters conserved in all microsporidian genomes and also in the genomes of related endoparasites. The universal retention among otherwise highly reduced genomes indicates an important role for these transporters for intracellular parasites. Using
, a Microsporidia isolated from an HIV/AIDS patient, as our experimental model, we show that the proteins are ATP and GTP transporters located on the surface of parasites during their intracellular growth and replication. Our work identifies a new route for the acquisition of essential energy and nucleotides for a major group of intracellular parasites that infect most animal species including humans.
Exacerbations of COPD are one of the commonest causes of admission and readmission to hospital. The role of digital interventions to support self-management in improving outcomes is uncertain. We ...conducted an open, randomised controlled trial of a digital health platform application (app) in 41 COPD patients recruited following hospital admission with an acute exacerbation. Subjects were randomised to either receive usual care, including a written self-management plan (
= 21), or the myCOPD app (
= 20) for 90 days. The primary efficacy outcome was recovery rate of symptoms measured by COPD assessment test (CAT) score. Exacerbations, readmission, inhaler technique quality of life and patient activation (PAM) scores were also captured by a blinded team. The app was acceptable in this care setting and was used by 17 of the 20 patients with sustained use over the study period. The treatment effect on the CAT score was 4.49 (95% CI: -8.41, -0.58) points lower in the myCOPD arm. Patients' inhaler technique improved in the digital intervention arm (101 improving to 20 critical errors) compared to usual care (100 to 72 critical errors). Exacerbations tended to be less frequent in the digital arm compared to usual care; 34 vs 18 events. Hospital readmissions risk was numerically lower in the digital intervention arm: OR for readmission 0.383 (95% CI: 0.074, 1.987;
= 35). In this feasibility study of the digital self-management platform myCOPD, the app has proven acceptable to patients to use and use has improved exacerbation recovery rates, with strong signals of lower re-exacerbation and readmission rates over 90 days. myCOPD reduced the number of critical errors in inhaler technique compared to usual care with written self-management. This provides a strong basis for further exploration of the use of app interventions in the context of recently hospitalised patients with COPD and informs the potential design of a large multi-centre trial.
Non-typeable
Haemophilus influenzae
(NTHi) is an ubiquitous commensal-turned-pathogen that colonises the respiratory mucosa in airways diseases including Chronic Obstructive Pulmonary Disease (COPD). ...COPD is a progressive inflammatory syndrome of the lungs, encompassing chronic bronchitis that is characterised by mucus hypersecretion and impaired mucociliary clearance and creates a static, protective, humid, and nutrient-rich environment, with dysregulated mucosal immunity; a favourable environment for NTHi colonisation. Several recent large COPD cohort studies have reported NTHi as a significant and recurrent aetiological pathogen in acute exacerbations of COPD. NTHi proliferation has been associated with increased hospitalisation, disease severity, morbidity and significant lung microbiome shifts. However, some cohorts with patients at different severities of COPD do not report that NTHi is a significant aetiological pathogen in their COPD patients, indicating other obligate pathogens including
Moraxella catarrhalis, Streptococcus pneumoniae
and
Pseudomonas aeruginosa
as the cause. NTHi is an ubiquitous organism across healthy non-smokers, healthy smokers and COPD patients from childhood to adulthood, but it currently remains unclear why NTHi becomes pathogenic in only some cohorts of COPD patients, and what behaviours, interactions and adaptations are driving this susceptibility. There is emerging evidence that biofilm-phase NTHi may play a significant role in COPD. NTHi displays many hallmarks of the biofilm lifestyle and expresses key biofilm formation-promoting genes. These include the autoinducer-mediated quorum sensing system, epithelial- and mucus-binding adhesins and expression of a protective, self-produced polymeric substance matrix. These NTHi biofilms exhibit extreme tolerance to antimicrobial treatments and the immune system as well as expressing synergistic interspecific interactions with other lung pathogens including
S. pneumoniae
and
M. catarrhalis
. Whilst the majority of our understanding surrounding NTHi as a biofilm arises from otitis media or
in-vitro
bacterial monoculture models, the role of NTHi biofilms in the COPD lung is now being studied. This review explores the evidence for the existence of NTHi biofilms and their impact in the COPD lung. Understanding the nature of chronic and recurrent NTHi infections in acute exacerbations of COPD could have important implications for clinical treatment and identification of novel bactericidal targets.
Under normal physiological conditions, the lung remains an oxygen rich environment. However, prominent regions of hypoxia are a common feature of infected and inflamed tissues and many chronic ...inflammatory respiratory diseases are associated with mucosal and systemic hypoxia. The airway epithelium represents a key interface with the external environment and is the first line of defense against potentially harmful agents including respiratory pathogens. The protective arsenal of the airway epithelium is provided in the form of physical barriers, and the production of an array of antimicrobial host defense molecules, proinflammatory cytokines and chemokines, in response to activation by receptors. Dysregulation of the airway epithelial innate immune response is associated with a compromised immunity and chronic inflammation of the lung. An increasing body of evidence indicates a distinct role for hypoxia in the dysfunction of the airway epithelium and in the responses of both innate immunity and of respiratory pathogens. Here we review the current evidence around the role of tissue hypoxia in modulating the host-pathogen interaction at the airway epithelium. Furthermore, we highlight the work needed to delineate the role of tissue hypoxia in the pathophysiology of chronic inflammatory lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease in addition to novel respiratory diseases such as COVID-19. Elucidating the molecular mechanisms underlying the epithelial-pathogen interactions in the setting of hypoxia will enable better understanding of persistent infections and complex disease processes in chronic inflammatory lung diseases and may aid the identification of novel therapeutic targets and strategies.
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