EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Hypertrophic cardiomyopathy management: a systematic review of the clinical practice guidelines and recommendations.

Aims: In light of recent advances in imaging techniques, molecular understanding and therapeutic options in hypertrophic cardiomyopathy (HCM), we performed a systematic review of current guidelines for the diagnosis and management of HCM in order to identify consensus and discrepant areas in the clinical practice guidelines.

Methods And Results: We systematically reviewed the English language guidelines and recommendations for the management of HCM in adults. MEDLINE and EMBASE databases were searched for guidelines published in the last 10 years.

Association between adult-onset hearing loss and dementia biomarkers: A systematic review.

Background And Objective: People with adult-onset hearing loss (AoHL) are at increased dementia risk. In this study, we explore potential aetiological mechanisms by synthesising the evidence on the association between AoHL and neuropathological, cerebrospinal fluid (CSF), blood and imaging biomarkers of dementia.

Methods: We systematically searched electronic databases from inception to 30 April 2024 for cross-sectional and longitudinal studies, including quantitative data on the association between AoHL and dementia biomarkers.

Amelioration of signaling deficits underlying metabolic shortfall in TREM2 human iPSC-derived microglia.

The microglial triggering receptor expressed on myeloid cells 2 (TREM2) is required for diverse microglia responses in neurodegeneration, including immunometabolic plasticity, phagocytosis, and survival. We previously identified that patient iPSC-derived microglia (iPS-Mg) harboring the Alzheimer's disease (AD) TREM2 hypomorph display several functional deficits linked to metabolism. To investigate whether these deficits are associated with disruptions in metabolite signaling, we generated common variant, TREM2 and TREM2 variant human iPS-Mg.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials.

Background: Relapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).

Preoperative activation of the renin-angiotensin system and myocardial injury in noncardiac surgery: exploratory mechanistic analysis of the SPACE randomised controlled trial.

Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.

Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles).

Investigating the complementary value of OCT to MRI in cognitive impairment in relapsing-remitting multiple sclerosis.

Background: Cognitive decline in multiple sclerosis (MS) is associated with neuro-axonal loss, quantifiable by optical coherence tomography (OCT). Associations between OCT measures and cognition in relapsing-remitting MS (RRMS) remain incompletely investigated, particularly the added value of OCT when combined with magnetic resonance imaging (MRI). We investigated the contributions of OCT and MRI while applying stringent criteria to control for subclinical optic neuropathy.

Postnatal Outcome After Ultrasound Findings of an Abnormal Fetal Gallbladder: A Systematic Review and Meta-Analysis.

Objective: To describe postnatal outcome following the prenatal diagnosis of an abnormal fetal gallbladder.

Methods: We conducted a systematic review of studies from January 1980 to January 2023 that described FGB abnormalities, which included agenesis or non-visualisation, abnormal content presence of sludge, abnormal shape or size and abnormal position, and postnatal outcome to determine the association with pathology.

Results: In 51 studies, 842 fetuses had abnormal FGB.

The role of healthcare professionals' communication in trial participation decisions: a qualitative investigation of recruitment consultations and patient interviews across three RCTs.

Background: Although the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients' participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions.

Auditory processing deficits in subacute stroke.

Background: Stroke is the second leading cause of disability worldwide. Stroke results in focal neurological deficit and often leads to auditory problems due to its impact on the auditory pathway. Altered connections in the auditory pathway, caused by stroke, can result in hearing difficulties ranging from impaired sound detection to altered auditory perception.

Weight and metabolic changes with long-acting cabotegravir and rilpivirine or bictegravir/emtricitabine/tenofovir alafenamide.

Background: Modest weight and lipid changes have been observed in cabotegravir plus rilpivirine long-acting (CAB+RPV LA) Phase 3/3b studies. The SOLAR study included standardized evaluations of weight and metabolic changes in people living with HIV switching to CAB+RPV LA dosed every 2 months (Q2M) vs. continuing bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF).

Association of the Cervical Canal Area With Disability and Progression in People With Multiple Sclerosis.

Background And Objectives: In multiple sclerosis (MS), brain reserve serves as a protective factor against cognitive impairment. Previous research has suggested a structural counterpart in the spine-spinal cord reserve-seemed to be associated with physical disability. This study aimed to investigate the potential of the cervical canal area (CCaA) as a proxy for spinal cord reserve in a multicentric cohort of people with MS (PwMS).

The ZFHX3 GGC Repeat Expansion Underlying Spinocerebellar Ataxia Type 4 has a Common Ancestral Founder.

Background: The identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25-year diagnostic conundrum. We used adaptive long-read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat expansion in affected individuals from Utah, Sweden, and Germany, highlighting the current pivotal time for detection of novel repeat expansion disorders.

Beyond the cochlea: exploring the multifaceted nature of hearing loss in primary mitochondrial diseases.

Primary mitochondrial diseases, with diverse systemic manifestations, often present with auditory impairments due to mitochondrial dysfunction. This study provides an in-depth exploration of auditory deficits in primary mitochondrial diseases, highlighting the impact of various pathogenic variants on both cochlea and neural/central auditory functions. An observational study involving 72 adults with primary mitochondrial diseases was conducted.

Preconception and antenatal care for women with a history of haematopoietic stem cell transplantation: Results of a UK clinician survey.

Background: Female childhood cancer survivors with history of bone marrow transplant with or without total body irradiation have increased pregnancy risks. Preconception counselling and early referral to appropriate clinical pathways may improve pregnancy outcomes.

Methods: UK-wide survey of clinicians, promoted via social media and conferences, jointly funded by Action Medical Research/Borne.

Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records.

Background: Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised.

Methods: In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital.