Systematic Literature Review of Real-world Outcomes of Benralizumab in Eosinophilic Granulomatosis with Polyangiitis.

Background: Several real-world cohorts and numerous case reports investigating benralizumab outcomes in eosinophilic granulomatosis with polyangiitis have been published. These studies complement the limited clinical trial data available by providing early insights on benralizumab use in a broader, real-world population.

Objective: The objective of this systematic literature review (SLR) was to provide an overview of the real-world outcomes of benralizumab in EGPA.

Observational analysis of biological remission as a treatment target for severe asthma: UK severe asthma registry.

Background: The aim of biologic therapies in severe asthma is inhibition of T2 inflammatory pathways.

Objective: We hypothesized that patients who achieve complete suppression of IL-5 & IL4/IL13 pathways with biologic therapy (FeNO <20ppb & blood eosinophil count (BEC) <0.15x10ˆ9, 'biological remission') would have better outcomes than patients with incomplete suppression of T2 biology.

VEXAS syndrome and immune-mediated rheumatic diseases: overlaps in clinical features and mechanisms.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome is a newly identified disorder caused by an acquired monogenic somatic UBA1 gene mutation, affecting nuclear and cytoplasmic ubiquitination. This mutation triggers immune dysregulation, leading to diverse clinical and pathological features resembling inflammatory rheumatic diseases. Blood abnormalities stem from myeloid precursor dysfunction, presenting as elevated concentrations of inflammatory markers and cytokines, leukopenia, and macrocytosis.

Development and validation of a prognostic model for predicting the risk of allopurinol-induced severe cutaneous adverse reactions: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data.

Background: Allopurinol, the most prescribed urate-lowering drug, is a known cause of severe cutaneous adverse reactions. We aimed to develop and validate a model to assess the risk of allopurinol-induced severe cutaneous adverse reactions in adults newly prescribed allopurinol.

Methods: In this retrospective new-user cohort study, we developed and validated a prognostic model using primary care, hospitalisation, and mortality data extracted from the UK Clinical Practice Research Datalink (CPRD) primary care database, for the period Jan 1, 2001, to March 29, 2021.

Consortium profile: the methylation, imaging and NeuroDevelopment (MIND) consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults.

GABA receptor availability in clinical high-risk and first-episode psychosis: a [C]Ro15-4513 positron emission tomography study.

Disrupted gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of schizophrenia. Reductions in hippocampal GABAergic neurons have been found in schizophrenia, and increased hippocampal perfusion has been described in schizophrenia and in people at clinical high-risk for psychosis (CHRp). We have also found decreases in hippocampal GABA receptors containing the α5 subunit (GABARα5) in a well-validated neurodevelopmental rat model of relevance for schizophrenia.

Sensitivity of the Patient-Health Questionnaire (PHQ-9) items to change in three clinical trials in low- and middle-income countries.

Background: The 9-item Patient Health Questionnaire (PHQ-9) is a valid and widely used self-reported tool for assessing depressive symptoms. Although previous studies have demonstrated its sensitivity to change at the summary score level, there is limited investigation of the sensitivity of individual PHQ-9 items to change over time. This study aims to evaluate the sensitivity of PHQ-9 items to change using data from three separate samples.

Visually assessed ischaemia on cardiac magnetic resonance, but not quantitative perfusion metrics, predicts symptomatic improvement in coronary artery bypass.

Background: Serial perfusion cardiovascular magnetic resonance (CMR) in symptomatic patients undergoing coronary artery bypass grafting (CABG) may provide mechanistic insight into dynamic abnormalities of the myocardium.

Objectives: To assess how changes in cardiac reperfusion and remodelling associate with symptom improvement in patients undergoing CABG METHODS: Patients awaiting elective CABG completed serial quality of life questionnaires and detailed CMR at baseline and at 6-12 months post CABG as per protocol. Automated fully quantitative stress and rest myocardial blood flow was calculated, alongside assessment of the visual ischaemic burden.

Differential interference with actin-binding protein function by acute cytochalasin B.

Dynamic actin filament remodeling is crucial for a plethora of fundamental cell biological processes, ranging from cell division and migration to cell communication, intracellular trafficking, or tissue development. Cytochalasin B (CB) and D (CD) are fungal secondary metabolites frequently used for interference with such processes. Although they are generally assumed to block actin filament polymerization at their rapidly growing barbed ends and compete with regulators at these sites, precise molecular understanding of their effects in dynamic actin structures requires further study.

How accurate are witnesses of first suspected seizures in recalling semiology at clinically relevant timepoints? A UK experimental study with a pilot intervention.

Objective: A key diagnostic challenge at "first seizure" clinic appointments is determining whether the reported event was epileptic. Witness accounts are often critical, yet such appointments typically occur weeks after the event. Guidelines recommend review within 2 weeks.

Too vulnerable? Successful practices for conducting research with children and young people who have life-limiting or life-threatening illness.

Background: A dearth of evidence exists on how to include children and young people in palliative care research.

Aim: We aimed to identify successful practices in involvement, recruitment and data collection with children and young people with life-limiting illness in research.

Design: We synthesised methods from five primary studies from three geographical regions in which children with life-limiting conditions were recruited and interviewed.

Erector spinae plane block facilitating rapid weaning in an anticoagulated V-V ECMO patient with chest trauma.

IntroductionWe report the successful use of erector spinae (ESP) plane block in the management of a patient with severe respiratory failure secondary to chest trauma requiring invasive ventilation and Veno-venous extracorporeal membrane oxygenation (V-V ECMO).Case reportA 64-year-old man with flail chest and severe respiratory failure required V-V ECMO. An ESP plane block on day 3 enabled extubation, mobilisation, and secretion clearance, leading to ECMO weaning after six days and discharge 18 days post-injury.

Association Between Pulse Pressure and Structural Brain Changes in Aging: A Systematic Review and Meta-Analysis of Cross-Sectional and Longitudinal Studies.

Background: The aim of this study was to investigate the associations between pulse pressure (PP) and age-related structural brain changes including brain volumes, white matter hyperintensities (WMH), fractional anisotropy, silent brain lesions, microbleeds, cerebral blood flow and metabolism, and beta-amyloid accumulation.

Methods: Systematic review of PubMed (MEDLINE), Scopus, and Ovid Embase (from inception to January 2023) and references of included studies among adult populations was conducted. Findings were summarized narratively and by performing a fixed-effects meta-analysis.

Mapping advance care planning and advance directives in Latin America.

Background/aims: The extent to which low- and middle-income countries have implemented Advance Care Planning (ACP) and Advance Directives (AD) remains unclear. We aimed to map the current status of ACP/AD in Latin America.

Methods: This cross-sectional, mixed-methods survey of ACP/AD in LA comprised interviews with 18 key informants from 18 out of 20 countries, most of whom were appointed by national Palliative Care Associations.

Food insecurity and postnatal depression: the mediating effect of perceived social support among women in Khayelitsha, South Africa.

Purpose: Understanding the mechanisms through which poverty influences perinatal depression can provide insight into how to develop interventions to improve maternal mental health. To address this question, we aim to estimate indirect effects of important mediators on the causal relationship between food insecurity and symptoms of postnatal depression.

Methods: We used data from the control arm of the Africa Focus on Intervention Research for Mental health - South Africa (AFFIRM-SA) trial that included pregnant women with perinatal depression.

The role of low subcortical iron, white matter myelin, and oligodendrocytes in schizophrenia: a quantitative susceptibility mapping and diffusion tensor imaging study.

Iron-the most abundant magnetic brain substance-is essential for many biological processes, including dopamine and myelin synthesis. Quantitative susceptibility mapping (QSM) MRI has recently linked altered subcortical magnetic susceptibility (χ) to schizophrenia. Since χ is increased by iron and decreased by myelin, abnormal levels of either could underlie these QSM differences.

Impulsivity and neuroticism share distinct functional connectivity signatures with alcohol-use risk in youth.

Increases in impulsivity and negative affect (e.g., neuroticism) are common during adolescence and are both associated with risk for alcohol-use initiation and other risk behaviors.

Defining self-monitoring in postpandemic maternity care: Perspectives from women, partners, healthcare professionals, and policymakers.

Introduction: We aimed to explore the conceptualization and perception of self-monitoring amongst women, partners, healthcare professionals (HCPs), and policymakers, with particular interest in those living with social/medical complexity.

Material And Methods: Across the United Kingdom, 96 semi-structured in-depth qualitative interviews were conducted with 40 women, 15 partners, 21 HCPs, and 20 policymakers to discuss their lived experience of utilizing, delivering, or developing policy for self-monitoring during the COVID-19 pandemic. A thematic framework analysis was undertaken to develop themes, considered by participant type, ethnicity, geographical region, personal experience of self-monitoring, and social complexity, and a content analysis was used to explore how self-monitoring was conceptualized.

The Power of Precision: Unravelling the Radiobiology of Targeted Radionuclide Therapy.

Targeted radionuclide therapy (TRT) involves systemic administration of a radionuclide attached to a cancer-targeting moiety. It has been proven to be a promising approach for primary cancer and metastasis treatment with minimal damage to surrounding tissues. TRT integrates the precision of molecular targeting with the therapeutic efficacy of radiation.

Cellular fibronectin exacerbates α-synuclein aggregation via integrin alpha4beta1 mediated PARP1 and SCD elevation.

Mitochondrial dysfunction and lipid metabolic disturbance may promote pathologic α-synuclein (α-syn) aggregation, accelerating the progression of Parkinson's disease (PD). Whether extracellular matrices are associated with those pathological mechanisms in PD remains elusive. Here, we aimed to identify if cellular fibronectin (cFn), a component of extracellular matrices, contributes to α-syn abnormality via inducing mitochondrial energy depletion or disrupting lipid homeostasis.

Real-world effectiveness of autologous haematopoietic stem cell transplantation for multiple sclerosis in the UK.

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used as a one-off disease-modifying therapy for aggressive forms of multiple sclerosis (MS). We report real-world effectiveness of AHSCT for MS in the UK.

Methods: This retrospective open-label study included patients with (pw)MS treated with AHSCT between 2002 and 2023 in 14 UK centres.