Tocilizumab and rituximab for systemic sclerosis interstitial lung disease: a real-world cohort analysis.

Objectives: Systemic sclerosis (SSc)-interstitial lung disease (ILD) is one of the leading causes of mortality in SSc. Data from randomised controlled trials (RCTs) supports rituximab and tocilizumab monotherapy but there is limited data regarding their use for those who fail standard immunomodulatory therapies.

Methods: SSc patients treated with rituximab or tocilizumab were retrospectively identified in a single centre cohort.

Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids.

Importance: Current evidence of the association between prenatal exposure to glucocorticoids and long-term mental disorders is scarce and has limitations.

Objective: To investigate the association between prenatal exposure to systemic glucocorticoids and mental disorders in offspring at the age of 15 years, comparing exposed vs unexposed offspring born to mothers with the same underlying disease (risk of preterm delivery and autoimmune or inflammatory disorders).

Design, Setting, And Participants: This nationwide population-based cohort study used data from registries in Denmark with follow-up until December 31, 2018.

Health state utilities associated with invasive pneumococcal disease, pneumonia, and recurrent acute otitis media in young children.

Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children.

Basic Science and Pathogenesis.

Background: Cardiovascular disease causes vascular dementia and contributes to most clinical dementia. This is embodied in the concept of vascular contributions to cognitive impairment and dementia (VCID). The potent endogenous peptide endothelin-1 (ET1) causes small artery vasoconstriction and fibrosis.

Basic Science and Pathogenesis.

Background: Knowledge of the chemical composition of amyloid plaques and tau tangles at the earlier stages of Alzheimer's disease (AD) pathology is sparse. This is due to limited access to human brain during life and at the earlier stages of AD pathophysiology and technical limitations in quantifying amyloid and tau species at a subcellular level. Understanding the chemical composition of plaques and tangles, how rapidly they grow and what factors drive growth is important for developing and refining therapeutics.

Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Clinical Manifestations.

Background: Subjective Cognitive Decline (SCD) may represent the initial symptom of Alzheimer's disease (AD), but SCD may be absent and/or unrelated to actual cognitive decline. Objective Subtle Cognitive Decline (obj-SCD) can be identified through longitudinal standardized neuropsychological tests in individuals not yet meeting criteria for Mild Cognitive Impairment (MCI). We argue that the relationship between SCD and obj-SCD might help to inform clinical and research criteria in pre-MCI stages.

Clinical Manifestations.

Background: Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language abilities, with clinical variants (nonfluent/agrammatic variant [nfvPPA], semantic variant [svPPA], logopenic variant [lvPPA], and mixed-PPA [mPPA]) categorized based on linguistic features. This study aims to compare PPA cohorts of native speakers of two different languages: English (an analytic language with deep orthography) and Italian (a synthetic language with shallow orthography).

Methods: We considered 166 English participants (70 nfvPPA, 45 svPPA, 42 lvPPA, 9 mPPA) and 106 Italian participants (14 nfvPPA, 20 svPPA, 42 lvPPA, 31 mPPA).

Clinical Manifestations.

Background: Remote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings.

Method: Here we evaluate the usability, validity and reliability of unsupervised remote memory assessments via mobile devices (see Figure 1) in individuals without dementia from the Swedish BioFINDER-2 study and explore their prognostic utility regarding future cognitive decline in combination with a plasma marker for p-tau217.

Result: Usability was rated positively.

Clinical Manifestations.

Background: Speech and language impairments are associated with cognitive decline in neurodegenerative dementias, particularly Alzheimer's Disease (AD), where subtle speech changes may precede clinical dementia onset. As clinical trials prioritize early identification for disease-modifying treatments, digital biomarkers for timely screening become imperative. Digital speech-based biomarkers can be employed for screening populations at the earliest AD stages.

Clinical Manifestations.

Background: Alzheimer's disease (AD) causes increasing cognitive and functional impairments, and both are therefore important outcome measures for intervention studies. Cognition and everyday functioning are often used interchangeably, yet the extent of their relationship is still unclear. We therefore aim to assess the relationship between different cognitive domains and everyday functioning across the AD spectrum.

Clinical Manifestations.

Background: Each year, millions of Americans experience mild traumatic brain injury (mTBI). Current research on the long-term effects of mTBI vary considerably. Several mechanisms linking mTBI to dementia have been proposed including amyloid plaque formation and cerebrovascular injury following mTBI.

Clinical Manifestations.

Background: Alzheimer's disease (AD) is classically viewed as a predominantly amnestic syndrome, with other cognitive and neuropsychiatric symptoms (NPS) being non-integral associations. Emerging Evidence suggests that within typical AD, these symptoms are core features from the onset.

Methods: We employed K-modes clustering on 2483 cognitively impaired (CI) individuals (CDR ≥ 0.

Clinical Manifestations.

Background: Psychological factors such as repetitive negative thinking, proneness to experience distress, and perceived stress are associated with increased risk of neurodegeneration and clinical dementia, whereas having a sense of life-purpose, self-reflection, and dispositional mindfulness may be protective. However, whether combinations of these risk and protective factors may inform distinct psychological profiles, which may be differential associated with age-related health outcomes is currently unknown.

Method: We included 742 middle-aged (mean age 51.

Evaluation of Phoenix Sepsis Score Criteria: Exploratory Analysis of Characteristics and Outcomes in an Emergency Transport PICU Cohort From the United Kingdom, 2014-2016.

Objectives: To assess characteristics and outcomes of children with suspected or confirmed infection requiring emergency transport and PICU admission and to explore the association between the 2024 Phoenix Sepsis Score (PSS) criteria and mortality.

Design: Retrospective analysis of curated data from a 2014-2016 multicenter cohort study.

Setting: PICU admission following emergency transport in South East England, United Kingdom, from April 2014 to December 2016.

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.

Determinants and progression of stigma in amyotrophic lateral sclerosis/motor neuron disease.

: Stigma in amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) may be felt or enacted; felt stigma covers feeling devalued by the illness, whereas enacted stigma refers to being treated differently because of it. Stigma in ALS/MND has been shown to increase social withdrawal, worsen quality of life, and reduce use of assistive devices, so we explored prevalence and factors influencing stigma. : Participants in the Trajectories of Outcome in Neurological Conditions-ALS study completed scales measuring stigma, fatigue, spasticity, functioning, mood, worry, self-esteem, and perceived health, as well as demographic information and symptoms like head drop or emotional lability.

The Role of WNT5a and TGF-β1 in Airway Remodelling and Severe Asthma.

Background: Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF-β in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling.

Methods: WNT5a and TGF-β protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1-3, n-8 and GINA 4-5, n-14) and healthy subjects (n-9), alongside relevant remodelling markers.

Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series).

Pulmonary vascular disease is not a single condition; rather it can accompany a variety of pathologies that impact the pulmonary vasculature. Applying precision medicine strategies to better phenotype, diagnose, monitor, and treat pulmonary vascular disease is increasingly possible with the growing accessibility of powerful clinical and research tools. Nevertheless, challenges exist in implementing these tools to optimal effect.

Outcomes of Knee Dislocations and Subluxations in Polytrauma Patients at a Major Trauma Center.

Background This is a retrospective service evaluation of outcomes of polytrauma patients sustaining knee dislocations and subluxations within a major trauma center (MTC). Polytrauma patients with knee dislocations are complex to manage and often sustain multiple life-threatening injuries. Although treatments have progressed, no consensus remains on management timing and strategy.

A mixed method exploration of job morale of physicians working in public healthcare settings in Kazakhstan during the COVID-19 pandemic.

Background: Physicians faced increased workloads during the COVID-19 pandemic, which exposed them to considerable physical and psychological stress. Gaining insight into shapers of job morale of physicians can help healthcare administrators assess the effectiveness of current work conditions and support systems, enabling them to develop policies that improve work environments and prepare healthcare systems for future resurgences of COVID-19 and other future unknown challenges. Therefore, the present study aimed to improve the understanding of physicians' experiences of job morale in Kazakhstan during the COVID-19 pandemic.

Influence of next-generation artificial intelligence on headache research, diagnosis and treatment: the junior editorial board members' vision - part 2.

Part 2 explores the transformative potential of artificial intelligence (AI) in addressing the complexities of headache disorders through innovative approaches, including digital twin models, wearable healthcare technologies and biosensors, and AI-driven drug discovery. Digital twins, as dynamic digital representations of patients, offer opportunities for personalized headache management by integrating diverse datasets such as neuroimaging, multiomics, and wearable sensor data to advance headache research, optimize treatment, and enable virtual trials. In addition, AI-driven wearable devices equipped with next-generation biosensors combined with multi-agent chatbots could enable real-time physiological and biochemical monitoring, diagnosing, facilitating early headache attack forecasting and prevention, disease tracking, and personalized interventions.

Estimating undiagnosed dementia in England using capture recapture techniques.

Background: To our knowledge capture-recapture techniques have not been used to estimate dementia prevalence using routinely collected data in England, nor have they been used to estimate changes in undiagnosed dementia over time. In this study we aimed to use routinely collected electronic health records to estimate the number of undiagnosed dementia cases there are in England and how this has changed over time. We also aimed to assess whether proportion of undiagnosed cases differed by age group, ethnicity, socioeconomic deprivation and sex.

Update on B-cell maturation antigen-directed therapies in AL amyloidosis.

Systemic light chain (AL) amyloidosis is a rare clonal plasma cell disorder characterized by the production of amyloidogenic immunoglobulin light chains, which causes the formation and deposition of amyloid fibrils, leading to multi-organ dysfunction. Current treatment is directed at the underlying plasma cell clone to achieve a profound reduction in the monoclonal free light chain production. The standard-of-care first-line therapy is a combination of daratumumab, cyclophosphamide, bortezomib and dexamethasone (D-VCd regimen), resulting in high rates of haematological and organ responses.

Guided Self-Help Treatment for Children and Young People With Eating Disorders: A Proof-Of-Concept Pilot Study.

Objective: To conduct a proof-of-concept pilot study of a CBT guided self-help intervention for children and young people with eating disorders.

Method: Children and young people were recruited from two outpatient eating disorder services in England. They received a CBT guided self-help intervention consisting of eight modules and weekly support sessions.