Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.

Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.

Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.

Tuberculosis and people who use drugs: why focus on this overlooked population is important and why adapted interventions are necessary.

People who use drugs show a higher incidence and prevalence of tuberculosis than people who do not use drugs in areas where Mycobacterium tuberculosis is endemic. However, this population is largely neglected in national tuberculosis programmes. Strategies for active case finding, screening, and linkage to care designed for the general population are not adapted to the needs of people who use drugs, who are stigmatised and difficult to reach.

The kinetics of aqueous thiolated arsenic oxidation.

Thiolated arsenic (As) compounds have been identified in various natural and engineered environments worldwide and are important for the biogeochemical cycling of As, yet quantitative data regarding their stability and transformation rates remains scarce. This study investigates the oxidation kinetics of mono-, di-, and tri-thioarsenate at varying pH, Fe, and (thio-)As concentrations in the aqueous phase. Experiments conducted over four weeks revealed that all thioarsenates were oxidized faster at lower pH, with rates of up to several μmoles/L/d at a pH of 3.

Isolated subsegmental pulmonary embolism identification based on international classification of diseases (ICD)-10 codes and imaging reports.

Background: Isolated subsegmental pulmonary embolism (issPE) is a commonly encountered diagnosis. Although the International Classification of Diseases (ICD)-10 codes are used for research, their validity for identifying issPE is unknown. Moreover, issPE diagnosis is challenging, and the findings from radiology reports may conflict with those from expert radiologists.

Lung function-associated exposome profile in the era of climate change: Pooled analysis of 8 population-based European cohorts within the EXPANSE project.

Background: The independent and interrelated long-term effects of the exposome such as air pollution, greenness, and ambient temperature on lung function are not well understood, yet relevant in the light of climate change.

Methods: Pre-bronchodilation FEV1 from five mature birth cohorts (N = 4724) and three adult cohorts (N = 6052) from five European countries were used to assess cross-sectional associations with air pollution, greenness, and ambient temperature, assigned to their residential address. All two-way interactions and square terms were a priori included in building the final elastic net regression model.

Post-Kasai cholangitis evaluation and management strategies: Review of the literature with insights from the Swiss Biliary Atresia Registry.

Cholangitis, defined as the inflammation of the bile ducts, is the most frequent complication after Kasai hepatoportoenterostomy in patients with biliary atresia (BA). This review seeks to provide a comprehensive synthesis of current knowledge on diagnosing and managing BA-associated cholangitis while identifying gaps in the existing literature. A scoping literature review was conducted to gather global insights into the definition, evaluation, and management of post-Kasai cholangitis, illustrated through data from the Swiss Biliary Atresia Registry (SBAR).

Psychedelics and connectedness to natural and social worlds: An examination of the evidence and a proposed conceptual framework.

Recent research suggests that serotonergic psychedelics may simultaneously enhance connectedness to both social and natural worlds. This article synthesizes current evidence regarding psychedelics' effects on nature relatedness and social connectedness, examining underlying mechanisms through the framework of self-other overlap. Psychedelics appear to facilitate self-expansion through two complementary mechanisms: ego dissolution, which temporarily alters self-boundaries, and enhanced emotional processing, which increases empathic concern.

Enhancing information for action: A strategic tool for strengthening public health emergency management systems.

Background: This paper addresses the importance of timely and robust information systems that underpin emergency response decision-making, as evidenced during the COVID-19 pandemic in the WHO European Region. Recognizing the relevance of these systems, we propose the strengthening of national emergency response information management systems (ERIMS) within the broader digital health information system (HIS) framework. We aim to develop and present an innovative assessment tool designed to evaluate and assist in the strengthening of ERIMS, contributing to a more resilient and effective emergency response.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

From Vision to Reality: The EU's Pharmaceutical Reforms and the Path to Improved Access.

Disparities in access to oncology medicines in European Union (EU) member states can impact patient outcomes profoundly, with availability and timely access varying significantly across and within member states. This paper discusses the intersection of the new European Health Technology Assessment Regulation (HTAR), the provisions of the proposed pharmaceutical legislation and their potential impacts on access to oncology medicines across EU member states. The HTAR, seeking to standardise the clinical evaluation of new medicines, has the potential to streamline the evaluation process but also risks oversimplifying diverse national healthcare needs.

Unmet clinical needs in women with polycystic ovary syndrome regarding fertility and obesity: a cross-sectional study from the patient's perspective.

Purpose: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, often leading to anovulatory infertility. Obesity exacerbates the reproductive, metabolic and psychological features of PCOS, making fertility treatment and patient satisfaction difficult. Despite guidelines from the European Society of Human Reproduction and Embryology (ESHRE) emphasizing lifestyle modifications and specific treatments, there remains a significant gap in adherence to these guidelines by both healthcare providers and patients.

Which patients with negative PSMA-PET imaging can safely avoid biopsy for prostate cancer? a novel step towards PSMA-based biopsy-free strategy.

Purpose: This study aimed to identify if a subset of men can safely avoid or delay prostate biopsy based on negative results of prostate-specific membrane antigen positron emission tomography (PSMA-PET).

Materials And Methods: Among 341 consecutive cases in a prospective biopsy cohort (NCT05073653), 111 treatment-naïve men with negative PSMA-PET (PRIMARY-score 1/2) were included. All participants underwent PSMA-PET and histopathological examinations.

A generalized structured coalescent for purifying selection without recombination.

Purifying selection is a critical factor in shaping genetic diversity. Current theoretical models mostly address scenarios of either very weak or strong selection, leaving a significant gap in our knowledge. The effects of purifying selection on patterns of genomic diversity remain poorly understood when selection against deleterious mutations is weak to moderate, particularly when recombination is limited or absent.

Cranioplasty infection in porous hydroxyapatite: Potential antibacterial properties.

Introduction: Intensive research is dedicated to the development of novel biomaterials and medical devices to be used as grafts in reconstructive surgery, with the purpose of enhancing their therapeutic effectiveness, safety, and durability. A variety of biomaterials, from autologous bone to polymethylmetacrylate, polyether ether ketone, titanium, and calcium-based ceramics are used in cranioplasty. Porous hydroxyapatite (PHA) is reported as a possible material for bone reconstruction, with good signs of biocompatibility, osteoconductive and osteointegrative properties.

2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Self-reported health status of patients with acute retinal ischemia and stroke related hemianopia.

Background: We aimed to assess impairments on health-related quality of life, and mental health resulting from Retinal artery occlusion (RAO) with monocular visual field loss and posterior circulation ischemic stroke (PCIS) with full or partial hemianopia using patient-reported outcome measures (PROMs).

Methods: In a prospective study, consecutive patients with acute RAO on fundoscopy and PCIS on imaging were recruited during their surveillance on a stroke unit over a period of 15 months. Baseline characteristics were determined from medical records and interviews.

Fenestrated Anaconda Endograft for the Treatment of Complex Aortic Aneurysms: Systematic Review and Meta-Analysis.

Purpose: To perform a systematic review and meta-analysis of the outcomes of Anaconda fenestrated endograft for the treatment of complex abdominal aortic aneurysms (cAAA).

Material And Methods: A systematic search of all the literature reported until May 2024 was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The pooled 30-day mortality rate, technical success rate, reintervention rate as well as bridging stent occlusion rate, and corresponding 95% confidence intervals (CIs) were estimated using fixed or random effect methods.

A Comprehensive Weightbearing Computed Tomography Study on Patients With Hallux Valgus: Exploring Multiplanar Deformity Interrelationships.

Background: Hallux valgus (HV) is a complex, multiplanar deformity. In this study, we examined the interrelationships between various components of this deformity using weightbearing computed tomography (WBCT). We hypothesized that the severity of traditional axial plane deformities would correlate with malpositioning of the metatarsosesamoid complex, first-ray coronal rotational deformity, and malalignment of the hindfoot and midfoot.

Patterns of Treatment and Real-World Outcomes of Patients With Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations Receiving Mobocertinib: The EXTRACT Study.

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.

Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).

Validity of non-traditional measures of obesity compared to total body fat across the life course: A systematic review and meta-analysis.

IntroductionTraditional obesity measures including body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio have limitations. The primary objective of this study was to identify and review the validity of non-traditional obesity measures, using measures of total body fat as the reference standard, that have been used across multiple life stages. MethodsWe conducted a systematic review and searched MEDLINE, Embase, and PsycINFO.

Feline Papillomatosis.

Different types of feline papillomaviruses (PVs) are associated with a variety of skin lesions and neoplasia, such as papillomas and cell carcinomas, but the virus can also be found in healthy skin. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of veterinary experts on feline infectious diseases from 11 European Countries, discusses the current knowledge of feline PV infections. Cats most likely become infected through lesions or abrasions of the skin.

Viral Hepatitis B and Its Implications for Public Health in DR Congo: A Systematic Review.

The prevalence of hepatitis B virus infection remains high in the Democratic Republic of Congo (DRC), constituting a public health problem in view of the fatal complications it causes, notably cirrhosis and hepatocellular carcinoma. The aim of this study was to provide an overview of the situation of viral hepatitis B in the DRC and in particular its implications for public health. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) group guidelines.