Posaconazole for Prevention of COVID-19-Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients: A European Multicentre Case-Control Study (POSACOVID).

Background: This study investigated the impact of posaconazole (POSA) prophylaxis in COVID-19 patients with acute respiratory failure receiving systemic corticosteroids on the risk for the development of COVID-19-associated pulmonary aspergillosis (CAPA).

Methods: The primary aim of this prospective, multicentre, case-control study was to assess whether application of POSA prophylaxis in mechanically ventilated COVID-19 patients reduces the risk for CAPA development. All consecutive patients from centre 1 (cases) who received POSA prophylaxis as standard-of-care were matched to one subject from centre 2 and centre 3 who did not receive any antifungal prophylaxis, using propensity score matching for the following variables: (i) age, (ii) sex, (iii) treatment with tocilizumab and (iv) time at risk.

Comparison of the efficacy and safety of Landiolol and Esmolol in critically ill patients: a propensity score-matched study.

Background: Excessive tachycardia is associated with impaired hemodynamics and worse outcome in critically ill patients. Previous studies suggested beneficial effect of β-blockers administration in ICU patients, including those with septic shock. However, comparisons in ICU settings are lacking.

The effect of degenerative scolioisis on segmental thoracolumbar sagittal alignment compared to age- and pelvic incidence-matched reference values.

Introduction: In asymptomatic subjects, variations of sagittal alignment parameters according to age and pelvic incidence (PI) has been reported. The aim of this observational study was to describe thoraco-lumbar sagittal alignment in patients with degenerative scoliosis and to compare them to asymptomatic individuals, seeking for the specific effect of deformity in similar age and PI groups.

Materials And Methods: Full spine radiographs of 235 asymptomatic subjects and 243 scoliosis patients were analyzed: cervico-thoracic inflexion point (CTIP), thoraco-lumbar inflexion point (TLIP), lumbar lordosis (LL) L1-S1, LL (TLIP-S1), LL superior arch (TLIP-lumbar apex), LL inferior arch (lumbar apex-S1), PI, thoracic kyphosis (TK) T5-T12, TK T1-T12, number of vertebrae CTIP-TLIPandTLIP-S1.

Integration of clinical, pathological, radiological, and transcriptomic data improves prediction for first-line immunotherapy outcome in metastatic non-small cell lung cancer.

Immunotherapy is improving the survival of patients with metastatic non-small cell lung cancer (NSCLC), yet reliable biomarkers are needed to identify responders prospectively and optimize patient care. In this study, we explore the benefits of multimodal approaches to predict immunotherapy outcome using multiple machine learning algorithms and integration strategies. We analyze baseline multimodal data from a cohort of 317 metastatic NSCLC patients treated with first-line immunotherapy, including positron emission tomography images, digitized pathological slides, bulk transcriptomic profiles, and clinical information.

Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature.

Autosomal dominant CDK13-related disease is characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Heterozygous pathogenic variants, particularly missense variants in the kinase domain, have previously been described as disease causing. Using the determination of a methylation pattern and comparison with an established episignature, we reveal the first hypomorphic variant in the kinase domain of CDK13, leading to a never before described autosomal recessive form of CHDFIDD in a boy with characteristic features.

H3K9 post-translational modifications regulate epiblast/primitive endoderm specification in rabbit blastocysts.

Post-translational modifications of histone H3 on lysine 9, specifically acetylation (H3K9ac) and tri-methylation (H3K9me3), play a critical role in regulating chromatin accessibility. However, the role of these modifications in lineage segregation in the mammalian blastocyst remains poorly understood. We demonstrate that di- and tri-methylation marks, H3K9me2 and H3K9me3, decrease during cavitation and expansion of the rabbit blastocyst.

Patient views on continued immune checkpoint inhibition following progression in advanced melanoma: A qualitative study.

Introduction: Immune checkpoint inhibition has revolutionized the management of metastatic melanoma, including in the final stages of disease progression: because it is well tolerated, some teams do not discontinue it in hopes of slowing disease progression. The risks are that treatment may be continued unnecessarily, causing side effects, and reduce access to specialist palliative care, in addition to increasing the cost of treatment.

Method: We explored the experiences of 10 patients in a university hospital with metastatic melanoma under continued immune checkpoint inhibitors combined with specialist palliative care.

Prevalence of orofacial and head pain: an umbrella review of systematic reviews.

Head pain (HP) and orofacial pain (OFP) are the most prevalent types of pain worldwide, encompassing cranial, oral and facial pain. The aim of this umbrella review was to answer the following questions: "What is the overall prevalence of HP/OFP and the different prevalences of HP/OFP conditions in adults and children?". We searched for studies investigating the prevalence of HP/OFP in four major databases and two databases from the grey literature, based on the following PECOS inclusion criteria: (P)opulation: Adults and children; (E)xposure: Orofacial or head pain conditions such as (1) dental, periodontal and gingival, (2) temporomandibular disorders (TMD), (3) neuropathic conditions, (4) headaches, and (5) idiopathic pain conditions; (C)omparison: None; (O)utcome: Prevalence; (S)tudies: Systematic reviews and/or meta-analyses.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Usefulness of Cerebrospinal Fluid Alzheimer's disease biomarkers in older patients: Evidence from a national multicenter prospective study.

Background: The use of cerebrospinal (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) has been gaining interest in clinical practice. Although their usefulness has been demonstrated, their potential value in older patients remains debated.

Objectives: To assess whether knowledge of the results of CSF AD biomarkers was associated with the same gain in diagnostic confidence in older adults > 80 than in younger patients.

Informal care for people with dementia in Europe.

Introduction: Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.

Methods: A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Can aortic valve calcium score predict a need for permanent pacemaker implantation after transcatheter aortic valve implantation?

Introduction: Conductive disturbances requiring permanent pacemaker (PPM) implantation remain a major concern after transcatheter aortic valve implantation (TAVI).

Aims: To assess the impact of aortic valve calcium score (AVCS) on conductive disturbances requiring PPM after TAVI.

Methods: All patients who underwent TAVI with accessible AVCS from the preprocedural CT scan report were included in this retrospective single-centre study.

Long-term outcome of oesophageal atresia in adolescence (TransEAsome): a national French cohort study protocol.

Introduction: The project, funded by the Agence Nationale de la Recherche, aims to evaluate the long-term outcomes of patients with oesophageal atresia (OA) between 13 and 14 years old and establish multiomics profiles using data from the world's biggest OA registry.

Methods And Analysis: is a national multicentre population-based cohort study recruiting participants from all qualified French centres for OA surgery at birth. The primary objective is to assess the prevalence of gastro-oesophageal reflux disease in adolescence among patients with OA, with several secondary objectives including the identification of risk factors and multiomic profiles from oesophageal biopsies and blood samples collected between 13 and 14 years old, compared with a control group.

Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke.

Objectives: To investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in several European and non-European countries during 2018-2019.

Design: This is an observational registry study using prospectively collected data from the Safe Implementation of Treatment in Stroke (SITS) registry. Comparisons will be performed between patients treated post-approval (July 2018 to December 2021) period with those treated pre-approval (June 2015 to June 2018) period using propensity score matching (PSM).

The role of meal timing in appetitive responses to acute exercise in adolescents with and without obesity: A systematic review and meta-analysis.

Physical activity has been shown to improve various aspects of metabolic health and is frequently applied as an intervention in the management and prevention of overweight/obesity. Chrono-exercise can be studied in relation to time of day and timing in relation to a meal, which encompasses chronology and duration of the temporal interval, but the latter has received limited attention to date. This brief review and meta-analysis investigates whether the timing of a meal subsequent to acute exercise, in children and adolescents with and without overweight/obesity, moderates eating behaviour and appetite.

Monocytic reactive oxygen species-induced T cell apoptosis impairs cellular immune response to SARS-CoV-2 mRNA vaccine.

Background: We have recently shown that, during acute severe COVID-19, SARS-CoV-2 spike protein (S) induces a cascade of events resulting in T cell apoptosis. Indeed, by neutralizing the protease activity of its receptor, ACE2, S induces an increase in circulating Angiotensin II (AngII), resulting in monocytic release of reactive oxygen species (ROS) and programmed T cell death.

Objective: Here, we tested whether SARS-CoV-2 mRNA vaccines, known to cause the circulation of the vaccine antigen, S-protein receptor binding domain (RBD), might trigger the same cascade.

Tolerance to Factor VIII in the Era of Non-Factor Therapies: Immunological Perspectives and a Systematic Review of the Literature.

Persons with hemophilia A (PWHA) lack clotting factor VIII (FVIII) due to a genetic mutation in the F8 gene. The administration of FVIII concentrate leads to the development of neutralizing anti-FVIII antibodies (inhibitors) in about 30% of children with severe hemophilia A. The other 70% of children do not mount a detectable antibody response, suggesting that they may have developed tolerance towards FVIII.

Intranasal delivery of extracellular vesicles: A promising new approach for treating neurological and respiratory disorders.

Background: Extracellular vesicles (EVs) are membrane vesicles secreted by all types of cells, including bacteria, animals, and plants. These vesicles contain proteins, nucleic acids, and lipids from their parent cells and can transfer these components between cells. EVs have attracted attention for their potential use in diagnosis and therapy due to their natural properties, such as low immunogenicity, high biocompatibility, and ability to cross the blood-brain barrier.

A lipidated peptide derived from the C-terminal tail of the vasopressin 2 receptor shows promise as a new β-arrestin inhibitor.

β-arrestins play pivotal roles in seven transmembrane receptor (7TMR) signalling and trafficking. To study their functional role in regulating specific receptor systems, current research relies mainly on genetic tools, as few pharmacological options are available. To address this issue, we designed and synthesised a novel lipidated phosphomimetic peptide inhibitor targeting β-arrestins, called ARIP, which was developed based on the C-terminal tail (A343-S371) of the vasopressin V2 receptor.

Balloon atrioseptostomy for transposition of the great arteries in Europe: characteristics and outcomes.

Introduction And Objectives: Balloon atrial septostomy (BAS) improves oxygenation in neonates with transposition of the great arteries (TGA) and restrictive foramen ovale. Currently, there is a global shortage of dedicated BAS catheters, while new unmarked catheters have recently become available at some European centers. This study aimed to characterize BAS outcomes using the currently available BAS catheters in Europe.

The stoichiometry of the α4β2 neuronal nicotinic acetylcholine receptors determines the pharmacological properties of the neonicotinoids, and recently introduced butenolide and sulfoximine.

Although neonicotinoids were considered safe for mammals for many decades, recent research has proven that these insecticides can alter cholinergic functions by interacting with neuronal nicotinic acetylcholine (ACh) receptors (nAChRs). One such receptor is the heteromeric α4β2 nAChR, which exists under two different stoichiometries: high sensitivity and low sensitivity α4β2 nAChRs. To replace these insecticides, new classes of insecticides have been developed, such as, sulfoximine, sulfoxaflor, and the butanolide, flupyradifurone.

Statistical harmonization of versions of measures across studies using external data: self-rated health and self-rated memory.

Purpose: Harmonizing variables for constructs measured differently across studies is essential for comparing, combining, and generalizing results. We developed and fielded a brief survey to harmonize Likert and continuous versions of measures for two constructs, self-rated health and self-rated memory, for use in studies of French older adults.

Methods: We recruited 300 participants from a French memory clinic in 2023 to answer both the Likert and continuous versions of self-rated health and self-rated memory questions.

Emergence of Invasive Streptococcus dysgalactiae subsp. equisimilis in Spain (2012-2022): Genomic Insights and Clinical Correlations.

Objectives: An increase in Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections has been documented worldwide. This study aims to analyse invasive disease caused by SDSE (iSDSE) in adults over an 11-year period in Spain.