Spotlight on the 2024 ESC/EACTS management of atrial fibrillation guidelines: 10 novel key aspects.

Atrial fibrillation (AF) remains the most common cardiac arrhythmia worldwide and is associated with significant morbidity and mortality. The European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) have recently released the 2024 guidelines for the management of AF. This review highlights 10 novel aspects of the ESC/EACTS 2024 Guidelines.

MARC1 downregulation reduces hepatocyte lipid content by increasing beta-oxidation.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic. MASLD has a strong genetic component, and a common missense variant (rs2642438) in the mitochondrial amidoxime-reducing component 1 (MARC1) gene confers protection against its onset and severity. However, there are contrasting results regarding the mechanisms entangling this protection.

Assessing the comparative effects of interventions in COPD: a tutorial on network meta-analysis for clinicians.

To optimize patient outcomes, healthcare decisions should be based on the most up-to-date high-quality evidence. Randomized controlled trials (RCTs) are vital for demonstrating the efficacy of interventions; however, information on how an intervention compares to already available treatments and/or fits into treatment algorithms is sometimes limited. Although different therapeutic classes are available for the treatment of chronic obstructive pulmonary disease (COPD), assessing the relative efficacy of these treatments is challenging.

Changes in iPSC-Astrocyte morphology reflect Alzheimer's disease patient clinical markers.

Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer's disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms. Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer's disease (AD) reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets.

Assessing usability of electronic patient-reported outcome measures in older people with and without a rare dermatologic disorder.

Background: Robust and well-defined data collection is important when using electronic patient-reported outcome measures (ePROMs) in clinical studies. Questions have been raised as to whether older age may be a barrier to data collection due to patients' unfamiliarity with electronic devices. Older adults may also have underlying health conditions that affect their ability to fill out patient-reported outcome measures (PROMs) on electronic devices.

Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma.

Background: Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.

Methods: Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries.

From Crisis to Complications: A Nationwide Cohort Study Assessing One-Year Cardiovascular and Thromboembolic Risks After Severe COVID-19 Compared to Matched Controls.

The long-term risk of cardiovascular and thrombotic events following severe COVID-19 remains largely unknown. This study aimed to assess the risk of atherosclerotic cardiovascular disease (ASCVD) within one year after hospital discharge in patients who received intensive care for severe COVID-19. A register-based nationwide case-control study on a cohort of patients with severe COVID-19 (cases) requiring mechanical ventilation and discharged alive without experiencing cardiovascular or thrombotic events during their hospital stay.

Current State and New Horizons in Applications of Physiologically Based Biopharmaceutics Modeling (PBBM): A Workshop Report.

This report summarizes the proceedings for Day 3 of the workshop titled "". This day focused on the current and future drug product quality applications of PBBM from the innovator and generic industries as well as the regulatory agencies perspectives. The presentations, which included several case studies, covered the applications of PBBM in generic drug product development, applications of virtual bioequivalence trials to support formulation bridging and the utility of absorption modeling in clinical pharmacology assessments.

Ferric carboxymaltose with or without phosphate substitution in iron deficiency or iron deficiency anemia before elective surgery - The DeFICIT trial.

Background: Iron deficiency anemia in the perioperative setting is treated predominantly with intravenous iron formulation, of which ferric carboxymaltose may induce hypophosphatemia by modulating fibroblast growth factor 23.

Methods: In this single-center, prospective, randomized, double-blind trial, we consented 92 adult patients scheduled for elective major abdominal or thoracic surgery. These patients either had isolated iron deficiency (plasma ferritin <100 ng/mL or transferrin saturation < 20 %) or iron deficiency anemia (hemoglobin (Hb) 100-130 g/L with plasma ferritin <100 ng/mL or transferrin saturation < 20 %).

Chronic kidney disease-associated pruritus: a comparison of instruments and associations with patient-reported outcomes using an electronic patient-reported outcome survey in Europe.

Background: The associations between self-reported chronic kidney disease-associated pruritus (CKD-aP) and patient-reported outcomes (PROs) have been reported using various instruments to assess itch. Data collection via multiple CKD-aP instruments allows the evaluation of different domains and measurements of CKD-aP burden and may help tailor data capture for future research or clinical care.

Methods: An electronic PRO (ePRO) survey was distributed to European hemodialysis (HD) patients enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in 2021-23.

Kinetics of endothelin-1 and effect selective ET antagonism on ET activation: a mathematical modeling analysis.

Introduction: Endothelin-1 (ET-1) regulates renal and vascular function, but the clinical utility of selective ET receptor antagonists has been limited due to associated fluid retention. The mechanisms underlying fluid retention remain poorly understood but could be a consequence of changes in ET-1 binding to the unantagonized ET receptor, either through increased ET-1 or non-selective ET.

Methods: A mathematical model of ET-1 kinetics was developed to quantify effects of ET antagonist exposure and selectivity on concentrations of ET-1 and its complexes with ET and ET receptors.

Discovery of 6-Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4-dihydroquinoxalin-6-yl)methyl]piperazin-1-yl}--methylpyridine-2-carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor.

PARP inhibitors have attracted considerable interest in drug discovery due to the clinical success of first-generation agents such as olaparib, niraparib, rucaparib, and talazoparib. Their success lies in their ability to trap PARP to DNA; however, first-generation PARP inhibitors were not strictly optimized for trapping nor for selectivity among the PARP enzyme family. Previously we described the discovery of the second-generation PARP inhibitor AZD5305, a selective PARP1-DNA trapper.

Intravenous thrombolysis in young adults with ischemic stroke: A cohort study from the international TRISP collaboration.

Background And Aims: Previous observational data indicate that young adults treated with intravenous thrombolysis (IVT) for acute ischemic stroke have more favorable outcomes and less complications when compared to older adults. Given the limited data on this topic, we aimed to provide more evidence on clinical outcomes and safety in such patients, using a large international thrombolysis registry.

Methods: In this prospective multicenter study, we used data from the Thrombolysis in Ischemic Stroke Patients (TRISP) registry from 1998 to 2020.

Childhood lung function is associated with adolescent-onset and persistent asthma.

Background: Asthma is associated with impaired lung function; however, it is uncertain if a lower childhood lung function is associated with asthma onset and persistence during adolescence. The aims of the present study were to investigate the association between childhood lung function and onset and persistence of asthma during adolescence.

Methods: In the population-based BAMSE (Sweden), PIAMA (Netherlands) and MAAS (UK) birth cohorts, we analysed the association of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC and forced expiratory volume at 75% of FVC at age 8 years with asthma onset and persistence in adolescence (age 12-16 years) using cohort-specific logistic regression analysis followed by meta-analysis.

The use of automated insulin delivery around physical activity and exercise in type 1 diabetes: a position statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD).

Regular physical activity and exercise (PA) are cornerstones of diabetes care for individuals with type 1 diabetes. In recent years, the availability of automated insulin delivery (AID) systems has improved the ability of people with type 1 diabetes to achieve the recommended glucose target ranges. PA provide additional health benefits but can cause glucose fluctuations, which challenges current AID systems.

Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an excess of lipids, mainly triglycerides, in the liver and components of the metabolic syndrome, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence that MASLD clusters with cardiometabolic disease, several leading genetic risk factors for MASLD do not increase the risk of cardiovascular disease, suggesting no causal relationship between MASLD and cardiometabolic derangement. In this work, we leveraged measurements of visceral adiposity identifying 27 previously unknown genetic loci associated with MASLD (n = 36,394), six replicated in four independent cohorts (n = 3,903).

Cell Painting: a decade of discovery and innovation in cellular imaging.

Modern quantitative image analysis techniques have enabled high-throughput, high-content imaging experiments. Image-based profiling leverages the rich information in images to identify similarities or differences among biological samples, rather than measuring a few features, as in high-content screening. Here, we review a decade of advancements and applications of Cell Painting, a microscopy-based cell-labeling assay aiming to capture a cell's state, introduced in 2013 to optimize and standardize image-based profiling.

Assessing Human Lung Pharmacokinetics Using Exhaled Breath Particles.

It remains challenging to quantify lung pharmacokinetics (PK) of a drug administered and targeted to act in the lung. Exhaled breath particles (PEx), which are generated when collapsed distal airways reopen during inhalation, offer a noninvasive way to access undiluted epithelial lining fluid (ELF). Therefore, it was the aim of this study to investigate whether PK data can be derived from PEx.

The analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably?

Background: Pathologist-read tumor-infiltrating lymphocytes (TILs) have showcased their predictive and prognostic potential for early and metastatic triple-negative breast cancer (TNBC) but it is still subject to variability. Artificial intelligence (AI) is a promising approach toward eliminating variability and objectively automating TILs assessment. However, demonstrating robust analytical and prognostic validity is the key challenge currently preventing their integration into clinical workflows.

The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea.

Background: Obstructive sleep apnoea (OSA) is a common disease with breathing disturbances during sleep. Sulthiame (STM), a carbonic anhydrase (CA) inhibitor, was recently shown to reduce OSA in a significant proportion of patients. CA activity and hypoxia-inducible factor (HIF)-1α are two potential biomarkers reported in severe OSA and hypoxia.

Consensus Report on the Use of Continuous Glucose Monitoring in Chronic Kidney Disease and Diabetes.

This report represents the conclusions of 15 experts in nephrology and endocrinology, based on their knowledge of key studies and evidence in the field, on the role of continuous glucose monitors (CGMs) in patients with diabetes and chronic kidney disease (CKD), including those receiving dialysis. The experts discussed issues related to CGM accuracy, indications, education, clinical outcomes, quality of life, research gaps, and barriers to dissemination. Three main goals of management for patients with CKD and diabetes were identified: (1) greater use of CGMs for better glycemic monitoring and management, (2) further research evaluating the accuracy, feasibility, outcomes, and potential value of CGMs in patients with end-stage kidney disease (ESKD) on hemodialysis, and (3) equitable access to CGM technology for patients with CKD.