Managing thrombosis risk in flow diversion: A review of antiplatelet approaches.

Flow diversion is a transformative approach in neurointerventional surgery for intracranial aneurysms that relies heavily on effective antiplatelet therapy. The ideal approach, including the timing of treatment, the use of dual antiplatelet therapy (DAPT), and the number of flow-diverter devices to use, remains unknown. DAPT, which combines aspirin with a thienopyridine like clopidogrel, prasugrel, or ticagrelor, is the standard regimen, balancing thromboembolic protection and hemorrhagic risk.

Comparison of PREMM5 and PREMMplus Risk Assessment Models to Identify Lynch Syndrome.

Purpose: Clinical risk assessment models can identify patients with hereditary cancer susceptibility, but it is unknown how multigene cancer syndrome prediction models compare with syndrome-specific models in assessing risk for individual syndromes such as Lynch syndrome (LS). Our aim was to compare PREMMplus (a 19-gene cancer risk prediction model) with PREMM5 (a LS gene-specific model) for LS identification.

Methods: We analyzed data from two cohorts of patients undergoing germline testing from a commercial laboratory (n = 12,020) and genetics clinic (n = 6,232) with personal and/or family histories of LS-associated cancer.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.

Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan.

Individualized temporal patterns drive human sleep spindle timing.

Sleep spindles are cortical electrical oscillations considered critical for memory consolidation and sleep stability. The timing and pattern of sleep spindles are likely to be important in driving synaptic plasticity during sleep as well as preventing disruption of sleep by sensory and internal stimuli. However, the relative importance of factors such as sleep depth, cortical up/down-state, and temporal clustering in governing sleep spindle dynamics remains poorly understood.

Bosniak Classification of Cystic Renal Masses Version 2019: Proportion of Malignancy by Class and Subclass-Systematic Review and Meta-Analysis.

Bosniak classification version 2019 (v2019) was a major revision to version 2005 (v2005) that defined cystic renal mass subclasses based on wall or septa features. To determine the proportion of malignancy within cystic renal masses stratified by Bosniak classification v2019 class and feature-based subclass. MEDLINE and EMBASE databases were searched on July 24, 2023 for studies published in 2019 or later that reported cystic renal masses that underwent renal-mass CT or MRI, were assessed using Bosniak v2019, and had a reference standard (histopathology indicating benignity or malignancy or ≥5-year imaging follow-up indicating benignity).

Demographic-Based Personalized Left Ventricular Hypertrophy Thresholds for Hypertrophic Cardiomyopathy Diagnosis.

Background: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death. Current diagnosis emphasizes the detection of left ventricular hypertrophy (LVH) using a fixed threshold of ≥15-mm maximum wall thickness (MWT). This study proposes a method that considers individual demographics to adjust LVH thresholds as an alternative to a 1-size-fits-all approach.

Genetically Engineered T Cells and Recombinant Antibodies to Target Intracellular Neoantigens: Current Status and Future Directions.

Recombinant antibodies and, more recently, T cell receptor (TCR)-engineered T cell therapies represent two immunological strategies that have come to the forefront of clinical interest for targeting intracellular neoantigens in benign and malignant diseases. T cell-based therapies targeting neoantigens use T cells expressing a recombinant complete TCR (TCR-T cell), a chimeric antigen receptor (CAR) with the variable domains of a neoepitope-reactive TCR as a binding domain (TCR-CAR-T cell) or a TCR-like antibody as a binding domain (TCR-like CAR-T cell). Furthermore, the synthetic T cell receptor and antigen receptor (STAR) and heterodimeric TCR-like CAR (T-CAR) are designed as a double-chain TCRαβ-based receptor with variable regions of immunoglobulin heavy and light chains (VH and VL) fused to TCR-Cα and TCR-Cβ, respectively, resulting in TCR signaling.

Navigating Heart-Lung Interactions in Mechanical Ventilation: Pathophysiology, Diagnosis, and Advanced Management Strategies in Acute Respiratory Distress Syndrome and Beyond.

Patients in critical condition who require mechanical ventilation experience intricate interactions between their respiratory and cardiovascular systems. These complex interactions are crucial for clinicians to understand as they can significantly influence therapeutic decisions and patient outcomes. A deep understanding of heart-lung interactions is essential, particularly under the stress of mechanical ventilation, where the right ventricle plays a pivotal role and often becomes a primary concern.

An Overview of Recent Clinical Trials for Diabetic Foot Ulcer Therapies.

Diabetic foot ulcers (DFUs) are a major complication of diabetes, leading to high mortality, reduced quality of life, neuropathy, ischemia, infection, and amputation risks. The prevalence of these ulcers is only on the rise as more people suffer from type 2 diabetes and obesity. The current wound management involves wound dressings, offloading, debridement, and infection control, but more must be done to keep up with the rising prevalence of DFUs and the strain they put on patients and the healthcare system.

Dulaglutide and Dapagliflozin Combination Concurrently Improves the Endothelial Glycocalyx and Vascular and Myocardial Function in Patients with T2DM and Albuminuria vs. DPP-4i.

: The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. : Overall, 60 patients were randomized to combined dulaglutide and dapagliflozin treatment (n = 30) or DPP-4 inhibitors (DPP-4i, n = 30) (ClinicalTrials.

Advancing 3D Engineered In Vitro Models for Heart Failure Research: Key Features and Considerations.

Heart failure is characterized by intricate myocardial remodeling that impairs the heart's pumping and/or relaxation capacity, ultimately reducing cardiac output. It represents a major public health burden, given its high prevalence and associated morbidity and mortality rates, which continue to challenge healthcare systems worldwide. Despite advancements in medical science, there are no treatments that address the disease at its core.

Stem and Progenitor Cells for Musculoskeletal Disease Modeling and Tissue Repair.

Musculoskeletal conditions such as osteoarthritis (OA), bone fracture, and sarcopenia are highly prevalent [...

Side- and Disease-Dependent Changes in Human Aortic Valve Cell Population and Transcriptomic Heterogeneity Determined by Single-Cell RNA Sequencing.

Background: Calcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than aortic valve repair or replacement. CAVD develops preferentially on the fibrosa side, while the ventricularis side remains relatively spared through unknown mechanisms. We hypothesized that the fibrosa is prone to the disease due to side-dependent differences in transcriptomic patterns and cell phenotypes.

Artificial Intelligence-Based Methodologies for Early Diagnostic Precision and Personalized Therapeutic Strategies in Neuro-Ophthalmic and Neurodegenerative Pathologies.

Advancements in neuroimaging, particularly diffusion magnetic resonance imaging (MRI) techniques and molecular imaging with positron emission tomography (PET), have significantly enhanced the early detection of biomarkers in neurodegenerative and neuro-ophthalmic disorders. These include Alzheimer's disease, Parkinson's disease, multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. This review highlights the transformative role of advanced diffusion MRI techniques-Neurite Orientation Dispersion and Density Imaging and Diffusion Kurtosis Imaging-in identifying subtle microstructural changes in the brain and visual pathways that precede clinical symptoms.

Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson's Disease.

The maintenance of healthy mitochondria is essential for neuronal survival and relies upon mitochondrial quality control pathways involved in mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy (mitophagy). Mitochondrial dysfunction is critically implicated in Parkinson's disease (PD), a brain disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Consequently, impaired mitochondrial quality control may play a key role in PD pathology.

POCUS-first in acute diverticulitis: Quantifying cost savings, length-of-stay reduction, and radiation risk mitigation in the ED.

Background: Recent studies have validated the efficacy of point-of-care ultrasound (POCUS) as an alternative diagnostic imaging approach to computed tomography (CT) for patients with suspected acute diverticulitis. This study aimed to quantify the national impact of this approach in cost savings, ED length-of-stay (LOS), and radiation risk mitigation using a POCUS-first approach for acute diverticulitis in the emergency department (ED).

Methods: Using published data, we constructed a Monte Carlo simulation model to compare two POCUS-first strategies (nonselective and selective approaches) for evaluating patients with suspected acute diverticulitis in the ED.

Preeclampsia and eclampsia: Enhanced detection and treatment for morbidity reduction.

Preeclampsia is a life-threatening complication that develops in 2-8% of pregnancies. It is characterized by elevated blood pressure after 20 weeks of gestation and may progress to multiorgan dysfunction, leading to severe maternal and fetal morbidity and mortality. The only definitive treatment is delivery, and efforts are focused on early risk prediction, surveillance, and severity mitigation.

Postpartum hemorrhage assessment and targeted treatment.

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, and mitigating it is a global health priority. In this review, we discuss the measurement, assessment, and treatment of PPH. We review different methods of quantifying blood loss, including gravimetry, calibrated drapes and canisters, and colorimetric techniques.

Uterotonics update.

Uterotonics are the mainstay of management for postpartum haemorrhage and an understanding of their use is essential for the obstetric anaesthetist. First-line uterotonics comprise oxytocin and carbetocin, which act on the oxytocin receptor, and recent research has shown that lower doses of first-line uterotonics can be used to adequate effect. The oxytocin receptor is known to undergo desensitisation with exposure to the agonist over time and with increasing concentrations.

Epidemiology, trends, and disparities in maternal mortality: A framework for obstetric anesthesiologists.

Since 2015, reductions in maternal mortality have stalled globally. In some parts of the world, severe maternal morbidity and mortality have increased, and most cases are thought to be from preventable causes. This is further exacerbated by significant racial, ethnic, and geographic disparities in maternal health outcomes, particularly among countries with diverse populations.

Refinement of a Published Gene-Physical Activity Interaction Impacting HDL-Cholesterol: Role of Sex and Lipoprotein Subfractions.

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).