Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography.

Importance: Disease characteristics of genetically mediated coronary artery disease (CAD) on coronary angiography and the association of genomic risk with outcomes after coronary angiography are not well understood.

Objective: To assess the angiographic characteristics and risk of post-coronary angiography outcomes of patients with genomic drivers of CAD: familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP).

Design, Setting, And Participants: A retrospective cohort study of 3518 Mass General Brigham Biobank participants with genomic information who underwent coronary angiography was conducted between July 18, 2000, and August 1, 2023.

Comparative Effectiveness of Individual Sodium-Glucose Cotransporter 2 Inhibitors.

Importance: Evidence on cardiovascular benefits and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors is mainly from placebo-controlled trials. Therefore, the comparative effectiveness and safety of individual SGLT-2 inhibitors remain unknown.

Objective: To compare the use of canagliflozin or dapagliflozin with empagliflozin for a composite outcome (myocardial infarction [MI] or stroke), heart failure hospitalization, MI, stroke, all-cause death, and safety outcomes, including diabetic ketoacidosis (DKA), lower-limb amputation, bone fracture, severe urinary tract infection (UTI), and genital infection and whether effects differed by dosage or cardiovascular disease (CVD) history.

Generative Artificial Intelligence in Anatomic Pathology.

Context.—: Generative artificial intelligence (AI) has emerged as a transformative force in various fields, including anatomic pathology, where it offers the potential to significantly enhance diagnostic accuracy, workflow efficiency, and research capabilities.

Objective.

Impact of lesion preparation-induced calcified plaque defects in vascular intervention for atherosclerotic disease: in silico assessment.

Percutaneous coronary interventions in highly calcified atherosclerotic lesions are challenging due to the high mechanical stiffness that significantly restricts stent expansion. Intravascular lithotripsy (IVL) is a novel vessel preparation technique with the potential to improve interventional outcomes by inducing microscopic and macroscopic cracks to enhance stent expansion. However, the exact mechanism of action for IVL is poorly understood, and it remains unclear whether the improvement in-stent expansion is caused by either the macro-cracks allowing the vessel to open or the micro-cracks altering the bulk material properties.

Bacterium-Phage Symbiosis Facilitates the Enrichment of Bacterial Pathogens and Antibiotic-Resistant Bacteria in the Plastisphere.

The plastisphere, defined as the ecological niche for microbial colonization of plastic debris, has been recognized as a hotspot of pathogenic and antibiotic-resistant bacteria. However, the interactions between bacteria and phages facilitated by the plastisphere, as well as their impact on microbial risks to public health, remain unclear. Here, we analyzed public metagenomic data from 180 plastisphere and environmental samples, stemming from four different habitats and two plastic types (biodegradable and nonbiodegradable plastics) and obtained 611 nonredundant metagenome-assembled genomes (MAGs) and 4061 nonredundant phage contigs.

Targeted detection of sequence variants in cell-free DNA from cerebrospinal fluid in pediatric central nervous system tumors.

The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors.

Diagnostic and prognostic performance of urine ubiquitin carboxy-terminal hydrolase L1 across multiple acute brain injury types - A longitudinal prospective cohort study.

Introduction: Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is recognized as a diagnostic and prognostic blood biomarker for traumatic brain injury (TBI). This study aimed to evaluate whether UCH-L1 concentrations measured in patients' urine post-injury could serve as a diagnostic or prognostic biomarker for outcomes in various types of acute brain injuries (ABI).

Material And Methods: This pilot study included 46 ABI patients: aneurysmal subarachnoid hemorrhage (n = 22), ischemic stroke (n = 16), and traumatic brain injury (n = 8), along with three healthy controls.

A Bayesian Interpretation of CABANA and Other Randomized Controlled Trials for Catheter Ablation in Patients With Atrial Fibrillation.

Background: Catheter ablation improves symptoms and quality of life in atrial fibrillation patients, but its effect on adverse cardiovascular outcomes and mortality remains uncertain. Bayesian analysis of randomized controlled trials offers a deeper understanding of treatment effects beyond conventional p-value thresholds.

Methods: We conducted a post hoc Bayesian reanalysis of CABANA and four similar trials to estimate catheter ablation's effect on cardiovascular and survival outcomes.

Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players.

 Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players.

Integrating pharmacogenomics and cheminformatics with diverse disease phenotypes for cell type-guided drug discovery.

Background: Large-scale pharmacogenomic resources, such as the Connectivity Map (CMap), have greatly assisted computational drug discovery. However, despite their widespread use, CMap-based methods have thus far been agnostic to the biological activity of drugs as well as to the genomic effects of drugs in multiple disease contexts. Here, we present a network-based statistical approach, Pathopticon, that uses CMap to build cell type-specific gene-drug perturbation networks and integrates these networks with cheminformatic data and diverse disease phenotypes to prioritize drugs in a cell type-dependent manner.

Association between chronic fatigue syndrome/myalgic encephalomyelitis and cardiovascular disease.

Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a medical condition characterized by severe and prolonged fatigue that is not relieved by rest or attributed to any underlying medical or psychological condition. Individuals with CFS/ME are considered to have an increased risk of a wide range of comorbid conditions, including cardiovascular disease (CVD). The association between CFS/ME and CVD is not fully understood.

DepRescribing inapprOpriate Proton Pump InhibiTors (DROPIT): study protocol of a cluster-randomised controlled trial in Swiss primary care.

Objectives: Proton pump inhibitors (PPIs) are widely prescribed medications and commonly used for the treatment of gastric acid-related disorders. Nevertheless, PPIs are often overused leading to potential adverse effects and unnecessary healthcare costs. Deprescribing strategies have emerged to safely reduce or substitute inappropriate PPIs and optimise patient care in an evidence-based manner.

Epidemiology and outcomes of patients with cardiac arrest in the emergency department of a lower middle-income country.

Background: Advanced cardiovascular life support (ACLS) for cardiac arrest is a cornerstone of emergency care and yet remains poorly studied in low- and middle-income countries. We characterised the clinical epidemiology and outcomes of cardiac arrest and ACLS in an ED in central Haiti, a lower middle-income country with a nascent emergency care system.

Methods: We conducted a prospective observational study of adult and paediatric patients who suffered cardiac arrest in an academic hospital ED in central Haiti from January 2019 to August 2020.

Characterization of occupational endotoxin-related small airway disease with longitudinal paired inspiratory/expiratory CT scans.

Background: Although small airway disease has been recognized as a major contributor to obstructive respiratory diseases, the association between occupational endotoxin exposure and small airway disease, as characterized by CT scans, requires further investigation.

Research Question: What is the association between occupational endotoxin exposure and small airway disease, and which CT imaging biomarkers effectively detect pre-clinical airway dysfunction?

Study Design And Methods: This study includes 404 subjects from the Shanghai Textile Worker Cohort. We collected longitudinal inspiratory/expiratory CT scans, spirometry data, and endotoxin levels in 2011 and 2016.

Analysis of longitudinal social media for monitoring symptoms during a pandemic.

Objective: Current studies leveraging social media data for disease monitoring face challenges like noisy colloquial language and insufficient tracking of user disease progression in longitudinal data settings. This study aims to develop a pipeline for collecting, cleaning, and analyzing large-scale longitudinal social media data for disease monitoring, with a focus on COVID-19 pandemic.

Materials And Methods: This pipeline initiates by screening COVID-19 cases from tweets spanning February 1, 2020, to April 30, 2022.

Yield of Esophageal Biopsy Patterns for the Diagnosis of Eosinophilic Esophagitis.

Background And Aims: The pattern of inflammation in eosinophilic esophagitis (EoE) is patchy, necessitating multiple biopsies to optimize diagnostic yield. Current consensus-based guidelines recommend 6 total biopsies at two sites: distal and either middle or proximal esophagus, although based on limited data. We aimed to determine whether this biopsy protocol sufficiently captures EoE diagnoses by evaluating the distribution of eosinophilia in a large EoE cohort.

Anti-correlation of KLRG1 and PD-1 expression in human tumor CD8 T cells.

Recently, combination checkpoint therapy of cancer has been recognized as producing additive as opposed to synergistic benefit due in part to positively correlated effects. The potential for uncorrelated or negatively correlated therapies to produce true synergistic benefits has been noted. Whereas the inhibitory receptors PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT have been collectively characterized as exhaustion receptors, another inhibitory receptor KLRG1 was historically characterized as a senescent receptor and received relatively little attention as a potential checkpoint inhibitor target.

Case Report: Percutaneous Peripheral Nerve Stimulation for the Treatment of Occipital Neuralgia.

Headaches are among the most prevalent medical complaints globally. Occipital neuralgia is a chronic headache disorder characterized by unilateral or bilateral severe pain originating in the neck or skull base and radiating up along the occipital nerve distribution. Effective treatment options for occipital neuralgia can be challenging and some patients may prove to be refractory to conventional medical and interventional therapies.

Consensus Recommendations for the Management of Neurosarcoidosis: A Delphi Survey of Experts Across the United States.

Background And Objectives: Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies.

Methods: In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis.

National Trends in Stroke Presentation, Treatments, and Outcomes During the First 2 Years of the COVID-19 Pandemic.

Background And Objectives: Early presentation and acute treatment for patients presenting with ischemic stroke are associated with improved outcomes. The onset of the COVID-19 pandemic was associated with a large decrease in patients presenting with ischemic stroke, but it is unknown whether these changes persisted.

Methods: This study analyzed emergency department (ED) stroke presentations (n = 158,060) to all nonfederal hospitals in the 50 states and Washington, D.

The Impact of Idiopathic Intracranial Hypertension on Cardiovascular Disease Risk Among UK Women: An Obesity-Adjusted Analysis.

Introduction: Idiopathic intracranial hypertension (IIH) is known to elevate cardiovascular disease (CVD) risk, but the extent to which obesity and IIH-specific factors contribute to this risk is not well understood. WE aim to separate the effects of obesity from IIH-specific factors on the risk of stroke and CVD, building on previous findings that indicate a two-fold increase in cardiovascular events in women with IIH compared to BMI-matched controls.

Methods: An obesity-adjusted risk analysis was conducted using Indirect Standardization based on data from a cohort study by Adderley et al.