Left Atrial Thrombus in Atrial Fibrillation/Flutter Patients in Relation to Anticoagulation Strategy: LATTEE Registry.

Background: Atrial fibrillation (AF) and flutter (AFl) increase the risk of thromboembolism. The aim of the study was to assess the prevalence of left atrial thrombus (LAT) in AF/AFl in relation to oral anticoagulation (OAC). Methods: LATTEE (NCT03591627) was a multicenter, prospective, observational study enrolling consecutive patients with AF/AFl referred for transesophageal echocardiography before cardioversion or ablation.

Generalizability of the EAST-AFNET 4 Trial: Assessing Outcomes of Early Rhythm-Control Therapy in Patients With Atrial Fibrillation.

Background EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) demonstrated clinical benefit of early rhythm-control therapy (ERC) in patients with new-onset atrial fibrillation (AF) and concomitant cardiovascular conditions compared with current guideline-based practice. This study aimed to evaluate the generalizability of EAST-AFNET 4 in routine practice. Methods and Results Using a US administrative database, we identified 109 739 patients with newly diagnosed AF during the enrollment period of EAST-AFNET 4.

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.

Background: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial.

Methods: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling.

Privacy-preserving federated neural network learning for disease-associated cell classification.

Training accurate and robust machine learning models requires a large amount of data that is usually scattered across data silos. Sharing or centralizing the data of different healthcare institutions is, however, unfeasible or prohibitively difficult due to privacy regulations. In this work, we address this problem by using a privacy-preserving federated learning-based approach, , for complex models such as convolutional neural networks.

Prevalence and Significance of the Vessel-Cluster Sign on Susceptibility-Weighted Imaging in Patients With Severe Small Vessel Disease.

Background And Objectives: Magnetic resonance susceptibility-weighted imaging (SWI) can identify small brain blood vessels that contain deoxygenated blood due to its induced magnetic field disturbance. We observed focal clusters of possible dilated small vessels on SWI in white matter in severe small vessel disease (SVD). We assessed their prevalence, associations with SVD lesions, and vascular reactivity in patients with sporadic SVD and in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Adverse Effects and Safety in Glaucoma Patients: Agreement on Clinical Trial Outcomes for Reports on Eye Drops (ASGARD)-A Delphi Consensus Statement.

Purpose: The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops.

Design: Modified Delphi method.

Methods: Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in 2 sequential web-based surveys administered from June 27 to August 29, 2021.

Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally.

Spastic Paraplegia Type 7 and Movement Disorders: Beyond the Spastic Paraplegia.

Background: Spastic paraplegia type 7 (SPG7) mutations can present either as a pure form or a complex phenotype with movement disorders.

Objective: Describe the main features of subjects with SPG7 mutations associated with movement disorders.

Methods: We analyzed the clinical and paraclinical information of subjects with SPG7 mutations associated with movement disorders.

Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy.

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort.

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials.

Objective: To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3-4) enrolled in clinical trials.

Research Design And Methods: This analysis pooled data from 19 randomized, placebo-controlled, phase 1-4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models.

Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia.

Objective: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (Mendelian Inheritance in Man # 615683).

Evaluation Challenges for the Application of Extended Reality Devices in Medicine.

Augmented and virtual reality devices are being actively investigated and implemented for a wide range of medical uses. However, significant gaps in the evaluation of these medical devices and applications hinder their regulatory evaluation. Addressing these gaps is critical to demonstrating the devices' safety and effectiveness.

Integration of Infant Metabolite, Genetic, and Islet Autoimmunity Signatures to Predict Type 1 Diabetes by Age 6 Years.

Context: Biomarkers that can accurately predict risk of type 1 diabetes (T1D) in genetically predisposed children can facilitate interventions to delay or prevent the disease.

Objective: This work aimed to determine if a combination of genetic, immunologic, and metabolic features, measured at infancy, can be used to predict the likelihood that a child will develop T1D by age 6 years.

Methods: Newborns with human leukocyte antigen (HLA) typing were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY).

Impact of the external school food environment on the associations of internal school food environment with high schoolers' diet and BMI.

Objective: To examine associations of school food availability with student intake frequency and BMI, and whether the number of neighbourhood food outlets modifies these associations.

Design: Baseline assessment of a nationally representative cohort study of US 10th graders. Students reported intake frequency of fruits and vegetables (FV), snacks and soda.

Rare occult macular dystrophy with a pathogenic variant in the RP1L1 gene in a patient of Swiss descent.

Purpose: We report a first case of bilateral occult macular dystrophy (OMD) with a c.133C>T (p.Arg45Trp) pathogenic variant in the retinitis pigmentosa 1-like 1 () gene in a patient of Caucasian Swiss decent.

MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study.

Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified.

Applying systems thinking to identify enablers and challenges to scale-up interventions for hypertension and diabetes in low-income and middle-income countries: protocol for a longitudinal mixed-methods study.

Introduction: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million.

Percutaneous Transvalvular Microaxial Flow Pump Support in Cardiology.

The Impella device (Impella, Abiomed, Danvers, MA) is a percutaneous transvalvular microaxial flow pump that is currently used for (1) cardiogenic shock, (2) left ventricular unloading (combination of venoarterial extracorporeal membrane oxygenation and Impella concept), (3) high-risk percutaneous coronary interventions, (4) ablation of ventricular tachycardia, and (5) treatment of right ventricular failure. Impella-assisted forward blood flow increased mean arterial pressure and cardiac output, peripheral tissue perfusion, and coronary blood flow in observational studies and some randomized trials. However, because of the need for large-bore femoral access (14 F for the commonly used Impella CP device) and anticoagulation, the incidences of bleeding and ischemic complications are as much as 44% and 18%, respectively.

Quadruple genetic variants in a sporadic ALS patient.

Objectives: Due to upcoming gene-specific therapy approaches for ALS patients, understanding familial and sporadic ALS genetics is becoming increasingly important. In this study, we wanted to investigate underlying genetic causes for an SALS patient.

Methods: We performed ALS gene panel sequencing and subsequent segregation analysis in the family.

Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia.

Background And Aims: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3α,7α,12α-trihydroxy-5β-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration.