Citations

ABSTRACT Background Obesity is an important risk factor associated with atrial fibrillation (AF). The impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on recurrent AF among patients undergoing catheter ablation is not well described. Objective This study aimed to evaluate the effect of GLP‐1 RA on the recurrence of AF among obese patients after catheter ablation. Methods Utilizing the TriNetX research network, we identified patients aged over 18 with obesity (BMI ≥ 30) who underwent AF ablation from January 1, 2015, to December 1, 2022, using Current Procedural Terminology codes. Patients were categorized based on their baseline GLP‐1 RA use. Through propensity‐score matching, each cohort comprised 1558 patients. The primary outcome encompassed a composite of cardioversion, initiation of new antiarrhythmic drug (AAD) therapy, or redo AF ablation. Additional outcomes during the 12‐month follow‐up included AF readmission, heart failure readmissions, readmissions due to ischemic stroke, and mortality, with a separate analysis done for patients with BMI > 40. Results GLP‐1 RA use in patients with obesity undergoing AF ablation was linked to a significantly reduced risk of cardioversion, new AAD therapy, and the need for redo AF ablation (hazard ratio [HR] 0.72 [0.65–0.80]; p < 0.001). At 12 months, individuals on GLP‐1 agonists exhibited a lower likelihood of mortality (HR 0.61 [0.40–0.93]; p < 0.001). Although all other secondary outcomes were lower in the GLP‐1 RA group, there was no significant difference in ischemic stroke between the groups. These results were consistent among patients with BMI > 40, although apart from ischemic stroke, there was no difference in mortality between the two groups. Conclusion The utilization of GLP‐1 RA in individuals with obesity is linked to a decreased likelihood of arrhythmia recurrence following AF ablation, leading to a reduced requirement for cardioversion, AAD therapy, or redo AF ablation.

Infective endocarditis (IE) remains a diagnostic challenge, particularly in cases where microbiological diagnosis is not established. Advances in molecular diagnostics have expanded the ability to identify causative pathogens beyond traditional culture-based methods. This review explores the role of molecular assays, including pathogen-specific PCR, multiplex PCR, broad-range PCR, and shotgun metagenomic sequencing, in diagnosing IE. These molecular techniques enhance pathogen detection, especially in patients with prior antibiotic exposure, and improve diagnostic accuracy in culture-negative IE. Broad-range PCR assays and metagenomic sequencing offer the untargeted detection of a wide spectrum of organisms. Despite their advantages, limitations such as availability, interpretation challenges, and a lack of antimicrobial susceptibility testing remain. A multimodal approach integrating molecular diagnostics with conventional methods is essential to optimize patient management. Further research is needed to refine diagnostic algorithms and improve cost-effectiveness in clinical practice.

With their unique therapeutic properties and amenability to engineering modifications, exosomes are considered a promising tool for treating peripheral nerve injuries. Through genetic engineering or physicochemical modifications, the targeting ability and functionality of exosomes can be further enhanced, enabling efficient delivery of therapeutic molecules and significantly boosting their therapeutic potential. This review aims to explore exosome-based therapies in peripheral nerve repair and their mechanisms and summarizes recent advances in the roles of exosomes in neuroprotection, axonal regeneration, vascular regeneration, and inflammatory modulation. Exosomes act as natural messengers between cells, carrying genetic materials, cytokines, and growth factors that can modulate the local microenvironment and foster peripheral nerve regeneration. Studies have shown that exosomes derived from Schwann cells, macrophages, neurons, and mesenchymal stem cells can all promote axonal regeneration and modulate inflammatory responses through various mechanisms. Compared with cell therapy, exosome therapy offers greater stability and safety, with the ability to traverse biological barriers, presenting new possibilities for regenerative medicine and precision therapy. However, challenges such as the heterogeneity and complexity of exosomes, uncertainty of in vivo distribution and metabolic pathways, and the limitations of targeting remain to be addressed. Future research will focus on the engineering modifications of exosomes to enhance their therapeutic efficiency and targeting precision.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Abstract There is a bidirectional relationship between substance use disorders and sleep disturbances. Substance misuse, including chronic use of alcohol, cannabis, opioids, and cocaine, impacts both the subjective quality and objective measures of sleep. In turn, sleep disturbances, including insomnia, have been linked to the initiation, maintenance, and relapse of substance use disorder. This chapter summarizes recent research findings on the characteristics of sleep disturbances among individuals with substance use disorders. It then discusses available tools to aid sleep clinicians in diagnosing substance use disorders in their patients. Finally, it outlines key options and considerations for non-pharmacological and pharmacological treatments of sleep disorders in the substance use disorder population.

ABSTRACT The lower infrastructure requirements of portable ultra‐low field MRI (ULF‐MRI) systems have enabled their use in diverse settings such as intensive care units and remote medical facilities. The UNITY Project is an international neuroimaging network harnessing this technology, deploying portable ULF‐MRI systems globally to expand access to MRI for studies into brain development. Given the wide range of environments where ULF‐MRI systems may operate, there are external factors that might influence image quality. This work aims to introduce the quality control (QC) framework used by the UNITY Project to investigate how robust the systems are and how QC metrics compare between sites and over time. We present a QC framework using a commercially available phantom, scanned with 64 mT portable MRI systems at 17 sites across 12 countries on four continents. Using automated, open‐source analysis tools, we quantify signal‐to‐noise, image contrast, and geometric distortions. Our results demonstrated that the image quality is robust to the varying operational environment, for example, electromagnetic noise interference and temperature. The Larmor frequency was significantly correlated to room temperature, as was image noise and contrast. Image distortions were less than 2.5 mm, with high robustness over time. Similar to studies at higher field, we found that changes in pulse sequence parameters from software updates had an impact on QC metrics. This study demonstrates that portable ULF‐MRI systems can be deployed in a variety of environments for multi‐center neuroimaging studies and produce robust results.

Background Topical timolol appears to provide a curative effect in managing chronic ulcers. However, the pooled evidence of its effect hasn’t been established yet. This is the first Meta-analysis to evaluate and assess the efficacy of topical timolol in accelerating wound healing in patients with chronic refractory ulcers. Methods We comprehensively searched different electronic databases; PubMed, Scopus, Web of Science, Cochrane library and ClinicalTrials.gov from their inception to November 2024. The search was conducted without imposing any restrictions on publication date or study design. The ROB-II tool was used to assess the quality of included RCTs. NIH tools were used to evaluate the quality of included cohort and single arm studies. Risk ratios (RR) and mean differences (MD), with 95% confidence intervals (CIs), were used as effect estimates. Results Six studies were included in this systematic review, comprising two single-arm studies and four double-arm studies (3 RCTs and 1 cohort study). Data from the four double-arm studies on venous ulcers were pooled for meta-analysis. The results showed that topical timolol significantly reduced ulcer area compared to control at 2 weeks (−23.63%; 95% CI: −29.26 to −18.00; p < 0.00001), 4 weeks (−41.40%; 95% CI: −49.57 to −33.23; p < 0.00001), and 12 weeks (−23.38%; 95% CI: −39.43 to −7.33; p = 0.004). Complete ulcer healing was observed at 4 weeks (RR: 12.00; 95% CI: 1.68 to 85.84; p = 0.01) and 12 weeks (RR: 3.79; 95% CI: 0.44 to 32.54; p = 0.22). Conclusion Topical timolol has the potential to promote healing in chronic unhealed ulcers. This meta-analysis, focusing on chronic venous ulcers, consistently showed favorable results across different time points. However, the small sample sizes, lack of blinding, and inclusion of only four studies limit the generalizability of the findings.

Abstract Background: The hidden curriculum refers to the implicit norms and behaviors in academic environments that can particularly disadvantage scholars from backgrounds underrepresented in the scientific workforce (URSW). Critically, scientific mentors can support URSW mentees by making the hidden curriculum explicit to help these scholars navigate academia more effectively. However, mentors often lack the lived experience or training necessary to understand and fully address relevant hidden curriculum challenges. Methods: We developed a set of 16 hidden curriculum competencies specifically for scientific mentors working with URSW mentees. A survey was conducted among diversity, equity, inclusion, and accessibility experts in translational science to assess the perceived importance of each competency. Their feedback was used to refine the final competencies, from which a conceptual framework was developed. Results: Survey results (n = 62) showed broad agreement on the competencies’ critical importance for mentoring across diversity, with several competencies, including identifying unconscious biases, acting as allies, and demystifying career pathways, receiving over 90% agreement for their importance for mentoring URSW mentees. Respondents from URSW backgrounds placed greater emphasis (p < 0.05) on several competencies, including understanding mentee perspectives, expanding professional networks, and allyship. Conclusion: The 16 competencies, grouped into four domains (Foundation, Career, Science, and Overcoming Bias), collectively offer a comprehensive approach for mentors to build trust, support mentee career development, overcome practical barriers to mentee engagement in research, and actively combat bias. Our conceptual framework offers structured guidance for mentors and mentor training programs, identifying the skills needed to foster inclusive academic environments and enhance URSW retention and success.

Abstract Aims Tricuspid valve regurgitation (TR) is common and associated with increased mortality. The interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) and association with outcomes is incompletely understood. The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the pulmonary vascular load that the RV must overcome to eject blood. Whether PA Ea discriminates mortality risk in unselected patients with significant TR is unknown. Methods and results In consecutive patients with ≥moderate TR, we compared all-cause mortality at 5 years based on the PA Ea (defined as the RV systolic pressure/stroke volume as measured by transthoracic echocardiography). In a total of 12 682 patients, the median PA Ea was 0.7 mm Hg/mL (interquartile range 0.5, 0.9). Increasing levels of PA Ea were associated with heart failure, liver and kidney disease, and clinical markers of risk such as the Tricuspid Regurgitation Impact on Outcomes score. Increasing levels of PA Ea were associated with larger RVs, worse RV systolic function, higher N-terminal pro-brain natriuretic peptide levels, and greater degrees of right heart failure. After adjusting for age and sex, PA Ea was associated with higher risk of death (hazard ratio 1.55 per 0.5 mm Hg/mL change of PA Ea; 95% confidence intervals 1.51–1.60; P &lt; 0.0001). In multivariable modelling incorporating available clinical variables, PA Ea was independently predictive of outcome compared with other indexes of RV–PA coupling. Conclusion In patients with significant TR, higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify risk.