Citations

Abstract Background/Introduction Patients with transthyretin cardiac amyloidosis (ATTR-CA) and atrial fibrillation (AF) have increased risk for left atrial thrombi, necessitating anticoagulation therapy if bleeding risk is not prohibitive. Limited data is available comparing the use of direct oral anticoagulants (DOACs) to warfarin in this population. Purpose To evaluate and compare clinical efficacy and safety outcomes of DOACs versus warfarin in patients with ATTR-CA and AF. Methods We conducted a retrospective cohort study using the TriNetX Network, which includes data from over 140 million patients, between 2014 and 2022. Adults (aged ≥18 years) with ATTR-CA and AF were identified. These patients were further categorized into two groups: one cohort which utilized DOACs for oral anticoagulation and the other cohort on warfarin. 1:1 propensity score matching (PSM) was utilized to balance baseline characteristics between the two cohorts. The primary outcome was rate of stroke, with secondary outcomes including all-cause death, all-cause hospitalizations, and acute heart failure exacerbations. Safety outcomes included intracranial hemorrhage, gastrointestinal hemorrhage, and hematuria. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Results Among 8,214 adults with ATTR-CA and AF, 5,774 patients were on a DOAC while 2,440 patients were on warfarin. After PSM, 2,425 patients were included in each group. The use of DOACs for AF in patients with ATTR-CA was associated with a significantly lower risk of ischemic stroke compared to warfarin (5.7% versus 7.3%, aOR 0.771 [95% CI, 0.612-0.971]) by the end of the one year follow up. There were no differences in all-cause mortality (19.8% versus 21%, aOR 0.927 [95% CI, 0.806-1.066]), all-cause hospitalizations (19.2% versus 21.6%, aOR 0.863 [95% CI, 0.624-1.195]) or heart failure exacerbations (43.6% versus 46%, aOR 0.906 [95% CI, 0.809-1.015]). Safety outcomes favored DOACs over warfarin, with a lower risk of intracranial hemorrhage (4.5% versus 7.8%, aOR 0.565 [95% CI, 0.444-0.720]), and comparable rates of GI hemorrhage and hematuria. Conclusions DOACs may be safely used in ATTR-CA patients with AF, offering a lower risk of stroke compared to warfarin and a more favorable safety profile. These findings emphasize the potential advantages of DOACs in this population and underline the need for prospective studies to validate these results.

Abstract Background Women with advanced chronic kidney disease (CKD) encounter reproductive health challenges, including reduced fertility, menstrual irregularity, and sexual dysfunction. This study examined changes in sex hormones in patients with CKD, their correlation with sexual function, and changes after transplant. Methods This study recruited women aged 18–51 years with CKD stages 3b-5 from outpatient clinics and dialysis units. Exclusion criteria included active pregnancy, menopause, prior hysterectomy/bilateral oophorectomy, or use of hormonal contraceptives/therapy. Data were collected at enrollment and at 6 months post-transplant. Results Thirty-eight subjects met eligibility criteria and enrolled in the trial (8 in CKD stage 3b, 10 in CKD stage 4, and 20 in CKD stage 5/5D). Sexual dysfunction (25/38, 65.8%), defined as total female sexual function index score < 26.55, and menstrual irregularities (17/38, 44.7%) were common, with abnormal elevation of luteinizing hormone present in the follicular phase in the majority of patients. There was a significant negative association between total female sexual function index score and prolactin (β = -0.26, P = 0.03) and dehydroepiandrosterone sulfate (β = -0.07, P = 0.01) after adjusting for age. After transplant, there was also a significant improvement in both prolactin and dehydroepiandrosterone sulfate levels, although sexual dysfunction persisted. Conclusions This study highlights the complex interplay between advanced CKD, reproductive endocrinology, and sexual health. Significant hormonal dysregulation and associated reproductive challenges were observed. The prominent role of dehydroepiandrosterone sulfate in sexual dysfunction among women with CKD requires further study.

Background/Objectives: Despite immune checkpoint inhibitors (ICPIs)’s transformation of lung cancer treatment, pneumonitis remains a potentially serious immune-related adverse event. However, reliable data on the comparative risks of individual ICPIs remain unknown. We conducted this network meta-analysis (NMA) to, therefore, quantify and compare the exact pooled burden of pneumonitis risk across multiple ICPI analogs. Methods: We searched the following databases, PubMed, Embase, Scopus MEDLINE and Cochrane Database of Systematic Reviews, as well as gray literature on Google Scholar for eligible studies reporting on the prevalence of pneumonitis following immune check point inhibitor exposures. Pairwise and network meta-analyses were performed to estimate pooled odds ratios (ORs) for pneumonitis, using placebo as the common comparator. Sensitivity analyses assessed the impact of study quality and combination therapies. Results: A total of 29 studies enrolling 15,271 patients with non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) satisfied the inclusion criteria and are included in the meta-analysis. Pembrolizumab was associated with a significantly increased risk of pneumonitis compared to placebo (odds ratio [OR] = 2.67, 95% confidence interval [CI]: 1.70–4.17), with similar elevated risk observed for sugemalimab (odds ratio [OR] = 2.45, 95% confidence interval [CI]: 1.52–3.95). Nivolumab was associated with increased odds of pneumonitis, although with unstable point estimate (odds Ratio [OR] = 2.69, 95% confidence interval [CI]: 0.64–11.35). Statistical heterogeneity was low (H statistics = 1.34). Atezolizumab and ipilimumab demonstrated modest or uncertain risk. Heterogeneity was low (I2 = 12%), and results were robust to sensitivity analyses. Higher pneumonitis rates were observed in combination regimens. Conclusions: Our analysis demonstrates that pneumonitis risk varies among ICPIs, with pembrolizumab and sugemalimab showing the highest odds. Although the absolute incidence is low, the potential severity of pneumonitis warrants vigilant monitoring. These results should guide clinicians in risk stratification and treatment planning, and they should support the development of standardized reporting criteria and further comparative research.

Coronary artery disease (CAD) remains the leading cause of cardiovascular morbidity and mortality worldwide, with plaque composition and morphology being as key determinants of disease progression and clinical outcomes. Accurate plaque characterization is essential for risk stratification and therapeutic decision-making, yet conventional image interpretation is limited by inter-observer variability and time-intensive workflows. Artificial intelligence (AI) models have emerged as a transformative tool for automated coronary plaque analysis across multiple imaging modalities. AI-driven models demonstrate high diagnostic accuracy for plaque detection, segmentation, quantification, and vulnerability assessment. Integration of AI-derived imaging biomarkers with clinical risk scores can further enhance prediction of major adverse cardiovascular events and supports personalized management. These advances position AI-enhanced imaging as a powerful adjunct for both invasive and non-invasive evaluation of CAD. Despite its promise, important barriers to widespread clinical adoption remain, including data heterogeneity, algorithmic bias, limited model transparency, insufficient prospective validation, regulatory challenges, and incomplete integration into clinical workflows. Addressing these challenges will be essential to ensure safe, generalizable, and cost-effective implementation of AI in routine cardiovascular care.

ABSTRACT Background Cardiac amyloidosis (CA) is frequently complicated by atrial fibrillation (AF), yet outcomes after left atrial appendage occlusion (LAAO) in this population remain poorly defined. Methods We conducted a retrospective TriNetX study of adults with AF undergoing LAAO, comparing patients with and without CA after 1:1 propensity matching. Outcomes were assessed using Kaplan–Meier analyses and Cox regression. Results Among 532 matched pairs, mortality and major adverse cardiovascular events were similar between groups, whereas major bleeding was higher in CA (HR 1.90). Conclusions LAAO yields comparable ischemic outcomes in CA, though bleeding risk is increased.

Background: Direct oral anticoagulants (DOACs) are now the preferred anticoagulant over vitamin K antagonists for patients with atrial fibrillation (AF) and venous thromboembolism (VTE). Variability in drug exposure raises concerns about bleeding and thrombotic events, highlighting the potential value of therapeutic drug monitoring (TDM). Methods: This systematic review and meta-analysis conducted a systematic search of PubMed, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov (from inception to May 2025) and identified studies reporting DOAC levels and clinical outcomes. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment (RoB 2.0, Newcastle–Ottawa Scale). Random-effects meta-analytical models generated pooled estimates, with meta-regression exploring potential sources of variability (DOAC type, drug levels) and exposure–response relationships. Results: Nineteen studies comprising 5770 patients were included in the review. The pooled event rates were 8% for major bleeding (95% CI: 0.05–0.11), 7% for thrombotic events (95% CI: 0.05–0.09), and 3% for mortality (95% CI: 0.03–0.04). Heterogeneity was substantial for bleeding and thrombotic events (I2 = 95.6% and 87.3%, respectively) but negligible for mortality (I2 = 0%). Meta-regression analyses showed no significant association between mean DOAC concentration and either major bleeding (β = −0.00021, p = 0.35, Adj R2 ≈ 0%) or thrombotic events (β = 0.00005, p = 0.78, Adj R2 ≈ 0%), indicating that variations in measured plasma levels did not meaningfully explain event rate differences across studies. Conclusions: In this systematic review and meta-analysis, measured DOAC concentrations show limited and inconsistent association with clinical outcomes. While the present synthesis does not demonstrate a statistically robust linear correlation between DOAC plasma concentrations and adverse outcomes, it highlights the multifactorial determinants of bleeding and thrombosis risk underscores the potential value of selective TDM in individualized care. Further prospective, standardized studies are needed to define clinically actionable thresholds and to validate TDM-guided strategies that optimize the delicate balance between safety and efficacy in DOAC therapy.

Abstract Aims Obesity, particularly visceral adiposity, is a key driver of cardiovascular mortality (CVM), yet conventional measures such as body mass index (BMI) inadequately capture fat distribution. The Body Roundness Index (BRI) is a novel anthropometric measure integrating waist circumference and height to better reflect body shape and visceral fat. This study examined the association between BRI and CVM in U.S. adults and across sociodemographic subgroups. Methods and results We analysed data from 31 351 adults (median age 43 yrs, 50% females) aged ≥20 years in NHANES 1999–2018, excluding those with prior cardiovascular disease or cancer. BRI was computed using a validated equation and categorized into quintiles (Q3 as reference). The primary outcome was CVM; secondary outcomes included all-cause, heart disease, and cerebrovascular mortality. Weighted Cox proportional hazards and restricted cubic spline (RCS) models evaluated associations after adjustment for demographic, behavioural, and clinical factors. Subgroup and sensitivity analyses tested consistency and effect modification. During a median follow-up of 10.1 years (IQR: 5.3–14.9 years), 883 cardiovascular deaths occurred. In fully adjusted models, participants in the highest BRI quintile had a 54% higher risk of CVM (HR, 1.54; 95% CI, 1.13–2.08; P = 0.006) vs. Q3. This risk remained high even among those with normal BMI. RCS analysis indicated a modest U-shaped association. Stronger effects were observed among middle-aged adults (45–64 years) and those with higher educational attainment. Conclusion Higher BRI is independently associated with increased cardiovascular mortality, particularly among middle aged adults and those with normal BMI, underscoring its potential as a practical, noninvasive tool for cardiovascular risk stratification. Incorporating BRI into clinical and public health assessment may improve identification of individuals at elevated risk.

ABSTRACT Intraocular lymphomas, including vitreoretinal and choroidal lymphoma, can simulate the clinical presentation of other benign and malignant ocular diseases resulting in diagnostic delays. Multimodal imaging features can raise early clinical suspicion to support appropriate subspecialty referrals and treatment for patients affected by these conditions. This review synthesises current evidence on the diagnostic and prognostic value of characteristic imaging features of these rare malignancies. Findings are reviewed based on imaging modality, including fundus photography, optical coherence tomography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, and ultrasound. We emphasise discriminative biomarkers that heighten suspicion for either vitreoretinal or choroidal lymphoma, as well as key findings to discriminate between lymphoma and alternative diagnoses. We further describe longitudinal changes in multimodal imaging features that can facilitate tracking disease progression or treatment response. By consolidating modality‐specific findings, this review aims to facilitate early referral and accurate diagnosis of these rare malignancies.

Background: ALG13-CDG is an X-linked N-linked glycosylation disorder caused by pathogenic variants in the glycosyltransferase ALG13, leading to severe neurological manifestations. Despite the clear CNS involvement, the impact of ALG13 dysfunction on human brain glycosylation and neurodevelopment remains unknown. We hypothesize that ALG13-CDG causes brain-specific hypoglycosylation that disrupts neurodevelopmental pathways and contributes directly to cortical network dysfunction. Methods: We generated iPSC-derived human cortical organoids (hCOs) from individuals with ALG13-CDG to define the impact of hypoglycosylation on cortical development and function. Electrophysiological activity was assessed using MEA recordings and integrated with multiomic profiling, including scRNA-seq, proteomics, glycoproteomics, N-glycan imaging, lipidomics, and metabolomics. X-inactivation status was evaluated in both iPSCs and hCOs. Results: ALG13-CDG hCOs showed reduced glycosylation of proteins involved in ECM organization, neuronal migration, lipid metabolism, calcium homeostasis, and neuronal excitability. These pathway disruptions were supported by proteomic and scRNA-seq data and included altered intercellular communication. Trajectory analyses revealed mistimed neuronal maturation with early inhibitory and delayed excitatory development, indicating an E/I imbalance. MEA recordings demonstrated early network hypoactivity with reduced firing rates, immature burst structure, and shortened axonal projections, while transcriptomic and proteomic signatures suggested emerging hyperexcitability. Altered lipid and GlcNAc metabolism, along with skewed X-inactivation, were also observed. Conclusions: Our study reveals that ALG13-CDG is a disorder of brain-specific hypoglycosylation that disrupts key neurodevelopmental pathways and destabilizes cortical network function. Through integrated multiomic and functional analyses, we identify early network hypoactivity, mistimed neuronal maturation, and evolving E/I imbalance that progresses to compensatory hyperexcitability, providing a mechanistic basis for seizure vulnerability. These findings redefine ALG13-CDG as disorders of cortical network instability, offering a new framework for targeted therapeutic intervention.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide, with its prevalence continuing to rise due to an aging population and the increasing burden of cardiometabolic diseases. Advances in understanding HF pathophysiology—neurohormonal, inflammatory, and metabolic mechanisms—have led to significant improvements in diagnosis and management, emphasizing earlier detection and patient-centered approaches. Novel biomarkers have the potential to enhance risk assessment beyond traditional natriuretic peptides. Imaging advances can enhance structural and functional assessment, enabling more accurate phenotyping, disease characterization, and risk stratification. Recent advances and real-world data have been used to implement and optimize guideline-directed medical therapy (GDMT) for HF to reduce HF hospitalizations and cardiovascular mortality across the spectrum of HF etiologies. Adjunctive therapies are reserved for select patients with persistent symptoms or high-risk features despite optimal GDMT. Device- and transcatheter-based interventions include established and emerging technologies that address persistent symptoms, structural abnormalities, and hemodynamic abnormalities despite optimal GDMT, thereby expanding treatment options for high-risk patients. Collectively, these advancements highlight a paradigm shift toward precise, personalized approaches to HF management, thereby improving long-term outcomes across the spectrum of HF etiologies.