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Abstract Background Nearly 40,000 people in the U.S. experience recurrent pericarditis with up to 90% of cases having no identifiable cause, often making the journey to diagnosis arduous. Understanding the challenges that patients and health care professionals (HCP) face will help address gaps and barriers in patient diagnosis and care. In addition, the lack of U.S. based guidelines for recurrent pericarditis clinical care, coupled with the time lapse from the last published European guideline, has created an opportunity to discover workflow solutions for U.S. based healthcare professionals. Purpose The American Heart Association’s (AHA) Addressing Recurrent Pericarditis Initiative is a three-year effort utilizing a quality improvement approach to address gaps/barriers in patient care, educate HCPs, and develop patient education resources to improve diagnosis, treatment, and quality of life. To accomplish this, the lived experiences and challenges patients face on their journey to diagnosis was integrated into the qualitative research process. Methods To assess quality improvement opportunities, the AHA engaged HCPs with recurrent pericarditis experience from 15 diverse health systems to participate in a learning collaborative strategy for quality improvement and implementation to share successful strategies, provide input on professional education topics, and participate in process mapping. Data collection strategies include 1:1 consultations, quarterly learning collaborative calls, surveys and questionnaire completion. To assess patient education needs, the AHA Market Research Team held 1-hour video interviews with ten diverse patients. Results AHA-led HCP interviews produced process maps of clinical workflows and identified opportunities for standardization to improve clinical workflow and patient outcomes (Figure 1). From these data collection methods, preliminary results include care coordination across clinical settings, exploring treatment options, standardization of follow-up cadence, and provider awareness of misdiagnoses/underdiagnosis rates. The patient interviews revealed that there is a lack of symptom recognition, persistent rate of misdiagnosis, delay in accurate diagnosis and treatment, and discrepancies in diagnosis and treatment for various demographics including female and younger adult patients (Figure 2). Conclusion(s) In Year 2 of this three-year initiative, we will continue to refine identified areas of opportunities to improve patient outcomes by creating and disseminating educational materials and launch awareness campaigns, while also producing a national education series for HCPs that provide guidance for system-level quality improvement to emphasize consistency in care and reductions in health inequities. Key findings from this study highlight the care coordination involved in the treatment of patients with recurrent pericarditis and the need to provide multidiscipline educational approaches to achieve this goal.Figure. 1 Summary of care pathway Figure. 2 Summary of patient interviews

Post-COVID syndrome comprises persistent neuropsychiatric manifestations for more than 12 weeks after recovery from acute SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. Ferroptosis, an iron-dependent form of cell death with three hallmarks, iron dysregulation, antioxidant failure, and lipid peroxidation, seems to be involved in COVID-19/post-COVID-19 pathophysiology. Here, we administered the SARS-CoV-2 spike protein S1 subunit intranasally to K18-hACE2 transgenic mice and quantified ferroptotic marker protein expression in four brain regions (hippocampus, prefrontal cortex, cerebellum, and olfactory bulb) at 2, 6, and 12 weeks post-administration, alongside ultrastructural assessment by transmission electron microscopy (TEM) that was limited to the hippocampus and prefrontal cortex. Two-way ANOVA revealed region- and time-dependent modulation of iron-handling, antioxidant, and lipid peroxidation markers. In the hippocampus, FPN1 was significantly increased at 2 weeks, while TFR1 showed a time-dependent pattern without significant week-specific differences. In the prefrontal cortex, DMT1 significantly increased at 2 weeks, and GPx4 showed an overall treatment effect with a trend of increase at 6 weeks. The cerebellum exhibited early increases in FPN1 and GPx4 and a delayed increase in MDA-conjugated proteins. In the olfactory bulb, FPN1 increased at 12 weeks, with GPx4 showing an overall treatment effect and an early trend of decrease. TEM identified ferroptosis-consistent features in the hippocampus and prefrontal cortex at all time points. These findings suggest that spike protein exposure may be associated with time-dependent and brain-region-specific alterations of ferroptosis-related markers. These preliminary findings are based on a limited sample size, which needs further research to elucidate the clinical implication and to study the mechanism in more depth as well as future validation with pharmacological inhibitors.

Background and Aims: Cholangiocarcinoma (CCA) is a rare but aggressive malignancy with poorly understood genetic susceptibility. To date, genome-wide association studies (GWAS) investigating germline variants associated with CCA risk remain limited. We aimed to identify genetic risk loci for CCA and its clinical subtypes through comprehensive GWAS and post-GWAS analyses. Approach and Results: We conducted a GWAS of 2366 CCA cases and 11,750 controls of European ancestry. Genome-wide significant loci ( p <5×10 −8 ) were identified and further examined through fine-mapping, functional annotation, and HLA imputation. Subgroup analyses were conducted by CCA subtypes and primary sclerosing cholangitis (PSC) status. Cross-trait linkage disequilibrium score regression and Mendelian randomization were employed to investigate the shared genetic architecture and potential causal relationships with a diverse range of traits. We identified 1 new genome-wide significant variant, rs535777 (OR=1.44), near HLA-DRB1/DQA1 associated with CCA, and 2 variants associated with extrahepatic CCA: rs116224263 (OR=0.17) in LINC02506 at 4p15.1 and rs6914950 (OR=1.63) near HLA-DRB1/DQB1 . Stratified analyses revealed rs2395184 (OR=3.51) near HLA-DRA/DRB5 associated with PSC-related CCA, and rs142674434 (OR=2.98) in THSD7A at 7p21.3 associated with non-PSC-related CCA. HLA imputation uncovered new amino acid residues associated with disease risk. Cross-trait analyses identified shared genetic signals between CCA and anthropometric, lipidemic, lifestyle, and medical traits. Mendelian randomization supported putative causal associations for 12 traits with CCA or its subtypes. Conclusions: Our large-scale GWAS highlights new genetic variants and HLA-linked mechanisms underlying CCA susceptibility. Integrating multi-step post-GWAS approaches enhances understanding of CCA pathogenesis and may facilitate the development of risk biomarkers for early detection and precision prevention strategies.

Abstract Aims Heart failure (HF) continues to portend significant morbidity and mortality within the USA. Data regarding the efficacy of mineralocorticoid receptor antagonists (MRAs) in HF with preserved ejection fraction (HFpEF) remains unclear. Finerenone, a non-steroidal MRA, has demonstrated reduction in hospitalizations in this population. However, the comparative efficacy of different MRA classes in these patients remains elusive. Methods and results We conducted a retrospective observational cohort study using the TriNetX research network. We applied 1:1 propensity score matching (PSM) to compare patients with HFpEF initiated on finerenone vs. spironolactone. We examined 1-year risks of HF exacerbation, acute kidney injury (AKI), electrolyte derangements, and cardiovascular outcomes. We identified 254,417 patients with HFpEF and MRA use. After PSM, each cohort contained 491 patients. Analysis revealed that finerenone use was associated with a significantly lower risk of HF exacerbation (hazard ratio [HR] = 0.63 [95% confidence interval [CI]: 0.54, 0.74], P &lt; 0.001), all-cause mortality (HR = 0.38 [95% CI: 0.23, 0.64], P &lt; 0.001), and hypokalaemia (HR = 0.58 [95% CI: 0.40, 0.85], P = 0.001). The aforementioned results, along with a reduction in AKI risk, were statistically significant after stratified subgroup analysis by diabetes mellitus and chronic kidney disease. Conclusion In this large real-world HFpEF cohort, finerenone use was associated with lower risks of HF exacerbation and all-cause mortality compared with spironolactone. These observational findings are hypothesis-generating and warrant confirmation in randomized trials.

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 Diabetes mellitus is a prevalent global health issue, affecting approximately 14% of individuals as latest reported. Among its complications, diabetic peripheral polyneuropathy (DPN) is a major cause of morbidity, impacting up to half of patients with long-standing diabetes. Given the limitations of current diagnostic methods, there is an urgent need for reliable biomarkers for early detection and management of DPN. Neurofilament light chain (NFL), a structural neuronal protein, has been proposed as a potential biomarker due to its release into the blood and cerebrospinal fluid following axonal damage. This systematic review and meta-analysis aim to evaluate serum NFL levels in diabetic patients with and without polyneuropathy compared to healthy controls. Methods A systematic search was conducted in four databases: Web of Science, PubMed, Scopus, and Embase. Studies were included if they measured serum NFL levels in diabetic patients, with or without polyneuropathy, and compared these levels to healthy controls. The Newcastle-Ottawa Scale (NOS) and JBI Critical Appraisal tools were used for quality assessment. We performed a meta-analysis using Review Manager 5.4 version, and assessed heterogeneity through chi-square tests and I² statistics. Results Eight studies (n = 2980 participants, including 950 diabetic patients and 2030 healthy controls) met the inclusion criteria. Three studies specifically evaluated serum NFL levels in diabetic patients with polyneuropathy. Meta-analysis revealed significantly elevated serum NFL levels in diabetic patients compared to healthy controls. Similarly, diabetic patients with polyneuropathy exhibited higher NFL levels than healthy controls. However, due to the limited number of studies comparing diabetic patients with and without neuropathy, a definitive conclusion on NFL's specificity to DPN remains uncertain. Heterogeneity analysis showed a moderate to high variation among studies, with a slight reduction after sensitivity analysis. Conclusion This study highlights elevated serum NFL levels in diabetic patients, irrespective of polyneuropathy status, suggesting that diabetes itself may contribute to increased NFL release. However, due to limited studies assessing NFL in DPN, further research is required to clarify its role as a specific biomarker for DPN.

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.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

Enhancing stability is a crucial factor in selecting bioactive compounds in most applications, while encapsulation techniques have proven to be a promising solution.

Lay Summary This meta-analysis of 8 randomized controlled trials compares the effectiveness of using high-definition scopes with virtual chromoendoscopy vs dye chromoendoscopy for detecting dysplasia in inflammatory bowel disease patients. Overall, the odds of dysplasia detection were not significantly different between dye chromoendoscopy and virtual chromoendoscopy.