BACKGROUND:Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive, underdiagnosed cause of heart failure (HF). Diagnostic delays may increase cardiac injury at treatment initiation, but the relationship between delay and outcomes remains poorly defined. OBJECTIVES:The purpose of this study was to evaluate time from HF diagnosis to ATTR-CM diagnosis as a proxy for disease progression and its association with HF hospitalization (HFH) and mortality. METHODS:This retrospective cohort study used Medicare fee-for-service and Veterans Health Administration (VHA) data. We identified patients diagnosed with ATTR-CM between 2016 and 2022 using a validated algorithm based on diagnoses and medications. Time-to-diagnosis was defined as days between each patient's first HF diagnosis and first amyloid diagnosis. Using multivariable Cox models, we evaluated its association with death or HFH. RESULTS:We identified 7,770 Medicare beneficiaries and 2,557 Veterans with HF and ATTR-CM. Median age at diagnosis was 81 years in both cohorts (Medicare IQR: 76-86; VHA IQR: 74-87); women comprised 1,775 (22.8%) of Medicare and 13 (0.5%) of VHA patients. Median time-to-diagnosis was 494 days (IQR: 63-1,340) for Medicare and 490 days (IQR: 69-1,286) for VHA. After adjustment for sociodemographics, each 1-year delay was associated with a 7% increased risk of the primary outcome (Medicare HR: 1.07; 95% CI: 1.06-1.08; VHA HR: 1.07; 95% CI: 1.05-1.09). Results were similar after adjusting for comorbidities. CONCLUSIONS:Across 2 real-world populations, diagnostic delay in ATTR-CM is a clinically meaningful marker of disease progression, with longer delays associated with increased HFH and mortality.

Adipose tissue serves as a primary approach for soft tissue defect repair, but clinical regeneration remains limited by inadequate adipogenic capacity. While astaxanthin (AST) can ameliorate adipose dysfunction, the underlying mechanisms governing its pro-adipogenic activity remain elusive. Here, we developed an AST-loaded decellularized adipose tissue (DAT) hydrogel with the aim of boosting adipogenic potential. Subcutaneous implantation of DAT-AST hydrogel into rabbit inguinal fat pad defects significantly enhanced adipogenesis and tissue restoration. In human adipose-derived stem cells (ADSCs), astaxanthin significantly promoted the adipogenic differentiation by suppressing phosphorylation of RhoGDI1 at Ser174 - a newly identified AST-binding target. RhoGDI1 knockdown abolished AST-induced lipid accumulation and disrupted RhoGDI1 related signaling axis (RhoA/FAK/ERK1/2), demonstrating that RhoGDI1 dephosphorylation is essential for AST's pro-adipogenic action. Collectively, this work reveals a targetable pathway for adipose regeneration and establishes DAT as a promising delivery platform for AST therapeutics.

BACKGROUND:Despite strong evidence, adoption of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction remains suboptimal. The Get With The Guidelines-Heart Failure (GWTG-HF) program was designed to close gaps in care. We evaluated whether hospital participation in GWTG-HF was associated with greater GDMT intensity and improved outcomes. METHODS:We conducted a retrospective analysis (2013-2021) of Medicare beneficiaries with part A and part D hospitalized with heart failure with reduced ejection fraction. Using a multiple baseline time series design, we compared changes in GDMT and outcomes before and after GWTG-HF enrollment with hospitals that never participated. Coprimary outcomes were a 90-day postdischarge GDMT score under a parallel and nonparallel slopes model. Secondary outcomes included class-specific medication fills, achievement of ≥50% target doses, and 30-day, 90-day, and 1-year all-cause and HF readmission and mortality. Mortality and first HF readmission were also evaluated using Cox proportional hazards models. We adjusted for baseline hospital performance, patient characteristics, and temporal trends. RESULTS:Among 1274 863 Medicare beneficiaries hospitalized for heart failure with reduced ejection fraction, 53.5% were treated at hospitals that never participated in GWTG-HF and 9.6% at GWTG-HF hospitals. Unadjusted median GDMT scores increased from 3.0 in both groups to 4.0 in nonparticipating hospitals and 4.5 in GWTG-HF hospitals at 90 days (P<0.001). Hospital enrollment was associated with a higher 90-day GDMT score (+0.15 points [95% CI, 0.12-0.20]; P<0.001) and greater use of β-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists but not angiotensin receptor-neprilysin inhibitors. GWTG-HF participation was associated with lower all-cause mortality at 30 days (odds ratio, 0.95 [95% CI, 0.92-0.98]) and 1 year (0.97 [95% CI, 0.95-0.1.00]; both P<0.05). Mortality differences were attenuated and no longer significant in the nonparallel slopes model. CONCLUSIONS:Hospital participation in GWTG-HF was associated with modest but significant improvements in postdischarge GDMT intensity, supporting the value of quality improvement initiatives to address persistent treatment gaps in heart failure with reduced ejection fraction.

INTRODUCTION:The development of small-diameter vascular grafts remains clinically challenging. Decellularized small intestinal submucosa (SIS) is a promising candidate biomaterial for vascular grafts owing to the satisfactory biocompatibility and low immunogenicity. Nevertheless, its efficacy remains limited, primarily by thrombosis or dilation-induced failure. OBJECTIVES:This study presents a novel SIS / Poly (L-Lactide-co-caprolactone) (PLCL) composite graft co-functionalized with heparin and human adipose-derived stem cell exosomes (HASCs-Exo) , aiming to meet the standards of blood vessel replacement. METHODS:In this study, we fabricated SIS/PLCL hierarchical fibrous grafts via electrospinning, followed by a dual-functionalization strategy to load heparin and HASCs-Exo. The grafts were then evaluated in vitro and in vivo. RESULTS:Comprehensive in vitro characterization revealed that the composite graft possessed optimal surface topography, enhanced tensile strength, sustained in situ release of HASCs-Exo, and favorable hemocompatibility. In a rat subcutaneous implantation model, the HASCs-Exo-modified SIS/PLCL grafts exhibited significantly improved biocompatibility, as evidenced by reduced inflammatory cell infiltration compared to unmodified SIS/PLCL grafts. In rabbit carotid artery replacement experiments, HASCs-Exo-modified SIS/PLCL grafts demonstrated superior performance, evidenced by a higher patency rate on Doppler ultrasound and enhanced endothelialization confirmed by CD31 and eNOS immunofluorescent staining. Mass spectrometry and Western blot showed that ATP2B1 was enriched in HASCs-Exo. Mechanistic studies further demonstrated that HASCs-Exo promoted endothelial cell functionality by upregulating eNOS and VEGF through ATP2B1. CONCLUSION:This study presents a novel strategy that combinines HASCs-Exo with SIS/PLCL grafts to fabricate functional small-diameter vascular grafts, achieving dual optimization of mechanical integrity and endothelialization capacity.

Importance:Timely diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) is critical for early treatment to reduce morbidity and mortality, yet the timeliness of contemporary ATTR-CM diagnosis remains poorly understood. Objective:To describe the time from incident heart failure (HF) diagnosis to ATTR-CM diagnosis and identify predictors of delayed diagnosis among Medicare beneficiaries. Design, Setting, and Participants:This was a cohort study using US Medicare fee-for-service data from January 2016 to December 2022. Medicare fee-for-service beneficiaries with HF and ATTR-CM were included. Data were analyzed from November 2024 to July 2025. Exposures:HF diagnosis with ATTR-CM diagnosis following HF diagnosis or within 1 year prior. Main Outcomes and Measures:The primary outcome was time to ATTR-CM diagnosis, measured as the number of days between each patient's first HF diagnosis and first ATTR-CM diagnosis. Multivariable logistic regression assessed demographic, clinical, and socioeconomic factors associated with delayed ATTR-CM diagnosis (defined as >6 months from HF diagnosis to ATTR-CM diagnosis). Results:A total of 7770 patients with HF and ATTR-CM were identified in the Medicare dataset. The median (IQR) age at the time of ATTR-CM diagnosis was 81 (76-86) years; 5995 enrollees (77%) were men. The median (IQR) time from HF diagnosis to ATTR-CM diagnosis was 494 (63-1340) days. For the 6175 patients with a loop diuretic prescription before ATTR-CM diagnosis, the median (IQR) time between initial loop prescription and ATTR-CM diagnosis was 840 (252-1768) days. After adjustment, older age (odds ratio [OR], 0.68; 95% CI, 0.63-0.74), history of atrial fibrillation (OR, 0.39; 95% CI, 0.33-0.49), and carpal tunnel syndrome (OR, 0.85; 95% CI, 0.74-0.97) were associated with lower odds of delayed diagnosis. Female sex (OR, 1.28; 95% CI, 1.13-1.45), a history of aortic stenosis (OR 1.39; 95% CI, 1.20-1.62), chronic obstructive pulmonary disease (OR, 1.18; 95% CI, 1.03-1.34), coronary artery disease (OR, 1.26; 95% CI, 1.13-1.40), diabetes (OR, 1.21; 95% CI, 1.07-1.37), and hypertension (OR, 1.28; 95% CI, 1.13-1.45) were associated with higher odds of delayed diagnosis. Conclusions and Relevance:There were substantial delays between incident HF and diagnosis of ATTR-CM found in this study. Female sex and having a history of aortic stenosis, coronary artery disease, diabetes, hypertension, or chronic obstructive pulmonary disease, which are each associated with cardiomyopathy and breathlessness, were associated with delayed diagnosis. These findings highlight the need for a heightened index of suspicion for ATTR-CM in patients with other possible etiologies of cardiomyopathy or HF symptoms.

Funding This work was funded by Novartis. Background/Synopsis Prediction of those at high risk of atherosclerotic cardiovascular disease (ASCVD) is crucial for guiding primary prevention. The Predicting Risk of cardiovascular disease Events (PREVENT) equation is the latest risk prediction model for ASCVD, but has not yet been compared to the prior Pooled Cohort Equations (PCE) in the Veteran's Health Administration (VA), the nation's largest integrated health system. Objective/Purpose To compare the discrimination and calibration of the PREVENT equation and the PCE to predict ASCVD risk in the VA. Methods This was a retrospective analysis of Veterans ages 30 to 79 years old. Veterans were included if they had no diagnosis of ASCVD event (prior MI, stroke, revascularization) before January 1, 2012, had all required PREVENT and PCE variables in the VA electronic health record, and had at least one primary care visit between 2010-2011. The outcome was ASCVD event, a composite of coronary heart disease death, non-fatal MI, or fatal or non-fatal stroke from 2012-2021. Cause of death was ascertained by death certificate data. Non-fatal stroke and MI were identified from the principal diagnosis of MI or stroke during any hospitalization. Discrimination of the PCE and PREVENT equations to predict ASCVD risk was evaluated with Harrell's C-statistic for a time-to-event model. Calibration of the PCE and PREVENT equations was evaluated using calibration plots of observed versus predicted 10-year ASCVD risk, with calibration slope calculated by dividing the observed by predicted risk (ideal calibration = 1.0). Results 2,552,340 Veterans met inclusion criteria. The median age was 61, with 7.5% female, 18.3% Black, and 5.0% Hispanic participants. The mean 10-year ASCVD predicted risk was 13.1% with the PCE and 6.6% with the PREVENT equation. We observed 212,942 (0.9% per year) ASCVD events over the 10-year follow-up period. The discrimination of the PREVENT equation was greater than the PCE (C = 0.714 vs. C = 0.686, p < 0.05). The calibration of the PREVENT equation was superior to the PCE (calibration slope 1.04 vs. 0.36, Figure 1). Conclusions Among a primary prevention cohort of VA patients, the discrimination of the PREVENT equation was fair, and the calibration was excellent. Both the discrimination and calibration of PREVENT were superior to the PCE at the VA. The PREVENT equation markedly improves the ability to accurately predict 10-year ASCVD risk in a Veteran cohort.

Adipose tissue regeneration has emerged as a transformative strategy for addressing soft-tissue defects resulting from trauma, oncologic resection, and burn injuries, leveraging adipose tissue's dual role as a dynamic endocrine organ that regulates systemic metabolism. Decellularized adipose tissue (DAT) scaffolds hold significant promise in adipose tissue regeneration due to their unique preservation of pro-adipogenic and structurally preserved extracellular matrix (ECM) components. However, their clinical translation faces bottlenecks, including inadequate compressive modulus, unpredictable biodegradation kinetics and limited neovascularization capacity. This review critically synthesizes methodological advancements in DAT processing, systematically evaluating protocol efficacy in DAT preservation versus immunogenic residue elimination while assessing their translational potential as implant materials. Building upon methodological innovations in DAT composite hydrogel engineering since 2013, this overview concurrently elucidates mechanobiological regulation paradigms governing hydrogel functionality and evaluates crosslinking strategies that optimize structural fidelity. Critical challenges and emerging frontiers are also discussed. The current comparative assessment of material performance metrics may offer new insights for further investigation and translational optimization in DAT based composite hydrogels for repair of soft tissue defects.

Background: Timely diagnosis of transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is important for early treatment, which can improve outcomes. Aim: To characterize the clinical impact of delayed diagnosis of ATTR-CM in real-world populations. Methods: This retrospective cohort study used Medicare fee-for-service and Veterans Health Affairs (VHA) data. We identified patients with ATTR-CM diagnosed between 2016 and 2022. The time-to-diagnosis was defined as the number of days between each patient’s first heart failure (HF) diagnosis and their first ATTR-CM diagnosis. Using multivariable Cox models, we evaluated the association between the time-to-diagnosis and the composite primary outcome of all-cause mortality or heart failure hospitalization (HFH). Secondary outcomes were HFH, all- cause mortality and cardiovascular death (VHA cohort only). Results: We identified 7,770 Medicare beneficiaries and 2,557 Veterans with HF and ATTR-CM. The mean age at the time of ATTR-CM diagnosis was 81 years (interquartile range [IQR] 76, 86) for the Medicare cohort and 81 years in the VHA (IQR 74, 87). This included 1,775 (22.8%) women in the Medicare cohort and 13 (0.5%) in the VHA cohort. The median time-to-diagnosis for ATTR-CM was 494 days (IQR 63, 1340) in the Medicare cohort and 490 days in the VHA (IQR 69, 1286). After adjustment for sociodemographics, diagnostic delays of 6 months to 2 years were associated with a 41% increased risk for the primary outcome in the Medicare cohort (HR 1.41; CI 1.30-1.54) and a 66% increased risk in the VHA cohort (HR 1.66;CI 1.49-1.86) compared with a time-to-diagnosis < 6 months. The results were similar after adjusting for clinical comorbidities. After adjustment, each one-year delay in diagnosis was associated with a 7% increased risk of the composite outcome for both cohorts (Medicare HR 1.07; 95% CI 1.06-1.08 and VHA HR 1.07; 95% CI 1.05-1.09). Each one-year delay was associated with a 7-8% increase in risk of HFH (Medicare HR 1.08; CI 1.06, 1.09 and VHA HR 1.07; 1.04, 1.09) and a 7-8% increase in risk of death (Medicare HR 1.07; CI 1.06-1.09 and VHA HR 1.08; 1.06, 1.10). Conclusions: The significant delays between incident HF and diagnosis of ATTR-CM are associated with an increased risk of heart failure hospitalization and mortality. This highlights the critical need for education around ATTR-CM and novel approaches to shorten the diagnostic delay, initiate early treatment and improve outcomes for patients with ATTR-CM.

Background: Documentation of atrial fibrillation (AF)-associated stroke risk with the CHA 2 DS 2 -VASc score is an AHA/ACC clinical performance measure for outpatient AF management. Patterns of stroke risk documentation for patients with incident AF are not well-characterized. Research Question: What are rates and predictors of CHA 2 DS 2 -VASc/CHADS 2 (CHADS) documentation for patients with incident AF across the Veterans Health Administration (VA)? Methods: We developed a text searching algorithm to assess clinical notes for CHADS documentation. We included patients with outpatient AF diagnoses from 1/2022-9/2023 with primary care or cardiology visits within 90 days. We assessed rates of CHADS documentation in primary care/cardiology notes. We identified predictors of documentation using a multivariable logistic regression model including patient age, sex, race/ethnicity, rurality, distance from care, comorbidities, number of visits, diagnosis year, telehealth use, cardiology care use, and facility random intercepts. Results: There were 36,924 patients with new AF with 80,585 visits at 125 VA medical centers. Average age was 74 with 2.9% female, 78% White, 12% Black/African American, and 36% rural/highly rural. Across medical centers, the median rate of CHADS documentation within 90 days was 14.6% (range 0-40.8%) (Figure 1). In the adjusted analysis, CHADS documentation was less likely for patients who were older [age 70-77 adjusted odds ratio (aOR) 0.86 (95% CI 0.80-0.92) and >77 aOR 0.75 (0.70-0.81) vs <70], Black/African American [aOR 0.84 (0.76-0.94) vs White], and rural or highly rural [aOR 0.91 (0.84, 0.99) and aOR 0.80 (0.66, 0.96) vs urban] and for those with certain comorbidities (chronic kidney disease, coronary artery disease, heart failure, and peripheral artery disease) and telehealth visits [aOR 0.89 (0.82, 0.95)]. Documentation was more likely for those with more visits, diagnosed in 2023 [aOR 1.15 (1.08, 1.23) vs 2022], and seen by cardiology [aOR 9.14 (8.50, 9.82)] (Figure 2). Conclusions: Though CHA 2 DS 2 -VASc documentation is a performance measure for AF management, we found low documentation rates in clinical notes with significant variation across VA medical centers. Documentation rates were lower for patients who were Black/African American, lived in rural areas, received telehealth care, and whose age/comorbidities resulted in higher scores. Interventions are needed to promote high quality AF care across patient groups and care modalities.

BackgroundTelehealth is a potential tool to alleviate geographic clinician shortages, but there are limited data regarding current telehealth use for common cardiology conditions, including atrial fibrillation (AF). ObjectiveWe aimed to evaluate variation in telehealth use in primary care and cardiology clinics for patients with incident AF in the Veterans Health Administration. MethodsWe included patients diagnosed with AF in the outpatient setting between January 2022 and September 2023. We assessed the association between any video visit and any telehealth use (including phone) for primary care or cardiology visits within 90 days of an AF diagnosis, adjusting for selected patient- and facility-level characteristics using Bayesian logistic regression with facility-level random intercepts. We evaluated facility variation in video visit and telehealth use with the median odds ratio (MOR). ResultsOur cohort included 36,929 patients with 80,596 visits across 125 facilities. Of the 63,835 primary care visits, 2088 (3.27%) were delivered via video and 13,403 (21%) via telehealth; of the 16,761 cardiology visits, 323 (1.93%) were delivered via video and 3288 (19.62%) via telehealth. On average, the mean age of the patients was 73.6 (SD 10.9) years; 2.91% (1075/36,929) were female; 77.71% (28,698/36,929) were White. In adjusted analyses, older age was associated with lower use of video visits for both primary and cardiology care and lower use of any telehealth for cardiology care (eg, adjusted odds ratio [AOR] 0.61, 95% credible interval [CrI] 0.42-0.85 for the use of video cardiology care for patients aged above 77 years). Living more than 65 km from the care site was associated with increased use of both video and any telehealth for primary and cardiology care (eg, AOR 1.91, 95% CrI 1.21-3.00 for video cardiology care); however, living in a rural location was associated with lower odds of using video or any telehealth for primary care (video: AOR 0.73, 95% CrI 0.64-0.84; telehealth: AOR 0.89, 95% CrI 0.83-0.96). There was marked variability across facilities in the use of video care (range 0%-17.4% of visits for cardiology care; 0%-12.5% for primary care) and telehealth (range 0%-82.6% for cardiology care; 3.8%-61.6% for primary care). The facility-level adjusted MOR for video care use was 1.97 (95% CrI 1.77-2.24) for primary care and 4.95 (95% CrI 3.39-7.98) for cardiology care. Similarly, the adjusted MOR for any telehealth use was 1.79 for primary care (95% CrI 1.65-1.96) and 2.61 for cardiology care (95% CrI 2.25-3.13). ConclusionsFollowing an incident AF diagnosis, telehealth may increase access to primary and cardiology care for veterans living at a distance, but its use remains lower for older patients and those in rural areas. There was substantial variation in telehealth use across facilities, which was not explained by differences in patient and facility characteristics. Standardizing telehealth use across Veterans Health Administration facilities may improve access to AF care.

This study comprehensively examines the global burden of atrial fibrillation and atrial flutter (AF/AFL) attributable to high alcohol use from 1990 to 2021, analyzing temporal trends, regional disparities, and sociodemographic determinants using data from the Global Burden of Disease Study 2021 (GBD 2021). We extracted GBD 2021 estimates on deaths, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) for AF/AFL due to high alcohol use across 204 countries. Joinpoint analysis and age-period-cohort (APC) modeling were employed to assess temporal trends and disentangle age, period, and cohort effects. In 2021, AF/AFL attributable to high alcohol use contributed to 11,908 deaths (95

BACKGROUND:Dronedarone and sotalol are antiarrhythmic drugs (AADs) recommended in similar populations per atrial fibrillation (AF) guidelines; however, comparative safety data are limited. OBJECTIVES:The goal of this study was to assess the safety of dronedarone vs sotalol for treatment of AF in AAD-naive patients. METHODS:This was a prespecified noninterventional meta-analysis of 4 retrospective observational cohort studies from 4 databases (Optum Clinformatics Data Mart, Merative MarketScan, Veterans Health Administration Electronic Health Record, and the Swedish National Patient Register) conducted by using one master protocol. Each analysis emulated the target trial using an active comparator (dronedarone vs sotalol), new user design with an as-treated approach. Primary outcomes were tested hierarchically for dronedarone vs sotalol: first for statistical significance of cardiovascular (CV) hospitalization, and then for statistical significance of ventricular arrhythmias. Propensity score matching (PSM) was used for confounding control, and negative control outcomes were used to assess residual confounding. Outcomes were evaluated by using Cox proportional hazards regression; meta-analysis was performed by using fixed effects models. RESULTS:The dronedarone and sotalol cohorts were well balanced within databases before and after PSM (after PSM mean age range: 62.5-70.9 years; mean CHA2DS2-VASc score range: 1.81-3.15). Negative control outcomes exhibited little-to-no evidence of residual confounding. Meta-analysis found significantly lower rates of CV hospitalization (pooled HR: 0.91; 95% CI: 0.85-0.97) and ventricular arrhythmias (pooled HR: 0.77; 95% CI: 0.69-0.85) with dronedarone vs sotalol. CONCLUSIONS:In this retrospective meta-analysis, dronedarone exhibited significantly lower rates of CV hospitalization and ventricular arrhythmias compared with sotalol. These findings provide real-world evidence to support selection of the most appropriate first-line AAD for rhythm control in patients with AF.

Funding This study was funded by Novartis. Background/Synopsis The Predicting Risk of cardiovascular disease Events (PREVENT) equation predicts atherosclerotic cardiovascular disease (ASCVD) events, incorporating several new variables compared to the prior Pooled Cohort Equations (PCE). Elevation of lipoprotein(a) [Lp(a)] is linked to increased risk of ASCVD. It is unknown whether Lp(a) is associated with ASCVD risk after adjustment for contemporary risk models. Objective/Purpose To evaluate if Lp(a) is independently associated with ASCVD risk after adjustment for the PCE and PREVENT ASCVD risk models among a cohort from the Veteran's Health Administration (VA). Methods This was a retrospective cohort study of Veterans ages 30-79 years old. Patients were included if they had no prior MI, stroke, or revascularization before January 1, 2012, had all required PREVENT and PCE variables, had a primary care visit between 2010-2011, and at least 1 Lp(a) measurement in their lifetime. The outcome was ASCVD event, a composite of coronary heart disease death, non-fatal MI, or fatal or non-fatal stroke from 2012-2021. To assess the independent association between Lp(a) and ASCVD risk, Lp(a) was modeled in Cox survival models with adjustment for PCE and PREVENT. We calculated the discrimination of the PCE and PREVENT with and without Lp(a) to predict ASCVD events using Harrell's C-statistic. Results 9,302 Veterans met inclusion criteria. The median age was 57, with 11.4% female, 19.6% Black, and 5.3% Hispanic. The mean 10-year ASCVD predicted risk was 10.9% with the PCE and 5.5% with the PREVENT equation. We observed 852 (0.9% per year) ASCVD events over 10 years follow-up. The hazard ratio (HR) for 1 standard deviation (SD) increase in the PCE was 1.53 (1.44-1.63) and 1.65 (1.56-1.75) for PREVENT. When adjusting for PCE and PREVENT, the hazard ratio for Lp(a) level 35 - 50 mg/dL was 0.92 (0.71-1.21) and 0.88 (0.67-1.15) respectively, for Lp(a) level 50-100 mg/dL was 1.02 (0.85-1.23) for both models, and for Lp(a) level > 100 mg/dL was 1.34 (1.06-1.70) for both models. The model discrimination was modestly improved with inclusion of Lp(a) for PREVENT (C = 0.662 vs. 0.660, p < 0.05) and PCE (C = 0.627 vs. 0.624, p < 0.05). Conclusions Elevated Lp(a) level was significantly associated with ASCVD events after adjustment for contemporary risk prediction equations. Lp(a) had a small, but significant effect on both PCE and PREVENT model discrimination. Lp(a) can be used to improve risk stratification for individuals at high risk of ASCVD when added to contemporary risk models.

Abdominal aortic aneurysm (AAA) is a progressive aortic disease featured by inflammation, vascular smooth muscle cells (VSMCs) depletion, and elastin degradation. MicroRNAs were related to AAA formation, which bring the approach for precise and targeted drug therapy for AAA. We developed a new strategy based on decellularized adipose matrix (DAM) hydrogel immobilized on the adventitia to release antagomir150-5p for preventing the AAA development. In this study, Cacl2-induced and elastase-induced rat AAA models were established. We found that miR-150-5p was upregulated while Notch3 was downregulated in two rat AAA models. Then a mold was designed for shaping hydrogel for miR-150-5p delivery around the abdominal aorta. Interestingly, inhibition of miR-150-5p in AAA by local release of antagomir150-5p with DAM hydrogel significantly prevented aortic dilation and elastin degradation. Moreover, inflammatory cell infiltration, the expression of inflammatory cytokines (MCP-1, TNF-α, and NF-κB (p65)), and matrix metalloproteinases (MMP-2, MMP-9) were increased while Notch3 and α-SMA were decreased in rat AAA, which can be attenuated by antagomir150-5p treatment. In VSMCs with TNF-α stimulation, we further demonstrated that inhibition of miR-150-5p downregulated NF-κB (p65), MMP-2, and MMP-9 and upregulated elastin via Notch3. This work presents a translational potential strategy for AAA repair via DAM hydrogel sustained release of antagomir150-5p, and highlights the mechanism of miR-150-5p during AAA progression by regulating Notch3.

Following peripheral nerve anastomosis, the anastomotic site is prone to adhesions with surrounding tissues, consequently impacting the effectiveness of nerve repair. This study explores the development and efficacy of a decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair. Firstly, the entire epineurium was extracted from fresh porcine sciatic nerves, followed by a decellularization process. The decellularization efficiency was then thoroughly assessed. Subsequently, the decellularized epineurium underwent proteomic analysis to determine the remaining bioactive components. To ensure biosafety, the decellularized epineurium underwent cytotoxicity assays, hemolysis tests, cell affinity assays, and assessments of the immune response following subcutaneous implantation. Finally, the functionality of the biofilm was determined using a sciatic nerve transection and anastomosis model in rats. The result indicated that the decellularization process effectively removed cellular components from the epineurium while preserving a number of bioactive molecules, and this decellularized epineurium was effective in preventing adhesion while promoting nerve repairment and functional recovery. In conclusion, the decellularized epineurium represents a novel and promising anti-adhesion biofilm for enhancing surgical outcomes of peripheral nerve repair.

Autologous nerve grafts have been considered the gold standard for peripheral nerve grafts. However, due to drawbacks such as functional loss in the donor area and a shortage of donor sources, nerve conduits are increasingly being considered as an alternative approach. Polymer materials have been widely studied as nerve repair materials due to their excellent processing performance. However, their limited biocompatibility has restricted further clinical applications. The epineurium is a natural extra-neural wrapping structure. After undergoing decellularization, the epineurium not only reduces immune rejection but also retains certain bioactive components. In this study, decellularized epineurium (DEP) derived from the sciatic nerve of mammals was prepared, and a bilayer nerve conduit was created by electrospinning a poly (l-lactide-co-ε-caprolactone) (PLCL) membrane layer onto the outer surface of the DEP. Components of the DEP were examined; the physical properties and biosafety of the bilayer nerve conduit were evaluated; and the functionality of the nerve conduit was evaluated in rats. The results demonstrate that the developed bilayer nerve conduit exhibits excellent biocompatibility and mechanical properties. Furthermore, this bilayer nerve conduit shows significantly superior therapeutic effects for sciatic nerve defects in rats compared to the pure PLCL nerve conduit. In conclusion, this research provides a novel strategy for the design of nerve regeneration materials and holds promising potential for further clinical translation.