ObjectivesThis study aimed to identify multidimensional factors associated with hypertension self-management and examine candidate self-care support domains to inform the development of a person-centered nursing-based self-care bundle.MethodsA cross-sectional study was conducted among 152 patients with hypertension aged 40-59 years in primary healthcare centers in Bali, Indonesia, using multistage random sampling. Data were collected using researcher-developed questionnaires informed by established instruments, theories, and previous studies, and preliminarily tested for validity and reliability, measuring patient, family, socio-cultural, healthcare service, candidate self-care support domains, and self-management ability. Partial least squares structural equation modeling was used to examine associations among constructs.ResultsPatient factors were associated with candidate self-care support domains (β=0.593, p<0.001) and self-management ability (β=0.379, p<0.001). Family, sociocultural, and healthcare-service factors were associated with candidate self-care support domains but not directly with self-management ability. Candidate self-care support domains were also associated with self-management ability (β=0.481, p<0.001).ConclusionsThe findings provide a cross-sectional needs-assessment foundation for developing a person-centered nursing-based integrated self-care bundle for hypertension self-management. Future studies should refine the bundle through expert validation and test its feasibility and effectiveness using intervention designs.

ObjectiveTo investigate adherence to four direct oral anticoagulants (DOACs) and its influencing factors in patients with non-valvular atrial fibrillation (NVAF), providing evidence for strategies to improve adherence.MethodsA retrospective cohort study included NVAF patients initiating DOAC therapy at a tertiary hospital (January 2016-November 2023). Adherence was evaluated using the proportion of days covered (PDC), with PDC ≥ 0.8 defined as good adherence. Adherence levels for dabigatran, rivaroxaban, apixaban, and edoxaban were compared at 3, 6, 9, and 12 months. Logistic regression identified factors influencing 1-year adherence, assessing the impact of initiation year and the National Volume-Based Drug Procurement (NVBP) policy.ResultsA total of 1,150 NVAF patients were enrolled (dabigatran: n = 401; rivaroxaban: n = 656; apixaban: n = 18; edoxaban: n = 75),In this main cohort, overall adherence progressively declined, with only 40.78% achieving PDC ≥ 0.8 at 1 year. Significant differences existed among groups (P<0.001). Dabigatran demonstrated the highest 1-year adherence (53.62%), followed by rivaroxaban (34.91%), apixaban (27.78%), and edoxaban (26.67%). Compared with dabigatran, rivaroxaban (OR=0.47) and edoxaban (OR=0.33) were independently associated with poorer adherence. Age ≥75 years (OR=0.62) and self-pay (OR=0.49) were risk factors for poor adherence, while diabetes (OR=1.48) and prior stroke (OR=1.48) predicted better adherence. Patients initiating therapy in 2017 showed the highest adherence. Post-NVBP, generic dabigatran adherence exceeded the original formulation at 6 months (P=0.038), but this difference disappeared at 1 and 2 years.ConclusionDOAC adherence among NVAF patients is suboptimal and decreases over time. Among the four DOACs, dabigatran was associated with the highest adherence. Elderly (≥75 years) and self-paying patients are at higher risk of poor adherence, whereas those with diabetes or stroke history show better adherence. The NVBP policy improves adherence short-term, but long-term effects are limited. Targeted interventions are necessary for high-risk populations.

Despite an overall decline in incidence rate, the burden of stroke may be rising in young adults. We aimed to characterize the incidence rates, 30-day case fatality rates (CFRs), and the burden of stroke risk factors over time in young adults in a representative population-based study of stroke.

Using validated methods, hospitalized stroke cases in a 5-county region were ascertained and adjudicated by stroke-trained physicians in 6 study periods: July 1993-June 1994 and calendar years 1999, 2005, 2010, 2015, and 2020. Stroke in the young was defined as those occurring among individuals who were aged 20-54 years. Incidence rates were generated using US Census data standardized to the 2010 population, and trends were tested with linear regression. Temporal trends in 30-day CFR were evaluated with logistic regression after adjusting for age, race, and sex.

Across all study periods, there were 2,076 first-ever strokes in young adults. Hypertension, diabetes, atrial fibrillation, and substance use were more common over time (p < 0.001). The stroke incidence rate increased in young adults over time (33.90 cases/100,000 person-years in 1993/4 to 62.18 cases/100,000 person-years in 2020, trend p = 0.04), while declining in older adults (618.78 cases/100,000 person-years in 1993/4 to 453.04 cases/100,000 person-years in 2020, trend p = 0.02). The rise in stroke incidence appeared driven by ischemic stroke, with an almost doubled incidence rate of 23.8 cases/100,000 person-years in 1993/4 to 47.3 cases/100,000 person-years in 2020 (trend p = 0.02). There was a modest decline in the 30-day CFR in young adults (11.7% in 1993/4 to 9.4% in 2020, trend p = 0.002), driven by intracerebral hemorrhage (27.5% in 1993/4 to 21.2% in 2020, trend p = 0.03) and subarachnoid hemorrhage (27.9% in 1993/4 to 18.6% in 2020, trend p = 0.09).

The incidence of stroke in young adults is rising over time, while the CFR simultaneously declines. This coincides with a rise in both traditional vascular risk factors and substance use.

Long-term risk of dementia after TIA remains poorly characterized, despite a known impact on cognition. We aimed to quantify the rate, relative risk, and time course of incident dementia after TIA compared with a matched reference population (controls) and individuals with stroke.

We conducted a population-wide cohort study using linked administrative health data for the province of Ontario, Canada (2002-2022). Adults with a first TIA were identified from emergency department visits or hospital admissions and followed from 90 days after the index event. Individuals with prior dementia, prior stroke, early death, or long-term care admission were excluded. Patients with TIA were matched to population controls on age, sex, neighborhood-level deprivation, rurality, and vascular comorbidities. Patients with TIA were also matched to those with first stroke. Incident dementia was ascertained using a validated algorithm based on hospital diagnoses, physician claims, and dementia-specific medications. Cause-specific and subdistribution hazard models accounting for competing risk of death were used for 1-, 5-, and 10-year risk of dementia, with time-varying analyses.

Among 113,081 matched patients with TIA (mean age 70 years; 50% female), dementia was diagnosed in 19.3% over a mean follow-up of 7.11 years (SD 5.16). Dementia rates after TIA were consistently higher than in matched controls across all time horizons (overall rate 2.71 vs 2.03 per 100 person-years). The hazard ratio for dementia after TIA was highest within the first year (hazard ratio [HR] 1.75, 95% CI 1.66-1.85) and remained elevated over 20 years of follow-up (overall HR 1.34, 95% CI 1.31-1.36). Compared with stroke, the hazard of dementia was lower after TIA early on (1-year HR 0.67, 95% CI 0.64-0.70) but converged and became similar after 5 years of follow-up. Dementia incidence substantially exceeded stroke incidence, and adjustment for incident stroke minimally attenuated results.

TIA is associated with a large and sustained increase in dementia risk, approaching that observed after stroke over long-term follow-up. Dementia occurs far more frequently than incident stroke after TIA, highlighting cognitive decline as a major long-term complication and a target for prevention with new strategies that include and extend beyond stroke prevention.

The 2023 Duke-International Society for Cardiovascular Infectious Diseases (Duke-ISCVID) Criteria classified coagulase-negative staphylococci (CoNS), Corynebacterium striatum, Corynebacterium jeikeium, Serratia marcescens, Pseudomonas aeruginosa, Cutibacterium acnes, non-tuberculous mycobacteria, and Candida species as typical microorganisms when intracardiac prosthetic material is present. We critically appraised the evidence supporting these additions and their diagnostic implications.

We conducted a focused narrative review of observational cohorts, bloodstream-infection studies, systematic reviews, and international guidance, supplemented by relevant studies identified during peer review. We distinguished prosthetic valve and CIED-lead endocarditis from pocket and left ventricular assist device infections.

Evidence was strongest for CoNS, C. acnes, and Candida species; moderate but limited by rarity for C. striatum/C. jeikeium and non-tuberculous mycobacteria; and less consistent or indirect for S. marcescens and P. aeruginosa. Comparative validation studies indicate that the diagnostic impact of the expanded Duke-ISCVID microbiological criteria is population- and organism-dependent. The largest sensitivity gains have been observed in populations directly affected by the newly designated typical microorganisms, whereas differences are smaller in broader IE cohorts and may be accompanied by changes in specificity and reclassification as possible IE.

The expanded criterion may improve case ascertainment and should prompt targeted evaluation in patients with intracardiac prosthetic material. However, its diagnostic contribution is not uniform across microorganisms, and fulfilment of the microbiological major criterion should not be interpreted as confirmation of IE in isolation. Multimodality imaging, assessment of bloodstream-infection source and persistence, and clinical judgement remain essential.

Regulated cell death is essential for tissue homeostasis, and its dysregulation contributes to numerous human diseases. Cuproptosis and ferroptosis are metal-dependent forms of regulated cell death distinguished by different biochemical triggers and pathological consequences. Cuproptosis arises from copper-mediated disruption and aggregation of lipoylated mitochondrial proteins, whereas ferroptosis is driven by iron-dependent phospholipid peroxidation. Despite these mechanistic differences, the two pathways intersect through mitochondrial metabolism, redox imbalance, iron-sulfur cluster biology, and organelle crosstalk. Lysosomes, mitochondria, and the endoplasmic reticulum act as critical regulatory hubs that influence cellular susceptibility to both death modalities. This review summarizes current understanding of the molecular mechanisms governing cuproptosis and ferroptosis. It examines the genetic, epigenetic, transcriptional, post-transcriptional, and protein-level networks that regulate these processes. Evidence linking cuproptosis and ferroptosis to cardiovascular, neurodegenerative, autoimmune, metabolic, oral, infectious, and neoplastic diseases is critically evaluated. Therapeutic approaches are discussed, including metal ionophores, chelators, small-molecule modulators, nanomedicine-based delivery systems, and rational combination strategies. Particular attention is given to the context-dependent consequences of activating or suppressing these pathways, and to the challenge of selectively targeting diseased tissues without disrupting systemic metal homeostasis. Successful clinical translation will require reliable biomarkers, mechanistically informed patient stratification, tissue-selective delivery, and a clearer understanding of interactions between metal metabolism, immune responses, and treatment resistance. The review further identifies unresolved questions concerning pathway specificity, temporal regulation, biomarker validation, and the clinical safety of systemic or prolonged therapeutic modulation. Integrating these concepts may enable more precise exploitation of cuproptosis and ferroptosis as therapeutic targets across diverse diseases.

Despite remarkable advances in lipid-lowering therapies, atherosclerotic cardiovascular disease (ASCVD) continues to be a major cause of morbidity and mortality worldwide, and chronic inflammation has been shown to contribute to residual cardiovascular risk.Autoimmune diseases are increasingly recognized as being associated with an increased risk of ASCVD that cannot be explained by traditional cardiovascular risk factors, such as dyslipidemia and hypertension.High-density lipoprotein (HDL) is an anti-atherogenic lipoprotein involved in reverse cholesterol transport. Recent studies have demonstrated that HDL possesses anti-inflammatory and immunomodulatory properties. In autoimmune diseases, both HDL dysfunction and immune dysregulation have been reported, including an impaired cholesterol efflux capacity (CEC), reduced paraoxonase-1 activity, alterations in HDL particle composition, and serum amyloid A enrichment. These findings suggest that crosstalk between HDL and immune cells may play an important role in atherosclerosis progression.Accordingly, this review summarizes the current evidence on HDL-immune cell interactions, discusses how HDL dysfunction contributes to accelerated atherosclerosis in autoimmune diseases, and highlights the therapeutic potential of targeting the HDL function to reduce residual cardiovascular risk or ASCVD risk.

The development of cardiovascular interventional therapies has always been closely linked to synergistic innovation in devices, materials, and methodologies. Taking occlusion technique as an example, traditional metal occluders have a fixed shape and are relatively rigid; their inadequate morphological and mechanical adaptation to the dynamic structure of the heart may affect patients' long-term prognosis. This article reviews biodegradable occluders and magnetofluid-based in situ adaptive shaping technique, exploring the progress and challenges in the field of interventional occlusion regarding device design, material systems, and tissue repair concepts, and discusses the methodological value of ultrasound-guided intervention in the translation of novel materials and non-metallic devices. In the future, it will be necessary to deepen our understanding of these topics, strengthen multidisciplinary collaboration and the development of clinical translation platforms, and drive cardiovascular interventional occlusion therapy toward greater precision, lower physiological burden, evidence-based practices, and scalable technologies.

Osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) plays a fundamental role in chronic kidney disease (CKD)-associated vascular calcification (VC). Despite its significance, the post-transcriptional control mechanisms driving VSMC osteogenic switching remain poorly understood. Here, we sought to elucidate the THOC5-dependent post-transcriptional regulatory mechanisms that control VSMC transdifferentiation and contribute to CKD-associated VC.

Von Kossa staining and immunohistochemistry were used to detect calcification and THOC5 expression in arterial tissues from patients with CKD and mice. In vitro and in vivo models of VSMC calcification were used to assess the effects of THOC5. RNA immunoprecipitation sequencing (RIP-Seq), RNA fluorescence in situ hybridization (RNA-FISH), and electrophoretic mobility shift assays (EMSA) were employed to elucidate the underlying regulatory mechanisms.

THOC5 expression was upregulated in calcified arteries from patients with CKD and mouse models. Functionally, THOC5 deficiency exacerbated VSMC calcification, while THOC5 overexpression mitigated calcification both in vitro and in vivo. Mechanistically, THOC5 selectively associated with guanine nucleotide exchange factor (GEF) mRNAs and facilitated their nuclear export and maintained their transcript stability, thereby sustaining RhoA GTPase activity. Under pro-calcifying conditions, this engagement was diminished, resulting in reduced RhoA activity and decreased expression of VSMC contractile markers. Pharmacological inhibition of RhoA signaling (Y27632) reversed the protective effects of THOC5. Notably, THOC5 overexpression restored GEF mRNA transport and suppressed osteogenic transition.

Our study identifies a THOC5-GEF-RhoA regulatory axis that post-transcriptionally governs VSMC phenotypic stability during CKD-associated vascular calcification. Endogenous THOC5 upregulation in calcified vasculature likely represents a compensatory but insufficient response, as osteogenic stress impairs the formation of functional THOC5-containing export complexes. THOC5 overexpression restores this process and attenuates vascular calcification.

Elderly patients with obstructive coronary artery disease (CAD) frequently present a high bleeding risk (HBR). In this category of patients, percutaneous coronary intervention (PCI) is also associated with a higher risk of periprocedural and long-term ischemic and bleeding complications. PCI with drug-coated balloons (DCB) with short dual antiplatelet therapy (DAPT) is a valid alternative to stenting in this group of elderly or HBR patients. To date, no dedicated trial has prospectively evaluated the safety and efficacy of a PCI with solo-DCB followed by single antiplatelet therapy (SAPT).

The study aims to evaluate the incidence of ischemic and bleeding adverse events following SAPT after only-DCB PCI in elderly patients or those with high bleeding risk, either with chronic or acute coronary syndromes.

PICCOLETO IV-EPIC38 study (clinicaltrial.gov: NCT06535568) is a prospective, international, multicenter, investigator-driven, open-label, randomized (1:1), superiority clinical trial. The study will enroll elderly patients aged 75 years or older (≥75 years) or HBR patients, as defined by the Academic Research Consortium criteria, who are undergoing successful DCB-only PCI for native coronary artery disease in vessels with a diameter between 2.0 and 4.0 mm. Participants will be randomized in a 1:1 ratio between two treatment groups: the experimental arm receiving SAPT and the comparative arm receiving DAPT. Patients in the experimental arm will receive either aspirin or clopidogrel. In the comparative arm, patients will receive standard care. The primary endpoint of this study is the incidence of Net Adverse Clinical Events (NACE), defined as the composite of major adverse cardiac events (MACE), including total mortality, target vessel revascularization, and spontaneous myocardial infarction, and clinically relevant bleeding events (BARC 2, 3, or 5), assessed over 12 months. A superiority hypothesis will be tested. A total of 576 patients will be enrolled in the study, with primary analysis conducted on an intention-to-treat basis and secondary analysis performed on an as-treated basis. Randomization will take place after successful intervention.

The PICCOLETO IV-EPIC38 study is a randomized trial assessing the safety and efficacy of SAPT post-PCI with DCB treatment, which could significantly impact treatment for elderly or HBR patients with CAD.