Search Results (943)

We report an unusual case of simultaneous left and right atrial appendage thrombosis identified on contrast-enhanced cardiac computed tomography angiography (CT) during pre-procedural evaluation in a patient with permanent atrial fibrillation and structural heart disease. Cardiac CT demonstrated well-defined filling defects within both atrial appendages on arterial and delayed phases, consistent with intracavitary thrombi. The patient was already receiving long-term oral anticoagulation for atrial fibrillation. In this case, antithrombotic management was not modified after multidisciplinary clinical assessment, as the patient remained asymptomatic and at high bleeding risk. This case highlights the diagnostic value of multiphasic cardiac CT in pre-procedural imaging, and underscores that systematic bilateral appendage assessment is essential, as right atrial appendage thrombus may otherwise go undetected. Full article

Goat blood, a major slaughterhouse by-product, was systematically valorized into dual-function bioactive peptides through an optimized four-step process. Four blood preparations—whole blood (HB), anticoagulant-treated blood (HBS), red blood corpuscles (BC), and plasma (PM)—were subjected to heat pretreatment (90 °C, 15 min) and enzymatic hydrolysis. Neutrase hydrolysis of heat-pretreated whole blood at 8% substrate concentration for 4 h (HBN-8) yielded optimal protein recovery (44.38%) with dual ACE (88.24%) and DPP-IV (81.13%) inhibition. Ultrafiltration enriched bioactive peptides in the ≤3 kDa fraction (DPP-IV: 87.8%; ACE: 65.5%). LC-MS/MS de novo sequencing identified 14 novel peptide sequences (4–9 amino acids), with the most potent SEC fraction showing IC₅₀ values of 0.89 and 0.45 mg Leu eq./mL for DPP-IV and ACE inhibition, respectively. Critically, simulated gastrointestinal digestion enhanced rather than diminished bioactivity, with ACE inhibition increasing progressively to 60.91% at the intestinal phase, supported by predicted generation of bioactive fragments from parent sequences. Caco-2 assays confirmed peptide safety (100–1000 µg/mL) and demonstrated 10.47% transepithelial transport with retained dual inhibitory activities. This study establishes goat blood as a sustainable source of orally bioavailable, GI-stable peptides for the development of functional foods targeting hypertension and type 2 diabetes. Full article

Background: Anticoagulation management in very elderly patients with atrial fibrillation (AF) is particularly challenging due to the coexistence of high thromboembolic and bleeding risks, often compounded by multiple comorbidities. Randomized clinical trials rarely include patients aged ≥85 years, leaving important gaps in our understanding of how anticoagulant therapies are selected in this growing population. Methods: We analyzed data from the CRAFT registry, including 2914 patients hospitalized with AF. Patients were stratified into two age groups: <85 years (n = 2322) and ≥85 years (n = 592). Baseline clinical characteristics, comorbidities, and laboratory parameters were compared between groups. Separate multivariable logistic regression analyses were performed for each age group to identify independent predictors of anticoagulant therapy selection. Results: Patients aged ≥85 years exhibited a distinct clinical profile, characterized by higher thromboembolic risk and a greater prevalence of heart failure, renal dysfunction, anemia, and structural heart disease. Renal function was significantly impaired (median eGFR 47.6 vs. 60.0 mL/min; p < 0.001), while NT-proBNP levels were higher and hemoglobin levels lower in this group. Multivariable analysis revealed clear age-related differences in determinants of treatment selection. In patients < 85 years, anticoagulant choice was influenced by multiple clinical factors, including CHA₂DS₂-VA score, renal function, bleeding risk, coronary artery disease, and prior revascularization. In contrast, in patients ≥ 85 years, only two independent predictors remained significant: thromboembolic risk (CHA₂DS₂-VA score; OR 1.34, 95% CI 1.11–1.64) and renal function (eGFR; OR 0.64, 95% CI 0.47–0.89). Anticoagulation in this group was predominantly based on reduced-dose DOACs, with apixaban used most frequently. Conclusions: Very elderly patients with AF represent a clinically distinct, high-risk population. While anticoagulant selection in younger elderly patients reflects a multifactorial decision process, treatment in those aged ≥85 years appears to rely primarily on thromboembolic risk and renal function, suggesting a more streamlined—and potentially oversimplified—approach. Full article

Background/Objectives: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is common in dentistry, mainly for pain and inflammation. However, their coadministration with warfarin may lead to serious potential drug-drug interactions (PDDIs), increasing the risk of bleeding. This study aimed to identify and describe the frequency of PDDIs between warfarin and NSAIDs prescribed by dentists and dispensed by the Unified Health System (SUS) in Minas Gerais, Brazil, from January 2011 to December 2021. Methods: A descriptive analysis was conducted using data from Integrated Pharmaceutical Services Management System (Sigaf), considering prescriptions of warfarin and NSAIDs issued during the same period. Results: The prescribed NSAIDs were diclofenac sodium 50 mg, diclofenac potassium 50 mg, ibuprofen 600 mg, nimesulide 100 mg, and nimesulide 50 mg/mL oral suspension. Warfarin sodium 5 mg is the prescribed oral anticoagulants. The results showed a marked increase in both warfarin (from 6017 to 59,945 prescriptions; +896%) and NSAID use (from 2644 to 84,408 prescriptions; +3093%), paralleling the rise in PDDIs, which grew from 2 in 2011 to 62 in 2021. Despite this 3000% relative increase, the absolute frequency of PDDIs remained low, corresponding to approximately 0.7 interactions per 1000 NSAID prescriptions in 2021. Conclusions: Although these PDDIs are low, they are clinically significant and may have important implications for patients and the healthcare system. In conclusion, PDDIs between NSAIDs and warfarin, though low in absolute numbers, have increased over the years, reinforcing the need for greater awareness among dental professionals and for the implementation of clinical decision support strategies to promote safe care. Full article

Background: Left atrial appendage occlusion (LAAO) requires a significant upfront investment, which is in contrast with the more gradual, long-term costs of direct oral anticoagulants (DOACs). Objective: We performed a budget impact analysis exploring the financial impact of increasing the number of LAAO procedures in a high-stroke-risk population over a 10-year time horizon from the perspective of the healthcare providers under the Italian National Healthcare Service. Methods: Two alternative scenarios simulating an increased uptake of the LAAO therapy were compared to the estimated volume of LAAO procedures performed (baseline scenario: 1341 procedures): (1) Alternative Scenario I (3314 procedures) based on the level of penetration observed in the Italian region performing the highest rate of LAAO procedures; (2) Alternative Scenario II (7672 procedures): LAAO therapy uptake set to attain 5% of the estimated target population. Clinical data were extracted from a propensity-matched, multicenter cohort of 554 AF patients at a very high thromboembolic risk profile (CHA₂DS₂-VASc score ≥ 5) treated with LAAO or DOACs. Results: Cumulative cost savings in Alternative Scenario I were around €4.9 million compared to the baseline. When comparing Scenario II to the baseline scenario, savings added up to €15.8 million over 10 years. The break-even point occurred between the seventh and eighth years. Cost savings were observed even in the instance that all DOAC prices would decrease as generics became available. Conclusions: The widespread use of LAAO therapies in a population of AF patients at very high stroke risk may yield substantial long-term benefits, as the initial investment in the LAAO procedure and device would be counterbalanced within 8 years. Full article

Aspirin has been the default backbone of antiplatelet therapy after percutaneous coronary intervention (PCI) for over two decades, anchored by landmark trials that established 12-month dual antiplatelet therapy (DAPT) as the standard of care. Three developments have prompted reassessment of this paradigm: the markedly lower thrombotic risk of contemporary drug-eluting stents, the greater potency and consistency of potent P2Y₁₂ inhibitors (ticagrelor, prasugrel), and increasing recognition that major bleeding independently worsens outcomes after PCI. Recent randomised trials have systematically tested aspirin withdrawal at varying time points. Immediate aspirin-free strategies (NEO-MINDSET, STOPDAPT-3) demonstrated an early signal of excess ischaemic events in the ACS component of enrolled populations, suggesting that aspirin remains important during the earliest post-PCI period in ACS. One-month strategies (T-PASS, ULTIMATE-DAPT, TARGET-FIRST) and three-month strategies (TWILIGHT, TICO, DUAL-ACS) showed that transition to P2Y₁₂ monotherapy after an initial DAPT period significantly reduces bleeding without increasing ischaemic events in selected populations. Beyond one year, long-term randomised trials including the HOST-EXAM 10-year follow-up (Lancet 2026) and the STOPDAPT-2 5-year landmark analysis (Circ Cardiovasc Interv 2026), together with study-level meta-analyses (PANTHER) and recent individual patient data meta-analyses, provide converging evidence that clopidogrel monotherapy outperforms aspirin for chronic secondary prevention without excess bleeding. The choice of P2Y₁₂ agent is critical: clopidogrel monotherapy in ACS during the first post-procedural year carries excess thrombotic risk owing to CYP2C19 pharmacogenomic variability, whereas ticagrelor and prasugrel provide more reliable protection. This review synthesises the mechanistic rationale, trial evidence across all time points, special clinical contexts (oral anticoagulation, coronary artery bypass grafting, high bleeding risk), guideline evolution, and methodological considerations, providing a practical framework for individualising post-PCI antiplatelet therapy. Full article

Purpose: Proton pump inhibitors are commonly used during oral anticoagulant therapy in patients with atrial fibrillation, but evidence regarding outcomes beyond upper gastrointestinal bleeding remains limited. We evaluated whether concomitant proton pump inhibitor use during oral anticoagulant therapy was associated with thromboembolic events, bleeding outcomes, and all-cause mortality. Methods: This retrospective multicenter cohort study included patients with atrial fibrillation who initiated oral anticoagulant therapy. Concomitant proton pump inhibitor use was modeled as a time-varying exposure with a prespecified 7-day lag. The primary outcome was a composite of thromboembolic events, major bleeding, and all-cause mortality. Secondary outcomes included each component outcome and gastrointestinal bleeding. Associations were estimated using time-dependent Cox proportional hazard models after multiple imputation of missing baseline variables. Results: Among 11,203 patients (median age 71 years [interquartile range 62–78]; 4743 women [42.3%]), 7-day lagged time-varying proton pump inhibitor exposure was associated with a higher risk of the composite outcome (hazard ratio 1.29, 95% confidence interval 1.08–1.55), major bleeding (1.80, 1.36–2.37), gastrointestinal bleeding (1.77, 1.18–2.66), and all-cause mortality (1.58, 1.00–2.48). No statistically significant association was observed for thromboembolic events. Across robustness analyses, the overall pattern was broadly maintained, although estimates varied according to exposure timing. Conclusions: In this observational cohort of patients with atrial fibrillation receiving oral anticoagulant therapy, concomitant proton pump inhibitor use modeled with a 7-day lagged time-varying framework was associated with higher risks of several bleeding-related outcomes and all-cause mortality, but not thromboembolism. These findings should be interpreted as associations rather than causal effects. Full article

Direct oral anticoagulants (DOACs) are the standard first treatment for patients with venous thromboembolism. Unfortunately, some patients develop recurrent thromboembolism despite adherence to anticoagulation. This remains a significant clinical challenge with no randomized data to guide therapy. This review summarizes the available evidence for the management of recurrent venous thromboembolism (VTE) and DOAC failure, and we propose our group consensus and management algorithm. Full article

Background: Lower limb arterial calcification (LLAC) is a robust imaging biomarker of peripheral artery disease (PAD) severity. Vitamin K antagonists are presumed to accelerate cardiovascular calcification. Direct oral anticoagulants (DOACs) may influence vascular calcification differently, but lower limb data are limited. Methods: We performed a single-center retrospective cross-sectional study comparing LLAC on clinically acquired non-contrast CT between DOAC users and controls without anticoagulation. Patients were propensity score-matched 1:1 (48 DOAC vs. 48 control; n = 96) using baseline clinical covariates. Associations between LLAC scores and perioperative or cardiovascular events were assessed. Segment-specific LLAC was quantified on non-contrast CT and normalized for arterial segment length. A prespecified exposure–duration sensitivity analysis compared the outcomes in patients with ≥5 years of continuous DOAC therapy (n = 22) versus matched controls. Results: In the matched cohort, total LLAC scores did not differ significantly between DOAC and control groups (infrarenal aorta: median 7596.0 vs. 8637.0 (p = 0.487), iliac segment: median 5689.5 vs. 5193.5 (p = 0.602). However, in patients with ≥5 years of DOAC use, LLAC scores were significantly lower in proximal segments: infrarenal aorta median 5593.5 vs. 11,185.0 (p = 0.001997) and iliac arteries 5624.5 vs. 11,501.0 (p = 0.001867)). Higher LLAC was associated with major adverse cardiovascular events (such as myocardial infarction, stroke, or significant bleeding) in controls (p = 0.0023) but not in DOAC-treated patients. Conclusions: In this propensity-matched, cross-sectional CT study, long-term DOAC exposure was associated with lower proximal LLAC scores in a small duration-defined subgroup, while the primary matched analysis showed no overall difference in total LLAC scores. Because baseline (pre-DOAC) imaging was unavailable and residual confounding/survivor bias is possible, these findings should be considered hypothesis-generating and require prospective validation. The cohort reflected a mixed lower-extremity vascular population rather than exclusively classic chronic atherosclerotic PAD, which may limit biological interpretation and generalizability. Full article

Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening subtype of stroke, characterized by thrombus formation within the dural venous sinuses and cerebral veins. Recent advances have deepened our understanding of CVT pathophysiology, highlighting a multifactorial process that encompasses thrombus initiation, subsequent thrombus propagation, venous hypertension with blood–brain barrier disruption, and secondary parenchymal brain injury. Comprehensive clinical assessment, including diagnosis and differential diagnosis, disease severity scores, imaging-based metrics, and prognostic scoring systems, enables accurate evaluation and risk stratification. Emerging therapeutic strategies, including direct oral anticoagulants, corticosteroids for selected patients, natural-origin agents, immunomodulatory therapy, endovascular treatment, optic nerve sheath fenestration, and neuromodulation, provide novel and alternative options for the management of CVT. This review provides a comprehensive overview of CVT pathophysiology, clinical assessment tools, and novel therapeutic strategies to guide clinical decision-making and inform future research. Full article

Background: Left ventricular (LV) thrombosis after blunt trauma is uncommon and is most often attributed to traumatic coronary artery injury; however, it can also arise from severe myocardial contusions. Here, we report a case of LV thrombosis due to severe myocardial contusion without coronary artery injury. Case Presentation: A 36-year-old man struck by industrial fan fragments presented with hemorrhagic shock. Focused Assessment with Sonography for Trauma revealed cardiac tamponade. An emergent sternotomy was performed under cardiopulmonary bypass via the femoral vessels, which exposed severe contusion-associated hemorrhage with epicardial–myocardial dissection at the LV apex. On postoperative day (POD) 5, transthoracic echocardiography showed apical akinesia with mural thrombi; prophylactic anticoagulation was escalated and later transitioned to warfarin. Coronary computed tomography on POD 21 and invasive angiography at 6 months revealed negative findings. The thrombi resolved within 3 months; however, apical akinesia persisted. After discontinuing anticoagulation, a transient ischemic event occurring at 9 months prompted direct oral anticoagulant therapy. Apical akinesia persisted for over 7 years without recurrent thrombosis. Conclusions: This case underscores the importance of vigilance for intracardiac thrombosis in severe contusions, as well as the value of stepwise imaging (contrast echocardiography) and cautious, individualized discontinuation of anticoagulation when regional dysfunction persists. Full article

Background: COVID-19 is primarily a respiratory disease, but increasing evidence suggests possible oral and maxillofacial complications. This study presents a case series of post-COVID maxillary osteonecrosis (PC-RONJ) cases from western Romania and explores the possible association between SARS-CoV-2 infection, its treatment, and this complication. Methods: We conducted a multicenter retrospective case series of two patients with recent PCR-confirmed SARS-CoV-2 infection who subsequently developed maxillary osteonecrosis (ONC) between 2021 and 2023. Clinical examination, CT imaging (including 3D reconstructions), and ENT assessment were used to assess the severity of the disease. All medical records were reviewed to identify comorbidities, details of COVID-19 treatment, and the appearance of maxillofacial symptoms. Results: Both patients had been hospitalized for severe COVID-19 and treated according to the national protocol with systemic corticosteroids, oxygen therapy, anticoagulation, and antivirals. CT scans revealed marked osteolytic destruction of the maxilla and maxillary sinus walls, with extension toward adjacent facial bones. Microbiological analysis revealed a complex polymicrobial profile, including Gram-positive and Gram-negative bacteria as well as opportunistic fungal species, consistent with a chronic biofilm-associated infectious process. Patients received surgical treatment, followed by local care and, in both cases, prosthetic rehabilitation with maxillary obturators, which improved speech, chewing, and oral function. Conclusions: This case series suggests a possible association between severe COVID-19, its treatment, and subsequent maxillary osteonecrosis in susceptible patients; however, the small number of cases precludes causal inference. To our knowledge, this is the first Romanian report describing such cases in patients without prior antiresorptive therapy. These findings highlight the need for careful use of systemic corticosteroids and vigilant post-recovery monitoring of maxillofacial complications. Further studies are required to clarify the underlying mechanisms and risk factors. Full article

Background/Objectives: Atrial fibrillation (AF) is highly prevalent among older adults and is associated with increased thromboembolic risk. Although anticoagulant therapy (AC) is strongly recommended, its use in elderly and multimorbid patients remains suboptimal. This study aimed to describe long-term trends in AC prescribing patterns among hospitalized older patients with AF. Methods: We conducted a retrospective observational analysis using data from the Italian REPOSI registry, including patients aged ≥65 years hospitalized with AF between 2010 and 2023. AC at admission and discharge was analyzed, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and antiplatelet agents. Temporal trends, admission-to-discharge treatment changes, and patient characteristics associated with therapy modification were assessed descriptively. Results: The study included 2061 AF patients, characterized by multimorbidity and high thromboembolic risk. A marked shift from VKAs to DOACs was observed over time. However, a substantial proportion of cases remained without AC or received only antiplatelet therapy at both admission and discharge, with untreated individuals being generally older and more clinically complex. DOAC use increased steadily but showed a slight decline at discharge after 2020. Clinical variables available in the registry only partially explained AC changes during hospitalization. Conclusions: Despite increasing adoption of DOACs, AC underuse remains frequent among elderly hospitalized patients with AF. These real-world data highlight persistent challenges in AC management in complex older adults and underscore the need for more comprehensive clinical information and data-driven tools to support individualized therapeutic decision-making. Full article

Protease-activated receptor-1 (PAR-1) is a key regulator of mesenchymal stem cell (MSC) migration and tissue integration. Dabigatran, a direct thrombin inhibitor widely used as a non-vitamin K oral anticoagulant (NOAC), may affect PAR-1-mediated signaling pathways. This study investigated the effects of dabigatran on cell viability, apoptosis, and PAR-1 activity in adipose-derived MSCs (ADMSCs) in vitro. ADMSCs were exposed to five concentrations of dabigatran etexilate with thrombin activation. Cell viability was assessed using the MTT assay, apoptosis and morphological changes were evaluated via acridine orange/propidium iodide staining, and PAR-1 expression was analyzed by immunofluorescence. Results showed that high dabigatran concentration significantly reduced cell viability and induced apoptotic morphological changes. In contrast, lower, non-cytotoxic concentrations preserved normal fibroblastic morphology and maintained cell viability while reducing PAR-1 surface expression compared with thrombin-activated controls. These findings indicate that dabigatran at non-cytotoxic doses can modulate PAR-1 activity without compromising ADMSC survival. In conclusion, dabigatran influences MSC-related cellular functions beyond its anticoagulant properties. Full article

Background/Objectives: Cognitive impairment is highly prevalent in atrial fibrillation (AF) and frequently occurs in the absence of overt stroke, implicating non-embolic mechanisms. We hypothesized that atrial remodeling and impaired cerebral hemodynamics are associated with mild cognitive impairment (MCI) in permanent AF. Methods: In this cross-sectional study, 252 stroke-free patients with permanent AF receiving direct oral anticoagulants (DOACs) underwent transthoracic echocardiography and transcranial Doppler (TCD) assessment of middle cerebral artery flow. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were analyzed. Multivariable logistic regression identified factors independently associated with MCI, and receiver operating characteristic (ROC) curves evaluated discriminative performance. Results: MCI was present in 40% of patients (101/252). AF-MCI patients were older and showed greater left atrial remodeling, reflected by increased left atrial diameter and left atrial volume index (LAVI) (both p ≤ 0.001), without differences in left ventricular systolic function. TCD demonstrated reduced EDV and increased RI in the MCI group (all p ≤ 0.01), whereas PSV showed minimal differences. In multivariable analysis, age, LAVI, and average RI were independently associated with MCI. Age showed excellent discrimination (AUC 0.858), whereas maximum RI demonstrated moderate discrimination (AUC 0.645; p < 0.001 for comparison). Conclusions: In stroke-censored permanent atrial fibrillation, cognitive impairment was associated with atrial remodeling and impaired diastolic cerebral perfusion, consistent with a potential contribution of chronic hypoperfusion and increased microvascular resistance. Combined echocardiographic and cerebral hemodynamic assessment may help characterize hemodynamic patterns associated with cognitive impairment in AF. Full article