Screening of a novel VHH pair targeting different epitopes of D-dimer and development of a sandwich luminex immunoassay for plasma D-dimer detection.

Prolyl hydroxylase inhibitors, roxadustat and daprodustat, inhibit platelet activation and thrombosis through the PI3K/AKT/HIF-1α pathway.

Myxomas are considered the most common among primary tumors. But right atrial myxomas are relatively rare.[1] A 49 year old male presented with left upper and lower limb hemiparesis which recovered spontaneously without residual weakness within 24 h without thrombolysis. A known diabetic and hypertensive, he was thoroughly evaluated which revealed a multifocal right atrial myxoma attached to the right atrial free wall and extending into the superior venacava. Serum anti-cardiolipin antibody IgG was positive. The myxoma was promptly excised under general anaesthesia. Cardiopulmonary bypass was instituted with cannulation of the aorta, right femoral vein draining the inferior venacava (IVC) and high superior venacava (SVC) under transesophageal echocardiography guidance. The sieve like infiltrations into the SVC were excised by briefly decannulating the SVC followed by immediate recannulation. Myocardial protection was ensured with pulmonary artery venting, del Nido cardioplegia, sterile topical ice saline and terminal warm reperfusion. The patent foramen ovale was directly closed with prolene sutures. Right atrial myxomas are known to be associated with antiphospholipid antibody syndrome, thus making it mandatory to be ruled out.[2] Right atrial myxomas are rare and those associated with patent foramen ovale are a further rarity.[4] Our approach to the excision of the myxoma has been unique since the inferior venacava was drained with right femoral vein cannulation to prevent disrupting the mass and further embolism, pulmonary artery venting was done instead of left atrial venting to prevent manipulation of the mass during right atrial retraction and the resection of the mass infiltrating into the SVC wall was done carefully by briefly decannulating the SVC and immediately recannulating post resection.

Introduction: Venous thromboembolism is a common clinical problem. Its diagnosis in patients who have sustained trauma can be difficult due to nonspecific symptoms and the lack of characteristic findings on imaging studies. Thrombosis of the intramuscular veins of the lower leg is an uncommon manifestation of thrombotic disease, and due to its location and difficult diagnosis, it remains an underestimated and overlooked cause of painful lower limb edema. Case description: A 36-year-old man who suffered a knee injury while skiing presented with persistent swelling of the knee and shin lasting three weeks. Magnetic resonance imaging and ultrasound examination revealed no significant pathology, intra-articular damage, cartilaginous structures. An initial assessment of the venous system revealed no significant changes in the popliteal fossa and no signs of thrombosis. Due to increasing pain, tenderness and persistent swelling, the diagnosis was expanded to include a comprehensive ultrasound examination of the lower limb. Examination of the intramuscular veins revealed extensive thrombosis of the soleal and gastrocnemius veins, with preserved patency of the larger superficial and deep venous vessels. Conclusions: The presented case highlights the importance of intramuscular veins as the starting point for thromboembolic disease, which carries a risk of serious complications. Assessment of intramuscular veins is essential in the diagnosis of patients with persistent lower limb edema after trauma. A limited or cursory examination of the venous system may lead to delayed diagnosis and the development of complications. A comprehensive evaluation of the superficial and deep venous system, including intramuscular veins, should be standard practice in trauma patients.

Venous thromboembolic disease is a chronic, recurrent condition. The optimal duration of anticoagulation therapy remains uncertain. We aim to evaluate D-dimer and lower limb ultrasonography as prognostic tools for the recurrence of venous thromboembolism. A search was conducted on May 28, 2022, in the Medline, Embase, and Cochrane databases. Inclusion criteria encompassed cohort studies, case-control studies, and clinical trials. Two reviewers independently screened all records and analyzed studies for inclusion/exclusion criteria, as well as risk of bias, using a structured framework (PROSPERO ID: CRD42022341082). The initial search yielded 4652 titles and abstracts. After removing 777 duplicates and reviewing 3875 titles and abstracts, 48 articles providing information on D-dimer and/or lower limb ultrasonography as prognostic factors were finally included. Very low-certainty evidence suggests that both residual vein thrombosis (RVT) at anticoagulation discontinuation and a positive post-treatment D-dimer are significantly associated with an increased risk of recurrent venous thromboembolism (VTE). For RVT, the pooled analysis showed a two-fold increase in risk (OR 2.00, 95% CI 1.02 to 3.94; I² = 85.7) while for positive D-dimer, the risk was similarly elevated (OR, 2.48; 95% CI, 1.85–3.33; I² = 56.0). In conclusion, very low-quality evidence suggests that abnormal D-dimer and RVT are associated with recurrent VTE; however, this association is inconsistent due to significant heterogeneity and wide prediction intervals. These biomarkers should be interpreted with caution as isolated predictors in clinical practice.

Effective imaging is lacking for intravascular lesions in pulmonary vascular diseases. Optical coherence tomography (OCT) offers micron-level resolution, enabling improved diagnosis and treatment guidance. This study aimed to evaluate pulmonary arterial lesions using OCT. This retrospective study reviewed consecutive patients with pulmonary arterial lesions undergoing OCT at The First Affiliated Hospital of Guangzhou Medical University between August 2022 and November 2024. Patients with chronic thromboembolic pulmonary disease, Takayasu arteritis, Behçet's disease, or fibrosing mediastinitis were included in the study. Arterial lesions assessed included fresh, subacute, and chronic thrombus, vascular dissection, and other OCT findings. Seventy-two patients (median age 57.5 years [interquartile range 48.0-66.0 years]; 39 [54.17%] males) were included in the study. The OCT features were as follows: fresh thrombus showed irregular regions with marked signal attenuation; subacute thrombus appeared as intraluminal clumps surrounding the catheter; chronic thrombus presented as multichambered mesh-like structures; Takayasu arteritis and Behçet's disease exhibited bead-like eccentric intimal thickening with vacuole-like changes; fibrosing mediastinitis showed an irregular lumen with high attenuation behind the wall; and vascular dissection presented as dark areas with occasional lumen communication and a streak-like longitudinal appearance. OCT yields high-resolution imaging for detailed assessment of pulmonary vascular diseases and holds promise for clinical application.

Abstract Introduction&Objective Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major cause of thromboembolic stroke in clinical practice. This condition often recurs frequently, emphasizing the urgent need to understand its long-term progression, especially when triggered by acute events. Growing evidence indicates a relationship between AF and oxidative processes. During AF episodes, the atrial myocardium sustains significant oxidative damage, which may contribute to atrial remodeling. Nitric oxide (NO) is produced by enzymes called NO synthases (NOS). The three isoforms of NOS are neuronal NOS (nNOS, NOS1), inducible NOS (iNOS, NOS2), and endothelial NOS (eNOS, NOS3). Similar to acute coronary syndrome, AF has been shown to reduce left atrial endocardial eNOS levels and significantly decrease NO production. However, no research currently exists that examines the relationship between AF recurrence and NOS activity. The aim of this study is to evaluate the potential of eNOS levels as a marker for predicting AF recurrence. Material & Method The study population included 320 consecutive patients admitted to our hospital between August 2023 and January 2025 with AF. A total of 44 patients were excluded from the study. Ultimately, the study sample comprised 276 patients. Blood samples were collected into tubes for NT-proBNP, NO, eNOS, and iNOS. The samples were centrifuged (4000g, 4°C) for 10 minutes, and the serum was separated and stored at −25°C until analysis. Patients were divided into two groups based on whether AF recurred during their 6-month follow-up. Results The mean age of the sample was 73.1±9.7 years. 138 (50%) patients were male. There was no significant difference between the levels of NT-proBNP, NO and iNOS. Univariate logistic regression analysis revealed significant correlations between eNOS and recurrnes of AF. The eNOS level was lower in patients with recurrent AF patients, and the optimal eNOS cut-off value of ≤ 93.4 pg/mL predicted recurrent AF patients with 68% sensitivity and 93.4% specificity (AUC:0.803 [95% CI: 0.751-0.848, p<0.001]). Conclusion This study investigates the role of eNOS activity in AF recurrence for the first time in the literature. It has been shown that lower eNOS levels are linked to a higher risk of AF recurrence.Figure 1:ROC curve analysis of eNOSFor image description, please refer to the figure legend and surrounding text. Graphical Abstract-Central FigureFor image description, please refer to the figure legend and surrounding text.

Cerebral Venous Thrombosis (CVT) is a rare condition. Diagnosis must be made urgently despite highly varied neurological symptoms, initially dominated by headaches. In some cases, CVT may have an unusual presentation, making diagnosis difficult. A purely psychiatric manifestation is exceptional and can lead to diagnostic uncertainty and delay. Diagnosis is radiological and treatment is based on early anticoagulation. The prognosis for CVT is much better than that for cerebral infarcts of arterial origin. We present a case of postpartum cerebral thrombophlebitis with late diagnosis revealed by psychotic disorders, which had a favorable outcome. Cerebral Venous Thrombosis (CVT) is a rare and urgent thrombotic vascular disease. Its clinical presentation is varied. The diagnosis must be considered in the presence of any acute psychiatric manifestation during the postpartum period.

AI-driven discovery of an allosteric thrombin-targeting anticoagulant peptide from traditional Chinese medicine Dilong (Pheretima aspergillum).

Retinal thrombotic diseases, a major cause of vision impairment, lack effective treatments that directly resolve vascular occlusion. To address this challenge, we developed a novel multifunctional nanoplatform for targeted thrombolysis: PLGA-PFP-rtPA nanoparticles modified with the fibrin-targeting peptide CREKA (PPrC NPs). The nanoparticles were successfully fabricated with a spherical morphology, a mean size of 289 ± 4.1 nm, and a zeta potential of -13.6 ± 1.1 mV, indicating good stability.In vitrothrombolysis assays demonstrated that PPrC NPs, combined with low-intensity ultrasound (US), exhibited significantly superior thrombolytic efficacy compared with controls (P< 0.05), owing to a synergistic effect of fibrin targeting, US-responsive drug release, and phase-transition enhancement. Cytotoxicity assays on human retinal microvascular endothelial cells confirmed high biocompatibility, with cell viability exceeding 90% at concentrations up to 1000 µg ml-1. Furthermore, comprehensive hemocompatibility evaluations, including hemolysis, coagulation function, complement activation (C3a), and platelet activation, revealed no adverse effects within the therapeutically relevant concentration range (⩽800 µg ml-1). Collectively, these findings indicate that the CREKA-modified nanoplatform provides a safe and effective strategy for targeted thrombolysisin vitro, presenting a promising foundation for developing minimally invasive therapies for retinal thrombotic diseases.

Thrombotic diseases represent a major global health challenge, yet current theranostic systems suffer from bleeding risks, rapid agent clearance, and external irradiation reliance. To tackle these issues, we developed a shear stress-responsive platform integrating endogenous piezoelectric thrombolysis and on-site chemiluminescence imaging. Specifically, calcium-/zirconium-doped barium titanate (BCTZ) nanorods (NRs) modified with chlorin e6 (Ce6), luminol, and Arg-Gly-Asp (RGD) peptides, yielding BCTZ@CeLu-R NRs. A strong correlation is demonstrated between piezoelectric potentials and the degree of stenosis, providing rational mechanical signals for stenosis-adaptive thrombus imaging and thrombolysis. The shear force-triggered piezocatalysis operates according to energy band theory, as evidenced by thoroughly monitoring degradation rates of various dyes in media with different pH values. Piezocatalysis of NRs primarily generates ·OH and ·O2 - to oxidize luminol and generate chemiluminescence, which, in turn, activates Ce6 to emit fluorescence for imaging and producing 1O2 for photodynamic therapy (PDT), creating a piezocatalysis-chemiluminescence-energy transfer cascade. In a rat model of carotid artery thrombosis, RGD-targeted NRs achieve four-fold higher luminescence for deep-tissue imaging without external excitation, and combined piezocatalysis, PDT, and RGD-mediated targeting realize 97.7% thrombolysis efficiency. This work pioneers an innovative theranostic approach driven by endogenous shear force, enabling clot site-specific and stenosis degree-adaptive thrombosis imaging and thrombus dissolution.

To estimate the effect of combined oral contraceptives (COCs) compared with non-estrogen-containing oral contraceptives on the risk of stroke among individuals with migraine with aura. Using U.K. primary care medical records with linked hospital data from the Clinical Practice Research Datalink, the authors evaluated the risk of stroke associated with use of COCs, containing estrogen and progestogen, compared with progestogen-only pills (POPs) among individuals with migraine with aura. The study included individuals aged 15-49 years who initiated either contraceptive of interest from 2000 to 2024, with no history of stroke, other thrombotic disease, or menopause at the time of initiation. Risk of ischemic and any stroke was compared after application of treatment and censoring weights using risk differences and ratios from the Kaplan-Meier estimator. Individuals were censored on medication discontinuation in primary analyses. Among the 12,429 initiators of COCs and 41,984 initiators of POPs included in the study, 1-year risk of ischemic stroke was 17.36 and 17.62 per 100,000 people, respectively. After weighting, the 1-year risk difference for ischemic stroke for COCs compared with POPs was 9.53 per 100,000 people (95% CI, -38.65 to 57.71). For stroke of any type, the risk difference was 3.49 per 100,000 people (95% CI, -45.17 to 52.16). Effects were larger with shorter follow-up periods (3-month ischemic stroke risk difference of 17.62/100,000 people) but were still imprecisely measured. Findings were similar when individuals were not censored at medication discontinuation (ischemic stroke intent-to-treat risk difference of 10.36/100,000 people). The risk of stroke in this reproductive-age population of individuals with migraine with aura was low overall and similar between users of COCs and POPs.

Multifactorial Pulmonary Hypertension: Converging Roles of Sarcoidosis, Heart Failure With Reduced Ejection Fraction, and Chronic Thromboembolic Disease

Abstract Background Pneumatosis intestinalis (PI) is the imaging finding of air within the bowel wall. It constitutes a diagnostic challenge due to its broad differential and overlap in imaging appearances between benign and serious causes. A multidisciplinary approach is essential for accurate diagnosis and timely intervention, to optimize outcomes and minimize unnecessary procedures. Objective This article aims to synthesize the literature to lay out the current state of the art in diagnosing and managing PI and discuss future perspectives. We review a series of associated imaging features including portomesenteric venous gas, vascular thrombosis, abnormal bowel wall enhancement, and bowel wall thickening or thinning. We also discuss less specific but commonly seen findings like pneumoperitoneum, ascites and fat stranding, emphasizing their context-dependent significance. We review nuances in clinical interpretation of the severity of PI, discuss the discordance in interpretation of certain clinical markers, and important considerations in specific populations. To finish, we describe ongoing efforts related to risk stratification and its importance in PI management. Graphical abstract

Abstract Introduction Computed Tomography (CT) pulmonary angiography is an integral part of the assessment of thromboembolic disease. Changes in penetration of the contrast in the parenchyma have been described in thromboembolic disease- with decreased signal intensity in the parenchyma with acute PE and mosaicism in CTEPH. In this study we sought to compare the statistical properties of the lung parenchyma as assessed by CT angiography between patients with PE, CTEPH and those without evidence of pulmonary thromboembolism. Methods Patients with appropriate CT imaging were enrolled from consecutive CTEPH patients undergoing PTE at Northwestern University Medical Center. From a larger cohort of patients with CT Pulmonary angiography patients with a diagnosis of PE and those without (Controls) were selected to match the CTEPH cohort based on age, sex and BMI. Lung mask generation and statistical analysis of the lung parenchyma were performed using the Chest Imaging Platform. Medians are presented. Comparisons were made using the Wilcoxon Rank-Sum Test, performed using R version 4.1. Results 87 CTEPH patients, 151 PE patients and 176 control patients were used for the analysis. There was no significant difference in lung volume between the three groups (2.88L vs 3.01L vs 2.97L, p = 0.07, 0.63, 0.31). The mean intensity was lower in both PE and CTEPH patients as compared to controls (PE: -674, CTEPH -675, control -656, p = 0.002 for acute PE, p = 0.07 for CTEPH). The standard deviation was lowest in PE (186 vs 211, p &amp;lt; 0.0001) but the same when compared between CTEPH and Controls (208 vs 211, p = 0.56). Skewness was highest in the PE cohort (2.27 vs 2.03, p = 0.004) with minimal difference between CTEPH and control (2.13 vs 2.03, p = 0.22). On the other hand, Kurtosis was highest in CTEPH (8.2 vs 5.1, p &amp;lt; 0.0001) with PE following second (6.1 vs 5.1, p = 0.003). Mean intensity aside, STD, Skewness and Kurtosis were all statistically significantly different between CTEPH and Acute PE. Discussion In this comparison of patients with established CTEPH undergoing PTE and those with diagnosis of acute PE and those without evidence of PE, we found statistically significant differences between the mean and moments of the parenchymal density values. These differences could reflect differences in perfusion patterns though other processes such as infiltrates and atelectasis may also be playing a part. Assessment of the parenchymal density patterns may serve as an imaging marker for thromboembolic disease. This abstract is funded by: R01HL164717

Thrombotic diseases pose a serious threat to human life and health. Anticoagulant drugs are used to treat and prevent thrombotic diseases. However, although the anticoagulant drugs currently used in clinical practice are effective, they have limitations such as narrow therapeutic window and high risk of bleeding. Therefore, the development of new safe and effective anticoagulants based on natural products and their structural modifications has become an important research direction to overcome the current treatment bottlenecks in this field. In this paper, "thrombotic diseases", "anticoagulant-active molecules", "natural products" and "structural modifications" were used as keywords to search the research data on anticoagulant-active molecules published in the past decade in PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases. The research progress of anticoagulant- active molecules from animals and plants was reviewed, which provide basic data for promoting the development of innovative anticoagulant drugs. In this paper, the classification of thrombotic diseases and the clinical drugs currently used in clinical practice are reviewed. Next, the coagulation mechanism and the fact that an imbalance between coagulation and anticoagulation in vivo can lead to thrombosis are described. Finally, the research reports on anticoagulant active compounds and their structural modifications from plants and animals in the past 10 years are summarized. A total of 68 anticoagulant molecules were identified, which provide an important direction and candidate molecules for the development of new, efficient and low-risk anticoagulant drugs.

Prevalence of venous thromboembolic disease among patients with patent foramen ovale-related arterial ischemic events.

A PU-PLGA based implantable device as a platform for sustained therapeutic delivery of rivaroxaban in thromboembolic diseases

Self-sacrificing templated-derived chitosan microcapsules for targeted drug delivery in thrombolytic therapy.

Antithrombotic effects and underpinning mechanisms of food-derived bioactive peptides: A review.