Anticoagulant Medication Research Articles

Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy – A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg

BackgroundCancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent. MethodsWe examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). ResultsA significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301). ConclusionOur study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.

Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association.

Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.

Abstract 4143227: Incidence of Hemorrhagic Stroke in Hypertrophic Cardiomyopathy

Background: Individuals with hypertrophic cardiomyopathy (HCM) have an elevated risk of ischemic stroke, primarily driven by the increased risk of atrial fibrillation (AF) development in this patient population. This risk remains elevated regardless of CHADS2VASC score; thus, anticoagulation is recommended for all HCM patients with AF. Given the known association between anticoagulant medications and hemorrhagic events, there is likely an assumed risk of hemorrhagic stroke in these individuals. Currently, the incidence of hemorrhagic stroke in HCM and its relationship to AF and anticoagulation has not been well-established in the literature. The goal of this study was to establish the presence of and risk factors for hemorrhagic stroke in individuals with HCM. Methods: A retrospective review of all HCM patients ages 18 and older in our institution’s health system was performed from 2019-2023. ICD 10 codes were used to identify individuals with hemorrhagic stroke. Patient charts were reviewed for additional data including demographics, comorbid conditions, anticoagulant prescription, and other inciting factors prior to the hemorrhagic event. Results: The study cohort comprised 343 HCM patients, of which 47.1% were female and 72.7% were Caucasian. Concurrently, 30% (n=103) had a diagnosis of AF. The overall incidence of hemorrhagic stroke was 2.9% (5.8%, n=6 in those with AF vs 1.7%, n=4 in those without AF); furthermore, AF was associated with a non-statistically significant increased risk of hemorrhagic stroke (RR = 3.36, 95% CI 0.97-11.7). Anticoagulant use at the time of hemorrhagic event was observed in 4 individuals (67%) with AF and 1 individual (25%) without AF. Head trauma and falls were frequently observed as precipitating events prior to hospital admission for hemorrhagic stroke, occurring in 83% (n = 5) of patients with AF and 50% (n = 2) of those without AF. Conclusions: While ischemic stroke and anticoagulant use are commonly studied in those with HCM, the incidence of hemorrhagic stroke in this population is not negligible. Risk of hemorrhagic events in HCM appears largely influenced by anticoagulant use, particularly in those with concurrent AF, and by head trauma. Given the known benefits of anticoagulation on ischemic stroke risk in the HCM population, appropriate counseling and careful attention to individual patient factors may be warranted in the administration of anticoagulants.

Autologous Serum Tear Production in Anticoagulated Patients.

Autologous serum tears (ASTs) are produced from serum obtained by blood draw and used to treat severe dry eye diseases. Multiple cases of failed AST production occurred due to serum becoming a solidified, gel-like substance after centrifugation. The aim of this study was to identify risk factors associated with inability to compound AST. From January 2019 to December 2022, 99 patients received AST produced at Mayo Clinic in Arizona. Patient demographics, medical diagnoses, medications, laboratory results, and events surrounding blood draws were obtained through an IRB-approved retrospective chart review. The laboratory and pharmacy protocol procedures were observed in person after the occurrence of the last production issue. Ten total clotted serum episodes occurred in 4 patients, each with multiple occurrences. The indication for AST was chronic ocular graft-vs-host disease (n = 3) and Sjögren syndrome (n = 1). Eighty percent of episodes were associated with either a systemic infection (n = 7) or pulmonary embolism (n = 1) within the prior month. At the time of blood draw, all 4 patients were treated with antiplatelet and/or anticoagulation medications, including rivaroxaban, apixaban, aspirin, and low-molecular-weight heparin. The AST protocol was increased from 30 to 60 minutes of resting time to allow clotting before centrifugation. Inadequate clotting during this stasis period likely resulted in fibrinogen remaining suspended in the serum, leading to solidified plasma instead of liquid serum. We hypothesize risk of inadequate clotting would be increased in patients taking anticoagulation or antiplatelet medications. Our recommendations include ensuring 60-minute collection tube resting time for all patients, including those on anticoagulation medication.

Periodontal and peri-implant bleeding on probing in patients undergoing supportive maintenance: a cross-sectional study

ObjectiveAssessment of periodontal and peri-implant inflammation, evidenced by bleeding on probing (BOP), among partially dentate patients receiving supportive periodontal care (SPC).Material & methodsPatient charts from the Center for Dentistry and Oral Medicine of Goethe-University Frankfurt with at least one dental implant were reviewed. Measurements included probing pocket depth (PPD), BOP, and full-mouth bleeding and plaque scores for all teeth and implants.Results100 patients (median; lower/upper quartile: age 68.9; 62.6/76.5 years; 51 females, 6 smokers, 16 with anticoagulative medication, 6 localized stage III, 57 generalized stage III, 37 stage IV, 70 grade B, 30 Grade C, 22; 20/25 teeth left, 2; 1/4 implants) were examined. Peri-implant BOP (24; 11.5/41.5%) was significantly higher than BOP at teeth (14; 8/21.5%) (p < 0.001). A median of 0 (0/1) implants exhibited no BOP and 0 (0/1) only one site with BOP. Shallow pockets (PPD 1–3 mm) were significantly more frequent in teeth (93; 87/97%) than in implants (72.5; 58/94.5%; p < 0.001). Moderately deep pockets (PPD 4 and 5 mm) were less frequent in teeth compared to implants (6; 2/11%; 22; 5.5/33%; p < 0.001).ConclusionsPeri-implant sites exhibit a higher prevalence of BOP compared to periodontal sites in SPC patients.Clinical relevancePractitioners providing supportive periodontal care to patients with dental implants should anticipate a greater prevalence of BOP around implants compared to teeth.

Chronic Subdural Hematomas-A Retrospective Analysis of the Internal Architecture and Evaluation of Risk Factors for Recurrences After Surgical Therapy.

Background: Chronic subdural hematoma (CSDH) is increasingly common due to the aging population and widespread use of anticoagulant and antiplatelet medications. The objective of this study is to examine the internal composition of CSDH and explore potential risk factors associated with its recurrence. Methods: This retrospective study analyzed data from 189 patients who underwent surgery in our department between 2014 and 2018. Recorded data included demographics, clinical information, details of surgical interventions, computer tomography (CT) scans, neurological assessments, and follow-up data. The outcome was evaluated clinically and through CT follow-up conducted 4-12 weeks post-surgery. CT scans measured various parameters, including hematoma thickness, hyperdense regions, chronic components, and membrane presence. Results: Patients after the evacuation of CSDH were significantly more common males (66.1%, p > 0.001) had a significantly higher BMI (p < 0.001, 61.6%), arterial hypertension (p < 0.001, 68.3%), and the intake of anticoagulant therapy (p < 0.001, 58%). The recurrence rate was 18.6% after 4 weeks and 2.1% after 8-12 weeks. After uni- and multivariable analysis, the initial hemispheric type (p = 0.019, HR: 3.191; p = 0.012, HR: 3.810) and the increasing preoperative midline shift in CT (p = 0.028, HR: 1.114; p = 0.041, HR: 1.107) were found as independent predictors for recurrence. Overall, outcomes were favorable with a modified Rankin scale (mRS) of 0-2 at discharge (72%), after 4 (89.7%) and 12 (87%) weeks. Conclusion: According to our data, increasing midline shift before surgery and initial hemispheric type of hematoma were independent predictors of recurrence. Most patients achieved an excellent outcome with a low-risk profile.

Risk of Hematuria-related Complications Associated With Anticoagulant and Antiplatelet Medications: A Single-Institution Retrospective Cohort Study

ObjectiveTo evaluate enteral and parenteral anticoagulant and antiplatelet medications and their associated risks of hematuria-related complications. Materials and MethodsThis was a single-institution, retrospective cohort study. Primary outcomes were counts of ED visits, hospital admissions, and urologic procedures to manage gross hematuria that occurred while patients were exposed to anticoagulant/antiplatelet medications. Multivariable negative binomial regression was used to identify incidence density rates and rate ratios for hematuria-related complications associated with each anticoagulant/antiplatelet medication. ResultsAmong 119,528 patients in the study cohort, 10,601 were exposed to rivaroxaban and 108,927 were not exposed to rivaroxaban. Patients who were prescribed rivaroxaban were more likely to be male (55.5% vs. 52.0%, p <.001), of white race (95.9% vs. 92.8%, p <.001), and have higher BMIs (median BMI, 29.3 vs. 28.3, p <.001). Those not exposed to rivaroxaban had lower incidence density rates than those exposed to rivaroxaban for any hematuria-related complication (29.4 vs. 39.3). Exposure to enoxaparin compared to rivaroxaban was associated with higher rates of any hematuria-related complication (adjusted risk ratio (aRR) 2.74, 95% CI 2.43-3.10), emergency department visits related to hematuria (aRR 3.34, 95% CI 2.73-4.11), and hematuria-related hospitalizations (aRR 4.58, 95% CI, 3.70-5.70). All other oral anticoagulant and antiplatelet medications studied were associated with lower risk than rivaroxaban for hematuria-related complications. ConclusionsAmong enteral and parenteral anticoagulant and antiplatelet medications studied, enoxaparin is associated with the highest rates of hematuria-related events. Further work is needed to elucidate the mechanisms by which distinct anticoagulant and antiplatelet medications contribute to hematuria.

Treatment and outcome after hip fracture for patients on oral anticoagulation

AimsAn increasing number of patients with hip fracture are taking oral anticoagulation medication including direct oral anticoagulants (DOAC). The management of these patients regarding the timing of surgery and occurrence of complications remains contentious. The aim of this study was to compare treatment and outcomes for hip fracture patients taking anticoagulation. MethodsData from a consecutive series of 3,707 hip fracture patients admitted to a single centre was collected over a seven-year period. ResultsThe proportion of patients taking warfarin fell slightly over the study period (6.1% to 4.7%) whilst the proportion taking DOAC increased greatly (1.4% to 11.4%). Patients on oral anticoagulation were slight older (mean age 83 years for warfarin, 85 years for DOAC versus 80 years for those not on anticoagulation), more likely to have atrial fibrillation, less likely to take anti-platelet medication and less likely to have spinal anaesthesia. Patients taking oral anticoagulant had an increased delay to theatre (mean hours admission to theatre 37.9 for warfarin, 39.5 for DOAC, 31.1 for no anticoagulation). There was no difference in the number of patients transfused, wound complications, post-operative haemoglobin or 30 -day mortality between groups. ConclusionCurrent policies on the timing of surgery and anticoagulation are safe.

Outcomes Associated with Novel Oral Anticoagulants and Warfarin in Patients with Cardiac Thrombus Following STEMI

The treatment of cardiac thrombus after ST-segment elevation myocardial infarction (STEMI) is anticoagulation. There is conflicting data on effectiveness and safety of novel oral anticoagulants (NOACs) vs. warfarin. Using the national Medicare data, we identified patients with an admission diagnosis of STEMI and cardiac thrombus within six months after STEMI. Patients were divided into two groups based on initial type of anticoagulation medication (NOACs vs. warfarin). The two main outcomes were ischemic stroke/transient ischemic attack (TIA) and bleeding. Follow-up was performed through the end of 2023. Kaplan-Meier (KM) Curves and Cox proportional hazard models were utilized. Of 881 patients prescribed anticoagulation after STEMI with subsequent cardiac thrombus, 496 patients were prescribed NOACs (56.3%) and 385 patients (43.7%) warfarin. For ischemic stroke, the median follow-up time was 177 days (95% CI: 148-193) for warfarin and 266 days (95% CI: 204-326) for NOACs. There was significantly lower risk of ischemic stroke or TIA in cardiac thrombus patients treated with NOACs compared to warfarin [HR 0.73 (0.57-0.93)]. For bleeding, the median follow-up time was 192 days (95% CI: 175-232) for warfarin and 277 days (95% CI: 212-332) for NOACs. There was also a lower risk of bleeding in patients treated with NOACs compared to warfarin [HR 0.78 (CI 0.66-0.92)]. In conclusion, STEMI patients with cardiac thrombus had lower risk of ischemic stroke and bleeding when treated with NOACs compared to warfarin. Prospective randomized studies are needed to confirm these findings and further examine the comparative effectiveness of different anticoagulant strategies.

The effect of Vitamin K antagonists as anticoagulants on bleeding in patients post-dental procedures

Background: Individuals undergoing continuous treatment and taking vitamin K antagonist (VKA) and other anticoagulant medications are at a higher risk of experiencing bleeding complications during and after dental surgery procedures. Objective: To determine the effect of vitamin K antagonists in post-dental procedure patients by exploring existing literature on managing patients on vitamin K antagonist therapy as anticoagulants. Methods: This research utilized a literature review based on a database search of studies published between 2019-2024. The literature search used strategies with the terms “Tooth extraction bleeding,” “Odontectomy bleeding,” “Vitamin K Antagonist,” and “Anticoagulant,” utilizing databases such as PubMed, Science Direct, and SCOPUS related to the research topic and meeting eligibility criteria. The studies were then reviewed, summarized, and conclusions were drawn using tables to reveal all data regarding study characteristics and results. Results: Patients using anticoagulants are categorized as high risk for bleeding when undergoing invasive dentistry procedures. VKA is the most commonly used anticoagulant to prevent blood clotting. The consumption of VKA does not significantly affect bleeding post-procedure. Dental procedures can be performed on patients taking anticoagulants without discontinuing the therapy. Conclusion: Based on several studies from various literature sources, it can be concluded that dental procedures in patients taking vitamin K antagonist anticoagulants can still be performed without the risk of bleeding complications with proper local hemostatic measures and perioperative management.

Impact of systemic diseases on oral health and facial surgery outcomes

Systemic diseases have a profound influence on oral health and maxillofacial surgical outcomes, presenting challenges that require comprehensive management. Diabetes mellitus is a prominent example, with its impact on periodontal health and healing processes being well-established. Elevated blood glucose levels in diabetic patients impair immune response, reduce collagen synthesis, and delay wound healing, increasing the risk of periodontitis and postoperative complications following surgical interventions such as dental implants. Similarly, cardiovascular diseases exacerbate the inflammatory response linked to periodontal disease, potentially worsening both oral health and systemic conditions, thus complicating the recovery process after maxillofacial surgery. These patients often face heightened risks of infections and slower healing, partly due to the frequent use of anticoagulant medications, which can interfere with surgical procedures. Immunocompromised individuals, such as those with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or undergoing chemotherapy, also experience significant oral health challenges, including higher susceptibility to oral infections and delayed tissue repair. Reduced immune function and mucosal integrity make it difficult for these patients to recover effectively after maxillofacial surgery, increasing the risk of complications such as infection and wound dehiscence. Moreover, osteoporosis, a systemic condition characterized by reduced bone density, affects the success of dental implants and bone grafting procedures. The decreased bone quality in osteoporotic patients compromises the ability to achieve stable osseointegration, leading to higher implant failure rates and additional surgical challenges. Addressing these complex interactions between systemic health and oral conditions requires an interdisciplinary approach, integrating medical and dental care to enhance treatment outcomes. Proper management of systemic diseases, along with individualized dental and surgical protocols, is essential to improving the prognosis for patients with concurrent systemic and oral health issues.

Direct annual healthcare costs in survivors of acute pulmonary embolism: estimates based on a prospective multicentre cohort study

Abstract Background Patients surviving acute pulmonary embolism (PE) necessitate long-term care and follow-up. However, the economic impact of PE on healthcare systems after the acute event remains largely unknown. Purpose To estimate the direct cost of PE during the first year after discharge from hospital for the index event, focusing on rehospitalizations, anticoagulant medication, and outpatient follow-up. Methods We analyzed the data from a multicentre cohort study of 1017 unselected patients with confirmed acute symptomatic PE in Germany. After the index episode, the costs of which were not considered, patients prospectively followed an outpatient visit plan at 3, 12 and 24 months. All rehospitalisations were documented with the main and accompanying diagnoses; hospital costs were calculated based on current reimbursement in the German Diagnosis Research Groups (G-DRG) system. The duration and type (central unique drug identifier) of anticoagulant treatment was documented at each visit. Per-patient costs of ambulatory follow-up visits and tests were calculated by multiplying (i) the costs of each visit/test (German ambulatory healthcare services reimbursement catalogue) by (ii) the probability π (0.0≤π≤1.0) of needing that specific service, based on the PE follow-up algorithm of the ESC Guidelines which we populated with the actual results per step in the present study (Figure). The primary analysis was conducted in all patients with ≥3-month follow-up. An additional sensitivity analysis included only the patients completing ≥12-month follow-up. We additionally identified the baseline predictors for the number of rehospitalizations and costs using multivariable zero-inflated Poisson and hurdle regression and accounting for censored data. Results Of 1017 enrolled patients, 958 (94%) were included in the primary analysis. Of them, 24% were rehospitalized, for a marginal mean of 0.34 (bootstrapped 95% CI: 0.30-0.39) readmissions per PE survivor. Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis) cancer, emerged as independent cost predictors by multivariable hurdle gamma regression (Table). Estimated overall rehospitalisation costs were €1138 (95% CI 896-1420) per patient (€1171 [908-1479] in the sensitivity analysis). Mean anticoagulation duration was 330 days, with estimated per-patient costs of €1050 (€1190 in the sensitivity analysis). Per-patient costs of ambulatory follow-up visits and tests were estimated at €182, yielding a total cost of illness per PE survivor of €2370-2543. For the entire country, the annual direct costs after acute PE would thus amount to €202-217 million. Conclusions By estimating per-patient costs and identifying major cost drivers of post-PE care, the present study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved overall cardiovascular prevention.TableFigure

A bioanalytically validated RP-HPLC method for simultaneous quantification of rivaroxaban, paracetamol, and ceftriaxone in human plasma: a combination used for COVID-19 management

Rivaroxaban is a direct oral anticoagulant medication that has been found to be beneficial for the management of thromboembolic events linked to the Corona virus disease 2019 (COVID-19) pandemic, which has resulted in more than 6 million deaths worldwide. Hence, a sensitive, selective, and green bioanalytically validated method was developed using RP-HPLC coupled with DAD for the simultaneous determination of rivaroxaban in human plasma, and two co-administered drugs, namely, paracetamol, an analgesic, and ceftriaxone, an antibiotic, that are used in the management of COVID-19. An Exsil 100 ODS C18 column (250 × 4.6 mm, 5 μm) was used as the stationary phase, and acetonitrile: water: methanol at a ratio of 60:30:10 (v/v/v) was used in isocratic mode as the mobile phase with a flow rate of 0.7 ml/min. The method was validated over a concentration range of 0.1–10.0 µg/mL for rivaroxaban, and 1.0–15.0 µg/mL for paracetamol and ceftriaxone. The lower limits of detection (LLODs) were found to be 0.03, 0.32, and 0.32 µg/ml for rivaroxaban, paracetamol, and ceftriaxone, respectively. Moreover, the lower limits of quantitation (LLOQs) were found to be 0.1, 0.96, and 0.98 µg/ml. The developed method showed excellent accuracy and precision for the determination of the aforementioned drugs. Four metrics were used to evaluate the greenness of the developed method. The results revealed that the suggested method is green, with values of 81 and 0.6 for the analytical eco-scale and analytical greenness assessment (AGREE), respectively.

Proton pump inhibitors and cardiovascular risk: a critical review.

Proton pump inhibitors (PPI) are widely used medications for gastrointestinal disorders. Recent research suggests a potential association between long-term PPI use and increased cardiovascular (CV) risk, creating a complex clinical dilemma. This review critically evaluates the current evidence for this association, considering the limitations of observational studies and the lack of definitive confirmation from randomized controlled trials.This review delves into the reported association between PPIs and adverse CV events, examining proposed mechanisms such as drug interactions, electrolyte imbalances induced by PPIs and their potential impact on cardiac and vascular function. Evidence suggests these mechanisms converge, with varying influence depending on patient populations.Clinicians require a risk-benefit analysis for each patient considering their CV risk profile. Alternative gastrointestinal therapies should be explored for high-bleeding risk patients. Medications with lower cytochrome-P450 interaction potential may be preferable among essential PPI users. Elucidating the specific mechanisms by which PPIs might influence CV health, assessing long-term vascular effects and investigating interactions with newer anticoagulant medications are crucial for future research.

Outcomes and management of Haemoptysis in the Fontan population

Abstract Background Patients with a Fontan circulation for palliation of a univentricular congenital heart defect commonly possess pulmonary vascular abnormalities including arteriovenous malformations (AVM), aortopulmonary and venous-venous collaterals (1). These vessels are prone to haemorrhage which may result in life-threatening haemoptysis (2). This risk is increased with oral anticoagulant medication, given to reduce the risk of thromboembolism in Fontan patients (3). Management of these patients is difficult, and strategies vary across institutions. Purpose We aim to describe our experience with managing adult Fontan patients presenting with haemoptysis in a tertiary centre with a large Fontan cohort. Methods We retrospectively reviewed the records of 410 adult Fontan patients. Individuals admitted to our institution with an episode of haemoptysis were included. Details relating to anticoagulation regimens, interventions and mortality of patients were captured. Results From a cohort of 410 Fontan patients, 35 haemorrhagic events were observed in 11 patients (2.68%). The median age at initial haemoptysis was 24.5 years (range 19 to 43 years). 6 of the 11 patients were female (54.5%). Haemoptysis recurred in 8 of the 11 patients (72.7%). 2 out of 11 had a prior history of haemoptysis in childhood. All patients were administered with oral vitamin K antagonists at presentation. 24 of the 35 events were managed conservatively with IV fluids, anticoagulation reversal and tranexamic acid (66.7%). 11 events required catheter-based interventions, with coil and/or plug embolization of bleeding vessels. Prior to intervention, CT successfully identified potential bleeding sites in 10 of the 11 events (90.9%) but could not visualise all vessels that were subsequently embolized. The most common culprits for haemoptysis were aortopulmonary collaterals, followed by AVMs and venous-venous collaterals. In severe cases, more extensive management was required including transfusions, bronchoscopy, intubation, surgical exploration (1 patient) and pneumonectomy (1 patient). 3 patients died following recurrent severe haemoptysis (27.3%), and 2 patients died of subsequent Fontan failure and sudden cardiac death respectively. Total mortality of the cohort is 5 out of 11 (45.5%) with a median follow up of 10.75 years (range 3 days to 27 years). Conclusions Haemoptysis is a rare but potentially fatal complication in patients who have undergone a Fontan procedure. The variability in presentation of this condition mandates an individualised approach to management with involvement of a multidisciplinary team. There is a high rate of recurrence following haemoptysis and a comprehensive assessment of all potential bleeding sites is necessary. CT is a useful tool to help facilitate this and guide further management. Our policy is to close all potential sources of bleeding as CT and invasive angiography rarely identifies an active point of bleeding.

Advanced Applications of Nanomaterials in Atherosclerosis Diagnosis and Treatment: Challenges and Future Prospects.

Atherosclerosis-induced coronary artery disease is a major cause of cardiovascular mortality. Clinically, conservative treatment strategies for atherosclerosis still focus on lifestyle interventions and the use of lipid-lowering and anticoagulant medications. Despite achieving some therapeutic effects, these approaches are limited by low bioavailability, long intervention periods, and significant side effects. With the advancement of nanotechnology, nanomaterials have demonstrated extraordinary potential in the biomedical field. Their excellent biocompatibility, surface modifiability, and high targeting capability not only enable efficient diagnosis of plaque progression but also allow precise drug delivery within atherosclerotic plaques, significantly enhancing drug bioavailability and reducing systemic side effects. Here, we systematically review the current research progress of nanomaterials in the field of atherosclerosis to summarize not only the types of nanomaterials but also their applications in both the diagnosis and treatment of atherosclerosis. Notably, in the context of plaque therapy, we provide a comprehensive overview of current nanomaterial applications based on their targeted therapeutic systems for different cell types within plaques. Additionally, we address the persistent challenge of clinical translation of nanomaterials by summarizing current issues and providing directions for innovation and improvement in nanomaterial design. Overall, we believe that this review systematically summarizes the applications and challenges of biomedical nanomaterials in atherosclerosis diagnosis and therapy, thereby offering insights and references for the development of therapeutic materials for atherosclerosis.

A Review on Venous Thrombosis: Management with anticoagulants

Thrombosis is the most common condition and the world's leading cause of death due to blood clot development in blood arteries. Thromboembolism includes classification based on where the thrombus gets attached to the blood vessels. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two of the main causes of vascular death globally, making up venous thromboembolism (VTE). According to estimates, the yearly incidence rates of VTE in individuals with European ancestry vary from 104 to 183 per 100,000 person-years. Thrombus development and propagation are dependent upon the existence of anomalies in blood flow, blood vessel wall, and blood clotting components, which are together referred to as Virchow's triad. A comprehensive diagnostic approach, which includes clinical evaluation, D-dimer testing, ultrasonography, and lung scan, provided a non-invasive diagnosis for most outpatients with suspected venous thromboembolism. Anticoagulant medication is the primary and established treatment for people who have acute venous thromboembolism (VTE). Among the treatment options available, UFH &amp; LMWH are found to be safe for the growing fetus as they appear to not cross the placenta. Oral anticoagulants targeting thrombin or factor Xa have been introduced, replacing vitamin K antagonists. In a study involving DOACs vs VKAs in patients with pre-existing heart conditions, patients receiving DOACs for non-valvular atrial fibrillation had predominantly superior efficacy and safety. Keywords: Venous thromboembolism, Anticoagulants, Deep vein thrombosis, Pulmonary embolism, Thrombus

Cystoid macular edema after low-energy femtosecond-assisted cataract surgery.

This study aimed to evaluate the occurrence of pseudophakic cystoid macular edema (PCME) post low-energy femtosecond laser-assisted cataract surgery (FLACS) in a high-volume surgical setting. The medical records of 242 FLACS patients were retrospectively reviewed. The central subfield macular thickness (CSMT) was measured via optical coherence tomography (OCT) before and 4-6weeks after surgery, and the results were compared for PCME detection. Macular edema was defined as a 10% increase in CSMT, a new onset of intraretinal fluid, or a decrease in visual acuity (VA). VA development in PCME patients was reviewed at 2-3months and 6months. The median patient age was 72years (49-92years). Among 242 eyes, seven eyes (2.89%) developed PCME. The median preoperative CSMT in these eyes was 255μm (minimum 231μm, maximum 326μm), whereas the median CSMT at 4-6weeks after surgery was 317μm (minimum 255μm, maximum 463μm). 4- to 6-week postoperative visual acuity decreased in comparison with 1-week postoperative values in three eyes of two patients, remained stable in two patients, and improved in one patient, whereas one patient did not return for his 1-week appointment but improved from 0.4 to 0.2 logMAR 2.5months postoperatively. By 3-6months, all eyes with PCME had gained visual acuity in comparison with their preoperative values. None of the PCME patients had diabetes or used prostaglandin analogues. Three patients were receiving anticoagulation medication. A 2.89% incidence of PCME after low-energy FLACS matched published standard phacoemulsification rates. In our series of uncomplicated cases, PCME caused only a transient postoperative decrease in visual acuity. What is known Increased prostaglandin levels have been detected in the aqueous humour of cataract patients after femtosecond laser application. Prostaglandins are mediators of inflammation. Femtosecond lasers come in low energy and high energy variants. There is contrasting evidence of increased incidence of PCME after femtosecond laser assisted cataract surgery (FLACS) What is new The incidence of PCME after low-energy FLACS in our high volume surgical setting is 2.89% Low-energy FLACS does not seem to have a causative effect on PCME.

Silent brain ischemia within the TAXINOMISIS framework: association with clinical and advanced ultrasound metrics.

IntroductionThe relationship between carotid artery stenosis (CAS) and ipsilateral silent brain ischemia (SBI) remains unclear, with uncertain therapeutic implications. The present study, part of the TAXINOMISIS project (nr. 755,320), aimed to investigate SBIs in patients with asymptomatic CAS, correlating them with clinical, carotid ultrasonographic data, and CFD analyses.MethodsThe TAXINOMISIS clinical trial study (nr. NCT03495830) involved six vascular surgery centers across Europe, enrolling patients with asymptomatic and symptomatic CAS ranging from 50 to 99%. Patients underwent carotid ultrasound and magnetic resonance imaging (MRI), including brain diffusion-weighted, T2-weighted/FLAIR, and T1-weighted sequences. Brain MRI scans were analyzed for the presence of SBI according to established definitions. Ultrasound assessments included Doppler and CFD analysis. Only asymptomatic patients were included in this substudy.ResultsAmong 195 asymptomatic patients, the mean stenosis (NASCET) was 64.1%. Of these, a total of 33 patients (16.9%) had at least one SBI detected on a brain MRI scan. Specifically, 19 out of 33 patients (57.6%) had cortical infarcts, 4 out of 33 patients (12.1%) had ipsilateral lacunar infarcts, 6 out of 33 patients had (18.2%) subcortical infarcts, 1 out of 33 patients (3.0%) had both cortical and lacunar infarcts, and 3 out of 33 patients (9.1%) both cortical and subcortical infarcts. Patients with SBIs exhibited significantly higher risk factors, including a higher body mass index (28.52 ± 9.38 vs. 26.39 ± 3.35, p = 0.02), diastolic blood pressure (80.87 ± 15.73 mmHg vs. 80.06 ± 8.49 mmHg, p = 0.02), creatinine levels (93.66 ± 34.61 μmol/L vs. 84.69 ± 23.67 μmol/L, p = 0.02), and blood triglycerides (1.8 ± 1.06 mmol/L vs. 1.48 ± 0.78 mmol/L, p = 0.03). They also had a higher prevalence of cardiovascular interventions (29.6% vs. 13.8%, p = 0.04), greater usage of third/fourth-line antihypertensive treatment (50%vs16%, p = 0.03), and anticoagulant medications (60% vs. 16%, p = 0.01). Additionally, the number of contralateral cerebral infarcts was higher in patients with SBIs (35.5% vs. 13.4%, p &amp;lt; 0.01). Moreover, carotid ultrasound revealed higher Saint Mary’s ratios (15.33 ± 12.45 vs. 12.96 ± 7.99, p = 0.02), and CFD analysis demonstrated larger areas of low wall shear stress (WSS) (0.0004 ± 0.0004 m2 vs. 0.0002 ± 0.0002 m2, p &amp;lt; 0.01).ConclusionThe TAXINOMISIS clinical trial provides valuable insights into the prevalence and risk factors associated with SBIs in patients with moderate asymptomatic carotid stenosis. The findings suggest that specific hemodynamic and arterial wall characteristics may contribute to the development of silent brain infarcts.

A superior material with antithrombotic properties serves as a secure adsorbent for the elimination of bilirubin in vitro and in pig models

Hyperbilirubinemia is primarily treated through hemoperfusion, a process that utilizes biomaterials as adsorbents to eliminate excessive bilirubin from the bloodstream. However, extracorporeal circuits are prone to thrombus formation due to the frequent use of blood-contacting devices, potentially leading to treatment failure and adverse clinical outcomes. In this study, using a resin substance treated with sulfated polysaccharides (GLU-ERM-0100), we present a reliable and safe approach for removing excessive bilirubin from blood. The resin’s pore size facilitates bilirubin adsorption, while sulfonic and hydroxyl groups incorporated within the material enable like-heparinization. GLU-ERM-0100 serves as a temporary blood-thinning agent, binding coagulation factors in the extracorporeal circuit, thereby eliminating the need for conventional anticoagulant medications. Both in vitro and animal studies demonstrate the material’s exceptional bilirubin adsorption capacity and effective anticoagulation properties.