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Factor XIa (FXIa) may be involved in thrombus formation, but only to a lesser extent involved in haemostasis. Several novel FXIa inhibitors are under investigation, and Phase II trials demonstrated marked reduction of bleeding compared with standard treatment by factor Xa inhibitors. Asundexian is a small molecule that selectively inhibits FXIa. A large-scale Phase III clinical trial, OCEANIC-AF, has been initiated to compare the efficacy and safety between asundexian and apixaban. However, the OCEANIC-AF study was recently halted due to the inferior efficacy of asundexian versus the apixaban control arm. The present report describes up-to-date evidence of FXIa inhibitors and discusses the future position of FXIa inhibitors for patients with AF.
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BACKGROUND: Poor anticoagulation management of warfarin may lead to patient admission, prolonged hospital stays, and even death due to anticoagulation-related adverse events. Traditional non-web-based outpatient clinics struggle to provide ideal anticoagulation management services for patients, and there is a need to explore a safer, more effective, and more convenient mode of warfarin management. OBJECTIVE: This study aimed to compare differences in the quality of anticoagulation management and clinical adverse events between a web-based management model (via a smartphone app) and the conventional non-web-based outpatient management model. METHODS: This study is a prospective cohort research that includes multiple national centers. Patients meeting the nadir criteria were split into a web-based management group using the Alfalfa app or a non-web-based management group with traditional outpatient management, and they were then monitored for a 6-month follow-up period to collect coagulation test results and clinical events. The effectiveness and safety of the 2 management models were assessed by the following indicators: time in therapeutic range (TTR), bleeding events, thromboembolic events, all-cause mortality events, cumulative event rates, and the distribution of the international normalized ratio (INR). RESULTS: This national multicenter cohort study enrolled 522 patients between June 2019 and May 2021, with 519 (99%) patients reaching the follow-up end point, including 260 (50%) in the non-web-based management group and 259 (50%) in the web-based management group. There were no observable differences in baseline characteristics between the 2 patient groups. The web-based management group had a significantly higher TTR than the non-web-based management group (82.4% vs 71.6%, P<.001), and a higher proportion of patients received effective anticoagulation management (81.2% vs 63.5%, P<.001). The incidence of minor bleeding events in the non-web-based management group was significantly higher than that in the web-based management group (12.1% vs 6.6%, P=.048). Between the 2 groups, there was no statistically significant difference in the incidence of severe bleeding and thromboembolic and all-cause death events. In addition, compared with the non-web-based management group, the web-based management group had a lower proportion of INR in the extreme subtreatment range (17.6% vs 21.3%) and severe supertreatment range (0% vs 0.8%) and a higher proportion in the treatment range (50.4% vs 43.1%), with statistical significance. CONCLUSIONS: Compared with traditional non-web-based outpatient management, web-based management via the Alfalfa app may be more beneficial because it can enhance patient anticoagulation management quality, lower the frequency of small bleeding events, and improve INR distribution.
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Anticoagulantes , Relación Normalizada Internacional , Internet , Warfarina , Humanos , Warfarina/uso terapéutico , Warfarina/efectos adversos , Estudios Prospectivos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Hemorragia , Aplicaciones Móviles , Estudios de CohortesRESUMEN
BACKGROUND: Data on the incidence of type 2 non-ST-segment-elevation myocardial infarction (T2MI) in hospitalized patients with COVID-19 has been limited to single-center studies. Given that certain characteristics, such as obesity and type 2 diabetes, have been associated with higher mortality in COVID-19 infections, we aimed to define the incidence of T2MI in a national cohort and identify pre-hospital patient characteristics associated with T2MI in hospitalized patients with COVID-19. METHODS AND RESULTS: Using the national American Heart Association COVID-19 Cardiovascular Disease Quality Improvement Registry, we performed a retrospective 4:1 matched (age, sex, race, and body mass index) analysis of controls versus cases with T2MI. We performed (1) conditional multivariable logistic regression to identify predictive pre-hospital patient characteristics of T2MI for patients hospitalized with COVID-19 and (2) stratified proportional hazards regression to investigate the association of T2MI with morbidity and mortality. From January 2020 through May 2021, there were 709 (2.2%) out of 32 015 patients with T2MI. Five hundred seventy-nine cases with T2MI were matched to 2171 controls (mean age 70; 43% female). Known coronary artery disease, heart failure, chronic kidney disease, hypertension, payor source, and presenting heart rate were associated with higher odds of T2MI. Anti-hyperglycemic medication and anti-coagulation use before admission were associated with lower odds of T2MI. Those with T2MI had higher morbidity and mortality (hazard ratio, 1.40 [95% CI, 1.13-1.74]; P=0.002). CONCLUSIONS: In hospitalized patients with COVID-19, those with a T2MI compared with those without had higher morbidity and mortality. Outpatient anti-hyperglycemic and anti-coagulation use were the only pre-admission factors associated with reduced odds of T2MI.
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COVID-19 , Hospitalización , Infarto del Miocardio sin Elevación del ST , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/complicaciones , COVID-19/terapia , COVID-19/diagnóstico , Femenino , Masculino , Anciano , Infarto del Miocardio sin Elevación del ST/epidemiología , Infarto del Miocardio sin Elevación del ST/terapia , Infarto del Miocardio sin Elevación del ST/mortalidad , Infarto del Miocardio sin Elevación del ST/diagnóstico , Estudios Retrospectivos , Prevalencia , Hospitalización/estadística & datos numéricos , Estados Unidos/epidemiología , Factores de Riesgo , Persona de Mediana Edad , Sistema de Registros , Incidencia , Mortalidad Hospitalaria , Anciano de 80 o más Años , ComorbilidadRESUMEN
Clinical use of small-diameter vascular grafts remains a challenging issue in neovessel regeneration in view of thrombosis and intimal hyperplasia. Developing a vascular graft with structure and function similar to those of the native vessels necessitates a major direction of vascular tissue regeneration. Thus, this study sought to design and fabricate a range of tri-phasic scaffolds (0, 2, and 5 wt% gastrodin-polyurethane (PU)) with spatiotemporally defined structure and gastrodin-release for regulating the highly coordinated processes in growth of the intima and media. While the small pores of inner layer guided infiltration of human umbilical vein endothelial cells (HUVECs), the bigger pores of medial layer could offer smooth muscle cell (SMC)-friendly habitat, and external fibers conferred adequate mechanical properties. Correspondingly, spatial distribution and differential regulation of key proteins in HUVECs and SMCs were mediated by hierarchical release of gastrodin, of which rapid release in inner layer elicited enhanced HUVEC proliferation and migration against those of the SMC via activated endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) signal. Of note, superior anti-coagulation was reflected in 2 wt% gastrodin-PU ex vivo extracorporeal blood circulation experiment. After in vivo implantation for 12 weeks, there was no formation of obvious thrombosis and intimal hyperplasia in 2 wt% gastrodin-PU. The scaffold maintained high patency and improved vascular remodeling, including the formation of thin endothelialization in lumen and dense extracellular matrix deposition in medial layer. Taken together, the results demonstrate the positive function of hierarchical releasing system that responded to tri-phasic structure, which not only suppressed intimal thickening but also tightly controlled tissue regeneration.
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Introduction: Pre-therapeutic histologic diagnosis through image-guided core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) for suspicious breast findings is a standard procedure. Despite the moderate risk of bleeding, a significant proportion of patients are on temporary or permanent anti-coagulation therapy (ACT) or anti-platelet therapy (APT). Currently, there are no established guidelines for managing biopsies in such patients, leading to varying approaches in clinical practice. Methods: An online survey was conducted among all members of the breast ultrasound working group at the German Society for Ultrasound in Medicine (DEGUM) and the working group for breast diagnostics at the German Radiology Society (DRG). It included n = 51 questions about individual risk perception of biopsy-related bleeding complications and the specific management of biopsies on ACT/APT. Results: A total of 332 experts participated, with 51.8% reporting the absence of a standardized management plan for breast biopsies on ACT/APT. Concerning specific ACT/APT medications, the survey revealed discrepancies in risk perception and management: The majority preferred discontinuing medication with directly acting oral anti-coagulants (DOACs; CNB: 66.9%; VAB: 91.1%), phenprocoumon (CNB: 74.9%; VAB: 96.7%), or therapeutic heparin (CNB: 46.1%; VAB: 72.7%). However, there was a lower inclination to discontinue acetylsalicylic acid (ASA; CNB: 15.2%; VAB: 50.3%) or prophylactic heparin (CNB: 11.9%, VAB: 36.3%). Conclusion: Breast biopsies for patients on ASA or prophylactic heparin are deemed safe and part of standard clinical practice. However, despite available feasibility studies, conducting breast biopsies on ACT medications such as DOACs or phenprocoumon appears feasible only for a minority of experts.
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Mesenteric ischemia is an urgent event and requires prompt recognition and treatment, in order to reduce the risk of mortality. It results from the sudden onset of small intestinal hypoperfusion, from a reduction or cessation of arterial perfusion, which can occur from an embolic obstruction at the superior mesenteric artery. We present a case of transient mesenteric ischemia from an episode of atrial fibrillation with a rapid ventricular response rate. Despite being on chronic anticoagulation therapy, the patient developed transient mesenteric ischemia from an embolic clot. The patient's heart rate was controlled and no surgical intervention was required, a rare finding; however, it is very important to recognize and treat promptly.
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In response to the critical demand for advancements in coronary artery stents, this study addresses the challenges associated with arterial recoil and restenosis post-angioplasty and the imperative to encourage rapid re-endothelialization for minimizing thrombosis risks. We employed an innovative approach inspired by mussel adhesion, incorporating placental anticoagulant protein (AnnexinV) on stent design. The introduction of a post-translationally modified catecholic amino acid L-3,4-dihydroxyphenylalanine (L-Dopa), mimicking mussel characteristics, allowed for effective surface modification of Stainless steel stents through genetic code engineering in AnnexinV (AnxDopa). The efficacy of AnxDopa was analyzed through microscale thermophoresis and flow cytometry, confirming AnxDopa's exceptional binding with phosphatidylserine and activated platelets. AnxDopa coated stainless steel demonstrates remarkable bio-, hemo-, and immuno-compatibility, preventing smooth muscle cell proliferation, platelet adhesion, and fibrin formation. It acts as an interface between the stent and biological fluid, which facilitates the anticoagulation and rapid endothelialization. Surface modification of SS verified through XPS analysis and contact angle measurement attests to the efficacy of AnxDopa mediated surface modification. The hydrophilic nature of the AnxDopa-coated surface enhanced the endothelialization through increased protein absorption. This approach represents a significant stride in developing coronary stents with improved biocompatibility and reduced restenosis risks, offering valuable contributions to scientific and clinical realms alike.
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Materiales Biocompatibles Revestidos , Stents , Humanos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Vasos Coronarios/efectos de los fármacos , Adhesividad Plaquetaria/efectos de los fármacos , Anticoagulantes/farmacología , Anticoagulantes/química , Propiedades de Superficie , Proliferación Celular/efectos de los fármacos , Acero Inoxidable/química , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/citología , Animales , Levodopa/química , Levodopa/farmacologíaRESUMEN
Bioprosthetic heart valve (BHV) replacement has been the predominant treatment for severe heart valve diseases over decades. Most clinically available BHVs are crosslinked by glutaraldehyde (GLUT), while the high toxicity of residual GLUT could initiate calcification, severe thrombosis, and delayed endothelialization. Here, we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs. In particular, recombinant humanized collagen type III (rhCOLIII), which was precisely customized with anti-coagulant and pro-endothelialization bioactivity, was first incorporated into the polyvinyl alcohol (PVA)-based hydrogel via hydrogen bond interactions. Then, tannic acid was introduced to enhance the mechanical performance of PVA-based hydrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates. In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLIII and TA possessed long-term anti-coagulant, accelerated endothelialization, mild inflammatory response and anti-calcification properties. Therefore, our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.
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The immunomodulatory properties of the polysaccharides (carrageenan, xylan) from Chondrus crispus (CC), Ahnfeltiopsis devoniensis (AD), Sarcodiotheca gaudichaudii (SG) and Palmaria palmata (PP) algal species were studied. Using RAW264.7 macrophages, we investigated the proliferation and migration capacity of different extracts along with their immunomodulatory activities, including nitric oxide (NO) production, phagocytosis, and secretion of pro-inflammatory cytokines. Polysaccharides from C. crispus and S. gaudichaudii effectively mitigated inflammation and improved scratch-wound healing. Polysaccharide fractions extracted under cold conditions (25 °C), including CC-1A, SG-1A and SG-1B stimulated cell proliferation, while fractions extracted under hot conditions (95 °C), including CC-3A, CC-2B and A. devoniensis (AD-3A), inhibited cell proliferation after 48 h. Furthermore, RAW264.7 cells treated with the fractions CC-3A, AD-1A, and SG-2A significantly reduced LPS-stimulated NO secretion over 24 h. Phagocytosis was significantly improved by treatment with C. crispus (CC-2B, CC-3B) and A. devoniensis (AD-3A) fractions. RAW264.7 cells treated with the CC-2A and SG-1A fractions showed elevated TGF-ß1 expression without affecting TNF-α expression at 24 h. Polysaccharide fractions of A. devoniensis (ι/κ hybrid carrageenan; AD-2A, AD-3A) showed the highest anti-coagulation activity. CC-2A and SG-1A fractions enhanced various bioactivities, suggesting they are candidates for skin-health applications. The carrageenan fractions (CC-3A: λ-, µ-carrageenan, SG-2A: ν-, ι-carrageenan) tested herein showed great potential for developing anti-inflammatory and upscaled skin-health applications.
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Chondrus , Algas Comestibles , Rhodophyta , Algas Marinas , Carragenina/farmacología , Xilanos , Polisacáridos/farmacología , Algas Marinas/metabolismo , Antiinflamatorios/farmacología , AnticoagulantesRESUMEN
Thrombosis is a serious threat to human health and life. Fucoidan, a sulfated polysaccharide from brown algae, could prevent coagulation and thrombus after intravenous administration. However, more efforts are still needed to develop its oral agent. In the present study, the absorption and excretion of fucoidan (90.8 kDa) and its degradation products, Dfuc1 (19.2 kDa) and Dfuc2 (5.5 kDa), were determined by HPLC-MS/MS after acid degradation and 1-phenyl-3-methyl-5-pyrazolone derivatization, and their anticoagulation and antithrombotic activities were evaluated in vivo after oral administration. Results showed that the maximum concentrations of fucoidan, Dfuc1 and Dfuc2 in rat plasma all achieved at 2 h after oral administration (150 mg/kg), and they were 41.1 ± 10.6 µg/mL, 45.3 ± 18.5 µg/mL and 59.3 ± 13.7 µg/mL, respectively. In addition, fucoidan, Dfuc1 and Dfuc2 could all prolong the activated partial thromboplastin time in vivo from 23.7 ± 2.7 s (blank control) to 25.1 ± 2.6 s, 27.1 ± 1.7 s and 29.4 ± 3.6 s, respectively. Moreover, fucoidan and its degradation products showed similar antithrombotic effect in carrageenan-induced thrombosis mice, and untargeted metabolomics analysis revealed that they all markedly regulated the carrageenan-induced metabolite disorders, especially the arachidonic acid metabolism. Thus, the degradation products of fucoidan with lower molecular weights are more attractive for the development of oral antithrombotic agents.
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Anticoagulantes , Trombosis , Ratas , Ratones , Humanos , Animales , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Peso Molecular , Carragenina , Espectrometría de Masas en Tándem , Trombosis/tratamiento farmacológico , Polisacáridos/farmacología , Polisacáridos/uso terapéuticoRESUMEN
STUDY OBJECTIVE: Four-factor prothrombin complex concentrate (4F-PCC) is standard of care for emergent vitamin K antagonist (VKA) reversal but optimal dosing is uncertain. This meta-analysis estimated the proportion of patients treated with fixed dose (FD) 4F-PCC who achieved adequate reversal and compared safety and efficacy of FD versus weight-based dose (WB) strategies. METHODS: This review was conducted according to PRISMA guidelines. Medline and Scopus were searched and included studies evaluating FD regimens and comparing FD and WB for emergent VKA reversal. Data was pooled using random effects. Subgroup analyses examined heterogeneity. Risk of bias was assessed with Newcastle-Ottawa Scale and RoB2 score. RESULTS: Twenty-three studies (n = 2055) were included with twelve (n = 1143) comparing FD versus WB. The proportion of patients achieving goal INR with FD varied depending on the INR target, being significantly higher for INR <2 (90.9%, 95% Confidence Interval (CI) 87.2, 94.06) compared to INR <1.6 (70.97%, 95%CI 65.33, 76.31). Compared to WB, FD was less likely to achieve a goal INR <1.6 (Risk Difference (RD) -13%, 95% CI -21, -4) but achieved similar reversal for a goal INR <2.0, (RD -1%, 95%CI -7, 4). There was no difference in hospital mortality (RD 4%, 95%CI -2, 9) or thrombosis (RD 0.0%, 95%CI -3, 3). CONCLUSION: FD VKA reversal was associated with significantly lower attainment of goal INR compared to WB with lower INR targets. This did not translate to differences in hospital mortality, but these results should be interpreted cautiously in light of the observational nature of the included studies.
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Factores de Coagulación Sanguínea , Vitamina K , Humanos , Relación Normalizada Internacional , Factores de Coagulación Sanguínea/uso terapéutico , Anticoagulantes/efectos adversos , Fibrinolíticos/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: There have been significant changes in the optimal antithrombotic regimen post transcatheter aortic valve implantation (TAVI) after the results of major clinical trials in the past few years. Given the clinical importance of the optimal antithrombotic therapy post TAVI, we performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes, as well the current guideline recommendations and knowledge gaps. METHODS: We performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes. We used PubMed as a major source to collect the major clinical trials including the following key words: "transcatheter aortic valve replacement", "transcatheter aortic valve implantation", "antithrombotic", "antiplatelet" and "anticoagulation". We selected the major clinical trials on this topic. This is not a systematic review or meta-analysis. RESULTS: We describe the results of the major clinical trials on antithrombotic therapy post TAVI: POPULAR-TAVI A, POPULAR-TAVI B, ENVISAGE-TAVI AF, GALILEO, ATLANTIS and ADAPT-TAVR trials. Based on the results of these trials, single antiplatelet therapy is recommended post TAVI in patients without concomitant indication for oral anticoagulation or dual antiplatelet therapy, especially in elderly patients. In younger patients, it is advised to evaluate the patient's bleeding and thrombotic risk, and dual antiplatelet therapy may be reasonable in patients with a high thrombotic risk and low bleeding risk. In patients with a concurrent indication for oral anticoagulation or dual antiplatelet therapy, it is recommended to continue oral anticoagulation or dual antiplatelet therapy post TAVI. CONCLUSION: In most patients without concomitant indication for oral anticoagulation, single antiplatelet therapy is recommended post TAVI.
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Protein S is a glycoprotein created by the body that aids in the prevention of a hypercoagulable state. Protein S-deficient patients are placed on anticoagulant regimens, as there is no current definitive cure. Failure to bring balance to the hematological system in these patients will lead to complications such as widespread clot formation and pulmonary embolisms. Here, we present a 74-year-old female who was admitted to the ICU after collapsing. She presented with respiratory failure, urinary tract infection (UTI), and pneumonia. Magnetic resonance imaging (MRI) scans depicted a thrombus in the distal right transverse sinus and sigmoid sinus. Her hematologic workup showed normal levels of homocysteine, fibrinogen, and protein C levels but protein S levels were reduced to 24%. This case displays the intricate presentation of a rare hematological disease as well as the importance of routine follow-up to maintain patient health.
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OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.
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Anticoagulantes , Análisis Costo-Beneficio , Neoplasias Endometriales , Histerectomía , Tromboembolia Venosa , Femenino , Humanos , Anticoagulantes/administración & dosificación , Anticoagulantes/economía , Anticoagulantes/uso terapéutico , Quimioprevención/economía , Quimioprevención/métodos , Quimioprevención/estadística & datos numéricos , Análisis de Costo-Efectividad , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Enoxaparina/administración & dosificación , Enoxaparina/economía , Enoxaparina/uso terapéutico , Histerectomía/efectos adversos , Histerectomía/economía , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/economía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Estadificación de Neoplasias , Estudios Retrospectivos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlRESUMEN
Currently, glutaraldehyde (GA)-crosslinked bioprosthetic heart valves (BHVs) still do not guarantee good biocompatibility and long-term effective durability for clinical application due to their subacute thrombus, inflammation, calcification, tearing and limited durability. In this study, double-modified xanthan gum (oxidized/vinylated xanthan gum (O2CXG)) was acquired from xanthan gum for subsequent double crosslinking and modification platform construction. Sulfonic acid groups with anticoagulant properties were also introduced through the free radical polymerization of vinyl sulfonate (VS) and vinyl on O2CXG. Taking advantage of the drug-loading function of xanthan gum, the treated pericardium was further loaded with inflammation-triggered dual drug-loaded nanogel (heparin (Hep) and atorvastatin (Ator)). Mechanical properties of O2CXG-crosslinked porcine pericardium (O2CXG-PP) were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Due to the presence of sulfonic acid groups as well as the dual drug release from nanogels under the stimulation of H2O2, the hemocompatibility, anti-inflammatory, pro-endothelialization and anti-calcification properties of the crosslinked pericardium modified with nanogels loaded with Hep and Ator (O2CXG+VS+(Hep+Ator) nanogel-PP) was significantly better than that of GA-crosslinked PP (GA-PP). The collaborative strategy of double crosslinking and sequential release of anticoagulant/endothelium-promoting drugs triggered by inflammation could effectively meet the requirement of enhanced multiple performance and long-term durability of bioprosthetic heart valves and provide a valuable pattern for multi-functionalization of blood contacting materials. STATEMENT OF SIGNIFICANCE: Currently, glutaraldehyde-crosslinked bioprosthetic heart valves (BHVs) are subject to subacute thrombus, inflammation, calcification and tearing, which would not guarantee good biocompatibility and long-term effective durability. We developed a cooperative strategy of double crosslinking and surface modification in which double-modified xanthan gum plays a cornerstone. The mechanical properties of this BHV were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Inflammation-triggered combination delivery of heparin and atorvastatin has been demonstrated to enhance anticoagulation, anti-inflammatory and pro-endothelialization of BHVs by utilizing local inflammatory response. The collaborative strategy could effectively meet the requirement of enhanced multiple performance and long-term durability of BHVs and provide a valuable pattern for the multi-functionalization of blood-contacting materials.
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Bioprótesis , Calcinosis , Prótesis Valvulares Cardíacas , Trombosis , Animales , Porcinos , Nanogeles , Glutaral/química , Peróxido de Hidrógeno/química , Atorvastatina/farmacología , Bases de Schiff , Válvulas Cardíacas , Heparina , Inflamación , Antiinflamatorios , Anticoagulantes , Ácidos SulfónicosRESUMEN
Portal venous thrombosis (PVT) is a rare diagnosis in the general population. However, it is seen in patients with liver cirrhosis with an estimated prevalence ranging from 0.6% to 26%. Literature reports that about one-third of PVT cases have an unknown etiology. Identifying the precipitating factors implicated in the development of PVT is imperative as it may help guide therapy. Although the association between liver cirrhosis and PVT has been well established in current literature, there continues to be a relative lack of awareness of alcoholic hepatitis (AH) as a risk factor for PVT. Identifying AH as a trigger for thrombosis can help avoid extended anticoagulation and its complications. In the following case report and brief review, we discuss an uncommon case of a 33-year-old male who came to the hospital emergency department with complaints of nauseousness, abdominal discomfort, and yellow discoloration. Lab investigations showed transaminitis. The diagnosis of AH was established, and an abdominal duplex ultrasound revealed PVT. Heparin drip was started as a part of treatment, which improved his abdominal discomfort. He was eventually discharged on apixaban 5 mg twice daily for 3 months and a repeat abdominal duplex ultrasound in 3 months to check for the resolution of the PVT.
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Hepatitis Alcohólica , Trombosis , Trombosis de la Vena , Masculino , Humanos , Adulto , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/diagnóstico , Hepatitis Alcohólica/patología , Vena Porta/patología , Trombosis de la Vena/etiología , Trombosis de la Vena/complicaciones , Cirrosis Hepática/complicaciones , Trombosis/complicacionesRESUMEN
Jacobsen's syndrome is a rare genetic disorder caused by deletion of the long arm of chromosome 11 (11q) and is characterized primarily by craniofacial dysmorphism, congenital heart defects, intellectual disability, Paris-Treussaud hemorrhagic disorder, structural renal defects, and immunodeficiency. Although the frequency of intracranial hemorrhage associated with Jacobsen's syndrome is low, it is recognized as an important prognostic factor. In this report, we describe a case of acute and chronic subdural hematoma that developed during anticoagulation therapy after cardiac surgery for congenital heart defects associated with Jacobsen's syndrome, making it difficult to decide on a treatment plan.
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BACKGROUND: Many patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been widely studied. METHODS: Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analyzed using adjusted hazard ratios (HR) obtained via Cox proportional-hazard modeling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity-weighted Cox proportional-hazard models. RESULTS: Of 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-year follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 1.30; 95% confidence interval [CI], 1.16-1.47) and cardiovascular mortality (HR 1.59; 95% CI, 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-hemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (HR 0.74; 95% CI, 0.61-0.90) and major bleeding (HR 0.45; 95% CI, 0.29-0.70) was observed in vascular disease patients treated with NOACs, compared with VKAs. CONCLUSIONS: Atrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Adulto , Humanos , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Administración Oral , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/complicaciones , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Sistema de Registros , Factores de RiesgoRESUMEN
Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.
RESUMEN
Transcatheter aortic valve implantation (TAVI) is an effective and established treatment for symptomatic aortic stenosis. However, there is a lack of consensus concerning the need for peri- and post-procedural anti-thrombotic medication. Contemporary guidelines recommend that anti-thrombotic therapy is balanced against a patient's bleeding risk following TAVI, but do not fully consider the evolving evidence base. The purpose of the Delphi panel recommendations presented here is to provide a consensus elicited from a panel of experts who regularly prescribe anti-thrombotic therapy post-TAVI. The goal was to address evidence gaps across four key topics: anti-thrombotic therapy (anti-platelet and/or anti-coagulant) in TAVI patients in sinus rhythm; anti-thrombotic therapy in TAVI patients with AF; direct oral anti-coagulants versus vitamin K antagonists; and the need for UK/Ireland specific guidance. This consensus statement aims to inform clinical decision-making by providing a concise, evidence-based summary of best practice for prescribing anti-thrombotic therapies following TAVI and highlights areas where further research is needed.