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European Heart Journal Open May 2024Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and...
AIMS
Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed.
METHODS AND RESULTS
To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses.
CONCLUSION
These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.
PubMed: 38933427
DOI: 10.1093/ehjopen/oeae043 -
Health Science Reports Jun 2024Subclinical leaflet thrombosis (SLT) develops in 15% of patients undergoing trans-catheter aortic valve replacement (TAVR). TAVR is a procedure in which a faulty aortic...
OBJECTIVE
Subclinical leaflet thrombosis (SLT) develops in 15% of patients undergoing trans-catheter aortic valve replacement (TAVR). TAVR is a procedure in which a faulty aortic valve is replaced with a mechanical one. An aortic valve replacement can be done with open-heart surgery; this is called surgical aortic valve replacement (SAVR). A significant problem is defining the best course of treatment for asymptomatic individuals with SLT post-TAVR, including the use of oral anticoagulation (OAC) in it.
STUDY DESIGN
Systematic review.
METHOD
The most pertinent published research (original papers and reviews) in the scientific literature were searched for and critically assessed using the online, internationally indexed databases PubMed, Medline, and Cochrane Reviews. Keywords like "Transcatheter valve replacement" and "Subclinical leaflet thrombosis" were used to search the papers. Selected studies were critically assessed for inclusion based on predefined criteria.
RESULTS
The review examined the prevalence and characteristics of SLT after TAVR. To note, the incidence of SLT is seen to be higher in TAVR compared SAVR. Dual antiplatelet therapy, which is utilized in antithrombotic regimens post-TAVR, can possibly hasten SLT progression which could result in the impaired mobility of leaflets and the worsening of pressure gradients.
CONCLUSION
The use of dual antiplatelet drugs in routine antithrombotic therapy tends to accelerate initial subclinical leaflet thrombosis after TAVI, which results in a developing restriction of leaflet mobility and an increase in pressure differences.
PubMed: 38933424
DOI: 10.1002/hsr2.2200 -
Annals of Pediatric Cardiology 2024Retrieval of embolized ductal stents from the pulmonary or systemic circulation can be challenging. Most children benefit from surgical shunts in such scenarios....
Retrieval of embolized ductal stents from the pulmonary or systemic circulation can be challenging. Most children benefit from surgical shunts in such scenarios. Although early retrieval is advised, stents lodged in the peripheral pulmonary tree can be inaccessible, making the removal complicated. In such patients, stents can be "parked" in the segmental pulmonary arterial branches for retrieval later. In the low-pressure single ventricle pulmonary circulation, partially expanded embolized stents, if left , can precipitate pulmonary arterial thrombosis. This subset of patients may benefit from meticulous anticoagulation and antiplatelet agents. In our case report, we describe the successful extraction of an embolized ductal stent without damage to the right lower lobe pulmonary artery (PA). In the follow-up evaluation, the growth of the right PA is good.
PubMed: 38933049
DOI: 10.4103/apc.apc_177_23 -
Annals of Noninvasive Electrocardiology... Jul 2024To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. (Observational Study)
Observational Study
OBJECTIVE
To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation.
METHODS
This retrospective observational cohort study included 196 patients, 75-102-years-old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini-Nutritional Assessment-Short Form (MNA-SF). Patients with MNA-SF scores of 0-11 and 12-14 were included in the malnutrition and nonmalnutrition groups, respectively.
RESULTS
The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p < .05). The incidence of all-cause death in the malnutrition group was higher than that in the nonmalnutrition group (p = .007). Kaplan-Meier curve indicated that malnutrition patients have a higher risk of all-cause death (log-rank test, p = .001) and major bleeding events (p = .017). Multivariate Cox proportional hazard regression analysis corrected for confounders showed that malnutrition was an independent risk factor of all-cause death (HR = 1.780, 95%CI:1.039-3.050, p = .036). The malnutrition group had a significantly high incidence of major bleeding than the nonmalnutrition group (p = .026), and there was no significant difference in the proportion of anticoagulation therapy (p = .082) and the incidence of ischemic stroke/systemic embolism (p = .310) between the two groups.
CONCLUSIONS
Malnutrition is an independent risk factor of all-cause death in elderly patients with atrial fibrillation. The incidence of major bleeding in malnourished elderly patients with atrial fibrillation is high, and the benefit of anticoagulation therapy is not obvious.
Topics: Humans; Atrial Fibrillation; Retrospective Studies; Female; Male; Aged; Nutritional Status; Aged, 80 and over; Malnutrition; Cohort Studies; Risk Factors; Nutrition Assessment; Geriatric Assessment
PubMed: 38932572
DOI: 10.1111/anec.13130 -
Pharmaceutics Jun 2024Unfractionated heparin is administered in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Anticoagulation monitoring is recommended,...
BACKGROUND
Unfractionated heparin is administered in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Anticoagulation monitoring is recommended, with an anti-activated factor X (anti-Xa) targeting 0.3 to 0.7 IU/mL. Owing to heparin's heterogeneous pharmacokinetic properties, anti-Xa is unpredictable, generating a challenge in anticoagulation practices. The aim of this study was to build a pharmacokinetic model of heparin accounting for potential confounders, and derive an optimized dosing regimen for a given anti-Xa target.
METHODS
Adult patients undergoing VA-ECMO were included between January 2020 and June 2021. Anticoagulation was managed with an initial 100 IU/kg heparin loading dose followed by a continuous infusion targeting 0.2 to 0.7 IU/mL anti-Xa. The data were split into model development and model validation cohorts. Statistical analysis was performed using a nonlinear mixed effects modeling population approach. Model-based simulations were performed to develop an optimized dosing regimen targeting the desired anti-Xa.
RESULTS
A total of 74 patients were included, with 1703 anti-Xa observations. A single-compartment model best fitted the data. Interpatient variability for distribution volume was best explained by body weight, C-reactive protein and ECMO indication (post-cardiotomy shock or medical cardiogenic shock), and interpatient variability for elimination clearance was best explained by serum creatinine and C-reactive protein. Simulations using the optimized regimen according to these covariates showed accurate anti-Xa target attainment.
CONCLUSION
In adult patients on VA-ECMO, heparin's effect increased with serum creatinine and medical indication, whereas it decreased with body weight and systemic inflammation. We propose an optimized dosing regimen accounting for key covariates, capable of accurately predicting a given anti-Xa target.
PubMed: 38931891
DOI: 10.3390/pharmaceutics16060770 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Venous thromboembolism (VTE) represents one of the leading causes of death during pregnancy. The greatest risk for it is the presence of medical or family history of... (Review)
Review
Venous thromboembolism (VTE) represents one of the leading causes of death during pregnancy. The greatest risk for it is the presence of medical or family history of VTE, stillbirth, cesarean section and selected thrombophilia. Appropriate thromboprophylaxis has the potential to decrease the risk of VTE in at-risk pregnant patients by 60-70%. Based on this, the authors reviewed the PubMed, Web of Science and Scopus databases to identify the possibilities of thromboprophylaxis in pregnant patients with a high risk of VTE. Moreover, they summarized its management in specific situations, such as cesarean delivery or neuraxial blockade. Currently, low-molecular-weight heparins (LMWH) are the preferred drugs for anticoagulant thromboprophylaxis in the course of pregnancy and postpartum due to easy administration and a lower rate of adverse events.
PubMed: 38931440
DOI: 10.3390/ph17060773 -
Pharmaceuticals (Basel, Switzerland) Jun 2024The extensive use of rodenticides poses a severe threat to non-target species, particularly birds of prey and scavengers. In this study, a GC-MS/MS-based method was used...
The extensive use of rodenticides poses a severe threat to non-target species, particularly birds of prey and scavengers. In this study, a GC-MS/MS-based method was used to unlock the cause of bird deaths in Poland. Organs (liver, heart, kidney, and lungs) collected during autopsies of two rooks () and one carrion crow (), as well as fecal samples, were analyzed for the presence of anticoagulant coumarin derivatives, i.e., warfarin and bromadiolone. As for warfarin, the highest concentration was found in crow samples overall, with concentrations in the feces and lungs at 5.812 ± 0.368 µg/g and 4.840 ± 0.256 µg/g, respectively. The heart showed the lowest concentration of this compound (0.128 ± 0.01 µg/g). In the case of bromadiolone, the highest concentration was recorded in the liver of a rook (16.659 ± 1.499 µg/g) and this concentration significantly exceeded the levels in the other samples. By revealing the reality of the threat, these discoveries emphasize the need to regulate and monitor the trade in rodenticides.
PubMed: 38931431
DOI: 10.3390/ph17060764 -
Pharmaceuticals (Basel, Switzerland) May 2024Literature on the preferred anticoagulant for treating left ventricular thrombus (LVT) is lacking. Thus, our objective was to compare the efficacy of DOACs versus... (Review)
Review
BACKGROUND
Literature on the preferred anticoagulant for treating left ventricular thrombus (LVT) is lacking. Thus, our objective was to compare the efficacy of DOACs versus warfarin in treating LVT.
METHODS
Databases were searched for RCTs and adjusted observational studies that compared DOAC versus warfarin through March 2024. The primary efficacy outcomes of interest were LVT resolution, systemic embolism, composite of stroke, and TIA. The primary safety outcomes encompassed all-cause mortality and bleeding events.
RESULTS
Our meta-analysis including 31 studies demonstrated that DOAC use was associated with higher odds of thrombus resolution (OR: 1.08, 95% CI: 0.86-1.31, : 0.46). A statistically significant reduction in the risk of stroke/TIA was observed in the DOAC group versus the warfarin group (OR: 0.65, 95% CI: 0.48-0.89, : 0.007). Furthermore, statistically significant reduced risks of all-cause mortality (OR: 0.68, 95% CI: 0.47-0.98, : 0.04) and bleeding events (OR: 0.70, 95% CI: 0.55-0.89, 0.004) were observed with DOAC use as compared to warfarin use.
CONCLUSION
Compared to VKAs, DOACs are noninferior as the anticoagulant of choice for LVT treatment. However, further studies are warranted to confirm these findings.
PubMed: 38931375
DOI: 10.3390/ph17060708 -
Plants (Basel, Switzerland) Jun 2024The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into...
The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into pharmaceuticals is (L.) Sch. Bip., also known as (Merat.) M. This plant has been shown to possess various biological activities, including anti-inflammatory, antimicrobial, and antimycotic activities, among others. However, a review of the current literature reveals a paucity of studies investigating the chemical composition of the herb (L.) Sch. Bip. This study presents the development of a method for obtaining an extract of the herb (L.) Sch. Bip. enriched with flavonoids, harvested before flowering and butonization. This study focused on determining the optimal conditions for extraction, including the concentration of the extractant (ethanol), extraction time, raw material/extractant ratio, extraction frequency, complexation reaction time, amount of aluminum chloride solution, and amount of diluted acetic acid. The results indicate that herbs harvested during this specific period exhibited a higher flavonoid content compared to those collected during butonization and flowering. Moreover, this study demonstrated that the flavonoid content could exceed 7% mg REq/100 g D.W. through a one-hour extraction process. Furthermore, the flavonoid content was found to be 7.65 ± 0.03 mg REq/100 g D.W. following a three-minute ultrasound-assisted extraction process, followed by thermal extraction. A qualitative analysis identified a variety of phenolic compounds in the extract, such as chlorogenic acid, 5--p-coumaroylquinic acid, 1--p-coumaroylquinic acid, luteolin-7-glucoside, quercetin-3-glucoside, luteolin-7-rutinoside, 3,5--dicaffeoylquinic acid, quercetin-3--malonylglucoside, apigenin-7-glucoside, luteolin-3-malonylglucoside, cynarin, rhamnetin-3-(-dimethyl rhamnosyl glucosylglucoside), and luteolin. Moreover, this study demonstrated the antimicrobial, anti-inflammatory, anticoagulant, anti-aggregation, and antioxidant activities of the aqueous alcoholic extract from herb (ETIH) against pathogens such as , , and . Additionally, the extract exhibited comparable anti-inflammatory effects on diclofenac sodium. These findings contribute to the understanding of the potential pharmacological applications of the developed herb extract.
PubMed: 38931061
DOI: 10.3390/plants13121629 -
Molecules (Basel, Switzerland) Jun 2024the creation of a dextran coating on cerium oxide crystals using different ratios of cerium and dextran to synthesize nanocomposites, and the selection of the best...
PURPOSE OF THE STUDY
the creation of a dextran coating on cerium oxide crystals using different ratios of cerium and dextran to synthesize nanocomposites, and the selection of the best nanocomposite to develop a nanodrug that accelerates quality wound healing with a new type of antimicrobial effect.
MATERIALS AND METHODS
Nanocomposites were synthesized using cerium nitrate and dextran polysaccharide (6000 Da) at four different initial ratios of Ce(NO)x6HO to dextran (by weight)-1:0.5 (Ce0.5D); 1:1 (Ce1D); 1:2 (Ce2D); and 1:3 (Ce3D). A series of physicochemical experiments were performed to characterize the created nanocomposites: UV-spectroscopy; X-ray phase analysis; transmission electron microscopy; dynamic light scattering and IR-spectroscopy. The biomedical effects of nanocomposites were studied on human fibroblast cell culture with an evaluation of their effect on the metabolic and proliferative activity of cells using an MTT test and direct cell counting. Antimicrobial activity was studied by mass spectrometry using gas chromatography-mass spectrometry against after 24 h and 48 h of co-incubation.
RESULTS
According to the physicochemical studies, nanocrystals less than 5 nm in size with diffraction peaks characteristic of cerium dioxide were identified in all synthesized nanocomposites. With increasing polysaccharide concentration, the particle size of cerium dioxide decreased, and the smallest nanoparticles (<2 nm) were in Ce2D and Ce3D composites. The results of cell experiments showed a high level of safety of dextran nanoceria, while the absence of cytotoxicity (100% cell survival rate) was established for Ce2D and C3D sols. At a nanoceria concentration of 10 M, the proliferative activity of fibroblasts was statistically significantly enhanced only when co-cultured with Ce2D, but decreased with Ce3D. The metabolic activity of fibroblasts after 72 h of co-cultivation with nano composites increased with increasing dextran concentration, and the highest level was registered in Ce3D; from the dextran group, differences were registered in Ce2D and Ce3D sols. As a result of the microbiological study, the best antimicrobial activity (bacteriostatic effect) was found for Ce0.5D and Ce2D, which significantly inhibited the multiplication of after 24 h by an average of 22-27%, and after 48 h, all nanocomposites suppressed the multiplication of by 58-77%, which was the most pronounced for Ce0.5D, Ce1D, and Ce2D.
CONCLUSIONS
The necessary physical characteristics of nanoceria-dextran nanocomposites that provide the best wound healing biological effects were determined. Ce2D at a concentration of 10 M, which stimulates cell proliferation and metabolism up to 2.5 times and allows a reduction in the rate of microorganism multiplication by three to four times, was selected for subsequent nanodrug creation.
Topics: Cerium; Dextrans; Nanocomposites; Humans; Wound Healing; Escherichia coli; Fibroblasts; Anti-Bacterial Agents; Cell Proliferation; Microbial Sensitivity Tests; Cell Line
PubMed: 38930918
DOI: 10.3390/molecules29122853