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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 -
The Role of Viscoelastic Testing in Assessing Hemostasis: A Challenge to Standard Laboratory Assays?Journal of Clinical Medicine Jun 2024Viscoelastic testing is increasingly being used in clinical and research settings to assess hemostasis. Indeed, there are potential situations in which viscoelastic... (Review)
Review
Viscoelastic testing is increasingly being used in clinical and research settings to assess hemostasis. Indeed, there are potential situations in which viscoelastic testing is reportedly superior to standard routine laboratory testing for hemostasis. We report the current testing platforms and terminology, as well as providing a concise narrative review of the published evidence to guide its use in various clinical settings. Notably, there is increasing evidence of the potential utility of viscoelastic testing for assessment of direct oral anticoagulants, and bleeding associated with chronic liver disease, orthotopic liver transplantation, cardiac surgery, trauma, obstetrics and pediatrics.
PubMed: 38930139
DOI: 10.3390/jcm13123612 -
Journal of Clinical Medicine Jun 2024: Antigen carbohydrate 125 (CA-125) is a complex glycoprotein extensively studied as a prognostic biomarker in heart failure, yet its potential role in the short-term...
: Antigen carbohydrate 125 (CA-125) is a complex glycoprotein extensively studied as a prognostic biomarker in heart failure, yet its potential role in the short-term prognosis of an acute pulmonary embolism (PE) remains unexplored. : In this observational, prospective, single-center study, consecutive patients aged 18 and older with a confirmed acute symptomatic PE and no history of prior anticoagulant therapy were enrolled. Primary and secondary objectives aimed to assess the prognostic capacity of CA-125 at PE diagnosis for 30-day mortality and major bleeding, respectively. : A total of 164 patients were included (mean age 69.8 years, SD 17), with 56.1% being male. Within 30 days, 17 patients (10.4%) died and 9 patients (5.5%) suffered major bleeding. ROC curve analysis for 30-day mortality yielded an area under the curve of 0.69 (95% CI 0.53-0.85) with an optimal CA-125 cut-off point of 20 U/mL and a negative predictive value of 96%. Multivariate analysis revealed a significant association between CA-125 levels exceeding 20 U/mL and 30-day mortality (adjusted odds ratio 4.95; 95% CI 1.61-15.2) after adjusting for age, cancer, NT-proBNP > 600 ng/mL, and the simplified pulmonary embolism severity index score. Survival analysis for 30-day mortality exhibited a hazard ratio of 5.47 (95% CI 1.78-16.8). No association between CA-125 levels and 30-day major bleeding was found. : CA-125 emerges as a promising surrogate biomarker for short-term mortality prediction in an acute symptomatic PE. Future investigations should explore the integration of CA-125 into PE mortality prediction scores to enhance the prognostic accuracy in this patient population.
PubMed: 38930129
DOI: 10.3390/jcm13123601 -
Journal of Clinical Medicine Jun 2024: Among the endovascular approaches for the management of endoleak type 2 (EL 2), transcaval embolization (TCE) has shown encouraging outcomes. However, the literature...
: Among the endovascular approaches for the management of endoleak type 2 (EL 2), transcaval embolization (TCE) has shown encouraging outcomes. However, the literature is still limited. This study aimed to present the early and mid-term outcomes of TCE for EL 2 after endovascular aortic repair. : A retrospective, single-center analysis of consecutive patients managed with TCE for EL 2 after standard or complex endovascular aortic repair, from August 2015 to March 2024, was conducted. The indication for TCE was the presence of an EL 2 related to ≥5 mm sac increase, compared to the first imaging after aneurysm exclusion or the smallest diameter during follow-up. Patients managed with TCE for other types of endoleaks were excluded. The primary outcomes were technical and clinical successes during follow-up. Forty-three patients were included (mean age: 75.1 ± 6.0 years, 90.7% males). Technical success was 97.7%. Selective embolization was performed in 48.8% and non-selective in 51.2%. No death was recorded at 30 days. The estimated clinical success was 90.0% (standard error; SE: 6.7%) and the freedom from EL 2 was 89.0% (SE 6.4%) at 36 months. Cox regression analysis showed that the type of embolization (selective vs. non-selective), type of previous repair (f/bEVAR vs. EVAR), and use of anticoagulants did not affect follow-up outcomes. Reinterventions related to EL 2 were performed in 12.5%; three underwent an open conversion. : TCE was related to high technical success and limited peri-operative morbidity, regardless of the type of initial endovascular aortic repair. Clinical success was encouraging with reinterventions for EL 2 affecting 12.5% of patients.
PubMed: 38930107
DOI: 10.3390/jcm13123578 -
Journal of Clinical Medicine Jun 2024Atrial fibrillation (AF) has been associated with higher morbidity and mortality rates, especially in older patients. Subclinical atrial fibrillation (SCAF) is defined... (Review)
Review
Atrial fibrillation (AF) has been associated with higher morbidity and mortality rates, especially in older patients. Subclinical atrial fibrillation (SCAF) is defined as the presence of atrial high-rate episodes (AHREs) > 190 bpm for 10 consecutive beats > 6 min and <24 h, as detected by cardiac implanted electronic devices (CIEDs). The selection of eligible patients for anticoagulation therapy among elderly individuals with AHREs detected through CIEDs remains a contentious issue. The meta-analysis of ARTESiA and NOAH-AFNET 6 clinical trials revealed that taking Edoxaban or Apixaban as oral anticoagulation therapy can reduce the risk of stroke by approximately 32% while increasing the risk of major bleeding by approximately 62%. However, it is still unclear which are, among patients with SCAF, those who can take the highest net clinical benefit from anticoagulant therapy. The present review summarizes the current evidence on this intriguing issue and suggests strategies to try to better stratify the risk of stroke and systemic embolism in patients with AHREs. We propose incorporating some parameters including chronic kidney disease (CKD), obesity, enlarged left atrial volume, the efficacy in blood pressure management, and frailty into the traditional CHADS-VASc score. Future trials will be needed to verify the clinical usefulness of the proposed prognostic score mainly in the view of a personalized therapeutic approach in patients with SCAF.
PubMed: 38930095
DOI: 10.3390/jcm13123566