Vitamin K antagonist anticoagulation in the antiphospholipid syndrome: time in therapeutic range and clinical outcomes.

BACKGROUND: Thrombosis in the antiphospholipid syndrome is still frequently treated with vitamin K antagonists with a target international normalized ratio of 2-3. Time in therapeutic range of international normalized ratio of ≥ 70% is considered optimal. Time in therapeutic range among antiphospholipid syndrome patients is not well documented and the clinical consequences of poor international normalized ratio control are uncertain. AIMS: To determine the proportion of vitamin K antagonist -treated antiphospholipid syndrome patients achieving time in therapeutic range ≥ 70%, to define the features associated with poor control and to determine its association with thrombotic and bleeding events. METHODS: This medical records review included antiphospholipid syndrome patients treated with vitamin K antagonists, between 2012-2023. The proportion of patients achieving a time in therapeutic range≥ 70% was determined and thrombotic and bleeding events were compared between patients with time in therapeutic range ​​≥ 70% versus < 70%. RESULTS: 67 antiphospholipid syndrome patients were studied. 29.9% achieved time in therapeutic range ≥ 70%. 9.1% of patients with 3 or more comorbidities achieved time in therapeutic range values ≥ 70% compared to 40% of patients with less than 3 comorbidities. Fewer recurrent arterial and overall thrombotic events occurred with time in therapeutic range ​​≥ 70%. CONCLUSIONS: A minority of antiphospholipid syndrome patients treated with vitamin K antagonist s achieve optimal anticoagulation and are at risk for recurrent thrombotic events, particularly arterial. Presence of multiple comorbidities is associated with poor international normalized ratio control. Careful monitoring of this patient population is warranted.

Direct Oral Anticoagulants for Rheumatic Heart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

BACKGROUND: The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. OBJECTIVES: This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. METHODS: We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. RESULTS: A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95% CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. CONCLUSIONS: Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

Vitamin K2 alleviates dextran sulfate sodium-induced colitis via inflammatory responses, gut barrier integrity, and the gut microbiota in mice.

Vitamin K2 (VK2) has been shown to have potential benefits in improving intestinal integrity, but its potential and mechanisms for alleviating intestinal inflammation are still unclear. The present results showed that VK2 supplementation significantly alleviated the symptoms of colitis and maintained the intestinal barrier integrity. In addition, VK2 significantly down-regulated the mRNA expression levels of pro-inflammatory cytokines including IL-1ß, IL-6, and TNF-α, while up-regulated the mRNA expression level of anti-inflammatory cytokines such as IL-10. Moreover, VK2 significantly alleviated DSS-induced intestinal epithelial barrier dysfunction by maintaining the tight junction function. Furthermore, VK2 also regulated DSS-induced gut microbiota dysbiosis by reshaping the structure of gut microbiota, such as increasing the relative abundance of Firmicutes, Euryarchaeota, Prevotellaceae, and Prevotella and reducing the relative abundance of Proteobacteria, Rikenellaceae, Enterobacteriaceae, Acetatifactor, and Alistioes. In conclusion, these results indicated that VK2 effectively alleviates DSS-induced colitis in mice by modulating the gut microbiota.

Safety and Effectiveness Outcomes between Apixaban Versus Vitamin K Antagonists in Atrial Fibrillation Patients on Dialysis.

Background: Anticoagulant therapy for atrial fibrillation (AF) in patients with end-stage kidney disease (ESKD) undergoing dialysis poses significant challenges. This review aimed to furnish clinicians with the latest clinical outcomes associated with apixaban and vitamin K antagonists (VKAs) in managing AF patients on dialysis. Methods: Literature from the PubMed and Embase databases up to March 2024 underwent systematic scrutiny for inclusion. The results were narratively summarized. Results: Six studies were included in this review, comprising the AXADIA-AFNET 8 study, the RENAL-AF trial, and four observational studies. In a French nationwide observational study, patients initiated on apixaban demonstrated a diminished risk of thromboembolic events (hazard ratios [HR]: 0.49; 95% confidence interval [CI]: 0.20-0.78) compared to those on VKAs. A retrospective review with a 2-year follow-up, encompassing patients with AF and ESKD on hemodialysis, evidenced no statistical difference in the risk of symptomatic bleeding and stroke between the apixaban and warfarin groups. Two retrospective studies based on the United States Renal Data System (USRDS) database both indicated no statistical difference between apixaban and VKAs in the risk of thromboembolic events. One study reported that apixaban correlated with a reduced risk of major bleeding relative to warfarin (HR: 0.72, 95% CI: 0.59-0.87), while the other study suggested that apixaban was associated with a decreased risk of mortality compared to warfarin (HR: 0.85, 95% CI: 0.78-0.92). The AXADIA-AFNET 8 study found no differences between apixaban and VKAs in safety or effectiveness outcomes for AF patients on dialysis. The RENAL-AF trial, however, was deemed inadequate for drawing conclusions due to its small sample size. Conclusions: Currently, the published studies generally support that apixaban exhibits non-inferior safety and effectiveness outcomes compared to VKAs for AF patients on dialysis.

Associations between vitamin A and K intake and lung function in the general US population: evidence from NHANES 2007-2012.

Introduction: While nutrition's critical role in enhancing respiratory health is acknowledged, the specific impacts of vitamins A and K on lung function remain largely unexplored. The study aimed to evaluate the relationships between vitamins A and K intake and lung function. Methods: The cross-sectional study focused on adults aged 20-79 with utilizing data from US National Health and Nutrition Examination Survey (NHANES) 2007-2012. Lung function was assessed by measuring forced expiratory volume (FEV1), forced vital capacity (FVC), and the ratio of these two values (FEV1/FVC). Regression model was performed to determine the associations between intake of vitamins A and K and outcomes. Results: Data of 10,034 participants (representing 142,965,892 adults in the US) were analyzed. After adjusting for relevant confounders, multivariable analysis revealed 1 µg/day increase of vitamin A intake was significantly associated with 0.03 ml increased FEV1 (p = 0.004) and 0.04 ml increased forced vital capacity (FVC) (p < 0.001). In addition, 1 µg/day increase in vitamin K intake was significantly associated with 0.11 ml increased FEV1 (p = 0.022). Neither vitamin A and K intake was associated with FEV1/FVC or presence of airway obstruction. Conclusions: In relatively healthy population of the US, greater vitamin A or K intake was independently associated with better lung function assessed by spirometry. Benefits of such vitamins for pulmonary health should be confirmed in future randomized controlled trials.

Increasing Vitamin K2 Synthesis in Bacillus subtilis by Controlling the Expression of MenD and Stabilizing MenA.

As an indispensable member of the family of lipid vitamins, vitamin K2 (MK-7) plays an important role in blood coagulation, cardiovascular health, and kidney health. Microbial fermentation is favored due to its high utilization rate of raw materials, simple operation, and moderate conditions. However, the biosynthesis pathway of vitamin K2 in microorganisms is highly complex, which hinders its industrial production in microbial cell factories. One of the major challenges is the stable expression and deregulation of key enzymes in the vitamin K2 biosynthesis pathway, which remains unclear and has undergone little investigation. In this study, 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase (MenD) and 1,4-dihydroxy-2-naphthoate polyprenyltransferase (MenA) were identified as pivotal enzymes in the biosynthesis of vitamin K2. To investigate the catalytic efficiency of MenD in the biosynthesis pathway of vitamin K2, structure-based mutation design and site-directed mutagenesis were performed. Three mutation sites were identified in MenD: A115Y, R96 M, and R323M, which improve the expression level and protein stability. Meanwhile, the MenA mutant T290M, which exhibits improved protein stability, was obtained by modifying its hydrophobic stacking structure. Finally, an engineered strain noted ZQ13 that combinatorially overexpressed MenD (A115Y) and MenA (T290M) mutants was constructed and achieved 338.37 mg/L vitamin K2 production in a 3-L fermenter.

Risks of oral anticoagulants: Analysis of adverse drug reactions reported to the Portuguese National Pharmacovigilance System.

Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was "Clinically Important" (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was "Gastrointestinal disorders," with the most commonly reported Preferred Term being "Gastrointestinal hemorrhage," and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population.

Direct Oral Anticoagulants in Antiphospholipid Syndrome-Associated Venous Thromboembolism: Real World Evidence.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APS-VTE. METHODS: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation. RESULTS: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41-2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17-0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32-0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34-2.69; P = 0.840). CONCLUSION: In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea.

Vitamin K3 derivative inhibits androgen receptor signaling in targeting aggressive prostate cancer cells.

Prostate cancer (PCa) is the second critical cause of cancer-related deaths, with African Americans dying at higher rates in the U.S. The main reasons for the higher mortality rate are ethnic differences and lack of understanding of prostate cancer biology and affordable treatments, as well as the financial burden of African American men to obtain the most effective and safe treatments. The effect of micronutrients, including Vitamin K, on various cancer cell lines has been widely studied, but the potential anticancer effect of VK3-OCH3, an analog of vitamin K3 (Menadione), on African American prostate cancer has not been evaluated. In this study, we compared the anticancer effect of VK3-OCH3 on targeting African American derived PCa cell lines namely RC77-T and MDA-PCa-2b. Our results show that VK3-OCH3 significantly inhibits the proliferation of both RC77-T and MDA-PCa-2b African American PCa cells and promotes apoptosis, and the underlying mechanism of cell death appears to be similar in both the cell lines. Notably, VK3-OCH3 inhibits colony-forming ability and induces apoptosis by blocking the cell cycle at G0 in African American PCa cells. VK3-OCH3 also acts as an anti-metastatic agent by inhibiting the migration ability of the metastatic properties of African American PCa cells. The cell death of African American PCa cells mediated by VK3-OCH3 is associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS). Interestingly, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines derived from African American patients. Of note, VK3-OCH3 reduces androgen receptor and prostate-specific antigen expression in these PCa cells. Furthermore, molecular dynamic studies reiterated that VK3-OCH3 strongly binds to the androgen receptor, suggesting that the androgen receptor is the potential molecular target of VK3-OCH3. In addition, Western blot analysis showed that VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP in the MDA-PCa-2b metastatic PCa cellular model. In conclusion, our results suggested that VK3-OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies.

A retrospective cohort study of coagulation function in patients with liver cirrhosis receiving cefoperazone/sulbactam with and without vitamin K1 supplementation.

BACKGROUND: Cefoperazone/sulbactam is commonly prescribed for the treatment of infected patients with cirrhosis. AIM: To investigate the effect of cefoperazone/sulbactam on coagulation in cirrhotic patients and assess the effectiveness of vitamin K1 supplementation in preventing cefoperazone/sulbactam-induced coagulation disorders. METHOD: This retrospective cohort study compared coagulation function in 217 cirrhotic patients who received cefoperazone/sulbactam with and without vitamin K1 supplementation (vitamin K1 group, n = 108; non-vitamin K1 group, n = 109). Propensity score matching (PSM) was used to to reduce confounders' influence, the SHapley additive exPlanations (SHAP) model to explore the importance of each variable in coagulation disorders. RESULTS: In the non-vitamin K1 group, the post-treatment prothrombin time (PT) was 16.5 ± 6.5 s and the activated partial thromboplastin time (aPTT) was 34.8 ± 9.4 s. These were significantly higher than pre-treatment values (PT: 14.6 ± 2.4 s, p = 0.005; aPTT: 30.4 ± 5.9 s, p < 0.001). In the vitamin K1 group, no differences were observed in PT, thrombin time, or platelet count, except for a slightly elevated post-treatment aPTT (37.0 ± 10.4 s) compared to that of pre-treatment (34.4 ± 7.2 s, p = 0.033). The vitamin K1 group exhibited a lower risk of PT prolongation (OR: 0.211, 95% CI: 0.047-0.678) and coagulation disorders (OR: 0.257, 95% CI: 0.126-0.499) compared to that of the non-vitamin K1 group. Propensity score matching analysis confirmed a reduced risk in the vitamin K1 group for prolonged PT (OR: 0.128, 95% CI: 0.007-0.754) and coagulation disorders (OR: 0.222, 95% CI: 0.076-0.575). Additionally, the vitamin K1 group exhibited lower incidences of PT prolongation, aPTT prolongation, bleeding, and coagulation dysfunction compared to the non-vitamin K1 group. CONCLUSION: Cefoperazone/sulbactam use may be linked to a higher risk of PT prolongation and coagulation disorders in cirrhotic patients. Prophylactic use of vitamin K1 can effectively reduce the risk.

Severe Coagulopathy and Intra-Alveolar Haemorrhage Due to Fat Malabsorption in Celiac Disease.

Celiac disease, a prevalent autoimmune disorder, can present atypically with fat malabsorption and coagulopathy due to vitamin K malabsorption. A 64-year-old male presented with haemoptysis and severe anaemia (Hb 6 g/dl). Despite normal previous coagulation tests, admission laboratory tests revealed an international normalised ratio (INR) of 7.0 and iron deficiency anaemia. Initial blood products and vitamin K treatment corrected the INR temporarily, but the patient's haemoptysis returned, and his INR values continued to rise. Further investigation revealed celiac disease with fat malabsorption, leading to vitamin K malabsorption and along with a previously prescribed antiplatelet aggregation therapy, this led to diffuse alveolar haemorrhage. A gluten-free diet and vitamin supplementation normalised the patient's INR and stopped the bleeding. This case highlights the importance of considering celiac disease in unexplained coagulopathies and the effectiveness of dietary management. LEARNING POINTS: Celiac disease can cause severe coagulopathy due to fat malabsorption and vitamin K deficiency.High suspicion is required for atypical presentations of celiac disease.A gluten-free diet is essential for managing celiac disease and normalising coagulation profiles.

Bromadiolone may cause severe acute kidney injury through severe disorder of coagulation: a case report.

BACKGROUND: Bromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning. CASE PRESENTATION: A 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient's serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient's kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL. CONCLUSION: Bromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

Dietary vitamin K intake in relation to skeletal muscle mass and strength among adults: a cross-sectional study based on NHANES.

Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength. Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively. Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (ß = 0.05747, p = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 µg/d (P nonlinear = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements. Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range.

Clinical implications of combination proton pump inhibitor and triple therapies in patients with atrial fibrillation following percutaneous intervention: a guide for clinicians.

INTRODUCTION: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy. AREAS COVERED: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization. EXPERT OPINION: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes.

Frozen/Thawed Samples Can Replace Fresh Samples for Assignment of ISI to Secondary Thromboplastin Standards for Multiple Reagent/Instrument Combinations: Data to Support Possible Revision of WHO Guidelines.

BACKGROUND: Calibration of thromboplastins is required for accurate calculation of the international normalised ratio (INR). Accurate INR results are required for optimal dosing of vitamin K antagonists. Decreases in vitamin K antagonist usage have made the recruitment of sample sets for international sensitivity index (ISI) calibrations more difficult. A possible solution to this would be to allow the use of frozen-thawed samples in place of fresh plasmas in the calibration of secondary standards. OBJECTIVES: We investigated the effect of freezing and thawing samples before usage in ISI calibrations of secondary standards. METHODS: Multiple reagent/instruments were tested to identify the degree of difference between a fresh sample ISI calibration and one performed on frozen-thawed samples. Where possible, the two ISI calibrations were performed on the same sample set. Alternatively, a separate set of samples from different patients was used. RESULTS: The difference in ISI values was <3% for those datasets where the same samples were used, and <6% for those datasets where two sample sets were used. Additionally, other parameters required for a valid ISI calibration showed only minor differences-some calibrations showed fewer outliers in the frozen-thawed datasets. Mean normal prothrombin time for the international reference thromboplastins was <3.5% different across four different calibrations (two for rabbit thromboplastin and two for recombinant human thromboplastin). CONCLUSIONS: This modification to the WHO guidelines would facilitate the recruitment of test plasmas in advance of calibration solving the problem of requiring availability of fresh patient samples with a range of INRs in a 5-h window. TRIAL REGISTRATION: Not a part of any clinical trial.

Shell Distribution of Vitamin K3 within Reinforced Electrospun Nanofibers for Improved Photo-Antibacterial Performance.

Personal protective equipment (PPE) has attracted more attention since the outbreak of the epidemic in 2019. Advanced nano techniques, such as electrospinning, can provide new routes for developing novel PPE. However, electrospun antibacterial PPE is not easily obtained. Fibers loaded with photosensitizers prepared using single-fluid electrospinning have a relatively low utilization rate due to the influence of embedding and their inadequate mechanical properties. For this study, monolithic nanofibers and core-shell nanofibers were prepared and compared. Monolithic F1 fibers comprising polyethylene oxide (PEO), poly(vinyl alcohol-co-ethylene) (PVA-co-PE), and the photo-antibacterial agent vitamin K3 (VK3) were created using a single-fluid blending process. Core-shell F2 nanofibers were prepared using coaxial electrospinning, in which the extensible material PEO was set as the core section, and a composite consisting of PEO, PVA-co-PE, and VK3 was set as the shell section. Both F1 and F2 fibers with the designed structural properties had an average diameter of approximately 1.0 µm, as determined using scanning electron microscopy and transmission electron microscopy. VK3 was amorphously dispersed within the polymeric matrices of F1 and F2 fibers in a compatible manner, as revealed using X-ray diffraction and Fourier transform infrared spectroscopy. Monolithic F1 fibers had a higher tensile strength of 2.917 ± 0.091 MPa, whereas the core-shell F2 fibers had a longer elongation with a break rate of 194.567 ± 0.091%. Photoreaction tests showed that, with their adjustment, core-shell F2 nanofibers could produce 0.222 µmol/L ·OH upon illumination. F2 fibers had slightly better antibacterial performance than F1 fibers, with inhibition zones of 1.361 ± 0.012 cm and 1.296 ± 0.022 cm for E. coli and S. aureus, respectively, but with less VK3. The intentional tailoring of the components and compositions of the core-shell nanostructures can improve the process-structure-performance relationship of electrospun nanofibers for potential sunlight-activated antibacterial PPE.

Risk of spontaneous intracerebral hemorrhage associated with NOACs compared with aspirin and warfarin: A long-term single hospital follow-up study.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are currently the mainstay treatment for preventing thrombosis-induced ischemic stroke in patients with atrial fibrillation (AF), deep vein thrombosis (DVT), or previous infarction. However, such management may potentially induce antithrombotic-associated intracranial hemorrhage, leading to significantly adverse clinical outcomes. To investigate the risk of spontaneous intracranial hemorrhage (sICH) in patients under therapeutic anticoagulation. METHODS: This retrospective cohort study used a database established by Kaohsiung Veterans General Hospital to estimate the risk of first onset sICH in patients with AF, DVT or previous stroke who were 18 years old or older, and who had been on at least three months continuous long-term treatment with the oral anticoagulants aspirin, warfarin, or NOACs. In addition, we used propensity-score matching to minimize bias and Cox proportional hazards ratio to compare the risk of sICH among patients prescribed these anticoagulants. RESULTS: We analyzed the data of 546 patients (182 aspirin users, 182 warfarin users, and 182 NOAC users). 180 (20 taking aspirin, 74 warfarin, and 86 NOACs) developed new onset sICH before seven years. No new onset cases were found after 7 years. Importantly, those taking NOACs were found to be at a higher risk of early onset hemorrhage (47.80 %) compared to the groups taking aspirin (11.10 %) and warfarin (47.80 %) with a median time-to-occurrence being 2.50, 4.00, and 4.40 years, respectively. CONCLUSIONS: Though NOACs prevented ischemic stroke, they were used with a higher risk of early onset spontaneous ICH at our large medical center.

Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Left Ventricular Thrombus After Myocardial Infarction: A Meta-Analysis.

Left ventricular (LV) thrombus formation remains a post-acute myocardial infarction (AMI) complication even in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario is poorly defined. The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for the management of LV thrombus after AMI. A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after AMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were conducted to synthesize pooled ORs. Eight studies comprising a total of 605 patients were included. DOACs were associated with an almost twofold higher likelihood of thrombus resolution compared with VKAs (pooled OR 1.95 [1.25 to 3.04], p = 0.003, I2 = 0%), and decreased the risk of systemic embolism by 70% (pooled OR 0.30 [0.12 to 0.75]; p = 0.01, I2 = 0%). The use of DOACs was associated with a 54% lower risk of bleeding compared with VKAs (pooled OR 0.46 [0.26 to 0.84], p = 0.01, I2 = 0%). Overall, patients receiving DOACs had a 63% lower risk of reaching the composite outcome of safety and efficacy compared with patients using VKAs (pooled OR 0.37 [0.23 to 0.60], p <0.0001, I2 = 0%). In conclusion, DOACs appear to have a more favorable efficacy and safety profile compared with VKAs for the management of LV thrombus related to AMI.

Dietary vitamin K intake is associated with decreased neurofilament light chain among middle-aged and older adults from the NHANES.

Purpose: Neurofilament-light chain (NfL) is associated with neurodegenerative diseases, which are increasingly prevalent with aging. Vitamin K has been shown a neuroprotective effect. Therefore, we aimed to explore the potential relationship between dietary vitamin K intake and serum NfL. Methods: This study was conducted on the 2013-2014 cycles of the National Health and Nutrition Examination Survey, a multi-site population-based study of the US general population. Serum NfL level was measured using a highly sensitive immunoassay. Dietary vitamin K intake was estimated from two-day dietary recall interviews, and its relationship with NfL was determined using linear regression models. Results: The study included a total of 1,533 participants with a median age of 46 years, comprising 801 women (52.2%) and 732 men (47.8%). The median dietary intake of vitamin K was 81.6 µg/d, and the median serum NfL was 12 pg./mL. After adjusting for potential confounding factors in the full model, individuals with higher dietary vitamin K intake had lower serum NfL levels (Q4 vs. Q1, ß = -4.92, 95%CI: -7.66, -2.19, p = 0.002). A non-linear negative dose-response association is found between dietary vitamin K intake and serum NfL levels (P for non-linearity = 0.008); this association reaches a plateau when the dietary vitamin K intake is higher than 200 µg/d. According to the results of stratified analysis, the relationship between dietary vitamin K intake and serum NfL levels was stronger in the population of middle-aged and older adults. Conclusion: The present study suggested a negative association between dietary vitamin K intake and serum NfL levels in the general US population, especially in middle-aged and older adults. This study might offer a novel nutritional idea for the primary prevention and mechanism exploration of neurodegenerative diseases.

Quantitative Study of Vitamin K in Plants by Pressurized Liquid Extraction and LC-MS/MS.

The health-promoting properties of vitamin K stimulate the growing interest in this compound, which translates into the development of new analytical methodologies for its determination. New, more efficient methods of its isolation are sought, paying increasingly more attention to the methods within currently available extraction techniques that, owing to the optimization of the process, not only increase the extraction efficiency but are also economical and environmentally friendly. This article proposes a procedure for the extraction and analysis of one of the vitamin K vitamers, i.e., vitamin K1, using PLE and LC-MS/MS. It has been shown that the PLE technique can be optimized with a mathematical model-accelerating and reducing the costs of the extraction process-which, together with process automation, bodes well for industrial applications. The optimized process was used to extract vitamin K1 from various vegetables, showing very different contents of the test compound ranging from 1.22 to 114.30 µg/g dry weight for avocado and spinach, respectively. In addition, by showing the effect of water within the material subjected to extraction on the variable yield of vitamin K1, attention was drawn to the need to standardize the analytical methods used in assessing the quality of food products.