Effects of Vitamin D and K on Interleukin-6 in COVID-19

BackgroundPathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.MethodsWe assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes.ResultsComparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; p < 0.0001). Dp-ucMGP levels as biomarker of extrahepatic vitamin K status was associated with IL-6 levels (r = 0.35; p < 0.0001). In contrast, 25(OH)D levels were only borderline statistically significant correlated with IL-6 (r = −0.14; p <0.050). A significant association was also found between IL-6 and elastic fiber degradation. Contrary to vitamin K status, 25(OH)D did not correlate with elastic fiber degradation.ConclusionsDp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.

Non-vitamin K Antagonist Oral Anticoagulants and Drug-Food Interactions: Implications for Clinical Practice and Potential Role of Probiotics and Prebiotics

Non-vitamin K antagonist oral anticoagulants (NOACs) are a therapeutic option to prevent stroke in patients with atrial fibrillation (AF). In fact, NOACs have become the recommended choice by international clinical practice guidelines over vitamin K antagonists (VKA), because of their efficacy and safety profile, especially in newly initiated patients. The more predictable pharmacokinetic and pharmacodynamic profile of this family of drugs allows preventing anticoagulation drug monitoring. Furthermore, NOACs have significantly fewer drug and food interactions in comparison with VKAs. Despite this, there are no studies that compare the effects on the quality of anticoagulation of NOACs with the intake of potential interactions drugs of P-glycoprotein and cytochrome P450 (CYP). This review brings an overview of NOACs pharmacokinetics profile and their potential drug-food interactions. We also briefly discuss the potential role of prebiotics and probiotics in patients under therapy with NOACs.

ĐẶC ĐIỂM LÂM SÀNG VÀ NỒNG ĐỘC ĐỘC CHẤT HUYẾT THANH CỦA BỆNH NHÂN NGỘ ĐỘC CẤP HÓA CHẤT DIỆT CHUỘT BROMADIOLON VÀ FLOCOUMAFEN

Mục tiêu: Mô tả đặc điểm lâm sàng và nồng độ độc chất huyết thanh của bệnh nhân ngộ độc hóa chất diệt chuột kháng vitamin K tác dụng kéo dài bromadiolon và flocoumafen tại Trung tâm Chống độc Bệnh viện Bạch Mai. Phương pháp: Nghiên cứu mô tả tiến cứu trên 37 bệnh nhân ngộ độc cấp bromadiolon/flocoumafen điều trị tại Trung tâm chống độc Bệnh viện Bạch Mai từ tháng 6/2020 đến tháng 6/2021. Kết quả: Trong số bệnh nhân nghiên cứu, nam chiếm tỷ lệ 62,2%, hầu hết là người lớn, chỉ có 2 bệnh nhi. Nguyên nhân ngộ độc hay gặp nhất là tự tử, tuy nhiên 27% không rõ nguồn ngộ độc. Triệu chứng lâm sàng thường gặp nhất xuất huyết dưới da (49%) và các ổ tụ máu trong cơ (35%). Một số bệnh nhân xuất huyết nặng như xuất huyết não (2,7%), tiêu hoá (27,03 %), tiết niệu (27,03 %), ổ bụng (13,51 %). 3 BN (8,11%) có sốc mất máu. Nồng độ Bromadiolon và Flocoumafen xu hướng cao hơn ở nhóm bệnh nhân có xuất huyết hoặc INR > 5 (p 0,06), và cao hơn có ý nghĩa ở nhóm có xuất huyết dưới da nặng (p 0,012 và p 0,027 tương ứng ở Bromadiolon và Flocoumafen). Kết luận: nghiên cứu đã cho thấy các đặc điểm lâm sàng và liên quan giữa biểu hiện xuất huyết với nồng độ độc chất huyết thanh của bệnh nhân ngộ độc cấp hóa chất diệt chuột bromadiolon và flocoumafen.

The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes

Vitamin K dependent coagulation factor deficiency type 1 (VKCFD1) is a rare hereditary bleeding disorder caused by mutations in γ-Glutamyl carboxylase (GGCX) gene. The GGCX enzyme catalyzes the γ-carboxylation of 15 different vitamin K dependent (VKD) proteins, which have function in blood coagulation, calcification, and cell signaling. Therefore, in addition to bleedings, some VKCFD1 patients develop diverse non-hemorrhagic phenotypes such as skin hyper-laxity, skeletal dysmorphologies, and/or cardiac defects. Recent studies showed that GGCX mutations differentially effect γ-carboxylation of VKD proteins, where clotting factors are sufficiently γ-carboxylated, but not certain non-hemostatic VKD proteins. This could be one reason for the development of diverse phenotypes. The major manifestation of non-hemorrhagic phenotypes in VKCFD1 patients are mineralization defects. Therefore, the mechanism of regulation of calcification by specific VKD proteins as matrix Gla protein (MGP) and Gla-rich protein (GRP) in physiological and pathological conditions is of high interest. This will also help to understand the patho-mechanism of VKCFD1 phenotypes and to deduce new treatment strategies. In the present review article, we have summarized the recent findings on the function of GRP and MGP and how these proteins influence the development of non-hemorrhagic phenotypes in VKCFD1 patients.

Overexpression of protein disulfide isomerase enhances vitamin K epoxide reductase activity

Vitamin K epoxide reductase (VKOR) activity is catalyzed by the VKORC1 enzyme. It is the target of vitamin K antagonists (VKA). Numerous mutations of VKORC1 have been reported and have been suspected to confer resistance to VKA and/or affect its velocity. Nevertheless, the results between studies have been conflicting, the functional characterization of these mutations in a cell system being complex due to the interweaving of VKOR activity in the vitamin K cycle. In this study, a new cellular approach was implemented to globally evaluate the vitamin K cycle in the HEK293 cells. This global approach was based on the vitamin K quinone/vitamin K epoxide (K/KO) balance. In the presence of VKA or when the VKORC1/VKORC1L1 were knocked out, the K/KO balance decreased significantly due to an accumulation of vitamin KO. On the contrary, when VKORC1 was overexpressed, the balance remained unchanged, demonstrating a limitation of the VKOR activity. This limitation was shown to be due to an insufficient expression of the activation partner of VKORC1, as overexpressing the protein disulfide isomerase (PDI) overcomes the limitation. This study is the first to demonstrate a functional interaction between VKORC1 and the PDI enzyme.

Biological Role of Vitamin K—With Particular Emphasis on Cardiovascular and Renal Aspects

Vitamin K (VK) plays many important functions in the body. The most important of them include the contribution in calcium homeostasis and anticoagulation. Vascular calcification (VC) is one of the most important mechanisms of renal pathology. The most potent inhibitor of this process—matrix Gla protein (MGP) is VK-dependent. Chronic kidney disease (CKD) patients, both non-dialysed and hemodialysed, often have VK deficiency. Elevated uncarboxylated matrix Gla protein (ucMGP) levels indirectly reflected VK deficiency and are associated with a higher risk of cardiovascular events in these patients. It has been suggested that VK intake may reduce the VC and related cardiovascular risk. Vitamin K intake has been suggested to reduce VC and the associated cardiovascular risk. The role and possibility of VK supplementation as well as the impact of anticoagulation therapy on VK deficiency in CKD patients is discussed.

Outcomes of left atrial appendage occlusion vs. non-vitamin K antagonist oral anticoagulants in atrial fibrillation

Background The effects of left atrial appendage (LAA) occlusion compared to non-vitamin K antagonist oral anticoagulant (NOAC) therapy in patients with atrial fibrillation (AF) remain unknown. Aims We aimed to evaluate the outcomes in patients with AF who received LAA occlusion vs. NOAC therapy. Methods We utilised data from TriNetX which is a global federated health research network currently containing data for 88.5 million patients. ICD-10 codes were employed to identify AF patients treated with either LAA occlusion or NOAC between 1st December 2010 and 17th January 2019. Clinical outcomes of interest were analysed up to 2 years. Results 108,697 patients were included. Patients who underwent LAA occlusion were younger, more likely to be white Caucasian and male, had a greater incidence of comorbidities, and were less likely to be prescribed other cardiovascular medications. Using propensity score matching, the risk of all-cause mortality was significantly lower among patients who received LAA occlusion compared to NOAC therapy [1.51% vs. 5.60%, RR 0.27 (95% CI 0.14–0.54)], but there were no statistical differences in the composite thrombotic or thromboembolic events [8.17% vs. 7.72%, RR 1.06 (95% CI 0.73–1.53)], ischaemic stroke or TIA [4.69% vs. 5.45%, RR 0.86 (95% CI 0.54–1.38)], venous thromboembolism [1.66% vs. 1.51%, RR 1.10 (95% CI 0.47–2.57)] and intracranial haemorrhage [1.51% vs. 1.51%, RR 1.00 (95% CI 0.42–2.39)]. Conclusion Overall, LAA occlusion might be a suitable alternative to NOAC therapy for stroke prevention in patients with AF. Graphical abstract