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Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains partly understood. Vascular calcification (VC) is the result of an ongoing process of misplaced calcium in the inner and medial layers of the arteries, which has emerged as a critical contributor to cardiovascular events in CKD. Beyond its established role in blood clotting and bone health, vitamin K appears crucial in regulating VC via vitamin K-dependent proteins (VKDPs). Among these, the matrix Gla protein (MGP) serves as both a potent inhibitor of VC and a valuable biomarker (in its inactive form) for reflecting circulating vitamin K levels. CKD patients, especially in advanced stages, often present with vitamin K deficiency due to dietary restrictions, medications, and impaired intestinal absorption in the uremic environment. Epidemiological studies confirm a strong association between vitamin K levels, inactive MGP, and increased CVD risk across CKD stages. Based on the promising results of pre-clinical data, an increasing number of clinical trials have investigated the potential benefits of vitamin K supplementation to prevent, delay, or even reverse VC, but the results have remained inconsistent.

Background: In observational studies, high levels of desphospho-uncarboxylated matrix gla protein (dp-ucMGP) that result from vitamin K deficiency were consistently associated with poor clinical outcomes during COVID-19. Vitamin K-activated matrix gla protein (MGP) is required to protect against elastic fibre degradation, and a deficiency may contribute to pathology. However, intervention trials assessing the effects of vitamin K supplementation in COVID-19 are lacking. Methods: This is a single-centre, phase 2, double-blind, randomised, placebo-controlled trial investigating the effects of vitamin K2 supplementation in 40 hospitalised COVID-19 patients requiring supplemental oxygen. Individuals were randomly assigned in a 1:1 ratio to receive 999 mcg of vitamin K2-menaquinone-7 (MK-7)-or a placebo daily until discharge or for a maximum of 14 days. Dp-ucMGP, the rate of elastic fibre degradation quantified by desmosine, and hepatic vitamin K status quantified by PIVKA-II were measured. Grade 3 and 4 adverse events were collected daily. As an exploratory objective, circulating vitamin K2 levels were measured. Results: Vitamin K2 was well tolerated and did not increase the number of adverse events. A linear mixed model analysis showed that dp-ucMGP and PIVKA-II decreased significantly in subjects that received supplementation compared to the controls (p = 0.008 and p = 0.0017, respectively), reflecting improved vitamin K status. The decrease in dp-ucMGP correlated with higher plasma MK-7 levels (p = 0.015). No significant effect on desmosine was found (p = 0.545). Conclusions: These results demonstrate that vitamin K2 supplementation during COVID-19 is safe and decreases dp-ucMGP. However, the current dose of vitamin K2 failed to show a protective effect against elastic fibre degradation.

Psoriasis vulgaris (PV) is a disease characterized by skin manifestations and systemic inflammation. There are no published studies to date on vitamin K status assessed by extrahepatic vitamin K-dependent proteins [e.g., osteocalcin (OC) and matrix Gla protein (MGP)] in patients with PV, even if vitamin K was found to promote wound contraction and decrease the healing time of the skin. Metabolic syndrome (MS), a comorbidity of PV, was found to influence vitamin K status, and vitamin D was found to be involved in the pathogenesis of PV. Therefore, our aim was to assess the status of vitamins K and D in subjects with PV. We enrolled 44 patients with PV and 44 age- and sex-matched subjects as a control group (CG), of which individuals with MS were designated the CG with MS subgroup. Furthermore, the PV patients were stratified into two subgroups: those with MS (n = 20) and those without MS (n = 24). In addition to the quantification of vitamin D and MGP in all subjects, the uncarboxylated OC/carboxylated OC (ucOC/cOC) ratio was also assessed as an inversely proportional marker of vitamin K status. We found an increased ucOC/cOC ratio in the PV group compared to CG but also a greater ucOC/cOC ratio in the PV with MS subgroup than in the CG with MS subgroup. MGP was decreased in the PV with MS subgroup compared to CG with MS subgroup. There was no difference in the vitamin D concentration between the groups. This is the first study to report decreased vitamin K status in patients with PV, independent of the presence of MS.

Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K-dependent factors. In cases of life-threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non-specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet-α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant-specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet-α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life-threatening bleeding.

BACKGROUND: Acute hepatitis A infection is common among children in developing nations. The clinical presentation in children is usually asymptomatic and anicteric, and it is a self-limiting infection. Rarely, it can be associated with extrahepatic complications such as pleural effusion, acalculous cholecystitis, and ascites.
METHODS: An 8-year-old middle eastern child presented with abdominal pain, jaundice in the sclera, yellowish color of urine, and poor appetite. In the last two days, abdominal distension developed. After conducting diagnostic investigations, the child was diagnosed with HAV hepatitis associated with bilateral pleural effusion, acalculous cholecystitis, and ascites. He was managed conservatively with vitamin K supplementation and supportive parenteral fluids. After 4 days, clinical improvement was observed.
CONCLUSIONS: Hepatitis A infections presented with extrahepatic manifestations like pleural effusion, acalculous cholecystitis, and ascites are very rare, especially in children. There have been some reports of these manifestations occurring in isolation, but for them to co-exist to our knowledge, this has only been reported in two cases in the literature, and this is the third case with all these three rare complications being presented simultaneously in a single child. Although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications, so pediatricians should be aware of this rare association to avoid unnecessary investigations.

OBJECTIVE: To investigate whether patients with severe motor and intellectual disability (SMID) have nutritional vitamin D and K insufficiencies and clarify the required vitamin supplementation.
METHODS: This prospective observational study enrolled Japanese adults with SMID receiving institutionalized care who underwent blood sampling between February 2020 and February 2022 during annual medical checkups. Serum vitamin K1 and 25-hydroxy vitamin D (25(OH)D) levels were measured to determine their relationship with serum uncarboxylated osteocalcin (ucOC) levels. Vitamin D and K intake was compared among tube-fed and oral-intake patients with SMID and control participants using corresponding serum levels.
RESULTS: The study included 124 patients with SMID (56 men and 68 women; mean age: 53.0 years) and 20 control participants. Serum 25(OH)D levels were significantly higher in the SMID group than in the control group and the oral intake SMID group than in the tube-fed SMID group. In the tube-fed SMID group, vitamin D intake was lower than the daily recommended intake and correlated with serum 25(OH)D levels. Daily vitamin K intake in the tube-fed group was lower than recommended but not correlated with serum vitamin K levels. Serum ucOC levels were significantly higher in the SMID group than in the control group. Tube feeding was significantly and positively correlated with serum 25(OH)D levels. Serum 25(OH)D levels were not correlated with serum vitamin K1 levels.
CONCLUSIONS: The SMID group had higher ucOC levels than the control group, possibly owing to daily vitamin K and D deficiencies. Vitamin D supplementation is recommended to decrease ucOC levels.

BACKGROUND: Warfarin is an effective anticoagulant but requires close International Normalized Ratio (INR) monitoring and may occasionally require correction of excessive anticoagulation. Current guidelines provide limited practical guidance on the administration of vitamin K for the management of supratherapeutic INR levels ≥ 5.0 in non-bleeding outpatients.
OBJECTIVE: Based on expert consensus and guidelines, the Atrius Health Anticoagulation Management Services (AMS) has developed internal guidance for oral vitamin K use in highly selected populations. This study will describe the internal guidance for oral vitamin K use and present associated results and clinical outcomes.
METHODS: Episodes with INR > 5.0 were included, with vitamin K considered for episodes with INR ≥ 6. Moreover, compelling indications and exclusions to select ideal patients for vitamin K intervention were also defined.
RESULTS: Overall, episodes were managed conservatively; of the 246 collected episodes of excessive anticoagulation, in 18 episodes (7%), patients received vitamin K, and in 228 (93%) episodes, patients did not receive vitamin K. The mean index INR was 6.0 (range 5.0 - 10.5, SD 1.07), with nearly 57% of episodes achieving INR correction and 15% of episodes developing INR overcorrection. High thrombotic risk patients, regardless of hemorrhagic risk, were less likely to receive vitamin K. Three episodes (1.2%) resulted in bleeding complications. No thrombotic complications occurred during the 30-day follow-up of the index INR value ≥ 5.0.
CONCLUSIONS: Our internal guidance is a novel, standardized approach that serves as a decision support tool for the management of warfarin-associated coagulopathy and vitamin K intervention using patient-specific characteristics and index INR values. This guidance may assist other anticoagulation management services with practical applications and require validation in a prospective clinical trial.

UNASSIGNED: Hypovitaminosis K has been linked to depression and suicide, but epidemiological research is scarce. This study aimed to explore the association among vitamin K with depression and suicidal attempts.
UNASSIGNED: This was a retrospective cross-sectional study involving 146 cases with a history of suicidal attempts and 149 subjects without a lifetime history of suicidal attempts. The levels of thyroid hormones, lipid profile, inflammatory cytokines, and vitamins were measured.
UNASSIGNED: Subjects who had suicidal attempts presented with a significant decrease in FT4, TC, vitamin D, and vitamin K but increased CRP levels. In these variables, vitamin K has a better diagnostic value for suicidal attempts in depressed patients, with a sensitivity of 0.842 and a specificity of 0.715. Correlation analysis suggested that vitamin K was significantly and positively related to FT4, TC, LDL, and sdLDL. Multivariate analysis showed that serum vitamin K level predicts suicidal attempts in depressive patients (OR = 0.614, P = 0.004, 95% CI 0.153-0.904). Moreover, a negative correlation between vitamin K and suicidal attempts was also noted for partial FT4, CRP, and vitamin D strata analysis.
UNASSIGNED: Our study suggests that low vitamin K levels were correlated with suicidal attempts in patients with depression, indicating that vitamin K deficiency might be a biological risk factor for depression.