Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial

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

Enhanced vitamin K expenditure as a major contributor to vitamin K deficiency in COVID-19

Objectives: Vitamin K deficiency consistently associates with worse clinical outcome in COVID-19 patients. However, whether this is due to increased expenditure during inflammation or poor vitamin K status prior to infection remained unknown. Methods: Dp-ucMGP levels of 128 individuals were measured for the post-MONICA study and were compared to SARS-CoV-2 PCR testing results. Results: Dp-ucMGP levels prior to COVID-19 infection were not significantly different comparing PCR-negative, PCR-positive and not hospitalized, and PCR-positive and hospitalized patients. Conclusion: In this study, we demonstrate normal vitamin K status prior to infection in SARS-CoV-2 positive patients, supporting the theory of increased utilisation during disease

Serious complications after button battery ingestion in children

Serious and fatal complications after button battery ingestion are increasing worldwide. The aim of this study is to describe serious complications after battery ingestion in children in the Netherlands. All pediatric gastroenterologists in the Netherlands performing upper endoscopies were asked to report all serious complications after battery ingestion in children (0–18 years) between 2008 and 2016 retrospectively. Sixteen serious complications were reported: death after massive bleeding through esophageal-aortal fistula (n = 1), esophageal-tracheal fistula (n = 5), stenosis after (suspected) perforation and mediastinitis (n = 5), (suspected) perforation and mediastinitis (n = 3), vocal cord paralysis (n = 1), and required reintubation for dyspnea and stridor (n = 1). The median time interval between ingestion and presentation was 5 (IQR 2–258) h. All children were ≤ 5 (median 1.4; IQR 0.9–2.1) years. Vomiting (31.3%), swallowing/feeding problems (31.3%), and fever (31.3%) were the most common presenting symptoms; however, 18.8% of the patients were asymptomatic (n = 1 missing). All batteries were button batteries (75% ≥ 20 mm; 18.8% < 20 mm; n = 1 missing). The batteries were removed by esophagogastroduodenoscopy (50%) and rigid endoscopy (37.5%) or surgically (12.5%). Conclusion: Sixteen serious complications occurred after small and large button batteries ingestion between 2008 and 2016 in both symptomatic and asymptomatic children in the Netherlands. Therefore, immediate intervention after (suspected) button battery ingestion is required.What is Known:• Button battery ingestion may result in serious and fatal complications.• Serious and fatal complications after button battery ingestion are increasing worldwide.What is New:• Sixteen serious complications after button battery ingestion occurred during 2008–2016 in children in the Netherlands.• Serious complications were also caused by small batteries (< 20 mm) in the Netherlands and also occurred in asymptomatic Dutch children