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Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.
De Niet, S, Trémège, M, Coffiner, M, Rousseau, AF, Calmes, D, Frix, AN, Gester, F, Delvaux, M, Dive, AF, Guglielmi, E, et al
Nutrients. 2022;14(15)
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Literature shows that having enough vitamin D can help prevent many diseases, such as heart disease, bone disease and cancer. Recent data also showed that vitamin D can reduce the risk of respiratory tract infections, and particularly, the risk of viral infections. The aim of this study was to assess whether the proposed dosing regimen of a daily dose of 25,000 international units (IU) vitamin D administered over 4 consecutive days, followed by a weekly dose of 25,000 IU, was adequate to rapidly increase the concentrations of calcifediol in patients hospitalized with COVID-19 and to explore its impact on hospital length and other clinical outcomes of the disease. This study is an interventional, randomized, parallel, two-treatment, two-arm, double-blind and placebo-controlled pilot study, carried out in one clinical site in Belgium. The patients (n=50) were randomized in the two different treatment groups (vitamin D (n=26) or placebo (n=24)). Patients participated in the study for a maximum of 9 weeks, including an up to 6-week treatment period and a maximum of 3-week follow-up period. Results show that the study’s regimen was adequate to rapidly raise the calcifediol level above 20 ng/mL and improve the clinical outcome of patients requiring hospitalization for COVID-19. In fact, administration of cholecalciferol significantly reduced the hospital length of stay, reduced the duration of supplemental oxygen and improved the clinical status assessed by the World Health Organisation scale. Authors conclude that further studies with a larger number of patients are needed in order to further confirm their study’s findings.
Abstract
Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D.
2.
Ferroptosis Induction and YAP Inhibition as New Therapeutic Targets in Gastrointestinal Stromal Tumors (GISTs).
Delvaux, M, Hagué, P, Craciun, L, Wozniak, A, Demetter, P, Schöffski, P, Erneux, C, Vanderwinden, JM
Cancers. 2022;(20)
Abstract
GISTs are sarcomas of the gastrointestinal tract often associated with gain-of-function mutations in KIT or PDGFRA receptor genes. While most GISTs initially respond to tyrosine kinase inhibitors, relapses due to acquired resistance frequently occur. The induction of ferroptosis, an iron-dependent form of non-apoptotic cell death, emerged as a novel therapeutic approach in cancers and remains poorly characterized in GISTs. We studied hallmarks of ferroptosis, i.e., lipid peroxidation, iron and glutathione content, and GPX4 protein expression in imatinib-sensitive (GIST882) and -resistant (GIST48) GIST cell lines. GIST cells were highly sensitive to the induction of ferroptosis by RSL3, which was reversed by liproxstatin and deferoxamine. Lipid peroxidation and ferroptosis were mediated by VP and CA3 in GIST cells through a significant decrease in antioxidant defenses. Moreover, VP, but surprisingly not CA3, inhibited a series of target genes downstream of YAP in GIST cells. The ferroptosis marker TFRC was also investigated by immunohistochemistry in GIST tissue arrays. TFRC expression was observed in all samples. High TFRC expression was positively correlated with high-risk GISTs, elevated mitotic count, and YAP nuclear localization, reflecting YAP activation. This study highlights ferroptosis as a novel cell death mechanism in GISTs, and a potential therapeutic target to overcome resistance to tyrosine kinase inhibitors.
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The management of irritable bowel syndrome: a European, primary and secondary care collaboration.
Thompson, WG, Hungin, AP, Neri, M, Holtmann, G, Sofos, S, Delvaux, M, Caballero-Plasencia, A
European journal of gastroenterology & hepatology. 2001;(8):933-9
Abstract
OBJECTIVE To develop recommendations for the diagnosis and management of irritable bowel syndrome for European doctors delivering primary care. These recommendations can be adapted by local medical groups according to their language, custom and health-care systems. METHODS Twenty-one general practitioners and gastroenterologists from Europe attended a workshop planned by a steering committee. After a state-of-the-art symposium, four working groups considered the following aspects of irritable bowel syndrome management: what to tell the patient, diagnosis, non-medical treatment and psychosocial management. Current and future drug management was reviewed by the steering committee. The resulting recommendations were considered at two plenary sessions during the meeting, and by circulation of the material during development of the manuscript. RESULTS The process permitted a unique dialogue between general practitioners and gastroenterologists, in which it was necessary to reconcile the specialists' emphasis on thoroughness with the practical, epidemiological and economic realities of primary care. Despite this dichotomy, consensus was achieved. CONCLUSIONS European general practitioners and gastroenterologists have produced recommendations that emphasize education of the patient, a positive symptom-based diagnosis, diet and lifestyle advice, psychological support and a critical analysis of current specific psychological and pharmacological treatments.