Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A case/non-case study was performed using AE reports registered in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to compare the risk of CV event reports related to TKIs indicated in the management of chronic myeloid leukemia (CML). Disproportionality of CV event-related TKIs was computed using the Reporting Odds Ratio (ROR) as a measure of potential risk increase. Nilotinib accounts for more than half of reported cases related to TKIs. Signal of Disproportionate Reporting (SDR) was found for cardiac failure, ischemic heart disease, cardiac arrhythmias, torsade de pointes/QT prolongation, hypertension, and pulmonary hypertension. Dasatinib and bosutinib were related to the highest disproportionality for cardiac failure. Nilotinib was associated with the highest SDR for ischemic heart disease, torsade de pointes/QT prolongation and cardiac arrhythmias. Only ponatinib was related to an SDR for hypertension, while dasatinib and imatinib were related to pulmonary hypertension. In the context of CML, TKIs have different safety profiles related to CV events, among which nilotinib seems particularly related to. These results claim for a revision of its CV safety profile mainly for the risk of torsade de pointes/QT prolongation.

The COVID-19 outbreak has rapidly expanded to a global pandemic; however, our knowledge is limited with regards to the protective factors against this infection. The aim of this systematic literature review and meta-analysis was to evaluate the impact of vitamin D supplementation on COVID-19 related outcomes. A systematic search of relevant papers published until January 2022 was conducted to identify randomized controlled trials (RCTs) and non-randomized studies of intervention (NRISs). The primary outcomes included the risk of COVID-19 infection (primary prevention studies on uninfected individuals), hospital admission (secondary prevention studies on mild COVID-19 cases), and ICU admission and mortality rate (tertiary prevention studies on hospitalized COVID-19 patients). We identified five studies (one RCT, four NRISs) on primary prevention, with five (two RCTs, three NRISs) on secondary prevention, and 13 (six RCTs, seven NRISs) on tertiary prevention. Pooled analysis showed no significant effect on the risk of COVID-19 infection. No meta-analysis was possible on hospitalization risk due to paucity of data. Vitamin D supplementation was significantly associated with a reduced risk of ICU admission (RR = 0.35, 95% CI: 0.20, 0.62) and mortality (RR = 0.46, 95% CI: 0.30, 0.70). Vitamin D supplementation had no significant impact on the risk of COVID-19 infection, whereas it showed protective effects against mortality and ICU admission in COVID-19 patients.

We thank Drs. Leong et al. for their comments

Vitamin D supplementation may improve asthma by modulating inflammation, but its effects in preschoolers with virus-induced asthma remain underexplored. To measure the association between serum 25-hydroxyvitamin D (25(OH)D) and inflammatory biomarkers and the impact of vitamin D supplementation on these biomarkers. We conducted a nested study within a 7-month randomized placebo-controlled trial. Children aged 1 to 5 years with virus-induced asthma received vitamin D₃ in 2 oral boluses (100,000 IU) 3.5 months apart, with a daily (400 IU) supplement, or placebo boluses and daily supplement. Serum 25(OH)D and C-reactive protein (CRP) were measured at baseline, 3.5 months, and 7 months, whereas blood cells were measured at baseline and 7 months. Primary outcomes were CRP across time points and change from baseline in CRP at 3.5 and 7 months, analyzed using generalized estimating equation and mixed-effects models. Among 236 (118 Vitamin D: 118 placebo) children (64.4% male), no significant association was observed between CRP and 25(OH)D. However, neutrophils were inversely associated with 25(OH)D (adjusted β [95% CI]= -0.016 (-0.027 to -0.005) × 10⁹ cells/L, n = 198). Compared with placebo, vitamin D supplementation led to a greater reduction from baseline in CRP over time (adjusted β [95% CI] = -3.154 [-5.978 to -0.330] mg/L, n = 174), and neutrophils at 7 months (adjusted β [95% CI] = -0.657 [-1.288 to -0.026] × 10⁹ cells/L, n = 110). No associations were observed with other blood cell biomarkers. In preschoolers with virus-induced asthma, serum 25(OH)D was inversely associated with neutrophils, and vitamin D supplementation significantly reduced CRP and neutrophils over time, suggesting modulation of neutrophilic inflammation. ClinicalTrials.gov Identifier: NCT03365687.