Efficacy and safety of vitamin D supplementation in hospitalized COVID-19 pediatric patients: A randomized controlled trial.

Background: Some studies suggested that adequate levels of vitamin D (VD) decrease the risk of severe COVID-19. Information about the effectiveness of VD supplementation in children is scarce. Objective: To assess the efficacy and safety of VD supplementation compared to the standard of care in hospitalized children with COVID-19. Patients and methods: An open-label randomized controlled single-blind clinical trial was carried out. We included patients from 1 month to 17 years, with moderate COVID-19, who required hospitalization and supplemental oxygen. They were randomized into two groups: the VD group, which received doses of 1,000 (children < 1 year) or 2,000 IU/day (from 1 to 17 years) and the group without VD (control). The outcome variables were the progression of oxygen requirement, the development of complications, and death. Statistical analysis: For comparison between groups, we used the chi-squared test or Fisher's exact test and the Mann-Whitney U test. Absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated. p ≤ 0.05 was considered statistically significant. Results: From 24 March 2020 to 31 March 2021, 87 patients were eligible to participate in the trial; 45 patients were randomized: 20 to the VD group and 25 to the control group. There was no difference in general characteristics at baseline, including serum VD levels (median 13.8 ng/ml in the VD group and 11.4 ng/ml in the control group). Outcomes: 2/20 (10%) in the VD group vs. 9/25 (36%) in the control group progressed to a superior ventilation modality (p = 0.10); one patient in the VD group died (5%) compared to 6 (24%) patients in the control group (p = 0.23). ARR was 26% (95% CI 8.8 to 60.2%) and NNT was 3 (2 to 11) for progression and ARR was 19% (95% CI -3.9 to 42.8%) and NNT was 6 (2 to 26) for death. None of the patients receiving VD had adverse effects. The trial was stopped for ethical reasons; since after receiving the results of the basal VD values, none of the patients had normal levels. Conclusion: In this trial, VD supplementation in pediatric patients seems to decrease the risk of COVID-19 progression and death. More studies are needed to confirm these findings. Clinical Trial Registration: This protocol was registered on ClinicalTrials.gov with the registration number NCT04502667.

Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance (MDR1) gene.

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (MDR1/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of MDR1 and its relation to ALL outcomes. Analysis of the MDR1 promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of MDR1 expression and function. The clinical roles of YY1 and MDR1 expression were evaluated in children with ALL. Expression of both proteins was increased in ALL patients compared to controls. We identified a positive correlation between YY1 and MDR1 expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of MDR1. Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.

A critical review of the prognostic value of the nutritional status at diagnosis in the outcome of therapy of children with acute lymphoblastic leukemia.

The impact of undernutrition in the outcome of treatment of children with ALL has been analyzed by several authors who have highlighted undernutrition as another relevant prognostic factor in children with acute lymphoblastic leukemia (ALL). There are, however, some papers which have not confirmed the prognostic value of malnutrition at diagnosis in children with ALL. Overall, data from 1,123 children with ALL worldwide support the concept of malnutrition at diagnosis being useful as a prognostic factor, whereas data from 1,271 children fail to support this concept. We here critically analyze the information of these publications referring to a total of 2,394 children with ALL. Detailed information was available only from 500 of the 2,394 patients, stemming from six publications; of these individuals, at diagnosis, 376 were well nourished and 124 were malnourished. In this subset of patients, the analysis of the data shows that the 5-year (or longer) overall survival of undernourished children (UNC) was 26%, whereas that of well-nourished children (WNC) was 59% (p < 0.001); along the same line the relative risk of dying during this period was 1.8 times higher for UNC than WNC (p < 0.01; Interval of Confidence [IC] 95%: 1.72-1.88). On the other hand, the censoring time of these 500 children is different: 293 were censored at 5 years after diagnosis, whereas 207 where censored at 8-10 years: The overall survival for each of these periods was also different: 36% versus 2% for UNC (p < 0.001), and 56% versus 63% (p > 0.10) for WNC, data which support the concept that the differences in survival are more apparent in UNC if the period of observation is extended. These data suggest that undernutrition at diagnosis by itself and without interacting with other variables, may be a significant prognostic factor in the long-term outcome of treatment of pediatric patients with ALL. After identifying these variables as important, imaginative approaches to the treatment of cancer in childhood in the years ahead may lead into the improvement of the results of these treatments.