Objective: To gain insight into vitamin A deficiency as a cause of anemia. Methods: Comprehensive review of the scientific literature. Results: Although vitamin A deficiency is recognized to cause anemia, 'vitamin A deficiency anemia' lacks complete characterization as a distinct clinical entity. Vitamin A appears to be involved in the pathogenesis of anemia through diverse biological mechanisms, such as the enhancement of growth and differentiation of erythrocyte progenitor cells, potentiation of immunity to infection and reduction of the anemia of infection, and mobilization of iron stores from tissues. Epidemiological surveys show that the prevalence of anemia is high in populations affected by vitamin A deficiency in developing countries. Improvement of vitamin A status has generally been shown to reduce anemia, but the actual public health impact on anemia is unclear. Conclusions: Further work is needed to elucidate the biological mechanisms by which vitamin A causes anemia. The inclusion of anemia as an outcome measure in future micronutrient intervention studies should help provide further insight into the anemia of vitamin A deficiency.

To investigate the association between vitamin A and iron metabolism, two studies were carried out: a cross-sectional study and an intervention trial. The cross-sectional analysis was carried out in 1060 children aged 1-8 y. Multiple-regression analysis was used to adjust for effects of age, gender, indices of the protein nutritional status, and infections. Retinol was significantly associated with hematocrit, serum Fe, transferrin, ferritin, and saturation of transferrin (%ST). To obtain further evidence as to whether this observed association is a causal one, an intervention trial was carried out. After collection of the baseline data of 300 children, 166 children with a hemoglobin concentration less than 7.5 mmol/L were selected. A random sub-sample of 78 children received vitamin A capsules; the other children served as control subjects. Two months after supplementation significant differences, adjusted for age, were found for retinol, retinol-binding protein, serum Fe, and %ST between the supplemented and the control group. After 4 mo none of the indices were found to be significantly different between the supplemented and the control group. Periodic massive doses of vitamin A may play a role in improving the Fe status as well.

A group of 134 school children aged 3-9 y, with signs of conjunctival xerosis, from the rural area of the Sakorn Nakhon province in Northeast Thailand were selected for a controlled study on the short-term effect (2 wk) of a single, oral high dose of vitamin A on iron metabolism. After collection of the baseline data, children within villages were randomly assigned to receive the capsules (n = 65) or serve as control subjects (n = 69). Two weeks after supplementation significant increases of retinol, retinol-binding protein, hemoglobin, hematocrit, serum iron, and saturation of transferrin were found in the supplemented group. Ferritin concentrations did not change significantly. These short-term changes completely exclude seasonal effects and change in morbidity. This study provides further evidence of a causal association between vitamin A and iron metabolism. In areas where vitamin A deficiency is endemic, periodic massive vitamin A dose programs can also improve iron status of the population.

Objective: To examine whether the relationship between vitamin A intake, from plant and animal foods, and vitamin A status is the same throughout a population. Design: Analysis of cross-sectional data on vitamin A intake, vitamin A status, physiological condition and socio-economic status. Setting: Central Java, Indonesia. Subjects: Women with a child 24 months old (n 600). Results: Mean serum retinol concentration of women with animal vitamin A intake below or above the median (50 REad) was 1.28 and 1.38 "molaL, respectively (P`0.05). For those with intake above the median the distribution curve for serum retinol concentration was shifted towards the right, to higher concentrations. Serum retinol concentration of women with plant vitamin A intake below or above the median (279 REad) was 1.30 and 1.36 "molaL, respectively (P`0.05). Again, the distribution curve for serum retinol was shifted towards higher concentrations for women with an intake above the median, except for the subgroup of 25% with the lowest serum retinol concentration (`1.10 "molaL). These women did not seem to bene®t from their relatively high vegetable intake. They also had the lowest socio-economic status. Conclusions: The subgroup that was most in need of vitamin A could not obtain it from plant foods. It may well be that, because of their lower socio-economic status, their hygiene conditions were worse and therefore hostrelated factors that affect carotene bioavailability, such as parasitic infestation, were less favourable in this group. They depended on supplements and, if affordable, on animal foods, fruits andaor forti®ed products.

The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients’ survival based on their baseline and disease characteristics.