Physical Fitness and Frailty in Males after Allogeneic Hematopoietic Stem Cell Transplantation in Childhood : A Long-Term Follow-Up Study

Simple Summary The prevalence of frailty is increased among young adult childhood cancer survivors and is associated with early morbidity and mortality. The aim of our study was to analyze physical fitness, physical activity and the prevalence of frailty in male long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation. We observed significantly lower muscle strength and muscle endurance in the hand-grip and sit-to-stand tests compared to the age and sex matched normative reference values of the tests. Furthermore, 30% of the survivors were considered pre-frail or frail. Chronic graft-versus-host disease, shorter stature, higher body fat mass and hazardous drinking predicted prefrail/frail status. Common cardiovascular risk factors were associated with poor physical fitness and low physical activity level. These results indicate a need for cardiometabolic follow up as well as health education in the decades following HSCT. Purpose and methods: To analyze physical fitness, physical activity and the prevalence of frailty in male long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation (HSCT). We performed a Nordic two-center study of 98 male survivors (mean age 28.7 years, range 18.5-47.0) treated with pediatric allogeneic hematopoietic stem cell transplantation (HSCT) 1980-2010 in denmark or finland. physical fitness was evaluated by the dominant hand grip-strength, timed up-and-go, sit-to-stand, gait speed and two-minute walk tests. Results: Survivors presented significantly lower muscle strength and muscle endurance in the dominant hand-grip strength (median Z-score -0.7, range -4.3-3.9) and sit-to-stand tests (median Z-score -1.5, range -3.5-2.5) compared to age and sex matched normative values of the tests. However, mobility and gait speed were not affected on a group level. The prevalence of frailty (pre-frail 20% or frail 10%) was high among the survivors. In multiple regression analysis, chronic graft-versus-host disease, shorter stature, higher body fat mass and hazardous drinking predicted prefrail/frail status. Common cardiovascular risk factors, such as increased levels of serum triglycerides, higher resting heart rate and diastolic blood pressure, were associated with lower physical fitness. Conclusion: Low muscle strength and a high incidence of frailty were observed in survivors of pediatric HSCT. There is a predominant risk of cardiovascular and metabolic diseases in the long-term.Peer reviewe

Does vitamin D supplementation improve bone density in vitamin D-deficient children? Protocol for an individual patient data meta-analysis

Introduction Our previous study-level (aggregate data) meta-analysis suggested that vitamin D supplements may be beneficial for bone density specifically in children with vitamin D deficiency. However, the misclassification of vitamin D status inherent in study-level data means that the results are not definitive and cannot provide an accurate assessment of the size of any effect. Therefore, we propose to undertake an individual patient data (IPD) meta-analysis to determine whether the effect of vitamin D supplementation on bone density in children differs according to baseline vitamin D status, and to specifically estimate the effect of vitamin D in children who are vitamin D deficient. Methods and analysis This study has been designed to adhere to the Preferred Reporting Items for Systematic Review and Meta-Analyses of IPD statement. We will include randomised placebo-controlled trials of vitamin D supplementation reporting hone density outcomes at least 6 months after the study commenced in children and adolescents (aged Ethics and dissemination Ethics approval will not be required as the data are to be used for the primary purpose for which they were collected and all original individual studies had ethics approval. Results of the IPD meta-analysis will be submitted for publication in a peer-reviewed journal.Peer reviewe

Iron requirements of infants and toddlers

Iron deficiency (ID) is the most common micronutrient deficiency worldwide and young children are a special risk group because their rapid growth leads to high iron requirements. Risk factors associated with a higher prevalence of ID anemia (IDA) include low birth weight, high cow's-milk intake, low intake of iron-rich complementary foods, low socioeconomic status, and immigrant status. The aim of this position paper was to review the field and provide recommendations regarding iron requirements in infants and toddlers, including those of moderately or marginally low birth weight. There is no evidence that iron supplementation of pregnant women improves iron status in their offspring in a European setting. Delayed cord clamping reduces the risk of ID. There is insufficient evidence to support general iron supplementation of healthy European infants and toddlers of normal birth weight. Formula-fed infants up to 6 months of age should receive iron-fortified infant formula, with an iron content of 4 to 8 mg/L (0.6-1.2 mg(-1) · kg(-1) · day(-1)). Marginally low-birth-weight infants (2000-2500 g) should receive iron supplements of 1-2 mg(-1) · kg(-1) · day(-1). Follow-on formulas should be iron-fortified; however, there is not enough evidence to determine the optimal iron concentration in follow-on formula. From the age of 6 months, all infants and toddlers should receive iron-rich (complementary) foods, including meat products and/or iron-fortified foods. Unmodified cow's milk should not be fed as the main milk drink to infants before the age of 12 months and intake should be limited to <500 mL/day in toddlers. It is important to ensure that this dietary advice reaches high-risk groups such as socioeconomically disadvantaged families and immigrant families

ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children: a Systematic Review and Meta-analysis

The aim of the present article was to perform a systematic review with meta-analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition-associated liver disease. A systematic review of the literature (up to March 2015) identified 23 randomized controlled trials (RCTs). Of these, 17 were performed in preterm infants or critically ill neonates with a short duration of intervention, 2 in older children with short-term use (following surgery or bone marrow transplantation), 1 in neonates with long-term use, and 3 in infants and children receiving long-term parenteral nutrition (PN). Meta-analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short-term use of different ILEs. Because of high heterogeneity of the long-term studies no meta-analysis could be performed. Available studies found that the use of multicomponent fish oil (FO)-containing ILE compared with pure soya bean oil (SO), ILE-reduced liver enzymes, and bilirubin levels in noncholestatic children on long-term PN and one other RCT found that FO-based ILE-reversed cholestasis in a proportion of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short-term use in neonates. The use of multicomponent FO-containing ILE may contribute to a decrease in total bilirubin levels in children with IF on prolonged PN. Well-designed RCTs are, however, lacking and long-term effects have not been determined

Immunofluorescent visualization of mouse interneuron subtypes [v3; ref status: indexed, http://f1000r.es/5hn]

The activity of excitatory neurons is controlled by a highly diverse population of inhibitory interneurons. These cells show a high level of physiological, morphological and neurochemical heterogeneity, and play highly specific roles in neuronal circuits. In the mammalian hippocampus, these are divided into 21 different subtypes of GABAergic interneurons based on their expression of different markers, morphology and their electrophysiological properties. Ideally, all can be marked using an antibody directed against the inhibitory neurotransmitter GABA, but parvalbumin, calbindin, somatostatin, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies on the market directed against these four markers. Searches in the literature databases allowed us to narrow it down to a subset of antibodies most commonly used in publications. However, in our hands the most cited ones did not work for immunofluorescence stainings of formaldehyde fixed tissue sections and cultured hippocampal neurons, and we had to immunostain our way through thirteen different commercial antibodies before finally finding a suitable antibody for each of the four markers. The antibodies were evaluated based on signal-to-noise ratios as well as if positive cells were found in layers of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, an antibody review database, stainings with high signal-to-noise ratios and location of the immunostained cells in accordance with the literature could be obtained, making these antibodies suitable choices for studying the GABAergic system

Arsenic in rice: a cause for concern

Inorganic arsenic intake is likely to affect long-term health. High concentrations are found in some rice-based foods and drinks widely used in infants and young children. In order to reduce exposure, we recommend avoidance of rice drinks for infants and young children. For all of the rice products, strict regulation should be enforced regarding arsenic content. Moreover, infants and young children should consume a balanced diet including a variety of grains as carbohydrate sources. Although rice protein-based infant formulas are an option for infants with cows' milk protein allergy, the inorganic arsenic content should be declared and the potential risks should be considered when using these products

Transition from F-75 to ready-to-use therapeutic food in children with severe acute malnutrition, an observational study in Uganda

An observational study was conducted among children aged 6–59 months treated for SAM at Mulago hospital, Kampala, Uganda.Background World Health Organization now recommends the transition from F-75 to ready-to-use therapeutic foods (RUTF) in the management of severe acute malnutrition (SAM). We described the transition from F-75 to RUTF and identified correlates of failed transition. Methods We conducted an observational study among children aged 6–59 months treated for SAM at Mulago hospital, Kampala, Uganda. Therapeutic feeding during transition phase was provided by first offering half of the energy requirements from RUTF and the other half from F-75 and then increasing gradually to RUTF as only energy source. The child was considered to have successfully transitioned to RUTF if child was able to gradually consume up to 135 kcal/kg/day of RUTF in the transition phase on first attempt. Failed transition to RUTF included children who failed the acceptance test or those who had progressively reduced RUTF intake during the subsequent days. Failure also included those who developed profuse diarrhoea or vomiting when RUTF was ingested. Results Among 341 of 400 children that reached the transition period, 65% successfully transitioned from F-75 to RUTF on first attempt while 35% failed. The median (IQR) duration of the transition period was 4 (3–8) days. The age of the child, mid-upper arm circumference, weight-for-height z-score and weight at transition negatively predicted failure. Each month increase in age reflected a 4% lower likelihood of failure (OR 0.96 (95% CI 0.93; 0.99). Children with HIV (OR 2.73, 95% CI 1.27; 5.85) and those rated as severely ill by caregiver (OR 1.16, 95% CI: 1.02; 1.32) were more likely to fail. At the beginning of the rehabilitation phase, the majority (95%) of the children eventually accepted RUTF while only 5% completed rehabilitation in hospital on F-100. Conclusion Transition from F-75 to RUTF for hospitalized children with SAM by gradual increase of RUTF was possible on first attempt in 65% of cases. Younger children, severely wasted, HIV infected and those with severe illness as rated by the caregiver were more likely to fail to transit from F-75 to RUTF on first attempt

Sugar in Infants, Children and Adolescents: A Position Paper of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition

The consumption of sugars, particularly sugar-sweetened beverages (SSBs; beverages or drinks that contain added caloric sweeteners (ie, sucrose, high-fructose corn syrup, fruit juice concentrates), in European children and adolescents exceeds current recommendations. This is of concern because there is no nutritional requirement for free sugars, and infants have an innate preference for sweet taste, which may be modified and reinforced by pre- and postnatal exposures. Sugar-containing beverages/free sugars increase the risk for overweight/obesity and dental caries, can result in poor nutrient supply and reduced dietary diversity, and may be associated with increased risk of type 2 diabetes mellitus, cardiovascular risk, and other health effects. The term "free sugars," includes all monosaccharides/disaccharides added to foods/beverages by the manufacturer/cook/consumer, plus sugars naturally present in honey/syrups/unsweetened fruit juices and fruit juice concentrates. Sugar naturally present in intact fruits and lactose in amounts naturally present in human milk or infant formula, cow/goat milk, and unsweetened milk products is not free sugar. Intake of free sugars should be reduced and minimised with a desirable goal of <5% energy intake in children and adolescents aged ≥2 to 18 years. Intake should probably be even lower in infants and toddlers <2 years. Healthy approaches to beverage and dietary consumption should be established in infancy, with the aim of preventing negative health effects in later childhood and adulthood. Sugar should preferably be consumed as part of a main meal and in a natural form as human milk, milk, unsweetened dairy products, and fresh fruits, rather than as SSBs, fruit juices, smoothies, and/or sweetened milk products. Free sugars in liquid form should be replaced by water or unsweetened milk drinks. National Authorities should adopt policies aimed at reducing the intake of free sugars in infants, children and adolescents. This may include education, improved labelling, restriction of advertising, introducing standards for kindergarten and school meals, and fiscal measures, depending on local circumstances