Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma.

BACKGROUND: Noninvasive diagnostic options are limited for invasive mold infections (IMIs). We evaluated the performance of a plasma microbial cell-free DNA sequencing (mcfDNA-Seq) test for diagnosing pulmonary IMI after hematopoietic cell transplant (HCT). METHODS: We retrospectively assessed the diagnostic performance of plasma mcfDNA-Seq next-generation sequencing in 114 HCT recipients with pneumonia after HCT who had stored plasma obtained within 14 days of diagnosis of proven/probable Aspergillus IMI (n = 51), proven/probable non-Aspergillus IMI (n = 24), possible IMI (n = 20), and non-IMI controls (n = 19). Sequences were aligned to a database including >400 fungi. Organisms above a fixed significance threshold were reported. RESULTS: Among 75 patients with proven/probable pulmonary IMI, mcfDNA-Seq detected ≥1 pathogenic mold in 38 patients (sensitivity, 51% [95% confidence interval {CI}, 39%-62%]). When restricted to samples obtained within 3 days of diagnosis, sensitivity increased to 61%. McfDNA-Seq had higher sensitivity for proven/probable non-Aspergillus IMI (sensitivity, 79% [95% CI, 56%-93%]) compared with Aspergillus IMI (sensitivity, 31% [95% CI, 19%-46%]). McfDNA-Seq also identified non-Aspergillus molds in an additional 7 patients in the Aspergillus subgroup and Aspergillus in 1 patient with possible IMI. Among 19 non-IMI pneumonia controls, mcfDNA-Seq was negative in all samples, suggesting a high specificity (95% CI, 82%-100%) and up to 100% positive predictive value (PPV) with estimated negative predictive values (NPVs) of 81%-99%. The mcfDNA-Seq assay was complementary to serum galactomannan index testing; in combination, they were positive in 84% of individuals with proven/probable pulmonary IMI. CONCLUSIONS: Noninvasive mcfDNA-Seq had moderate sensitivity and high specificity, NPV, and PPV for pulmonary IMI after HCT, particularly for non-Aspergillus species.

Use of Urine Biomarkers to Assess Sodium Intake: Challenges and Opportunities.

This article summarizes current data and approaches to assess sodium intake in individuals and populations. A review of the literature on sodium excretion and intake estimation supports the continued use of 24-h urine collections for assessing population and individual sodium intake. Since 2000, 29 studies used urine biomarkers to estimate population sodium intake, primarily among adults. More than half used 24-h urine; the rest used a spot/casual, overnight, or 12-h specimen. Associations between individual sodium intake and health outcomes were investigated in 13 prospective cohort studies published since 2000. Only three included an indicator of long-term individual sodium intake, i.e., multiple 24-h urine specimens collected several days apart. Although not insurmountable, logistic challenges of 24-h urine collection remain a barrier for research on the relationship of sodium intake and chronic disease. Newer approaches, including modeling based on shorter collections, offer promise for estimating population sodium intake in some groups.

US consumer attitudes toward sodium in baby and toddler foods.

Dietary data from a nationally representative survey indicate about 80% of US toddlers aged 1-3 years consume too much dietary sodium, which can influence their preference for salty foods in later life. Information on consumer attitudes can inform strategies to reduce sodium in baby and toddler foods. Data were obtained from a 2012 online survey sent to a sample of 11636 US adults aged ≥18 years enrolled in a national probability-based consumer panel; 6378 completed the survey and had non-missing responses to the question of interest, "It is important for baby and toddler foods to be low in sodium." Prevalence of agreement was estimated. Logistic regression was used to describe associations of respondent characteristics with agreement. The majority of respondents were non-Hispanic white and had a household income ≥$60,000. About 7 in 10 (68%, 95% CI: 66%-70%) respondents agreed it is important for baby or toddler foods to be low in sodium. More than 6 of 10 respondents in most subgroups agreed. Among parents with a child currently aged <2 years (N = 390), 82% agreed (95% CI: 77%-87%); the highest agreement included parents who thought sodium was very harmful to their own health (92%, 95% CI: 85%-99%) or who were watching/reducing their own sodium intake (95%, 95% CI: 90%-100%). After adjusting for sex, age, race-ethnicity, agreement was most strongly associated with being a parent of a child <2 years, thinking sodium was harmful, and watching/reducing sodium intake (adjusted odds ratios ≥ 2.5, 95% CI's ≠1.0). The majority of respondents including most parents agreed it is important for baby and toddler foods to be low in sodium, suggesting wide consumer support for strategies to lower sodium in these foods.

Reported use and perceived understanding of sodium information on US nutrition labels.

INTRODUCTION: Comparing nutrition labels and choosing lower sodium foods are tactics to help reduce excessive sodium intake, a major risk factor for hypertension. Our objective was to assess US adult consumers' reported use and perceived understanding of sodium information on nutrition labels by sociodemographic and health status. METHODS: We analyzed responses to questions from 3,729 adults aged 18 years or older participating in 2 national cross-sectional mail panel surveys in 2010. RESULTS: We found that 19.3% (95% confidence interval [CI], 17.2%-21.6%) of respondents agreed they were confused about how to figure out how much sodium is in the foods they eat; 57.9% (95% CI, 55.4%-60.5%) reported that they or the person who shops for their food buy items labeled low salt or low sodium; and 46.8% (95% CI, 44.3%-49.4%) reported they check nutrition labels for sodium content as a tactic to limit salt. Consumers with a high school education or less were more likely than college graduates to report they were confused about sodium content on labels (adjusted odds ratio [AOR], 1.9; 95% CI, 1.4-2.8) and less likely to check labels for sodium as a tactic to limit salt intake (AOR, 0.7; 95% CI, 0.6-0.98). CONCLUSION: Most survey respondents in our study reported buying low sodium food items. However, a higher proportion of respondents with low education than respondents with high education reported confusion with and less use of sodium content information, suggesting enhanced efforts may be needed to assist this group. Opportunity exists for health care professionals to educate patients about using and understanding nutrition labels and consuming a diet consistent with the Dietary Approaches to Stop Hypertension (DASH) eating plan.

Sodium content in packaged foods by census division in the United States, 2009.

Excess sodium intake correlates positively with high blood pressure. Blood pressure varies by region, but whether sodium content of foods sold varies across regions is unknown. We combined nutrition and sales data from 2009 to assess the regional variation of sodium in packaged food products sold in 3 of the 9 US census divisions. Although sodium density and concentration differed little by region, fewer than half of selected food products met Food and Drug Administration sodium-per-serving conditions for labeling as "healthy." Regional differences in hypertension were not reflected in differences in the sodium content of packaged foods from grocery stores.

Monitoring the sodium content of restaurant foods: public health challenges and opportunities.

We reviewed methods of studies assessing restaurant foods' sodium content and nutrition databases. We systematically searched the 1964-2012 literature and manually examined references in selected articles and studies. Twenty-six (5.2%) of the 499 articles we found met the inclusion criteria and were abstracted. Five were conducted nationally. Sodium content determination methods included laboratory analysis (n = 15), point-of-purchase nutrition information or restaurants' Web sites (n = 8), and menu analysis with a nutrient database (n = 3). There is no comprehensive data system that provides all information needed to monitor changes in sodium or other nutrients among restaurant foods. Combining information from different sources and methods may help inform a comprehensive system to monitor sodium content reduction efforts in the US food supply and to develop future strategies.

Gender differences in the heritability of musculoskeletal and body composition parameters in mother-daughter and mother-son pairs.

Bone mass and body composition traits are genetically programmed, but the timing and gender and site specificities of their heritability are unclear. Mother-child correlations of bone mineral density (BMD) and bone mineral content, lean mass, and fat mass were studied in 169 premenopausal mothers and their 239 children. Heritability estimates of lean mass, fat mass, BMD, and area were derived for each gender and pubertal stage. There were significant correlations for most densitometry-derived variables at the spine, hip, femoral neck (FN), and total body (r=0.192-0.388) in mother-postmenarcheal daughter pairs, for bone areas at all sites in early puberty (r=0.229-0.508) and for volumetric-derived density at FN and spine (r=0.238-0.368) in mother-son pairs. Fat mass correlations were significant in both genders after puberty (r=0.299-0.324) and lean mass in postmenarcheal girls only (r = 0.299). Heritability estimates varied between 21% and 37% for mother-daughter and 18% and 35% for mother-son pairs for density-derived variables and between 26% and 40% for body composition variables. Maternal inheritance of bone traits is expressed in early-pubertal boys for several skeletal site traits but consistently involves most site traits in girls and boys by late puberty. Body composition inheritance is more variable.

Nutrition and physical activity in child care centers: the impact of a wellness policy initiative on environment and policy assessment and observation outcomes, 2011.

INTRODUCTION: The child care environment has emerged as an ideal setting in which to implement policies that promote healthy body weight of children. The purpose of this study was to assess the effect of a wellness policy and training program on the physical activity and nutrition environment in 24 child care centers in Georgia. METHODS: We used the Environment and Policy Assessment and Observation instrument to identify changes to foods served, staff behaviors, and physical activity opportunities. Observations were performed over 1 day, beginning with breakfast and concluding when the program ended for the day. Observations were conducted from February 2010 through April 2011 for a total of 2 observations in each center. Changes to nutrition and physical activity in centers were assessed on the basis of changes in scores related to the physical activity and nutrition environment documented in the observations. Paired t test analyses were performed to determine significance of changes. RESULTS: Significant improvements to total nutrition (P < .001) and physical activity scores (P < .001) were observed. Results indicate that centers significantly improved the physical activity environments of centers by enhancing active play (P = .02), the sedentary environment (P = .005), the portable environment (P = .002), staff behavior (P = .004), and physical activity training and education (P < .001). Significant improvements were found for the nutrition environment (P < .001), and nutrition training and education (P < .001). CONCLUSION: Findings from this study suggest that implementing wellness policies and training caregivers in best practices for physical activity and nutrition can promote healthy weight for young children in child care settings.

Association of Inherited Chromosomally Integrated Human Herpesvirus 6 with Neurologic Symptoms and Management after Allogeneic Hematopoietic Cell Transplantation.

Reactivation of human herpesvirus 6 (HHV-6) after allogeneic hematopoietic cell transplantation (HCT) is associated with neurologic complications, but the impact of donor and/or recipient inherited chromosomally integrated HHV-6 (iciHHV-6) on post-HCT central nervous system (CNS) symptoms and diagnostic and therapeutic interventions is not well understood. The aims of the present study were (1) to compare the cumulative incidence of CNS symptoms in the first 100 days following allogeneic HCT among patients with donor and/or recipient iciHHV-6 (iciHHV-6pos)with that of patients with neither donor nor recipient iciHHV-6 (iciHHV-6neg) and (2) to assess the role of HHV-6 detection in driving potentially unnecessary interventions in iciHHV-6pos patients. We performed a retrospective matched cohort study of 87 iciHHV-6pos and 174 iciHHV-6neg allogeneic HCT recipients. HHV-6 testing was performed at the discretion of healthcare providers, who were unaware of iciHHV-6 status. The cumulative incidence of CNS symptoms was similar in iciHHV-6pos (n = 37; 43%) and iciHHV-6neg HCT recipients (n = 81; 47%; P = .63). HHV-6 plasma testing was performed in similar proportions of iciHHV-6pos (n = 6; 7%) and iciHHV-6neg (9%) patients and was detected in all tested iciHHV-6pos HCTs and 2 (13%) iciHHV-6neg HCTs. This resulted in more frequent HHV-6-targeted antiviral therapy after iciHHV-6pos HCT (odds ratio, 12.8; 95% confidence interval, 1.5 to 108.2) with associated side effects. HHV-6 plasma detection in 2 iciHHV-6pos patients without active CNS symptoms prompted unnecessary lumbar punctures. The cumulative incidence of CNS symptoms was similar after allogeneic HCT involving recipients or donors with and without iciHHV-6. Misattribution of HHV-6 detection as infection after iciHHV-6pos HCT may lead to unnecessary interventions. Testing for iciHHV-6 may improve patient management.

Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies.

BACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay. The primary outcome was the proportion of participants with IgG levels above a threshold correlated with seroprotection for vaccine-preventable infections.RESULTSWe enrolled 65 children and adults a median of 20 months after CD19- (n = 54) or BCMA- (n = 11) CAR-T cell therapy. Among 30 adults without IgG replacement therapy (IGRT) in the prior 16 weeks, 27 (90%) had hypogammaglobulinemia. These individuals had seroprotection to a median of 67% (IQR, 59%-73%) of tested infections. Proportions of participants with seroprotection per pathogen were comparable to population-based studies, but most individuals lacked seroprotection to specific pathogens. Compared with CD19-CAR-T cell recipients, BCMA-CAR-T cell recipients were half as likely to have seroprotection (prevalence ratio, 0.47; 95% CI, 0.18-1.25) and had fewer pathogen-specific epitope hits (mean difference, -90 epitope hits; 95% CI, -157 to -22).CONCLUSIONSeroprotection for vaccine-preventable infections in adult CD19-CAR-T cell recipients was comparable to the general population. BCMA-CAR-T cell recipients had fewer pathogen-specific antibodies. Deficits in both groups support the need for vaccine and immunoglobulin replacement therapy studies.FUNDINGSwiss National Science Foundation (Early Postdoc Mobility grant P2BSP3_188162), NIH/National Cancer Institute (NIH/NCI) (U01CA247548 and P01CA018029), NIH/NCI Cancer Center Support Grants (P30CA0087-48 and P30CA015704-44), American Society for Transplantation and Cellular Therapy, and Juno Therapeutics/BMS.

Reduction of radiation and contrast agent exposure in a cryoballoon ablation procedure with integration of electromagnetic mapping and intracardiac echocardiography: a single center experience.

BACKGROUND: Pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) is routinely guided by fluoroscopy and utilizes contrast injection to ensure catheter positioning and pulmonary vein occlusion. Non-fluoroscopic imaging techniques including electromagnetic mapping (EM) and intracardiac echocardiography (ICE) have demonstrated reduced fluoroscopy times and contrast exposure. Utilization of color flow Doppler to evaluate vein occlusion with the balloon has not been evaluated as an alternative to contrast injection. In this study we evaluate the effectiveness of cryoablation guided by EM and ICE along with color Doppler to achieve PVI. METHODS: We designed a retrospective cohort study comparing patients who were treated before and after implementation of EM (Carto 3, Biosense Webster) and ICE during CBA (AF Solutions, Medtronic). We analyzed patients receiving CBA with fluoroscopy plus EM and ICE (group 2; N = 24) versus fluoroscopy alone (group 1; N = 25). Procedural success was defined as freedom from atrial fibrillation or other atrial arrhythmias at 1 year post ablation. Primary outcomes were radiation time and contrast exposure. RESULTS: Procedural success was achieved in all cases. Total fluoroscopy time was reduced from 22.4 ± 9.8 min to 8.9 ± 5.1 min (P < 0.001) in patients receiving CBA guided by EM and ICE. Furthermore, exposure to contrast media was significantly lower at 75.4 ± 24.1 ml and 16.5 ± 21.1 ml (P ≤ 0.001) in group 1 and group 2, respectively. Neither the number of required cryotherapy treatments nor procedure duration was negatively impacted by the implementation of non-fluoroscopic techniques. The 1-year success rate was identical between both groups at 72% and 79%. There was no difference in complication rates. CONCLUSION: This single-center cohort study demonstrates that CBA guided by EM and ICE can markedly reduce radiation and contrast exposure with excellent rates of acute PVI. This technique may be particularly effective in patients sensitive to intravenous contrast exposure.

Efficacy of Implantable Cardioverter-defibrillators for Secondary Prevention of Sudden Cardiac Death in Patients with End-stage Renal Disease.

End-stage renal disease (ESRD) constitutes a major burden on the health-care system in the United States, with more than 300,000 patients nationwide being treated with renal replacement therapy. Very few studies to date have evaluated the benefit of implantable cardioverter-defibrillator (ICD) implantation for secondary prevention in patients with ESRD. In this study, we evaluated the efficacy of secondary-prevention ICDs in reducing all-cause mortality in patients on dialysis using the United States Renal Data System (USRDS) database. We queried the USRDS for relevant data between 2004 and 2010. Patients with diagnoses of ventricular fibrillation (VF), ventricular tachycardia (VT), or sudden cardiac arrest (SCA) were included in the study. Patients were excluded from the analysis if they were younger than 18 years; had missing age, sex, or race/ethnicity information; had experienced myocardial infarction; or had an ICD in situ at the time of VF, VT, or SCA diagnosis. The primary endpoint of this study was to determine the efficacy of secondary-prevention ICDs in reducing all-cause mortality in patients on dialysis. A total of 1,442 patients (3.4%) with ESRD had ICD insertion. Patients who received an ICD were predominantly younger, white males with lower Charlson Comorbidity Index and with fewer cardiovascular events. Survival at two years was 53% among those with an ICD relative to 27% among those without an ICD. In this study, we observed a substantial decrease in mortality in patients receiving an ICD for secondary prevention when compared with a cohort of similar patients with a history of VF, VT, or SCA.

Dietary Sodium Intake and Health Indicators: A Systematic Review of Published Literature between January 2015 and December 2019.

As the science surrounding population sodium reduction evolves, monitoring and evaluating new studies on intake and health can help increase our understanding of the associated benefits and risks. Here we describe a systematic review of recent studies on sodium intake and health, examine the risk of bias (ROB) of selected studies, and provide direction for future research. Seven online databases were searched monthly from January 2015 to December 2019. We selected human studies that met specified population, intervention, comparison, outcome, time, setting/study design (PICOTS) criteria and abstracted attributes related to the study population, design, intervention, exposure, and outcomes, and evaluated ROB for the subset of studies on sodium intake and cardiovascular disease risks or indicators. Of 41,601 abstracts reviewed, 231 studies were identified that met the PICOTS criteria and ROB was assessed for 54 studies. One hundred and fifty-seven (68%) studies were observational and 161 (70%) focused on the general population. Five types of sodium interventions and a variety of urinary and dietary measurement methods were used to establish and quantify sodium intake. Five observational studies used multiple 24-h urine collections to assess sodium intake. Evidence mainly focused on cardiovascular-related indicators (48%) but encompassed an assortment of outcomes. Studies varied in ROB domains and 87% of studies evaluated were missing information on ≥1 domains. Two or more studies on each of 12 outcomes (e.g., cognition) not previously included in systematic reviews and 9 new studies at low ROB suggest the need for ongoing or updated systematic reviews of evidence on sodium intake and health. Summarizing evidence from assessments on sodium and health outcomes was limited by the various methods used to measure sodium intake and outcomes, as well as lack of details related to study design and conduct. In line with research recommendations identified by the National Academies of Science, future research is needed to identify and standardize methods for measuring sodium intake.

Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy.

The long-term effects of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (CD19-CARTx) for B-cell malignancies on humoral immunity are unclear. We examined antiviral humoral immunity in 39 adults with B-cell malignancies who achieved durable complete remission without additional therapy for >6 months after CD19-CARTx. Despite CD19+ B-cell aplasia in all patients, the incidence of viral infections occurring >90 days post-CD19-CARTx was low (0.91 infections per person-year). Because long-lived plasma cells are CD19- and should not be direct targets of CD19-targeted chimeric antigen receptor T cells, we tested the hypothesis that humoral immunity was preserved after CD19-CARTx based on linear mixed-effects models of changes in serum total immunoglobulin G (IgG) concentration, measles IgG concentration, and the number of viruses or viral epitopes to which serum IgG was directed (the "antivirome") using the novel VirScan assay. Samples were tested pre-CD19-CARTx and ∼1, 6, and 12 months post-CD19-CARTx. Although total IgG concentration was lower post-CD19-CARTx (mean change, -17.5%), measles IgG concentration was similar (mean change, 1.2%). Only 1 participant lost measles seroprotection post-CD19-CARTx but had undergone allogeneic hematopoietic cell transplantation before CD19-CARTx. The antivirome was also preserved, with mean absolute losses of 0.3 viruses and 6 viral epitopes detected between pre- and post-CD19-CARTx samples. Most participants gained IgG to ≥2 epitopes for ≥2 viruses, suggesting that humoral immunity to some viruses may be maintained or recover after successful CD19-CARTx. These findings may differ in children. Studies of immunoglobulin replacement and vaccination after CARTx are warranted.

Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children.

BACKGROUND: Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D(3) administered to apparently healthy schoolchildren. METHODS: To assess short-term safety, 25 subjects randomly received placebo or vitamin D(3) at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D(3) as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8 wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study. RESULTS: In both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (+/- 11) to 54 (+/- 19) ng/ml in the treated groups (P = 0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 +/- 8 to 19 +/- 7 ng/ml (P < 0.0001) in subjects receiving 1,400 IU/wk and from 15 +/- 7 to 36 +/- 22 ng/ml (P < 0.0001) in the group receiving 14,000 IU/wk. No subject developed vitamin D intoxication. CONCLUSION: Vitamin D(3) at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels.

Sodium, sugar, and fat content of complementary infant and toddler foods sold in the United States, 2015.

Background: As part of a healthy diet, limiting intakes of excess sodium, added sugars, saturated fat, and trans fat has been recommended. The American Heart Association recommends that children aged <2 y should avoid added sugars.Objective: We sought to determine commercial complementary infant-toddler food categories that were of potential concern because of the sodium, added sugar, saturated fat, or trans fat content.Design: Nutrition label information (e.g., serving size, sodium, saturated fat, trans fat) for 1032 infant and toddler foods was collected from manufacturers' websites and stores from May to July 2015 for 24 brands, which accounted for >95% of infant-toddler food sales. The presence of added sugars was determined from the ingredient list. Reference amount customarily consumed (RACC) categories were used to group foods and standardize serving sizes. A high sodium content was evaluated on the basis of the Upper Intake Level for children aged 1-3 y and the number of potential servings per day ([i.e., 1500 mg/7 servings (>210 mg/RACC)], a sodium amount >200 mg/100 g, or a mean sodium density >1000 mg/1000 kcal.Results: In 2015, most commercial infant-only vegetables, fruit, dinners, and cereals were low in sodium, contained no saturated fat, and did not contain added sugars. On average, toddler meals contained 2233 mg Na/1000 kcal, and 84% of the meals had >210 mg Na/RACC (170 g), whereas 69% of infant-toddler savory snacks had >200 mg Na/100 g. More than 70% of toddler meals, cereal bars and breakfast pastries, and infant-toddler grain- or dairy-based desserts contained ≥1 sources of added sugar. Approximately 70% of toddler meals contained saturated fat (mean: 1.9 g/RACC), and no commercial infant-toddler foods contained trans fats.Conclusion: Most commercial toddler meals, cereal bars and breakfast pastries, and infant-toddler snacks and desserts have high sodium contents or contain added sugars, suggesting a need for continued public health efforts to support parents in choosing complementary foods for their infants and toddlers.

Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial.

BACKGROUND: Despite the high prevalence of hypovitaminosis D in children and adolescents worldwide, the impact of vitamin D deficiency on skeletal health is unclear. METHODS: One hundred seventy-nine girls, ages 10-17 yr, were randomly assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo-controlled, 1-yr protocol. Areal bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip, forearm, total body, and body composition were measured at baseline and 1 yr. Serum calcium, phosphorus, alkaline phosphatase, and vitamin D metabolites were measured during the study. RESULTS: In the overall group of girls, lean mass increased significantly in both treatment groups (P < or = 0.05); bone area and total hip BMC increased in the high-dose group (P < 0.02). In premenarcheal girls, lean mass increased significantly in both treatment groups, and there were consistent trends for increments in BMD and/or BMC at several skeletal sites, reaching significance at lumbar spine BMD in the low-dose group and at the trochanter BMC in both treatment groups. There was no significant change in lean mass, BMD, or BMC in postmenarcheal girls. CONCLUSIONS: Vitamin D replacement had a positive impact on musculoskeletal parameters in girls, especially during the premenarcheal period.

Do Lower Calorie or Lower Fat Foods Have More Sodium Than Their Regular Counterparts?

The objective of this study was to compare the sodium content of a regular food and its lower calorie/fat counterpart. Four food categories, among the top 20 contributing the most sodium to the US diet, met the criteria of having the most matches between regular foods and their lower calorie/fat counterparts. A protocol was used to search websites to create a list of "matches", a regular and comparable lower calorie/fat food(s) under each brand. Nutrient information was recorded and analyzed for matches. In total, 283 matches were identified across four food categories: savory snacks (N = 44), cheese (N = 105), salad dressings (N = 90), and soups (N = 44). As expected, foods modified from their regular versions had significantly reduced average fat (total fat and saturated fat) and caloric profiles. Mean sodium content among modified salad dressings and cheeses was on average 8%-12% higher, while sodium content did not change with modification of savory snacks. Modified soups had significantly lower mean sodium content than their regular versions (28%-38%). Consumers trying to maintain a healthy diet should consider that sodium content may vary in foods modified to be lower in calories/fat.

Persistent Effect of Vitamin D Supplementation on Musculoskeletal Parameters in Adolescents One Year After Trial Completion.

We showed a beneficial effect of vitamin D supplementation on musculoskeletal parameters in adolescent girls in a 1-year, randomized, double-blinded placebo-controlled trial (RCT). Our objective for this study was to investigate the residual effect of vitamin D supplementation on bone mineral content (BMC), bone mineral density (BMD), at the lumbar spine and hip, lean mass, and height, 1 year after trial completion. We performed post hoc analyses in 167 adolescents, 86 girls and 81 boys, age 13.9 ± 2 years, who received vitamin D or placebo during the trial, and continued into the follow-up trial. Musculoskeletal parameters were measured at baseline, 12 months (intervention), and 24 months (follow-up). ANOVA and t tests were used to compare results between the placebo group and the merged vitamin D arms (200 or 2000 IU/day), by gender. Baseline characteristics were comparable between treatment groups at entry into the extension. Girls who had received vitamin D during the trial, had significantly larger hip BMC increments compared to those assigned to placebo, at 24 months compared to study entry, but not 24 compared to 12 months, which persisted in adjusted analyses. There were no significant differences in bone mass changes between treatment groups in boys, at 24 months compared to 12 months or to baseline. The beneficial effect of vitamin D supplementation on hip bone mass, achieved in girls during the trial, persisted 1 year after trial completion. These net cumulative increments, 1 year after discontinuation of supplementation, may have important implications on optimizing peak bone mass accretion in adolescent girls. © 2016 American Society for Bone and Mineral Research.

The Relationship Between Calciotropic Hormones, IGF-1, and Bone Mass Across Pubertal Stages.

BACKGROUND: Little is known about the changes in calciotropic hormones during puberty and their relationship to bone mass during this critical period for skeletal accretion. OBJECTIVES: Investigate changes in calciotropic hormones, IGF-1, body composition, and their associations with bone metabolism in adolescents. METHODS: Post hoc analyses were performed from data on 335 healthy school children, ages 10-17 years, with hypovitaminosis D who participated in a vitamin D randomized controlled trial. Baseline serum biochemistries; hormonal studies; densitometry at the spine, hip, and total body; and body composition were used. ANOVA and regression analyses were implemented to evaluate changes in variables of interest across pubertal stages, within and between genders. RESULTS: Bone mass and body composition parameters increased substantially across Tanner stages in both genders. Serum calcium, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D levels did not vary by Tanner stages in both genders. Conversely, serum phosphorus, alkaline phosphatase, IGF-1, PTH, and osteocalcin peaked for the most part at Tanner stage II in girls and stage III in boys. 1,25-Dihydroxyvitamin D correlations with bone mass were not consistent, whereas IGF-1 was the most robust correlate of bone mass at several skeletal sites in early Tanner stages in both genders (R = 0.3-0.6). CONCLUSION: Serum phosphorus, alkaline phosphatase, IGF-1, PTH, and osteocalcin, but not calcium or 1,25-dihydroxyvitamin D, increased significantly in early puberty, with gender difference except for PTH, peaking earlier in girls than in boys. IGF-1 is a robust predictor of bone mass, an effect mediated in large part by increments in lean mass.