Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression (CREATINE-52): a protocol for a double-blind randomized controlled trial.

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

Safety and Efficacy of Early Vitamin D Supplementation in Critically Ill Extremely Preterm Infants: An Ancillary Study of a Randomized Trial.

BACKGROUND: Despite substantial evidence that vitamin D deficiency is highly prevalent among infants born extremely preterm (≤28 weeks' of gestation), several consensus statements do not recommend vitamin D doses >400 IU/day for these infants. Safety remains a concern. OBJECTIVE: The study aim was to determine safety and efficacy profiles of enteral vitamin D in Black and White infants randomized to three different vitamin D doses soon after birth. DESIGN: Ancillary study of a masked randomized clinical trial. PARTICIPANTS/SETTING: Seventy-three infants born extremely preterm between 2012 and 2015 at a southern US academic neonatal unit (33' latitude) who had >90% compliance with the assigned intervention were included. INTERVENTION: Infants were randomized to receive placebo (placebo group), 200 IU/day vitamin D (200 IU group), or 800 IU/day vitamin D (800 IU group) during the first 28 days after birth. MAIN OUTCOME MEASURES: Safety outcomes included serum 25-hydroxy vitamin D (25[OH]D) and calcium concentrations. Efficacy outcomes included the predictive risk of bronchopulmonary dysplasia. STATISTICAL ANALYSIS: Per-protocol analysis using unadjusted, repeated-measures mixed models. RESULTS: Mean birth weight was 815 ± 199 g. Half were male and 56% were Black. Of 58 infants with 25(OH)D measurements at birth, 40 (69%) had vitamin D deficiency (<20 ng/mL). The mean difference in 25(OH)D in nanograms per milliliter between Postnatal Day 28 and Postnatal Day 1 was +9 in the placebo group, +23 in the 200 IU group, and +62 in the 800 IU group (P < 0.0001). The increase observed in 25(OH)D was more significant among Black infants. The predictive risk of severe bronchopulmonary dysplasia in the 200 IU and 800 IU groups was lower, but this difference did not reach statistical significance. No vitamin D or calcium toxicity was observed. CONCLUSIONS: A vitamin D dose of 800 IU/day safely corrected vitamin D deficiency by Postnatal Day 14.

Human Milk Fortification: A Practical Analysis of Current Evidence.

Human milk (HM) with appropriate fortification is the recommended nutrition for very low birth weight (VLBW) infants. Fortification provides additional nutrients, vitamins, and minerals to support the growing preterm infant during critical periods of development. This article discusses the variability of HM including differences between maternal and pasteurized donor human milk (DHM), fortification of HM through the use of single- and multi-nutrient fortifiers, and clinical controversies including the timing of fortification, volume of feedings, and future innovations in HM fortification.

Review of the holistic management of pediatric atopic dermatitis.

Atopic Dermatitis (AD) is a chronic inflammatory skin disease that is broadly characterized by eczematous lesions and pruritus. This condition is detrimental in a multitude of ways, including patient quality of life (QOL), family QOL, economic burden, and psychosocial afflictions. Current management needs to incorporate a holistic approach which considers the financial, emotional, and physical limitations of both the treatments and the provider. A non-systematic search was conducted on the holistic management of pediatric AD. Various search queries were used such as the key terms of "atopic dermatitis," "pediatric," "eczema," "management," and more to encompass treatments, adherence, and comorbidities. There is an association with AD and depression in children, and its prevalence should be screened for routinely in children with AD. Collaboration with other specialties may prove to be prudent in addressing this comorbidity. Objective quality of life scores can open the door to much needed conversation with patients to get them the help they need. In expanding our scope, we find the extended consequences of AD have a ripple effect on families of pediatric patients. Lastly, we introduce a model for improving treatment adherence. CONCLUSION: Patient quality-of-life can be negatively affected by the symptoms, expense, stigma, and time commitment, and inconvenience imposed by complicated treatment regimens. To ensure proper, holistic management of pediatric AD, multiple factors must be considered; seasonal changes, lifestyle modifications, and the psychosocial impact are just a couple of factors that require monitoring. WHAT IS KNOWN: • Atopic dermatitis impacts patients and their families in quality of life, economically, and psychosocially. • Current treatment revolves largely around treating physical manifestation of disease with first line measures such as topical steroids. WHAT IS NEW: • The holistic management of AD incorporates a good physician-patient relationship, frequent follow-up, and providing structured written plans. • We introduce the house building model for improving treatment adherence. KEY POINTS: Pediatric AD can be managed in a more holistic manner which incorporates several factors from the lives of patients and their families. Pediatric patients suffer from many physical and mental comorbidities which should be screened for. Adherence with treatment may be improved by following a model which emphasizes establishing a good physician-patient relationship, frequent follow-up, and providing structured written plans.

Mainstreaming Genetic Testing for Epithelial Ovarian Cancer by Oncology Providers: A Survey of Current Practice.

PURPOSE: With limitations in early detection and poor treatment response, ovarian cancer is associated with significant morbidity and mortality. Up to 25% of epithelial ovarian cancer (EOC) is related to a hereditary predisposition. Current National Comprehensive Cancer Network guidelines recommend that all individuals diagnosed with EOC be offered germline genetic testing. Although this would ideally be performed by genetics professionals, a shortage of genetic counselors can affect timely access to these services. This study sought to investigate the current genetic testing practices of oncology providers to determine the feasibility of oncologist-led genetic testing for patients with EOC. METHODS: A survey was distributed to members of the Society of Gynecologic Oncologists with questions regarding timing, frequency, and type of cancer genetic testing, referrals to genetics professionals, confidence with aspects of genetic testing, and any barriers to these processes. RESULTS: We received 170 evaluable responses. Eighty-five percent of providers always ordered genetic testing for patients with EOC. Most providers ordered germline multigene panel testing (95.8%), generally at diagnosis (64.5%). Provider confidence with the genetic testing process was generally high and significantly differed by providers' testing practices, namely, respondents who reported always ordering genetic testing tended to be more confident in ordering testing (P = .008), interpreting results (P = .005), and counseling a patient (P = .002). Patient disinterest and concerns for insurance coverage were commonly cited as barriers to testing and referrals. CONCLUSION: The findings from this study suggest that oncologist-led genetic testing for patients with EOC, with referrals to genetics professionals when appropriate, has the potential to be a viable alternative service delivery model to increase access to genetic testing for patients diagnosed with EOC.

Treatment of keratosis pilaris and its variants: a systematic review.

INTRODUCTION: Keratosis pilaris (KP) is a common, benign skin condition of follicular hyperkeratosis. Although KP is asymptomatic, the cosmetic appearance of KP can lead to psychosocial distress among patients. New emerging treatments are increasingly being utilized. Yet, there is little to no summative data on the treatments of KP and its subtypes. OBJECTIVE: To summarize existing literature on treatments for KP and its subtypes. METHODS: A comprehensive search was performed using Pubmed/MEDLINE, Embase and Web of Science databases. The search identified 1150 non-duplicated articles, and 47 articles were included in the review. The primary outcomes measured were KP treatment type and the degree of improvement following therapy. FINDINGS: Our findings demonstrate that the most supported form of treatment for KP is laser therapy, particularly the QS:Nd YAG laser. Topical treatments - including Mineral Oil-Hydrophil Petrolat, tacrolimus, azelaic acid, and salicylic acid - are also effective at least for improving the appearance of KP. CONCLUSION: While the measured treatment outcomes varied among studies, laser therapy appears to be the most effective form of treatment. Use of topicals also improved KP lesions.

Effect of Enteral Protein Amount on Growth and Health Outcomes in Very-Low-Birth-Weight Preterm Infants: Phase II of the Pre-B Project and an Evidence Analysis Center Systematic Review.

Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.

Vitamin D in Toddlers, Preschool Children, and Adolescents.

BACKGROUND: Vitamin D supplementation is known to both prevent and treat rickets, a disease of hypomineralized bone. Childhood is a period of great bone development and, therefore, attention to the vitamin D needed to optimize bone health in childhood is imperative. SUMMARY: Observational studies have pointed to a vitamin D status, as indicated by a 25-hydroxyvitamin D concentration, of 50 nmol/L to ensure avoidance of rickets and of 75 nmol/L to optimize health. However, the benefits of achieving these levels of vitamin D status are less evident when pediatric randomized, controlled trials are performed. In fact, no specific pediatric vitamin D supplementation has been established by the existing evidence. Yet, study of vitamin D physiology continues to uncover further potential benefits to vitamin D sufficiency. This disconnection between vitamin D function and trials of supplementation has led to new paths of investigation, including establishment of the best method to measure vitamin D status, examination of genetic variation in vitamin D metabolism, and consideration that vitamin D status is a marker of another variable, such as physical activity, and its association with bone health. Nevertheless, vitamin D supplementation in the range of 10-50 µg/day appears to be safe for children and remains a promising intervention that may yet be supported by clinical trials as a method to optimize pediatric health. Key Message: Pediatric vitamin D status is associated with avoidance of rickets. Randomized, controlled trials of vitamin D supplementation for pediatric bone health are limited and equivocal in their results. Beyond bone, decreased risk for autoimmune, infectious, and allergic diseases has been associated with higher vitamin D status. The specific vitamin D supplementation to optimize toddler, child, and adolescent outcomes is unknown, but doses 10-50 µg/day are safe and may be beneficial.

Safety Aspects of a Randomized Clinical Trial of Maternal and Infant Vitamin D Supplementation by Feeding Type Through 7 Months Postpartum.

Background: The safety of higher dose vitamin D (vitD) supplementation in women who change from exclusive or full breastfeeding to combination feeding or who continue supplementation after cessation of breastfeeding is unknown. Objective: Compare vitD supplementation safety of 6,400 to 400 IU/day and 2,400 IU/day using specific laboratory parameters in postpartum women and their infants through 7 months postpartum by feeding type. Design: In this randomized controlled trial, mothers (exclusively breastfeeding or formula-feeding) were randomized at 4-6 weeks' postpartum to 400, 2,400, or 6,400 IU vitD3 (cholecalciferol)/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitD3/day; infants in 2,400 and 6,400 IU groups received placebo. Maternal safety parameters (serum vitD, 25-hydroxy-vitamin D [25(OH)D; calcidiol], calcium, phosphorus, intact PTH; urinary calcium/creatinine ratios; and feeding type/changes) were measured monthly; infant parameters were measured at months 1, 4, and 7. Sufficiency was defined as 25(OH)D >50 nmol/L. Feeding type was defined as exclusive/full, combination, or formula-feeding. Data were analyzed using SAS 9.4. Results: Four hundred nineteen mother-infant pairs were randomized into the three treatment groups and followed: 346 breastfeeding and 73 formula-feeding pairs. A dose of 6400 IU/day safely and significantly increased maternal vitD and 25(OH)D from baseline in all mothers regardless of feeding type (p < 0.0001) and was superior to the 400 and 2,400 IU groups in achieving vitD sufficiency with no other differences in safety parameters by treatment or feeding type. Infants in the 2,400 IU group were more likely vitD-deficient than the other groups; otherwise, there were no infant safety parameter differences. Conclusions: While 6,400 IU/day was more effective than 400 or 2,400 IU/day in achieving maternal vitD sufficiency in all feeding groups, the groups did not differ on other safety parameters. Similarly, infant safety parameters did not differ by treatment group or feeding status. Clinical Trial Registration: FDA IND Number: 66,346; ClinicalTrials.gov Number: NCT00412074.

In vitro evaluation of the metabolic enzymes and drug interaction potential of triapine.

PURPOSE: To investigate the metabolic pathways of triapine in primary cultures of human hepatocytes and human hepatic subcellular fractions; to investigate interactions of triapine with tenofovir and emtricitabine; and to evaluate triapine as a perpetrator of drug interactions. The results will better inform future clinical studies of triapine, a radiation sensitizer currently being studied in a phase III study. METHODS: Triapine was incubated with human hepatocytes and subcellular fractions in the presence of a number of inhibitors of drug metabolizing enzymes. Triapine depletion was monitored by LC-MS/MS. Tenofovir and emtricitabine were co-incubated with triapine in primary cultures of human hepatocytes. Triapine was incubated with a CYP probe cocktail and human liver microsomes, followed by LC-MS/MS monitoring of CYP specific metabolite formation. RESULTS: Triapine was not metabolized by FMO, AO/XO, MAO-A/B, or NAT-1/2, but was metabolized by CYP450s. CYP1A2 accounted for most of the depletion of triapine. Tenofovir and emtricitabine did not alter triapine depletion. Triapine reduced CYP1A2 activity and increased CYP2C19 activity. CONCLUSION: CYP1A2 metabolism is the major metabolic pathway for triapine. Triapine may be evaluated in cancer patients in the setting of HIV with emtricitabine or tenofovir treatment. Confirmatory clinical trials may further define the in vivo triapine metabolic fate and quantify any drug-drug interactions.

Human milk fortification: the clinician and parent perspectives.

This study reports on the human milk fortification session at the 2019 NEC Society Symposium, which included clinicians and parents discussing the evidence comparing fortification options such as efficacy, safety, cost effectiveness, and the need for parents to be informed about fortifier choice. With the current literature available and the varying standard of care practices for human milk fortification, further studies are needed to determine the most complete diet for preterm infants. The optimal diet would not only provide key nutrients and energy for growth and development, but also improve short- and long-term outcomes. Parents, as advocates and providers for their infant, should be informed, educated, and included in the discussion and decisions regarding fortification of human milk for their infant.

Growth in the High-Risk Newborn Infant Post-Discharge: Results from a Neonatal Intensive Care Unit Nutrition Follow-up Clinic.

Growth and nutrition in preterm infants have long-term implications for neurodevelopmental and cardiometabolic outcomes. Many infants are discharged from the neonatal intensive care unit (NICU) with growth restriction, but often without a specialized team to monitor postdischarge growth. At our institution, we addressed our ongoing concerns for the health and growth of these infants post-discharge by creating a Nutrition NICU Graduate Clinic. This clinic serves infants discharged from our NICU who were born with very low birth weight, had difficulty growing or feeding while inpatient, had a gastrostomy tube placed during hospitalization, or were deemed high risk for other reasons by our neonatal team, with the first clinic visit within 5 weeks of discharge. Data from our first 227 patients at time of discharge, first clinic visit, and any available second clinic visits are described. Anthropometrics show a high rate of extrauterine growth restriction at time of discharge with continued growth restriction at follow-up. Feeding regimens prescribed at discharge and variations from the prescribed regimen at time of follow-up are described. At time of first clinic visit, most patients (92.2%) required a medical or dietary intervention by our team. Our findings illustrate the need for early and specialized nutrition follow-up in this patient population to improve growth trajectory post-discharge.

Investigation of a Common Clinical Approach to Poor Growth in Preterm Infants.

OBJECTIVE: This study aimed to determine the effect of elevated energy intake with medium-chain triglyceride (MCT) oil or formula powder on growth velocity and weight z-score in very low birth weight infants receiving human milk and human milk fortifier. STUDY DESIGN: This was a cohort study of infants exposed to MCT oil or formula powder for at least 7 days. Mean 7-day change in growth velocity and weight z-scores were compared pre- and postintervention. RESULTS: Forty-three infants received increased energy with either MCT oil or formula powder. Infants receiving MCT oil were more preterm and had a lower birth weight. When evaluating 7-day changes pre- and postintervention, growth velocity increased from 10.0 g/kg/day to 19.8 g/kg/day, and change in weight Z-score increased from -0.24 to 0.05. CONCLUSION: This clinical approach using MCT oil or formula powder for additional energy was associated with improved, at least short-term, growth velocity and weight z-score trajectory.

Complementary and Integrative Therapies for Childhood Atopic Dermatitis.

BACKGROUND: Childhood atopic dermatitis is a chronic inflammatory skin condition that causes significant psychological and financial costs to the individual and society. Treatment regimens may require long-term medication adherence and can be associated with poor patient satisfaction. There is considerable interest in complementary and integrative medicine (CIM) approaches for childhood atopic dermatitis. OBJECTIVE: To assess the effects of CIM approaches on childhood atopic dermatitis outcomes as defined by randomized, controlled clinical trials. METHODS: A PubMed review of CIM-related treatments for pediatric atopic dermatitis was performed, and data related to age, study population, efficacy, treatment regimen, length of treatment, and sample size were included. RESULTS: The search yielded 20 trials related to probiotic/prebiotic treatments for atopic dermatitis, three on the effects of vitamins on children with atopic dermatitis, and two on the effects of Chinese herbal treatments for atopic dermatitis in children and adolescents. The strongest evidence was for supplementation with the probiotics L. fermentum and L. plantarum. CONCLUSIONS: Certain strains of probiotics, specifically L. plantarum and L. fermentum, may improve clinical severity scores in children with atopic dermatitis. However, additional trials are needed to more thoroughly delineate the effects of additional integrative therapies on childhood atopic dermatitis.

Review of future insights of Dragon's Blood in dermatology.

To assess the possible clinical implication of Dragon's Blood in dermatology, a PubMed search was conducted using the keyword "Dragon's Blood," "Croton lechleri," and more. Dragon's Blood from C. lechleri is an Amazonian medicinal plant with a characteristic red sap. Its array of phytochemical action in preclinical studies include anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic properties. Clinical studies reflect wound healing and antiviral properties. Although its popularity is rising in western medicine, C. lechleri offers limited use in dermatology and further investigation is necessary to gain further insight into its potential clinical implication.

ABM Clinical Protocol #29: Iron, Zinc, and Vitamin D Supplementation During Breastfeeding.

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols, free from commercial interest or influence, for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

Antenatal Treatment with Intravenous Immunoglobulin to Prevent Gestational Alloimmune Liver Disease: Comparative Effectiveness of 14-Week versus 18-Week Initiation.

BACKGROUND: Antenatal therapy with high-dose intravenous immunoglobulin (IVIG) may prevent gestational alloimmune liver disease (GALD). OBJECTIVE: The objective of this study was to determine the effectiveness of this approach in a large cohort of women at risk for poor pregnancy outcome due to GALD. METHODS: Women with a history of affected offspring were provided antenatal IVIG treatment and data were acquired prospectively from 1997 to 2015. The outcomes of treated pregnancies were compared to those of untreated pregnancies, and the effectiveness of starting at 14 weeks was compared to that of starting at 18 weeks. RESULTS: A total of 188 treated pregnancies in 151 women were analyzed. Only 30% (n = 105) of untreated gestations resulted in healthy offspring as compared to 94% (n = 177) of treated pregnancies (p < 0.0001). Treated gestations of both the 14-week (n = 108) and the 18-week (n = 80) start cohort showed a decreased rate of fetal loss relative to untreated gestations (p < 0.0001). Equivalent outcomes were recorded in the 18-week versus the 14-week start cohort (p > 0.05). Few adverse events or complications of antenatal therapy were recorded. CONCLUSION: Antenatal therapy with high-dose IVIG initiated at either 18 or 14 gestational weeks effectively prevents poor outcome of pregnancies at risk for GALD.