Substrate oxidation during exercise in childhood acute lymphoblastic leukemia survivors.

Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exercise in childhood ALL survivors. Indirect calorimetry was measured in 250 childhood ALL survivors to quantify substrate oxidation rates during a cardiopulmonary exercise test. A best-fit third-order polynomial curve was computed for fat oxidation rate (mg/min) against exercise intensity (%V̇O2peak) and was used to determine the MFO and the peak fat oxidation (Fatmax). The crossover point was also identified. Differences between prognostic risk groups were assessed (ie, standard risk [SR], high risk with and without cardio-protective agent dexrazoxane [HR + DEX and HR]). MFO, Fatmax and crossover point were not different between the groups (p = .078; p = .765; p = .726). Fatmax and crossover point were achieved at low exercise intensities. A higher MFO was achieved by men in the SR group (287.8 ± 111.2 mg/min) compared to those in HR + DEX (239.8 ± 97.0 mg/min) and HR groups (229.3 ± 98.9 mg/min) (p = .04). Childhood ALL survivors have low fat oxidation during exercise and oxidize carbohydrates at low exercise intensities, independently of the cumulative doses of doxorubicin they received. These findings alert clinicians on the long-term impact of cancer treatments on childhood ALL survivors' substrate oxidation.

Abnormal HDL lipid and protein composition following pediatric cancer treatment: an associative study.

BACKGROUND: Long-term childhood cancer survivors (CCS) are at high risk of having dyslipidemia including low high density lipoprotein cholesterol (HDL-C). However, little is known about the prevalence of low HDL-C and the impact of therapy exposure on HDL composition early after treatment is terminated. METHODS: This associative study included 50 children and adolescents who had completed their cancer treatments (< 4 years). Clinical characteristics (demographic, diagnosis, treatment, anthropometric parameters), fasting plasma lipids, apoliporoteins (Apo) A-I and composition of HDL fractions (HDL2 and HDL3) were assessed. Data were stratified according to the presence of dyslipidemia and median doses of therapeutic agents and compared using Fisher exact or Mann-Whitney tests. Univariate binary logistic regression analyses were carried out to evaluate the associations between the clinical and biochemical characteristics and having low HDL-C. Composition of HDL2 and HDL3 particles was assessed in a sub-group of 15 patients and compared to 15 age- and sex-matched healthy controls using Wilcoxon paired test. RESULTS: Of the 50 pediatric cancer patients included in this study (mean age: 11.30 ± 0.72 y; mean time since end of treatment: 1.47 ± 0.12 y; male: 38%), 8 had low HDL-C (16%), all of which were adolescent at diagnosis. Higher doses of doxorubicin were associated with lower HDL-C and Apo A-I levels. In hypertriglyceridemic patients and compared to normolipidemics, triglycerides (TG) content was greater in HDL2 and HDL3 fractions whereas esterified cholesterol (EC) content was lower in HDL2. Enrich TG content of HDL3 and lower EC of HDL2 was found in patients exposed to ≥ 90 mg/m2 doxorubicin. Factors positively associated with the risk of having low HDL-C were age, being overweight or obese and exposure to doxorubicin ≥ 90 mg/m2. Compared to healthy controls, a sub-group of 15 patients showed higher TG and free cholesterol (FC) content of HDL2 and HDL3 and lower EC content in HDL3. CONCLUSIONS: Overall, we found abnormalities in HDL-C and Apo A-I levels and in HDL composition early after pediatric cancer treatment that are influenced by age, overweight or obesity status and exposure to doxorubicin.

Improvement of Diet after an Early Nutritional Intervention in Pediatric Oncology.

Pediatric cancer survivors may experience cardiometabolic sequelae over the course of their lives as a result of the treatments they have received. While nutrition consists of an actionable target for cardiometabolic health, few nutritional interventions have been documented in this population. This study assessed the changes in diet during a one-year nutritional intervention for children and adolescents undergoing cancer treatments and the participants' anthropometric and cardiometabolic profiles. A total of 36 children and adolescents (mean age: 7.9 years, 52.8% male) newly diagnosed with cancer (50% leukemia) and their parents underwent a one-year individualized nutrition intervention. The mean number of follow-up visits with the dietitian during the intervention was 4.72 ± 1.06. Between the initial and one-year assessments, there was an improvement in diet quality reflected by the Diet Quality Index (5.22 ± 9.95, p = 0.003). Similarly, the proportion of participants with moderate and good adherence (vs. low adherence) to the Healthy Diet Index score almost tripled after one year of intervention (14% vs. 39%, p = 0.012). In parallel, there was an increase in the mean z-scores for weight (0.29 ± 0.70, p = 0.019) and BMI (0.50 ± 0.88, p = 0.002), and in the mean levels of HDL-C (0.27 ± 0.37 mmol/L, p = 0.002) and 25-hydroxy vitamin D (14.5 ± 28.1 mmol/L, p = 0.03). Overall, this study supports that a one-year nutritional intervention deployed early after a pediatric cancer diagnosis is associated with an improvement in the diets of children and adolescents.

Needs, Barriers and Facilitators of Adolescents Participating in a Lifestyle Promotion Program in Oncology: Stakeholders, Adolescents and Parents' Perspective.

Treatments for adolescent cancer can cause debilitating side effects in the short- and long-term such as nausea and malnutrition but also cardiometabolic disturbances. Although the risk for cardiometabolic complications is greater for adolescents with cancer than younger ones, adolescents typically respond poorly to family-oriented health promotion programs. This study aims to assess the needs, barriers and facilitators to healthy lifestyle promotion interventions for adolescents with cancer and how to best adapt these interventions for them. Interviews were held with adolescents treated for cancer (n = 9) and parents (n = 6), focus groups were conducted with stakeholders working in oncology (n = 12) and self-report questionnaires were sent to stakeholders involved in a health promotion intervention (n = 6). At the time of interview, mean age of adolescent participants (40% female) was 17.0 ± 1.9 years (mean age at diagnosis: 14.6 ± 1.6 years). Verbatim and responses to questionnaires were coded and analyzed using qualitative methods. Stakeholder stated that adolescents with cancer need to access activities adapted to their age, to communicate with peers going through a similar experience, and to preserve their schooling and friendships. Barriers to intervention reported by adolescents, parents and stakeholders include lack of motivation, schedule conflicts, fatigue and treatment side effects. Some of the barriers mentioned by adolescents and parents include pain, post-surgery problems, school, physical deconditioning, and lack of time. Facilitators mentioned by adolescents and parents comprise trust in stakeholders' expertise, personalized approaches, scheduling flexibility. Stakeholders recommended to build trust in the relationship, favoring non-moralizing teachings, adapt interventions to adolescents' limited attention span and avoiding the use of long-term health benefits as a motivator.

Cardiometabolic Health After Pediatric Cancer Treatment: Adolescents Are More Affected than Children.

This cross-sectional study aimed at comparing the cardiometabolic (CM) health of children and adolescents and identifying factors associated with CM complications shortly after cancer treatment. Cancer-related characteristics, blood pressure (BP), anthropometry, and biochemical parameters were collected in 80 patients (56.3% female, mean age: 11.8 years; range: 4.5 - 21.0) a mean of 1.4 years following therapy completion. Compared to children, adolescents had higher mean z-score of insulin (-0.47 vs. 0.20; P = 0.01), HOMA-IR (-0.40 vs. 0.25; P = 0.02), waist-to-height ratio (0.36 vs. 0.84; P = 0.01), subscapular skinfold thickness (-0.19 vs. 0.47; P = 0.02), total body fat (-1.43 vs. 0.26; P < 0.01), and lower mean z-score of HDL-C (0.07 vs. -0.53; P < 0.01). Adolescents were more likely to have high BP (42% vs. 15%; P < 0.01), dyslipidemia (64% vs. 15%; P < 0.001), and cumulating ≥ 2 CM complications (42% vs. 2%; P < 0.001) than children. Adiposity indices (z-scores) were associated with high BP [odds ratio (OR) ranging from 2.11 to 4.09] and dyslipidemia (OR ranging from 2.06 to 4.34). These results suggest that adolescents have a worse CM profile than children shortly after therapy and that adiposity parameters are associated with CM complications, highliting the importance to develop intervention strategies targeting this population.

Early Nutritional Intervention to Promote Healthy Eating Habits in Pediatric Oncology: A Feasibility Study.

This study aims to describe the feasibility of a nutritional intervention that promotes healthy eating habits early after cancer pediatric diagnosis in patients and their parents. Participants were recruited 4 to 12 weeks after cancer diagnosis as part of the VIE study. The one-year nutritional intervention included an initial evaluation and 6 follow-up visits every 2 months with a registered dietician. The feasibility assessment included rates of retention, participation, attendance, completion of study measures, and participants' engagement. A preliminary evaluation of the intervention's impact on the participants' dietary intakes was conducted. A total of 62 participants were included in the study (51.6% male, mean age = 8.5 years, mean time since diagnosis = 13.2 weeks). The retention and attendance rates were 72.6% and 71.3%, respectively. Attendance to follow-up visits declined over time, from 83.9% to 48.9%. A majority of participants had high participation (50.8%) and high engagement (56.4%). Measures of body-mass-index or weight-for-length ratio and dietary 24-h recalls were the procedures with the highest completion rates. Participants with refractory disease or relapse were less likely to complete the intervention. Post-intervention, participants (n = 21) had a lower sodium intake compared to the initial evaluation. These results suggest that a nutritional intervention that involves patients and parents early after a pediatric cancer diagnosis is feasible.

The Role of Oxidative Stress and Inflammation in Cardiometabolic Health of Children During Cancer Treatment and Potential Impact of Key Nutrients.

Significance: The 5-year survival rate of childhood cancers is now reaching 84%. However, treatments cause numerous acute and long-term side effects. These include cardiometabolic complications, namely hypertension, dyslipidemia, hyperglycemia, insulin resistance, and increased fat mass. Recent Advances: Many antineoplastic treatments can induce oxidative stress (OxS) and trigger an inflammatory response, which may cause acute and chronic side effects. Critical Issues: Clinical studies have reported a state of heightened OxS and inflammation during cancer treatment in children as the result of treatment cytotoxic action on both cancerous and noncancerous cells. Higher levels of OxS and inflammation are associated with treatment side effects and with the development of cardiometabolic complications. Key nutrients (omega-3 polyunsaturated fatty acids, dietary antioxidants, probiotics, and prebiotics) have the potential to modulate inflammatory and oxidative responses and, therefore, could be considered in the search for adverse complication prevention means as long as antineoplastic treatment efficiency is maintained. Future Directions: There is a need to better understand the relationship between cardiometabolic complications, OxS, inflammation and diet during pediatric cancer treatment, which represents the ultimate goal of this review. Antioxid. Redox Signal. 35, 293-318.

Prevalence of Malnutrition in Pediatric Hospitals in Developed and In-Transition Countries: The Impact of Hospital Practices.

Presently, undernutrition still goes undetected in pediatric hospitals despite its association with poor clinical outcomes and increased annual hospital costs, thus affecting both the patient and the health care system. The reported prevalence of undernutrition in pediatric patients seeking care or hospitalized varies considerably, ranging from 2.5 to 51%. This disparity is mostly due to the diversity of the origin of populations studied, methods used to detect and assess nutritional status, as well as the lack of consensus for defining pediatric undernutrition. The prevalence among inpatients is likely to be higher than that observed for the community at large, since malnourished children are likely to have a pre-existent disease or to develop medical complications. Meanwhile, growing evidence indicates that the nutritional status of sick children deteriorates during the course of hospitalization. Moreover, the absence of systematic nutritional screening in this environment may lead to an underestimation of this condition. The present review aims to critically discuss studies documenting the prevalence of malnutrition in pediatric hospitals in developed and in-transition countries and identifying hospital practices that may jeopardize the nutritional status of hospitalized children.

Assessment of Malnutrition Risk in Canadian Pediatric Hospitals: A Multicenter Prospective Cohort Study.

OBJECTIVE: To assess the prevalence, causes, and consequences of malnutrition, as well as the evolution of nutritional status, in Canadian pediatric health care institutions. STUDY DESIGN: In this multicenter prospective cohort study, a total of 371 patients were recruited from pediatric hospitals in 5 Canadian provinces. Subjects were aged 1 month to 18 years; admitted to a medical, surgical, or oncology ward; and had a planned hospital stay of >48 hours. Data on demographics, medical condition, anthropometric measures, and dietary intake were collected. The Screening Tool Risk on Nutritional Status and Growth (STRONGkids) and Subjective Global Nutritional Assessment (SGNA) were applied at admission. Malnutrition was defined as a weight-for-age, height-for-age, body mass index-for-age, or weight-for-length/height z score <-2 SD. RESULTS: Among 307 subjects (median age, 5.3 years; median length of stay, 5 days), 19.5% were malnourished on admission. Both STRONGkids and SGNA classifications were associated with baseline nutritional status. Mean weight-for-age z score was lower at discharge compared with admission (-0.14 vs -0.09; P < .01), and nearly one-half of all patients lost weight during their hospital stay. Only one-half of the children who were malnourished or screened as high risk of malnutrition were visited by a dietitian during their stay. The percentage of patients who lost weight during hospitalization was significantly greater in the group not visited by a dietitian (76.5 vs 23.5%; P < .01). CONCLUSION: Nutritional status deterioration and malnutrition are common in hospitalized Canadian children. Screening tools, anthropometric measurements, and dietitian consultation should be used to establish adequate nutritional support.

Research- and Practice-Based Nutrition Education and Cooking Workshops in Pediatric Oncology: Protocol for Implementation and Development of Curriculum.

BACKGROUND: Progresses in childhood cancer treatment, diagnosis, and management have resulted in childhood cancer survival rates of over 80%. However, this therapeutic success comes with a heavy price: two-thirds of childhood cancer survivors will be affected by further complications, including cardiovascular and metabolic diseases. Adequate nutrition during cancer treatment is essential to ensure the child's optimal development, improve tolerance to treatments, and can contribute to lower the risk of developing cardiometabolic diseases. Side effects of cancer treatments can negatively impact children's nutritional intake and eating behaviors. Involving the families of childhood cancer patients in educational workshops could be a promising avenue to promote healthy eating during and after cancer treatment. OBJECTIVE: The objectives of this study were to develop, validate, and implement a family-based nutrition education and cooking workshop curriculum in a pediatric oncology setting that addresses the nutritional issues encountered during treatments while promoting the adoption of healthy eating habits for the prevention of long-term cardiometabolic effects. METHODS: The workshops were developed and validated following an 8-step iterative process, including a review of the literature and consultations with a steering committee. An evaluation tool was also developed. A nonrandomized study protocol was elaborated to implement the workshops and measure their impact. The themes of the 6 research- and practice-based lessons are as follows: meal fortification during cancer treatment, changes in taste during cancer therapy and their impact on children, adapting diet to eating-related side effects of treatments, nutritional support during cancer treatment, Mediterranean diet and health, and planning quick and economic meals. The validation process included consultations with the institution's clinical nutrition professionals. Self-administered post questionnaires were developed according to the content of each workshop to measure short-term outcomes, namely, participants' perception of knowledge acquisition, behavioral intention, and satisfaction. Medium-term outcomes that will be evaluated are participants' anthropometric profile, quality of the diet, and circulating biomarkers of metabolic health. RESULTS: The project was funded in 2016 and enrollment will be completed in 2021. Data analysis is currently under way and the first results are expected to be submitted for publication in 2019. CONCLUSIONS: This research- and practice-based nutrition education and cooking demonstration curriculum could be a valuable complement to a multidisciplinary lifestyle intervention for the prevention of long-term cardiometabolic complications in childhood cancer.