Every Move Counts to Improve Bone Health at Clinical Sites in Young Pediatric Cancer Survivors: The iBoneFIT Project.

PURPOSE: We aimed to examine the associations of 24-h movement behaviors (moderate to vigorous physical activity [MVPA], light physical activity [LPA], sedentary behavior [SB], and sleep) with age-, sex-, and race-specific areal bone mineral density (aBMD) z -score parameters at clinical sites in young pediatric cancer survivors. METHODS: This cross-sectional multicenter study was carried out within the iBoneFIT framework in which 116 young pediatric cancer survivors (12.1 ± 3.3 yr old; 42% female) were recruited. We obtained anthropometric and body composition data (i.e., body mass, stature, body mass index, and region-specific lean mass), time spent in movement behaviors over at least seven consecutive 24-h periods (wGT3x-BT accelerometer, ActiGraph), and aBMD z -score parameters (age-, sex-, and race-specific total at the body, total hip, femoral neck and lumbar spine). Survivors were classified according to somatic maturity (pre or peri/postpubertal depending on the estimated years from peak height velocity). The adjusted models' coefficients were used to predict the effect of reallocating time proportionally across behaviors on the outcomes. RESULTS: In prepubertal young pediatric cancer survivors, reallocating time to MVPA from LPA, SB, and sleep was significantly associated with higher aBMD at total body ( B = 1.765, P = 0.005), total hip ( B = 1.709, P = 0.003), and lumbar spine ( B = 2.093, P = 0.001). In peri/postpubertal survivors, reallocating time to LPA from MVPA, SB, and sleep was significantly associated with higher aBMD at all sites ( B = 2.090 to 2.609, P = 0.003 to 0.038). Reallocating time to SB from MVPA or LPA was significantly associated with lower aBMD at most sites in prepubertal and peri/postpubertal survivors, respectively. Finally, reallocating time to sleep from MVPA, LPA, and SB was significantly associated with lower aBMD at total body ( B = -2.572, P = 0.036) and total hip ( B = -3.371, P = 0.015). CONCLUSIONS: These findings suggest that every move counts and underline the benefits of increasing MVPA or LPA, when low MVPA levels are present, for bone regeneration after pediatric cancer treatment completion.

Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors: The iBoneFIT project.

BACKGROUND: Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density (aBMD). However, the prevalence of muscle strength deficits is not well documented, and the associations of muscle strength with aBMD are unknown in this population. Therefore, this study aimed to investigate the prevalence of upper- and lower-body muscle strength deficits and to examine the associations of upper- and lower-body muscle strength with age-, sex, and race-specific aBMD Z-scores at the total body, total hip, femoral neck, and lumbar spine. METHODS: This cross-sectional study included 116 pediatric cancer survivors (12.1 ± 3.3 years old, mean ± SD; 42.2% female). Upper- and lower-body muscle strength were assessed by handgrip and standing long jump test, respectively. Dual­energy X­ray absorptiometry was used to measure aBMD (g/cm2). Associations between muscle strength and aBMD were evaluated in multivariable linear regression models. Logistic regression was used to evaluate the contribution of muscle strength (1-decile lower) to the odds of having low aBMD (Z-score ≤ 1.0). All analyses were adjusted for time from treatment completion, radiotherapy exposure, and body mass index. RESULTS: More than one-half of survivors were within the 2 lowest deciles for upper- (56.9%) and lower- body muscle strength (60.0%) in comparison to age- and sex-specific reference values. Muscle strength deficits were associated with lower aBMD Z-scores at all sites (B = 0.133-0.258, p = 0.001-0.032). Each 1-decile lower in upper-body muscle strength was associated with 30%-95% higher odds of having low aBMD Z-scores at all sites. Each 1-decile lower in lower-body muscle strength was associated with 35%-70% higher odds of having low aBMD Z-scores at total body, total hip, and femoral neck. CONCLUSION: Muscle strength deficits are prevalent in young pediatric cancer survivors, and such deficits are associated with lower aBMD Z-scores at all sites. These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.

Determinants of bone parameters in young paediatric cancer survivors: the iBoneFIT project.

BACKGROUND: Bone health is remarkably affected by endocrine side effects due to paediatric cancer treatments and the disease itself. We aimed to provide novel insights into the contribution of independent predictors of bone health in young paediatric cancer survivors. METHODS: This cross-sectional multicentre study was carried out within the iBoneFIT framework in which 116 young paediatric cancer survivors (12.1 ± 3.3 years old; 43% female) were recruited. The independent predictors were sex, years from peak height velocity (PHV), time from treatment completion, radiotherapy exposure, region-specific lean and fat mass, musculoskeletal fitness, moderate-vigorous physical activity and past bone-specific physical activity. RESULTS: Region-specific lean mass was the strongest significant predictor of most areal bone mineral density (aBMD), all hip geometry parameters and Trabecular Bone Score (ß = 0.400-0.775, p ≤ 0.05). Years from PHV was positively associated with total body less head, legs and arms aBMD, and time from treatment completion was also positively associated with total hip and femoral neck aBMD parameters and narrow neck cross-sectional area (ß = 0.327-0.398, p ≤ 0.05; ß = 0.135-0.221, p ≤ 0.05), respectively. CONCLUSION: Region-specific lean mass was consistently the most important positive determinant of all bone parameters, except for total hip aBMD, all Hip Structural Analysis parameters and Trabecular Bone Score. IMPACT: The findings of this study indicate that region-specific lean mass is consistently the most important positive determinant of bone health in young paediatric cancer survivors. Randomised clinical trials focused on improving bone parameters of this population should target at region-specific lean mass due to the site-specific adaptations of the skeleton to external loading following paediatric cancer treatment. After paediatric cancer diagnosis, years from peak height velocity (somatic maturity) is critical for bone development.

Is higher physical fitness associated with better psychological health in young pediatric cancer survivors? A cross-sectional study from the iBoneFIT project.

OBJECTIVE: To examine the associations of self-perceived and objectively-measured physical fitness with psychological well-being and distress indicators in young pediatric cancer survivors. MATERIALS AND METHODS: A total of 116 participants (12.1 ± 3.3 years, 56.9% boys) from the iBoneFIT project participated in this cross-sectional study. Objectively-measured physical fitness (muscular fitness) was obtained by handgrip strength and standing long jump tests for the upper and lower body, respectively. Self-perceived physical fitness was obtained by the International Fitness Scale (IFIS). Positive and negative affect were assessed by the positive affect schedule for children (PANAS-C), happiness by Subjective Happiness Scale (SHS), optimism by Life Orientation Test-Revised (LOT-R), self-esteem by the Rosenberg Self-Esteem Scale (RSE), anxiety by State-Trait Anxiety Inventory for Children (STAIC-R), and depression by Children Depression Inventory (CDI). Multiple linear regressions adjusted by key covariates were performed to analyze associations. RESULTS: No associations were found between objectively-measured muscular fitness and any of the psychological well-being and distress indicators (p > 0.05). Self-perceived overall fitness and flexibility were positively associated with positive affect (ß ≥ 0.258, p < 0.05). Self-perceived cardiorespiratory fitness, speed/agility, and flexibility were negatively associated with depression (ß ≥ -0.222, p < 0.05). Finally, self-perceived cardiorespiratory fitness was also negatively associated with anxiety and negative affect (ß ≥ -0.264, p < 0.05). CONCLUSIONS: Perceived physical fitness, but not objectively physical fitness, seems to be inversely related to psychological distress variables and to less extent positively related to psychological well-being. The findings from this study highlight the importance of promoting self-perceived fitness in the pediatric oncology population.

Impact of Physical Activity Intensity Levels on the Cardiometabolic Risk Status of Children: The Genobox Study.

Childhood obesity has been related to metabolic syndrome and low-grade chronic inflammation. This study aimed to evaluate the impact of physical activity intensities and practice on inflammation, endothelial damage, and cardiometabolic risk factors in children. There were 513 participants, aged 6-14 years, recruited for the study. Physical activity was measured by accelerometry, and the children were classified into four groups according to quartiles of moderate to vigorous physical activity (MVPA) practice as very low active, low active, moderate active, and high active. Anthropometric measures, blood pressure, and plasma metabolic and proinflammatory parameters were analyzed. Very low active group presented a worse lipid profile and higher insulin, leptin, adiponectin, resistin, matrix metallopeptidase-9, and tissue plasminogen activator inhibitor-1, while lower levels of tumor necrosis factor-alpha, Type 1 macrophages, and interleukin 8 than high-active children. Regression analyses showed that a higher MVPA practice was associated with lower levels of triacylglycerols (ß: -0.118; p = .008), resistin (ß: -0.151; p = .005), tPAI (ß: -0.105; p = .046), and P-selectin (ß: -0.160; p = .006), independently of sex, age, and body mass index (BMI). In contrast, a higher BMI was associated with higher levels of insulin (ß: 0.370; p < .001), Homeostasis Model Assessment (ß: 0.352; p < .001), triacylglycerols (ß: 0.209; p < .001), leptin (ß: 0.654; p < .001), tumor necrosis factor-alpha (ß: 0.182; p < .001), Type 1macrophages (ß: 0.181; p < .001), and tissue plasminogen activator inhibitor (ß: 0.240; p < .001), independently of sex, age, and MVPA. A better anthropometric, metabolic, and inflammatory profile was detected in the most active children; however, these differences were partly due to BMI. These results suggest that a higher MVPA practice and a lower BMI in children may lead to a better cardiometabolic status.

The effect of an online exercise programme on bone health in paediatric cancer survivors (iBoneFIT): study protocol of a multi-centre randomized controlled trial.

BACKGROUND: New approaches on paediatric cancer treatment aim to maintain long-term health. As a result of radiotherapy, chemotherapy or surgery, paediatric cancer survivors tend to suffer from any chronic health condition. Endocrine dysfunction represents one of the most common issues and affects bone health. Exercise is key for bone mass accrual during growth, specifically plyometric jump training. The iBoneFIT study will investigate the effect of a 9-month online exercise programme on bone health in paediatric cancer survivors. This study will also examine the effect of the intervention on body composition, physical fitness, physical activity, calcium intake, vitamin D, blood samples quality of life and mental health. METHODS: A minimum of 116 participants aged 6 to 18 years will be randomized into an intervention (n = 58) or control group (n = 58). The intervention group will receive an online exercise programme and diet counselling on calcium and vitamin D. In addition, five behaviour change techniques and a gamification design will be implemented in order to increase the interest of this non-game programme. The control group will only receive diet counselling. Participants will be assessed on 3 occasions: 1) at baseline; 2) after the 9 months of the intervention; 3) 4 months following the intervention. The primary outcome will be determined by dual energy X-ray absorptiometry (DXA) and the hip structural analysis, trabecular bone score and 3D-DXA softwares. Secondary outcomes will include anthropometry, body composition, physical fitness, physical activity, calcium and vitamin D intake, blood samples, quality of life and mental health. DISCUSSION: Whether a simple, feasible and short in duration exercise programme can improve bone health has not been examined in paediatric cancer survivors. This article describes the design, rationale and methods of a study intended to test the effect of a rigorous online exercise programme on bone health in paediatric cancer survivors. If successful, the iBoneFIT study will contribute to decrease chronic health conditions in this population and will have a positive impact in the society. TRIAL REGISTRATION: Prospectively registered in isrctn.com: isrctn61195625 . Registered 2 April 2020.

Cardiac Biomarkers of Low Cardiac Output Syndrome in the Postoperative Period After Congenital Heart Disease Surgery in Children.

INTRODUCTION AND OBJECTIVES: To assess the predictive value of atrial natriuretic peptide, ß-type natriuretic peptide, copeptin, mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I) as indicators of low cardiac output syndrome in children with congenital heart disease undergoing cardiopulmonary bypass (CPB). METHODS: After corrective surgery for congenital heart disease under CPB, 117 children (aged 10 days to 180 months) were enrolled in a prospective observational pilot study during a 2-year period. The patients were classified according to whether they developed low cardiac output syndrome. Biomarker levels were measured at 2, 12, 24, and 48 hours post-CPB. The clinical data and outcome variables were analyzed by a multiple logistic regression model. RESULTS: Thirty-three (29%) patients developed low cardiac output syndrome (group 1) and the remaining 84 (71%) patients were included in group 2. cTn-I levels >14 ng/mL at 2hours after CPB (OR, 4.05; 95%CI, 1.29-12.64; P=.016) and MR-proADM levels>1.5 nmol/L at 24hours following CPB (OR, 15.54; 95%CI, 4.41-54.71; P<.001) were independent predictors of low cardiac output syndrome. CONCLUSIONS: Our results suggest that cTn-I at 2hours post-CPB is, by itself, an evident independent early predictor of low cardiac output syndrome. This predictive capacity is, moreover, reinforced when cTn-I is combined with MR-proADM levels at 24hours following CPB. These 2 cardiac biomarkers would aid in therapeutic decision-making in clinical practice and would also enable clinicians to modify the type of support to be used in the pediatric intensive care unit.

Lung recruitment manoeuvres do not cause haemodynamic instability or oxidative stress but improve oxygenation and lung mechanics in a newborn animal model: an observational study.

BACKGROUND: Lung recruitment manoeuvres in neonates during anaesthesia are not performed routinely due to concerns about causing barotrauma, haemodynamic instability and oxidative stress. OBJECTIVE: To assess the influence of recruitment manoeuvres and positive end-expiratory pressure (PEEP) on haemodynamics, oxidative stress, oxygenation and lung mechanics. DESIGN: A prospective experimental study. SETTING: Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Eight newborn piglets (<48 h) with healthy lungs under general anaesthesia. INTERVENTIONS: The recruitment manoeuvres in pressure-controlled ventilation (PCV) were performed along with a constant driving pressure of 15 cmH2O. After the recruitment manoeuvres, PEEP was reduced in a stepwise fashion to find the maximal dynamic compliance step (maxCDyn-PEEP). Blood oxidative stress biomarkers (lipid peroxidation products, protein carbonyls, total glutathione, oxidised glutathione, reduced glutathione and activity of glutathione peroxidase) were analysed. MAIN OUTCOME MEASURES: Haemodynamic parameters, arterial partial pressure of oxygen (paO2), tidal volume (Vt), dynamic compliance (Cdyn) and oxidative stress biomarkers were measured. RESULTS: The recruitment manoeuvres did not induce barotrauma. Haemodynamic instability was not detected either in the maximum pressure step (overdistension step 5) or during the entire process. No substantial differences were observed in blood oxidative stress parameters analysed as compared with their baseline values (with 0 PEEP) or the values obtained 180 min after the onset of the recruitment manoeuvres (optimal PEEP). Significant maximal values were achieved in step 14 with an increase in paO2 (32.43 ±â€Š8.48 vs. 40.39 ±â€Š15.66 kPa; P = 0.037), Vt (47.75 ±â€Š13.59 vs. 73.87 ±â€Š13.56 ml; P = 0.006) and Cdyn (2.50 ±â€Š0.64 vs. 4.75 ±â€Š0.88 ml cmH2O; P < 0.001). Maximal dynamic compliance step (maxCdyn-PEEP) was 2 cmH2O. CONCLUSION: Recruitment manoeuvres in PCV with a constant driving pressure are a well tolerated open-lung strategy in a healthy-lung neonatal animal model under general anaesthesia. The recruitment manoeuvres improve oxygenation parameters and lung mechanics and do not cause barotrauma, haemodynamic instability or oxidative stress.