Exercise and tumor proteome: Insights from a neuroblastoma model.

BACKGROUND/AIM: The impact of exercise on pediatric tumor biology is essentially unknown. We investigated the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB). METHODS: Tumor samples of 14 male mice (aged 6-8 weeks) that were randomly allocated into an exercise (5-week combined aerobic and resistance training) or nonexercise control group (6 and 8 mice per group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level. RESULTS: Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, compared to controls [false discovery rate (FDR)<0.05], which were enriched in metabolic pathways, aminoacid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling pathway (FDR<0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR<0.01). Categories with lower abundance were involved in energy production while those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. CONCLUSION: Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying potential effects of exercise in HR-NB.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Lifestyle and cardiovascular risk in working young adults: insights from a nationwide Spanish cohort.

INTRODUCTION AND OBJECTIVES: This study aimed to describe the cardiovascular risk profile of working young adults from Spain and its association with lifestyle. METHODS: Participants (18-30 years) were recruited from a nationwide cohort of economically active adults insured by a large occupational risk prevention company, with data obtained from routine medical assessments. The participants were categorized as having an "unhealthy" cardiovascular risk profile based on the presence of prediabetes/diabetes, prehypertension/hypertension, or hypercholesterolemia, or a "healthy" profile if these conditions were completely absent. The association with lifestyle factors (weight, physical activity, sleeping characteristics, alcohol consumption, smoking) was assessed. RESULTS: A total of 78 421 young adults (27±2 years, 36% female) were evaluated at baseline. The "unhealthy" cardiovascular risk profile was prevalent (18%) and inversely associated (OR, 0.64; 95%CI, 0.57-0.80) with an optimal lifestyle (normal weight, regular physical activity, no drinking/smoking, and good sleep). The latter condition was found in only 3.5% of the participants. On the other hand, prospective analyses in 44 776 participants (median follow-up=2 [range 2-5] years) showed that 2.0% transitioned from a "healthy" to an "unhealthy" profile. Being physically active (OR, 0.95; 95%CI, 0.81-0.99) and having a normal weight (OR, 0.61; 95%CI, 0.51-0.70) were associated with a lower likelihood of this transition. No consistent associations were found for other lifestyle factors. CONCLUSIONS: The prevalence of cardiovascular risk factors is high in economically active young Spanish adults. An unhealthy cardiovascular risk profile is inversely associated with an optimal lifestyle, but the latter is highly infrequent in this population.

Impact of Physical Exercise on Melanoma Hallmarks: Current Status of Preclinical and Clinical Research.

In recent years, accumulating evidence from preclinical and clinical studies consistently indicated that physical activity/exercise plays a crucial role in reducing the incidence and recurrence of various malignancies, by exerting a beneficial modulation of cancer hallmarks. Moreover, physical activity is suggested to attenuate certain adverse effects of anticancer therapy, including the reduction of cardiovascular toxicity and symptoms related to depression and anxiety, among others, while preserving muscular strength. In the case of melanoma, the relationship with physical activity has been critically debated. Historically, several cohort studies and meta-analyses reported a positive association between physical activity/exercise and melanoma risk. This association was primarily attributed to outdoor activities that may expose the skin to UV radiation, a well-known risk factor for melanocyte transformation. However, more recent evidence does not support such association and recognizes physical activity/exercise role in both melanoma prevention and progression. Nevertheless, sun protection is recommended during outdoor training to minimize UV radiation exposure. This narrative review summarizes preclinical and clinical data about physical activity effects on melanoma hallmarks. Specifically, experimental evidence is reported concerning (i) invasion and metastasis, (ii) reprogramming of energy metabolism, (iii) angiogenesis, (iv) resistance to cell death, (v) evasion from immune destruction, and (vi) tumor-promoting inflammation.

Obesity, cardiovascular risk, and lifestyle: cross-sectional and prospective analyses in a nationwide Spanish cohort.

AIMS: To assess whether overweight and obesity are independently associated with cardiometabolic health [as categorized based on the presence/absence of cardiovascular disease (CVD) risk factors (diabetes, hypercholesterolaemia, or hypertension)], and the role of lifestyle on this association. METHODS AND RESULTS: A nationwide cohort of Spanish adults (18-64 years) was studied using a cross-sectional design and prospective observational design. Lifestyle-related factors (physical activity, sleeping characteristics, alcohol drinking, and smoking) were registered, and participants were classified as having an 'unhealthy' or 'healthy' cardiometabolic status attending to the presence or absence, respectively, of ≥1 CVD risk factor. A number of 596 111 participants (44 ± 9 years, 67% male) were studied at baseline, with prospective analyses in a subcohort [n = 302 061; median follow-up, 2 years (range, 2 to 5)]. Compared to normal weight, overweight and obesity were associated with a higher prevalence [odds ratio, 1.67 (95% confidence interval, 1.61-1.67) and 2.70 (2.69-2.78), respectively] and incidence [1.62 (1.59-1.67) and 2.70 (2.63-2.78)] of an unhealthy cardiometabolic status. Meeting physical activity guidelines reduced the odds of an unhealthy cardiometabolic status at baseline [0.87 (0.85-0.88)] among individuals with overweight/obesity, as well as of transitioning from a healthy status to an unhealthy status during the follow-up [0.87 (0.84-0.94)]. No significant associations were found for the remainder of lifestyle factors. CONCLUSION: Overweight and obesity are independently associated with an unhealthy cardiometabolic status. Regular physical activity attenuates not only the prevalence but also the incidence of CVD risk factors.

This study (n = 596 111, with 302 061 participants followed for ∼2 years) indicates that overweigh and obesity are independently associated with the prevalence and incidence of major cardiovascular disease (CVD) risk factors (hypertension, diabetes, and hypercholesterolaemia). Individuals with metabolically healthy overweight/obesity are more likely to develop CVD risk factors in the short-to-middle term than their peers with normal weight even after accounting for lifestyle. Regular physical activity is the only lifestyle factor that seems to be inversely and independently associated with the prevalence and incidence of the studied CVD risk factors among individuals with overweight/obesity.

Aortic Diameters and Calcifications in Former World-Class Cyclists.

PURPOSE: Concerns on whether athletes--particularly older ones--are at an increased risk of pathological aortic dilation exist, and the prevalence of aortic calcifications in these individuals is unknown. We aimed to compare the dimensions, distensibility, and prevalence of calcifications in the thoracic aorta between former male professional cyclists (cases) and sex/age-matched controls. METHODS: We used a retrospective cohort design, where cases were former finishers of at least one Grand Tour (Tour de France, Giro d' Italia or Vuelta a España) and controls were untrained individuals with no previous sports history and free of cardiovascular risk. All participants underwent magnetic resonance and computer tomography assessments for the measurement of aortic dimensions and calcifications, respectively. RESULTS: Cases showed larger ( P < 0.05) dimensions than controls for aortic annulus, sinus, and arch, as well as for ascending and descending aorta. However, none of the participants presented with pathological aortic dilation (all diameters <40 mm). A slightly higher prevalence of calcifications in the ascending aorta was observed in cases (13% vs 0% in controls, P = 0.020). Subanalyses confirmed that cases who were still competing (masters category, n = 8) had larger aortic diameters ( P < 0.05) and a greater presence of calcifications in the ascending/descending aorta (38% vs 0% for both segments, P = 0.032) than those who had become inactive ( n = 15). No between-group differences were found for aortic distensibility. CONCLUSIONS: Former professional cyclists, particularly those who are still competing after retirement, show enlarged aortic diameters (albeit without exceeding upper limits of normality). Former professional cyclists also showed a slightly higher prevalence of calcifications in the ascending aorta than controls, although aortic distensibility was not compromised. The clinical relevance of these findings should be the subject of future studies.

Combined exercise intervention in a mouse model of high-risk neuroblastoma: effects on physical, immune, tumor and clinical outcomes.

Background: Exercise might exert anti-tumoral effects in adult cancers but this question remains open in pediatric tumors, which frequently show a different biology compared to adult malignancies. We studied the effects of an exercise intervention on physical function, immune variables and tumoral response in a preclinical model of a highly aggressive pediatric cancer, high-risk neuroblastoma (HR-NB). Methods: 6-8-week-old male mice with orthotopically-induced HR-NB were assigned to a control (N = 13) or exercise (5-week combined [aerobic+resistance]) group (N = 17). Outcomes included physical function (cardiorespiratory fitness [CRF] and muscle strength), as well as related muscle molecular indicators, blood and tumor immune cell and molecular variables, tumor progression, clinical severity, and survival. Results: Exercise attenuated CRF decline (p=0.029 for the group-by-time interaction effect), which was accompanied by higher muscle levels of oxidative capacity (citrate synthase and respiratory chain complexes III, IV and V) and an indicator of antioxidant defense (glutathione reductase) in the intervention arm (all p≤0.001), as well as by higher levels of apoptosis (caspase-3, p=0.029) and angiogenesis (vascular endothelial growth factor receptor-2, p=0.012). The proportion of 'hot-like' (i.e., with viable immune infiltrates in flow cytometry analyses) tumors tended to be higher (p=0.0789) in the exercise group (76.9%, vs. 33.3% in control mice). Exercise also promoted greater total immune (p=0.045) and myeloid cell (p=0.049) infiltration within the 'hot' tumors, with a higher proportion of two myeloid cell subsets (CD11C+ [dendritic] cells [p=0.049] and M2-like tumor-associated macrophages [p=0.028]), yet with no significant changes in lymphoid infiltrates or in cirulating immune cells or chemokines/cytokines. No training effect was found either for muscle strength or anabolic status, cancer progression (tumor weight and metastasis, tumor microenvironment), clinical severity, or survival. Conclusions: Combined exercise appears as an effective strategy for attenuating physical function decline in a mouse model of HR-NB, also exerting some potential immune benefits within the tumor, which seem overall different from those previously reported in adult cancers.

Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often have functional dependency, multimorbidity, and polypharmacy, is inconclusive. We aimed to establish the effects of exercise interventions on the physical function of this population. METHODS: For this systematic review and network meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Rehabilitation & Sports Medicine Source, and SPORTDiscus to identify randomised controlled trials assessing the effects of exercise interventions (vs usual care) on physical function (ie, functional independence, physical performance, and other related measures, such as muscle strength, balance, or flexibility) in adults aged 60 years or older living in residential care. Relevant studies published in English or Spanish up to Jan 12, 2023, were included in the systematic review. The quality of studies was assessed using the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) score. A network meta-analysis was performed for physical function-related outcomes reported in at least ten studies, with subanalyses for specific intervention (ie, exercise type, training volume, and study duration) and participant (eg, having cognitive impairment or dementia, pre-frail or frail status, and being functionally dependent) characteristics. The study protocol was registered on PROSPERO (CRD42021247809). FINDINGS: 147 studies (11 609 participants, with mean ages ranging from 67 years [SD 9] to 92 years [2]) were included in the systematic review, and were rated as having overall good quality (median TESTEX score 9 [range 3-14]). In the meta-analysis (including 105 studies, n=7759 participants), exercise interventions were associated with significantly improved overall physical function, with a standardised mean difference [SMD] of 0·13 (95% credible interval [CrI] 0·04-0·21), which was confirmed in all analysed subpopulations. The strongest association was observed with 110-225 min per week of exercise, and the greatest improvements were observed with 170 min per week (SMD 0·36 [95% CrI 0·20-0·52]). No significant differences were found between exercise types. Subanalyses showed significant improvements for almost all analysed physical function-related outcomes (Barthel index, five-times sit-to-stand test, 30-s sit-to-stand test, knee extension, hand grip strength, bicep curl strength, Short Physical Performance Battery, 6-min walking test, walking speed, Berg balance scale, and sit-and-reach test). Large heterogeneity was found between and within studies in terms of population and intervention characteristics. INTERPRETATION: Exercise interventions are associated with improved physical function in older adults in residential care, and should, therefore, be routinely promoted in long-term care facilities. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Physical Exercise and the Hallmarks of Breast Cancer: A Narrative Review.

Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, (vi) resisting cell death, (vii) reprogramming energy metabolism, (viii) evading immune destruction, (ix) genome instability and mutations, (x) tumor-promoting inflammation, (xi) unlocking phenotypic plasticity, (xii) nonmutational epigenetic reprogramming, (xiii) polymorphic microbiomes, and (xiv) senescent cells. These hallmarks are also associated with the development of breast cancer, which represents the most prevalent tumor type in the world. The present narrative review aims to describe, for the first time, the effects of physical activity/exercise on these hallmarks. In summary, an active lifestyle, and particularly regular physical exercise, provides beneficial effects on all major hallmarks associated with breast cancer, and might therefore help to counteract the progression of the disease or its associated burden.

Diabetes, Hypertension, and the Mediating Role of Lifestyle: A Cross-Sectional Analysis in a Large Cohort of Adults.

INTRODUCTION: Whether diabetes is associated with hypertension risk remains controversial, potentially owing to the confounding effect of lifestyle. This study aims to analyze the association between diabetes and hypertension in adults and the mediating impacts of lifestyle. METHODS: A cohort of Spanish workers (aged 18-64 years) insured by an occupational risk prevention company participated in this nationwide cross-sectional study between 2012 and 2016 (data analysis was performed in 2021). Participants' lifestyle‒related factors-BMI, sleeping hours, alcohol, smoking, and physical activity-were assessed, and the prevalence of hypertension and diabetes was registered. RESULTS: A total of 451,157 participants (33.1% women, aged 44.5 [SD=9.2] years, 3.2% with diabetes, and 29.3% with hypertension) with complete data for all variables were assessed. Having diabetes was associated with a higher prevalence of hypertension even after adjusting for all lifestyle-related factors (OR=1.44, 95% CI=1.43, 1.48), and people with diabetes and hypertension had a higher prevalence of mild kidney function impairment than people with diabetes alone (OR=1.06, 95% CI=1.01, 1.13). However, people with diabetes and an optimal lifestyle-normal weight and sleeping hours, absent-to-little alcohol drinking, nonsmoking, and regular physical activity-presented a prevalence of hypertension comparable with that of those without diabetes (OR=1.00, 95% CI=0.71, 1.32). In separate analyses among people with diabetes, an optimal lifestyle was associated with a lower prevalence of hypertension than the worse-opposite-lifestyle (OR=0.29, 95% CI=0.18, 0.53). The lifestyle-related factors showing the strongest inverse association with adjusted risk of hypertension were normal weight (OR=0.49, 95% CI=0.42, 0.53 versus overweight/obesity) and regular physical activity (OR=0.79, 95% CI=0.74, 0.82 versus inactivity). CONCLUSIONS: Diabetes is positively and largely independently associated with hypertension risk. Yet, a healthy lifestyle can attenuate this association.

Exercise Training and Natural Killer Cells in Cancer Survivors: Current Evidence and Research Gaps Based on a Systematic Review and Meta-analysis.

BACKGROUND: Exercise training can positively impact the immune system and particularly natural killer (NK) cells, at least in healthy people. This effect would be of relevance in the context of cancer given the prominent role of these cells in antitumor immunity. In this systematic review and meta-analysis, we aimed to summarize current evidence on the effects of exercise training on the levels and function of NK cells in cancer survivors (i.e., from the time of diagnosis until the end of life). METHODS: Relevant articles were searched in PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (until January 11, 2022). Randomized controlled trials (RCT) of exercise training (i.e., non-acute) interventions vs usual care conducted in cancer survivors and assessing NK number and/or cytotoxic activity (NKCA) before and upon completion of the intervention were included. Methodological quality of the studies was assessed with the PEDro scale, and results were meta-analyzed using a random effects (Dersimoian and Laird) model. RESULTS: Thirteen RCT including 459 participants (mean age ranging 11-63 years) met the inclusion criteria. Methodological quality of the studies was overall fair (median PEDro score = 5 out of 10). There was heterogeneity across studies regarding cancer types (breast cancer, non-small cell lung cancer and other solid tumors), treatment (e.g., receiving vs having received chemotherapy), exercise modes (aerobic or resistance exercise, Tai Chi, Yoga) and duration (2-24 weeks). No consistent effects were observed for NK number in blood (mean difference [MD]: 1.47, 95% confidence interval [CI] - 0.35 to 3.29, p = 0.113) or NKCA as assessed in vitro (MD: - 0.02, 95%CI - 0.17 to 0.14, p = 0.834). However, mixed results existed across studies, and some could not be meta-analyzed due to lack of information or methodological heterogeneity. CONCLUSIONS: Current evidence does not support a significant effect of exercise training intervention on NK cells in blood or on their 'static response' (as assessed in vitro) in cancer survivors. Several methodological issues and research gaps are highlighted in this review, which should be considered in future studies to draw definite conclusions on this topic.

Mortality Risk from Neurodegenerative Disease in Sports Associated with Repetitive Head Impacts: Preliminary Findings from a Systematic Review and Meta-Analysis.

BACKGROUND: Professional athletes seem to have a lower overall mortality risk than the general population, but controversy exists about whether athletes in sports associated with repetitive head impacts have a higher risk of mortality from neurodegenerative diseases. OBJECTIVE: We aimed to determine the risk of mortality from neurodegenerative diseases in sports associated with repeated head impacts compared with the general population or compared with athletes with no such exposure. METHODS: We conducted a systematic review with meta-analysis, systematically searching PubMed, Web of Science, Scopus, and SPORTDiscus (since inception to 14 May 2021) for studies comparing the risk of death from neurodegenerative disease in athletes participating in contact sports in which their heads recurrently receive blows from the bodies of other participants or from a ball versus a control group or dataset representing the general population. RESULTS: Six moderate- to high-quality retrospective studies including data from 41,699 athletes participating in contact sports (boxing, basketball, ice hockey, American Football and soccer) met all inclusion criteria to be included in the systematic review. Of these, three studies (N = 37,065 male professional soccer players) could be meta-analysed. Despite no differences in the risk of all-cause (p = 0.138), cardiovascular (p = 0.085) and cancer-related mortality (p = 0.136), soccer players presented with a significantly higher mortality risk from motor neuron disease (standard mortality rate 8.43; 95% confidence interval 3.07-23.13; p < 0.001). CONCLUSIONS: Although more research is needed (particularly in other contact sports and with neurodegenerative disease as the cause of death), preliminary evidence suggests that participation in professional soccer might increase the risk of mortality from motor neuron disease compared with the general population. The present findings highlight the need for the design of preventive measures and for adequate neuropsychological monitoring in these athletes. PROSPERO REGISTRATION: CRD42020195647.

Moderate Intensity Functional Training as Adjuvant Treatment in Patients With Peripheral Arterial Disease: A Case Report.

BACKGROUND: Traditional aerobic training and muscle resistance ("strength") training have been shown to be effective for improving functional and health-related quality of life (HRQoL) outcomes in peripheral arterial disease (PAD). However, the transfer of the current resistance exercise modes proposed to other activities of daily living (ADLs) is questionable. Moderate intensity functional training (MIFT) has emerged with the aim of achieving cardiovascular and neuromuscular adaptations simultaneously with functional exercises typical of ADLs. The effect of MIFT in patients with PAD is not yet known. Our purpose is to verify the influence of the combination of intermittent treadmill walking exercise with MIFT on functional capacity and HRQoL in patients with PAD. METHODS: Three patients with PAD participated in a novel supervised exercise therapy program of 6 weeks duration based on intermittent treadmill walking exercise and MIFT. RESULTS: After the training period, the 3 patients showed high adherence to the program (95%) and they improved total distance (TD) (25%, 9%, and 21%), claudication onset distance (COD) (56%, 19%, and 151%), total number of repetitions (33%, 24%, and 33%) and total work capacity (80%, 79%, and 72%). Also, physical component in Short Form-36 Health Survey (SF-36) and Vascular Quality of Life Questionnaire-6 (VascuQol-6) showed increases in the patients. CONCLUSIONS: The 6-week intervention in patients with PAD, based on intermittent treadmill walking exercise and MIFT, seems to improve their functional status and total work capacity in functional exercises as well as their HRQoL.

Mortality from mental disorders and suicide in male professional American football and soccer players: A meta-analysis.

OBJECTIVE: To determine the risk of mortality from mental disorders and suicide in professional sports associated with repeated head impacts. METHODS: A systematic search was performed in PubMed, Web of Science, Scopus, and SPORTDiscus (since inception to June 8, 2021) to find studies comparing the incidence of mortality from mental disorders or suicide in former or active professional athletes of sports characterized by repeated head impacts vs athletes with no such exposure or the general non-athletic population. RESULTS: Seven retrospective studies of moderate-to-high quality that included data from boxers and from basketball, ice hockey, soccer, and National Football League (NFL) players, respectively (total = 27 477 athletes, 100% male) met all inclusion criteria. Former male NFL players (n = 13 217) had a lower risk of mortality from mental disorders (standard mortality rate [SMR] = 0.30; 0.12-0.77; p = 0.012) and suicide (SMR = 0.54; 0.37-0.78; p < 0.001) than the general population. This finding was also corroborated in male soccer players (n = 13,065; SMR = 0.55; 0.46-0.67; p < 0.001). Male athletes participating in sports associated with repeated head impacts (n = 18,606) had also a lower risk of all-cause, cardiovascular disease (CVD), and cancer mortality (all p < 0.01) than the general population. CONCLUSIONS: Participation of male athletes in American football or soccer at the professional level might confer a certain protective effect against mortality from mental disorders or suicide, besides its association with a lower risk of all-cause, CVD, or cancer-related mortality.

Tailored Exercise during Hematopoietic Stem Cell Transplantation Hospitalization in Children with Cancer: A Prospective Cohort Study.

We assessed the clinical effects of a supervised exercise (aerobic + resistance) intervention performed during inpatient hospitalization for pediatric hematopoietic stem cell transplantation (HSCT). Patients were placed in an exercise (n = 65 (47 and 18 with allogeneic (allo-) and autologous (auto-) HSCT, respectively)) or a control (n = 53 (39 and 14)) group. Exercise interventions were performed in isolated hospital patient rooms. Patients were followed-up from the beginning of the conditioning phase up to 6 years. We assessed survival, risk of graft-versus-host disease (GvHD) or graft failure (primary outcomes), and engraftment kinetics, supportive care, toxicity profile, and immune reconstitution for auto-HSCT and allo-HSCT. The exercise intervention was safe and did not affect the risk of mortality, acute/chronic GvHD, or graft failure (all p > 0.05). No between-group differences (p > 0.05) were found for the remainder of clinical endpoints, except for a reduced number of total and viral infections in the exercise group after allo-HSCT (unadjusted p = 0.005 for both total and viral infections, and adjusted p = 0.023 and 0.083, respectively). In conclusion, exercise performed during inpatient hospitalization for pediatric HSCT is safe and well tolerated during both auto and allo-HSCT and tends to decrease the risk of infection after allo-HSCT. These findings provide additional support to the notion that a multidisciplinary approach (i.e., including the work of exercise specialists) is suitable in the management of children undergoing HSCT. Further studies are needed to determine whether applying a different training stimulus (notably, higher exercise intensities) exerts positive effects on HSCT prognosis in these patients.

Physical exercise effects on metastasis: a systematic review and meta-analysis in animal cancer models.

Physical exercise is considered a well-tolerated adjuvant therapy to mitigate cancer-related side effects, but its impact on metastasis is unclear. The present systematic review and meta-analysis aimed to summarize the evidence on the effects of exercise on metastasis in animal cancer models. A systematic search was conducted to identify controlled studies in animals analyzing the impact of exercise interventions on any marker of metastasis incidence or severity. The pooled mean differences (PMD) were calculated for those endpoints for which a minimum of three studies used the same assessment method. We also calculated the pooled odds ratio (OR) of metastases. Twenty-six articles were included in the systematic review, of which 12 could be meta-analyzed. Exercise training in murine cancer models did not significantly modify the number of metastatic foci (PMD = - 3.18; 95% confidence interval [CI] - 8.32, 1.97; p = 0.23), the weight of metastatic tumors (PMD = - 0.03; 95% CI - 0.10, 0.04; p = 0.41), or the risk of developing metastasis (OR = 0.64; 95% CI 0.10, 4.12; p = 0.64). These findings suggest that exercise has no overall influence on any marker of cancer metastasis incidence or severity in animal models. However, the wide methodological heterogeneity observed between studies might be taken into account and the potential exercise effects on metastasis development remain to be determined in pediatric tumors.

Inhospital exercise benefits in childhood cancer: A prospective cohort study.

Childhood cancer patients are at risk of developing important adverse effects, mortality and disease relapse after treatments, which has a substantial economic impact on healthcare systems. The objective of this study was to determine the effects of supervised inhospital exercise on clinical endpoints during childhood cancer treatment. 169 children with a new diagnosis of cancer were divided into an exercise intervention (n = 68, 11 ± 4 years) or a control group (n = 101, 11 ± 3 years). The cohort was followed up from the start of treatment for up to five years. Supervised inhospital exercise intervention was performed during the neoadjuvant (for solid tumors) or intensive chemotherapy treatment period (for leukemias). The median duration of the intervention was 22 (interquartile range, 14-28) weeks. We assessed survival, risk of disease relapse or metastasis, and days of hospitalization (primary outcomes), and cardiovascular function, anthropometry and blood variables (secondary outcomes). No exercise-related adverse events were noted. The exercise group had significantly less days of hospitalization than the control group (P = .031), resulting in a lower (~-17%) mean total economic cost of hospitalization in the former. Moreover, echocardiography-determined left ventricular function (ejection fraction and fractional shortening) was significantly impaired in the control group after treatment compared with baseline, whereas it was maintained in the exercise group (P = .024 and .021 for the between-group differences, respectively). In conclusion, supervised inhospital exercise intervention is safe and plays a cardioprotective role, at least in the short term, in children with cancer, also reducing hospitalization time, and therefore alleviating the economic burden.

Is health status impaired in childhood cancer survivors? A systematic review and meta-analysis.

BACKGROUND: An increase in survival rates of childhood cancer is associated with long-term health issues in survivors. METHODS: We conducted a systematic review and meta-analysis comparing health status-related endpoints in childhood cancer survivors (CCS) versus controls. RESULTS: Eighty-six studies (n = 98,480 participants, 62% CCS) were included in the review. Of these, 73 studies (n = 96,550, 63% CCS) could be meta-analyzed. CCS showed a lower left ventricular ejection and fractional shortening (SMD=-0.59 and -0.55, respectively, both p < 0.01 [n=1,824 and 1,880]), a lower HDL-cholesterol concentration (SMD=-0.48, p<0.001, n=1,378) and a higher waist-to-hip ratio (SMD=0.61, p < 0.01, n=229) than their healthy peers. No significant differences were found for the remaining endpoints. CONCLUSIONS: CCS is associated with a lower left ventricular function and HDL-cholesterol level, and a higher waist-to-hip ratio than healthy controls. These findings support the need to closely monitor the cardiometabolic health status of CCS and to implement preventive lifestyle interventions for this population.

Systematic Review and Meta-Analysis of Randomized, Controlled Trials on Preoperative Physical Exercise Interventions in Patients with Non-Small-Cell Lung Cancer.

Preoperative physical exercise protocols prior to cancer surgery increased in popularity over recent years; however, the beneficial effect of such protocols is not well established, with conflicting results reported. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of different modalities or combinations of preoperative exercise interventions and/or prehabilitation multicomponent training in patients with non-small-cell lung cancer (NSCLC) after surgery on the outcomes related to functional capacity, mental wellness and medical care. We searched in OVID Embase, Pubmed, Cochrane Library, CINAHL, Scopus, and Web of Science. Characteristics of studies and program results and outcome data were extracted. Changes between the intervention and control groups, from baseline to follow-up (standardized mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI) for each intervention was pooled using weighted random-effects models). A total of 676 participants from 10 RCTs were included in the final analysis (aerobic training + inspiratory muscle training, n = 5; aerobic training + strength training + inspiratory muscle training, n = 2; aerobic training + strength training, n = 1; multicomponent training, n = 1; aerobic training alone, n = 1). The results showed intervention-induced improvement in walking endurance (SMD = 0.27; 95% CI, 0.11 to 0.44; I2 = 0.0%), peak exercise capacity (SMD = 0.78; 95% CI, 0.35 to 1.21; I2 = 76.7%), dyspnoea (SMD = -0.30; 95% CI, -0.51 to -0.10; I2 = 0.0%), risk of hospitalization (SMD = -0.58; 95% CI, -0.97 to -0.20; I2 = 70.7%), and postoperative pulmonary complications (relative risk (RR) = 0.50; 95% CI, 0.39 to 0.66; I2 = 0.0%). For the functional capacity and medical care parameters, preoperative combined aerobic, resistance, and inspiratory muscle training was shown to be effective if comprising one to four weeks, performing 1-3 sessions per week, with moderate intensity (50% for endurance capacity). Further studies with larger samples and higher methodological quality are needed to clarify the potential benefits of preoperative exercise training for patients with NSCLC.