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.

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.

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.

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.

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.

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.

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.

Circulating Free DNA and Its Emerging Role in Autoimmune Diseases.

Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid biopsy, we found clinical application in nontumour pathologies, including autoimmune diseases. Since the discovery of the presence of high levels of cfDNA in patients with systemic lupus erythaematosus (SLE) in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and its association with disease activity. However, with technological advancements and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity, interest in cfDNA and autoimmune diseases has not expanded until recently. In this review, we provide an overview of the basic biology of cfDNA in the context of autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response. We discuss and integrate available information about these important aspects.

Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer.

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

Exercise Benefits Meet Cancer Immunosurveillance: Implications for Immunotherapy.

Regular exercise reduces the risk of cancer. One potential mechanism for this efficacy is improved antitumor immunity. This is an important issue because evading immune destruction is a hallmark of cancer and immunotherapy is reshaping cancer treatment. Here we review recent developments reported by Wennerberg et al., Garritson et al., Martín-Ruiz et al., and Rundqvist et al. on the effects of exercise on anticancer immune cell effectors.

The Exposome and Immune Health in Times of the COVID-19 Pandemic.

Growing evidence supports the importance of lifestyle and environmental exposures-collectively referred to as the 'exposome'-for ensuring immune health. In this narrative review, we summarize and discuss the effects of the different exposome components (physical activity, body weight management, diet, sun exposure, stress, sleep and circadian rhythms, pollution, smoking, and gut microbiome) on immune function and inflammation, particularly in the context of the current coronavirus disease 2019 (COVID-19) pandemic. We highlight the potential role of 'exposome improvements' in the prevention-or amelioration, once established-of this disease as well as their effect on the response to vaccination. In light of the existing evidence, the promotion of a healthy exposome should be a cornerstone in the prevention and management of the COVID-19 pandemic and other eventual pandemics.

Exercise and Childhood Cancer-A Historical Review.

Childhood cancer survivors are at risk of developing important adverse effects, many of which persist for years after the end of treatment. The implementation of interventions aiming at attenuating tumor/treatment-associated adverse effects is therefore a major issue in pediatric oncology, and there is growing evidence that physical exercise could help in this regard. The present review aims to summarize the main milestones achieved in pediatric exercise oncology. For this purpose, we conducted a systematic review of relevant studies written in English in the electronic database PubMed (from inception to 14 August 2021). This review traces the field of pediatric exercise oncology throughout recent history based on three fundamental pillars: (i) exercise during childhood cancer treatment; (ii) exercise during/after hematopoietic stem cell transplantation; and (iii) exercise after childhood cancer treatment. Accumulating evidence--although still preliminary in many cases--supports the safety and potential benefits of regular exercise (with no major contraindications in general) in the childhood cancer continuum, even during the most aggressive phases of treatment. Exercise can indeed represent an effective coadjuvant therapy for attenuating cancer-related adverse effects.

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.

Reply: Letter to the Editor: Exercise Interventions and Cardiovascular Health in Childhood Cancer: A Meta-Analysis.

Dear EditorWe sincerely appreciate the nice comments by Drs. P.V. da Costa Ghignatti and R. Pereira de Lima 1 concerning our recent meta-analysis assessing the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors 2. They are quite right to remain that even non-significant improvements in cardiorespiratory fitness (CRF) might be clinically relevant. Indeed, we still do not know if CRF increments of a theoretically low magnitude (i. e., <1 metabolic equivalent) might have a prognostic value in the context of pediatric cancer and treatment-associated cardiotoxicity. We also agree that unsupervised exercise interventions are unlikely to be as effective as tailored programs, especially because the latter allow for intensity to being adequately controlled and thus gradually increased. It is indeed our opinion, after long years of experience working with children with cancer as well as with other debilitated clinical populations, that there is always room for physiological improvement and ideally loads should be gradually improved instead of remaining stable.

What are the effects of exercise training in childhood cancer survivors? A systematic review.

This systematic review aimed to summarize evidence on the effects of physical exercise interventions in childhood cancer survivors (CCS) who had finished anticancer therapy ≥ 1 year before the study. Relevant articles were identified in the electronic databases PubMed, Web of Science, and SPORTDiscus (from inception to June 27, 2019). The PEDro scale was used to assess methodological quality. Twelve studies including 109 CCS met all inclusion criteria and were included in the systematic review. The quality of the included studies was overall low. Physical exercise improved endothelial function, reduced waist circumference, and waist-to-hip ratio and increased physical activity levels. Preliminary evidence was found regarding benefits on brain volume and structure after exercise interventions in childhood brain tumor survivors. Only two studies reported exercise-related adverse events. Physical exercise seems to be safe and effective for improving several health markers in CCS, but further high-quality research and especially randomized controlled trials are needed to confirm these results.

Exercise Interventions and Cardiovascular Health in Childhood Cancer: A Meta-analysis.

This study analyzed the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors. Relevant articles were systematically searched in PubMed, CINAHL, and Web of Science databases (since inception to 11th September 2019). We performed a meta-analysis (random effects) to determine the mean difference (expressed together with 95% confidence intervals) between pre- and post-intervention values for those cardiovascular endpoints reported in more than three studies. Twenty-seven studies (of which 16 were controlled studies) comprising 697 participants were included. Only three studies reported adverse events related to exercise interventions. Exercise resulted in an increased performance on the 6-minute walk distance test (mean difference=111 m, 95% confidence interval=39-183, p=0.003) and a non-significant trend (mean difference=1.97 ml∙kg-1∙min-1, 95% confidence interval=-0.12-4.06, p=0.065) for improvement in peak oxygen uptake. Furthermore, left ventricular ejection fraction was preserved after exercise interventions (mean difference=0.29%, 95% confidence interval=-1.41-1.99, p=0.738). In summary, exercise interventions might exert a cardioprotective effect in childhood cancer survivors by improving - or attenuating the decline of - physical capacity and cardiovascular function. Further studies, particularly randomized controlled trials, are needed to confirm these benefits.