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Chronic diseases are the leading cause of death worldwide with increasing prevalence in all age groups, genders, and ethnicities. Most chronic disease deaths occur in middle- to low-income countries but are also a significant health problem in developed nations. Multiple chronic diseases now affect children and adolescents as well as adults. Being physically inactive is associated with increased chronic disease risk. Global societies are being negatively impacted by the increasing prevalence of chronic disease which is directly related to rising healthcare expenditures, workforce complications regarding attendance and productivity, military personnel recruitment, and academic success. However, increased physical activity (PA) and exercise are associated with reduced chronic disease risk. Most physiologic systems in the body benefit positively from PA and exercise by primary disease prevention and secondary disease prevention/treatment. The purpose of this brief review is to describe the significant global problem of chronic diseases for adults and children, and how PA and exercise can provide a non-invasive means for added prevention and treatment.

Physical activity, exercise, and chronic diseases: A brief review

Development of novel and effective therapeutics for treating various cancers is probably the most congested and challenging enterprise of pharmaceutical companies. Diverse drugs targeting malignant and nonmalignant cells receive clinical approval each year from the FDA. Targeting cancer cells and nonmalignant cells unavoidably changes the tumor microenvironment, and cellular and molecular components relentlessly alter in response to drugs. Cancer cells often reprogram their metabolic pathways to adapt to environmental challenges and facilitate survival, proliferation, and metastasis. While cancer cells' dependence on glycolysis for energy production is well studied, the roles of adipocytes and lipid metabolic reprogramming in supporting cancer growth, metastasis, and drug responses are less understood. This Review focuses on emerging mechanisms involving adipocytes and lipid metabolism in altering the response to cancer treatment. In particular, we discuss mechanisms underlying cancer-associated adipocytes and lipid metabolic reprogramming in cancer drug resistance.

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Adipocyte and lipid metabolism in cancer drug resistance.

Association of body mass index and survival in pediatric leukemia: a meta-analysis

Obesity as defined by body mass index percentile (BMI%) is strongly associated with relapse and poorer survival in childhood ALL. Whether BMI% accurately reflects body fat percentage (BF%) in this population is unknown. We conducted a prospective study assessing body composition during frontline ALL therapy. Dual-energy X-ray absorptiometry measured BF% and lean muscle mass (LMM) at diagnosis, end of Induction, and end of Delayed Intensification. Sarcopenic obesity (gain in BF% with loss of LMM) was surprisingly common during ALL treatment, resulting in poor correlation between changes in BMI% (expressed as Z-score) and BF% overall (r = -0.05) and within patients (r = -0.09). BMI Z-score and BF% changed in opposite directions in >50% of interval assessments. While BMI% at diagnosis is a suitable predictor of obesity/BF% for epidemiological studies, change in BMI% (as expressed as Z-score) does not reflect body composition. Studies evaluating obesity in leukemia should consider using direct measures of body composition.

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Limitations of body mass index to assess body composition due to sarcopenic obesity during leukemia therapy.

Obesity is a risk factor for mortality and relapse of certain cancers. However, existing evidence for pediatric leukemia is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the association between obesity at diagnosis and pediatric acute leukemia mortality and relapse. This study systematically searched MEDLINE and EMBASE from inception to February 5, 2015. Random-effect models were used to generate pooled estimates of study-specific hazard ratios (HR) and 95% confidence intervals (CI). Eleven studies were included. An increased risk of mortality with a high BMI at diagnosis was observed (overall survival: HR = 1.30, 95% CI = 1.16–1.46 and event-free survival: HR = 1.46, 95% CI = 1.29–1.64). Only two studies reported HR for relapse; one reported a reduced risk, while the other reported an increased risk. A high BMI at diagnosis is associated with poor overall and event-free survival among pediatric acute leukemia patients. Targeted therapeutic approaches for obese ...

Association between body mass index at diagnosis and pediatric leukemia mortality and relapse: a systematic review and meta-analysis

High body mass index (BMI) is associated with relapse of certain adult cancers, but limited knowledge exists on its association with pediatric leukemia relapse. We evaluated the association between overweight/obesity (BMI ≥ 85th percentile) at pediatric leukemia diagnosis and relapse or mortality. A meta-analysis combining our findings with those of previous studies was also performed. The study included 181 pediatric leukemia patients. Sporadic missing data were multiply imputed, and hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazard. Age- and sex-adjusted analysis for patients ≥10 years showed a trend towards increased risk of relapse for overweight/obese patients (HR = 2.89, 95% CI = 0.89-9.36, p=0.08) that was not evident among children<10 years (HR = 0.52, 95% CI = 0.08-3.54, p=0.49). We observed a statistically significant association between mortality and obesity status in unadjusted models (imputed: HR = 2.54, 95% CI = 1.15-5.60, p=0.021; complete set: HR = 2.72, 95% CI = 1.26-5.91, p=0.011) that was not statistically significant in both age- and sex-adjusted and multivariable adjusted analyses. The pooled estimate of our finding and previous studies showed an association between overweight/obese and increased risk of mortality for ALL (HR = 1.39, 95% CI = 1.16-1.46) and AML (HR = 1.64, 95% CI = 1.32-2.04). Although our study did not observe statistically significant associations due to a small sample size, the meta-analyses revealed an increased risk of mortality for overweight/obese patients. The findings of our study suggest an association of obesity status with relapse in children ≥10 years. However, our study was based on a small sample size from a single institution, and this association needs to be investigated in larger, multicenter studies.

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Ashleigh M. Saenz

Papers

Association between body mass index at diagnosis and pediatric leukemia mortality and relapse: a systematic review and meta-analysis

Body Mass Index at Pediatric Leukemia Diagnosis and the Risks of Relapse and Mortality: Findings from a Single Institution and Meta-analysis