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Fiuza-Luces C.,Hospital Universitario 12 Of Octubre Research Institute I12 | Simpson R.J.,University of Houston | Ramirez M.,Pediatric Hematology and Oncology | Lucia A.,European University at Madrid | Berger N.A.,Case Western Reserve University
Bone Marrow Transplantation | Year: 2016

Allogeneic hematopoietic stem cell transplant, to reconstitute the hematopoietic and immune status of patients undergoing myeloablative therapy for hematologic disorders, has been of great benefit in minimizing or eradicating disease and extending survival. Patients who undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) are subject to many comorbidities among which the most significant, affecting quality of life (QoL) and survival, are acute GvHD (aGvHD) and chronic GvHD (cGvHD), resulting from donor lymphocytes reacting to and damaging host tissues. Physical activity and exercise have clearly been shown, in both children and adults, to enhance fitness, improve symptomatology and QoL, reduce disease progression and extend survival for many diseases including malignancies. In some cases, vigorous exercise has been shown to be equal to or more effective than pharmacologic therapy. This review addresses how cGvHD affects patients' physical function and physical domain of QoL, and the potential benefits of exercise interventions along with recommendations for relevant research and evaluation targeted at incorporating this strategy as soon as possible after allo-HSCT and ideally, as soon as possible upon diagnosis of the condition leading to allo-HSCT. © 2016 Macmillan Publishers Limited. All rights reserved. Source

Sanchis-Gomar F.,Research Institute Hospital 12 Of Octubre I12 | Santos-Lozano A.,Research Institute Hospital 12 Of Octubre I12 | Pareja-Galeano H.,Research Institute Hospital 12 Of Octubre I12 | Pareja-Galeano H.,European University at Madrid | And 10 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2016

Background: Individuals who reach exceptional longevity (100+ years of age) free of common chronic age diseases (i.e. 'dodgers') arguably represent the paradigm of successful aging in humans. As such, identification of potential biomarkers associated with this phenomenon is of medical interest. Methods: We measured serum levels of galectin-3 and osteopontin, both of which have been shown to be linked with major chronic or aging-related disorders in younger populations, in centenarian 'dodgers' (n=81; 40 men; 100-104 years) and healthy controls (n=41; 24 men, 70-80 years). Results: Both biomarkers showed significantly lower values (p<0.001) in the former (galectin-3: 2.4±1.7 vs. 4.8±2.8 ng/mL; osteopontin: 38.1±27.7 vs. 72.6±33.1 μg/mL). Logistic regression analysis identified the combination of these two biomarkers as a significant predictor variable associated with successful aging regardless of sex (p<0.001). The area under the curve (AUC) classified the ability of galectin-3 and osteopontin to predict the likelihood of successful aging as 'fair' (AUC=0.75) and 'good' (AUC=0.80), respectively. Particularly, the combination of the two biomarkers showed good discriminatory power for successful aging (AUC=0.86), with sensitivity=83% and specificity=74%. Conclusions: Lower levels of both galectin-3 and osteopontin are associated with successful aging, representing potential biomarkers of this condition. Our cross-sectional data must be however approached with caution. Further research is necessary to replicate the present preliminary results in other cohorts and to identify the potential use of galectin-3 and osteopontin as potential targets (or at least predictors) in future personalized anti-aging therapies. © 2016 by De Gruyter. Source

Fiuza-Luces C.,European University at Madrid | Fiuza-Luces C.,Research Institute i12 | Soares-Miranda L.,University of Porto | Gonzalez-Murillo A.,Jesus University | And 10 more authors.
Medicine and Science in Sports and Exercise | Year: 2013

INTRODUCTION: Chronic graft versus host disease (cGVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation that generates considerable morbidity and compromises the physical capacity of patients. We determined the effects of an exercise training program performed after allogeneic hematopoietic stem cell transplantation on clinical and biological variables in a minor histocompatibility antigen-driven murine model of cGVHD treated with cyclosporine A. METHODS: Recipient BALB/C female mice (age 8 wk) received bone marrow cells and splenocytes from donor B10.D2 male mice and were randomly assigned to an exercise (n = 11) or control group (n = 12). For approximately 11 wk after transplant, the exercise group completed a moderate-intensity treadmill program. Variables assessed were clinical severity scores, survival, physical fitness, cytokine profile, immune cell reconstitution, molecular markers of muscle exercise adaptations, and histological scores in affected tissues. RESULTS: Exercise training increased survival (P = 0.011), diminished total clinical severity scores (P = 0.002), improved physical fitness (P = 0.030), and reduced blood IL-4 and tumor necrosis factor α levels (P = 0.03), while increasing circulating B220 (P = 0.008) and CD4 lymphocytes (P = 0.043). CONCLUSIONS: A moderate-intensity exercise program that mimics widely accepted public health recommendations for physical activity in human adults was well tolerated and positive effects on survival as well as on clinical and biological indicators of cGVHD. Copyright © 2013 by the American College of Sports Medicine. Source

Fiuza-Luces C.,European University at Madrid | Delmiro A.,Hospital Universitario 12 Of Octubre Research Institute I12 | Delmiro A.,A+ Network | Soares-Miranda L.,University of Porto | And 6 more authors.
Brain, Behavior, and Immunity | Year: 2014

Introduction: Chronic graft-versus-host disease (cGVHD) is a frequent cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and severely compromises patients' physical capacity. Despite the aggressive nature of the disease, aerobic exercise training can positively impact survival as well as clinical and functional parameters. We analyzed potential mechanisms underlying the recently reported cardiac function improvement in an exercise-trained cGVHD murine model receiving lethal total body irradiation and immunosuppressant treatment (Fiuza-Luces et al., 2013. Med Sci Sports Exerc 45, 1703-1711). We hypothesized that a cellular quality-control mechanism that is receiving growing attention in biomedicine, autophagy, was involved in such improvement. Methods: BALB/C female mice (aged 8. wk) with cGVHD were randomly assigned to a control/exercise group (n=12/11); the exercise group underwent moderate-intensity treadmill training during 11. wk after allo-HSCT. In the hearts of those few mice surviving the entire 11. wk period (n=2/5), we studied molecular markers of: macroautophagy induction, preservation of contractile/structural proteins, oxidative capacity, oxidative stress, antioxidant defense, and mitochondrial dynamics. Results: Mainly, exercise training increased the myocardial content of the macroautophagy markers LC3BII, Atg12, SQSTM1/p62 and phospho-ULK1 (S555), as well as of α-tubuline, catalase and glutathione reductase (all p<. 0.05). Conclusions: Our results suggest that exercise training elicits a positive autophagic adaptation in the myocardium that may help preserve cardiac function even at the end-stage of a devastating disease like cGVHD. These preliminary findings might provide new insights into the cardiac exercise benefits in chronic/debilitating conditions. © 2013 Elsevier Inc. Source

Fiuza-Luces C.,Hospital Universitario 12 Of Octubre Research Institute I12 | Fiuza-Luces C.,A+ Network | Santos-Lozano A.,Hospital Universitario 12 Of Octubre Research Institute I12 | Garcia-Silva M.T.,Hospital Universitario 12 Of Octubre Research Institute I12 | And 15 more authors.
Clinical Nutrition | Year: 2016

Background & aims: Mitochondrial diseases (MD) are the most frequent inborn errors of metabolism. In affected tissues, MD can alter cellular oxygen consumption rate leading to potential decreases in whole-body resting energy expenditure (REE), but data on pediatric children are absent. We determined, using indirect calorimetry (IC), whole-body oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ) and REE in pediatric patients with MD and healthy controls. Another goal was to assess the accuracy of available predictive equations for REE estimation in this patient population. Methods: IC data were obtained under fasting and resting conditions in 20 MD patients and 27 age and gender-matched healthy peers. We determined the agreement between REE measured with IC and REE estimated with Schofield weight and FAO/WHO/UNU equations. Results: Mean values of VO2, VCO2 (mL·min-1·kg-1) or RQ did not differ significantly between patients and controls (P = 0.085, P = 0.055 and P = 0.626 respectively). Accordingly, no significant differences (P = 0.086) were found for REE (kcal·day-1 kg-1) either. On the other hand, although we found no significant differences between IC-measured REE and Schofield or FAO/WHO/UNU-estimated REE, Bland-Altman analysis revealed wide limits of agreement and there were some important individual differences between IC and equation-derived REE. Conclusions: VO2, VCO2, RQ and REE are not significantly altered in pediatric patients with MD compared with healthy controls. The energy demands of pediatric patients with MD should be determined based on IC data in order to provide the best possible personalized nutritional management for these children. © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. Source

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