Inflammatory and Adipose Response in Solid Organ Transplant Recipients After a Marathon Cycling Race.

BACKGROUND: Organ transplant recipients frequently have chronic inflammation, with a weighty impact on cardiovascular risk. These patients can benefit from exercise, although the role of intense training is unclear. We evaluated the effect of a 130-km cycling race on inflammatory cytokines and adiponectin levels in transplant recipients. METHODS: Circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and adiponectin were assayed in 35 healthy subjects vs 19 transplant recipients (10 kidney, 8 liver, 1 heart), matched for sex, age, body mass index, and preparation workout. The determinations were performed before the race, at the end, and after 18 to 24 hours. Baseline values of 32 sedentary transplant recipients also were evaluated to explore the possible chronic impact of lifestyle. RESULTS: All cyclists had 6- to 8-fold increased IL-6 levels after the race that decreased, without returning to baseline, the day after. Conversely, serum TNF-α and IFN-γ showed a progressive increase starting during physical performance and enduring for the next 18 to 24 hours in healthy subjects, whereas they were unchanged over time in cyclists with transplants. In transplant recipients who did not perform exercise, all of the analytes were significantly higher in comparison to basal levels of physically active subjects. CONCLUSIONS: Our data suggest that clinically stable and properly trained transplant recipients can safely perform and progressively benefit from exercise, even at a competitive level. The changes in inflammation parameters were temporary and parallel with those of the healthy subjects. The comparison with sedentary transplant recipients revealed an overall amelioration of inflammatory indexes as a possible effect of regular physical activity on systemic inflammation.

Can Solid-Organ-Transplanted Patients Perform a Cycling Marathon? Trends in Kidney Function Parameters in Comparison With Healthy Subjects.

BACKGROUND: Few solid-organ-transplanted patients (TP) perform regular sport activity. Poor data are available on the safety of intense and prolonged physical exercise on this population. The aim of the study was to evaluate kidney function parameters in a group of TP in comparison with healthy volunteers (HV) involved in a long-distance road cycling race: length 130 km and total uphill gradient, 1871 m. METHODS: Nineteen TP were recruited: 10 renal, 8 liver, and 1 heart and compared with 35 HV. Renal function parameters, namely, creatinine, estimated glomerular filtration rate (eGFR), urea, uric acid, urine specific gravity, microalbuminuria, and proteinuria were collected and their values were compared the day before the race (T1), immediately after crossing the finish line (T2), and 18 to 24 hours after the competition (T3). RESULTS: No adverse events were recorded. At baseline, TP showed lower values of eGFR (69 ± 22 versus 87 ± 13 mL/min/1.73 m(2)), lower urine specific gravity (1015 ± 4 versus 1019 ± 6), and higher microalbuminuria (56 ± 74 versus 8 ± 15) and proteinuria values (166 ± 99 versus 74 ± 44) (in mg/L). At T2 in both groups, renal function parameters showed the same trends: decline of eGFR (54 ± 19 versus 69 ± 15 mL/min/1.73 m(2)) and rise in protein excretion. At T3, functional parameters returned to baseline, except for urine specific gravity values remaining stable in TP (1018 ± 6) and growing higher in HV (1028 ± 4). CONCLUSIONS: Selected and well-trained organ-transplanted patients can perform an intensive exercise, displaying temporary modifications on kidney function parameters comparable to healthy subjects, despite differences related to baseline clinical conditions and pharmacological therapies.

Sport activity and health-related quality of life after kidney transplantation.

OBJECTIVE: Considering the importance of sport activity for enhancing quality of life, the aim of this study was to investigate the effects of regular sport activity on quality of life of kidney transplant recipients. METHODS: Health-related quality of life (HRQoL) was assessed with the use of the SF-36 questionnaire on a group of 118 active kidney transplant patients (AKTPs) practicing different sports at low to moderate intensity (5±4 h/wk). Scores were compared with those of 79 sedentary kidney transplant patients (SKTPs) and with 120 active healthy control subjects (AHCs). RESULTS: AKTPs reported higher scores than SKTPs in the SF-36 scales of Physical Functioning (P<.05), Role Limitations due to Physical Problems (P<.05), General Health (P<.01), Vitality (P<.05), Social Functioning (P<.05), Role Limitations due to Emotional Problems (P<.05), and Mental Health (P<.01). AKTPs obtained higher scores than AHCs on the Mental Health (P<.01) and Social Functioning scales (P<.01) and similar scores (P>.05) on all the other scales. The effect of quantity of sport activity was significant on the General Health (P<.01; η2=0.05), and Role Physical scales (P=.04; η2=0.03), with higher sport activity associated with higher HRQoL. The effect of sex was significant for Bodily Pain (P=.05; η2=0.02), Vitality (P=.08; η2=0.06), Social Functioning (P=.08; η2=0.05), and Mental Health (P=.05; η2=0.02), with male participants scoring higher than female participants. CONCLUSIONS: This study indicates that regular sport activity significantly improves different dimensions of HRQoL among kidney transplant recipients. The benefits of sport activity go beyond its impact on physical health to involve psychologic and social components of quality of life. Spontaneous and low to moderate sport activity may play an important role after kidney transplantation that has been largely underestimated in the literature.

Physical activity in solid organ transplant recipients: organizational aspects and preliminary results of the Italian project.

Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project "Transplant … and Now Sport" was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8±10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3±1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t=1.966; P<.05) and a significant increase in peak aerobic power (t=4.535; P<.01) and maximum workload (t=4.665; P<.01) on the incremental cycling test. Also maximum strength of knee extensors (t=2.933; P<.05) and elbow flexors (t=2.450; P<.05) and countermovement jump performance (t=2.303; P<.05) significantly increased. Creatinine and proteinuria tended to decrease, but the differences were not significant. In health-related quality of life assessed by the SF-36 questionnaire, the Bodily Pain, General Health, Vitality, Social Functioning, and Role Emotional scale scores showed a significant improvement (P<.05). Preliminary results of the study protocol "Transplant…and Now Sport" show the positive effects of the model based on cooperation among transplantation centers, sports medicine centers, and gyms in the administration of a supervised exercise prescription. These data should be considered a contribution to developing and promoting further detailed exercise protocols and to fostering improved posttransplantation health and survival, helping to ensure that physical activity becomes a safe routine medical treatment plan of patient management.

Quality of life and energy expenditure in transplant recipient football players.

Football (soccer) is a highly motivating leisure activity with important potential as a health-promoting activity also for transplant recipients. The aim of this study was to assess the "on the field" energy expenditure during football games and the quality of life of transplant recipients practicing football. Twenty-two recipients of kidney (n = 11), bone marrow (n = 7), liver (n = 3) or corneal (n = 1) transplantations had an overall mean age of 37 ± 9 years, body mass index of 23.5 ± 2.4 kg/m(2), and time after transplantation of 9.3 ± 6.4 years. They were compared with 25 healthy football players of mean age 41 ± 10 years and body mass index of 26.3 ± 3.9 kg/m(2). There were no significant differences between transplant recipients and controls regarding mean energy expenditure (393 ± 113 vs 392 ± 132 kcal/h) number of steps (3.978 ± 1.317 vs 3.933 ± 1.563) during, and capillary blood lactate concentrations (4.8 ± 0.9 vs 5.2 ± 1.3 mmol/L) after the matches. The SF-36 questionnaire administered before the matches showed transplant recipient players to score significantly worse in the scales of general (P < .05) and mental health (P < .01). This study indicated that transplant recipients involved in football matches attained a level of energy expenditure and a quality of life consistent with a healthy lifestyle. Football has the potential to be implemented as a permanent health-promoting activity also for transplant recipients.

The Trop-2 signalling network in cancer growth.

Our findings show that upregulation of a wild-type Trop-2 has a key controlling role in human cancer growth, and that tumour development is quantitatively driven by Trop-2 expression levels. However, little is known about the regulation of expression of the TROP2 gene. Hence, we investigated the TROP2 transcription control network. TROP2 expression was shown to depend on a highly interconnected web of transcription factors: TP63/TP53L, ERG, GRHL1/Get-1 (grainyhead-like epithelial transactivator), HNF1A/TCF-1 (T-cell factor), SPI1/PU.1, WT (Wilms' tumour)1, GLIS2, AIRE (autoimmune regulator), FOXM1 (forkhead box M1) and FOXP3, with HNF4A as the major network hub. TROP2 upregulation was shown to subsequently drive the expression and activation of CREB1 (cyclic AMP-responsive-element binding protein), Jun, NF-κB, Rb, STAT1 and STAT3 through induction of the cyclin D1 and ERK (extracellular signal regulated kinase)/MEK (MAPK/ERK kinase) pathways. Growth-stimulatory signalling through NF-κB, cyclin D1 and ERK was shown to require an intact Trop-2 cytoplasmic tail. Network hubs and interacting partners are co-expressed with Trop-2 in primary human tumours, supporting a role of this signalling network in cancer growth.

Upregulation of Trop-2 quantitatively stimulates human cancer growth.

Trop-2 is a calcium signal transducer that is associated with transformed cell growth in experimental systems. However, its role in human cancer remains essentially unknown. In this study, we profiled Trop-2 expression in normal human tissues at the mRNA and protein levels. We then systematically compared Trop-2 mRNA and protein levels in tumours with their tissues of origin. We find that Trop-2 expression is invariably upregulated in tumours, regardless of baseline expression in normal tissues, which suggests a corresponding selective advantage. Thus, we investigated the outcome of Trop-2 upregulation on tumour growth. Overexpression of wild-type Trop-2 was shown to be necessary and sufficient to drive cancer growth in a widely invariant manner across cell type and species. Upregulation of Trop-2 was shown to quantitatively stimulate tumour growth, as proportional to expression levels in vivo, and tumour cell growth was abrogated by somatic knockdown of Trop-2 expression. On the other hand, we found no evidence of tumour-associated TROP2 mutations, nor of TROP2 induction of oncogenic transformation per se. Our data support a model where above-baseline expression of wild-type Trop-2 is a key driver of human cancer growth.