GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness

Growth differentiation factor 15 (GDF15) is a stress molecule produced in response to mitochondrial, metabolic and inflammatory stress with a number of beneficial effects on metabolism. However, at the level of skeletal muscle it is still unclear whether GDF15 is beneficial or detrimental. The aim of the study was to analyse the levels of circulating GDF15 in people of different age, characterized by different level of physical activity and to seek for correlation with hematological parameters related to inflammation. The plasma concentration of GDF15 was determined in a total of 228 subjects in the age range from 18 to 83 years. These subjects were recruited and divided into three different groups based on the level of physical activity: inactive patients with lower limb mobility impairment, active subjects represented by amateur endurance cyclists, and healthy controls taken from the general population. Cyclists were sampled before and after a strenuous physical bout (long distance cycling race). The plasma levels of GDF15 increase with age and are inversely associated with active lifestyle. In particular, at any age, circulating GDF15 is significantly higher in inactive patients and significantly lower in active people, such as cyclists before the race, with respect to control subjects. However, the strenuous physical exercise causes in cyclists a dramatic increase of GDF15 plasma levels, that after the race are similar to that of patients. Moreover, GDF15 plasma levels significantly correlate with quadriceps torque in patients and with the number of total leukocytes, neutrophils and lymphocytes in both cyclists (before and after race) and patients. Taken together, our data indicate that GDF15 is associated with decreased muscle performance and increased inflammation

Physical Activity in Solid Organ Transplant Recipients: Preliminary Results of the Italian Project

Background/Aims: The role of physical activity in transplanted patients is often underestimated. We discuss the Italian National Transplant Centre experience, which started in 2008 studying transplanted patients involved in sports activities. The study was then developed through a model of cooperation between surgeons, sports physicians and exercise specialists. Methods: A multicentre study was realized in 120 transplanted patients of which 60 treated with supervised physical activity (three sessions/week of aerobic and strengthening exercises) and 60 controls. We present the results of the first 26 patients (16 males, 10 females; 47.8±10.0 years; 21 kidney, 5 liver transplanted; time from transplant 2.3±1.4 years) who completed 12 months of supervised physical activity. Results: Data showed an increase of peak aerobic power (t=4.535; PConclusion: These preliminary results confirm the positive effects of supervised physical exercise. It can be considered as an input to promote other detailed exercise protocols

Renal function and physical fitness after 12-mo supervised training in kidney transplant recipients

To evaluate the effect of a 12-mo supervised aerobic and resistance training, on renal function and exercise capacity compared to usual care recommendations

Renal Function in Kidney and Liver Transplant Recipients After A 130-km Road Cycling Race

Background: A few patients, after receiving solid organ transplantation, return to performing various sports and competitions; however, at present, data no study had evaluated the effects of endurance cycling races on their renal function. Methods: Race times and short form (36) health survey questionnaires of 10 kidney transplant recipients (KTR) and 8 liver transplant recipients (LTR) transplanted recipients involved in a road cycling race (130 km) were compared with 35 healthy control subjects (HCS), also taking laboratory blood and urine tests the day before the race, at the end of the race, and 18 to 24 hours after competing. Results: The 3 groups showed similar race times (KTR, 5 hours 59 minutes \ub1 0 hours 39 minutes; LTR, 6 hours 20 minutes \ub1 1 hour 11 minutes; HCS, 5 hours 40 minutes \ub1 1 hour 28 minutes), similar short form (36) health survey scores, and similar trend of laboratory parameters which returned to baseline after 18 to 24 hours. After the race, there was an increase in creatinine (0.24 mg/dL; effect size [ES] = 0.78; P < 0.001), urea (22 mg/dL; ES = 1.42; P < 0.001), and a decrease of estimated glomerular filtration rate ( 1217 mL/min; ES = 0.85; P < 0.001). The increase of blood uric acid was more remarkable in HCS and KTR (2.3 mg/dL; ES = 1.39; P < 0.001). The KTR showed an increase of microalbuminuria (167.4 mg/L; ES = 1.20; P < 0.001) and proteinuria (175 mg/mL; ES = 0.97; P < 0.001) similar to LTR (microalbuminuria: 176.0 mg/L; ES = 1.26; P < 0.001; proteinuria: 213 mg/mL; ES = 1.18; P < 0.001), with high individual variability. The HCS had a nonsignificant increase of microalbuminuria (4.4 mg/L; ES = 0.03; P = 0.338) and proteinuria (59 mg/mL; ES = 0.33; P = 0.084). Conclusions: Selected and well-trained KTR and LTR patients can participate to an endurance cycling race showing final race times and temporary modifications of kidney function similar to those of HCS group, despite some differences related to baseline clinical conditions and pharmacological therapies. Patients involved in this study represent the upper limit of performance currently available for transplant recipients and cannot be considered representative of the entire transplanted population

Effects of combined strength and endurance training on exercise capacity in kidney transplant cyclists and runners

Introduction: After transplantation, engaging in regular physical activity (PA) or sport is recommended for health. Participation to competitive sports is increasingly common among kidney transplant recipients while little is known on how training affects the physical performance in transplanted athletes. Aim: The purpose of this case study was to assess the effects of a tailored training program on exercise parameters in kidney transplant cyclists (CKTRs) and runners (RKTRs). Methods: Twelve male transplanted athletes were enrolled. The workload at aerobic and anaerobic thresholds, the submaximal aerobic power (V'O2 stage) and rate of perceived exertion (RPE) during an incremental cycling or running test, and the peak instantaneous force (PIF) during a countermovement jump were assessed at baseline (T0) and after 6 months of tailored training (T6) consisting in strength and aerobic exercises. Exercise adherence, blood lipid profile and renal function were also investigated. Results: Eight CKTRs and 4 RKTRs completed the 6-month training period, with a significant increase of training volume (minutes/week). The exercise adherence was met by 90% in both groups. At T6, there were significant (p<0.05) improvements of maximum workload attained, the workload corresponding to the aerobic threshold and PIF, while workloads at anaerobic threshold, V'O2 stage and RPE were unchanged. Blood cholesterol significantly decreased (p<0.01), while the other blood parameters were unchanged. Conclusions: These findings indicate that the combined strength and endurance training is well tolerated and may improve exercise performance in this selected population of KTRs

Longitudinal Analysis of Cardiovascular Risk Factors in Active and Sedentary Kidney Transplant Recipients

Despite the benefits of physical activity on cardiovascular risk in kidney transplant recipients (KTRs), the long-term effects of exercise have been poorly investigated. This is a three-year observational study comparing graft function and cardiovascular risk factors in active KTRs (AKTRs) vs. sedentary KTRs (SKTRs). Methods: KTRs with stable renal function were assigned to active or sedentary group in relation to the level of daily physical activity based on World Health Organization (WHO) recommendations (<150 or >150 min/week, respectively). Complete blood count, renal function indices, lipid profile, blood pressure and anthropometric measures were collected yearly for an observation period of three years. The comparisons between the two groups were performed by repeated measures analyses of covariance (ANCOVAs), with age as a covariate. Results: Fifty-four subjects were included in the study. Thirty of them were identified as AKTRs (M/F 26/4, aged 45 \ub1 12 years) and 24 as SKTRs (M/F 18/6, aged 51 \ub1 14 years). Baseline characteristics were similar between the groups except body mass index (BMI) that was significantly higher in SKTRs (p = 0.043). Furthermore, over the three-year observation period, BMI decreased in AKTRs and increased in SKTRs (p = 0.006). Graft function was stable in AKTRs, while it showed a decline over time in SKTRs, as indicated by the rise in serum creatinine levels (p = 0.006) and lower eGFR (p = 0.050). Proteinuria, glucose and uric acid levels displayed a decrease in AKTRs and an increase in SKTRs during the three-year period (p = 0.015, p = 0.004 and p = 0.013, respectively). Finally, concerning lipid profiles, AKTRs had a significant reduction over time of triglycerides levels, which conversely showed a clinically relevant increase in SKTRs (p = 0.014). Conclusions: Our findings indicate that regular weekly exercise training may counteract the increased cardiovascular risks and also prevent graft function decline in KTRs

Efficacy of SARS-CoV-2 Vaccination in Dialysis Patients: Epidemiological Analysis and Evaluation of the Clinical Progress

This study investigated the impact of the fourth COVID-19 pandemic wave on dialysis patients of Romagna territory, assessing the associations of vaccination status with infection risk, clinical severity and mortality. From November 2021 to February 2022, an epidemiological search was conducted on 829 patients under dialysis treatment for at least one month. The data were then analyzed with reference to the general population of the same area. A temporal comparison was also carried out with the previous pandemic waves (from March 2020 to October 2021). The epidemiological evolution over time in the dialysis population and in Romagna citizens replicated the global trend, as the peak of the fourth wave corresponded to the time of maximum diffusion of omicron variant (B.1.1.529). Of 771 prevalent dialysis patients at the beginning of the study, 109 (14.1%) contracted SARS-CoV-2 infection during the 4-month observation period. Vaccine adherence in the dialysis population of the reference area was above 95%. Compared to fully or partially vaccinated subjects, the unvaccinated ones showed a significantly higher proportion of infections (12.5% vs. 27.0% p = 0.0341), a more frequent need for hospitalization (22.2% vs. 50.0%) and a 3.3-fold increased mortality risk. These findings confirm the effectiveness of COVID-19 vaccines in keeping infectious risk under control and ameliorating clinical outcomes in immunocompromised patients

Trauma coagulopathy and its outcomes

Background and Objectives: Trauma coagulopathy begins at the moment of trauma. This study investigated whether coagulopathy upon arrival in the emergency room (ER) is correlated with increased hemotransfusion requirement, more hemodynamic instability, more severe anatomical damage, a greater need for hospitalization, and hospitalization in the intensive care unit (ICU). We also analyzed whether trauma coagulopathy is correlated with unfavorable indices, such as acidemia, lactate increase, and base excess (BE) increase. Material and Methods: We conducted a prospective, monocentric, observational study of all patients (n = 503) referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for major trauma from 1 January 2018 to 30 January 2019. Results: Of the 503 patients, 204 had trauma coagulopathy (group 1), whereas 299 patients (group 2) did not. Group 1 had a higher hemotransfusion rate than group 2. In group 1, 15% of patients showed hemodynamic instability compared with only 8% of group 2. The shock index (SI) distribution was worse in group 1 than in group 2. Group 1 was more often hypotensive, tachycardic, and with low oxygen saturation, and had a more severe injury severity score than group 2. In addition, 47% of group 1 had three or more body districts involved compared with 23% of group 2. The hospitalization rate was higher in group 1 than in group 2 (76% vs. 58%). The length of hospitalization was >10 days for 45% of group 1 compared with 28% of group 2. The hospitalization rate in the ICU was higher in group 1 than in group 2 (22% vs. 14.8%). The average duration of ICU hospitalization was longer in group 1 than in group 2 (12.5 vs. 9.78 days). Mortality was higher in group 1 than in group 2 (3.92% vs. 0.98%). Group 1 more often had acidemia and high lactates than group 2. Group 1 also more often had BE <−6. Conclusions: Trauma coagulopathy patients, upon arrival in the ER, have greater hemotransfusion (p = 0.016) requirements and need hospitalization (p = 0.032) more frequently than patients without trauma coagulopathy. Trauma coagulopathy seems to be more present in patients with a higher injury severity score (ISS) (p = 0.000) and a greater number of anatomical districts involved (p = 0.000). Head trauma (p = 0.000) and abdominal trauma (p = 0.057) seem related to the development of trauma coagulopathy. Males seem more exposed than females in developing trauma coagulopathy (p = 0.018). Upon arrival in the ER, the presence of tachycardia or alteration of SI and its derivatives can allow early detection of patients with trauma coagulopathy

Evolving knowledge in surgical oncology of pancreatic cancer: from theory to clinical practice-a fifteen-year journey at a tertiary referral centre

Pancreatic ductal adenocarcinoma (PDAC) is an increasing disease having a poor prognosis. The aim of the present study was to evaluate the effect of different models of care for pancreatic cancer in a tertiary referral centre in the period 2006-2020. Retrospective study of patients with PDAC observed from January 2006 to December 2020. The demographic and clinical data, and data regarding the imaging techniques used, preoperative staging, management, survival and multidisciplinary tumour board (MDTB) evaluation were collected and compared in three different periods characterised by different organisation of pancreatic cancer services: period A (2006-2010); period B (2011-2015) and period C (2016-2020). One thousand four hundred seven patients were analysed: 441(31.3%) in period A; 413 (29.4%) in B and 553 (39.3%) in C. The proportion of patients increased significantly, from 31.3% to 39.3% (P = 0.032). Body mass index (P = 0.033), comorbidity rate (P = 0.002) and Karnofsky performance status (P &lt; 0.001) showed significant differences. Computed tomography scans (P &lt; 0.001), endoscopic ultrasound (P &lt; 0.001), fine needle aspiration, fine needle biopsy (P &lt; 0.001), and fluorodeoxyglucose-positron emission tomography/computed tomography (P &lt; 0.001) increased; contrast-enhanced ultrasound (P = 0.028) decreased. The cTNM was significantly different (P &lt; 0.001). The MDTB evaluation increased significantly (P &lt; 0.001). Up-front surgery and exploratory laparotomy decreased (P &lt; 0.001), neoadjuvant treatment increased (P &lt; 0.001). The present study showed the evolving knowledge in surgical oncology of pancreatic cancer at a tertiary referral centre over the time. The different models of care of pancreatic cancer, in particular the introduction of the MDTB and the institution of a pancreas unit to the decision-making process seemed to be influential

Knowledge and attitudes towards clinical trials among women with ovarian cancer: results of the ACTO study

Background Despite several initiatives by research groups, regulatory authorities, and scientific associations to engage citizens/patients in clinical research, there are still obstacles to participation. Among the main discouraging aspects are incomplete understanding of the concepts related to a clinical trial, and the scant, sometimes confused, explanations given. This observational, cross-sectional multicenter study investigated knowledge, attitudes and trust in clinical research. We conducted a survey among women with ovarian cancer at their first follow-up visit or first therapy session, treated in centers belonging to the Mario Negri Gynecologic Oncology (MaNGO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups. A questionnaire on knowledge, attitudes and experience was assembled ad hoc after a literature review and a validation process involving patients of the Alliance against Ovarian Cancer (ACTO). Results From 25 centers 348 questionnaire were collected; 73.5% of responders were 56 years or older, 54.8% had a high level of education, more than 80% had no experience of trial participation. Among participants 59% knew what clinical trials were and 71% what informed consent was. However, more than half did not know the meaning of the term randomization. More than half (56%) were in favor of participating in a clinical trial, but 35% were not certain. Almost all responders acknowledged the doctor's importance in decision-making. Patients' associations were recognized as having a powerful role in the design and planning of clinical trials. Conclusions This study helps depict the knowledge and attitudes of women with ovarian cancer in relation to clinical trials, suggesting measures aimed at improving trial "culture", literacy and compliance, and fresh ways of communication between doctors and patients