Health-Related Physical Fitness and Arterial Stiffness in Childhood Cancer Survivors

Introduction: Despite decreasing mortality in pediatric oncology as a result of standardized treatment protocols, the high number of functional and cardiovascular late sequelae due to anticarcinogenic therapy remains unchanged. The aim of this study was to further assess functional limitations in Health-related Physical Fitness (HRPF) and cardiovascular risk by means of markers of arterial stiffness in Childhood Cancer Survivors (CCS).Materials and Methods: Between March 2016 and August 2017 a total of 92 CCS (Age 12.5 ± 4.2 years, 43 girls) were recruited from their routine follow-up outpatient visit. HRPF was assessed using five Fitnessgram® tasks. Pulse Wave Velocity (PWV) along with peripheral and central blood pressure were assessed using oscillometric measurements performed by Mobil-O-Graph. Z-scores were used to compare the test results either to German reference values or to a recent healthy reference cohort.Results: In CCS, the HRPF was significantly reduced (z-score: −0.28 ± 1.01, p = 0.011) as compared to healthy peers. The peripheral Systolic Blood Pressure (pSBP) was significantly increased (z-score: 0.31 ± 1.11, p = 0.017) and the peripheral Diastolic Blood Pressure (pDBP) was decreased (z-score: −0.30 ± 1.25, p = 0.040), resulting in an increased pulse pressure. The PWV (p = 0.649) and cSBP (p = 0.408), were neither increased nor showed any association to HRPF.Discussion: CCS showed functional limitations in HRPF and an increased pulse pressure, which acts as an early onset parameter of arterial stiffness. Both a low HRPF and impaired hemodynamics are independent cardiovascular risk factors and needs to be taken into consideration in tertiary prevention of CCS

High-mobility group box 1 protein, receptor for advanced glycation end products and nucleosomes increases after marathon

Background: Prolonged and strenuous exercise has been linked to potential exercise-induced myocardial damages. One potential key to unmask the discussed underlying mechanisms of this subclinical cardiac damage could be markers of immunogenic cell damage (ICD). We investigated the kinetics of high-mobility group box 1 protein (HMGB1), soluble receptor for advanced glycation end products (sRAGE), nucleosomes, high sensitive troponin T (hs-TnT) and high sensitive C-reactive protein (hs-CRP) before and up to 12 weeks post-race and described associations with routine laboratory markers and physiological covariates. Methods: In our prospective longitudinal study, 51 adults (82% males; 43 ± 9 years) were included. All participants underwent a cardiopulmonary evaluation 10-12 weeks pre-race. HMGB1, sRAGE, nucleosomes, hs-TnT and, hs-CRP were analysed 10-12 weeks prior, 1-2 weeks before, immediately, 24 h, 72 h, and 12 weeks post-race. Results: HMGB1, sRAGE, nucleosomes and hs-TnT increased significantly from pre- to immediately post-race (0.82-2.79 ng/mL; 1132-1388 pg/mL; 9.24-56.65 ng/mL; 6-27 ng/L; p < 0.001) and returned to baseline within 24-72 h. Hs-CRP increased significantly 24 h post-race (0.88-11.5 mg/L; p < 0.001). Change in sRAGE was positively associated with change in hs-TnT (rs = 0.352, p = 0.011). Longer marathon finishing time was significantly associated with decreased levels of sRAGE [-9.2 pg/mL (β = -9.2, SE = 2.2, p < 0.001)]. Conclusion: Prolonged and strenuous exercise increases markers of ICD immediately post-race, followed by a decrease within 72 h. An acute marathon event results in transient alterations of ICD, we assume that this is not solely driven by myocyte damages

Measurement of the Ratio of b Quark Production Cross Sections in Antiproton-Proton Collisions at 630 GeV and 1800 GeV

We report a measurement of the ratio of the bottom quark production cross section in antiproton-proton collisions at 630 GeV to 1800 GeV using bottom quarks with transverse momenta greater than 10.75 GeV identified through their semileptonic decays and long lifetimes. The measured ratio sigma(630)/sigma(1800) = 0.171 +/- .024 +/- .012 is in good agreement with next-to-leading order (NLO) quantum chromodynamics (QCD)

High-mobility group box 1 protein, receptor for advanced glycation end products and nucleosomes increases after marathon

Background: Prolonged and strenuous exercise has been linked to potential exercise-induced myocardial damages. One potential key to unmask the discussed underlying mechanisms of this subclinical cardiac damage could be markers of immunogenic cell damage (ICD). We investigated the kinetics of high-mobility group box 1 protein (HMGB1), soluble receptor for advanced glycation end products (sRAGE), nucleosomes, high sensitive troponin T (hs-TnT) and high sensitive C-reactive protein (hs-CRP) before and up to 12 weeks post-race and described associations with routine laboratory markers and physiological covariates. Methods: In our prospective longitudinal study, 51 adults (82% males; 43 ± 9 years) were included. All participants underwent a cardiopulmonary evaluation 10–12 weeks pre-race. HMGB1, sRAGE, nucleosomes, hs-TnT and, hs-CRP were analysed 10–12 weeks prior, 1–2 weeks before, immediately, 24 h, 72 h, and 12 weeks post-race. Results: HMGB1, sRAGE, nucleosomes and hs-TnT increased significantly from pre- to immediately post-race (0.82–2.79 ng/mL; 1132–1388 pg/mL; 9.24–56.65 ng/mL; 6–27 ng/L; p < 0.001) and returned to baseline within 24–72 h. Hs-CRP increased significantly 24 h post-race (0.88–11.5 mg/L; p < 0.001). Change in sRAGE was positively associated with change in hs-TnT (rs = 0.352, p = 0.011). Longer marathon finishing time was significantly associated with decreased levels of sRAGE [−9.2 pg/mL (β = −9.2, SE = 2.2, p < 0.001)]. Conclusion: Prolonged and strenuous exercise increases markers of ICD immediately post-race, followed by a decrease within 72 h. An acute marathon event results in transient alterations of ICD, we assume that this is not solely driven by myocyte damages

The Effect of Exercise Intensity and Volume on Metabolic Phenotype in Patients with Metabolic Syndrome: A Randomized Controlled Trial

Background: Moderate intensity continuous training (MICT) ameliorates dysmetabolism in patients with metabolic syndrome (MetS). The impact of low- (1HIIT) versus high-volume high-intensity interval training (4HIIT) versus MICT on central adiposity, insulin resistance, and atherogenic dyslipidemia in patients with MetS has not yet been reported. Methods: Twenty-nine patients with MetS according to International Diabetes Federation criteria (nine females, age 61 ± 5 years, body mass index 31.1 ± 3.7 kg/m2, waist circumference (WC) ♀ 102.2 ± 10.6 cm, ♂ 108.5 ± 8.6 cm) were randomized (1:1:1) to 16 weeks of (1) MICT (5 × 30 min/week, 35%-50% heart rate reserve (HRR), (2) 1HIIT (3 × 17 min/week incl. 4 min @80%-90% HRR), and (3) 4HIIT (3 × 38 min/week incl. 4 × 4 min @80%-90% HRR). Peak oxygen uptake ([Formula: see text]O2peak), WC and anthropometric/metabolic indices indicative of MetS, fasting glucose/insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), dyslipidemia, and respiratory exchange ratio (RER) at warm-up were quantified at baseline and study completion. Analysis of variance and paired t tests were used for statistical analysis. Analyses were performed after checking for parametric distribution. Results: There were no significant differences between groups in waist-to-height ratio (♀: Δ -0.10 ± -0.05, ♂: Δ -0.08 ± -0.06, P = 0.916), WC (♀: Δ -1.4 ± -0.1 cm, ♂: Δ 0.1 ± 0.9 cm, P = 0.590), fasting glucose (Δ -1.18 ± 16.7 μU/mL, P = 0.773), fasting insulin (Δ 0.76 ± 13.4 μU/mL, P = 0.509), HOMA-IR (Δ 0.55 ± 4.1, P = 0.158), atherogenic dyslipidemia [triglycerides (TAG) Δ -10.1 ± 46.9 mg/dL, P = 0.468, high-density lipoprotein cholesterol (HDL-C) Δ 1.5 ± 5.4, P = 0.665, TAG/HDL-C -0.19 ± 1.3, P = 0.502], [Formula: see text]O2peak (P = 0.999), or RER (P = 0.842). In the entire group, waist-to-height-ratio and [Formula: see text]O2peak significantly improved by a clinically meaningful amount (Δ 2.7 ± 0.9 mL/min/kg; P < 0.001) and RER at warm-up significantly decreased (Δ -0.03 ± 0.06, P = 0.039). Conclusion: In patients with MetS, there was no significant difference between HIIT, irrespective of volume, to MICT for improving exercise capacity or metabolic health

Cluster Randomized Controlled Trial on the Effects of 12 Months of Combined Exercise Training during Hemodialysis in Patients with Chronic Kidney Disease-Study Protocol of the Dialysis Training Therapy (DiaTT) Trial

Patients with chronic kidney disease (CKD) on hemodialysis (HD) experience treatment-related immobility and physical deconditioning, which is responsible for an increased risk of frailty and a high burden of multi-morbidity. Exercise has been shown to counteract this vicious cycle; however, its effectiveness has only been investigated in small cohorts. Therefore, the objective of the Dialysis Training Therapy (DiaTT) trial will be to assess the effects of a 12-month intradialytic exercise program on physical functioning, frailty and health economics in a large cohort of HD patients in a real-world setting. DiaTT will be a prospective, cluster-randomized (1:1), controlled, multi-center, interventional clinical trial across 28 dialysis units, aiming at the recruitment of >1100 CKD patients on HD. The intervention group will receive 12 months' intradialytic exercise (combined aerobic and resistance training), whereas the usual care group will not receive intervention. The primary endpoint will be a change on the sit-to-stand test (STS60) result between baseline and 12 months. Secondary endpoints will include physical functioning, frailty, quality of life, 3-point MACE, hospitalizations, survival, quality of HD, health literacy and health care costs. By including almost as many patients as previously investigated in smaller trials, DiaTT will be the largest randomized, controlled trial assessing frailty, quality of life and mortality in the field of nephrology

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk