Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care

Objective: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. Design and Methods: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. Results: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. Conclusions: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease

Determination of 144^{144}Ce/238^{238}U atom ratio in spent nuclear fuel using double spike isotope dilution mass spectrometry.

International audienceThe low abundance cerium-144 radionuclide is one of the significant contributors to the decay heat from spent nuclear fuel for cooling times of less than ten years after nuclear reactor discharge. The accurate quantification of the $^{144}$Ce content (or $^{144}$Ce/$^{238}$U) in irradiated nuclear fuel is necessary to validate and extend the neutronic calculation codes as well as to improve the short-term nuclear waste management strategies. In order to quantify the $^{144}$Ce/$^{238}$U atomic ratios at low uncertainty, we developed a new analytical technique based on double spike isotope dilution associated with mass spectrometry. This includes (1) the chemical elimination of the major neodymium-144 isobaric interference by two steps of liquid chromatography prior to isotope analysis by Thermal Ionization Mass Spectrometry (TIMS) using both total evaporation and sequential methods, and (2) the preparation and use of an in-house double spike solution, using a mixture of a natural Ce solution with a $^{233}$U-enriched solution. This new approach was applied for the first time on two Mixed Oxide (MOx) spent nuclear fuel samples and allowed the determination of $^{144}$Ce/$^{238}$U atomic ratios ranging from 35 × 10$^{-6}$ to 59 × 10$^{-6}$ with a relative expanded uncertainty of measurement of around 1% at a 95% confidence level

Determination of the 144Ce/238U ratio in spent nuclear fuel samples by double spike isotope dilution mass spectrometry

International audiencePrecise knowledge of the energy released by radioactive decay of nuclides (decay heat) after the shut down of a nuclear reactor is of major importance for spent fuel management and nuclear safety. Among those radionuclides, the 144Ce isotope is a fission product that significantly contributes to the decay heat for cooling time less than 10 years. The accurate quantification of this low abundance isotope in nuclear fuels is therefore required (1) to bring new constrains on neutronic calculation codes that predict the evolution of the spent nuclear fuel composition with time and (2) to improve the short-term management of irradiated fuels.An innovative method combining liquid chromatography with double spike isotope dilution and state of the art mass spectrometric techniques (MC-ICP-MS, TIMS) has been developed for this purpose.This new method was applied for the first time on two Mixed Oxide (MOx) spent nuclear fuel samples. It enabled the determination of 144Ce/238U atomic ratios of less than a hundred of ppm with expanded measurement uncertainty at around 1 % at the 95 % confidence level. This corresponds to a reduction of at least three times of the measurement uncertainty compared to classical gamma-ray approaches. In the case of UOX samples or irradiated fuels cooled for longer periods, the 144Ce content is even lower, i.e. 144Ce/238U in the range of a few ppm. Consequently, specific developments were carried out based on either extration techniques or HPLC and will also be discussed

CKD complications in kidney-transplanted patients going backto dialysis: impact on patients outcomes

International audienceAims The management of chronic kidney disease (CKD) complications is not always adequate in patients with a failed kidney transplant. We aimed to evaluate the frequency of CKD complications and assess whether they may lead to worse outcomes in this patient population.Method We analyzed 49 kidney transplant recipients with a failed transplant (T+) and matched non-transplanted patients (T-) starting dialysis between 2000 and 2010 in five dialysis centers in France. CKD complications at dialysis initiation, hospitalizations and death were recorded and compared between the two groups.Results At dialysis initiation, T+ patients were more likely to have bicarbonate 1.5 mmol/l (77.6 vs. 59.2%, p = 0.03), arterial blood pressure > 130/80 mmHg (75.5 vs. 93.9%, p = 0.01), body mass index < 23 (59.2 vs. 32.7%, p = 0.01) and albumin < 38 g/l (69.4 vs. 36.7%) than T-patients. T+ patients were hospitalized more frequently in the year following dialysis initiation (40.8 +/- 7.0 vs. 16.3 +/- 5.3%, log rank p = 0.01) and 5-year survival rate was lower than in T-patients (82.1 +/- 6.2 vs. 64.0 +/- 7.4%, log rank p = 0.02). However risk of hospitalization and mortality was lesser after adjustments for CKD complications.Conclusion Despite regular follow-up by nephrologists, CKD complications before initiation of dialysis are more frequent in T+ patients than in T-patients. A better management of CKD complications in T+ patients could improve outcomes after dialysis initiation

Cardioprotective Effect of Acute Intradialytic Exercise: A Comprehensive Speckle-Tracking Echocardiography Analysis

Significance Statement Hemodialysis (HD) can lead to acute left ventricular (LV) myocardial wall motion abnormalities (myocardial stunning) due to segmental hypoperfusion. Exercise during dialysis is associated with favorable effects on central hemodynamics and BP stability, factors considered in the etiology of HD-induced myocardial stunning. In a speckle-tracking echocardiography analysis, the authors explored effects of acute intradialytic exercise (IDE) on LV regional myocardial function in 60 patients undergoing HD. They found beneficial effects of IDE on LV longitudinal and circumferential function and on torsional mechanics, not accounted for by cardiac loading conditions or central hemodynamics. These findings support the implementation of IDE in people with ESKD, given that LV transient dysfunction imposed by repetitive HD may contribute to heart failure and increased risk of cardiac events in such patients. Background Hemodialysis (HD) induces left ventricular (LV) transient myocardial dysfunction. A complex interplay between linear deformations and torsional mechanics underlies LV myocardial performance. Although intradialytic exercise (IDE) induces favorable effects on central hemodynamics, its effect on myocardial mechanics has never been comprehensively documented. Methods To evaluate the effects of IDE on LV myocardial mechanics, assessed by speckle-tracking echocardiography, we conducted a prospective, open-label, two-center randomized crossover trial. We enrolled 60 individuals with ESKD receiving HD, who were assigned to participate in two sessions performed in a randomized order: standard HD and HD incorporating 30 minutes of aerobic exercise (HDEX). We measured global longitudinal strain (GLS) at baseline (T0), 90 minutes after HD onset (T1), and 30 minutes before ending HD (T2). At T0 and T2, we also measured circumferential strain and twist, calculated as the net difference between apical and basal rotations. Central hemodynamic data (BP, cardiac output) also were collected. Results The decline in GLS observed during the HD procedure was attenuated in the HDEX sessions (estimated difference, −1.16%; 95% confidence interval [95% CI], −0.31 to −2.02; P = 0.008). Compared with HD, HDEX also demonstrated greater improvements from T0 to T2 in twist, an important component of LV myocardial function (estimated difference, 2.48°; 95% CI, 0.30 to 4.65; P = 0.02). Differences in changes from T0 to T2 for cardiac loading and intradialytic hemodynamics did not account for the beneficial effects of IDE on LV myocardial mechanics kinetics. Conclusions IDE applied acutely during HD improves regional myocardial mechanics and might warrant consideration in the therapeutic approach for patients on HD

Course of chronic kidney disease in French patients

Background: In 1998, a French survey showed that the referral of patients with chronic kidney disease to a nephrologist was delayed, resulting in many emergency initiations of dialysis. In 2009, the ORACLE study aimed to describe the renal course of dialysis patients from their first nephrology visit to their first dialysis session.Methods: The ORACLE study was a multicentre retrospective study of all patients who started chronic dialysis. Data were collected at the first nephrology visit and at the first dialysis session.Results: In total, 720 patients were included (69 centres). At the first nephrology visit, the mean Cockcroft-Gault (CG) indicator was 31.8 mL/min (22.7 in 1998) and 52.4% of patients (73% in 1998) had a CG <30. The mean time between the first nephrology visit and the first dialysis session was 48 months (35 months in 1998).Conclusion: In 2009, most patients were referred a long time before dialysis initiation, which likely allowed them to benefit from the impact of nephrology care on early outcomes when on dialysis. However, 34.2% of the dialysis sessions were still initiated under emergency conditions

Cardiac MR Strain: A Noninvasive Biomarker of Fibrofatty Remodeling of the Left Atrial Myocardium

Purpose To determine whether left atrial (LA) strain quantification with cardiac magnetic resonance (MR) imaging feature tracking is associated with the severity of LA fibrofatty myocardial remodeling at histologic analysis. Materials and Methods This prospective case-control study was approved by the institutional review board. LA strain was evaluated with cardiac MR feature tracking between January 2014 and March 2015 in 13 consecutive patients (mean age, 61 years ± 19; nine male) with mitral regurgitation in the 24 hours before mitral valve surgery and 13 age- and sex-matched healthy control subjects. LA strain parameters were compared first between control subjects and patients and then according to atrial fibrillation and mitral regurgitation status. Associations between LA strain and histology of preoperative biopsies were reported by using receiver operating characteristic curve analysis and Spearman correlation. Results Peak longitudinal atrial strain (PLAS) was significantly lower in patients with mitral regurgitation than in healthy control subjects (P &lt; .001). Increased LA remodeling was significantly related to altered LA strain, and the strongest association was found between PLAS and the degree of fibrofatty myocardial replacement at histologic analysis (r = -0.75, P = .017). LA end-diastolic volume was increased in patients with mitral regurgitation when compared with that in healthy volunteers (P &lt; .001) because of volume overload; however, volume did not correlate with the histologic degree of LA fibrofatty replacement (r = -0.35, P = .330). Conclusion LA strain, especially PLAS, correlates strongly with the degree of fibrofatty replacement at histologic analysis. Such functional imaging biomarker in combination with LA volumetry could help to guide clinical decisions, since myocardial structural remodeling is a known morphologic substrate of LA dysfunction leading to atrial fibrillation with adverse outcome. © RSNA, 2017 Online supplemental material is available for this article

Fractionated gemtuzumab ozogamicin in association with high dose chemotherapy: a bridge to allogeneic stem cell transplantation in refractory and relapsed acute myeloid leukemia

Optimization of the salvage regimen is required to improve prognosis in primary refractory or relapsed acute myeloid leukemia (AML). In fit patients, a bridge to allogeneic transplant is the primary purpose of salvage. We tested the combination of fractionated gemtuzumab ozogamicin with cytarabine and mitoxantrone (MYLODAM schema) with primary endpoint of efficacy and safety. We also attempted to define predictive factors for survival and response after salvage. We included 58 patients with a median age at salvage of 56 years. The overall response rate was 67%. Leukemia-free survival (LFS) and overall survival (OS) at 2 years was 36% (95% CI: 23-49) and 54% (95% CI: 39-68), respectively. Treatment-related mortality was 7%. Three veno-occlusive diseases (SOS/VOD) occurred during salvage. In the allogeneic group of 28 patients (48%), LFS and OS at 2 years was 57 % (95% CI: 36.3-77.5) and 69 % (95% CI: 49.3-88.7), respectively. Incidences of nonrelapse mortality, grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were 16%, 40%, and 45%, respectively. A GO-based intensive regimen is a viable option for salvage therapy and a feasible schedule as a bridge to allogeneic transplant

Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation

International audienceBackgroundPost-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce.ObjectivesThis study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy.MethodsThe study compared clinical outcomes between patients who received PT-Cy (n = 136) and patients who did not (n = 195), with a focus on early cardiac events (ECE) occurring within the first 100 days after HSCT. All patients had the same systematic cardiac monitoring.ResultsThe cumulative incidence of ECE was 19% in the PT-Cy group and 6% in the no–PT-Cy group (p < 0.001). The main ECE occurring after PT-Cy were left ventricular systolic dysfunction (13%), acute pulmonary edema (7%), pericarditis (4%), arrhythmia (3%), and acute coronary syndrome (2%). Cardiovascular risk factors were not associated with ECE. In multivariable analysis, the use of PT-Cy was associated with ECE (hazard ratio: 2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002]. Older age, sequential conditioning regimen, and Cy exposure before HSCT were also associated with a higher incidence of ECE. Finally, a history of cardiac events before HSCT and ECE had a detrimental impact on overall survival.ConclusionsPT-Cy is associated with a higher incidence of ECE occurring within the first 100 days after HSCT. Patients who have a cardiac event after HSCT have lower overall survival. These results may help to improve the selection of patients who are eligible to undergo HSCT with PT-Cy, especially older adult patients and patients with previous exposure to Cy