Late opportunistic infections (OI) occurring beyond the first year after kidney transplantation (KT) are poorly described and not targeted by prophylactic strategies. We performed a ten-year ...retrospective monocentric cohort study describing epidemiology, risk factors and impact of late OI occurring 1 year after KT. We included clinically symptomatic OI requiring treatment besides BK virus nephropathy. Control groups included early OI occurring in the first year after KT, and KT recipients without OI since KT and alive with a functional allograft at 1 year. Among 1066 KT recipients, 185 (19.4%) presented a first episode of OI 21.0 (8.0-45.0) months after KT: 120 late OI (64.9%) and 65 early OI (35.1%). Late OI were mainly viral (
= 83, 69.2%), mostly herpes zoster (HZ) (
= 36, 43.4%). Pneumocystis represented most late fungal infections (
= 12/25, 48%). Compared to early OI, we reported more pneumocystis (
= 0.002) and less invasive aspergillosis (
= 0.01) among late OI. Patients with late OI were significatively younger at KT (54.0 ± 13.3 vs. 60.2 ± 14.3 years,
= 0.05). Patient and allograft survival rates between late OI and control groups were similar. Only age was independently associated with mortality. While late OI were not associated with higher mortality or graft loss, implementing prophylactic strategies might prevent such infections.
Aim. The aim of this study was to develop and validate a prognostic score for 6-month mortality in elderly patients starting dialysis for end-stage renal disease. Methods. Using data from the French ...Rein registry, we developed a prognostic score in a training sample of 2500 patients aged 75 years or older who started dialysis between 2002 and 2006, which we validated in a similar sample of 1642 patients. Multivariate logistic regression with 500 bootstrap samples allowed us to select risk factors from 19 demographic and baseline clinical variables. Results. The overall 6-month mortality was 19%. Age was not associated with early mortality. Nine risk factors were selected and points assigned for the score were as follows: body mass index <18.5 kg/m2 (2 points), diabetes (1), congestive heart failure stages III to IV (2), peripheral vascular disease stages III to IV (2), dysrhythmia (1), active malignancy (1), severe behavioural disorder (2), total dependency for transfers (3) and unplanned dialysis (2). The median score was 2. Mortality rates ranged from 8% in the lowest risk group (0 point) to 70% in the highest risk group (≥9 points) and 17% in the median group (2 points). Seventeen percent of all deaths occurred after withdrawal from dialysis, ranging from 0% for a score of 0–1 to 15% for a score of 7 or higher. Conclusions. This simple clinical score effectively predicts short-term prognosis among elderly patients starting dialysis. It should help to illuminate clinical decision making, but cannot be used to withhold dialysis. It ought to only be used by nephrologists to facilitate the discussion with the patients and their families.
•We model particle size evolution during compression grinding, using PBM.•Model parameters vary with density to account of evolving conditions in the bed.•Model is calibrated using a large set of ...piston-die tests on monodisperse samples.•Model can then predict the evolution of any starting particle size distribution.•Predictive power of the model is tested on three different mineral materials.
Population Balance Models (PBM) are widely used to predict the evolution of the particle size distribution during various grinding processes, such as ball milling. They represent breakage through the definition of particle destruction and fragments generation rates. Their application to compression grinding (HPGR, vertical mills…) has been limited, due to the complexity of interactions between particles of different sizes.
In this work, we present a new PBM approach for compression grinding. Complex interactions between size classes are represented in a simplified manner by making particle destruction and fragment generation depend on the bed porosity. Model is tested by confrontation to an extensive collection of experimental results on a piston-die cell, on three different materials (cement clinker, limestone, and quartz). When properly calibrated with preliminary tests, the model is able to predict the evolution of the particle size with accuracy, for any starting grain size distribution and any load.
•Infections remain the second cause of death in end-stage kidney disease patients.•End Stage Kidney Disease patients are significantly immunocompromised.•Low IFN-γ levels in QuantiFERON-Monitor are ...associated with a ten-fold increased risk of infection.•QuantiFERON-Monitor could help to select patients who could benefit from therapeutic interventions to restore cellular immunity and to minimize both infections and rejections after kidney-transplantation.
Infections remain the second most common cause of death in patients with end-stage kidney disease (ESKD). We aimed to evaluate non-specific cell-mediated immunity in an ESKD cohort using a functional assay applicable to routine use, QuantiFERON-Monitor (Qiagen), and assess whether it can predict infectious events.
In this prospective study, we performed the QuantiFERON-Monitor test in 80 subjects including 54 patients with ESKD. QuantiFERON-Monitor is based on the measurement of plasma interferon-gamma (IFN-γ) after stimulation of NK-cells with a TLR-7 agonist, and T-cells with a TCR agonist. Patients were subsequently followed for 6 to 12 months.
QuantiFERON-Monitor showed lower stimulated IFN-γ production in ESKD patients (n = 54) compared to healthy donors (n = 19) (p < 0.0001) and to chronic kidney disease stage 3–4 patients (n = 7) (hemodialysis (n = 30): p < 0.01; peritoneal dialysis (n = 13): p = 0.03 and ESKD on conservative management (n = 11): p < 0.001). No significant difference in stimulated IFN-γ production was observed between ESKD patients with renal replacement therapies or conservative management. Stimulated IFN-γ production was significantly lower in patients later developing infections (13.9 5.5–48.3 IU/mL vs 85.8 35.5–236 IU/mL, p = 0.007). Using ROC analysis, we identified a cutoff value of 63.55 IU/mL (sensitivity = 80.95%, specificity = 79.17%, AUC = 0.78, p = 0.008) to discriminate patients at higher risk of infections. Patients with stimulated IFN-γ levels measured by QuantiFERON Monitor below 63.55 IU/mL (n = 21) had a hazard ratio of 10.71 (3.68–31.13, p < 0.0001) for the development of subsequent infections.
Monitoring of IFN-γ production after stimulation of innate and adaptive immunity may identify ESKD patients with high risk of infection. This allows for therapeutic interventions to restore cellular immunity, thereby minimizing both infections and rejections after kidney-transplantation.
BACKGROUND:The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure–lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment ...for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control.
METHODS:One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients.
RESULTS:The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was –6.7 mm Hg (P=0.0461) in fully adherent and –7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients.
CONCLUSIONS:In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone.
CLINICAL TRIAL REGISTRATION:URLhttp://www.clinicaltrials.gov. Unique identifierNCT01570777.
Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting ...progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
Summary
Background
In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir‐based regimens. Changes in serum creatinine or in the estimated ...glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable.
Aim
To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time.
Methods
In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease–Epidemiology Collaboration (CKD‐EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre‐treatment, on‐treatment and post‐treatment periods were 9 months, 3‐9 months and 4.5 months. Interactions between eGFR slopes and the pre‐treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On‐treatment eGFR slopes were separated in tertiles. Pre‐ and post‐treatment eGFR slopes were compared globally and according to tertiles.
Results
The post‐treatment eGFR slope was significantly better than pre‐treatment eGFR slope (+0.18 (IQR −0.76 to +1.32) vs −0.11 (IQR −1.01 to +0.73) mL/min/1.73 m2/month, P = 0.03) independently of the pre‐treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child‐Pugh B and C vs lower stages, P = 0.38). Tertiles of on‐treatment eGFR slopes were −1.71 (IQR −2.54 to −1.48), −0.78 (IQR −1.03 to −0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2/month. Pre‐ and post‐treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73).
Conclusion
The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir‐based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.
•We report on 3D DEM simulations of grain breakage in oedometric compression.•Stress transfers after grains break often trigger a cascade of breakage events.•Key parameters include initial density ...and typical elastic deformation at breakage.•We define the grinding process energy efficiency, observed to range from 1% to 15%.•Process parameters impact energy efficiency through two distinct physical mechanisms.
We report on discrete-element method (DEM) simulations of the breakage of fragile particles under growing oedometric load, motivated by applications to clinker grinding processes in the cement industry. The use of a simplified model, in which spherical beads break into smaller spherical fragments with some loss of volume, enables us to perform a systematic parametric study and to investigate collective effects, as the transfer of load to other particles following one breakage event may entail large scale avalanches or cascades involving the rupture of many grains. Particles are attributed random strengths, chosen according to Weibull distributions of varying width, and rupture criteria are defined either in terms of contact forces or of average stresses within the grain. A dimensionless parameter, κS, is defined, which combines the influence of particle strength and contact stiffness. κS expresses the characteristic contact deflection, relative to the particle diameter, at rupture. Model materials range from stiff-fragile (large κS) to soft-strong (small κS). Initial packings also differ in solid fraction Φ0. The energy efficiency, defined as the ratio to dissipated energy of elastic energy in each grain before its breakage, is strongly correlated to the importance of the cascading effect, either through the quantity of kinetic energy released in the system, or through the capacity to capture it back in the form of elastic energy without dissipation. It ranges from 1% to 15% in the simulation, an order of magnitude compatible with the efficiency claimed in the industrial processes. Energy efficiency is mainly determined, by order of decreasing importance, by κS, Φ0, distribution width and choice of rupture criterion.
Permeating air is known to have a negative impact on the roller compaction process, because the feed is destabilized by the flow of escaping gas, causing pressure to build-up and potentially damage ...compacts at release. Airflow during powder roller compaction and its effect on the rolling process are investigated in the rolling direction (1D), using an extension of the Johanson model for the solid. Fluid transport obeys Darcy's law, with permeability being a function of both material density and particle size, through the Kozeny–Carman relationship. In this modeling, the effect of the air pressure on the solid is neglected in the compaction zone. Assuming air at atmospheric pressure at the feeding angle and ignoring airflow through the gap, predictions of air pressure as a function of the rolling angle for bentonite material powder are presented and discussed. Results suggest the existence of two different stability zones within the operating conditions, where industrial systems could function without being affected by airflow effects. The model highlights the importance of the permeability/rotation speed ratio, which governs the proportion of air trapped in the compacts to the portion evacuated through the feed. We also investigate the effect of particle fragmentation during the rolling process. Finally, we provide guidelines for the scale-up of roller presses subjected to air flow issues, through a study of the effect of the system dimensions and rotation speed on the elimination of air.
In spite of the lack of available experimental data, this model allows for a better understanding of how air escapes by diffusing through the material during the rolling process, and opens interesting perspectives for the mitigation of its effect on the process.
•We explore the role of the air trapped into fine powders during roll compaction process.•We determine density and velocity of the solid during the process, using Johansson model and mass conservation.•We determine gas pressure distributions, using Darcy's law.•We investigate effect of powder density and particle fragmentation on air pressure using Kozeny–Carman law.•We discuss the initiation of instabilities based on the fluidization criterion and the impact of process parameters.
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