12 research outputs found
Kinetics of lead release from soils at historic mining and smelting sites, determined by a modified electro-ultrafiltration
Kinetics of lead release from soils at historic mining and smelting sites, determined by a modified electro-ultrafiltration
Blood volume-monitored regulation of ultrafiltration to decrease the dry weight in fluid-overloaded hemodialysis patients: a randomized controlled trial
Abstract Background Because chronic fluid volume overload is associated with higher mortality, we tested whether blood-volume monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) would facilitate dry weight reduction, in comparison to conventional dialysis (CONV). Methods We carried out a multicenter, 4-week, randomized controlled trial in hemodialysis patients â„15% above normal extracellular fluid volume (ECV), per bioimpedance spectroscopy, who were randomized 1:1:1. Applying UCR (Nikkiso), UTR (Fresenius) and CONV, initial dry weight was reduced rapidly to target. Dry weight reduction was attenuated and eventually stopped at the occurrence of dialysis complications. The primary outcome was defined as intra- and postdialytic complications. Secondary outcomes were magnitudes of dry weight and blood pressure reduction. Results Of 244 patients assessed, N = 95 had volume overload â„15% above normal ECV. Fifty patients received the allocated interventions (N = 16 UCR, N = 18 UTR, N = 16 CONV) and completed the trial. The rate of complications was significantly lower in UTR compared to CONV (21 ± 21% vs 34 ± 20%, p = 0.022), and also compared to UCR (vs 39 ± 27%, p = 0.028), but not statistically different between UCR and CONV (p = 0.93). Dry weight reduction was significantly higher in UTR compared to UCR (5.0 ± 3.4% vs 2.0 ± 2.7% body weight, p = 0.013), but not compared to CONV (vs 3.9 ± 2.1% body weight, p = 0.31). Systolic blood pressure reduction throughout the intervention phase was 17 ± 22 mmHg overall, but not significantly different between the three groups. Average maximum ultrafiltration rates were significantly higher in UTR than in UCR and CONV, at statistically similar dialysis times. Retrospective examination of randomly selected hemodialysis sessions in the UCR group identified technical mistakes in 36% of the dialysis sessions, despite considerable training efforts. Conclusions Even in patients with volume overload, fluid removal was challenging. Despite the relative advantage of UTR, which must be interpreted with caution in view of the poor technical execution of UCR, this study renders clear that fluid removal must not be reinforced rapidly. Apprehension of this obstacle is imperative for future clinical and academic endeavors aimed at improving dialysis outcomes by correcting volume status. Trial registration ClinicalTrials.gov ( NCT01416753 ), trial registration date: August 12, 2011
Solving the mystery of the FMC63-CD19 affinity
Abstract The majority of approved CAR T cell products are based on the FMC63-scFv directed against CD19. Surprisingly, although antigen binding affinity is a major determinant for CAR function, the affinity of the benchmark FMC63-scFv has not been unambiguously determined. That is, a wide range of affinities have been reported in literature, differing by more than 100-fold. Using a range of techniques, we demonstrate that suboptimal experimental designs can cause artefacts that lead to over- or underestimation of the affinity. To minimize these artefacts, we performed SPR with strictly monomeric and correctly folded soluble CD19, yielding an FMC63-scFv affinity of 2â6Â nM. Together, apart from analyzing the FMC63-scFv affinity under optimized conditions, we also provide potential explanations for the wide range of published affinities. We expect that this study will be highly valuable for interpretations of CAR affinity-function relationships, as well as for the design of future CAR T cell generations
Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial
Abstract Background Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. Methods/design BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as â„15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, âfinalâ dry weight is set to normohydration weight â7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1âkg per 10âkg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). Discussion Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. Trial registration ClinicalTrials.gov, NCT01416753</p