Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term

ADHERE: randomized controlled trial comparing renal function in de novo kidney transplant recipients receiving prolonged-release tacrolimus plus mycophenolate mofetil or sirolimus

ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolongedrelease tacrolimus-based immunosuppressive regimens. On Days 0?27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolongedrelease tacrolimus (?25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m2; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2)

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease

Passive pumping for the parallel trapping of single neurons onto a microsieve electrode array

Recent advances in brain-on-a-chip technology have led to the development of modified microelectrode arrays. Previously, the authors have contributed to this exciting field of neuroscience by demonstrating a fabrication process for producing microsieve chips that contain three-dimensional (3D) micropores at the electrodes [termed microsieve electrode arrays (μSEAs)]. This chip allows us to trap hundreds of single neuronal cells in parallel onto the electrodes [B. Schurink and R. Luttge, J. Vac. Sci. Technol., B 31, 06F903 (2013)]. However, trapping the neurons reproducibly under gentle, biocompatible conditions remains a challenge. The current setup involves the use of a hand-operated syringe that is connected to the back of the μSEA chip with a polydimethylsiloxane (PDMS) construct. This makes the capture process rather uncontrolled, which can lead to either cell damage by shear stress or the release of trapped neurons when unplugging the syringe and PDMS constructs. Although, the authors could achieve an efficient capture rate of single neurons within the 3D micropores (80%-90% filling efficiency), cell culture performance varied significantly. In this paper, the authors introduce a passive pumping mechanism for the parallel trapping of neurons onto the μSEA chip with the goal to improve its biological performance. This method uses the capillary pumping between two droplets (a "pumping droplet" on one side of the chip and a "reservoir droplet" on the other side) to create a stable and controllable flow. Due to simplification of the handling procedure, omitting the use of a syringe and additional connections to the μSEA chip, the set-up is compatible with real time microscopy techniques. Hence, the authors could use optical particle tracking to study the trapping process and record particle velocities by video imaging. Analyzing the particle velocities in the passive pumping regime, the authors can confirm a gentle uniform particle flow through the 3D micropores. The authors show that passive pumping particle velocity can be tightly controlled (from 5 to 7.5 to 10.4 μm/s) simply by changing the droplet volume of the pumping droplets from 20, 40, and 60 μl and keeping the reservoir drop constant (10 μl). The authors demonstrate that neuron capturing efficiency and reproducibility as well as neuronal network formation are greatly improved when using this passive pumping approach

Utilisation des pesticides et risques pour la sante dans la culture du coton au Togo

Aucune enquête d’évaluation des risques chimiques dans la culture du coton n’a été réalisée au Togo. Les objectifs de cette étude sont de préciser la nature des pesticides utilisés et l’état de santé des producteurs.Il s’agit d’une étude descriptive portant sur 346 sujets représentant environ 5 % de la population des producteurs de coton de la Préfecture de Sotouboua (Togo). Les pesticides utilisés étaient surtout des  organophosphorés associés à des pyréthrinoïdes de synthèse :48 % des cas. Les producteurs pulvérisaient aussi des organochlorés (11,5 %) et des produits interdits (22,4 %). Certains ne savaient pas quel pesticide ils emploient (8,9 %). Le risque pour la santé étaitconnu, mais la prévention était tout à fait déficiente. En particulier les équipements de protection individuelle étaient inexistants. L’état de santé des producteurs était caractérisé par une fréquence élevée d’intoxications. Ces intoxications concernaient, par contact cutanéo-muqueux et inhalation, 99,7 % des producteurs, et par absorption orale, 33,7 % d’entre eux. Elles laissaient des séquelles dans 10 à 15 % descas. L’utilisation des pesticides dans la culture du coton au Togo a un impact indiscutable sur la santé. Les intoxications sont liées essentiellement à des comportements à risque des producteurs. Les mesures de prévention tant légale que technique et médicale, doivent être revues. Not any assessment of chemical risks was made about cotton growing in Togo. The objectives of this presentation were to specify the nature of used pesticides and the health state of the growers. A descriptive study has been carried out among 346 subjects making up the 5 % of the cotton growers population in the prefecture of Sotouboua (Togo). Organophosphates associated with synthetic pyréthrynoids were used by 48.3 % of the growers. Other products were also employed:  organochlorates by 11.6 % and prohibited compounds by 22.5 %. The kindof pesticide was unknown by 8.9 % of the users. There was in the main, a satisfactory knowledge of the risks associated with the use of pesticides. On the other hand, the practice of prevention was wholly insufficient. Hazardous behaviours were common occurrences and, especially, the wearing of individual protection equipment was never observed. Health state of the growers was characterized by numerous acute poisonings by contact and ingestion: respectively 99.7 and 33.6 % of the subjects. After-effects were present with a prevalence of 10 to 15 % for these poisonings.The use of pesticides in cotton growing in Togo has clear repercussions on health with poisonings related to hazardous behaviours of the cotton-farmers. Changes in legal, technical and medical prevention appearnecessary

Prévalence des symptômes dans la maladie rénale chronique et association avec la qualité de vie

National audienc