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- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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- Friman, S., et al.
(author)
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Sotrastaurin, a Novel Small Molecule Inhibiting Protein-Kinase C : Randomized Phase II Study in Renal Transplant Recipients
- 2011
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:7, s. 1444-1455
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Journal article (peer-reviewed)abstract
- Sotrastaurin, a selective protein-kinase-C inhibitor, blocks early T-cell activation through a calcineurin-independent mechanism. In this study, de novo renal transplant recipients with immediate graft function were randomized 1: 2 to tacrolimus (control, n = 44) or sotrastaurin (300 mg b.i.d.; n = 81). All patients received basiliximab, mycophenolic acid (MPA) and steroids. The primary endpoint was the composite of treated biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up at month 3. The main safety assessment was estimated glomerular filtration rate (eGFR); modification of diet in renal disease (MDRD) at month 3. Composite efficacy failure at month 3 was higher for the sotrastaurin versus control regimen (25.7% vs. 4.5%, p = 0.001), driven by higher BPAR rates (23.6% vs. 4.5%, p = 0.003), which led to early study termination. Median (+/- standard deviation [SD]) eGFR was higher for sotrastaurin versus control at all timepoints from day 7 (month 3: 59.0 +/- 22.3 vs. 49.5 +/- 17.7 mL/min/1.73 m(2), p = 0.006). The most common adverse events were gastrointestinal disorders (control: 63.6%; sotrastaurin: 88.9%) which led to study-medication discontinuation in two sotrastaurin patients. This study demonstrated a lower degree of efficacy but better renal function with the calcineurin-inhibitor-free regimen of sotrastaurin+MPA versus the tacrolimus-based control. Ongoing studies are evaluating alternative sotrastaurin regimens.
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| 10. |
- Kasiske, Bertram L., et al.
(author)
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KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary
- 2010
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In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 77:4, s. 299-311
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Journal article (peer-reviewed)abstract
- The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere. Kidney International (2010) 77, 299-311; doi: 10.1038/ki.2009.377; published online 21 October 2009
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| 11. |
- Vincenti, F., et al.
(author)
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Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus
- 2007
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In: American journal of transplantation. - : Elsevier BV. - 1600-6135. ; 7:6, s. 1506-14
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Journal article (peer-reviewed)abstract
- DIRECT (Diabetes Incidence after Renal Transplantation: Neoral C(2) Monitoring Versus Tacrolimus) was a 6-month, open-label, randomized, multicenter study which used American Diabetes Association/World Health Organization criteria to define glucose abnormalities. De novo renal transplant patients were randomized to cyclosporine microemulsion (CsA-ME, using C(2) monitoring) or tacrolimus, with mycophenolic acid, steroids and basiliximab. The intent-to-treat population comprised 682 patients (336 CsA-ME, 346 tacrolimus): 567 were nondiabetic at baseline. Demographics, diabetes risk factors and steroid doses were similar between treatment groups. The primary safety endpoint, new-onset diabetes after transplant (NODAT) or impaired fasting glucose (IFG) at 6 months, occurred in 73 CsA-ME patients (26.0%) and 96 tacrolimus patients (33.6%, p = 0.046). The primary efficacy endpoint, biopsy-proven acute rejection, graft loss or death at 6 months, occurred in 43 CsA-ME patients (12.8%) and 34 tacrolimus patients (9.8%, p = 0.211). Mean glomerular filtration rate (Cockcroft-Gault) was 63.6 +/- 20.7 mL/min/1.73 m(2) in the CsA-ME cohort and 65.9 +/- 23.1 mL/min/1.73 m(2) with tacrolimus (p = 0.285); mean serum creatinine was 139 +/- 58 and 133 +/- 57 mumol/L, respectively (p = 0.005). Blood pressure was similar between treatment groups at month 6, but total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher with CsA than with tacrolimus (total cholesterol:HDL remained unchanged). The profile and incidence of adverse events were similar between treatments. The incidence of NODAT or IFG at 6 months post-transplant is significantly lower with CsA-ME than with tacrolimus without a significant difference in short-term outcome.
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| 12. |
- Zaïm, N., et al.
(author)
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Interaction of Ultraintense Radially-Polarized Laser Pulses with Plasma Mirrors
- 2020
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In: Physical Review X. - 2160-3308. ; 10:4
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Journal article (peer-reviewed)abstract
- We present experimental results of vacuum laser acceleration (VLA) of electrons using radially polarized laser pulses interacting with a plasma mirror. Tightly focused, radially polarized laser pulses have been proposed for electron acceleration because of their strong longitudinal electric field, making them ideal for VLA. However, experimental results have been limited until now because injecting electrons into the laser field has remained a considerable challenge. Here, we demonstrate experimentally that using a plasma mirror as an injector solves this problem and permits us to inject electrons at the ideal phase of the laser, resulting in the acceleration of electrons along the laser propagation direction while reducing the electron beam divergence compared to the linear polarization case. We obtain electron bunches with few-MeV energies and a 200-pC charge, thus demonstrating, for the first time, electron acceleration to relativistic energies using a radially polarized laser. High-harmonic generation from the plasma surface is also measured, and it provides additional insight into the injection of electrons into the laser field upon its reflection on the plasma mirror. Detailed comparisons between experimental results and full 3D simulations unravel the complex physics of electron injection and acceleration in this new regime: We find that electrons are injected into the radially polarized pulse in the form of two spatially separated bunches emitted from the p-polarized regions of the focus. Finally, we leverage on the insight brought by this study to propose and validate a more optimal experimental configuration that can lead to extremely peaked electron angular distributions and higher energy beams.
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