Renal effects of novel antiretroviral drugs Milburn, James; Jones, Rachael; Levy, Jeremy B
Nephrology, dialysis, transplantation,
03/2017, Letnik:
32, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Chronic kidney disease (CKD) is a critical comorbidity for patients living with HIV, with an estimated prevalence between 2.4 and 17%. Such patients are increasingly affected by diseases associated ...with ageing, including cardiovascular disease and CKD, and the prevalence of risk factors such as smoking and dyslipidaemia is increased in this population. Proteinuria is also now recognized as a common finding in individuals living with HIV. While combination antiretroviral (ARV) treatments reduce CKD in the HIV-infected population overall, some ARV drugs have been shown to be nephrotoxic and associated with worsening renal function. Over the last few years, several highly efficacious new ARV agents have been introduced. This brief review will look at the novel agents dolutegravir, raltegravir, elvitegravir, cobicistat, tenofovir alafenamide fumarate and atazanavir, all of which have been licensed relatively recently, and describe issues relevant to renal function, creatinine handling and potential nephrotoxicity. Given the prevalence of CKD, the wide range of possible interactions between HIV, ARV therapy, CKD and its treatments, nephrologists need to be aware of these newer agents and their possible effect on kidneys.
Oxide Nanoelectronics on Demand Cen, Cheng; Thiel, Stefan; Mannhart, Jochen ...
Science (American Association for the Advancement of Science),
02/2009, Letnik:
323, Številka:
5917
Journal Article
Recenzirano
Electronic confinement at nanoscale dimensions remains a central means of science and technology. We demonstrate nanoscale lateral confinement of a quasi-two-dimensional electron gas at a lanthanum ...aluminate-strontium titanate interface. Control of this confinement using an atomic force microscope lithography technique enabled us to create tunnel junctions and field-effect transistors with characteristic dimensions as small as 2 nanometers. These electronic devices can be modified or erased without the need for complex lithographic procedures. Our on-demand nanoelectronics fabrication platform has the potential for widespread technological application.
Nanoscale Phenomena in Oxide Heterostructures Sulpizio, Joseph A; Ilani, Shahal; Irvin, Patrick ...
Annual review of materials research,
07/2014, Letnik:
44, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Recent advances in creating complex oxide heterostructures, interfaces formed between two different transition-metal oxides, have heralded a new era of materials and physics research, enabling a ...uniquely diverse set of coexisting physical properties to be combined with an ever-increasing degree of experimental control. These systems have exhibited varied phenomena such as superconductivity, magnetism, and ferroelasticity, all of which are gate tunable, demonstrating their promise for fundamental discovery and technological innovation. To fully exploit this richness, it is necessary to understand and control the physics on the smallest scales, making the use of nanoscale probes essential. Using the prototypical LaAlO
3
SrTiO
3
interface as a guide, we explore the exciting developments in the physics of oxide-based heterostructures, with a focus on nanostructures and the nanoscale probes employed to unravel their complex behavior.
Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and ...long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN.
We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with life-threatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)<50 mg/mmol or partial remission (PR) if PCR>50 mg/mmol but non-nephrotic and >50% reduction.
A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4-200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11-58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19-58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20-112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required >2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode.
The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.
Obstructive sleep apnea (OSA) is a serious medical condition with a high prevalence, although diagnosis remains a challenge. Existing home sleep tests may provide acceptable diagnosis performance but ...have shown several limitations. In this retrospective study, we used 12,923 polysomnography recordings from six independent databases to develop and evaluate a deep learning model, called OxiNet, for the estimation of the apnea-hypopnea index from the oximetry signal. We evaluated OxiNet performance across ethnicity, age, sex, and comorbidity. OxiNet missed 0.2% of all test set moderate-to-severe OSA patients against 21% for the best benchmark.
SrTiO3-based heterointerfaces support quasi-two-dimensional (2D) electron systems that are analogous to III–V semiconductor heterostructures, but also possess superconducting, magnetic, spintronic, ...ferroelectric, and ferroelastic degrees of freedom. Despite these rich properties, the relatively low mobilities of 2D complex-oxide interfaces appear to preclude ballistic transport in 1D. Here we show that the 2D LaAlO3/SrTiO3 interface can support quantized ballistic transport of electrons and (nonsuperconducting) electron pairs within quasi-1D structures that are created using a well-established conductive atomic-force microscope (c-AFM) lithography technique. The nature of transport ranges from truly single-mode (1D) to three-dimensional (3D), depending on the applied magnetic field and gate voltage. Quantization of the lowest e 2/h plateau indicate a ballistic mean-free path l MF ∼ 20 μm, more than 2 orders of magnitude larger than for 2D LaAlO3/SrTiO3 heterostructures. Nonsuperconducting electron pairs are found to be stable in magnetic fields as high as B = 11 T and propagate ballistically with conductance quantized at 2e 2/h. Theories of one-dimensional (1D) transport of interacting electron systems depend crucially on the sign of the electron–electron interaction, which may help explain the highly ballistic transport behavior. The 1D geometry yields new insights into the electronic structure of the LaAlO3/SrTiO3 system and offers a new platform for the study of strongly interacting 1D electronic systems.
Genomes and transcriptomes are now typically sequenced by individual laboratories but analyzing them often remains challenging. One essential step in many analyses lies in identifying ...orthologs-corresponding genes across multiple species-but this is far from trivial. The Orthologous MAtrix (OMA) database is a leading resource for identifying orthologs among publicly available, complete genomes. Here, we describe the OMA pipeline available as a standalone program for Linux and Mac. When run on a cluster, it has native support for the LSF, SGE, PBS Pro, and Slurm job schedulers and can scale up to thousands of parallel processes. Another key feature of OMA standalone is that users can combine their own data with existing public data by exporting genomes and precomputed alignments from the OMA database, which currently contains over 2100 complete genomes. We compare OMA standalone to other methods in the context of phylogenetic tree inference, by inferring a phylogeny of Lophotrochozoa, a challenging clade within the protostomes. We also discuss other potential applications of OMA standalone, including identifying gene families having undergone duplications/losses in specific clades, and identifying potential drug targets in nonmodel organisms. OMA standalone is available under the permissive open source Mozilla Public License Version 2.0.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse ...alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.
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Abstract
Objectives
Glucocorticoids (GCs) are a mainstay of treatment for patients with ANCA-associated vasculitis (AAV) but are associated with significant adverse effects. Effective remission ...induction in severe AAV using extremely limited GC exposure has not been attempted. We tested an early rapid GC withdrawal induction regimen for patients with severe AAV.
Methods
Patients with active MPO- or PR3-ANCA vasculitis or ANCA-negative pauci-immune glomerulonephritis were included. Induction treatment consisted of two doses of rituximab, 3 months of low-dose CYC and a short course of oral GC (for between 1 and 2 weeks). Clinical, biochemical and immunological outcomes as well as adverse events were recorded.
Results
A total of 49 patients were included, with at least 12 months of follow-up in 46. All patients achieved remission, with decreases observed in creatinine, proteinuria, CRP, ANCA level and BVAS. Three patients requiring dialysis at presentation became dialysis independent. Two patients required the introduction of maintenance GC for treatment of vasculitis. Overall outcomes were comparable to those of two matched cohorts (n = 172) from previous European Vasculitis Society (EUVAS) trials, but with lower total exposure to CYC and GCs (P < 0.001) and reduced rates of severe infections (P = 0.02) compared with the RITUXVAS (rituximab versus cyclophosphamide in AAV) trial. We found no new cases of diabetes in the first year compared with historic rates of 8.2% from the EUVAS trials (P = 0.04).
Conclusion
Early GC withdrawal in severe AAV is as effective for remission induction as the standard of care and is associated with reduced GC-related adverse events.
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