Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

<p>Abstract</p> <p>Background</p> <p>Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).</p> <p>Methods</p> <p>Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.</p> <p>Results</p> <p>Forty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m²at baseline to 128.9 after 2 years (<it>p </it>= 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (<it>p </it>= 0.0003) and in TDF+PI group (<it>p </it>= 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.</p> <p>Conclusions</p> <p>Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.</p

Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (-6.60 [-7.70, -5.50] vs. -0.34 [-0.43, -0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy

Calcineurin-Inhibitor Minimization in Liver Transplant Patients with Calcineurin-Inhibitor-Related Renal Dysfunction: A Meta-Analysis

BACKGROUND: Introduction of calcineurin-inhibitor (CNI) has made transplantation a miracle in the past century. However, the side effects of long-term use of CNI turn out to be one of the major challenges in the current century. Among these, renal dysfunction attracts more and more attention. Herein, we undertook a meta-analysis to evaluate the efficacy and safety of calcineurin-inhibitor (CNI) minimization protocols in liver transplant recipients with CNI-related renal dysfunction. METHODS: We included randomized trials with no year and language restriction. All data were analyzed using random effect model by Review Manager 5.0. The primary endpoints were glomerular filtration rate (GFR), serum creatinine level (sCr) and creatinine clearance rate (CrCl), and the secondary endpoints were acute rejection episodes, incidence of infection and patient survival at the end of follow-up. RESULTS: GFR was significantly improved in CNI minimization group than in routine CNI regimen group (Z = 5.45, P<0.00001; I(2) = 0%). Likely, sCr level was significantly lower in the CNI minimization group (Z = 2.84, P = 0.005; I(2) = 39%). However, CrCl was not significantly higher in the CNI minimization group (Z = 1.59, P = 0.11; I(2) = 0%). Both acute rejection episodes and patient survival were comparable between two groups (rejection: Z = 0.01, P = 0.99; I(2) = 0%; survival: Z = 0.28, P = 0.78; I(2) = 0%, respectively). However, current CNI minimization protocols may be related to a higher incidence of infections (Z = 3.06, P = 0.002; I(2) = 0%). CONCLUSION: CNI minimization can preserve or even improve renal function in liver transplant patients with renal impairment, while sharing similar short term acute rejection rate and patient survival with routine CNI regimen

Distributed evolutionary algorithms and their models: A survey of the state-of-the-art

The increasing complexity of real-world optimization problems raises new challenges to evolutionary computation. Responding to these challenges, distributed evolutionary computation has received considerable attention over the past decade. This article provides a comprehensive survey of the state-of-the-art distributed evolutionary algorithms and models, which have been classified into two groups according to their task division mechanism. Population-distributed models are presented with master-slave, island, cellular, hierarchical, and pool architectures, which parallelize an evolution task at population, individual, or operation levels. Dimension-distributed models include coevolution and multi-agent models, which focus on dimension reduction. Insights into the models, such as synchronization, homogeneity, communication, topology, speedup, advantages and disadvantages are also presented and discussed. The study of these models helps guide future development of different and/or improved algorithms. Also highlighted are recent hotspots in this area, including the cloud and MapReduce-based implementations, GPU and CUDA-based implementations, distributed evolutionary multiobjective optimization, and real-world applications. Further, a number of future research directions have been discussed, with a conclusion that the development of distributed evolutionary computation will continue to flourish

Intensive care of the cancer patient: recent achievements and remaining challenges

A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of patients with solid and hematological malignancies benefit from intensive care support, with dramatically decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation (BMT) have less adverse prognostic implications than two decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill patients with cancer, we outline an easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to patients with cancer who can benefit. Lastly, we propose a research agenda to address unanswered questions

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

Hybridation de métaheuristiques pour la résolution distribuée de problèmes d'optimisation spatialisés

Les problèmes d'optimisation spatialisés font intervenir des entités (clients, demandes, trafic) réparties sur une étendue (la donnée) et des dispositifs physiques (antennes, véhicules) qui doivent leur être associés de manière optimale. Il en résulte de nombreux problèmes d'optimisation combinatoire difficile à résoudre (NP-hard). Pour résoudre ce type de problème, nous proposons des algorithmes à structure intermédiaire, des recherches locales et des approches de résolution collective selon des métaphores de systèmes naturels et biologiques. Le but est par exemple de prendre en compte dès le départ la potentialité d'application à des problèmes dynamiques, de fournir un canevas à la mise en œuvre distribuée possible des algorithmes, et de résoudre des problèmes de grandes tailles