Pharmacological effects of raas blockade in ischemic nephropathy

Background: The management of ischemic nephropathy due to atherosclerotic renal artery stenosis has become increasingly conservative in the modern era, with current guidelines recommending optimized medical therapy as the initial step. The doubts raised by the recently published trials of revascularization strategies have led to a renewed focus on pharmacological strategies promoting blood pressure control and renal protection. It is essential to further elucidate the pathophysiological mechanisms underlying hypoperfusion induced renal microvascular dysfunction with subsequent tissue injury and fibrogenesis. The role of renin angiotensin aldosterone system as a mediator of the main pathophysiological consequences of ischemic nephropathy is well known. However, more recent experimental evidence on the adrenergic system and intrarenal tubular feedback mechanisms has stimulated new interest towards a multi-target therapeutic approach. Methods: This review focuses on the pharmacology of the principle therapeutic drug classes currently used in the treatment of atherosclerotic renal artery stenosis with an analysis of their metabolic aspects and use in clinical practice based on evidence from clinical trials. Results and Conclusions: An optimal pharmacologic approach is crucial for a successful prevention of renal injury and cardiovascular events in this high-risk population. Antihypertensive treatment should include renin angiotensin aldosterone system blockade medication not only for their antihypertensive properties, but especially for those cardio and renoprotectiv

Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: different effects in different patients populations. Results from a large observational study

Tenofovir alafenamide (TAF) has similar efficacy compared to tenofovir disoproxil fumarate (TDF), but a less favorable effect on lipids. Aim of this study was to evaluate the impact on lipids of switching from rilpivirine (RPV)/ emtricitabine (FTC)/TDF to RPV/FTC/TAF in a large cohort of HIV-1 infected patients

Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/ emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: Different effects in patients with or without baseline hypercholesterolemia

open10noTenofovir alafenamide (TAF) has similar efficacy compared to tenofovir disoproxil fumarate (TDF), but a less favorable effect on lipids. Aim of this retrospective multicentre study was to evaluate the impact on lipids of switching from rilpivirine (RPV)/ emtricitabine (FTC)/TDF to RPV/FTC/TAF in a cohort of HIV-1 infected patients. Total cholesterol (TC), high density lipoproteins (HDL) and low density lipoproteins (LDL) were compared at the moment of the switch and at the first following evaluation, by using paired t-test. Overall, 573 patients were considered, 99% with HIV-RNA <50 copies/ml, with mean age of 49.7 (±0.4) years and median 13.4 (6.9-22.5) years of HIV infection. In the study population with available data (431/573, 75%), mean TC changed from 173 ±1.7 to 188 ±1.8 mg/dl; mean HDL from 46 ±0.7 to 51± 0.7 mg/dl; mean LDL from 111 ±1.5 to 120 ±1.8 mg/dl (p<0.0001 for all). Neither LDL/HDL nor TC/HDL ratio changed significantly, with LDL/HDL from 2.6 ±0.5 to 2.5 ±0.5 (p = 0.12) and TC/HDL from 4.0 ±0.6 to 3.9 ±0.6 (p = 0.11). In patients with baseline diagnosis of hypercholesterolemia (TC>200 mg/dl, N = 87), there was no significant change in TC (224 ±2.2 to 228 ±3.4 mg/dl, p = 0.286) or LDL (150±2.5 to 151±3.2 mg/dl, p = 0.751), while HDL increased from 51 ±1.6 to 55 ±1.7 mg/dl (p<0.0001) and both LDL/HDL and TC/HDL ratio decreased significantly, from 3.2±0.1 to 3.0 ±0.1 (p = 0.025) and from 4.7±0.1 to 4.4 ±0.1 (p = 0.004). In this real life study, a slight increase in lipids was found after switching from RPV/FTC/TDF to RPV/FTC/TAF, but these results were not confirmed in people with hypercholesterolemia, in which lipids did not change and LDL/HDL and TC/HDL ratio decreased.openTaramasso L.; Di Biagio A.; Riccardi N.; Briano F.; Di Filippo E.; Comi L.; Mora S.; Giacomini M.; Gori A.; Maggiolo F.Taramasso, L.; Di Biagio, A.; Riccardi, N.; Briano, F.; Di Filippo, E.; Comi, L.; Mora, S.; Giacomini, M.; Gori, A.; Maggiolo, F

Trend of estimated glomerular flitration rate in a large cohort of HIV mother-to -child infected patients, an observational multicenter study from 2010 to 2018

Background: People vertically infected with HIV (PVI-HIV) are a special population, due to exposition since birth to HIV and antiretroviral therapy (ART). Among ART, Tenofovir disoproxil fumarate (TDF) was widely used in recent years, but there are few data on safety in these patients; in particular, data about estimated glomerular filtration rate (eGFR) trend in this population. Aim of our study is to evaluate eGFR trend in a multicentre cohort of PVI-HIV exposed to TDF

Rs12979860 and rs8099917 single nucleotide polymorphisms of interleukin-28B gene: simultaneous genotyping in Caucasian patients infected with hepatitis C virus

Introduction. Recent studies have demonstrated the role of the interleukin 28B (IL28B) polymorphisms in predicting treatment induced and spontaneous clearance from Hepatitis C virus (HCV) infection, suggesting the possibility of tailored therapy in HCV infected patients. Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) near IL 28B gene on chromosome 19 are strong predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin. This study was aimed at analyzing the co-prevalence of two common and clinically significant SNPs in a cohort of Ligurian patients. Methods. Two SNPs (rs12979860, rs8099917) were genotyped in the IL28B locus from 175 DNA samples collected from HCV- infected consecutive patients in a Laboratory of Liguria Region, northern Italy. A real-time polymerase chain reaction in a Cor- bett Research Termocycler (Rotor Gene 3000A) by fluorescent probes (Fast Set IL 28B©, Arrow Diagnostics) was used for the detection, according to the manufacturer?s instructions. Results. Carriers of rs12979860CT genotype predominated (87/175, 50%), homozygotes for allele C were 68/175 (39%) and the remaining were homozygotes for IFN-resistant allele T (11%). As for the rs8099917 SNP, genotypes were thus distributed: 96/175 (55%) carried the rs8099917 TT genotype, whereas 70/175 (40%) and 9/175 (5%), were heterozygotes or homozygotes for the G allele. The variants rs12979860CC and rs8099917TT were found in 39% and 54% of overall patients with HCV genotype 1, respec- tively. The combined assessment of examined SNPs resulted in three most prevalent genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TG and rs12979860CT/rs8099917TT) with a frequency of 35%, 31% and 18%, respectively. Discussion. Recent findings demonstrated that in carriers of rs12979860CT the determination of additional genotype of rs8099917 SNP could significantly improve the prediction of SVR. In our study cohort carriers of rs12979860CT represented 50% of all patients, who could take advantage with respect to SVR prediction by further determination of the rs8099917 SNP. The simultaneous genotyping of two IL28B SNPs should thus be recommended in HCV infected patients prior to treatment initiation

Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir with or without Ribavirin in Patients with HIV-HCV Coinfection. Real Life Interim Analysis of an Italian Multicentre Compassionate Use Program

Background and Aims: An HCV cure is now possible in a large proportion of HIV-HCV patient. We present real life results of a compassionate use program promoted by SIMIT (Infectious and Tropical Diseases Italian Society) of Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir ± Ribavirin for 12 weeks in 213 HIV-HCV genotype 1 patients. Data on efficacy and tolerability of this strategy in HIV patients have been reported until now only in 43 non cirrhotic HIV subjects

Observations of surface radiation and stratospheric processes at Thule Air Base, Greenland, during the IPY

Ground-based measurements of atmospheric parameters have been carried out for more than 20 years at the Network for the Detection of Atmospheric Composition Change (NDACC) station at Thule Air Base (76.5°N, 68.8°W), on the north-western coast of Greenland. Various instruments dedicated to the study of the lower and middle polar atmosphere are installed at Thule in the framework of a long standing collaboration among Danish, Italian, and US research institutes and universities. This effort aims at monitoring the composition, structure and dynamics of the polar stratosphere, and at studying the Arctic energy budget and the role played by different factors, such as aerosols, water vapour, and surface albedo. During the International Polar Year (IPY), in winter 2008-2009, an intensive measurement campaign was conducted at Thule within the framework of the IPY project “Ozone layer and UV radiation in a changing climate evaluated during IPY” (ORACLE-O3) which sought to improve our understanding of the complex mechanisms that lead to the Arctic stratospheric O3 depletion. The campaign involved a lidar system, measuring aerosol backscatter and depolarization ratios up to 35 km and atmospheric temperature profiles from 25 to 70 km altitude, a ground-based millimeter-wave spectrometer (GBMS) used to derive stratospheric mixing ratio profiles of different chemical species involved in the stratospheric ozone depletion cycle, and then ground-based radiometers and a Cimel sunphotometer to study the Arctic radiative budget at the surface. The observations show that the surface radiation budget is mainly regulated by the longwave component throughout most of the year. Clouds have a significant impact contributing to enhance the role of longwave radiation. Besides clouds, water vapour seasonal changes produce the largest modification in the shortwave component at the surface, followed by changes in surface albedo and in aerosol amounts. For what concerns the middle atmosphere, during the first part of winter 2008-2009 the cold polar vortex allowed for the formation of polar stratospheric clouds (PSCs) which were observed above Thule by means of the lidar. This period was also characterized by GBMS measurements of low values of O3 due to the catalytic reactions prompted by the PSCs. In mid- January, as the most intense Sudden Stratospheric Warming event ever observed in the Arctic occurred, GBMS and lidar measurements of O3, N2O, CO and temperature described its evolution as it propagated from the upper atmosphere to the lower stratosphere

Evidence-based renewal of the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons

The Italian Society for Infectious and Tropical Diseases (SIMIT) in collaboration with the Technical Health Committee (Sections L and M) of the Italian Ministry of Health have supported the renewal of the recommendations for the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. This publication summarizes the latest updates to the 2017 version of the Italian Guidelines for the management of HIV-1 infected patients and the use of antiretroviral drugs. New recommendations were released framing the clinical questions the use of antiretrovirals according to the Patient Intervention Comparator Outcome (PICO) methodology and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Diagnostic tools for immunological and virological monitoring, when to start, what to start, optimization and therapeutic failure were updated in order to include the recommendation obtained with these newly developed methods. For a complete review of clinical and therapeutic relevant topics we refer the reader to the extended version of the Guidelines