Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Co-culture of Methanobrevibacter smithii with enterobacteria during urinary infection

International audienc

Hepatitis Rebound after Infection with Yellow Fever Virus

In 2018, yellow fever with hepatitis was diagnosed for 2 unvaccinated travelers returning to France from Brazil. Hepatitis persisted for >6 months; liver enzyme levels again increased 2 months after disease onset with no detection of yellow fever virus RNA or other pathogens. Persistent hepatitis with hepatic cytolysis rebound probably resulted from immune response

Humoral response after mRNA COVID-19 primary vaccination and single booster dose in people living with HIV compared to controls: a French nationwide multicenter cohort study - ANRS0001s COV-POPART

International audienceBACKGROUND: This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in PWH and HIV-negative individuals. METHODS: We included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (< 200/mm(3) and ≥ 200/mm(3) CD4 cell counts) at 1, 6 and 12 months after primary vaccination. RESULTS: A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm(3)) and 1092 controls. At 1 month, after adjustment on age, sex and BMI, PWH had lower seroneutralization titers than controls and PWH with < 200 CD4 cell/mm3 had lower anti- Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months post primary vaccination, we did not observe differences between PWH and controls at 12 months. CONCLUSION: PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after six months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline

Violencia y transiciones políticas a finales del siglo XX

Las últimas décadas del siglo XX corresponden a lo que Huntington definió como la «tercera ola» de democratización, que comienza en el sur de Europa en la década de los 70, continúa con los países latinoamericanos en los años 80 y en los del este europeo post-comunista en los años 90. Entre las cuestiones generadas por el surgimiento de estas democracias, el problema de la gestión de la violencia pasada (la de la dictadura), presente (la de la transición) y futura (la de la democracia restaurada o consolidada) aparece primordial. Al final del siglo XX, la democracia aparece tanto como un régimen-emancipación que como un régimen-refugio capaz de proteger los derechos humanos ante la tentación monopolística del Estado. La tradicional oposición entre violencia y democracia adquiere un sentido más fuerte puesto que se trata de pacif car un país devastado por el empleo institucionalizado de la violencia. Pero, ¿se puede identif car en la práctica de las transiciones la utopía de una democracia que libera del mal de la violencia política? ¿Cuáles son los mecanismos para la desaparición de la violencia, la gestión de los conf ictos pasados y la consolidación de la pacif cación? ¿En qué sentido se entiende la pervivencia de algunas formas de violencia? Estos son los principales interrogantes que recorren esta obra

High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019

International audienceBackgroundRecent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID‐19) infection. This characteristic is unusual and seems specific to COVID‐19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID‐19 infections.Methods and ResultsIn 89 consecutive patients hospitalized for COVID‐19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D‐dimer, fibrinogen, or CRP (C‐reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality.ConclusionsWe assess a high prevalence of positive tests detecting thrombophilia in COVID‐19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID‐19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID‐19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition

The global distribution of tetrapods reveals a need for targeted reptile conservation

The distributions of amphibians, birds and mammals have underpinned global and local conservation priorities, and have been fundamental to our understanding of the determinants of global biodiversity. In contrast, the global distributions of reptiles, representing a third of terrestrial vertebrate diversity, have been unavailable. This prevented the incorporation of reptiles into conservation planning and biased our understanding of the underlying processes governing global vertebrate biodiversity. Here, we present and analyse the global distribution of 10,064 reptile species (99% of extant terrestrial species). We show that richness patterns of the other three tetrapod classes are good spatial surrogates for species richness of all reptiles combined and of snakes, but characterize diversity patterns of lizards and turtles poorly. Hotspots of total and endemic lizard richness overlap very little with those of other taxa. Moreover, existing protected areas, sites of biodiversity significance and global conservation schemes represent birds and mammals better than reptiles. We show that additional conservation actions are needed to effectively protect reptiles, particularly lizards and turtles. Adding reptile knowledge to a global complementarity conservation priority scheme identifies many locations that consequently become important. Notably, investing resources in some of the world’s arid, grassland and savannah habitats might be necessary to represent all terrestrial vertebrates efficiently