In high-income countries, causes of death in people living with HIV (PLHIV) have changed. Three French national surveys from 2000 to 2010 showed a decrease in AIDS-related and an increase in ...non-AIDS-related deaths. Deaths notified in PLHIV followed between January 1, 2011 and December 31, 2015 in 1 of 13 participating hospitals northeast of Paris area were described. Risk factors for death were assessed, using a multivariable logistic regression model. Of 14,403 individuals, 295 died. Median age at death was 52 years (interquartile range = 47-60) and 77% were men. Sixty-seven individuals (23%) died from non-AIDS-defining nonviral hepatitis-related (NaNH) malignancy, 40 (14%) from AIDS, 34 (12%) from cardiovascular disease (CVD), 33 (11%) from non-AIDS infection, 21 (7%) from liver disease, and 12 (4%) from suicide. Men and women born in sub-Saharan Africa had a lower adjusted odds ratio (aOR) of dying than men having sex with men (MSM) born in France (0.70, 95% confidence interval = 0.45-1.09; and 0.45, 0.28-0.73, respectively). Risk factors for death were older age (aOR = 2.26, 1.36-3.77 for 40-49 years and 2.91, 1.75-4.84 for >50 years vs. 18-39 years), male intravenous drug users (IVDU) transmission (2.24, 1.42-3.54 vs. MSM born in France), AIDS (2.75, 2.10-3.59), antiretroviral therapy initiation in earlier periods, time since HIV diagnosis <1 year, low CD4 cell count nadir, hepatitis B virus and/or hepatitis C virus coinfection (1.69, 1.23-2.30), and psychiatric disorders (1.73, 1.27-2.38). Our study confirms the increasing frequency of non-AIDS-related deaths, mainly NaNH malignancies and CVD, in PLHIV, justifying overall and in some specific populations (psychiatric and IVDU) prevention and screening.
Objectives
The aim of the study was to assess whether the timing of combination antiretroviral therapy (cART) initiation, the choice of cART and virological response differ in migrants versus ...European natives in the north and east of Paris area, after dissemination of French recommendations for universal treatment.
Methods
Antiretroviral therapy‐naïve HIV‐1‐infected adults with at least two follow‐up visits at one of 15 participating centres between 1 January 2014 and 31 March 2015 were included in the study. Factors associated with cART initiation before 31 March 2015, with protease inhibitor (PI)‐containing cART among individuals initiating cART, and with 1‐year virological success after cART initiation were assessed using multivariable logistic regression models. Sex, age, region of origin Western Europe, sub‐Saharan Africa (SSA) or other, HIV transmission group, baseline AIDS status, CD4 cell count and plasma viral load (VL), and hepatitis B and/or C virus infection were considered in the analyses.
Results
Among 912 individuals, only 584 (64%) started cART during the study period. After adjustment, migrants from SSA were half as likely to initiate cART and to have a subsequent virological response compared with individuals from Western Europe adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36–0.82; and aOR 0.52; 95% CI 0.28–0.98, respectively. PI‐containing cART was more frequently prescribed in migrants from SSA, in people with lower CD4 cell counts and in people with higher VL.
Conclusions
Even in the context of universal cART recommendations and of free access to care, migrants from SSA still have delayed access to cART and a lower virological response. Efforts are still necessary to provide immediate cART to all people living with HIV.
Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant ...mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59 multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and de novo events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology.
Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive ...symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD.
Purpose
Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to ...postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO.
Methods
This retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT.
Results
A total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% 95% CI 0.21–0.52). Fourteen of 39 patients (35.9% 20.8–50.9) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (
p
= 0.073). The platelet course was similar between Confirmed and Excluded HIT (
p
= 0.65). Mortality rate was 33.3% 13.2–53.5 in Confirmed and 50% 23.8–76.2 in Excluded HIT (
p
= 0.48).
Conclusions
Prevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.
Intensive care unit (ICU)-acquired weakness often develops in patients who are undergoing invasive mechanical ventilation. Early active mobilization may mitigate ICU-acquired weakness, increase ...survival, and reduce disability.
We randomly assigned 750 adult patients in the ICU who were undergoing invasive mechanical ventilation to receive increased early mobilization (sedation minimization and daily physiotherapy) or usual care (the level of mobilization that was normally provided in each ICU). The primary outcome was the number of days that the patients were alive and out of the hospital at 180 days after randomization.
The median number of days that patients were alive and out of the hospital was 143 (interquartile range, 21 to 161) in the early-mobilization group and 145 days (interquartile range, 51 to 164) in the usual-care group (absolute difference, -2.0 days; 95% confidence interval CI, -10 to 6; P = 0.62). The mean (±SD) daily duration of active mobilization was 20.8±14.6 minutes and 8.8±9.0 minutes in the two groups, respectively (difference, 12.0 minutes per day; 95% CI, 10.4 to 13.6). A total of 77% of the patients in both groups were able to stand by a median interval of 3 days and 5 days, respectively (difference, -2 days; 95% CI, -3.4 to -0.6). By day 180, death had occurred in 22.5% of the patients in the early-mobilization group and in 19.5% of those in the usual-care group (odds ratio, 1.15; 95% CI, 0.81 to 1.65). Among survivors, quality of life, activities of daily living, disability, cognitive function, and psychological function were similar in the two groups. Serious adverse events were reported in 7 patients in the early-mobilization group and in 1 patient in the usual-care group. Adverse events that were potentially due to mobilization (arrhythmias, altered blood pressure, and desaturation) were reported in 34 of 371 patients (9.2%) in the early-mobilization group and in 15 of 370 patients (4.1%) in the usual-care group (P = 0.005).
Among adults undergoing mechanical ventilation in the ICU, an increase in early active mobilization did not result in a significantly greater number of days that patients were alive and out of the hospital than did the usual level of mobilization in the ICU. The intervention was associated with increased adverse events. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; TEAM ClinicalTrials.gov number, NCT03133377.).
Under wintertime quiescent conditions, thermally driven circulations represent one of the only sources of tracer dispersion over mountainous terrain. Those circulations can be unequally developed at ...a valley scale since they strongly depend on local morphological arrangement. At the same time, very heterogeneous pollutant distribution can be observed, as for instance in a French Alpine basin located in the Arve River valley. This complex basin regularly shows large variations in pollutant concentrations with certain sectors suffering from poor wintertime air quality. On the other hand, the surrounding tributary valleys appear to be less affected, suggesting that the basin local dynamics may participate in pollutant trapping. The present study intends to classify the pollutant transport mechanisms in terms of efficiency and to identify the most dynamically vulnerable atmospheric volumes regarding pollutant accumulation. This is achieved through a set of semi‐idealized high‐resolution numerical simulations reproducing a full diurnal cycle with passive tracers released continuously at a constant rate. The model is used as a laboratory in order to quantify the influence of several processes on transport mechanism efficiency. This approach underlines the high efficiency of vertical transport by anabatic winds while horizontal transport efficiency by up‐valley wind systems remains weak, leaving the surrounding tributary valleys almost unaffected by the basin pollution during daytime. At night, the efficiency of horizontal transport by the down‐valley wind systems depends on the tracer source location within the basin. In addition, the tracers emitted within the tributary valleys do not reach the basin bottom because of thermal stratification and local morphological arrangement but rather degrade the air quality of mid‐altitude villages lying along the basin sidewalls.
The transport of pollutants in an Alpine valley strongly depends on the local orography surrounding the emission sources. This local dependence may lead to very heterogeneous pollutant distribution over restricted areas, as is currently observed within a semi‐enclosed basin located in the French Alps. A passive tracer tracking is performed from high‐resolution mesoscale simulations in order to identify the most effective transport mechanisms and the most dynamically vulnerable atmospheric volumes regarding pollutant accumulation.
Abstract
Lactation, feeding conditions, microbial interventions and piglet growth in the first few weeks of life have important impact on the intestinal microbiota establishment and immune system ...development of piglets. Indeed, colostrum and milk contain various bioactive components such as immune factors, antimicrobial peptides and oligosaccharides that contribute to maintain intestinal homeostasis and regulate interactions between microbiota and host immune system. Recent results revealed that low birth weight piglet (LBWP) with poor weight gain during the first two weeks of life develop different intestinal microbiota and immune response profiles compared to high BWP (HBWP) littermates. Consequently, piglets within litters may have different resilience to infections after weaning and benefit from feed additives in a specific manner. A study has been performed to evaluate the potential of bovine colostrum extract (BC) as replacement to plasma proteins for improving gut health and resilience to Salmonella infection in piglets. Results revealed that in weaned piglets fed BC, intestinal microbiota was differently modulated and bacterial dysbiosis induced by Salmonella was restored faster. Moreover, expression of genes involved in innate immunity such as β-defensin-2 and glutathione peroxidase-2 was respectively down- and up-regulated in BC fed piglets. A combination of dietary supplementation with BC, cupper and vitamins A and D has also been tested in LBWP and HBWP, and there is clear evidence that BC in combination with other feed additives promote growth and gut health in both LBWP and HBWP. The porcine intestinal epithelial cell line IPEC-J2 was used to better understand the functional properties of BC. Results indicated that BC improves wound healing, enhances barrier function and modulates the expression of several genes involved in innate immune response. Finally, as microbial intervention, the potential of fecal transplantation to modulate intestinal microbiota and immune system development of piglets is under investigation and will be discussed.
Mountainous terrains are known for driving their own dynamics which respond to the local morphological arrangement of the area. Thermally driven flows in particular develop at slope and valley scales ...and ensure a certain degree of pollutant dispersion under quiescent wintertime synoptic conditions. The present study focuses on a section of the Arve River valley situated close to Mont Blanc which frequently suffers from severe pollution episodes under stable wintertime conditions whilst surrounding valleys appear to be less affected. The particular shape of this basin‐like section and its location at the confluence of several tributary valleys raises the question of the extent to which local circulations participate in pollutant trapping over restricted sectors. A set of high‐resolution numerical simulations are designed in order to improve our understanding of the local flow structure and their sensitivity to thermal stratification, radiative forcing and snow cover. The tributary valleys play a major role in both daytime and night‐time dynamics by deflecting the entering daytime flux and constraining the night‐time flow trajectories. In addition, the basin morphology greatly influences the circulations. During daytime a two‐layer wind structure is developed and driven by spatial variations in sun exposure which is particularly heterogeneous under wintertime forcing. Early spring radiative forcing or the presence of snow allow both of them to develop more homogeneous circulations through the reduction of sun exposure variations, except when snow cover is restricted to shaded basin sidewalls. At night, a three‐layer wind structure is developed. It favours air mass ventilation in the western linear branch of the basin whilst stagnation and recirculation prevail in the curved part of the valley which is also the most polluted. This study therefore highlights spatial variations in circulation patterns consistent with the accumulation of observed pollutants and their heterogeneous distribution.
Local thermally driven circulations play a major role in Alpine valleys by representing one of the only sources for pollutant dispersion under stratified wintertime conditions. The study focuses on the slope‐ and valley‐scale flows developed within a complex Alpine basin associated with poor air quality. The origins of the flows along with their sensitivity to several processes are characterized from a set of high‐resolution numerical simulations run in a semi‐idealized framework which is based on the Passy‐2015 field experiment.
Lactation, feeding conditions, microbial interventions and piglet growth in the first few weeks of life have important impact on the intestinal microbiota establishment and immune system development ...of piglets. Indeed, colostrum and milk contain various bioactive components such as immune factors, antimicrobial peptides and oligosaccharides that contribute to maintain intestinal homeostasis and regulate interactions between microbiota and host immune system. Recent results revealed that low birth weight piglet (LBWP) with poor weight gain during the first two weeks of life develop different intestinal microbiota and immune response profiles compared to high BWP (HBWP) littermates. Consequently, piglets within litters may have different resilience to infections after weaning and benefit from feed additives in a specific manner. A study has been performed to evaluate the potential of bovine colostrum extract (BC) as replacement to plasma proteins for improving gut health and resilience to Salmonella infection in piglets. Results revealed that in weaned piglets fed BC, intestinal microbiota was differently modulated and bacterial dysbiosis induced by Salmonella was restored faster. Moreover, expression of genes involved in innate immunity such as ß-defensin-2 and glutathione peroxidase-2 was respectively down- and up-regulated in BC fed piglets. A combination of dietary supplementation with BC, cupper and vitamins A and D has also been tested in LBWP and HBWP, and there is clear evidence that BC in combination with other feed additives promote growth and gut health in both LBWP and HBWP. The porcine intestinal epithelial cell line IPEC-J2 was used to better understand the functional properties of BC. Results indicated that BC improves wound healing, enhances barrier function and modulates the expression of several genes involved in innate immune response. Finally, as microbial intervention, the potential of fecal transplantation to modulate intestinal microbiota and immune system development of piglets is under investigation and will be discussed.
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