In-Hospital and 1-Year Clinical Results from the French Registry Using Polymer-Free Sirolimus-Eluting Stents in Acute Coronary Syndrome and Stable Coronary Artery Disease.

Objectives: The aim of this postmarket clinical study was to assess the safety and efficacy of the latest generation polymer-free sirolimus-eluting stents (PF-SES) in an all-comers population comparing outcomes in stable coronary artery disease (CAD) versus acute coronary syndrome (ACS) in France. Background: The efficacy and safety of the first-generation PF-SES have already been demonstrated by randomized controlled trials and "all-comers" observational studies. Methods: For this all-comers observational, prospective, multicenter study, 1456 patients were recruited in 22 French centers. The primary endpoint was target lesion revascularization (TLR) rate at 12 months and secondary endpoints included major adverse cardiac events (MACE) and bleeding. Results: 895 patients had stable CAD and 561 had ACS. At 12 months, 2% of patients had a TLR, with similar rates between stable CAD and ACS (1.9% vs 2.2%, p = 0.7). The overall MACE rate was 5.2% with an expected higher rate in patients with ACS as compared to those with stable CAD (7.3% vs 3.9%, p = 0.007). The overall bleeding event rate was 4.5%, with similar rates in stable CAD as compared to ACS patients (3.8% vs 5.6%, p = 0.3). Dual antiplatelet therapy (DAPT) interruptions prior to the recommended duration occurred in 41.7% of patients with no increase in MACE rates as compared to patients who did not prematurely interrupt DAPT (3.9% vs 6.1%, p = 0.073). Conclusions: The latest generation PF-SES is associated with low clinical event rates in these all-comers patients. There was a high rate of prematurely terminated DAPT, without any effect on MACE at 12 months. This trial is registered with NCT03809715.

Antimicrobial Susceptibility Profiles and Resistance Genes in Genus Aeromonas spp. Isolated from the Environment and Rainbow Trout of Two Fish Farms in France.

This study presents the occurrence and abundance of Aeromonas antibiotic-resistant bacteria (ARB) and genes (ARGs) isolated from water, biofilm and fish in two commercial trout farms before and one week after flumequine treatment. Wild (WT) and non-wild (NWT) strains were determined for quinolones (flumequine, oxolinic acid and enrofloxacin), oxytetracycline (OXY), florfenicol (FFN), trimethoprim-sulfamethoxazole (TMP) and colistin (COL), and pMAR (presumptive multi-resistant) strains were classified. Forty-four ARGs for the mentioned antibiotics, ß-lactams and multi-resistance were quantified for 211 isolates. BlaSHV-01, mexF and tetE were the dominant ARGs. A greater occurrence and abundance of tetA2, sul3, floR1, blaSHV-01 and mexF were observed for NWT compared to WT. The occurrence of pMAR and NWT Aeromonas for quinolones, OXY, FFN, TMP, COL and ARGs depended on the Aeromonas origin, antibiotic use and the presence of upstream activities. Our results revealed the impact of a flumequine treatment on Aeromonas present on a fish farm through an increase in NWT and pMAR strains. The link between fish and their environment was shown by the detection of identical ARB and ARGs in the two types of samples. There appears to be a high risk of resistance genes developing and spreading in aquatic environments.

Risk of ventricular arrhythmia in patients with myocardial infarction and non-obstructive coronary arteries and normal ejection fraction.

AIM: To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and non-obstructive coronary arteries (MINOCA) with normal ejection fraction (EF). METHODS: This is an observational analysis of 131 MINOCA patients with normal EF. Three cardiac magnetic resonance (CMR) diagnosis classes were recognized according to the late gadolinium enhancement (LGE) pattern: Myocardial infarction (MI) (n = 34), myocarditis (n = 47), and "no LGE" (n = 50). Ventricular events occurring during hospitalization were recorded and the entire population was followed-up at 1 year. RESULTS: Ventricular arrhythmia was observed in 18 (13.8%) patients during hospitalization. The "no LGE" patients experienced fewer ventricular events than the MI and myocarditis patients [4.0% vs 26.5% and 14.9%, respectively (P = 0.013)]. There was no significant difference between the MI and myocarditis groups. On multivariate analysis, LGE transmural extent [OR = 1.52 (1.08-2.15), P = 0.017] and ST-segment elevation [OR = 4.65 (1.61-13.40), P = 0.004] were independent predictors of ventricular arrhythmic events, irrespective of the diagnosis class. Finally, no patient experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year. CONCLUSION: MINOCA patients with normal EF presented no 1-year cardiovascular events, irrespective of the CMR diagnosis class. LGE transmural extent and ST segment elevation at admission are risk markers of ventricular arrhythmia during hospitalization.

Antibiotic exposure and bacterial resistance in human and veterinary medicine: a problem-based learning topic for Master's students.

This report describes a problem-based learning activity concerning antibiotic exposure and bacterial resistance in human and veterinary medicine. In addition, learning outcomes and satisfaction of students were recorded by the supervisors of the activity. The students all participated actively in the group work and considered that the small size of the group facilitated interpersonal communication. They believed that working in an interdisciplinary group helped them learn better than if they were following specific courses. They also reported that their mid-term meeting with one of the supervisors was a catalyst for the initiation of a real work group. Concerning the evaluation of the activity itself, the supervisors considered that the group provided a relevant analysis of the issue. These characteristics should encourage teachers to test this method of learning certain aspects of microbiology and infectious diseases with their students.

Widespread occurrence of chemical residues in beehive matrices from apiaries located in different landscapes of Western France.

BACKGROUND: The honey bee, Apis mellifera, is frequently used as a sentinel to monitor environmental pollution. In parallel, general weakening and unprecedented colony losses have been reported in Europe and the USA, and many factors are suspected to play a central role in these problems, including infection by pathogens, nutritional stress and pesticide poisoning. Honey bee, honey and pollen samples collected from eighteen apiaries of western France from four different landscape contexts during four different periods in 2008 and in 2009 were analyzed to evaluate the presence of pesticides and veterinary drug residues. METHODOLOGY/FINDINGS: A multi-residue analysis of 80 compounds was performed using a modified QuEChERS method, followed by GC-ToF and LC-MS/MS. The analysis revealed that 95.7%, 72.3% and 58.6% of the honey, honey bee and pollen samples, respectively, were contaminated by at least one compound. The frequency of detection was higher in the honey samples (n = 28) than in the pollen (n = 23) or honey bee (n = 20) samples, but the highest concentrations were found in pollen. Although most compounds were rarely found, some of the contaminants reached high concentrations that might lead to adverse effects on bee health. The three most frequent residues were the widely used fungicide carbendazim and two acaricides, amitraz and coumaphos, that are used by beekeepers to control Varroa destructor. Apiaries in rural-cultivated landscapes were more contaminated than those in other landscape contexts, but the differences were not significant. The contamination of the different matrices was shown to be higher in early spring than in all other periods. CONCLUSIONS/SIGNIFICANCE: Honey bees, honeys and pollens are appropriate sentinels for monitoring pesticide and veterinary drug environmental pollution. This study revealed the widespread occurrence of multiple residues in beehive matrices and suggests a potential issue with the effects of these residues alone or in combination on honey bee health.

Bees, honey and pollen as sentinels for lead environmental contamination.

Three beehive matrices, sampled in eighteen apiaries from West France, were analysed for the presence of lead (Pb). Samples were collected during four different periods in both 2008 and 2009. Honey was the matrix the least contaminated by Pb (min = 0.004 µg g(-1); max = 0.378 µg g(-1); mean = 0.047 µg g(-1); sd = 0.057). The contamination of bees (min = 0.001 µg g(-1); max = 1.869 µg g(-1); mean = 0.223 µg g(-1); sd = 0.217) and pollen (min = 0.004 µg g(-1); max = 0.798 µg g(-1); mean = 0.240 µg g(-1); sd = 0.200) showed similar levels and temporal variations but bees seemed to be more sensitive bringing out the peaks of Pb contamination. Apiaries in urban and hedgerow landscapes appeared more contaminated than apiaries in cultivated and island landscapes. Sampling period had a significant effect on Pb contamination with higher Pb concentrations determined in dry seasons.

Polycyclic aromatic hydrocarbons: bees, honey and pollen as sentinels for environmental chemical contaminants.

Three beehive matrices, sampled in six different apiaries from West France, were analyzed for the presence of four polycyclic aromatic hydrocarbons (PAH4: benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene and chrysene). Samples were collected during four different periods in both 2008 and 2009. Honey samples showed the lowest levels of PAH4 contamination (min=0.03 µg kg(-1); max=5.80 µg kg(-1); mean=0.82 µg kg(-1); Sd=1.17). Bee samples exhibited higher levels of PAH4 contamination (min=0.32 µg kg(-1); max=73.83 µg kg(-1); mean=7.03 µg kg(-1); Sd=17.83) with a great dispersion of the concentrations due to four main events of high concentrations. Pollen samples showed only one major episode with the highest PAH4 concentration found (min=0.33 µg kg(-1); max=129.41 µg kg(-1); mean=7.10 µg kg(-1); Sd=22.28). The PAH4 concentrations found were significantly influenced by the landscape context for all beehive samples.

Multi-residue analysis of 80 environmental contaminants in honeys, honeybees and pollens by one extraction procedure followed by liquid and gas chromatography coupled with mass spectrometric detection.

One of the factors that may explain nowadays honeybees' colonies losses is the increasing presence of chemicals in the environment. The aim of this study is to obtain a global view of the presence of environmental contaminants in beehives and, develop a fast, cheap and sensitive tool to analyze environmental contaminants in apiarian matrices. A multi residue analysis was developed to quantify 80 environmental contaminants, pesticides and veterinary drugs, belonging to different chemical classes, in honeys, honeybees and pollens. It consists in a single extraction, based on a modified "QuEChERS method", followed by gas chromatography coupled with Time of Flight mass spectrometry (GC-ToF) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The "QuEChERS method" combines salting-out liquid-liquid extraction with acetonitrile and a dispersive-SPE clean up. It was adjusted to honey and especially to honeybee and pollen, by adding a small fraction of hexane in acetonitrile to eliminate lipids that interfere with mass spectrometry analysis. This method, combined with accurate and sensitive detection, allowed quantification and confirmation at levels as low as 10 ng/g, with recoveries between 60 and 120%. Application to more than 100 samples of each matrix was achieved for a global view of pesticide presence in the honeybee environment. Relatively high percentages of honeys, honeybees and pollens were found to be contaminated by pesticides used to combat varroa but also by fungicides like carbendazim and ubiquitous contaminants.

Comparison of water, sediment, and plants for the monitoring of antibiotics: a case study on a river dedicated to fish farming.

Oxolinic acid, flumequine, oxytetracycline, and florfenicol are antibiotics commonly used in farming. Because an important percentage of these antibiotics given to fish and cattle ends up, directly or indirectly, in the freshwater environment, suitable tools for the monitoring of these antibiotics are needed. A French river was chosen because of the location of four fish farms and a sewage plant on its main course. First, a passive monitoring program involving water, sediment, and autochthonous bryophytes was performed at 25 sampling sites tested once every three months for one year. Second, an active monitoring method was performed using moss bags for a one-month exposure period, both upstream and downstream of each potential source of antibiotics. Sediment and bryophyte samples, but not water samples, were found to be useful for monitoring environmental contamination by oxolinic acid, flumequine, oxytetracycline, and florfenicol. Sediments and bryophytes also appeared to be complementary media for dating the river's contamination by antibiotics. Data collected by both active and passive monitoring methods confirmed contamination of the river, mainly by flumequine and oxytetracycline, attributable to fish farming but also to terrestrial animal farming and perhaps human pharmaceuticals.

Survey of antibiotic resistance in an integrated marine aquaculture system under oxolinic acid treatment.

The consequences of antibiotic use in aquatic integrated systems, which are based on trophic interactions between different cultured organisms and physical continuity through water, need to be examined. In this study, fish reared in a prototype marine integrated system were given an oxolinic acid treatment, during and after which the level of resistance to this quinolone antibiotic was monitored among vibrio populations from the digestive tracts of treated fish, co-cultured bivalves and sediments that were isolated on thiosulfate-citrate-bile-sucrose. Oxolinic acid minimum inhibitory concentration distributions obtained from replica plating of thiosulfate-citrate-bile-sucrose plates indicated that a selection towards oxolinic acid resistance had occurred in the intestines of fish under treatment. In contrast, and despite oxolinic acid concentrations higher than minimum inhibitory concentrations of susceptible bacteria, no clear evolution of resistance levels was detected either in bivalves or in sediments.

The bryophyte Fontinalis antipyretica Hedw. bioaccumulates oxytetracycline, flumequine and oxolinic acid in the freshwater environment.

In recent years, the fate of pharmacological substances in the aquatic environment have been more and more studied. Oxolinic acid (OA), flumequine (FLU) and oxytetracycline (OTC) are commonly used antibacterial agents. A large amount of these drugs is released into water directly by dissolved fraction and indirectly in urine and feces. Monitoring these compounds in the freshwater environment is difficult because of the lack of suitable indicators. The aim of this work was to evaluate the OA, FLU and OTC bioaccumulation abilities of Fontinalis antipyretica Hedw., known for heavy metal bioaccumulation. The experiment described was decomposed for two times: a 10-days accumulation period during which bryophytes were in contact with antibiotics and a 15-days post-exposure period during which bryophytes were in water with no antibiotic. This experiment showed that this bryophyte strongly accumulates OA, FLU and OTC in freshwater. Bioaccumulation factors (ratio of concentrations in bryophyte and water) ranged between 75 and 450. Moreover, OA, FLU and OTC persisted in the bryophyte for a long time with clearance between 0.19 and 3.04 ng/g/day. Mean residence times ranged between 18 and 59 days. Accumulation and decontamination mechanism models were proposed.

Experimental study on the bioaccumulation of oxytetracycline and oxolinic acid by the blue mussel (Mytilus edulis). An evaluation of its ability to bio-monitor antibiotics in the marine environment.

The ability of blue mussel (Mytilus edulis) to act as a potential antibiotic bioindicator in marine waters was experimentally tested by the study of the kinetics of two veterinary antibiotics (oxolinic acid: OA and oxytetracycline: OTC). Antibiotic uptake was fast in the soft parts of the mussels. OA was quickly eliminated while OTC was released more slowly (half-life in viscera=3.9 days). OA and OTC were preferentially accumulated in gills and in viscera, respectively. Bio-accumulation factors were low (maximum: 2 for OTC in viscera) in accordance with the low K(ow)s. It was assumed that the higher OTC bioaccumulation pattern was related to its binding to mineral and organic compounds that led to its activity inhibition (62%). The antibiotics were persistent in shells (OTC half-life=8.3 days). Most veterinary and human antibiotics such as tetracyclines and sulphonamides have low log K(ow)(<2) and should weakly accumulate in mussel. This might limit the use of blue mussel to bio-monitor antibiotics in the marine environment.

Determination of oxolinic acid in the bryophyte Fontinalis antipyretica by liquid chromatography with fluorescence detection.

A large amount of oxolinic acid administered in freshwater fish farms reaches the environment. In order to allow environmental monitoring, an HPLC method to determine oxolinic acid in the bryophyte Fontinalis antipyretica was developed. Nalidixic acid was used as an internal standard. Oxolinic and nalidixic acids were extracted by cracking the bryophytes in liquid nitrogen with 0.1 M acid oxalic solution in ethyl acetate and a liquid-liquid clean up procedure was then performed. Mobile phase was a 0.02 M orthophosphoric acid aqueous solution-acetonitrile mixture (70:30, v/v). The stationary phase was 5 microm PuroSpher RP18e and quinolones were detected by fluorescence. The linearity, accuracy and precision of this method were demonstrated by a validation assay. The limits of detection and quantitation were 1 and 10 ng/g respectively. The linearity range was 10 to 500 ng/g. This method was applied to a 25 days experimental study performed with the bryophyte Fontinalis antipyretica.