domain: phys sdu

text:
Laurence Lemelle
email: laurence.lemelle@ens-lyon.fr

Eléonore Mottin

Denis Le Tourneau

Sébastien Rouquette

Lucie Campagnolo

Cécile Thévenot

Alain Maillet

Sébastien Barde

Emmanuel Garre

Jérémie Teisseire

Thierry Dufour

Adriana Blachowicz

Christophe Place
email: christophe.place@ens-lyon.fr

Caroline Fontelaye

Vincent Jousseaume

Catherine Pudda

Olivier Constantin

Pierre Marcoux

Guillaume Nonglaton

Three campaigns of MATISS: multi-months experiments of surface contamination in the Columbus Module (ISS)

Keywords: life support, biomaterials, space applications, space habitation, earth applications, astrobiology, surface biocontamination

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

International space agencies are diligently striving to enhance manned spaceflight capabilities for prolonged durations, encompassing missions to diverse destinations, including low Earth orbit (LEO), cis-lunar space, the lunar surface, and ultimately Mars [START_REF] James | Aerospace toxicology and microbiology[END_REF][START_REF] Ott | Space habitation and microbiology: status and roadmap of space agencies[END_REF]ISECG, 2018;[START_REF] Salmela | Measurement and simulation of biocontamination in an enclosed habitat[END_REF]. However, the potential biocontamination of enclosed habitats by the microflora carried by the crew presents a significant and unavoidable concern [START_REF] Yamaguchi | Microbial monitoring of crewed habitats in space-current status and future perspectives[END_REF][START_REF] Santomartino | No effect of microgravity and simulated mars gravity on final bacterial cell concentrations on the international space station: applications to space bioproduction[END_REF]. The extended periods of isolation and dependence on closed-loop life support systems [START_REF] Baranov | Main results of the biorisk experiment on the international space station[END_REF] in manned stations further amplify this risk. The presence of biocontamination in the cabin not only poses threats to the health of astronauts but also entails potential damage to critical equipment [START_REF] Ichijo | Fouryear bacterial monitoring in the international space station-Japanese experiment module "kibo" with culture-independent approach[END_REF][START_REF] Farkas | Effects of spaceflight on human skin[END_REF]. Over time, microorganisms have the capacity to develop resistance, mutate, and increase their virulence, thus transforming benign microbes into pathogenic agents due to the immune system disruptions experienced in space [START_REF] Jorgensen | Development of an antimicrobial susceptibility testing method suitable for performance during space flight[END_REF][START_REF] Wilson | Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq[END_REF][START_REF] Wilson | Media ion composition controls regulatory and virulence response of Salmonella in spaceflight[END_REF][START_REF] Tirumalai | The adaptation of escherichia coli cells grown in simulated microgravity for an extended period is both phenotypic and genomic[END_REF][START_REF] Zea | Phenotypic changes exhibited by E. coli cultured in space[END_REF][START_REF] Huang | Effects of spaceflight and simulated microgravity on microbial growth and secondary metabolism[END_REF][START_REF] Mukhopadhyay | A microgravity responsive synthetic genetic device in Escherichia coli[END_REF][START_REF] Fajardo-Cavazos | Mechanotransduction in prokaryotes: A possible mechanism of spaceflight adaptation[END_REF]. Consequently, it is imperative to effectively mitigate these risks [START_REF] Siegel | Guideline for isolation precautions: preventing transmission of infectious agents in health care settings[END_REF].

The transmission of pathogens through the air and water present on spacecraft is a critical concern [START_REF] Novikova | Review of the knowledge of microbial contamination of the Russian manned spacecraft[END_REF][START_REF] Novikova | Survey of environmental biocontamination on board the international space station[END_REF][START_REF] Ichijo | Bacterial monitoring with adhesive sheet in the international space station-"Kibo", the Japanese experiment module[END_REF][START_REF] Lang | A microbial survey of the international space station (ISS)[END_REF][START_REF] Acres | The influence of spaceflight and simulated microgravity on bacterial motility and chemotaxis[END_REF]. To ensure safety, filtration systems play a vital role in purifying these elements and undergo regular monitoring [START_REF] Ott | Microbial characterization of free floating condensate aboard the Mir Space Station[END_REF][START_REF] Smirnov | Computational fluid dynamics study of air flow characteristics in the columbus module[END_REF][START_REF] Balistreri | International space station common cabin air assembly condensing heat exchanger hydrophilic coating operation, recovery, and lessons learned[END_REF]. Surfaces within the spacecraft harbor a diverse range of microorganisms that can act as sources of infection and contribute to pathogen transmission [START_REF] Otter | The role played by contaminated surfaces in the transmission of nosocomial pathogens[END_REF][START_REF] Weber | The role of the surface environment in healthcare-associated infections[END_REF][START_REF] Otter | Transmission of sars and mers coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination[END_REF][START_REF] Zea | Design of a spaceflight biofilm experiment[END_REF][START_REF] Vaishampayan | Multi-resistant biofilm-forming pathogens on the international space station[END_REF][START_REF] Zea | Potential biofilm control strategies for extended spaceflight missions[END_REF]. The formation of biofilms on solid surfaces gives rise to a resilient microbial community capable of withstanding changes in the environment and the effects of antimicrobial agents [START_REF] Pierson | Microbial contamination of spacecraft[END_REF][START_REF] Buchovec | Antimicrobial photoinactivation approach based on natural agents for control of bacteria biofilms in spacecraft[END_REF]. As a result, biofilms are strongly associated with the persistence of chronic bacterial infections in humans.

Manual disinfection of surfaces on the International Space Station (ISS) poses challenges for astronauts, particularly when dealing with hard-to-reach areas, due to its labor-intensive and time-consuming nature. Furthermore, in long-duration exploration scenarios where spacecraft may remain unoccupied and unsterilized during dormant periods, the necessity for autonomous microbial monitoring and control systems becomes evident [START_REF] Sethi | Recent progress in super hydrophobic/hydrophilic self-cleaning surfaces for various industrial applications: A review[END_REF][START_REF] Ichijo | Microbial monitoring in the international space station and its application on earth[END_REF][START_REF] Mahnert | Microbiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth[END_REF]. Implementing new solutions during the design phase of space modules has proven effective in mitigating the risks of surface biocontamination. Therefore, it is of utmost importance to prioritize the development of durable materials and equipment that limit the microbial growth and prevent its dissemination, thereby ensuring the future success of spacecraft missions [START_REF] Bauer | Microgravity and cell adherence[END_REF][START_REF] Lin | The impact of spaceflight and simulated microgravity on cell adhesion[END_REF]. Selection of materials that are unsuitable for microbial colonization and growth is a promising approach.

There are numerous strategies to limit surface biocontamination, including surfaces that passively repel microorganisms and facilitate their elimination through air purification systems. They constitute a viable option, provided certain constraints are met. These surfaces should be nanoparticle-free, have firmly anchored coatings, should be synthesized using solvent-free automated techniques, and should be compatible with various materials, including glass slides. In microgravity, microorganisms are primarily transported through droplets in non-turbulent laminar flows without thermal convection. Hydrophobic coatings act as a first line of defense by reducing the contact area between the surface and hydrophilic drops, rather than directly reducing adhesion forces [START_REF] Glavan | Rapid fabrication of pressure-driven open-channel microfluidic devices in omniphobic RF paper[END_REF][START_REF] Grinenval | Spatially controlled immobilisation of biomolecules: A complete approach in green chemistry[END_REF][START_REF] Sadri | Wearable and implantable epidermal paper-based electronics[END_REF][START_REF] Sala De Medeiros | Waterproof, breathable, and antibacterial self-powered e-textiles based on omniphobic triboelectric nanogenerators[END_REF]. Numerous studies support the effectiveness of hydrophobic coatings in this regard [START_REF] Moazzam | Investigating the BSA protein adsorption and bacterial adhesion of Al-alloy surfaces after creating a hierarchical (micro/nano) superhydrophobic structure[END_REF][START_REF] Chen | Superhydrophobic coatings on gelatin-based films: fabrication, characterization and cytotoxicity studies[END_REF][START_REF] Jiang | Lotus-leafinspired hierarchical structured surface with non-fouling and mechanical bactericidal performances[END_REF][START_REF] Kefallinou | Optimization of antibacterial properties of "hybrid" metal-sputtered superhydrophobic surfaces[END_REF][START_REF] Lee | Lubricantinfused directly engraved nano-microstructures for mechanically durable endoscope lens with anti-biofouling and anti-fogging properties[END_REF][START_REF] Wang | Robust biomimetic hierarchical diamond architecture with a self-cleaning, antibacterial, and antibiofouling surface[END_REF][START_REF] Li | Facile Li-Al layered double hydroxide films on Al alloy for enhanced hydrophobicity, anti-biofouling and anti-corrosion performance[END_REF][START_REF] Mandal | Bioinspired micro/nano structured aluminum with multifaceted applications[END_REF].

The MATISS (Microbial Aerosol Tethering on Innovative Surfaces, in the International Space Station) experiment was conducted to explore the application of hydrophobic coatings, commonly used in various industries, for reducing surface biocontamination in spacecraft [START_REF] Lemelle | Towards a passive limitation of particle surface contamination in the Columbus module (ISS) during the MATISS experiment of the Proxima Mission[END_REF]. In this experiment, surfaces within the Columbus module of the International Space Station were exposed for extended periods using a specially designed holder. This holder ensured the safe exposure of glass surfaces to astronauts and allowed for easy sealing within the station. Upon return to the laboratory, the sealed holder enabled the imaging of particles present on the exposed surfaces. The MATISS experiment was replicated three times between 2016 and 2020, involving the exposure of different surfaces for various durations. For example, the MATISS-1 campaign exposed surfaces for approximately 6 months starting in November 2016, the MATISS-2 campaign involved exposures of approximately 1, 3, and 12 months starting in August 2018, and the MATISS-2.5 campaign lasted for approximately 12 months starting in September 2019 (Figure 1).

In order to limit surface biocontamination, the MATISS experiment was carried out to assess the potential of a particular hydrophobic coating (FDTS) in reducing the biocontamination of surfaces on the ISS [START_REF] Lemelle | Towards a passive limitation of particle surface contamination in the Columbus module (ISS) during the MATISS experiment of the Proxima Mission[END_REF]2022). In these previous studies, we analyzed systematically all the particles that could be detected on the largest area possible and considered them as one set to get average exposure rate values. Here, we analyze more extensively the exposure rates for centimetersized sub-unit of surfaces. Sub-sets of rates were newly compiled to evaluate the biocontamination variation between different Columbus positions, different types of hydrophobic coatings, and different time periods. Analyses were performed to display the diversity and variability of the sources and pathways of surface biocontamination observed during extended periods on the ISS.

Materials and methods

2.1 Hydrophobic surfaces: coatings and patterning 2.1.1 CEA hydrophobic coatings on silica surfaces For this study, we selected chemical vapor deposition processes, all carried out in a vacuum on a glass lamella, to limit the use of potentially toxic organic solvents and to provide an excellent intraand inter-lot reproducibility (Figure 2A).

SiOCH films of 1 µm thickness were deposited using Octamethylcyclotetrasiloxane (OMCTS) as the precursor under vacuum conditions at 2 Torr and 100°C. The water contact angle on SiOCH films was approximately 105 ± 2°. A 1-µm-thick layer of parylene was deposited using the SCS Labcoter R 2 (PDS 2010) Vapor Deposition System with parylene C as the precursor. The water contact angle on the parylene layers was approximately 87 ± 4°. The protocols are described in [START_REF] Lemelle | Towards a passive limitation of particle surface contamination in the Columbus module (ISS) during the MATISS experiment of the Proxima Mission[END_REF].

The process of FDTS coating based on (1H, 1H, 2H, 2H)perfluorodecyltrichlorosilane (FDTS) (ABCR, 97%) was described in [START_REF] Lemelle | Passive limitation of surface contamination by perFluoroDecylTrichloroSilane coatings in the ISS during the MATISS experiments[END_REF]. The FDTS patterning protocol was as follows: the glass slides were cleaned before they were coated with a positive AZ1512HS photoresist and baked at 100°C. The samples were exposed for 25 s under UV light through a mask with radial and mirror symmetric patterns (Figure 2B). The development of the photoresist was carried out in AZ developer diluted in water under gentle shaking. The hydrophobic FDTS layer was deposited using the MVD100 equipment following the same protocol mentioned previously. Lastly, the rest of the photoresist layer was washed in acetone and ethanol in an ultrasonic bath. The water contact angle on FDTS films was 110 ± 2°.

Saint Gobain superhydrophobic silica surfaces

Pure silica micropatterns at the surface of a silica lamella were fabricated based on the combination of sol-gel process and nanoimprint lithography. The silica pattern was designed during the photolithographic step and functionalized with a vapor-phase deposition of fluorosilane molecules to obtain superhydrophobic surfaces [START_REF] Dubov | Superhydrophobic silica surfaces: fabrication and stability[END_REF]. All the characteristic geometrical parameters of the square lattice of circular pillars of the pattern, the height of the pillars (in the range 10 ± 0.5 µm) and the period of grating of 20 mm as well as the pillar diameter, the interpillar distance, and the longest dimension evaluated by interference profilometry and SEM (Figure 2C) and the corresponding water contact angle of approximately 135°, were reported in [START_REF] Dubov | Superhydrophobic silica surfaces: fabrication and stability[END_REF].

Holder and dedicated optical microscopy 2.2.1 The MATISS holder

In practice, the MATISS holder (8.5 cm × 6 cm × 1.2 cm, Figure 3A) can be considered a vented aluminum container with a 2-mm-thick slit between a transparent polycarbonate lid and the glass surfaces, allowing a laminar airflow on the surface of the mounted glass lamellae. The transition from the "laboratoryconfined" state to the "ISS-exposed" state of the glass surfaces was manually operated by removing Kapton tape that sealed the slit and reversely by repositioning the Kapton tape. The aluminum mounting base has two slots that can be plugged using Velcro bands. Here, the measurement was sorted by the window area for the particles observed on the circa (8 × 8 mm 2 ) area (Table 1).

Optical microscopy and image analyses

The MATISS sample holders were placed on an X-Y table for imaging (Figure 3B). A tile scanning mode with a Leica Z16 ApoA MacroFluo optical microscope and a camera setup was used to capture images of the glass surface through the polycarbonate cover. Image processing techniques were applied to identify and measure the position and area of each particle where images were cropped and sorted into different area classes (Figure 3C).

Segmentation and refinement methods were used to analyze the particles in the images. Fine particles have an area < 50 μm 2 , and coarse particles have an area > 50 μm 2 . These processes were described in [START_REF] Lemelle | Towards a passive limitation of particle surface contamination in the Columbus module (ISS) during the MATISS experiment of the Proxima Mission[END_REF]. The statistic properties could then be studied for different data sets and classically plotted as distributions, for example, the distribution per area for the coarse (Figure 3D left,top) and fine (Figure 3D left,bottom) particles on all coatings of MATISS-1, or boxplots, such as the boxplot of the area of fine particles in a holder on a given coating (Figure 3D right).

In this study, each glass lamella was observed below four windows (8 × 8 mm 2 ), and the surface density for each window (in particles.mm -2 ) was determined for both the fine and coarse particles to statistically investigate the surface contamination.

Results

Throughout the three MATISS campaigns, the holders were strategically positioned at two different locations within the Columbus module ("RGHS" for "Return Grid Sensor House" and "EDR" for "European Drawer Rack, " Figure 4), mounted with different hydrophobic coatings, and exposed during different periods. While the coarse (area > 50 μm 2 ) and fine (area < 50 μm 2 ) particles detected on the RGHS location were initially pooled to be investigated. Here we compile and analyze the contamination at a finer grained scale, for the 56 probed windows versus the locations, periods, types of coating (Table 1).

Exposure at different periods

The MATISS experiments were conducted in triplicate from 2016 to 2020. Surfaces were exposed over several months: ∼6 months from November 2016 for the MATISS-1 campaign; ∼1, ∼3, and ∼12 months from August 2018 for the MATISS-2 campaign; and ∼12 months from September 2019 for the MATISS-2.5 campaign (Figure 1). The three average values of the contamination rates of the FDTS coatings exposed at the RGSH location previously compiled for each of the three MATISS campaigns (from November 2016 to 2020, Figure 1) were shown to be similar in the MATISS-1 and MATISS-2 campaigns whereas notably lower in the MATISS-2.5 campaign for both coarse and fine particles [START_REF] Lemelle | Passive limitation of surface contamination by perFluoroDecylTrichloroSilane coatings in the ISS during the MATISS experiments[END_REF].

Statistical differences between the distributions of the rates compiled per window for all types of coatings, exposure times, and locations in the MATISS-2.5 campaign and the rates in MATISS-1 and 2 campaigns (Table 1; Figure 5A) were examined by unpaired Student's t-test. The values remain very significantly different for both the coarse and fine particles (p-values < 10 -3 ). The average rate of coarse particles in the MATISS-1 and MATISS-2 campaigns (0.30 ± 0.09 particles.mm -2 .month -1 for N = 24) is higher than that in MATISS-2.5 (0.23 ± 0.07 particles.mm -2 .month -1 , mean ± SD for N = 12). The average rate of fine particles in the MATISS-1 and MATISS-2 campaigns (0.79 ± 0.40 particles.mm -2 .month -1 for N = 24) is higher than that in MATISS-2.5 (0.08 ± 0.04 particles.mm -2 .month -1 for N = 8).

Exposure rates at RGHS and EPM

During the MATISS-1 campaigns, holders were installed simultaneously in two specific locations on the Columbus module for approximately 6 months starting from November 2016 (Figure 1). The first location was in close proximity to the return grid, where the majority of the cabin air in Columbus was extracted at a rate of 400 m 3 /h and reintroduced into the adjacent module. Two holders were positioned near the hatch (Figure 4). The crew's activities in this area were limited to manual filter maintenance or cleaning tasks. Throughout the monthly exposure periods, particles were continuously transported by the airflow. The air velocity near the holders was modeled to be 0.21 m/s (approximately 40 ft/min). The second location was situated in front of the EPM (European Physiology Module) rack on the EDR, located in the central section of the Columbus cabin (Figure 4). The primary source of the airflow in this area was an air outlet positioned approximately 1 m above the exposure area. This outlet expelled 55 m 3 /h of air, but the flow was directed toward the center of the cabin rather than the surface of the holder.

We examine the contamination rate values in the RGSH and EDR locations after exposure over 6 months during the MATISS-1 campaign (Table 1; Figure 5B). The statistical difference in coarse particle rate distributions between RGSH and EDR was examined by unpaired Student's t-test and found to be significantly different (p-values < 0.03) contrary to that of the fine particle rates (p = 0.43). The average rate distribution of coarse particles in the RGSH location (0.30 ± 0.09 particles.mm -2 .month -1 for N = 24) is higher than that in EDR (0.23 ± 0.07 particles.mm -2 .month -1 , mean ± SD for N = 12). The average rate distribution of the fine particles (0.63 ± 0.33 particles.mm -2 .month -1 , mean ± SD for N = 12) is higher than that of the coarse particles.

Exposure rates on different hydrophobic coatings

The biocontamination was, therefore, probed from the MATISS-1 campaigns in the RGHS location versus the three types of hydrophobic coatings (FDTS, SiOCH, and parylene). The contours of the fine particles, observed on the Saint Gobain superhydrophobic surfaces, could not be sorted with the same data treatment. The pillars of the textured surface show brighter contrasts on their edge, impeding and altering a systematic and exhaustive image processing. Therefore, the particle's area and the fine and coarse particle sets herein sorted are difficult to compare to those observed on the hydrophobic coatings. Similarly, the FDTSpatterned surfaces displayed numerous particles, among which coarse particles were identified as default products of the process. For higher hydrophobicity (FDTS > SiOCH > parylene), the coating should favor adhesion of the coarse hydrophobic particles. Conversely, it hinders more the fine particles, that are brought to the surface with their own hydrous sphere or through water droplet deposition.

Given the significant difference in the contamination rates in the RGSH and EDR locations for the coarse particles, these rates were not pooled compared to the fine particles. Statistical differences between the distributions of the rates compiled per window on the FDTS and either on SiOCH or parylene (Table 1; Figure 5C) were examined by unpaired Student's t-test. The rates on FDTS are found to be significantly higher for the coarse particles (pvalues = 0.01), which is less clear for the fine particle rates (p = 0.35). The average rate of coarse particles on FDTS (0.40 ± 0.11 particles.mm -2 .month -1 , mean ± SD for N = 8) is higher than that on both the SiOCH (0.24 ± 0.03 particles.mm -2 .month -1 , mean ± SD for N = 8) and parylene (0.25 ± 0.04 particles.mm -2 .month -1 , mean ± SD for N = 8). The average rate value for the fine particles is 0.63 ± 0.33 particles.mm -2 .month -1 , mean ± SD for N = 12.

Discussion and conclusion

The significant difference among the tested distributions of rates is particularly evident when comparing the various campaigns. As previously proposed, these rates can be presented in regard of the two range values of the occupancy rates of the Columbus module for each campaign, η EU (%). The occupancy rate is estimated as the fraction of time an EU astronaut (green line in Figure 1) is present in the ISS during the holder's exposure (violet line in Figure 1). Values reported in Figure 1 were evaluated considering only the occupancy periods of the European astronauts who are the module's main occupants. The values were found to be 100% for MATISS-1 and some of the holders of MATISS-2 and approximately 35% for MATISS-2.5 and one holder of MATISS-2 [START_REF] Lemelle | Passive limitation of surface contamination by perFluoroDecylTrichloroSilane coatings in the ISS during the MATISS experiments[END_REF]. These findings support the conclusion drawn for the sets of all the particles of each campaign, suggesting that contamination rate differences are associated with ISS activity, likely influenced by astronaut occupancy [START_REF] Lemelle | Passive limitation of surface contamination by perFluoroDecylTrichloroSilane coatings in the ISS during the MATISS experiments[END_REF]. During periods of high occupancy in MATISS-1 and MATISS-2 (in black in Figure 5A), there is a noticeable increase in coarse and fine particle contamination levels. In contrast, when the occupancy is low (approximately 35%, in gray in Figure 5A), contamination remains relatively low in both MATISS-2 and MATISS-2.5. To some extent, the rates appear to be lower in MATISS-2.5, which may be correlated with an even lower activity of the astronauts during the COVID period. MATISS-2.5 may be close to the lower contamination rates that can be detected with our experimental setup.

Occupancy integrates multi-parameters from various sources and routes of surface contamination by fine and coarse particles over long periods of exposure. During these periods, both the sources and modes of contamination can change and evolve. In long-duration space missions, the astronaut microbiome evolves [START_REF] Voorhies | Study of the impact of long-duration space missions at the International Space Station on the astronaut microbiome[END_REF], and these changes differ among the crew members [START_REF] Morrison | Investigation of spaceflight induced changes to astronaut microbiomes[END_REF]. Despite the dynamic nature of the individual crew members' microbiome composition and diversity, a delayed process of microbial homogenization between the crew and habitat surfaces is expected [START_REF] Mahnert | Microbiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth[END_REF]. The crew's microbiome effectively contaminates abiotic surfaces in a confined cabin. The specific pathways of contamination, like through aerosols or shed skin fragments, and the amount of contamination can vary based on the number of astronauts, types, and intensity of activities carried out by the crew members.

The tested distributions show a difference near the RGSH and EDR positions regarding coarse particles. No such distinction is observed for fine particles despite contamination rates being twice higher. The surface contamination by the coarse particles, even if cumulated over more than 6 months, is not averaged at the scale of the Columbus modulus. The involvement of astronauts in activities near RGSH and EDR likely contributes to the local contamination by the coarse particles, and this factor should not be underestimated. Conversely, surface contamination by fine particles is spatially uniform, emphasizing that coatings are relevant at the first order to limit the rate of fine particle contamination. For fine particles, a noticeable property of rate distribution is the much higher relative error value (∼50%) than the coarse particle rates (∼30%). This may be interpreted by a spatial homogeneity higher for the coarse than the fine particles at the scale of the holders, likely displaying different advection and deposition modes.

A difference between the rates of FDTS and other coatings among the tested distributions is only observed for coarse particles and is somewhat uncertain, primarily due to over-sampling. Additional investigations such as the fraction of thinner particles [START_REF] Lemelle | Towards a passive limitation of particle surface contamination in the Columbus module (ISS) during the MATISS experiment of the Proxima Mission[END_REF], kinetics, or spatial distribution analysis at the window scale are needed to determine the potential benefits of hydrophobic coatings in reducing biocontamination on surfaces within the ISS [START_REF] Lemelle | Passive limitation of surface contamination by perFluoroDecylTrichloroSilane coatings in the ISS during the MATISS experiments[END_REF]. The substantial relative error for each coating type indicates a high level of heterogeneity at the holder and possibly lamella scales, suggesting the presence of a surface depot resulting from an irregular and heterogeneous aerosol pathway.

In this study, the comprehensive analysis conducted at a finegrain scale offers an approach to investigate the sources and pathways of contamination in the Columbus module over extended periods. The findings confirm that, regardless of the parameters considered, the contamination rate per window area is low, indicating the effectiveness of the long-term air purification system. Moreover, it is observed that higher contamination rates occur during periods when astronaut occupancy increases. Although there may be temporary variations linked to specific activities, especially for coarse particles, this trend suggests that surface contamination over periods exceeding 6 months can be approximated by a constant rate directly proportional to the number of astronauts present. Consequently, unmanned spacecraft during dormant periods, as expected in long-duration exploration, are likely to exhibit significantly lower levels of surface contamination [START_REF] Ott | Risk of adverse health effects due to host-microorganism interactions[END_REF][START_REF] Lapelusa | Microbiome for mars: surveying microbiome connections to healthcare with implications for long-duration human spaceflight, virtual workshop july 13 2020[END_REF][START_REF] Bijlani | Advances in space microbiology[END_REF].

FIGURE 1

 1 FIGURE 1 Timelines of the MATISS campaigns. (A) Dates of MATISS-1. Exposure dates of the holders (bottom, violet). Dates of the visiting vehicles (middle, one color per vehicle, squared tops for line). Dates of each astronaut in the ISS during the campaign (top, blue for the US astronauts, red for the Russian astronauts, and green for the EU astronauts, circled tops for line). The occupancy rate of the EU astronauts (∼η EU ) during each campaign is reported in green. (B) Same for MATISS-2. (C) Same for MATISS-2.5.

FIGURE 2

 2 FIGURE 2 Hydrophobic surfaces exposed in the MATISS campaigns. (A) Atomic diagram of the molecules constituting the three uniform layers of nanometric thickness and different chemical compositions: fluorinated silane (FDTS, on the left), organic silica (SiOCH, in the middle), and parylene C polymer (on the right). (B) Optical images of the masks from which radial and mirror symmetric patterns of FDTS layers have been prepared. (C) Patterned layers of micrometric SiO 2 dots.

FIGURE 3

 3 FIGURE 3Optical microscopy and image analyses. (A) MATISS sample holder has lateral openings, here sealed with golden Kapton tape. (B) Holder was mounted on a scanning table. All the surface lamellae were imaged across the four windows of the holder (see inset and the blue frame) using a microscope. (C) Data treatment of each image at ×3 and ×30 magnifications generated crops for each particle. They are sorted and classified versus their X and Y coordinates and their area in the two sets of coarse (area > 50 μm 2 ) and fine (area < 50 μm 2 ) particles. (D) Particle size distributions are displayed as histograms, here all the coarse particles of MATISS-1 (top, left) and the fine particles (bottom, left), or as boxplots if the numbers are small (here FDTS and parylene coatings in a holder of MATISS-1).

FIGURE 4

 4 FIGURE 4 Photographs of the sample holders installed in the Columbus module. (A) Two holders installed near the Return Grid Sensor Housing (RGHS) and (B) one holder installed in front of the European Physiology Module's (EPM facility) front panel on the EDR front panel. Crops are photograph courtesy of NASA/ESA, which are permissible to use within the public domain superimposed on a Google Street View of the Columbus module.

FIGURE 5

 5 FIGURE 5 Surface contamination rates. (A) Coarse particle rates (left) and fine particle rates (right) versus the different MATISS campaigns versus the occupancy rate value (100% in black; approximately 35% in gray). (B) Coarse particle rates (left) and fine particle rates (right) in the MATISS-1 campaign versus the different locations. (C) Coarse particle rates (left) and fine particle rates (right) in the MATISS-1 campaign and RGSH location versus the different coatings. The mean values are shown as horizontal lines. All data are tabulated in Table1.

TABLE 1 Coarse and fine particle rate values (particles.mm -2 .month -1 ) measured on each window from the density (d in particles.mm -2 ) during the three MATISS campaigns. Exposure location, exposure duration, types of coating [FDTS, SiOCH, and parylene (par.)], and nature of the lamella (glass or quartz) are reported.

 1

	Campaign	Location	Lamella		Total exposure time	Coarse particle Fine particle
	Name	Year	Holder Position Support Coating Begin	End	N	N	d	Rate	d	Rate
									(Days)	(months)
	MATISS-1 2016/2017	H02	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	1.70	0.26	1.43	0.22
	MATISS-1 2016/2017	H02	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	1.37	0.21	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	2.52	0.39	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	2.38	0.37	ND	ND
	MATISS-1 2016/2017	H03	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	2.18	0.34	8.35	1.30
	MATISS-1 2016/2017	H03	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	4.48	0.70	ND	ND
	MATISS-1 2016/2017	H03	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	3.08	0.48	ND	ND
	MATISS-1 2016/2017	H03	RGHS	Glass	FDTS	20/11/16 01/06/17	193	6	3.23	0.50	ND	ND
	MATISS-1 2016/2017	H04	EDR	Glass	FDTS	20/11/16 01/06/17	193	6	1.73	0.27	2.65	0.41
	MATISS-1 2016/2017	H04	EDR	Glass	FDTS	20/11/16 01/06/17	193	6	2.05	0.32	5.35	0.83
	MATISS-1 2016/2017	H04	EDR	Glass	FDTS	20/11/16 01/06/17	193	6	2.73	0.42	ND	ND
	MATISS-1 2016/2017	H04	EDR	Glass	FDTS	20/11/16 01/06/17	193	6	1.97	0.31	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	2.33	0.36	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	1.65	0.26	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	0.75	0.12	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	1.43	0.22	2.18	0.34
	MATISS-1 2016/2017	H03	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	1.80	0.28	1.07	0.17
	MATISS-1 2016/2017	H03	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	0.98	0.15	ND	ND
	MATISS-1 2016/2017	H03	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	0.92	0.14	ND	ND
	MATISS-1 2016/2017	H03	RGHS	Glass	SiOCH	20/11/16 01/06/17	193	6	1.85	0.29	ND	ND
	MATISS-1 2016/2017	H04	EDR	Glass	SiOCH	20/11/16 01/06/17	193	6	1.42	0.22	4.60	0.72
	MATISS-1 2016/2017	H04	EDR	Glass	SiOCH	20/11/16 01/06/17	193	6	1.27	0.20	7.35	1.14
	MATISS-1 2016/2017	H04	EDR	Glass	SiOCH	20/11/16 01/06/17	193	6	0.87	0.13	ND	ND
	MATISS-1 2016/2017	H04	EDR	Glass	SiOCH	20/11/16 01/06/17	193	6	1.32	0.20	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	1.42	0.22	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	1.30	0.20	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	1.48	0.23	ND	ND
	MATISS-1 2016/2017	H02	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	1.28	0.20	3.45	0.54
	MATISS-1 2016/2017	H03	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	1.92	0.30	5.98	0.93
	MATISS-1 2016/2017	H03	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	2.05	0.32	ND	ND
	MATISS-1 2016/2017	H03	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	1.37	0.21	ND	ND
	MATISS-1 2016/2017	H03	RGHS	Glass	Par.	20/11/16 01/06/17	193	6	1.48	0.23	ND	ND
	MATISS-1 2016/2017	H04	EDR	Glass	Par.	20/11/16 01/06/17	193	6	1.37	0.21	2.37	0.37
	MATISS-1 2016/2017	H04	EDR	Glass	Par.	20/11/16 01/06/17	193	6	1.00	0.16	1.67	0.26
	MATISS-1 2016/2017	H04	EDR	Glass	Par.	20/11/16 01/06/17	193	6	0.75	0.12	ND	ND
	MATISS-1 2016/2017	H04	EDR	Glass	Par.	20/11/16 01/06/17	193	6	0.50	0.08	ND	ND
	MATISS-2	2018	H05	RGHS	Glass	FDTS	23/08/18 03/10/18	41	1	0.47	0.34	2.25	1.65
	MATISS-2	2018	H05	RGHS	Glass	FDTS	23/08/18 03/10/18	41	1	0.55	0.40	1.72	1.26

(Continued on the following page)

TABLE 1 (Continued) Coarse and fine particle rate values (particles.mm -2 .month -1 ) measured on each window from the density (d in particles.mm -2 ) during the three MATISS campaigns. Exposure location, exposure duration, types of coating [FDTS, SiOCH, and parylene (par.)], and nature of the lamella (glass or quartz) are reported.

 1

	Campaign	Location	Lamella		Total exposure time	Coarse particle Fine particle
	Name	Year	Holder Position Support Coating Begin	End	N	N	d	Rate	d	Rate
									(Days)	(months)
	MATISS-2	2018	H05	RGHS	Glass	FDTS	23/08/18 03/10/18	41	1	0.67	0.49	1.82	1.33
	MATISS-2	2018	H05	RGHS	Glass	FDTS	23/08/18 03/10/18	41	1	0.63	0.46	1.50	1.10
	MATISS-2	2018	H06	RGHS	Glass	FDTS	23/08/18 26/11/18	95	3	0.75	0.24	2.47	0.78
	MATISS-2	2018	H06	RGHS	Glass	FDTS	23/08/18 26/11/18	95	3	1.57	0.49	2.13	0.67
	MATISS-2	2018	H06	RGHS	Glass	FDTS	23/08/18 26/11/18	95	3	1.48	0.47	6.60	2.08
	MATISS-2	2018	H06	RGHS	Glass	FDTS	23/08/18 26/11/18	95	3	1.62	0.51	4.07	1.28
	MATISS-2	2018	H08	RGHS	Glass	FDTS	23/08/18 12/08/19	354	12	3.33	0.28	2.05	0.17
	MATISS-2	2018	H08	RGHS	Glass	FDTS	23/08/18 12/08/19	354	12	1.13	0.10	2.73	0.23
	MATISS-2	2018	H08	RGHS	Glass	FDTS	23/08/18 12/08/19	354	12	2.12	0.18	7.15	0.61
	MATISS-2	2018	H08	RGHS	Glass	FDTS	23/08/18 12/08/19	354	12	1.47	0.12	6.78	0.57
	MATISS-2.5 2019/2020	H09	RGHS	Glass	FDTS	25/09/19 24/09/20	365	12	0.30	0.02	0.58	0.05
	MATISS-2.5 2019/2020	H09	RGHS	Glass	FDTS	25/09/19 24/09/20	365	12	0.33	0.03	0.58	0.05
	MATISS-2.5 2019/2020	H09	RGHS	Glass	FDTS	25/09/19 24/09/20	365	12	0.27	0.02	0.47	0.04
	MATISS-2.5 2019/2020	H09	RGHS	Glass	FDTS	25/09/19 24/09/20	365	12	0.35	0.03	0.37	0.03
	MATISS-2.5 2019/2020	H10	RGHS	Quartz	FDTS	25/09/19 24/09/20	365	12	0.65	0.05	1.62	0.13
	MATISS-2.5 2019/2020	H10	RGHS	Quartz	FDTS	25/09/19 24/09/20	365	12	0.42	0.03	2.08	0.17
	MATISS-2.5 2019/2020	H10	RGHS	Quartz	FDTS	25/09/19 24/09/20	365	12	0.28	0.02	1.07	0.09
	MATISS-2.5 2019/2020	H10	RGHS	Quartz	FDTS	25/09/19 24/09/20	365	12	0.25	0.02	1.37	0.11

Frontiers in Astronomy and Space Sciences

frontiersin.org

Acknowledgments

The authors thank the NASA and ESA astronauts that were involved in the MATISS experiments. The authors also acknowledge the contribution of SFR BioSciences (UMS3444/CNRS, US8/Inserm, ENS de Lyon, UCBL) PLATIM facility. CEA-Leti acknowledges the support of the Agence Nationale de la Recherche through the LabEx ARCANE program (ANR-11-LABX-0003-01) and the Graduate School on Chemistry, Biology and Health of Université Grenoble Alpes CBH-EUR-GS (ANR-17-EURE-0003). Anne-Dominique Malinge and Philippe Boulez contributed to the final integration of the MATISS experiments.

Funding

The CNES, the French space agency, provided financial support for the MATISS hardware design and for the MATISS experiments.

Data availability statement

The original contributions presented in the study are included in the article; further inquiries can be directed to the corresponding authors.

Author contributions

LL, CP, LC, AM, and SB designed the MATISS-1 project; LL, CP, and SR designed the MATISS-2 project; LL, CP, GN, and SR designed the MATISS-2.5 project; DL and EM machined the sample holder and carried out the microscopy imaging; GN, CF, VJ, CaP, OC, JT, and EG prepared the surfaces; PM carried out the microbiological investigations; LC, CT, AM, and SB managed the qualification for spaceflight of the MATISS-1 experiment and the communication with the astronauts; CT and SR managed the qualification for spaceflight of the MATISS-2 and MATISS-2.5 experiments and the communication with the astronauts; LL, CP, and GN wrote the paper. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Lucie Sebastien

Marta Avalos

Developing Autonomy through an Entrepreneurial Project

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Developing Autonomy through an Entrepreneurial Project

Autonomy through an Entrepreneurial Project

From the idea to the project Taking initiative and responsability

Self-directed learning

Initial curriculum and field experience

Accompanying teacher

Literature Review Methodology and Survey Techniques as part of the MPH program

Enhancing the Management of Low Back Pain in France :

My Project

School of Public Health, University of Bordeaux Lucie Sebastien lucie.sebastien@etu.u-bordeaux.fr Marta Avalos marta.avalos-fernandez@u-bordeaux.fr


MD Matthieu Revest
email: matthieu.revest@chu-rennes.fr

Lucas Fischer

Keywords: Infection sur prothèse vasculaire, biofilm, traitement médicochirurgical Vascular prosthesis infections Secondary Vascular prosthesis-related infection, biofilm, antibiotherapy combined with surgical treatment Vascular prosthesis-related infection, biofilm, antibiotherapy combined with 53 surgical treatment 54 55

Il existe peu de données disponibles concernant les infections sur prothèse vasculaire et encore moins concernant les endoprothèses dont l'usage augmente pour assurer une prise en soin moins invasive pour des patients plus fragiles. Cette complication touche 1,5 % de l'ensemble des prothèses vasculaires, qu'elles soient posées par voie chirurgicale ou par procédure endovasculaire, et est associée à une importante mortalité. Elle survient le plus souvent suite à une contamination par contiguité, ce qui engendre un spectre microbiologique associant des staphylocoques, des entérobactéries et des infections plurimicrobiennes. Leur diagnostic reste complexe devant une expression clinique peu bruyante avec l'important rôle de l'imagerie par tomodensitométrie avec injection. Le traitement repose sur l'association entre antibiothérapie de longue durée et chirurgie, et des recommandations européennes viennent récemment d'être émises permetant d'aider les cliniciens dans la gestion de ces patients.

Infections sur prothèse vasculaire

Lucas Fischer 1 et Matthieu Revest

Points forts:

 Les infections de prothèse vasculaires sont des complications rares mais graves de la chirurgie prothétique vasculaire  La fréquence des infections d'endoprothèses est la même que celles des prothèses posées par voie chirurgicale classique  Le diagnostic est parfois difficile avec une place centrale du scanner injecté  Le traitement repose sur une antibiothérapie prolongée associée à une chirurgie radicale retirant l'ensemble du matériel infecté  En l'absence d'une chirurgie complète, un traitement antibiotique suspensif est envisagé

Key points :

 Vascular prosthesis infections are rare but very severe complications of vascular prosthesis surgery  Endoprosthesis infections are as frequent as surgically inserted vascular prosthesis infections  Diagnosis of vascular prosthesis infections is often difficult and CT-scan plays a paramount to ascertain these infections  A prolonged antibiotherapy and a surgery that removes all the infected material are mandatory to cure these infections  If radical surgery cannot be performed, a life-long suppressive antibiotherapy has to be discussed

Points forts

Accepted manuscript De nombreuses classifications ont été publiées mais n'apportent finalement qu'une aide limitée 71 en pratique clinique. Le plus aidant est tout de même de distinguer les IPV sus-inguinales 72 touchant les prothèses aortiques et/ou iliaques des IPV sous-inguinales dites périphériques du 73 fait de différences épidémiologiques, et surtout diagnostiques et pronostiques [START_REF] Teebken | Recommendations for reporting treatment 327 of aortic graft infections. European journal of vascular and endovascular surgery : the official 328[END_REF][START_REF] Bunt | Synthetic vascular graft infection. The continuing headache[END_REF]. 74

En termes de délai de survenue, il est souvent différencié dans la littérature les infections 75 survenant dans les 4 mois suivant la mise en place de la prothèse des infections survenant au -76 delà. Mais cette limite des 4 mois ne repose sur rien de concret et la prise en soin des patients 77 n'est pas différente si on la considère. A l'image de ce qui est fait pour les infections de 78 prothèses ostéo-articulaires, peut-être qu'un délai d'un mois dans les suites de l'implantation 79 serait plus pertinent en tant que limite permettant de traiter l'infection en laissant le matériel en 80 place. Certains centres le font d'ailleurs déjà et, sous réserve d'un lavage chirurgical optimal, autorisent le maintien de la prothèse en place sous réserve d'une antibiothérapie prolongée. 82

Cependant aucune donnée comparative solide n'existe, il est donc pour l'instant trop tôt pour 83 recommander à large échelle une telle attitude qui ne peut être autorisée qu'après concertation 84 pluridisciplinaire au sein d'un centre expert. 85 86

Terrain et physiopathologie 87

Le terrain est celui de l'indication de la pose de la prothèse, c'est-à-dire celui de 88 l'athérosclérose. Les IPV touchent donc généralement des hommes âgés en moyenne de 65 ans 89

(5). La probabilité de survenue d'une IPV est de 1,5 % avec des disparités selon le site 90 anatomique : 1 % pour les prothèses aortiques, et plus particulièrement 0,2 % au niveau 91 abdominal et 1 à 3 % au niveau thoracique, contre 4,8 % pour les périphériques. Les délais de 92 survenue sont très variables, même si en général, les IPV périphériques surviennent plus 93 précocement que les IPV aortiques : respectivement 12 (1-27) et 56 mois (4-97) [START_REF] Lyons | 335 Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft 336 Infection Collaboration (MAGIC). European journal of vascular and endovascular surgery : the 337 official[END_REF]. 94 95

Spectre microbiologique 96

Les données disponibles ne sont pas d'une fiabilité conséquente, faute d'essai de grande 97 ampleur multicentrique. Il semble cependant se dégager certains éléments mis en évidence dans 98 le tableau 1 [START_REF] Wilson | 332 Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific 333 Statement From the American Heart Association[END_REF]. 99

Il n'est pas retrouvé de différences microbiologiques significatives selon le site ou le délai de 100 survenue [START_REF] Legout | Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective 340 observational cohort study. Clinical microbiology and infection : the official publication of the 341[END_REF]. 101 102

Impacts de la maladie 103

Les IPV sont des maladies graves : elles se compliquent d'hémorragies digestives en cas de 104 prothèse aortique ou iliaque dans une proportion non négligeable (2 à 61 % selon les études), d'emboles avec un risque d'ischémie de membres (29 %) nécessitant une amputation dans 13% 106 des cas. La thrombose de prothèse secondaire à l'infection est également non rare (2 à 24 %). 107 La mortalité varie selon le site touché : autour de 0,5 % en cas d'IPV périphérique, contre en 108 moyenne 15 à 25 % à 30 jours du diagnostic et 20 à 45 % à un an pour les IPV sus-inguinales 109 [START_REF] Wilson | 332 Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific 333 Statement From the American Heart Association[END_REF][START_REF] Lyons | 335 Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft 336 Infection Collaboration (MAGIC). European journal of vascular and endovascular surgery : the 337 official[END_REF][START_REF] Legout | Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective 340 observational cohort study. Clinical microbiology and infection : the official publication of the 341[END_REF][START_REF] Argyriou | Endograft Infection After Endovascular 343 Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis[END_REF][START_REF] Kahlberg | A systematic review of infected descending 346 thoracic aortic grafts and endografts[END_REF]. Devant une fistule prothéto-digestive, la mortalité devient supérieure à 50 % à un 110 an et est plus importante en cas d'atteinte de l'aorte thoracique [START_REF] Chiesa | Aorto-oesophageal and Aortobronchial 348 Fistulae Following Thoracic Endovascular Aortic Repair : A National Survey[END_REF]. [START_REF] Argyriou | Endograft Infection After Endovascular 343 Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis[END_REF][START_REF] Kahlberg | A systematic review of infected descending 346 thoracic aortic grafts and endografts[END_REF][START_REF] Vogel | The incidence and factors associated with graft infection 351 after aortic aneurysm repair[END_REF][START_REF] Smeds | Treatment and outcomes of aortic 353 endograft infection[END_REF]. 123 La mortalité associée s'avère être similaire et dépend du traitement chirurgical entrepris allant 124 de 26,6 % à 30 jours puis 54 % à 1 an, alors qu'en cas de traitement conservateur, elle se majore 125 à 38 voire 63,3 % à J30 et jusqu'à 75 % à 1 an [START_REF] Argyriou | Endograft Infection After Endovascular 343 Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis[END_REF][START_REF] Kahlberg | A systematic review of infected descending 346 thoracic aortic grafts and endografts[END_REF]. 126

Pour les fistules, la fréquence varie de 0,56 à 1,7 % et est responsable d'une forte mortalité avec 127 seulement 46 à 63 % de survie à 1 an [START_REF] Chiesa | Aorto-oesophageal and Aortobronchial 348 Fistulae Following Thoracic Endovascular Aortic Repair : A National Survey[END_REF][START_REF] Vogel | The incidence and factors associated with graft infection 351 after aortic aneurysm repair[END_REF][START_REF] Czerny | New insights regarding the incidence, 355 presentation and treatment options of aorto-oesophageal fistulation after thoracic 356 endovascular aortic repair: the European Registry of Endovascular Aortic Repair 357 Complications[END_REF] [START_REF] Legout | Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective 340 observational cohort study. Clinical microbiology and infection : the official publication of the 341[END_REF]. 150

Les difficultés de cicatrisation précoce doivent faire penser à une IPV, mais n'en sont pas 151 pathognomoniques a contrario des fistules à la cicatrice [START_REF] Samson | A modified classification and 362 approach to the management of infections involving peripheral arterial prosthetic grafts[END_REF]. retarder la chirurgie en cas de délais d'obtention longs. La scintigraphie aux polynucléaires 178 marqués (SLM) semble aussi performante que le TEP-scanner au 18 F-FDG [START_REF] Roca | Guidelines for the labelling of 365 leucocytes with (111)In-oxine. Inflammation/Infection Taskgroup of the European Association of Nuclear Medicine[END_REF]

111 112 A

 112 propos des endoprothèses 113 La place des techniques endovasculaires pour la mise en place des prothèses ne cesse de croitre. 114 Cette technique permet une diminution de la mortalité (1,2 %) et des complications péri-115 interventionnelles (4,7 %) comparitivement à une chirurgie ouverte (respectivement 4,6 % et 116 9,8 %) (11). L'absence d'effraction importante du tissu cutané pourrait laisser penser que ces 117 techniques endovasculaires sont moins à risque d'IPV que les techniques chirurgicales 118 conventionnelles, mais cela n'est pas retrouvé dans la littérature. La fréquence des IPV, tout 119 comme celle des fistules, semble identique : 0,2 à 5 % d'IPV en cas d'endoprothèses variant 120 selon le site avec 0,6 % au niveau abdominal contre 1 à 6 % au niveau thoracique. Tandis que 121 les délais de survenue semblent en moyenne plus courts entre 17,1 mois au niveau thoracique 122 et 25 mois au niveau abdominal

200  2 Figure 1 : 437 Figure 2 :Tableau 1 :

 2002143721 Figure 1 : Infection d'une prothèse aortique visualisée au scanner avec flèche blanche signalant 410

FièvreTableau 3 :

 3 antibiothérapie probabiliste des IPV proposée par la SPILF 477 Antibiotiques Dosage et voie Alternatives Sepsis avec ou sans colonisation ni infection à EBLSE dans les 3 mois Ou choc septique sans colonisation ni infection à EBLSE dans les 3 kg/j en perfusion prolongée ou continue après 4 g de dose de charge IV (jusqu'à 16 g/j) 10 mg/kg/j IV en une prise 30 mg/kg/j IV sur 30 minutes Si allergie à la pénicilline : Céfépime 2 g 3 fois/j en perfusion prolongée ou continue après 2 g de dose de charge Et Métronidazole 500 mg 3 fois/j IV ou PO Vancomycine 40 mg/kg/j IV, en perfusion continue après 30 mg/kg de dose de charge en 120 minutes Choc septique et colonisation connue dans les 3 mois à EBLSE Méropénème Et Daptomycine Avec Amikacine 100 mg/kg/j en 3 à 4 perfusions de 4 heures 10 mg/kg/j IV en une prise 30 mg/kg/j IV sur 30 minutes Si allergie à la pénicilline : avis d'experts Vancomycine 40 mg/kg/j IV, en perfusion continue après 30 mg/kg de dose de charge en 120 minutes EBLSE : Entérobactérie productrice de bétalactamase à spectre étendu ; IV : intraveineuse 478 479 480

  1,2* 1 Service des Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, CHU Rennes, 35033 Rennes Cedex 9 2 CIC-Inserm 1414, CHU Rennes, Inserm U1230, Université Rennes 1, 35033, Rennes Cedex 9

related infections, vascular prosthesis infections are probably the less 42 studied. The situation is even worse regarding the endoprosthesis while this kind of procedure 43

  Il existe peu de données disponibles concernant les infections sur prothèse vasculaire et encore 27 moins concernant les endoprothèses dont l'usage augmente pour assurer une prise en soin moins 28 invasive pour des patients plus fragiles. Cette complication touche 1,5 % de l'ensemble des 29 prothèses vasculaires, qu'elles soient posées par voie chirurgicale ou par procédure 30 endovasculaire, et est associée à une importante mortalité. Elle survient le plus souvent suite à 31 une contamination par contiguité, ce qui engendre un spectre microbiologique associant des 32 staphylocoques, des entérobactéries et des infections plurimicrobiennes. Leur diagnostic reste 33 complexe devant une expression clinique peu bruyante avec l'important rôle de l'imagerie par 34 tomodensitométrie avec injection. Le traitement repose sur l'association entre antibiothérapie 35 de longue durée et chirurgie, et des recommandations européennes viennent récemment d'être 36 émises permetant d'aider les cliniciens dans la gestion de ces patients. celle des autres infections sur prothèse et une mortalité allant jusqu'à 25% 65 à un mois du diagnostic (2). Il semble donc important d'harmoniser les conduites diagnostiques 66 et thérapeutiques afin d'assurer à chaque patient une prise en soin optimale.

	Manuscrit (avec liste des auteurs)
	Infections sur prothèse vasculaire Lucas Fischer 1 et Matthieu Revest 1,2* 1 Service des Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, CHU Rennes, 35033 Rennes Cedex 9 2 CIC-Inserm 1414, CHU Rennes, Inserm U1230, Université Rennes 1, 35033, Rennes Cedex 9 * Auteur correspondant : Matthieu Revest, service des Maladies Infectieuses et Réanimation Médicale matthieu.revest@chu-rennes.fr; tel : 02 99 28 95 64 Titre en Anglais: Vascular Prosthesis-related Infections Conflits d'intérêt : Aucun Résumé : Mots clés : Infection sur prothèse vasculaire, biofilm, traitement médicochirurgical Abstract : Among all material-is clearly expanding. This complication affects 1.5 % of all vascular prostheses, whether they are surgically or by endovascular procedure inserted, and is associated with a significant mortality. It most often occurs as a result of the prosthesis' contamination by contiguity, with a large microbiological spectrum involving staphylococci, enterobacteria and multi-microbial infections. Vascular prosthesis infections' diagnosis remains complex du to an often noiseless Les recommandations concernant l'antibiothérapie des infections sur prothèse vasculaire (IPV) sont encore récentes, publiées en 2019 par la Société de Pathologie Infectieuse de Langue Française (SPILF) suivies par les recommandations européennes en 2020 (1). De ce fait, les prises en soin de ces patients restent inhomogènes à l'échelle du territoire ce qui n'est pas le cas pour d'autres infections sur matériel pour lesquelles les recommandations sont plus anciennes et donc plus largement appliquées. Finalement, ces IPV apparaissent comme le parent-pauvre des infections sur matériel et des infections cardiovasculaires, et ce malgré une fréquence similaire à 67 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 26 37 38 39 40 41 44 45 46 47 48 57 58 59 60 61 62 63 64 68 Epidémiologie : 69 clinical expression and CT-scan is of paramount importance to confirm the diagnosis. Introduction : Classifications 70
	25
	1 2
	Accepted manuscript

  ).Pour ce qui est de la présentation clinico-radiologique, du spectre microbiologique et des issues 129 thérapeutiques, les données de la littérature concernant les IPV secondaires aux techniques 130 endovasculaires sont similaires à celles des IPV après chirurgie ouverte.

	131
	132
	133	Diagnostic des IPV
	134	Clinique et biologie
	135	La présentation est variable, pouvant associer tout ou partie des manifestations suivantes (14) :
	136	 Choc septique avec fièvre ;
	137	 Signes locaux dépendants de la localisation : douleurs abdominales ou lombalgies lors
	138	d'atteinte de l'aorte abdominale ou thoracique basse, inflammation locale avec
	139	érythème, douleur et oedème, etc. ;
	140	 Signes d'avals allant du purpura embolique jusqu'à l'ischémie d'aval ;
	141	 Hémorragies digestives en cas de fistules prothéto-digestives observées lors d'IPV sus-
	142	iliaques : 27 à 33 % des cas ;
	143	 Hémoptysie en cas de fistule prothéto-bronchique ;
	144	 Symptômes associés à une infection pouvant être responsable ou bien secondaire à
	145	l'IPV via contamination par contiguité (spondylodiscite, arthrite, abcès profond, etc.) ;
	146	 Altération de l'état général peu voire pas fébrile ;
	147	 Absence de symptômes : jusqu'à 10 % des cas.
	148	De façon plus schématique, en cas d'IPV aortique, il y a 75 % de fièvre et 25 % de douleurs
	149	abdominales. Tandis que lors d'IPV périphérique, la fièvre est moins fréquente (50 %) et les
		signes locaux, à type d'inflammation et déhiscence de cicatrice, sont plus fréquents (75 %)

  ). 467

	473	Tableau 2 : Critères diagnostiques du groupe MAGIC (Management of Aortic Graft Infction
	474	Germe Collaboration) repris par les recommandations européennes (3, 5) Fréquence	Commentaire
		Plurimicrobien Cliniques/chirurgicaux 20 à 30 %	Particulièrement observé en cas de fistule prothéto-digestive Radiologiques Biologiques
		Staphylococcus aureus Présence de pus autour de la prothèse 38,3 % (20 à 50 %) Germe le plus fréquemment rencontré Collection liquidienne Culture de la prothèse positive.
		Entérobactéries ou dans le sac anévrysmal 20 à 40 %	périprothétique sur la TDM > 3	Culture d'un prélèvement
		Pseudomonas aeruginosa (confirmation microscopique). 15 %	mois après l'implantation.	peropératoire positif.
		Exposition de la prothèse via une	Bulles d'air périprothétique sur la	Culture	d'une	ponction
		Staphylocoques à coagulase négative Entérocoques et streptocoques plaie ou présence d'une fistule. 15 à 20 % Critères Présence d'une fistule aortodigestive majeurs 13 % ou aortobronchique.	TDM > 7 semaines après l'implantation. Augmentation du volume des	percutanée périprothétique positive. de collection Si microorganisme pouvant
		Anaérobies strictes Implantation d'une prothèse dans un 4,5 %	Présents en cas de fistule prothéto-digestive bulles d'air périprothétique sur être une	contamination,
		site	infecté		(anévrysme	ou	Surtout observé en cas d'usage de drogues intraveineuses ou plusieurs TDM consécutives. requiert ≥ 2 prélèvements
		Candida sp. pseudoanévrysme	infecté,	3 % zone	lors de fistule prothéto-digestive (majoration de la fréquence positifs.
		fistulisée).			jusqu'à 40 %)
		Signes	locaux	inflammatoires	Responsable de fistule prothéto-digestive donc à risque
		(érythème,	oedème,	Difficilement chaleur,	d'infection polymicrobienne.
		Coxiella burnetti écoulement purulent, douleur). estimable	A rechercher en cas de contexte évocateur ou de prélèvements
						négatifs, voire systématiquement devant une fistule.
		Absence de documentation		10 %
		Critères
	468	mineurs
	469
	470
	471