Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center

Background: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients.Methods: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves.Results: Forty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6-303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulasenegative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE.Conclusions: Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded

Large-Area RPE Removal by Microsecond Laser followed by hiPS-RPE transplantation

Cell therapeutics for AMD were often implanted regardless of RPE status in the target zone. This may result in RPE multilayering. Here we study a novel laser to remove RPE without collateral damage prior to RPE implantation to encourage better subretinal integration. Pigment rabbits (n=24) were immunosuppressed with Sirolimus, Doxycyclin and Minocyclin. Using a SLO/ OCT (Heidelberg Engineering) extended with a prototype laser (Meridian Medical; wavelength: 532 nm; pulse duration, 8 µs), a large area of RPE was selectively removed in 19 rabbits. Animals without laser lesions served as controls (n=5). A 25 gauge vitrectomy (Geuder) with removal of posterior hyaloid membrane was performed thereafter. Human iPS-RPE (1000 cells/ µl) were manually injected using a 100 µl syringe (Hamilton) connected to a 38G cannula (MedOne) into the RPE laser lesion, or over healthy RPE in controls, monitored by intraoperative OCT imaging (RESCAN 700, Zeiss). In vivo follow up/ retinal imaging was up to 12 weeks including fluorescein and indocyanine angiography, as well as SD-OCT (Spectralis ®, Heidelberg Engineering). Representative RPE laser wounds exhibited mild late phase FA& ICGA leakage, without abnormal outer retinal or choroidal hyperreflectivity on OCT. By contrast, lesions with earlier leakage on FA/ ICGA showed beam-sized outer retinal hyperreflectivity on OCT, suggesting coagulation. The size of the RPE wounds was typically 10-12mm2.iOCT demonstrated in an immediate and directed spread of the bleb retinal detachment (bRD) within the lasered zone. By contrast, bRDs performed over non-lasered RPE raised slower with a circular spread. Subretinal injection ranged from 5-70µl, with lesser volumes/ larger bRDs areas over lasered regions.At 6 and 12 weeks, none of implanted regions showed FA/ICGA leakage, some lesions had blockage due to hyperpigmentation; on OCT, representative areas showed preserved ellipsoid bands, with some RPE undulations. Lasered/implanted areas with a peripheral hyperpigmentation showed central outer retinal atrophy along with irregular RPE. Control implantation sites showed retinal atrophy and a variably thickened RPE band. Large-area RPE removal with laser disruption is feasible in healthy rabbits and appears to facilitate superior integration of RPE suspension grafts, compared to subretinal injection alone. Future work aims to correlate histology with in vivo imaging. This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually

Short-term follow up after Large-Area RPE Removal by Microsecond Laser followed by hiPS-RPE suspension transplantation in rabbits

Cell therapy is a promising treatment for retinal pigment epithelium (RPE)-associated eye diseases. Herein, microsecond laser irradiation targeting RPE cells was used for large-area RPE removal followed by subretinal injection of human induced pluripotent stem cell derived RPE (hiPS-RPE). 19 immunosuppressed pigmented rabbits (Chinchilla bastard hybrid) underwent a large area RPE removal using an infrared reflectance (IR) confocal scanning laser ophthalmoscope (cSLO) with spectral-domain optical coherence tomography (SD-OCT) system (Heidelberg Engineering ) extended with a prototype laser (modified Merilas 532 shortpulse ophthalmic laser photocoagulator, Meridian Medical) (wavelength, 532 nm; pulse duration, 8 µs), followed by a 25G vitrectomy. Subsequently, a suspension of hiPS-RPE (1000 cells/ µl) was grafted subretinally into the RPE laser lesion under real-time intraoperative OCT imaging (RESCAN 700, Zeiss) by manual injection via a 25/38G cannula connected to a 100µl Hamilton syringe. 5 rabbits served as a control with hiPS-RPE injected subretinally over healthy RPE. The rabbits were followed with in vivo multimodal retinal imaging at baseline after laser and then for 7 days including fluorescein (FA) and indocyanine angiography (ICGA), aw well as SD-OCT (Spectralis ®, Heidelberg Engineering). Baseline imaging of RPE laser wounds showed mild late phase FA/ICGA leakage, with normal outer retinal and choroidal reflectivity on OCT, without signs of coagulation. The size of the RPE wounds was typically 10-12mm2. Real time iOCT showed a directed spread of the bleb retinal detachment (bRD) within the lasered zone, in contrast to a circular spread in controls. Subretinal injection ranged from 5-20µl, with lesser volumes/ larger bRD areas over lasered regions. At 7 days, implanted regions showed FA/ICGA leakage, blockage due to hyperpigmentation was observed mostly at the edges of the lasered zone; OCT showed hyperreflectivity of the outer retina with RPE irregularities. Control implantation sites showed hyperreflectivity in all retinal layers and a variably thickened RPE band suggesting clumping. Microsecond laser irradiation to the RPE seems to accelerate the subretinal integration of hiPS-RPE, when compared to subretinal injection over intact RPE. Future work will address correlation of multimodal imaging and histology. This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually

Bias in carbon concentration and δ13C measurements of organic matter due to cleaning treatments with organic solvents

We acknowledge the financial support from the UnivEarths Labex program of Sorbonne Paris Cite (ANR 11-IDEX-00005-02). CH and AL acknowledge support from the Max Planck Society. EES and RB were funded by the NASA Exobiology grant NNX16AI37G and the Virtual Planetary Laboratory of the NASA Astrobiology Institute and were technically assisted by Andy Schauer.Interpreting the organic carbon content (TOC) and stable carbon isotopic composition (δ13C) of organic matter in the sedimentary rock record depends on our capability to accurately measure them, while excluding sources of contamination. This however becomes increasingly problematic as we analyze samples with ever-lower organic carbon content. Accordingly, organic solvents are sometimes used to remove contaminating traces of modern organic matter from ancient rock samples. However, especially for very low TOC samples, traces of solvents or their impurities remaining in the sample may contribute a significant organic contamination that can impact the bulk measurements of both TOC and δ13C values. This study, including three independent investigations performed in different laboratories, is the first detailed examination of the effect of cleaning treatments on the reliability of TOC and δ13C values in a range of natural rock samples and synthetic materials with low TOC content from below detection limit to 3330 ppm. We investigated the four most common organic solvents used to remove modern organic matter: dichloromethane (DCM), n-hexane, methanol and ethanol, and evaluated the effect of grain size and mineralogy. We find that (i) cleaning treatments with methanol, n-hexane and dichloromethane contaminate rock samples when used directly on sample powder, regardless of the grain size; (ii) this pollution buffers the natural variability and homogenizes the δ13C values of samples around the isotopic composition of the solvent, i.e. between −27 and −29‰; (iii) the extent of contamination depends on the solvent used, DCM being the most contaminating (up to 6000 ppm) and ethanol the only solvent that does not seem to contaminate rock samples above our detection limit; (iv) sample mineralogy also exerts an influence on the extent of contamination, clay minerals being more prone to adsorb contaminants. We conclude that the response of carbon concentrations and the stable carbon isotopic composition of organic matter in geological samples to cleaning treatments is neither negligible nor systematic when investigating samples with low carbon content.PostprintPeer reviewe

Physiopathologie de l infection à Legionella pneumophila dans un modèle expérimental murin

To progress in the understanding of L. pneumophila infection, we investigated host-pathogen interaction in vitro through lung epithelial cell cultures and in vivo through an A/J murine model focusing on two aspects: the studies of alveolar-capillary barrier injury and lung inflammatory response. Three parts have been developed: 1) a study of the mechanisms leading to L. pneumophila attachment to respiratory epithelia; 2) a study of virulence factor type IV secretion system (Dot/Icm system) involvement in L. pneumophila pathogenesis; 3) a primary characterization of mucosal innate response. The main results of this work are : -in vitro, the zinc ion is an important co-factor of L. pneumophila adherence to alveolar type II pneumocytes via a protein adhesin. -In vivo, sulphated saccharide heparin co-instilled intratracheally with L. pneumophila challenge has a protective effect on the alveolar-capillary barrier and prevents bacterial dissemination. It tends to confirm the competitive inhibition by heparin of L. pneumophila attachment to lung epithelium in vivo, and point to the possible involvement of a heparan-sulfate adhesin in L. pneumophila binding to pneumocytes. -In vivo, L. pneumophila Dot/Icm system of serogroup 1 strains Lens and Paris is central to pathogenesis and is associated with the development of acute lung injury, lung bacterial replication and systemic spread. -In vivo, at 4 and 48 hours post-infection by L. pneumophila both gene expressions of lung -defensins mBD-1 and mBD-3 were detected in a constitutive and inducible way respectively. However, the absence of ccl20 gene expression was observed, a key chemokine for dendritic cells recruitment after bacterial infectionLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Necrotic sore throat, tender lymphadenopathies, hepatitis and activated lymphocytes in circulating blood as a clinical presentation of severe infectious mononucleosis

International audienc

Coûts cachés comme vecteur d’implication au travail des enseignants du secteur de l’enseignement technique secondaire au Cameroun.

Les entités publiques font aujourd’hui face à des risques relatifs à l’incertitude et à la complexité des situations organisationnelles et environnementales rencontrées. L’objet de ce travail est de mettre en exergue l’impact des coûts cachés sur l’implication au travail des enseignants dans les établissements secondaire d’enseignement technique au Cameroun. Dans le cadre de cette étude, nous avons opté pour une approche qualitative à travers des entretiens semi-directifs auprès de dix enseignants dans trois établissements. La démarche analytique suivie nous a permis d’une part d’identifier les principaux coûts cachés ; d’autre part de mettre en exergue les coûts cachés les plus adaptées au contexte. Le traitement des informations collectées s’est opéré uniquement par la méthode d’analyse de contenu. Cette technique a permis de regrouper les résultats à deux niveaux à savoir les coûts cachés endogènes et les coûts cachés exogènes. Il ressort des analyses effectuées que, les coûts cachés endogènes influencent l’engagement et le dévouement au travail, et que les coûts cachés exogènes influencent le rendement au travail