Meniscus sutures by arthrotomy for a non-transfixing horizontal lesion associated with a cyst.

INTRODUCTION: Meniscal cysts are rare in Stoller grade II horizontal lesions. Several techniques are described in the literature for their management, without any real gold standard. The objective of this work was to report a series of meniscal sutures associated with cyst resection by arthrotomy. The hypothesis was that the results were satisfactory and comparable with the data in the literature regardless of the technique reported without morbidity added by arthrotomy. MATERIALS AND METHODS: This was a monocentric retrospective study on 13 patients, aged 33 on average with a grade II meniscus lesion associated with a cyst (9 lateral and 4 medial menisci). Pre-operative data available was the VAS (5.7/10) and the Lysholm score (61/100). Primary endpoints were as follows: pain (visual analogue scale), global satisfaction, Lysholm functional score, and return to sports and professional activities at a minimum of two years. Secondary endpoints were complications, possible recurrence, and/or surgical revision. Recurrences, complications, and surgical recovery were gathered. RESULTS: Patients were evaluated with an average follow-up of 32 months. All patients were satisfied or very satisfied. The VAS significantly improved (0.2/10, p < 0.05) as well as the Lysholm score (97/100, p < 0.05). All patients returned to their professional activity: 11 within two months, one within six weeks, and one in the first post-operative week (this patient being a student). Only one patient did not resume pre-operative sport level due to a femoropatellar syndrome, not linked to the meniscal surgery performed. However, only 11 patients resumed their previous sport level (84.6%). No recurrence or surgical revision occurred. DISCUSSION: The results are good and similar to the literature, confirming the working hypothesis. These results are equivalent to partial meniscectomies and arthroscopic sutures associated with a procedure on the cyst by arthroscopy or arthrotomy. The literature is in favour of a procedure on the cyst. CONCLUSION: The results confirm the effectiveness of a direct approach suture of non-transfixing meniscal lesions associated with a cyst resection with a good functional recovery, without additional morbidity. The hypothesis was confirmed.

Discovery and process development of a novel TACE inhibitor for the topical treatment of psoriasis.

Targeting the TNFα pathway is a validated approach to the treatment of psoriasis. In this pathway, TACE stands out as a druggable target and has been the focus of in-house research programs. In this article, we present the discovery of clinical candidate 26a. Starting from hits plagued with poor solubility or genotoxicity, 26a was identified through thorough multiparameter optimisation. Showing robust in vivo activity in an oxazolone-mediated inflammation model, the compound was selected for development. Following a polymorph screen, the hydrochloride salt was selected and the synthesis was efficiently developed to yield the API in 47% overall yield.

Evaluation of the GADD45α-GFP GreenScreen HC assay for rapid and reliable in vitro early genotoxicity screening.

Twenty-two of Galderma's proprietary compounds were tested in the GADD45α-GFP 'GreenScreen HC' assay (GS), the SOS-ChromoTest and the Mini-Ames to evaluate GSs performance for early genotoxicity screening purposes. Forty more characterized compounds were also tested, including antibiotics: metronidazole, clindamycin, tetracycline, lymecycline and neomycin; and catecholamines: resorcinol mequinol, hydroquinone, one aneugen carbendazim, one corticoid dexamethasone, one peroxisome proliferator-activated receptor rosiglitazone, one pesticide carbaryl and two further proprietary molecules with in vitro genotoxicity data. With proprietary molecules, this study concluded that the GS renders the SOS-ChromoTest obsolete for in vitro screening. The GS confirmed all results of the Mini-Ames test (100% concordance). Compared with the micronucleus test, the GS showed a concordance of 82%. With known compounds, the GS ranked the potency of positive results for catecholamines in accordance with other genotoxicity tests and showed very reproducible results. It confirmed positive results for carbendazim, for tetracycline antibiotics and for carbaryl. The GS produced negative results for metronidazole, a nitroreduction-specific bacterial mutagen, for dexamethasone (a non-genotoxic apoptosis inducer), for rosiglitazone (a GADD45γ promoter inducer) and for clindamycin and neomycin (inhibitors of macromolecular synthesis in bacteria). As such, the GS appears to be a reproducible, robust, specific and sensitive test for genotoxicity screening.

Successful proof of concept of a micronucleus genotoxicity assay on reconstructed epidermis exhibiting intrinsic metabolic activity.

We investigated the commercially available Episkin LM™ reconstructed epidermis test system as a potential 3D model for human genotoxicity assessment by cytokinesis-block micronucleus assay to mitigate limitations of the currently accepted micronucleus test. We established appropriate culture conditions for cytokinesis-block micronucleus assay in maximizing the frequency of binucleated cells by choice of culture medium and calibration of the system exposure to the cytokinesis inhibitor Cytochalasin B, without affecting the basal frequency of micronuclei in the model. We confirmed that the application of the classic solvents had no significant effect on this basal level of micronuclei. We determined the performance of cytokinesis-block micronucleus assay in Episkin LM™ reconstructed epidermis to predict in vivo genotoxins by testing the genotoxicity potential of 17 well known in vivo genotoxic, progenotoxic and non-genotoxic reference chemicals over a 48 h and 72 h exposure period. We found that cytokinesis-block micronucleus assays in Episkin™ reconstructed epidermis following the 48 h-topical regimen had a specificity of 60-75% and a sensitivity of 83-85%, resulting in an overall accuracy of 76-82% for genotoxicity assessment in tissues depending on the assessment of the reference chemicals with equivocal genotoxic profiles in the literature. The positive micronucleus test results obtained without addition of any exogenous metabolic activation system confirmed the ability of Episkin LM™ reconstructed epidermis to intrinsically bioactivate progenotoxic chemicals. The evidence showed that the 72-h exposure protocol significantly improved the detection of progenotoxins. Taken together, our data demonstrated that the Episkin LM™ reconstructed epidermis system is a relevant in vitro tool in the study of genetic toxicology.