78 research outputs found

    Identifier et cibler les meilleurs antigĂšnes pour l’immunothĂ©rapie du cancer

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    Dans un contexte oĂč le transfert adoptif de lymphocytes T (ATC) reprĂ©sente l’avenir de l’immunothĂ©rapie du cancer, l’identification des meilleurs antigĂšnes associĂ©s aux molĂ©cules de classe I du CMH (MAP) Ă  cibler sur les cellules cancĂ©reuses est d’une importance capitale. Plusieurs types de MAP sont des cibles potentielles pour l’ATC : 1) les antigĂšnes mineurs d’histocompatibilitĂ© (MiHA) qui dĂ©rivent de polymorphismes gĂ©nĂ©tiques entre un donneur et un receveur lors d’un ATC, 2) les antigĂšnes associĂ©s aux tumeurs (TAA) qui peuvent dĂ©river de transcrits surexprimĂ©s et 3) les antigĂšnes spĂ©cifiques aux tumeurs (TSA) qui dĂ©rivent de mutations somatiques ou de transcrits exprimĂ©s de façon aberrante. Des centaines d’essais cliniques ont mis en Ă©vidence un potentiel thĂ©rapeutique pour chacune de ces classes de MAP. NĂ©anmoins, les ATC ciblant ces antigĂšnes sont utilisĂ©s en contextes largement diffĂ©rents: des lymphocytes T MiHA-spĂ©cifiques provenant d’un donneur compatible sont utilisĂ©s pour le traitement de cancers hĂ©matologiques tandis que des lymphocytes T TAA- ou TSA-spĂ©cifiques provenant du patient sont utilisĂ©s pour traiter des tumeurs solides. De fait, jamais ces diffĂ©rents types de MAP n’ont Ă©tĂ© comparĂ©s pour leur potentiel thĂ©rapeutique dans un mĂȘme modĂšle tumoral. L’objectif de cette thĂšse Ă©tait donc de mesurer et de comparer le potentiel thĂ©rapeutique de MiHA, TAA et TSA exprimĂ©s dans la lignĂ©e cellulaire EL4 afin de mieux comprendre les mĂ©canismes dictant leur immunogĂ©nicitĂ©. Nous avons donc sĂ©lectionnĂ© des MiHA et des TAA rapportĂ©s dans la littĂ©rature, puis avons dĂ©veloppĂ© une approche protĂ©ogĂ©nomique permettant d’identifier tous les types de TSA prĂ©sentĂ©s sur ces cellules. Nous avons ainsi dĂ©terminĂ© que : 1) Seuls les MAP perçus comme du non-soi (MiHA et TSA) peuvent induire de fortes rĂ©ponses anti-cancĂ©reuses, 2) Leur immunogĂ©nicitĂ© dĂ©pend de l’abondance et de l’aviditĂ© fonctionnelle des lymphocytes T antigĂšne-spĂ©cifiques et 3) La clonalitĂ© des antigĂšnes et la nature de leurs altĂ©rations gĂ©nĂ©tique dictent Ă©galement l’immunogĂ©nicitĂ© des TSA. En rĂ©sumĂ©, nous avons dĂ©veloppĂ© une plateforme permettant l’identification de MAP prĂ©sentĂ©s par les cellules cancĂ©reuses et identifiĂ© des paramĂštres permettant la priorisation de ceux-ci en contexte clinique.In a context where adoptive transfer of T lymphocytes (ATC) represents the future of cancer immunotherapy, the identification of the best antigens associated to major histocompatibility complex class I (MAPs) to target on cancer cells is of capital importance. Several types of MAPs expressed at the surface of cancer cells can be targeted for ATC: 1) minor histocompatibility antigens (MiHAs), that derive from germline polymorphisms between a donor and a recipient during an ATC, 2) tumor associated antigens (TAAs) that include antigens that derive from overexpressed transcripts in cancer cells compared to their normal counterpart and 3) tumor specific antigens (TSAs) that derive from somatic mutations or from aberrantly expressed transcripts in cancer cells. Hundreds of clinical trials have highlighted the therapeutic potential of each of these classes of antigens. Nonetheless, ATCs targeting these antigens have been studied in dramatically different contexts: donor-derived T cells targeting MiHAs are used for treating hematologic malignancies while patient-derived T cells targeting TAAs or TSAs are used for the treatment of solid tumors. As such, the therapeutic potential of these MAPs has never been assessed in a single tumor model. Thus, the goal of this thesis was to evaluate and compare the therapeutic potential of MiHAs, TAAs and TSAs expressed on the EL4 cell line to better understand the mechanisms dictating their immunogenicity. We first selected MiHAs and TAAs previously reported in the literature, then developed a proteogenomic approach that enabled us to identify all types of TSAs presented by EL4 cells. By doing so, we found that : 1) Only MAPs that are seen as non-self by T cells (MiHAs and TSAs) can induce strong antitumor responses, 2) Both the abundance and functional avidity of MiHA- or TSA-specific T cells dictated the immunogenicity of these antigens, and 3) The clonality of the antigen and the nature of their genetic alterations also represented an important parameter dictating TSAs’ immunogenicity. In conclusion, we developed a proteogenomic platform that will enable the identification of all types of cancer antigens and identified metrics that will guide the priorization of MiHAs and TSAs in a clinical setting

    Anatomic pitfalls for excision of deep endometriosis nodules of the sciatic nerve:Three-dimensional reconstruction and Surgical educational video

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    International audienceSTUDY OBJECTIVE: To highlight the anatomic keys in order to perform safely an excision of deep endometriosis nodule of sciatic nerve DESIGN: We present a didactic video combining: an anatomic three-dimensional reconstruction of the pelvis using the Anatomage¼ table and a surgical dissection video of the removal of deep endometriosis nodule of the left sciatic nerve. The patient’s approval was obtained. The patient consented that this surgical video is used for publication. SETTING: Tertiary referral center

    Determination of a Central Avascular Triangle within the Obturator Foramen: A Radioanatomic Study.

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    To map the vascular anatomy of the obturator foramen using fixed anatomic landmarks.Twenty obturator regions were dissected in 10 fresh female cadavers after vascular blue dye injection in five cadavers (50%). Furthermore, 104 obturator regions were reconstructed by angiotomodensitometry from 52 women under investigation for suspected arterial disease. The anatomy of the obturator region was mapped by measuring the distance of vascular structures from the middle of the two branches of the ischiopubic bone, which were used as fixed landmarks.The bifurcation of the obturator artery was at a mean (SD) distance of 30.0 mm (4.5) from the middle of the ischiopubic branch (MISP). The anterior branch of the obturator vessels was 15.2 mm (10.1) from the MISP. The posterior branch of the obturator vessels was 5.5 mm (4.0) and 23.6 mm (8.7) from the middle of the outer edge of the obturator foramen (MOE) and the MISP, respectively. Using 5° and 95° percentiles of these measurements we defined a central avascular triangle.Our data show that, beyond inter-individual variations, a central triangular avascular area can be identified in the obturator foramen between the posterior and anterior obturator artery using fixed landmarks

    Review of automated performance metrics to assess surgical technical skills in robot-assisted laparoscopy

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    International audienceIntroduction Robot-assisted laparoscopy is a safe surgical approach with several studies suggesting correlations between complication rates and the surgeon's technical skills. Surgical skills are usually assessed by questionnaires completed by an expert observer. With the advent of surgical robots, automated surgical performance metrics (APMs)-objective measures related to instrument movements-can be computed. The aim of this systematic review was thus to assess APMs use in robot-assisted laparoscopic procedures. The primary outcome was the assessment of surgical skills by APMs and the secondary outcomes were the association between APM and surgeon parameters and the prediction of clinical outcomes. Methods A systematic review following the PRISMA guidelines was conducted. PubMed and Scopus electronic databases were screened with the query "robot-assisted surgery OR robotic surgery AND performance metrics" between January 2010 and January 2021. The quality of the studies was assessed by the medical education research study quality instrument. The study settings, metrics, and applications were analysed. Results The initial search yielded 341 citations of which 16 studies were finally included. The study settings were either simulated virtual reality (VR) (4 studies) or real clinical environment (12 studies). Data to compute APMs were kinematics (motion tracking), and system and specific events data (actions from the robot console). APMs were used to differentiate expertise levels, and thus validate VR modules, predict outcomes, and integrate datasets for automatic recognition models. APMs were correlated with clinical outcomes for some studies. Conclusions APMs constitute an objective approach for assessing technical skills. Evidence of associations between APMs and clinical outcomes remain to be confirmed by further studies, particularly, for non-urological procedures. Concurrent validation is also required

    Étude observationnelle de la faisabilitĂ© et de la morbiditĂ© de l'hystĂ©rectomie vaginale ambulatoire: Ă  propos de 30 cas

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    International audienceObjective Outpatient surgery is nowadays a major evolution axis of the surgery in France. Outpatient vaginal hysterectomy is possible with the use of electrosurgical bipolar vessel sealing allowing the reduction of operative time and postoperative pain. Our aim was to study the feasibility and morbidity of outpatient vaginal hysterectomy by assessment of postoperative pain and satisfaction. Patients and methods Thirty patients were enrolled in this observational study. All patients underwent an outpatient vaginal hysterectomy with a standardized operative technic. Pain was evaluated by administering a 10 cm visual analogic scale (VAS) at the first and second postoperative days. The total duration of analgesic treatment was noticed. Patient's satisfaction was recorded at the postoperative visit one month after the intervention and by a telephonic interview. Results The mean operative time was 59.3 (25-110) minutes and the mean uterine weight was 170.2 (60-710) grams. No intraoperative complications were reported. Among the thirty patients, 3 (10%) were not discharged the same day. At the first and second postoperative days, the VAS was 4.40 and 4.35 respectively. The mean total duration of analgesic's use was 5 days (3-8 days). Patients were very satisfied of medical care in 36.7% of cases (11/30), satisfied in 53.3% (16/30) and not much satisfied in 10% (3/30). In total, 83.3% (25/30) have agreed to repeat the procedure in the ambulatory sector. Discussion and conclusion Outpatient vaginal hysterectomy seems to be a possible and a safe technique with a high patient's satisfaction in France at the present time

    Case report: Dyspareunia as a symptom of a pelvic schwannoma

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    International audienceSchwannomas are benign nerve tumors arising mainly in the intracranial, cervical, or lumbar regions. We describe the case of a presacral schwannoma in a 42-year-old woman. This atypical localization is most often discovered by symptoms related to compression of nervous structures. Our patient presented only with deep dyspareunia. The schwannoma was diagnosed on MRI which revealed a presacral hyperintense mass with an antero-posterior diameter of 47 mm opposite the S3 sacral orifice. After 6 years of follow-up, the mass was resected because of worsening dyspareunia and sudden lesion growth. The resection was performed through an open abdominal anterior approach and resulted in alleviation of the symptoms without postoperative complications. To our knowledge, this is the first case of pelvic schwannoma expressing a gynecological symptom such as dyspareunia

    Local injection of methotrexate ultrasound guided-transvaginal

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    International audienceNon-tubal ectopic pregnancies can be located in the uterine portion of the tube (interstitial or cornual), in the cervix (cervical), in a cesarian scar, in the ovary, or intra-abdominally. Even though they are rare, they are associated with a high mortality. Invasive surgeries such as cornuectomy and hysterectomy were common to treat them in case of hemorrhage. Thanks to recent advances in imaging techniques, diagnosis of non-tubal ectopic pregnancy is made earlier and conservative management has been developed in order to respect fertility of patients. Beyond these treatments, systemic or local injection of Methotrexate shows very good success.In the article, we aimed to describe the technics of vaginal injection of in situ methotrexate with ultrasound guidance

    Serum hCG threshold to assess medical abortion success

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    International audienceObjectives The main aim of the study was to establish a threshold for serum human chorionic gonadotropin (hCG) level that ruled out ongoing pregnancy after induced medical abortion (MA). The secondary aim was to discover risk factors for the need for uterine aspiration. Methods This prospective study included women who underwent MA with mifepristone-misoprostol at = 900 IU/l to diagnose ongoing pregnancy gave 100% sensitivity and 81.5% specificity, compared with 85.7% sensitivity and 83.5% specificity using a threshold >= 1000 IU/l. Independent risk factors for uterine aspiration requirement were gravidity (OR 3.8; 95% CI 1.1, 13.2; p = .001), gestational age >6 weeks (OR 6.0; 95% CI 1.8, 6.0; p = .006) and previous surgical abortion (OR 2.4; 95% CI 1.1, 5.2; p < .001). Conclusion Serum hCG measurement <900 IU/l, 14-21 days after MA, is an efficient strategy for excluding ongoing pregnancy after first trimester MA

    RÎle du gÚne sigma s de staphylococcus aureus dans la sévérité des mammites bovines

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    Staphylococcus aureus est un pathogĂšne opportuniste responsable de mammites chez les ruminants laitiers. Le degrĂ© de sĂ©vĂ©ritĂ© des mammites staphylococciques est trĂšs variable et dĂ©pend pour l’essentiel des souches impliquĂ©es. Cependant les facteurs staphylococciques associĂ©s Ă  la sĂ©vĂ©ritĂ© des infections sont encore mĂ©connus. Le gĂšne spĂ©cifiant le facteur sigma S (sigS) intervient dans la pathogenĂšse de S. aureus en modĂšle murin (septicĂ©mie et arthrite). Son inactivation conduit Ă  une rĂ©duction de la sĂ©vĂ©ritĂ© de l’infection, de la rĂ©ponse immunitaire et de la survie de la bactĂ©rie (Shaw et al., 2008, Miller et al., 2012). Nous avons prĂ©cĂ©demment caractĂ©risĂ© deux souches de S.aureus gĂ©notypiquement proches mais gĂ©nĂ©rant des mammitessĂ©vĂšres (souche O11) ou modĂ©rĂ©es (O46) (Le MarĂ©chal et al.,2011). L’une des diffĂ©rences caractĂ©risant O46 est une courte dĂ©lĂ©tion inactivant sigS. Pour vĂ©rifier l’implication de sigS dans la sĂ©vĂ©ritĂ© des mammites, nous avons construit un mutant du gĂšne sigS chez O11 reproduisant Ă  l’identique la copie tronquĂ©e de O46. Ce mutant a Ă©tĂ© caractĂ©risĂ© par des tests phĂ©notypiques, des infections de cultures cellulaires et des infections expĂ©rimentalessur un modĂšle de mammite murine. Le mutant ne prĂ©sente pas de baisse de virulence ni de survie en contexte mammite. Toutefois il induit chez les souris une rĂ©ponse immunitaire diffĂ©rente de celle de la souche sauvage.Le gĂšne sigS n’explique donc pas Ă  lui seul la moindre sĂ©vĂ©ritĂ© associĂ©e Ă  O46

    Local injection of methotrexate ultrasound guided-transvaginal

    No full text
    International audienceNon-tubal ectopic pregnancies can be located in the uterine portion of the tube (interstitial or cornual), in the cervix (cervical), in a cesarian scar, in the ovary, or intra-abdominally. Even though they are rare, they are associated with a high mortality. Invasive surgeries such as cornuectomy and hysterectomy were common to treat them in case of hemorrhage. Thanks to recent advances in imaging techniques, diagnosis of non-tubal ectopic pregnancy is made earlier and conservative management has been developed in order to respect fertility of patients. Beyond these treatments, systemic or local injection of Methotrexate shows very good success.In the article, we aimed to describe the technics of vaginal injection of in situ methotrexate with ultrasound guidance
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