Synaptotagmins 1 and 7 in vesicle release from rods of mouse retina.

Synaptotagmins are the primary Ca2+ sensors for synaptic exocytosis. Previous work suggested synaptotagmin-1 (Syt1) mediates evoked vesicle release from cone photoreceptor cells in the vertebrate retina whereas release from rods may involve another sensor in addition to Syt1. We found immunohistochemical evidence for syntaptotagmin-7 (Syt7) in mouse rod terminals and so performed electroretinograms (ERG) and single-cell recordings using mice in which Syt1 and/or Syt7 were conditionally removed from rods and/or cones. Synaptic release was measured in mouse rods by recording presynaptic anion currents activated during glutamate re-uptake and from exocytotic membrane capacitance changes. Deleting Syt1 from rods reduced glutamate release evoked by short depolarizing steps but not long steps whereas deleting Syt7 from rods reduced release evoked by long but not short steps. Deleting both sensors completely abolished depolarization-evoked release from rods. Effects of various intracellular Ca2+ buffers showed that Syt1-mediated release from rods involves vesicles close to ribbon-associated Ca2+ channels whereas Syt7-mediated release evoked by longer steps involves more distant release sites. Spontaneous release from rods was unaffected by eliminating Syt7. While whole animal knockout of Syt7 slightly reduced ERG b-waves and oscillatory potentials, selective elimination of Syt7 from rods had no effect on ERGs. Furthermore, eliminating Syt1 from rods and cones abolished ERG b-waves and additional elimination of Syt7 had no further effect. These results show that while Syt7 contributes to slow non-ribbon release from rods, Syt1 is the principal sensor shaping rod and cone inputs to bipolar cells in response to light flashes.

Predictive value of FDG-PET imaging for relapse in metastatic melanoma patients treated with immunotherapy.

BACKGROUND: Anti-PD1 immunotherapy has shown a sustainable clinical activity in patients with metastatic melanoma. However, strong predictive factors of the long-term response or risk of relapse remain to be identified. OBJECTIVES: To determine whether FDG-PET imaging could be superior to CT scan in distinguishing residual tumours versus the absence of tumour in patients with a partial response (PR) or stable disease (SD) and whether a complete metabolic response (CMR) was associated with better outcomes. METHODS: Retrospective study conducted in all patients with metastatic melanoma treated with anti-PD1 immunotherapy between October 2014 and October 2017 considered to be in complete remission. The primary outcome was the occurrence of a relapse during the follow-up. CT scan and FDG-PET scan had to be performed within a maximum of 2 months of treatment discontinuation. For CT imaging, the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 were used and included progressive disease (PD), SD, PR and complete response (CR). For FDG-PET imaging, the metabolic responses were classified as progressive metabolic disease, stable metabolic disease, residual FDG avidity (RFA) and CMR. RESULTS: Twenty-six patients were in complete remission after collegial decision. Two patients had a SD on CT scan and a CMR on FDG-PET scan, and none of them relapsed. Ten patients had a PR on CT scan and a CMR on FDG-PET scan, and none of them relapsed. The mean treatment duration to achieve a complete remission was 7 months (3-23). A univariate analysis showed that a RFA assessed on the FDG-PET scan was significantly associated with a relapse (P = 0.00231). CONCLUSIONS: Most patients with a PR on the CT scan and a CMR on the FDG-PET scan should be considered with a CR. Our study showed that FDG-PET imaging could play a crucial role in predicting the long-term outcome and help to decide whether treatment should be discontinued.

Protocol for a randomized controlled trial to assess two procedures of vaginal native tissue repair for pelvic organ prolapse at the time of the questioning on vaginal prosthesis: the TAPP trial.

BACKGROUND: Native tissue cystocele repair has been the cornerstone of prolapse surgery, especially since the learned societies warned clinicians and patients about serious mesh-related complications. Surgical techniques mainly consist in anterior colporraphy and vaginal patch plastron. However, success rates of native tissue cystocele repair are heterogeneous, depending on the design of studies and definition of outcomes. To date, high-quality data comparing vaginal native tissue procedures are still lacking. METHODS: Herein we aimed to describe the design of the first randomized controlled trial (TAPP) comparing anterior colporraphy (plication of the muscularis and adventitial layers of the vaginal wall) and vaginal patch plastron (bladder support anchored on the tendinous arch of the pelvic fascia by lateral sutures) techniques. Our aim is to assess the effectiveness of vaginal native tissue repair at 1 year for cystocele with a combined definition of success-anatomic and functional. The primary endpoint will be the success rate 1 year after surgery with a composite of objective and subjective measures (Aa and Ba points < 0 from POP-Q (Pelvic Organ Prolapse Quantification System) and a negative answer to question 3 of Pelvic Floor Distress Inventory and no need for additional treatment). DISCUSSION: A prospective study has found a success rate at 35% for anterior colporraphy based on a combined definition, both anatomic and functional, as recently recommended. However, the definition of anatomic was strict (POP-Q< 2), while it seems that the best definition of anatomic success is "no prolapse among the hymen", that is to say Aa and Ba points from the POP-Q classification < 0. We hypothesize that vaginal patch plastron will have a better anatomic and functional success comparatively to anterior colporraphy because native tissue is added, as it corrects both median and lateral cystoceles thanks to bilateral paravaginal suspension. TRIAL REGISTRATION: CHU LIMOGES is the sponsor of this research (n°87RI18_0013). This research is supported by the French Department of Health (PHRC 2018-A03476-49) and will be conducted with the support of DGOS (PHRC interregional - GIRCI SOHO). The study protocol was approved by the Human Subjects Protection Review Board (Comité de Protection des Personnes) on May 16, 2019. The trial is registered in the ClinicalTrials.gov registry ( NCT03875989 ).

[Risk of axillary recurrence after sentinel lymph node biopsy before neoadjuvant chemotherapy in breast cancer]. / Récidive axillaire après prélèvement du ganglion sentinelle avant chimiothérapie néoadjuvante dans le cancer du sein.

OBJECTIVES: In case of large breast cancer, neoadjuvant chemotherapy (NAC) can be performed to reduce the size of the tumor and thus perform a conservative surgery. The place of the sentinel lymph node biopsy (SLNB) in case of NAC is still debated. The main aim of this study is to assess the risk of axillary recurrence after negative SLNB before NAC. METHODS: It is a retrospective, observational and uni-centric study. We included 18 to 80-year-old patients with unilateral breast cancer requiring a NAC and with a negative SLNB before NAC. Our primary endpoint was axillary recurrence. RESULTS: Between August 2006 and October 2016, 64 patients had a negative GS performing before a NAC and did not benefit from axillary dissection after NAC. The average duration of follow-up was 37 months. During our follow-up, we did not find any cases of axillary recurrence. CONCLUSION: This study supports the reliability of lymph node status assessment using the SLNB before CNA.

[Reliability and reproducibility of introcular pressure (IOP) measurement with the Icare® Home rebound tonometer (model TA022) and comparison with Goldmann applanation tonometer in glaucoma patients]. / Fiabilité et reproductibilité des mesures de la pression intraoculaire par le tonomètre Icare® Home (modèle TA022) et comparaison avec les mesures au tonomètre à aplanation de Goldmann chez des patients glaucomateux.

PURPOSE: The Icare® Home tonometer is a new rebound tonometer, developed for intraocular pressure (IOP) self-monitoring. The main objective of our study was to evaluate the reliability and reproducibility of measurements taken with the Icare® Home tonometer in glaucoma patients compared to the Goldmann applanation tonometer. A secondary objective was to investigate factors that could influence the reproducibility of these measurements. MATERIALS AND METHODS: Fifty-two glaucoma patients were included in this prospective, non-randomized, monocentric study. IOP measurements were performed on the right eye and then on the left eye in the following order (3 measurements of IOP for each method): air tonometer (T-Air), Icare® Home tonometer by the patient (RT-P), Icare® Home tonometer by an ophthalmologist (RT-O), Goldmann applanation tonometer (GAT). RESULTS: Forty-four patients (85%) managed to take their IOP on both eyes with the Icare® Home tonometer. Mean IOPs were 14.35±3.93mmHg (T-Air), 13.43±4.65mmHg (RT-P), 14.13±4.29mmHg (RT-O), 14.74±3.84mmHg (GAT). The intraclass correlation indices (ICC) on the 3 repeated IOP measurements were 0.924, 0.872, 0.947 and 0.957, respectively. Bland-Altman analysis found a mean difference (bias) between GAT and RT-P, between GAT and RT-O, and between RT-O and RT-P, respectively, of 1.31, 0.61 and 0.70mmHg, with a 95% confidence interval of -3.34 to 5.96, -3.91 to 5.14 and -3.44 to 4.84mmHg, respectively. The reproducibility of the measurements taken with the Icare® Home tonometer did not vary according to corneal thickness or age of the patients. CONCLUSION: The Icare® Home tonometer provides reliable and reproducible IOP values in glaucoma patients, although it appears to slightly underestimate the IOP measurements compared to the Goldmann applanation tonometer.

[Uterus transplantation. Current situation]. / Transplantation utérine. État des lieux.

Except adoption, absolute uterine factor infertility lacks solution in case of motherhood desire. Gestational surrogacy is still not approved in France. Over the last decade, uterus transplantation experimentation made advances. Data from animal research, progress in immunosuppressive treatment and knowledge about pregnancy after transplantation provide a scenario in which a human allotransplantation project can become reality.