A2A adenosine receptor deletion is protective in a mouse model of Tauopathy.

Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.

Concomitant hysteroscopic endometrial ablation and Essure procedure: feasibility, efficacy and satisfaction.

OBJECTIVE: Hysteroscopic endometrial destruction procedures for abnormal uterine bleeding are an alternative to hysterectomy. Such procedures are not contraceptive and are performed on fertile patients, requiring long-term contraception. This is the first study evaluating long-term results of a combined procedure associating endometrial destruction and concomitant hysteroscopic tubal sterilization by Essure(®) micro-inserts. Our goal is to evaluate efficacy of endometrial destruction as well as hysteroscopic sterilization and satisfaction after a combined procedure in the case of abnormal uterine bleeding in non-menopausal patients. STUDY DESIGN: This is a retrospective study (Canadian task force II-2) that includes 131 patients operated with combined endometrial destruction and hysteroscopic tubal sterilization between 2002 and 2011 at our university hospital. The patients were contacted to answer a questionnaire. Statistical analysis was performed with SAS© version 9.2. (SAS Institute Inc., Cary, NC). RESULTS: Ninety-three patients out of 131 could be reached. The mean follow-up was of 37.8 months (min=8, max=87, SD=6.2). Thirty-eight patients (29%) were lost to follow-up. Essure(®) micro-inserts introduction success rate (evaluated on 131 patients) was 95.8%, and their position was appropriate in 81.1% of the 106 patients with position control. Efficacy of the procedure on the haemorrhagic symptoms (evaluated on 93 patients) was 80.6%. Twelve patients (12.9%) underwent a hysterectomy, 7 of which (58.3%) were a direct consequence of treatment failure. No pregnancies were reported. Satisfaction rate was of 90.3%. CONCLUSION: Inadequate position rates of the micro-inserts after 3 months seem somewhat above literature findings, though no pregnancy has been reported. However, recurrent bleeding symptoms and hysterectomy rates are consistent with those observed after an endometrial destruction procedure alone. Limitations are the limited number of patients, the bias inherent to retrospective studies (lost of follow-up, selection bias). The concomitant endometrial destruction and tubal sterilization by micro-inserts is a safe and efficient procedure.

[Complications of presumed benign ovarian tumors]. / Complications des tumeurs ovariennes présumées bénignes.

The main risk factor of adnexal torsion is a previous adnexal torsion (LE3). There is no clinical, biological or radiological sign that may exclude the diagnosis of adnexal torsion (LE3). The presence of flow at color Doppler imaging does not allow exclusion of the diagnosis (LE2). An emergent laparoscopy is recommended for adnexal untwisting (Grade B), except in postmenopausal women where oophorectomy is recommended (grade C). A persistent black color of the adnexa after untwisting is not an indication for systematic oophorectomy (grade C), since a functional recovery is possible (LE3). Ovariopexy is not routinely recommended following adnexal untwisting (grade C). The clinical signs of intra-cystic hemorrhage and those of rupture of the corpus luteum are not specific (LE4). MRI is not recommended to confirm the diagnosis of intra-cystic hemorrhage (grade C). Malignant transformation of an ovarian cyst is very rare. The presence of a benign ovarian cyst is not associated with an increased risk of ovarian cancer at long-term follow-up (LE2). For these women, an ultrasound follow-up is not recommended (grade C). Dermoid ovarian cyst containing nerve tissue can trigger the production of pathogenic auto-antibody-anti-NMDA, leading to encephalitis. A high proportion of thyroid tissue in a mature teratoma (struma ovarii) may cause hyperthyroidism.

[PROSPERE randomized controlled trial: laparoscopic sacropexy versus vaginal mesh for cystocele POP repair]. / Étude randomisée comparant la promontofixation cœlioscopique à la chirurgie prothétique par voie vaginale pour le traitement des cystocèles : PROSPERE (PROSthetic PElvic organ prolapse REpair).

BACKGROUND: Cystocele is a frequent and invalidating type of genital prolapse in woman. Sacropexy using synthetic mesh is considered the surgical gold standard, and the laparoscopic approach has supplanted the open abdominal route because it offers the same anatomical results with a lower morbidity. The use of mesh through the vaginal route may have many advantages: easiness to perform, shorter operative time and recovery, but may increase morbidity. In France, both laparoscopic sacropexy and vaginal mesh are commonly used to treat cystoceles. The French Haute Autorité de santé (HAS) has highlighted the lack of evaluation of safety assessment for vaginal meshes. METHOD/DESIGN: The main objective of the study is to compare the morbidity of laparoscopic sacropexy with vaginal mesh for cystocele repair. The primary endpoint will be the rate of surgical complications greater or equal to grade 2 of the Clavien-Dindo classification at 1-year follow-up. The secondary aims are to compare the functional results in the medium term (sexuality, urinary and bowel symptoms, pain), the impact on quality of life as well as anatomical results. PROSPERE is a randomized controlled trial conducted in 12 participating French hospitals. 262 patients, aged 45 to 75years old, with cystocele greater or equal to stage 2 of the POP-Q classification (isolated or not) will be included. Exclusion criterias are a previous surgical POP repair, and inability or contra-indication to one or the other technique. We have designed this study to answer the question of the choice between laparoscopic sacropexy and vaginal mesh for the treatment of cystocele. The PROSPERE trial aims to help better determine the indications for one or the other of these techniques, which are currently based on subjective choices or school attitudes. This is the reason why competent authorities have asked for such studies.

[Repeat mid-urethral sling procedure for recurrent female urinary stress incontinence after previous mid-urethral sling]. / Réintervention par bandelette sous-urétrale pour récidive d'incontinence urinaire d'effort féminine après une première bandelette sous-urétrale.

INTRODUCTION: There are few data concerning the results of the treatment of recurrent stress urinary incontinence (SUI) after redo mid-urethral sling (MUS) procedure. METHODS: Retrospective study concerning 34 patients presenting with recurrent SUI following the placement of a first MUS procedure and who have undergone a second MUS procedure. Results were evaluated objectively (cough stress test) and subjectively using international consultation on incontinence questionnaire-short form (ICIQ-SF). RESULTS: The surgical technique for the placement of the first MUS was a retropubic approach in seven (20.5%) cases and a transobturator approach in 27 (79.5%) cases. Concerning the redo MUS procedure, a retropubic procedure was performed in 25 (73.5%) patients and a transobturator procedure in nine (26.5%) patients. Among the 34 patients, 32 (94%) were re-examined at 2 months follow-up, and contacted through telephone after 1-year follow-up. Post-operatively, the cough stress test revealed no urine leakage in 27/32 (84%) patients. Median follow-up was 15.5 months. ICIQ-SF score was 0 (complete continence) in 19/32 (59%) patients; between 4 and 12 in 11/32 (34%) and between 13 and 20 in 2/32 (6%) patients. A bladder injury was diagnosed during the surgical procedure in two patients. A reintervention was required in 2/34 (5%) patients because of postoperative urinary retention or bladder outlet obstruction. A partial sling resection was required in 2/34 (5%) patients because of vaginal exposure of the synthetic sling. CONCLUSION: In this study, redo MUS procedure was associated with good functional results despite a high rate of complications.

[Pregnancy and postpartum of women with mid-urethral sling procedure: a review of the literature]. / Grossesse et post-partum des patientes porteuses de bandelette sous-urétrale: revue de la littérature.

OBJECTIVE: To realize a review of literature to observe the impact of pregnancy and delivery in patients who underwent mid-urethral sling procedure for stress urinary incontinence (SUI), in order to provide recommendations on the route of delivery. MATERIAL AND METHODS: Literature review from 1995 to 2012 on the database Pubmed/Medline including only studies involving pregnant women with mid-urethral sling procedure. RESULTS: Of the 35 published cases, 14 % of patients had a recurrence of SUI symptoms during pregnancy. Nineteen percent of patients who underwent a c-section had SUI symptoms in the immediate postpartum period, against 33 % of patients with vaginal deliveries (P=0.56). In the follow-up of delivery (>3 months), there was a persistent SUI in 20 % (7/34) of patients: 12.5 % (2/16) of women who underwent a c-section and 27.7 % (5/18) of women who had a vaginal delivery (P=0.75). CONCLUSION: Although c-section seems to slightly decrease the risk of recurrence of SUI comparing to the vaginal route, we do not recommend to propose a systematic elective c-section in these patients because of its morbidity and mortality and the possibility of repeat mid-urethral sling procedure.

[Superficial hysteroscopic resection for polypoid endometrium: preliminary results of an innovative approach for women of childbearing age]. / Résection superficielle par hystéroscopie d'un endomètre polypoïde : résultats préliminaires d'une approche novatrice pour les femmes en âge de procréer.

OBJECTIVE: To evaluate the reproductive safety and long-term efficacy of hysteroscopic superficial endometrial resection for polypoid endometrium in symptomatic patients (menorrhagia, dysmenorrhea and unexplained infertility). PATIENTS AND METHODS: The present retrospective descriptive case series study included 44 patients of reproductive age who underwent superficial hysteroscopic endometrial resection between January 1st, 2004 and December 31, 2009. Reproductive outcome, and the patients' perceptions of menstrual symptoms after the surgical intervention were collected from the clinical notes and a semi-structured telephone interview. RESULTS: Of the patients presenting abnormal uterine bleeding, 59% reported long-term improvement of this symptom; of those with dysmenorrhea, 52% reported long-term relief. Among 26 infertile women who wanted to become pregnant immediately after the procedure, 58% succeeded (n=15), with a live-born rate of 38%. The pregnancy rate in primary and secondary infertility cases was respectively 53% (n=8/15) and 64% (n=7/11). CONCLUSION: Superficial endometrial resection is an alternative for treating polypoid endometrium when it is associated with menorrhagia, dysmenorrhea and infertility. It treats menstrual symptoms successfully, with no adverse impact on fertility.

[Widespread of clinical practice guidelines, concerning urinary incontinence in women]. / Diffusion des recommandations pour la pratique clinique concernant l'incontinence urinaire de la femme.

OBJECTIVE: Recommendations for good clinical practice concerning the treatment of urinary incontinence in women are available from the HAS (Haute Autorité de santé or French National Authority for Health), the Collège national des gynécologues obstétriciens français (French national college of gynaecologists and obstetricians) and Association française des urologues (French association of urologists). We wanted to conduct the first investigation of these recommendations to primary care physicians (GPs) and gynaecologists in the cities located in the same area of health. METHODS: A questionnaire was sent to GPs and gynaecologists (French administrative divisions 78 and 92), with questions on the recommendations, as well as the methods of dissemination of these recommendations. Response rate: 22%. RESULTS: A total of 72 questionnaires were usable from 51 (71%) GPs and 21 (29%) gynaecologists. Of these, 76% of gynecologists and 47% of GPs were aware of recommendations from the HAS for clinical practice for urinary incontinence in women (P=0.04). Only 56% of doctors prescribed a urinalysis (dipstick or bacteriological urinalysis) and evaluated the residual urine in women seeking care for symptoms of urinary incontinence. Training for one or two days was the most desirable/popular method of dissemination of the recommendations (30 out of 72 doctors), followed by journals such as Prescrire, then the mailing and forms provided by the HAS, especially when combined with office visits from a representative of the HAS. CONCLUSION: This study provided an interesting perspective on the knowledge, dissemination and application of recommendations for good clinical practice concerning urinary incontinence in women.

[Peritoneal closure using absorbable knotless device during laparoscopic sacrocolpopexy]. / Péritonisation avec un fil cranté résorbable sans nœud en cours de promontofixation laparoscopique.

Laparoscopic sacrocolpopexy is one of the gold standards of pelvic organ surgery. However, this intervention is associated with long operation duration. One of the steps of this intervention (peritoneal closure) can be shortened using several methods of suturing (e.g. staples). Recently, a self-anchoring barbed suture has been described for wound closure. The goal of this initial feasibility study was to describe the use of the barbed suture (V-Loc™) in peritoneal closure during laparoscopic sacrocolpopexy.

[Fertility following myomectomy by laparotomy in women aged over 38]. / Fertilité après myomectomie par laparotomie pour les femmes de plus de 38 ans.

OBJECTIVES: Uterine fibroids is the most common benign pathology during reproductive age. Fibroids are implicated as a possible cause of infertility. The mechanism of infertility may depend on the size and the location of the fibroids and remain unclear. Myomectomy is performed in case of symptomatic patients who want to preserve their reproductive potential or in case of infertile patients. There are few data concerning fertility following abdominal myomectomy in patients over the age of 38. PATIENTS AND METHODS: Retrospective study of a case series. Assessment of reproductive outcome after abdominal myomectomy among patients older than 38 years. RESULTS: Abdominal myomectomy was performed on 34 patients aged over 38 during. Among these patients, 25 (74%) were contacted and 15 (60%) tried to obtain a pregnancy. Seven patients (46%) needed a new intervention. Five patients (33%) required intra-uterine insemination or in vitro fertilization and embryo transfer postoperatively. Three patients obtained a pregnancy and two (13%) had a delivery. All pregnancies were obtained spontaneously. None infertile or nulliparous woman before surgery became pregnant postoperatively. CONCLUSION: After 38 years old, nulliparity and infertility before abdominal myomectomy seem to be a factor of poor prognostic to become pregnant after surgery.

Use of bioluminescence imaging to track neutrophil migration and its inhibition in experimental colitis.

Inflammatory bowel disease (IBD) is associated with neutrophil infiltration into the mucosa and crypt abscesses. The chemokine interleukin (IL)-8 [murine homologues (KC) and macrophage inflammatory protein (MIP)-2] and its receptor CXCR2 are required for neutrophil recruitment; thus, blocking this engagement is a potential therapeutic strategy. In the present study, we developed a preclinical model of neutrophil migration suitable for investigating the biology of and testing new drugs that target neutrophil trafficking. Peritoneal exudate neutrophils from transgenic ß-actin-luciferase mice were isolated 12h after intraperitoneal injection with thioglycollate, and were assessed phenotypically and functionally. Exudate cells were injected intravenously into recipients with dextran sodium sulphate (DSS)-induced colitis followed by bioluminescence imaging of whole-body and ex vivo organs at 2, 4 and 16-22h post-transfer. Anti-KC antibody or an isotype control were administered at 20 µg/mouse 1h before transfer, followed by whole-body and organ imaging 4h post-transfer. The peritoneal exudate consisted of 80% neutrophils, 39% of which were CXCR2(+) . In vitro migration towards KC was inhibited by anti-KC. Ex vivo bioluminescent imaging showed that neutrophil trafficking into the colon of DSS recipients was inhibited by anti-KC 4h post-cell transfer. In conclusion, this study describes a new approach for investigating neutrophil trafficking that can be used in preclinical studies to evaluate potential inhibitors of neutrophil recruitment.

[Fetomaternal hemorrhage caused by intraplacental choriocarcinoma]. / Hémorragie foetomaternelle sur choriocarcinome placentaire.

A male infant was born at 41 weeks' gestation to a 34-year-old primiparous woman after an uneventful pregnancy. Physical examination showed extreme paleness. Fetal hemoglobin was 7.6g/dl and Kleihauher exam revealed fetomaternal hemorrhage. Pathology revealed in situ intraplacental choriocarcinoma. Serum human chorionic gonadotrophin level was undetectable 1 month after the delivery both in woman and in newborn. We suggest that a pathological examination of the placenta should be performed in any case of fetomaternal hemorrhage in order to avoid misdiagnosis of intraplacental choriocarcinoma.

Sacral reflexes and urinary incontinence in women: new concepts.

OBJECTIVE: The physiology of urinary continence is complex and the respective role of active and passive mechanisms is still subject to debate. Many different sacral reflexes are involved in these processes. The present literature review focuses on the neuromuscular mechanisms, which are involved in the pathophysiology of female stress urinary incontinence (SUI). MATERIAL AND METHODS: We performed a systematic review of the literature in the Medline, Pascal and Embase databases by using the following keywords: reflex, perineal, sacral, urethral pressure, urethra, pelvic floor, fatigue, continence, incontinence and muscle. RESULTS: In recent years, new pathophysiological hypotheses concerning abnormal pelvic floor muscle reflex responses to stress have been discussed and included an abnormal time course of pelvic floor muscle activation during coughing. It has also been suggested that unusually rapid fatigue of the pelvic floor muscle reflex may be involved in some women. CONCLUSION: Overall, there are arguments in favour of the involvement of neuromuscular dysfunction in the pathophysiology of female SUI - particularly dysfunctional and delayed pelvic floor muscle reflex responses during coughing. It would be useful to establish whether these neuromuscular dysfunctions may be remedied by physiotherapeutic pelvic floor muscle training.

[Cervical cerclage in 2008]. / Le cerclage du col utérin en 2008.

Cervical cerclage is a common surgical technique that has been used for more than 50 years to prevent preterm deliveries and in the management of a threatened second trimester loss. However, it remains one of the most controversial interventions in obstetrics and this is probably due to difficulties in diagnosing cervical insufficiency, which is based on a history of recurrent second trimester loss or early preterm delivery following painless cervical dilatation in the absence of contractions or bleeding. This article reviews in 2008 the current literature regarding the efficacy of elective cerclage, ultrasound-indicated cerclage, emergency cerclage, and cervico-isthmic cerclage for singletons and multiple pregnancies.