Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex.

Optogenetics has revolutionized neurosciences by allowing fine control of neuronal activity. An important aspect for this control is assessing the activation and/or adjusting the stimulation, which requires imaging the entire volume of optogenetically-induced neuronal activity. An ideal technique for this aim is fUS imaging, which allows one to generate brain-wide activation maps with submesoscopic spatial resolution. However, optical stimulation of the brain with blue light might lead to non-specific activations at high irradiances. fUS imaging of optogenetic activations can be obtained at these wavelengths using lower light power (< 2mW) but it limits the depth of directly activatable neurons from the cortical surface. Our main goal was to report that we can detect specific optogenetic activations in V1 even in deep layers following stimulation at the cortical surface. Here, we show the possibility to detect deep optogenetic activations in anesthetized rats expressing the red-shifted opsin ChrimsonR in V1 using fUS imaging. We demonstrate the optogenetic specificity of these activations and their neuronal origin with electrophysiological recordings. Finally, we show that the optogenetic response initiated in V1 spreads to downstream (LGN) and upstream (V2) visual areas.

Fertility preservation after fertility-sparing surgery in women with borderline ovarian tumours.

OBJECTIVE: To present a case series of women with borderline ovarian tumours (BOTs) who underwent oocyte vitrification in addition to fertility-sparing surgery. STUDY DESIGN: Observational study of all women referred to a French fertility preservation unit between 2015 and 2019 for counselling regarding a fertility preservation (FP) strategy after BOT fertility-sparing surgery. All eligible women underwent one or more cycles of controlled ovarian stimulation (COS) using an antagonist protocol, followed by oocyte retrieval. Metaphase II (MII) oocytes were vitrified. RESULTS: Twenty-five women with BOTs were referred during the study period. Among them, 11 women underwent at least one cycle of COS. One hundred and seven MII oocytes were vitrified. The mean number of vitrified MII oocytes per woman was 9.7 (standard deviation 5.2). Five live births were reported during follow-up of four women with vitrified oocytes: three spontaneous pregnancies, one in-vitro fertilization cycle with fresh embryo transfer, and one live birth after return of vitrified oocytes. CONCLUSION: Conservative surgery for BOTs offers a high spontaneous pregnancy rate but has a higher risk of relapse than radical treatment. Furthermore, women who undergo conservative BOT surgery have a higher risk of surgery-induced premature ovarian failure. Oocyte cryopreservation after COS appears to be an effective technique after the conservative management of BOTs in women of reproductive age. Although the available short-term data are reassuring, further long-term studies evaluating the safety and cost-effectiveness of this systematic FP strategy after BOT fertility-sparing surgery are required.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

The French national network dedicated to rare gynecological cancers diagnosis and management could improve the quality of surgery in daily practice of granulosa cell tumors. A TMRG and GINECO group Study.

OBJECTIVE: The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs). METHODS: This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines. RESULTS: Median age at diagnosis was 49 years old (range 10-89). The median size of tumor was 94 mm (range 5-400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p < 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p < 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery. CONCLUSION: Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors.

Suspended sediment flux at the Rhone River mouth (France) based on ADCP measurements during flood events.

Suspended sediment distribution and fluxes were estimated within the dominant channel at the mouth of the Rhone River for two annual flood events. The estimates were based on ADCP acoustic backscatter intensity and using calibration and post-processing methods to account for the grain-size distribution (GSDs). The fluxes were very similar to those obtained from suspended sediment measurements based on surface sampling at an automated station located 35 km upstream. Suspended sediment concentrations (SSC) and GSDs showed little variation along the channel cross-section, except for a graduate suspension that appeared at the maximum of discharge, corresponding to velocities lower than 1 m s-1 near the bottom. However, without post processing to account for the GSD, an under-estimation of 10% was observed during the two flood periods. The two flood events (12 November 2012 and 29 November 2012), separated by only 2 weeks, had clear differences in suspended sediment fluxes (SSF) and SSC during the peak of the river discharge, with twice more flux during the first, respectively, 925,226 and 430,879 tons of SSF.

Pelvic exenterations for gynecologic cancers: A retrospective analysis of a 30-year experience in a cancer center.

INTRODUCTION: The objective of this study was to report a 30-year experience of PE for gynecologic malignancies in a cancer center. MATERIALS AND METHODS: A retrospective study was conducted at Institut Paoli-Calmette including patients who underwent PE for gynecologic malignancies. Four periods were evaluated: P1 before 1992, P2 between 1993 and 1999, P3 between 2000 and 2006 and P4 after 2006. The study evaluated the number of PE performed during each period, the type of PE, its level, indication, location of the primary tumor, patient age, previous radiotherapy ≥45 Gy, the rate of "curative" PE and exenteration-related reconstructive techniques. 90-day post-operative mortality and morbidity using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 4.03 were reported. RESULTS: 277 PE were performed. The number of PE performed for recurrences rose during the study period (p = 0.042), PE performed for central tumors increased during P3 (64.4%) and P4 (67.4%) (p < 0.0001) and administration of radiotherapy ≥45 Gy was more frequent (p < 0.0001). The rate of "curative" PE increased (p < 0.0001). In multivariate analysis, "curative" PE were correlated with PE type, central locations and study period. Pelvic filling was progressively more frequently performed (p = 0.002). 90-day complication rate was 56.3%. In multivariate analysis there was a significant difference in distribution of CTCAE grade 3-4-5 morbidity depending on the period. Overall survival (OS) improved during the 2 last periods (p = 0.008). CONCLUSION: A better selection of eligible patients for PE, namely through improvement in imaging techniques, has enabled to raise the rate of curative PE.

5-year overall survival after early breast cancer diagnosed during pregnancy: A retrospective case-control multicentre French study.

BACKGROUND: Breast cancer diagnosed during pregnancy (BCP) is rare, but the prevalence is expected to rise. Long-term follow-up data regarding this clinically challenging condition are scarce. The main objective of this multicentre case-control French study was to compare the survival between pregnant patients and matched controls. METHODS: Patients from 27 centres diagnosed between 2000 and 2009 with histologically proven invasive breast cancer occurring during pregnancy were retrospectively included. Controls were matched to BCP patients on age, clinical T stage, hormone receptor, HER2, administration of neo-adjuvant chemotherapy and pathological node involvement in the absence of neo-adjuvant chemotherapy. Five-year overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS) rates were estimated using the Kaplan-Meier method. RESULTS: One hundred and eleven BCP patients and 253 controls were included. Median age was 33 and 35 years, respectively. Both populations were managed similarly, except for less frequent sentinel node dissection (p = 0.026) and taxane administration (p = 0.03) among BCP patients. Median follow-up was 7.5 years. Survival rates were similar between both BCP and control patients: 5-year OS rates were 83.1% (95% CI: 74.5-89.0) vs 85.5% (95% CI: 80.4-89.4), respectively, p = 0.31; 5-year DFS rates 60.0% (95% CI: 50.1-68.6) vs 68.5% (95% CI: 62.3-73.9), respectively, p = 0.12 and 5-year MFS rates 71.0% (95% CI: 61.3-78.6) and 74.5% (95% CI: 68.6-79.5), respectively, p = 0.21. CONCLUSION: Our study showed that the survival outcomes of patients diagnosed with BCP were not significantly different as compared to those of matched non-pregnant controls. A proper management of women diagnosed with BCP is crucial.

Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer.

BACKGROUND: PM01183 is a new compound that blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. PM01183 showed strong antitumor activity in preclinical models of cisplatin-resistant epithelial ovarian cancer. PATIENTS AND METHODS: Patients with platinum-resistant/refractory ovarian cancer were included in a two-stage, controlled, randomized (in a second stage), multicenter, phase II study. Primary endpoint was overall response rate (ORR) by RECIST and/or GCIG criteria. The exploratory first stage (n = 22) confirmed the activity of PM01183 as a single agent at 7.0 mg flat dose every 3 weeks (q3wk). The second stage (n = 59) was randomized and controlled with topotecan on days 1-5 q3wk or weekly (every 4 weeks, q4wk). RESULTS: ORR was 23% (95% CI, 13%-37%) for 52 PM01183-treated patients. Median duration of response was 4.6 months (95% CI, 2.5-6.9 months), and 23% (95% CI, 0%-51%) of responses lasted 6 months or more. Ten of the 12 confirmed responses were reported for 33 patients with platinum-resistant disease [ORR = 30% (95% CI, 16%-49%)]; for the 29 patients treated with topotecan in the second stage, no responses were found. Median PFS for all PM01183-treated patients was 4.0 months (95% CI, 2.7-5.6 months), and 5.0 months (95% CI, 2.7-6.9 months) for patients with platinum-resistant disease. Grade 3/4 neutropenia in 85% of patients; febrile neutropenia in 21% and fatigue (grade 3 in 35%) were the principal safety findings for PM01183. CONCLUSION: PM01183 is an active drug in platinum-resistant/refractory ovarian cancer and warrants further development. The highest activity was observed in platinum-resistant disease. Its safety profile indicates the dose should be adjusted to body surface area (mg/m2). TRIAL CODE: EudraCT 2011-002172-16.

Buccodental side effects of sunitinib in patients with metastatic renal cell carcinoma.

BACKGROUND: Sunitinib is a tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC). Few data evaluated severe buccodental adverse events. The aim of this study was to evaluate sunitinib buccodental toxicity in patients with metastatic RCC and to compare it with that of standard chemotherapy in patients with other solid cancers. METHODS: Patients with RCC treated with sunitinib and patients with other solid tumours treated with chemotherapy were followed for 3 months. Data on dental appliances, oral hygiene/care practices before and during treatment were collected. RESULTS: A total of 116 patients were included (58 RCC treated by sunitinib: group S, and 58 treated by chemotherapy: group C). No differences in dental care habits were noted before treatment. In group S, patients reported significantly more frequent pain (P<0.01), teeth instability (P=0.01), gingival bleeding (P=0.01) and change in teeth colour (P=0.02). In all, 58% of patients in this group had to modify their diet (P<0.01). Frequency of dentist visits for teeth removal was increased (25% vs 8%, P=0.01). CONCLUSION: Sunitinib seems to increase buccodental toxicity as compared with chemotherapy. This finding emphasises the need for optimal dental care and standardised dental follow-up in patients treated with sunitinib.

Ultrasound monitoring in patients undergoing in-vitro fertilization after methotrexate treatment for ectopic pregnancy.

OBJECTIVES: To compare sonographic characteristics of the endometrium and follicles during in-vitro fertilization (IVF) before and after methotrexate (MTX) treatment for ectopic pregnancy. METHODS: This retrospective study, conducted at Conception Hospital from January 2000 to July 2007, included all patients diagnosed with an ectopic pregnancy resulting from IVF treatment that was treated with MTX and who then underwent another IVF cycle. We compared the number and size of follicles and the endometrial thickness and quality on the day of human chorionic gonadotropin injection in the cycles before and after the MTX treatment to determine whether MTX had any effect. RESULTS: Eleven patients were included in the study. The median interval between the IVF cycle resulting in ectopic pregnancy and the first IVF cycle after MTX therapy was 180 (range, 150-900) days. There was no statistically significant difference between the before and after MTX treatment groups with respect to number of follicles (14 (3-20) vs. 9 (4-16), P = 0.12), follicle size (16.5 (14.7-21.7) mm vs. 17.8 (14.9-19.8) mm, P = 0.37), endometrial thickness (10.0 (9.5-12.0) mm vs. 10.0 (7.5-14.0) mm, P = 0.31) or endometrial quality (P = 0.32). Four women became pregnant during the IVF cycle following MTX treatment. CONCLUSIONS: Ultrasound monitoring showed no modification of the characteristics of the endometrium or follicles during IVF after MTX treatment for ectopic pregnancy.

[Medical abortion at home and at hospital: a trial of efficacy and acceptability]. / Interruption volontaire de grossesse médicamenteuse à domicile et à l'hôpital : étude d'efficacité et d'acceptabilité

OBJECTIVES: To evaluate the efficacy and the acceptability of medical abortion at home and at hospital. PATIENTS AND METHODS: From 11 February 2008 to 16 July 2008, 399 patients were included in the study: 173 at home and 226 at hospital. RESULTS: Efficacy was evaluated for 305 patients because 94 were lost of follow-up (23.6%). Efficacy of medical abortion was 86.7% (124/143) at home and 95.8% (155/162) at hospital. There were one ongoing pregnancy and 25 surgical aspirations (8.6%). The family planning nurse received a phone call from five patients after mifepristone at home (2.9%) and seven patients after mifepristone at hospital (3.1%). Only one patient "at home" had an emergency consultation (0.6%) and nine patients "at hospital" (4%). Ten patients went back to their gynecologist before their appointment for follow-up (2.5%): five "at home" (2.9%) and five "at hospital" (2.2%). Thirteen patients were referred by the private provider to the hospital medical specialist. Acceptability is known for 70.2% of patients: 98% thought that medical abortion at home was acceptable and 92.9% at hospital. DISCUSSION AND CONCLUSION: The failure rate of medical abortion is higher at home and is due to aspirations for incomplete abortion. The procedure at home seems to be more acceptable than at hospital. It will be interesting to realize a prospective randomized study to compare the procedures at home and at hospital.

[Maternal morbidity after Thierry's spatulas and vacuum deliveries]. / Morbidité maternelle immédiate après extraction instrumentale par spatules de Thierry et par ventouse obstétricale.

OBJECTIVE: To compare maternal morbidity after Thierry's spatulas or vacuum-assisted deliveries. PATIENTS AND METHODS: Retrospective study, at the French hospital la Conception, in Marseilles. All successful instrumental deliveries between November 2003 and May 2005 were reviewed, that is to say 264. Univariate and multivariate analysis were performed comparing maternal morbidity in the two groups. The primary outcome measure was perineal trauma. Secondary outcomes were blood loss and duration of hospitalization. RESULTS: Among the 264 deliveries, there were 96 vacuum deliveries and 168 Thierry's spatulas extraction. Thierry's spatulas were use more often in nulliparous patient (<0.001). Patients in the group of Thierry's spatulas have a higher rate of epidural analgesia (p=0.05), a longer duration of first (p=0.002) and second stage of labor (p=0.03). There was no difference in incidence of sphincter tears between women who underwent Thierry's spatulas and those who underwent vacuum delivery with respective incidence of 4.2 and 3.2% (p=0.67). There was a significant difference in post-partum hemoglobin value with a higher blood loss in the group of Thierry's spatulas (<0.001). Mean duration of hospitalization was longer in the group with Thierry's spatulas (5.6 days) than in the group who underwent vacuum delivery (4.7 days) (p<0.001). DISCUSSION AND CONCLUSION: Incidence of third degree tears was similar between the vacuum and Thierry's spatulas group. Deliveries with vacuum are associated with less blood loss and a shorter hospitalization stay.

[Isolated tubal torsion: about three cases]. / Torsion tubaire isolée: à propos de trois cas.

Isolated torsion of the Fallopian tube is a rare event and diagnosis is difficult. Coelioscopy is necessary to establish the diagnosis, but surgery often occurs too late for tube conservation. This report focuses on three cases of isolated tubal torsion. The laparoscopy confirms the diagnosis but conservative treatment was not possible. Based on this experience, diagnostic difficulties, echography, treatment and causes are discussed. Isolated Fallopian tube torsion should be suspected in case of acute pelvic pain in female patient. Early surgical intervention is necessary.

[Good practice and accuracy of office hysteroscopy and endometrial biopsy]. / Bonne pratique et valeur diagnostique de l'hystéroscopie diagnostique et des prélèvement histologiques.

Office hysteroscopy may be performed without anaesthesia. Endometrial biopsy can be performed during hysteroscopy. Antalgics or other treatment to reduce discomfort are not indicated. Prophylactic antibiotics are not indicated. Diagnostic value of hysteroscopy for endometrial pathology is interesting. Pipelle is the most appropriate instrument for endometrial biopsy.

[Low urinary tract symptoms after Thierry's spatula delivery at first pregnancy]. / Symptômes urinaires après extraction instrumentale par spatules de Thierry au cours du premier accouchement.

OBJECTIVE: This study was undertaken to evaluate prevalence of low urinary tract symptoms (LUTS) after Thierry's spatula delivery at first pregnancy. PATIENTS AND METHODS: A retrospective study of 236 primiparous with instrumental delivery or spontaneous delivery who had delivered from January 2001 to December 2002. Low urinary tract symptoms (LUTS) were evaluated one year after delivery with a questionnaire. Incidence of LUTS was compared depending on mode of delivery. RESULTS: Of the 236 patients included, 88.1% replied to the questionnaire, 106 who delivered spontaneously and 102 who underwent Thierry's spatula delivery. The incidence of urinary incontinence was similar after instrumental deliveries and after spontaneous vaginal deliveries (34.9 versus 24.5%, p=0.10). In univariate analysis, symptoms of urinary urgency and urinary frequency were higher after instrumental delivery than after spontaneous delivery, respectively, 34.9 versus 22.5%, p=0.049 and 19.8 versus 8.8%, p=0.03. After controlling for confounding factors, no difference in LUTS was observed between the two groups; the respective adjusted odds-ratios (95% IC) were 1,5 (0.8-3) for urinary incontinence, 1.7 (0.9-3.5) for urgency and 2.5 (0.9-6.3) for urinary frequency. DISCUSSION AND CONCLUSION: One year after delivery, one third of patients will present urinary incontinence and more than 50% will complain of bladder instability symptoms. Compared to spontaneous vaginal delivery, the use of Thierry's spatulas at first pregnancy does not induce higher risk of LUTS.

[What are at present the real hopes of pregnancy after ovarian cryopreservation?]. / Quels sont actuellement les espoirs réels de grossesse après cryoconservation ovarienne?

Survival rates for cancers that occur in childhood and adolescence have improved over the last decades, and preservation of future fertility in these patients has become a relevant issue. Premature ovarian failure is a consequence of exposing women to chemotherapeutic drugs and ionizing radiation. Ovarian cryopreservation is an alternative to cryopreservation of embryos or oocytes for theses patients. Ovarian cryopreservation aims to reimplant ovarian tissue after complete remission into the pelvic cavity (orthotopique site) or a heterotopic site like the abdominal wall or the forearm. In vitro folliculogenesis, that aims at the maturation of ovarian cortex primordial follicles cryopreserved for a FIV, is still in an experimental research stage. In this review, the objective was to evaluate the real hopes of pregnancy after ovarian cryopreservation. Indeed, many teams offer ovarian cryopreservation at present time, although only two pregnancies have been achieved to date. In both cases, it can be discussed whether the fertilized oocyte originated from the transplant or from the native ovary. Furthermore, the potential for reintroduction of cancerous cells may limit this technique in cancers that are known to have a risk of ovarian dissemination. The hopes engendered by ovarian cryopreservation, but also its limits, must be explained to the patients before an ovarian surgery for cryopreservation.

Proteomics of primary mesenchymal stem cells.

Tissue and functional regeneration takes place in the body at various stages throughout life. However, bone, cartilage, tendons, blood vessels and cardiac muscle have a limited capacity for self repair and, after injury or disease, the regenerative ability of these adult tissues is often insufficient and leads to nonfunctional scar tissue. In this context, mesenchymal stem cells, which are adult multipotential progenitors of mesoderm cells (osteoblasts, chondrocytes, adipocytes and stroma cells), represent a major hope for tissue-engineered replacement and regenerative medicine. Furthermore, the autologous use of these cells prevents immunological responses against new tissues and the risks of disease transmission from donors, which are both common problems of organ transplantation. While the existence of mesenchymal stem cells is undisputed, many questions remain regarding their self-renewal and capacity to differentiate, their homogenous nature as a cell population throughout the body and their true potential in regenerative medicine. In this article, the proteomics studies carried out to characterize mesenchymal stem cells and to help understand their physiology are reviewed.

Strouhal-Reynolds number relationship for bluff-body flows numerically simulated by an artificial boundary method.

The incidence of the numerical resolution and the blockage effect are investigated in an embedding method for solving bidimensional bluff body flows. This method consists of using an artificial boundary instead of imposing exact conditions on the body surface. It requires us to define a blur frontier ratio and a blockage effect ratio. The blockage effect ratio is found using the mean flow of a circular cylinder directly. The blur frontier ratio is obtained by comparison of the present method with another numerical method where explicit boundary conditions on the body are imposed. For this ratio, the investigations are based on the flow past a square cylinder which discard the uncertainty on the surface of the body for the embedding method. Hence, the two factors allow the transformations of the Strouhal and the Reynolds numbers for the flow past a circular cylinder. The universal Strouhal-Reynolds number relationship of the circular cylinder is finally recovered.