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The long-term consequences of pre-eclampsia (PrE) for renal function have never been determined in patients with sickle cell disease (SCD). Between 2008 and 2015, we screened 306 pregnancies in women with SCD and identified 40 with PrE (13%). The control group consisted of 65 pregnant SCD patients without PrE. In multivariable analysis, PrE events were associated with an increase of 1 log of lactate dehydrogenase level (adjusted odds ratio, aOR = 3·83, P = 0·05), a decrease of 10 g/l of haemoglobin levels (aOR = 2·48, P = 0·006) and one or more vaso-occlusive crisis during pregnancy (aOR = 16·68, P = 0·002). Estimated glomerular filtration rate (eGFR) was similar in the two groups at steady state but was significantly lower in the PrE group after one year of follow-up and at last follow-up (130 vs 148 ml/min/1·73 m2 , P < 0·001 and 120 vs 130 ml/min/1·73 m2 , P < 0·001, respectively). In multivariable analysis, eGFR had returned to steady-state levels one year after pregnancy in patients without PrE but continued to decrease in patients with PrE (β = -18·15 ml/min/1·73 m2 , P < 0·001). This decline was more marked at the end of follow-up (β = -31·15 ml/min, P < 0·001). In conclusion, PrE episodes are associated with a significant risk of subsequent renal function decline in SCD patients.

Background/aim Magnetic resonance (MR) and ultrasound (US) fusion imaging (MR-US fusion) is already used to guide prostate biopsies and has been proven accurate for diagnosing cervical cancer. In this study, we aimed to evaluate the feasibility and performance of MR-US fusion for characterizing adnexal masses. Patients and methods A retrospective study was conducted between 2014 and 2018 including women referred to our Gynaecological Oncology Department for characterization of an adnexal mass (n=106). Performance of MR-US fusion was evaluated in a subgroup of patients who underwent surgery (n=26). Two readers, blinded to final histology, performed and rated US findings according to the International Ovarian Tumor Analysis simple rules score, MR according to Ovarian-Adnexal Reporting Data System Magnetic score, and MR-US fusion through a tailored score. The reference outcome was the final pathology. Results MR-US fusion had a sensitivity of 100% (95%CI=80-100), specificity of 89% (95%CI=52-99), positive likelihood ratio of 9 (95%CI=1.4-57), and accuracy of 96% (95%CI=80-99). Conclusion MR-US fusion is feasible for characterizing adnexal masses to predict ovarian cancer.

International audience; Introduction: Gestational age at delivery seems to be a risk factor of recurrence of preeclampsia. The objective of this study was to analyze adverse pregnancy outcomes and recurrence of preeclampsia during the subsequent pregnancy in women with a history of pre-eclampsia delivered before 26 weeks of gestation.Material and method: We performed a retrospective study in two French tertiary care hospitals between 2000 and 2018. Patients with a history of pre-eclampsia delivered before 26 weeks of gestation were analyzed. Information on the immediate subsequent pregnancy was collected. Adverse composite outcome was defined as recurrent preeclampsia, HELLP syndrome, placental abruption, fetal growth restriction

Chronic hypertension affects 1 to 5% of women of childbearing age. During pregnancy, chronic hypertension is associated with an increased risk of vascular disease such as superimposed preeclampsia (PE), intrauterine growth retardation (IUGR), placental abruption, and preterm delivery. These serious and frequent pathologies, specific to pregnancy, carry a particularly high risk of maternal complications (HELLP syndrome, eclampsia, maternal death) and perinatal complications (perinatal death, neurological disorders). To date, there is no curative treatment of vascular complications of chronic hypertension during pregnancy. The only effective treatment, once the complications are established, is usually stopping the pregnancy and delivering the placenta. Some recommendations suggest the use of low dose aspirin in the prevention of these complications. Although the efficacy of low-dose aspirin is assumed in patients with previous preeclampsia, few studies have evaluated its efficacy in patients with chronic hypertension. Controlled prospective studies using very low doses of aspirin (less than 100 mg) and started after 15 weeks of gestation do not seem conclusive. The objective of this work is first to detail the complications of chronic hypertension during pregnancy, then to analyze the studies which evaluated the interest of low dose aspirin in prevention of the placental vascular complications of the pregnancy in patients with chronic hypertension. We also propose an update on the European and North American national recommendations for the prevention of preeclampsia by low dose aspirin in the high-risk population of patients with chronic hypertension. Finally we present the CHASAP (Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy) trial (NCT04356326), a multicentric prospective randomized double-blind superiority trial, which will compare, in pregnant women with chronic hypertension, the efficacy of low dose aspirin (150 mg/day) with a placebo, in the prevention of maternal-fetal morbidity and mortality (preeclampsia, placental abruption, IUGR, perinatal death, maternal death, and preterm delivery).

International audience; Objective: Severe preeclampsia may require the delivery of the placenta to avoid life-threatening complications for the mother. Before 26 weeks of gestation, this often results in perinatal death. A decrease in soluble fms-like tyrosine kinase 1 (sFlt1), an anti-angiogenic factor central to the pathophysiology of the maternal syndrome, has been reported after LDL- apheresis. The present study tested whether LDL-apheresis could be used to allow women with early and severe preeclampsia to reach a gestational age where the baby had a viable chance of survival.Study Design: A phase II prospective study. Adult women were included if they had very early (

Background Recent studies have challenged radical procedures for less extensive surgery in selected patients with early-stage cervical cancer at low risk of parametrial invasion. Our objective was to identify a subgroup of patients at low risk of parametrial invasion among women having undergone surgical treatment. Methods Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with early-stage (IA2–IIA) disease treated by radical surgery including hysterectomy and trachelectomy, were selected for further analysis. The Kaplan–Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariate analysis, was used to account for the influence of multiple variables. Results Out of the 263 patients included for analysis, on final pathology analysis 28 (10.6%) had parametrial invasion and 235 (89.4%) did not. Factors significantly associated with parametrial invasion on multivariate analysis were: age > 65 years, tumor > 30 mm in diameter measured by MRI, lymphovascular space invasion (LVSI) on pathologic analysis. Among the 235 patients with negative pelvic lymph nodes, parametrial disease was seen in only 7.6% compared with 30.8% of those with positive pelvic nodes (p

Background Actual European pathological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely stratify recurrence risk, leading to potential over or under treatment. Micro-RNAs are post-transcriptional regulators involved in carcinogenic mechanisms, with some micro-RNA patterns of expression associated with EC characteristics and prognosis. We previously demonstrated that downregulation of micro-RNA-184 was associated with lymph node involvement in low-risk EC (LREC). The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from LREC women can be correlated with the occurrence of recurrences. Methods MicroRNA expression was assessed by chip analysis and qRT-PCR in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R−), matched for grade and age. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. Results The expression levels of micro-RNAs-184, -497-5p, and -196b-3p were significantly lower in R+ compared to R− women. Women with a micro-RNA-184 fold change 0.083 (n = 1; 8%), p = 0.016. Women with a micro-RNA-196 fold change 0.56 (n = 2; 13%), p = 0.001. Conclusions These findings confirm the great interest of micro-RNA-184 as a prognostic tool to improve the management of LREC women.

Background Congenital arteriovenous malformations (AVMs) are infrequent but represent a serious medical challenge because of their unpredictable progression and high hemodynamic activity. Case We report on the treatment of a voluminous vulvar AVM in a 16-year-old girl. After failure of medical therapy, we performed a radical surgical resection with preliminary embolization and flap reconstruction. Summary and Conclusion A multidisciplinary approach is required for AVM management. Early intervention and complete surgical resection combined with preliminary embolization represents the ideal therapy.

Objective To evaluate whether daily low-molecular-weight (LMW) heparin prophylaxis during pregnancy alters profile of circulating angiogenic factors that have been linked with the pathogenesis of preeclampsia and fetal growth restriction. Methods This is a planned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive LMW heparin or aspirin alone. In this study, we measured serum levels of circulating angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin by immunoassay) at the following gestational windows: 10-13 6/7 weeks, 14-17 6/7 weeks, 18-21 6/7 weeks, 22-25 6/7 weeks, 26-29 6/7 weeks, 30-33 6/7 weeks, and 34-37 6/7 weeks. Results Samples were available from 185 patients: LMW heparin+aspirin (n=92) and aspirin alone (n=93). The two groups had comparable baseline characteristics and had similar adverse composite outcomes (35/92 [38.0%] compared with 36/93 [38.7%]; P=.92). There were no significant differences in serum levels of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin in the participants who received LMW heparin and aspirin compared with those who received aspirin alone regardless of gestational age period. Finally, women who developed an adverse composite outcome at less than 34 weeks of gestation demonstrated significant alterations in serum angiogenic profile as early as 10-13 6/7 weeks that was most dramatic 6-8 weeks preceding delivery. Conclusion Prophylactic LMW heparin therapy when beginning from before 14 weeks of gestation with aspirin during pregnancy is not associated with an improved angiogenic profile. This may provide a molecular explanation for the lack of clinical benefit noted in recent trials. Clinical trial registration ClinicalTrials.gov, NCT00986765.

Background The most appropriate management for patients with stage IV ovarian cancer remains unclear. Our objective was to understand the main determinants associated with survival and to discuss best surgical management. Methods Data of 1038 patients with confirmed ovarian cancer treated between 1996 and 2016 were extracted from maintained databases of 7 French referral gynecologic oncology institutions. Patients with stage IV diseases were selected for further analysis. The Kaplan–Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariable analysis, was used to account for the influence of multiple variables. Results Two hundred and eight patients met our inclusion criteria: 65 (31.3%) never underwent debulking surgery, 52 (25%) underwent primary debulking surgery (PDS) and 91 (43.8%) neoadjuvant chemotherapy and interval debulking surgery (NACT-IDS). Patients not operated had a significantly worse overall survival than patients that underwent PDS or NACT–IDS (p Conclusions Presence of distant metastases should not refrain surgeons from performing radical procedures, whenever the patient is able to tolerate. Maximal surgical efforts should be done to minimize residual disease as it is the main determinant of survival.

The particularity of pelvic actinomycosis lies in the difficulty of establishing the diagnosis prior to treatment. The objective of this retrospective bicentric study was to evaluate the pertinence and efficacy of the different diagnostic tools used pre- and post-treatment in a cohort of patients with pelvic actinomycosis. The following data were collected: clinical, paraclinical, type of treatment, and the outcome and pertinence of the two diagnostic methods, bacteriological or histopathological, were evaluated. Twenty-seven women were included, with a pre-treatment diagnosis proposed for 66.7% (n = 18) of them. The diagnosis was established in 13.6% (n = 3) of cases through bacteriological samples, and in 93.8% (n = 15) of cases through histopathological samples, with endometrial biopsy positive in 100% of cases. The treatment was surgical with antibiotics for 55.6% (n = 15) of patients, medical with antibiotic therapy for 40.7% (n = 11) of patients, and surgical without antibiotics for one patient. All patients achieved recovery without recurrence, with a median follow-up of 96 days (4&ndash, 4339 days). Our study suggested an excellent performance of histopathological analysis, and in particular endometrial biopsy, in the diagnosis of pelvic actinomycosis. This tool allowed early diagnosis and, in some cases, the use of antibiotic therapy alone, making it possible to avoid surgery.

International audience; Introduction: Patients with Mayer - Rokitansky - Küster - Hauser (MRKH) syndrome often experience chronic pelvic pain negatively impacting their life's quality. Our understanding of the factors involved in this symptom remains poor. The aim of our study was to further investigate the different components of this pelvic pain in patients with MRKH undergoing pelvic surgery. Our second objective was to assess the evolution of this pain in patients undergoing surgical removal of their uterine horn remnant.Material and methods: We conducted a retrospective analysis of a cohort of patients treated in our tertiary referring gynaecological department. Patients included had a MRKH syndrome with at least one uterine horn remnant and all underwent at least one surgical procedure in our centre. Descriptive analysis of the main characteristics and of the management of these patients was conducted. Postoperative pain was evaluated using simple words and / or analgesic consumption evaluation.Results: Between 1991 and 2013, twenty-one patients were included in our centre. Out of them, 20 (95 %) had chronic pelvic pain, mostly cyclic pain lasting 2-3 days. Fourteen patients had surgical removal of their uterine horns remnant and only 3 patients (21 %) had persistent pain at their postoperative visit. Surgical findings included peritoneal endometriosis in 8 patients (38 %) and other unexpected findings in 6. At pathological analysis, secretary endometrium in the uterine horn remnant was found in 11 patients (79 %).Conclusion: The origin of chronic pain in MRKH is combining several factors such as endometriosis or secretary endometrium. Surgical removal of uterine horn remnant improved most of our patients' pelvic chronic pain. Further studies should help improve our understanding of this specific entity.

Preeclampsia is characterized by the association of hypertension and a de novo proteinuria in the second half of pregnancy. Currently, obstetrical teams do not have any tool to detect during the first trimester of pregnancy, in low risk population, the patients likely to develop early and severe preeclampsia. On the other hand, there is no diagnostic/prognostic tool in case of strong suspicion of preeclampsia. The Placental Growth Factor (PIGF) and soluble receptor of the Vascular Endothelial Growth Factor (sFlt-1) are respectively two molecules pro- and anti-angiogenic released mainly by the placenta during pregnancy. Numerous experimental and clinical results suggest that an imbalance of pro/anti-angiogenic factors is involved in the pathophysiology of preeclampsia. We selected and analyzed the main studies that have evaluated the predictive, diagnostic and prognostic value of these two biomarkers for preeclampsia.

Resume La pre-eclampsie est une pathologie hypertensive de la grossesse compliquant 1 a 5 % des grossesses. Il n’existe actuellement pas de traitement curatif de la pre-eclampsie mis a part l’arret de la grossesse. Lorsque la pre-eclampsie survient prematurement la poursuite de la grossesse peut se justifier afin de limiter les sequelles post-natales de la prematurite. Les modalites de prise en charge de la pre-eclampsie dependent essentiellement de la severite de la pathologie et l’âge gestationnel. L’objectif de cet article est de proposer une synthese des modalites de prise en charge de la pre-eclampsie.

The prevention of perinatal brain damage following preterm birth remains a public health priority. Melatonin has been shown to be a promising neuroprotectant in neonatal preclinical models of brain damage, but few studies have investigated melatonin secretion in newborns. We hypothesized that melatonin circulating levels would be lower in preterm compared to term infants. We conducted a prospective, longitudinal, multicenter study to assess melatonin, and 6-sulfatoxy-melatonin (aMT6s) concentrations, measured by radioimmunoassay. Among 209 neonates recruited, 110 were born before 34 gestational weeks (GW) and 99 born after 34 GW. Plasma melatonin concentrations, measured at birth and on Day 3 were below detectable levels (&le, 7 pg/mL) in 78% and 81%, respectively, of infants born before 34 GW compared to 57% and 34%, respectively, of infants born after 34 GW. The distribution of plasma melatonin concentrations was found to be correlated with gestational age at both time-points (p &lt, 0.001). Median urine aMT6s concentrations were significantly lower in infants born before 34 GW, both on Day 1 (230 ng/L vs. 533 ng/L, p &lt, 0.0001) and on Day 3 (197 ng/L vs. 359 ng/L, p &lt, 0.0001). In conclusion, melatonin secretion appears very low in preterm infants, providing the rationale for testing supplemental melatonin as a neuroprotectant in clinical trials.

International audience; OBJECTIVE:To evaluate whether urinary levels of placental growth factor (PlGF) during pregnancy are associated with the subsequent development of composite adverse outcomes (preeclampsia, fetal growth restriction, placental abruption, perinatal death, maternal death) occurring at less than 34 weeks of gestation.METHODS:This is a preplanned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive either low-molecular-weight (LMW) heparin or aspirin alone. For this substudy we measured urinary levels of PlGF and urinary creatinine at the following gestational windows: 10-13 6/7, 14-17 6/7, 18-21 6/7, 22-25 6/7, 26-29 6/7, 30-33 6/7, and 34-37 6/7 weeks of gestation.RESULTS:Urine samples were available from 187 patients: LMW heparin plus aspirin (n=93) and aspirin alone (n=94). The two groups had comparable baseline characteristics and had similar adverse composite outcomes at less than 34 weeks of gestation (14/93 [15.1%] vs 11/94 [11.7%]; P=.50). There were no significant differences in urine PlGF levels in the patients who received LMW heparin plus aspirin compared with those who received aspirin alone. However, median [interquartile range] urinary PlGF/creatinine concentrations (pg/mg) measured at mid-pregnancy (22-26 weeks of gestation) were significantly lower among women who developed composite adverse outcome at less than 34 weeks of gestation (42.7 [32.4-80.8] vs 255.6 [118.7-391.8] P

Female sexual mutilations result in an important physical and mental suffering. A large number of women have been affected and require a global management, including surgical clitoral transposition. This surgical technique is allowing a rapid improvement of clinical symptoms. In this article, we will describe the indications and operative technique of the clitoral transposition.

Objective To compare neonatal morbidity and mortality rates in preterm singleton breech deliveries from 26 0/7 to 29 6/7 weeks of gestation in centers with a policy of either planned vaginal delivery (PVD) or planned cesarean delivery (PCD). Study design Women with preterm singleton breech deliveries occurring after preterm labor or preterm premature rupture of membranes (pPROM) were identified from the databases of five perinatal centers and classified as PVD or PCD according to the center's management policy. The independent association between planned mode of delivery and the risk of neonatal hospital death or morbidity was tested and quantified with ORs through two-level multivariable logistic regression modeling. Results Of 142 782 deliveries during the study period, 626 (0.4%) were singletons in breech presentation from 26 0/7 to 29 6/7 weeks of gestation: after exclusions, 130 were in the PVD group and 173 in the PCD group. Severe newborn morbidity was similar in the two groups. Newborn mortality was 12% in the PCD group and 16% in the PVD group. Three neonates (1.7%, 95% CI: 0.34–5.0) died from head entrapment after vaginal delivery in the PVD group. Nonetheless, the policy of PVD was not associated with increased risks of neonatal death (aOR: 1.01, 95% CI: 0.33–2.92) or severe morbidity. Conclusion Risks of mortality and severe morbidity in preterm breech were not increased by a policy of vaginal delivery. Head entrapment leading to death is however possible in cases of vaginal delivery but its rarity should be balanced with the maternal consequences of early preterm cesarean delivery.

International audience; Among women with vaginal delivery who received prophylactic oxytocin, the use of tranexamic acid did not result in a rate of postpartum hemorrhage of at least 500 ml that was significantly lower than the rate with placebo. (Funded by the French Ministry of Health; TRAAP ClinicalTrials.gov number, NCT02302456 .).

Background The prognostic impact of surgical paraaortic staging remains unclear in patients with locally advanced cervical cancer (LACC). The objective of our study was to evaluate the survival impact of surgical staging in patients with LACC and no evidence of paraaortic lymph node (PALN) metastasis on pre-operative imaging work-up. Methods Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with locally advanced disease (IB2 or more) treated by concurrent chemoradiation therapy (CRT) and no evidence of paraaortic metastasis on pre-operative imaging work-up were selected for further analysis. The Kaplan–Meier method was used to estimate the survival distribution. A Cox proportional hazards model was used to account for the influence of multiple variables. Results Six hundred and forty-seven patients were included, 377 (58.3%) with surgical staging and 270 (41.7%) without, with a mean follow up of 38.1 months (QI 13.0–56.0). Pathologic analysis revealed positive lymph nodes in 47 patients (12.5%). In multivariate model analysis, surgical staging remained an independent prognostic factor for DFS (OR 0.64, CI 95% 0.46–0.89, p = 0.008) and OS (OR 0.43, CI 95% 0.27–0.68, p

To assess systolic (SBP) and diastolic (DBP) blood pressure values during labor and to analyze their predictive value for early postpartum preeclampsia.This 6-month prospective observational study included 1435 women in labor who had no hypertensive disorders either before or during pregnancy. SBP and DBP were measured every 15 min during labor and signs of preeclampsia were checked for in the early postpartum period.Mean maximum SBP and DBP were significantly higher during the first stage of labor without any treatment compared to the last prenatal visit: 135 vs. 119 mmHg and 81 vs. 74 mmHg, respectively (p0001). Epidural analgesia had no effect on maximum SBP or DBP during labor whereas oxytocin administration moderately increased SBP (137.8 vs. 135.2 mmHg; p0.05). Early postpartum preeclampsia was identified in 0.9% of the women. A maximum SBP equal or higher than 150 mmHg or DBP equal or higher than 91 mmHg during labor were predictive of early postpartum preeclampsia with a sensitivity of 77% and a specificity of 71%.SBP and DBP values during labor are higher than those observed in the antepartum period. An SBP equal or higher than 150 mmHg or DBP equal or higher than 91 mmHg are associated with an increased risk of early postpartum preeclampsia.

Background Evaluating locoregional extension of cervical cancer is a key step in patient management. This study evaluated the feasibility of fusion imaging - a combination of magnetic resonance imaging (MRI) with real-time high-resolution ultrasound (US) - to diagnose cervical cancer and its extension. Patients and methods This prospective bi-center study included 13 women who underwent a 1.5-T MRI protocol including at least one T2-weighted plane. The results of imaging fusion were then compared with US and MRI results alone. Results Cervical cancer was detected as a hyperechogenic hypervascularized lesion. Parametrial extension was detected by exploration of the stromal ring and the use of color Doppler mode in fusion imaging, and characterized by visualization of a vascular bridge. Conclusion Fusion imaging could be used as a complementary technique for MRI to enhance diagnostic performance for cervical cancer lesions. While MRI remains the reference, real-time fusion imaging could improve its characterization and detect parametrial infiltration.

The objective of our study was to determine survival and prognostic factors associated with isolated local recurrence of endometrial cancer.Data of 1229 patients with endometrial carcinoma treated between 2000 and 2012 were extracted from maintained databases of nine French University Hospitals as well as from the Senti-Endo trial. Patients with isolated central pelvic and vaginal recurrence were selected for further analysis.Two hundreds and twenty five patients recurred during the inclusion period, 20 with isolated central pelvic recurrence and 23 with vaginal recurrence. Patients without recurrence had initially significantly less lymphovascular space invasion (p = 0.01), less advanced diseases (stage II) (p 0.001) and more often low or intermediate risk tumours than patients with local recurrence. Local recurrence was statistically associated with better overall survival than non-local recurrence (p = 0.028) but dramatically decreased overall survival when compared to patients without any recurrence (p 0.001). The site of recurrence, i.e. vaginal or central pelvic, was significantly associated with overall survival (p = 0.015). Patients without brachytherapy at initial management were more likely to have local recurrence of their disease when compared to those without recurrence (p = 0.03). None of the prognostics factors for survival in patients with local recurrence was statistically significant in multivariate analysis.Local recurrence is a key event in endometrial cancer evolution severely impacting overall survival. Better understanding of the factors associated with prolonged survival is mandatory to improve our management of these patients.

Obesity is a major risk factor for endometrial cancer (EC). Yet, its impact on prognosis is controversial. Obesity is associated with metabolic and hormonal dysregulation as well as adipokines increase. The aim of this study was to characterize the expression of biological factors related to obesity within the tumor and evaluate their impact on prognosis. One hundred and thirty-six patients, including 55 obese patients, with endometrioid type I EC operated by total hysterectomy were included in this retrospective study conducted in a Tertiary teaching hospital between 2000 and 2013. Immunohistochemistry (IHC) study was performed on type I EC tumor samples using five adipokines (SPARC, RBP4 (Retinol Binding Protein 4), adiponectin, TNF α, IL-6) and hormonal receptors (estrogen receptor and progesterone receptor). Supervised clustering of immunohistochemical markers was performed to identify clusters that could be associated with prognostic groups. The prognosis of the obese population was not different from the prognosis of the general population. Adipokine expression within tumors was not different in these two populations. In obese population, we found three clusters where co-expression was associated with a recurrence group in comparison with a non-recurrence group and four clusters where co-expression was associated with the high risk FIGO (International Federation of Gynecology and Obstetrics) stage I group in comparison of low risk FIGO stage I group. While obesity does not appear as a prognostic factor in endometrioid type I EC, the co-expression of biological factors in IHC on hysterectomy specimens allowed to distinguish two prognostic groups in obese population.

Background To evaluate fertility and pregnancy outcomes in patients with uterus bicorporeal and blind hemivagina. Our second objective was to investigate factors predicting fertility and pregnancy outcomes in those patients. Material and methods We conducted a retrospective analysis in a tertiary referring gynaecological department, in France. We included all patients with uterus bicorporeal and blind hemivagina who underwent at least one surgery in our centre. Initial characteristics of the patients included were extracted from their medical charts and patients were contacted to assess their fertility and pregnancies outcomes upon their consent to participate to the study. Results Between 1989 and 2010, 79 patients fulfilled inclusion criteria and were selected for analysis. Mean follow up of those patients was of 16.15 (QI 10–21) years. Forty-six patients (58.2%) returned the survey and among them, 21 (45.7%) were fertile, 8 (17.4%) were infertile and 17 (37%) never attempted to get pregnant following initial management. Forty-nine pregnancies were included to assess pregnancies outcomes: 11 (22.5%) early miscarriages, 1 (2.0%) extra-uterine pregnancy, 2 (4.1%) second semester miscarriages and 35 (71.4%) leaded to living birth. Nineteen (54.3%) deliveries occurred by caesarean section and 14 (40.0%) by vaginal delivery. Fifteen pregnancies (42.9%) were complicated. In univariate analysis, adhesiolysis performed at the time of initial surgery was the only factor associated with infertility (p = 0.004). Conclusions Fertility seems to be perfectly conserved in those patients and they do not have increased rate of adverse pregnancies outcomes.

International audience; Objective We recently developed an algorithm based on five clinical and pathological characteristics to predict lymph node (LN) metastasis in endometrial cancer. The aim of this study was to evaluate the accuracy of using this algorithm with preoperative characteristics. Study design In this retrospective multicenter study, we evaluated the accuracy of using an algorithm to predict LN metastasis using preoperative tumor characteristics provided by endometrial sampling pathological characteristics (histological subtype and grade) and by magnetic resonance imaging (MRI) for primary site tumor extension. Results In total, 181 patients were included in this study, and 14 patients had pelvic LN metastasis (7.7%). Using preoperative tumor characteristics, the algorithm showed good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% confidence interval (IC 95 ) = 0.79-0.87) and was well calibrated (average error = 1.9% and maximal error = 8.5%). LN metastasis prediction by the algorithm using preoperative data was as accurate as that obtained using the final tumor characteristics (AUC = 0.77 (CI 95 = 0.70-0.83), average error = 2.8% and maximal error = 23.2%). Conclusion Our algorithm was accurate in predicting pelvic LN metastasis even with the use of preoperative tumor characteristics provided by endometrial sampling and MRI. These findings, however, should be verified in a larger database before our algorithm is implemented for widespread use.

International audience; Objective: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on nomogram-based predictions of lymph node (LN) metastasis in endometrial cancer. Methods: The data from 485 patients with presumed stage I or II endometrial cancer who underwent hysterectomy and lymphadenectomy were analyzed. Calibration curves were designed and compared for three different subgroups: LVSI-positive tumors (n = 113), LVSI-negative tumors (n = 213) and LVSI-undetermined tumors (n = 159). Results: In the entire population, the nomogram showed good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.80 and was well calibrated. In the subgroup analyses, in LVSI-positive, LVSI-negative and LVSI-undetermined patients, the nomogram was not well calibrated (p of the U index of 0.028, 0.087 and 0.011, respectively) with underestimation in LVSI-positive patients and overestimation in LVSI-negative and LVSI-undetermined patients of LN metastasis. In the univariate analysis and after adjusting for the LN metastasis probability provided by the nomogram, LVSI-positive tumors were associated with an increased risk for LN metastasis compared with LVSI-negative tumors (RR = 7.29 [3.87-13.7] and 5.04 [2.30-11.08], respectively). In contrast, the univariate analysis and after adjusting for the LN metastasis probability provided by the nomogram showed that LVSI-undetermined tumors were not associated with an increased risk for LN metastasis compared with LVSI-negative tumors (RR = 0.73 [0.32-1.69] and 1.26 [0.47-3.37], respectively). Conclusions: Our results suggested that LVSI should be considered to be an independent risk factor for LN metastasis. In this multicenter study, the risk for LN metastasis is similar when the LVSI is negative or is not detailed in the pathological report.

During the past decade, prophylactic doses of low-molecular-weight heparin (LMWH) have been suggested to decrease the risk of placental-mediated complications. Herein, we review the prospective randomized trials that addressed the usefulness of LMWH in preventing placental-mediated complications in high-risk women. Inclusion criteria and results of these trials are heterogeneous. Unlike older trials (3 of 4 are single center), recent trials (all are multicenter) do not show beneficial effect of LMWH. There is certainly a need of complementary research before stating on the usefulness of LMWH in the prevention of placenta-mediated pregnancy complications in women at high risk.

The placental growth factor (PlGF) and its soluble receptor (sFlt-1) are circulating angiogenic factors. During pregnancy these factors are released by the placenta into the maternal circulation. Preeclampsia affects 2-7% of pregnant women according to their risk factors and is characterized by high blood pressure and the onset of de novo proteinuria in the second half of pregnancy. Alterations of the sFlt-1/PlGF ratio in preeclampsia correlate with the diagnosis and adverse outcomes, particularly when the disease presents prematurely (

Objective To describe pregnancy outcomes for pregnant women with sickle cell disease (SCD) receiving prophylactic transfusions. Study design This retrospective case–control study compared pregnancy outcomes among women with SCD receiving prophylactic transfusions and women without any hemoglobinopathy, matched for ethnicity, parity, age and hospital. Results The study included two groups of pregnancies: 128 in women with SCD (95 with SS phenotype and 33 with SC) and 128 in women with AA phenotype. No woman died. Two perinatal deaths (2.1%) and five alloimmunizations (5.3%) occurred, all in the SS group. Compared with the control group, HbSS disease was more often associated with pre-eclampsia (9.4% versus 2.3%, p =.03), preterm delivery (15.8% versus 6.2%, p =.01), birth weight p =.008) and caesarean delivery (73.6% versus 26.4%, p Conclusion Despite prophylactic blood transfusions, SCD remains a severe complicating factor in pregnancy. The policy of systematic transfusions should be analyzed in a sufficiently large randomized trial.

Cervical length measurement by transvaginal ultrasound is commonly used to assess the risk of preterm birth (PTB) and refine the clinical management in cases of preterm labor (PTL). The transvaginal route is considered to be the reference for the measurement of the uterine cervix. Cervical length measurement has a good diagnostic value irrespective of the clinical context or past history associated with an increased risk of PTB. In case of PTL, the measurement of the cervical length by ultrasonography allows to reduce the number of hospitalizations, and to focus on the women who really need a treatment. In case of twin pregnancy, systematic systematic measurement of cervical length at 20-25 weeks gestation is not recommended because of the lack of therapeutic applications. In cases of high risk of PTB (PTB history, conization, uterine exposure to DES, etc.), selecting a group at high risk for PTB by a systematic cervical length measurement at 20-25 weeks gestation could be useful to select women for whom treatment with progesterone would be most beneficial. In this group, a follow-up of the cervical length since 16 weeks gestation may also be useful to indicate a cerclage if the cervical length is less than 15mm. In the general population, cervical length measurement may be useful during the second trimester of pregnancy in so far as a treatment by progesterone in cases of short cervix (

Background Management of noncephalic second twin delivery rests on the results of population-based retrospective studies of twin births that have shown higher neonatal mortality and morbidity for second twins with noncephalic, compared with cephalic, presentations after vaginal delivery of the first twin. Because these studies are flawed by data of questionable validity, do not report the obstetrical practices at delivery, and do not allow collection of potential confounding variables, we performed a national prospective study specially designed to evaluate the management of twins’ delivery. Objective We sought to assess neonatal mortality and morbidity according to second twin presentation after vaginal birth of the first twin. Study Design The Jumeaux Mode d’Accouchement study was a nationwide prospective population-based cohort study of twin deliveries performed in 176 maternity units in France from February 2014 through March 2015. The primary outcome was a composite of intrapartum mortality and neonatal mortality and morbidity. Neonatal outcomes of second twins born ≥32 weeks of gestation after vaginal delivery of the first cephalic or breech twin were compared according to the noncephalic or cephalic second twin presentation. Multivariable logistic regression models controlled for potential confounders. Subgroup analyses were conducted according to the breech or transverse presentation of the noncephalic second twin, and gestational age at delivery, before or after 37 weeks of gestation. Results Among 3903 second twins enrolled in the study, 2384 (61.1%) were in cephalic and 1519 (38.9%) in noncephalic presentations, of whom 999 (25.6%) were in breech and 520 (13.3%) in transverse presentation. Composite neonatal mortality and morbidity did not differ between the noncephalic and cephalic group (47/1519 [3.1%] vs 59/2384 [2.5%]; adjusted odds ratio, 1.23; 95% confidence interval, 0.81–1.85). No significant difference between groups was shown for the primary outcome in subgroup analyses according to type of noncephalic second twin presentation or gestational age at delivery. Cesarean delivery rates for the second twin were lower in the breech than in the cephalic group (14/999 [1.4%] vs 75/2384 [3.1%], P = .003) and lower in the cephalic than in the transverse group (75/2384 [3.1%] vs 35/520 [6.7%], P Conclusion Noncephalic and cephalic second twin presentations after vaginal delivery of the first twin ≥32 weeks of gestation are associated with similar low composite neonatal mortality and morbidity. Vaginal delivery of noncephalic second twin is a reasonable option.

Few studies establishing clear criteria for the medical interruption of a pregnancy complicated by PE are available today. Most of these studies are either retrospective or observational. When combining an analysis of the available literature together with the experts' opinions, one can propose the following set of criteria for therapeutic interruption of pregnancy in the setting of PE, which apply mainly for the severe forms of the disease. These criteria can be subdivided into maternal and fetal criteria. Maternal criteria are a severe uncontrollable HT, eclampsia, acute pulmonary edema, retro placental haematoma, oligura (

SummaryAdministration of heparin in the secondary prevention of placental vascular complications is still experimental. In women with a previous placental abruption, we investigated the effectiveness of enoxaparin, a low-molecular-weight heparin, in preventing these complications. Between January 2000 and January 2009, 160 women from the NOHA First cohort, with previous abruptio placentae but no foetal loss during their first pregnancy and negative for antiphospholipid antibodies, were randomised to either a prophylactic daily dose of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin (n=80). The primary outcome was a composite of at least one of the following: abruptio placentae, preeclampsia, birthweight < 5th percentile, or foetal loss after 20 weeks. Enoxaparin was associated with a lower frequency of primary outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio = 0.37, 95% confidence interval (0.18–0.77), p=0.011. Enoxaparin was safe, with no obvious side-effect, no thrombocytopenia nor major bleeding event excess. This pilot study shows that enoxaparin given early during the second pregnancy decreases the occurrence of placental vascular complications in women with a previous placental abruption during their first pregnancy.

As Arabic is known for its highly inflectional morphological structure, this hybrid approach is utilizing morphological knowledge in form of consistent root-pattern relationships, and some morpho-syntactical knowledge based on affixation and morphographemic rules to specify the word recognition and non-word correction process. Furthermore this paper is proposing novel probabilistic measures for completing the task of the correction by locating, reducing and ranking of the most probable correction candidates in Arabic derivative words. In this context based on frequency of occurrence analysis, two probabilistic measures are introduced, Root-Pattern Predictive Value, RPV, and Pattern-Root Predictive Value, PPV. Moreover, keyboard effect, letter sound and similarity are considered in addition to some lexical features as a supplementary aid to improve the process of error detection and correction.

Research on semantic processing of Arabic language and in particular on deep semantic analysis considering the compositionality of its syntactical structure has so far received very little computational research. This work is therefore attempting to fill some essential aspects of this gap in introducing a logic-based compositional model covering fundamental issues involved in semantic analysis of Arabic sentences. The focus of attention is relying on studying the compositionality of important Arabic syntactical constituents and on extending the concept of the generalized natural language quantification to Generalized Arabic Quantifiers GAQ utilizing lambda-calculus and the type theoretical analysis of Arabic structure. Since semantic representation has to be compositional in natural language understanding systems this approach attempts to propose an element framework for developing more practical and intelligent Arabic natural language processing systems.

Objective This study was undertaken to determine maternal and perinatal outcomes after expectant management of severe preeclampsia between 24 and 33 weeks' gestation. Study design A prospective observational study of 239 women with severe preeclamptic and undelivered after antenatal steroid prophylaxis was performed. Pregnancy prolongation and maternal and perinatal morbidities were analyzed according to the gestational age at time of expectant management: 24 to 28, 29 to 31, and 32 to 33 weeks. Statistical analysis was performed by Student t test and χ2 test. Results The days of pregnancy prolongation were significantly higher among those managed at less than 29 weeks (6) compared with the other groups (4). There were 13 perinatal deaths: 12 in those managed at less than 29 weeks and 1 in those managed at 29 to 31 weeks. Neonatal morbidities were significantly higher among those managed at less than 29 weeks compared with the other groups. There were no instances of maternal death or eclampsia. Maternal morbidities were similar among the groups. Conclusion Expectant management of severe preeclampsia at 24 to 33 weeks in a tertiary care center is associated with good perinatal outcome with a minimal risk for the mother.

Objective: The purpose of this study was to describe subsequent pregnancy outcome in women with a history of hemolysis, elevated liver enzymes, and low platelet count syndrome for which delivery occurred at ≤ 28 weeks of gestation during the index pregnancy. Study Design: A descriptive report of women with previous hemolysis, elevated liver enzymes, and low platelet count syndrome who were delivered between August 1984 and July 1998 at the E.H. Crump Women's Hospital (Memphis, Tenn) and between March 1994 and July 1998 at the Central Baptist Hospital (Lexington, Ky). To have adequate time to study subsequent pregnancy outcome, only patients who were delivered >2 years before the analysis were included. Medical records of the index pregnancy and subsequent outcomes were available for review. Results: Adequate follow-up data were available in 69 patients; the median duration of follow-up was 5 years (range: 2-14 years). There were 76 subsequent pregnancies among 48 women, of which 62 pregnancies (82%) progressed beyond 20 weeks of gestation. Preeclampsia developed in 34 of 62 subsequent pregnancies (55%). Recurrent hemolysis, elevated liver enzymes, and low platelet count syndrome developed in 4 of these pregnancies (6%), and abruptio placentae developed in 3 of these pregnancies (5%). There were no cases of eclampsia in our population. Delivery before 37 weeks of gestation occurred in 33 of the cases (53%), and 17 of the newborn infants (27%) were small for gestational age ( Conclusion: Patients with a history of hemolysis, elevated liver enzymes, and low platelet count syndrome at ≤ 28 weeks of gestation during the index pregnancy are at increased risk for obstetric complications in subsequent pregnancies. Overall, however, the rate of recurrent hemolysis, elevated liver enzymes, and low platelet count syndrome is only 6%. (Am J Obstet Gynecol 2003;188:1504-8.)

Background The aim of this study was to evaluate the impact of modifications of extent (medial inguinal and medial femoral lymphadenectomy, inguinal lymphadenectomy, inguinal and medial femoral lymphadenectomy, and inguinofemoral lymphadenectomy) and surgical technique of lymphadenectomy (including sartorius transposition, preservation of the fascia lata, and preservation of the saphenous vein) on morbidity, groin recurrence, and survival in patients with vulvar carcinoma. Study design A retrospective review of 194 patients with primary squamous cell cancer of the vulva was conducted. Clinical, surgical, histopathologic, postoperative short- and longterm complications, and followup data were collected from patient records. Results Inguinal lymphadenectomy and medial inguinal and medial femoral lymphadenectomy produced about half fewer nodes than did other surgical procedures. On the other hand, number of lymph nodes removed did not differ notably between inguinofemoral lymphadenectomy and inguinal and medial femoral lymphadenectomy. Logistic regression showed that obesity was associated with increased risk of cellulitis. Age greater than 70, obesity, and extent of lymphadenectomy increased wound breakdown risk. Factors associated with leg edema persisting for more than 6 months were: extent of lymphadenectomy, sartorius transposition, and adjuvant irradiation of groin area. With a mean followup time of 38 months, neither groin recurrence rate nor disease-specific survival markedly differed according to technique of lymphadenectomy. Conclusion Techniques of lymphadenectomy with preservation of fascia lata and saphenous vein are associated with a decreased risk of postoperative morbidity without jeopardizing outcomes.

Objective: The objective of the study was to evaluate the efficacy of gentamicin and clindamycin given once daily versus the more common 8-hour dosing regimen for the treatment of postpartum endometritis. Study Design: In a prospective, placebo-controlled, double-blinded study, patients who had postpartum endometritis diagnosed were randomly selected to receive 1.5 mg/kg gentamicin and 900 mg clindamycin phosphate administered every 8 hours versus gentamicin 5 mg/kg and clindamycin phosphate 2700 mg administered as a single-daily dose. The single-dose group received an infusion of gentamicin and clindamycin, followed by an administration of intravenous placebo 8 and 16 hours later to maintain blinding. Treatment success was defined as absence of fever 72 hours after initiation of antibiotic therapy. Results: One hundred ten patients were enrolled. The daily-dose group (n = 55) and the thrice-daily dose group (n = 55) were similar with respect to age, gravidity, parity, gestational age, and maternal weight. Clinical characteristics (including maximum temperature, presence of predelivery chorioamnionitis, white blood cell count, and mode of delivery) were also similar. There was no difference in the mean time from initiation of therapy until becoming afebrile in the daily-dose group (27.4 ± 24.9 hours) compared with the thrice-daily dose group (32.9 ± 26.3 hours). Forty-five of 56 (82%) patients in the daily-dose group and 38 of 55 (69%) patients in the thrice-daily dose group had treatment success ( P = .12). Conclusion: Once-daily dosing with gentamicin and clindamycin in women with postpartum endometritis has a similar success rate as the standard every 8-hour dosing schedule. (Am J Obstet Gynecol 2003;188:149-52.)

This paper intends to present a large-scale dataset for Arabic morphology from a cognitive point of view considering the uniqueness of the root–pattern phenomenon. The center of attention is focused on studying this singularity in terms of estimating associative relationships between roots as a higher level of abstraction for words meaning, and all their potential occurrences with multiple morpho-phonetic patterns. A major advantage of this approach resides in providing a novel balanced large-scale language resource, which can be viewed as an instantiated global root–pattern network consisting of roots, patterns, stems, and particles, estimated statistically for studying the morpho-phonetic level of cognition of Arabic. In this context, this paper asserts that balanced root-distribution is an additional significant key criterion for evaluating topic coverage in an Arabic corpus. Furthermore, some additional novel probabilistic morpho-phonetic measures and their distribution have been estimated in the form of root and pattern entropies besides bi-directional conditional probabilities of bi-grams of stems, roots, and particles. Around 29.2 million webpages of ClueWeb were extracted, filtered from non-Arabic texts, and converted into a large textual dataset containing around 11.5 billion word forms and 9.3 million associative relationships. As this dataset is predominantly considering the root–pattern phenomenon in Semitic languages, the acquired data might be significant support for researchers interested in studying phenomena of Arabic such as visual word cognition, morpho-phonetic perception, morphological analysis, and cognitively motivated query expansion, spell-checking, and information retrieval. Furthermore, based on data distribution and frequencies, constructing balanced corpora will be easier.

ObjectiveThe purpose was to compare logistic regression model (LRM) and recursive partitioning (RP) to predict lymph node metastasis in early-stage endometrial cancer.Methods/MaterialsThree models (1 LRM and 2 RP, a simple and a complex) were built in a same training set extracted from the Surveillance, Epidemiology, and End Results database for 18,294 patients who underwent hysterectomy and lymphadenectomy for stage I or II endometrial cancer. The 3 models were validated in a same validation set of 499 patients. Model performance was quantified with respect to discrimination (evaluated by the areas under the receiver operating characteristics curves) and calibration.ResultsIn the training set, the areas under the receiver operating characteristics curves were similar for LRM (0.80 [95% confidence interval [CI], 0.79–0.81]) and the complex RP model (0.79 [95% CI, 0.78–0.80]) and higher when compared with the simple RP model (0.75 [95% CI, 0.74–0.76]). In the validation set, LRM (0.77 [95% CI, 0.75–0.79]) outperformed the simple RP model (0.72 [95% CI, 0.70–0.74]). The complex RP model had good discriminative performances (0.75 [95% CI, 0.73–0.77]). Logistic regression model also outperformed the simple RP model in terms of calibration.ConclusionsIn these real data sets, LRM outperformed the simple RP model to predict lymph node metastasis in early-stage endometrial cancer. It is therefore more suitable for clinical use considering the complexity of an RP complex model with similar performances.

To evaluate the risk factors for local relapse in vulvar cancer patients and its impact on survival as a function of its different patterns, which include local recurrences at the primary tumor site, recurrences remote from the primary tumor, and skin bridge recurrences. Between January 1978 and June 1999, 215 patients were treated for vulvar squamous cell carcinoma. The median follow-up was 38 months. To evaluate the role of local relapse in survival, a Cox regression multivariable analysis was performed using local relapse as a time-dependent covariate. The local relapse-free survival rate was 78.6% (+/- 7.1%) at 5 years. Multivariable analyses showed that the local relapse was increased by the factors margin status and depth of invasion. Pathologic nodal status, tumor size, margin status, and depth of invasion were predictors of cancer-related death in the Cox multivariable model with fixed covariates. The contribution of local relapse for disease-specific survival at the site of the primary tumor (relative risk [RR] 6.35; 95% confidence interval [CI] 2.07, 15.76) or skin bridge recurrence (RR 6.48; 95% CI 2.54, 16.49) was highly significant, whereas the contribution of local relapse at the other sites was not (RR 2.29; 95% CI 0.53, 9.91). In this model, margin status was not significant. The risk of cancer-related death after local relapse was 58.4% (+/- 18.3%) at 1 year and 70.9% (+/- 17.6%) at 3 years.Local relapses at the site of the primary tumor or skin bridge recurrences are strong predictors for cancer-related death, but not local relapse at a distant site.