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Introduction/Background*Because of inter-tumor heterogeneity of endometrial carcinoma (EC), prognostication remains challenging. We aimed to develop a RNAseq signature to stratify EC patient prognosis beyond molecular subtyping.MethodologyA prognostic signature was identified using a LASSO-penalized Cox regression model on TCGA (N=543 patients). A polyA-RNAseq-based method was developed for validation of the signature in a cohort of stage I-IV EC patients treated in two Paris Hospitals between 2010 and 2017. Model performances were evaluated using time-dependent ROC curves (prediction of disease-specific-survival (DSS)). The additional value of the RNAseq signature was evaluated using uni/multivariable Cox models (hazard ratio (HR) with [95% confidence interval]) and Kaplan-Meier analysis.Result(s)*Among 209 patients included in the validation cohort (median follow-up 55 months IQR [41-69]), 61 (30%), 10 (5%), 52 (25%), and 82 (40%), had mismatch repair-deficient, POLE-mutated, TP53-mutated tumors, and tumors with no specific molecular profile, respectively. The 38-genes signature accurately predicted DSS (AUC=80%). Using a composite classifier accounting for the RNAseq signature and the TP53-mutated group, three groups were identified: good prognosis tumors based on RNAseq signature and without TP53 mutation, characterized by excellent outcome (N=103 patients, 5-years DSS rates of 99%) (reference), poor prognosis tumors based on RNAseq signature and without TP53 mutation (N=49 patients, 5-years DSS rates of 81%; HR: 5.86 [1.16; 29.7]), and TP53-mutated tumors whatever the RNAseq signature (N=52 patients, 5-years DSS rates of 52%; HR: 11.14 [2.40; 51.7]) (HR adjusted on FIGO stage). In 81 (38%) patients with adverse features (2020 ESGO/ESTRO/ESP guidelines: non-endometrioid histology or stage III-IVA or TP53-mutated tumors), TP53-mutated molecular group was not significantly associated with poor prognosis (p=0.18). A The composite classifier identified three classes within this subgroup: RNAseq-good prognosis (N=24), non-TP53/RNAseq-poor prognosis (N=16), and TP53-mutated tumors (N=41), with 5-years DSS rates of 100%, 59%, and 71%, respectively (p=0.015). Transcriptome analyses suggested the underlying involvement of immune deprivation and wound healing processes in tumors with poor prognosis.Conclusion*We demonstrate that RNAseq characterization can refine prognostication in EC beyond molecular subgroups and main prognostic features, and warrants validation for potential RNAseq-based adjuvant therapeutic strategies in EC.

Background/Aims: Deep infiltrating endometriosis is a very painful condition and the mechanism of pain is still poorly understood. Pain and hyperalgesia can partly be explained by an increased number of nerve structures in the painful lesion. In order to clarify this issue, we assessed the nerve density in deep infiltrating endometriotic nodules of the posterior vagina and in the adjacent healthy vaginal tissue of the same patient. Methods: A prospective clinical and pathological study of 31 cases of deep infiltrating vaginal endometriotic nodules was conducted. Fifteen patients were in the proliferative phase and 16 in the secretory phase. The nerve density was studied by immunohistochemistry with the monoclonal antibody NF against neurofilaments in deep infiltrating endometriosis and in the adjacent unaffected vaginal tissue in the proliferative and in the secretory phases. Neurofilaments constitute the main structural elements of neuronal axons and dendrites. Results: The nerve density was significantly different in the endometriotic nodule than in the adjacent unaffected vaginal tissue (p = 0.0013). The same significant difference was found between endometriotic nodules and the unaffected vagina in the proliferative phase (p = 0.009) and in the secretory phase (p = 0.04). This difference was not significant between the proliferative and the secretory phases in the endometriotic lesions and in the controls. Conclusions: We hypothesize that the significantly increased number of nerve structures in the endometriotic nodules may contribute to the occurrence of severe and neuropathic pain that characterizes these lesions

Objective: Experimental endotoxaemia induces subcutaneous adipose tissue inflammation and systemic insulin resistance in lean subjects. Glyceroneogenesis, by limiting free fatty acids (FFA) release from adipocytes, controls FFA homoeostasis and systemic insulin sensitivity. The roles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in metabolic deregulation are intrinsically different. We compared the effect of lipopolysaccharide (LPS) on the inflammation profiles of SAT and VAT explants from lean women, as well as on glyceroneogenesis, to test whether these two fat depots have intrinsically different responses to this metabolic endotoxin. Design: Abdominal SAT and VAT explants from eight lean women were treated in vitro with LPS. Their inflammatory status was evaluated by cytokine gene expression and secretion; glyceroneogenesis was evaluated by cytosolic phosphoenolpyruvate carboxykinase activity and FFA vs glycerol release. Results: In the basal state, the cytokine status and expression of macrophage markers were lower in SAT than VAT. In the presence of 100 ng ml −1 LPS, SAT exhibited a strong inflammatory response (increased interleukin-6 and tumor necrosis factor-α expression) and increased release of FFA due to inhibition of glyceroneogenesis, whereas VAT was only mildly affected. The effects of LPS on both tissues were blocked by the nuclear factor-κB (NF-κB) inhibitor, parthenolide. A significant effect of LPS on VAT occurred only at 1 μg ml −1 LPS. Conclusion: SAT explants from lean women are more sensitive to LPS-induced NF-κB activation than are VAT explants, leading to a depot-specific dysfunction of FFA storage. As SAT is the major player in FFA homoeostasis, this SAT dysfunction could be associated with visceral fat hypertrophy and systemic lipid disorders.

The multiplexing scheme presented in this paper is part of the readout chain of the QUBIC instrument devoted to cosmic microwave background polarization observations. It is based on time domain multiplexing using superconducting quantum interference devices (SQUIDs) to read out a large array of superconducting bolometers. The originality of the multiplexer presented here lies in the use of capacitors for the SQUID addressing. Capacitive coupling allows us to bias many SQUIDs in parallel (in a 2D topology), with low crosstalk and low power dissipation of the cryogenic front-end readout. However, capacitors in series with the SQUID require a modification of the addressing strategy. This paper presents a bias reversal technique adopted to sequentially address the SQUIDs through capacitors using a cryogenic SiGe integrated circuit. We further present the different limitations of this technique and how to choose the proper capacitance for a given multiplexing frequency and current source compliance.

Endometriosis may exert a profound negative influence on the lives of individuals with the disorder, adversely affecting quality of life, participation in daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Over the course of a lifetime, these daily challenges may translate into limitations in achieving life goals such as pursuing or completing educational opportunities; making career choices or advancing in a chosen career; forming stable, fulfilling relationships; or starting a family, all of which ultimately alter one's life trajectory. The potential for endometriosis to impact the life course is considerable, as symptom onset generally occurs at a time of life (menarche through menopause, adolescence through middle age) when multiple life-changing and trajectory-defining decisions are made. Using a life-course approach, we examine how the known effects of endometriosis on life-domain satisfaction may impact health and well-being across the life course of affected individuals. We provide a quasi-systematic, narrative review of the literature as well as expert opinion on recommendations for clinical management and future research directions.

Scar endometriosis is a rare disease which is difficult to diagnose. The symptoms are nonspecific, typically involving abdominal wall pain at the time of menstruation. Clinical examination may reveal a painful nodule, if the scar involved is located on the abdominal wall, but is normal, when the lesion is located on the uterine scar. Other means of investigation (transvaginal ultrasonography, computed tomography) may be useful in case of lesions on the abdominal wall, or if the nodule is large, but give no specific results. The diagnosis is frequently made only after excision of the lesion. We report here 4 patients operated for scar endometriosis (two abdominal and two uterine scars) for whom MRI had suggested the diagnosis. Thanks to its very high spatial resolution, MRI enables very small lesions to be detected and can distinguish the hemorrhagic signal of endometriotic lesions. Furthermore, it performs better than the CT scan in detecting the limits between muscles and abdominal subcutaneous tissues.

The aim of the study was to determine Monarc (American Medical Systems) sling position after surgical treatment of stress urinary incontinence (SUI) through the transobturator approach. A total of 54 consecutive women with SUI were evaluated post-operatively with transvaginal ultrasound. A concomitant hysterectomy was performed in ten cases and a concomitant prolapse surgery in six cases. Ultrasound measurements include urethral length, the distance between the upper edge of the sling and the bladder neck (BN-S) and the BN-S/U ratio. The mean distance between the transobturator tape and the bladder neck was found to be 12.6±3.2 mm in the group of patients who underwent the transobturator procedure alone, 13±3.1 mm in the transobturator plus hysterectomy group and 12±2.8 mm in the transobturator plus prolapse group. The superior tape margin was at the mid-urethra in 81.5% of patients and always at a distance greater than 7 mm from the bladder neck. Eight patients did not have satisfactory results after the surgery. Only in one out of these eight patients was the transobturator sling not found to be at the mid-urethra. The superior tape margin of the Monarc sling remained at the level of mid-urethra in the majority of cases. It was never located too proximally beneath the bladder neck.[PUBLICATION ABSTRACT]

Endometriosis corresponds to ectopic endometrial glands and stroma outside the uterine cavity. Clinical symptoms include dysmenorrhoea, dyspareunia, infertility, painful defecation or cyclic urinary symptoms. Pelvic ultrasound is the primary imaging modality to identify and differentiate locations to the ovary (endometriomas) and the bladder wall. Characteristic sonographic features of endometriomas are diffuse low-level internal echos, multilocularity and hyperchoic foci in the wall. Differential diagnoses include corpus luteum, teratoma, cystadenoma, fibroma, tubo-ovarian abscess and carcinoma. Repeated ultrasound is highly recommended for unilocular cysts with low-level internal echoes to differentiate functional corpus luteum from endometriomas. Posterior locations of endometriosis include utero-sacral ligaments, torus uterinus, vagina and recto-sigmoid. Sonographic and MRI features are discussed for each location. Although ultrasound is able to diagnose most locations, its limited sensitivity for posterior lesions does not allow management decision in all patients. MRI has shown high accuracies for both anterior and posterior endometriosis and enables complete lesion mapping before surgery. Posterior locations demonstrate abnormal T2-hypointense, nodules with occasional T1-hyperintense spots and are easier to identify when peristaltic inhibitors and intravenous contrast media are used. Anterior locations benefit from the possibility of MRI urography sequences within the same examination. Rare locations and possible transformation into malignancy are discussed.

The aim of this study was to evaluate precisely the microvascularisation of endometrium, superficial and deep endometriotic lesions, in progestin-treated and non-treated patients suffering from endometriosis. A population of 66 women was constituted. Immunohistochemistry was carried out with a specific marker of the endothelial cells (CD31). The number of vessels and the vessel area were assessed by a computer image analysis system. The number of vessels per mm2 were 211, 216, 225 and the vessel area was 270, 141 and 194 microm2, respectively in endometria, superficial and deep endometriotic lesions of untreated women. In endometria, superficial and deep endometriotic lesions of progestin-treated women the number of vessels were respectively 129, 149, and 181 per mm2 and the vessel area was 369, 474 and 254 microm2. Statistically significant data indicate that endometriotic lesions are heterogeneous and suggest that progestin treatment induces a reduction in number and a concomitant dilation of microvessels with more microvascular changes in endometrium and superficial endometriotic lesions than in deep endometriotic lesions.