Co-occurrence of the cephalosporinase cepA and carbapenemase cfiA genes in a Bacteroides fragilis division II strain, an unexpected finding.

BACKGROUND: Bacteroides fragilis, an anaerobic gut bacterium and opportunistic pathogen, comprises two genetically divergent groups (or divisions) at the species level. Differences exist both in the core and accessory genomes and the beta-lactamase genes, with the cephalosporinase gene cepA represented only in division I and the carbapenemase gene cfiA only in division II. METHODS: Multidrug resistance in a clinical B. fragilis strain was examined by whole-genome sequencing. RESULTS: Strain CNM20200260 carried the antimicrobial resistance genes cepA, cfiA2, ant(6'), erm(F), mef(En2), est(T), tet(Q) and cat(A), along with 82-Phe mutation in gyrA (together with 47 amino acid changes in gyrA/B and parC/parE). bexA/B and other efflux pump genes were also observed. None of the detected insertion sequences was located upstream of cfiA2. The genome-based taxonomy coefficients (average nucleotide identity, DNA-DNA hybridization similarity and difference in genomic G + C%) with respect to genomes of the strains of B. fragilis division II and the novel species Bacteroides hominis (both cfiA-positive) met the criteria for CNM20200260 to belong to either species (>95%, >70% and <1%, respectively). No such similarity was seen with type strain NCTC 9343 or the representative genome FDAARGOS 1225 of B. fragilis (division I, cfiA-negative). Strain CNM20200260 harboured four out of nine Kyoto Encyclopedia of Genes and Genomes orthologues defined for division I and one of two defined for division II. CONCLUSIONS: This is the first description of the co-occurrence of cepA and cfiA in a Bacteroides strain, confirming the complexity of the taxonomy of this species.

Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA-1 multinomial regression model: validation study.

OBJECTIVES: To assess the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. METHODS: This was a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). The IETA-3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow-up of non-endometrial pathology, in the work-up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow-up of at least 1 year if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver-operating-characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). RESULTS: The median age of the women in the IETA-3 cohort was 51 (range, 20-85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI, 0.73-0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32-0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62-0.73) (n = 1532). The IETA-1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95-0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75-0.91), compared with 0.62 (95% CI, 0.52-0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08-0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI, 0.71-0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60-0.81) (difference in AUC, 0.11; 95% CI, 0.01-0.20). CONCLUSION: The IETA-1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Validation of ADNEX and IOTA two-step strategy and estimation of risk of complications during follow-up of adnexal masses in low-risk population.

OBJECTIVES: The aim is to evaluate the ability of the Assessment of Different NEoplasias in the adneXa model (ADNEX) and the International Ovarian Tumour Analysis (IOTA) two-step strategy to predict malignancy in adnexal masses detected in an outpatient low-risk setting, and to estimate the risk of complications in masses with benign ultrasound morphology managed with clinical and ultrasound follow-up. METHODS: This single center (Hospital Universitari Dexeus Barcelona) study was performed using interim data of the ongoing prospective observational IOTA phase 5 study. The primary aim of the IOTA 5 study is to describe the cumulative incidence of complications during follow-up of adnexal masses classified as benign on ultrasound. Consecutive patients with adnexal masses detected between June 2012 and September 2016 in a private center offering screening for gynecological cancers were included and followed-up until February 2020. Tumors were classified as benign or malignant based on histology (if patients underwent surgery) or outcome of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when follow-up information was uncertain. The ability of the ADNEX model without CA125 and of the IOTA two-step strategy to distinguish benign from malignant masses was evaluated retrospectively using the prospectively collected data. We describe performance as discrimination (area under the receiver operating characteristic curve, AUC), calibration, classification (sensitivity and specificity) and clinical utility (Net Benefit). In the group of patients with a benign looking mass selected for conservative management we evaluated the occurrence of spontaneous resolution or any mass complication during the first 5 years of follow-up by assessing the cumulative incidence for malignancy, torsion, cyst rupture, or minor mass complications (inflammation, infection, or adhesions) and the time to occurrence of an event. RESULTS: A total of 2654 patients were recruited to the study. After application of exclusion criteria, 2039 patients with a newly detected mass were included for the model validation. 1684 (82.6%) masses were benign, 49 (2.4%) masses were malignant and for 306 (15.0%) masses the outcome was uncertain and imputed. The AUC was 0.95 (95% CI 0.89-0.98) for ADNEX and 0.94 (95% CI 0.88-0.97) for the two-step strategy. Calibration performance could not be meaningfully interpreted due to few malignancies resulting in very wide confidence intervals. The two-step strategy had better clinical utility than ADNEX at malignancy risk thresholds < 3%. 1472 (72%) patients had a mass judged to be benign based on pattern recognition by an experienced ultrasound examiner and were managed with clinical and ultrasound follow-up. In this group, the 5-year cumulative incidence was 66% for spontaneous resolution of the mass (95% CI 63-69), 0% for torsion (95%CI 0-0.002), 0.1% for cyst rupture (<0.1-0.6), 0.2% for a borderline tumor (<0.1-0.6), and 0.2% (0.1-0.6) for invasive malignancy. CONCLUSIONS: The ADNEX model and IOTA two-step strategy performed well to distinguish benign from malignant adnexal masses detected in a low-risk population. Conservative management is safe for masses with benign ultrasound appearance in such a population. This article is protected by copyright. All rights reserved.

Short-term outcomes of chemoradiotherapy and local excision versus total mesorectal excision in T2-T3ab,N0,M0 rectal cancer: a multicentre randomised, controlled, phase III trial (the TAU-TEM study).

BACKGROUND: The standard treatment of T2-T3ab,N0,M0 rectal cancers is total mesorectal excision (TME) due to the high recurrence rates recorded with local excision. Initial reports of the combination of pre-operative chemoradiotherapy (CRT) and transanal endoscopic microsurgery (TEM) have shown reductions in local recurrence. The TAU-TEM study aims to demonstrate the non-inferiority of local recurrence and the improvement in morbidity achieved with CRT-TEM compared with TME. Here we describe morbidity rates and pathological outcomes. PATIENTS AND METHODS: This was a prospective, multicentre, randomised controlled non-inferiority trial including patients with rectal adenocarcinoma staged as T2-T3ab,N0,M0. Patients were randomised to the CRT-TEM or the TME group. Patients included, tolerance of CRT and its adverse effects, surgical complications (Clavien-Dindo and Comprehensive Complication Index classifications) and pathological results (complete response in the CRT-TEM group) were recorded in both groups. Patients attended follow-up controls for local and systemic relapse. TRIAL REGISTRATION: NCT01308190. RESULTS: From July 2010 to October 2021, 173 patients from 17 Spanish hospitals were included (CRT-TEM: 86, TME: 87). Eleven were excluded after randomisation (CRT-TEM: 5, TME: 6). Modified intention-to-treat analysis thus included 81 patients in each group. There was no mortality after CRT. In the CRT-TEM group, one patient abandoned CRT, 1/81 (1.2%). The CRT-related morbidity rate was 29.6% (24/81). Post-operative morbidity was 17/82 (20.7%) in the CRT-TEM group and 41/81 (50.6%) in the TME group (P < 0.001, 95% confidence interval 42.9% to 16.7%). One patient died in each group (1.2%). Of the 81 patients in the CRT-TEM group who received the allocated treatment, 67 (82.7%) underwent organ preservation. Pathological complete response in the CRT-TEM group was 44.3% (35/79). In the TME group, pN1 were found in 17/81 (21%). CONCLUSION: CRT-TEM treatment obtains high pathological complete response rates (44.3%) and a high CRT compliance rate (98.8%). Post-operative complications and hospitalisation rates were significantly lower than those in the TME group. We await the results of the follow-up regarding cancer outcomes and quality of life.

Diagnostic accuracy of ultrasound signs for detecting adnexal torsion: systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of different ultrasound signs for diagnosing adnexal torsion, using surgery as the reference standard. METHODS: This was a systematic review and meta-analysis of studies published between January 1990 and November 2021 evaluating ovarian edema, adnexal mass, ovarian Doppler flow findings, the whirlpool sign and pelvic fluid as ultrasound signs (index tests) for detecting adnexal torsion, using surgical findings as the reference standard. The search for studies was performed in PubMed/MEDLINE, CINAHL, Scopus, The Cochrane Library, ClinicalTrials.gov and Web of Science databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of the studies. Pooled sensitivity, specificity, and positive and negative likelihood ratios were calculated separately, and the post-test probability of adnexal torsion following a positive or negative test was also determined. RESULTS: The search identified 1267 citations after excluding duplicates. Eighteen studies were ultimately included in the qualitative and quantitative syntheses. Eight studies (809 patients) analyzed the presence of ovarian edema, eight studies (1044 patients) analyzed the presence of an adnexal mass, 14 studies (1742 patients) analyzed ovarian Doppler flow, six studies (545 patients) analyzed the whirlpool sign and seven studies (981 patients) analyzed the presence of pelvic fluid as ultrasound signs of adnexal torsion. Overall, the quality of most studies was considered to be moderate or good. However, there was a high risk of bias in the patient-selection and index-text domains (with the exception of the whirlpool sign) in a significant proportion of studies. Pooled sensitivity, specificity, and positive and negative likelihood ratios of each ultrasound sign were 58%, 86%, 4.0 and 0.49 for ovarian edema, 69%, 46%, 1.3 and 0.67 for adnexal mass, 65%, 91%, 7.6 and 0.38 for the whirlpool sign, 53%, 95%, 11.0 and 0.49 for ovarian Doppler findings and 55%, 69%, 1.7 and 0.66 for pelvic fluid. Heterogeneity was high for all analyses. CONCLUSIONS: The presence of an adnexal mass or pelvic fluid have poor diagnostic accuracy as ultrasound signs of adnexal torsion, while the presence of ovarian edema, the whirlpool sign and decreased or absent ovarian Doppler flow have good specificity but moderate sensitivity for detecting adnexal torsion. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Congenital and Infantile Hemangiomas: Epidemiological, Clinical, and Treatment Characteristics Based on 3 Years' Experience at a Tertiary Care Hospital - A Retrospective Case Comparison and Review of the Literature. / Características clínico-epidemiológicas y consideraciones terapéuticas de los hemangiomas congénitos e infantiles de un hospital de tercer nivel durante un periodo de 3 años: estudio comparativo y revisión de la literatura.

Distinguishing between congenital and infantile hemangiomas is challenging, but essential for appropriate treatment. The immunohistochemical marker glucose transporter type 1 is helpful, but biopsies are uncommon in this setting. The aim of this retrospective study was to describe and compare epidemiological, clinical, and treatment characteristics of congenital and infantile hemangiomas diagnosed at a tertiary care hospital over 3 years. We studied 107 hemangiomas: 34 congenital hemangiomas (rapidly involuting, partially involuting, and noninvoluting), 70 infantile hemangiomas, and 3 hemangiomas pending classification. Superficial infantile hemangiomas of the head and neck were the most prevalent tumors. Congenital hemangiomas were most often located on the trunk. Studied risk factors were more common in patients with infantile hemangiomas. In this group of patients, treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment.

Diagnostic accuracy of sliding sign for detecting pouch of Douglas obliteration and bowel involvement in women with suspected endometriosis: systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of the sliding sign on transvaginal ultrasound (TVS) in detecting pouch of Douglas obliteration and bowel involvement in patients with suspected endometriosis, using laparoscopy as the reference standard. METHODS: A search for studies evaluating the role of the sliding sign in the assessment of pouch of Douglas obliteration and/or bowel involvement using laparoscopy as the reference standard published from January 2000 to October 2021 was performed in PubMed/MEDLINE, Web of Science, CINAHL, The Cochrane Library, ClinicalTrials.gov and SCOPUS databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the studies. Analyses were performed using MIDAS and METANDI commands in STATA. RESULTS: A total of 334 citations were identified. Eight studies were included in the analysis, resulting in 938 and 963 patients available for analysis of the diagnostic accuracy of the sliding sign for pouch of Douglas obliteration and bowel involvement, respectively. The mean prevalence of pouch of Douglas obliteration was 37% and the mean prevalence of bowel involvement was 23%. The pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the sliding sign on TVS for detecting pouch of Douglas obliteration were 88% (95% CI, 81-93%), 94% (95% CI, 91-96%), 15.3 (95% CI, 10.2-22.9), 0.12 (95% CI, 0.07-0.21) and 123 (95% CI, 62-244), respectively. The heterogeneity was moderate for sensitivity and low for specificity for detecting pouch of Douglas obliteration. The pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the sliding sign on TVS for detecting bowel involvement were 81% (95% CI, 64-91%), 95% (95% CI, 91-97%), 16.0 (95% CI, 9.0-28.6), 0.20 (95% CI, 0.10-0.40) and 81 (95% CI, 34-191), respectively. The heterogeneity for the meta-analysis of diagnostic accuracy for bowel involvement was high. CONCLUSION: The sliding sign on TVS has good diagnostic performance for predicting pouch of Douglas obliteration and bowel involvement in women with suspected endometriosis. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound features of endometrial pathology in women without abnormal uterine bleeding: results from the International Endometrial Tumor Analysis study (IETA3).

OBJECTIVES: The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB. METHODS: This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology. RESULTS: In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized. CONCLUSIONS: We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy of transvaginal ultrasound for detection of endometriosis using International Deep Endometriosis Analysis (IDEA) approach: prospective international pilot study.

OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) in predicting deep endometriosis (DE) following the International Deep Endometriosis Analysis (IDEA) consensus methodology. METHODS: This was an international multicenter prospective diagnostic accuracy study involving eight centers across six countries (August 2018-November 2019). Consecutive participants with endometriosis suspected based on clinical symptoms or historical diagnosis of endometriosis were included. The index test was TVS performed preoperatively in accordance with the IDEA consensus statement. At each center, the index test was interpreted by a single sonologist. Reference standards were: (1) direct visualization of endometriosis at laparoscopy, as determined by a non-blinded surgeon with expertise in endometriosis surgery; and (2) histological assessment of biopsied/excised tissue. Surgery was performed within 12 months following the index TVS. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR-) of TVS in the diagnosis of DE were calculated. RESULTS: Included in the study were 273 participants with complete clinical, TVS, laparoscopic and histological data. Of these, based on histology, 256 (93.8%) were confirmed to have endometriosis, including superficial endometriosis, and 190 (69.6%) were confirmed to have DE. Based on surgical visualization, 207/273 (75.8%) patients had DE. For DE overall, the diagnostic performance of TVS based on surgical visualization as the reference standard was as follows: accuracy, 86.1%; sensitivity, 88.4%; specificity, 78.8%; PPV, 92.9%; NPV, 68.4%; LR+, 4.17; LR-, 0.15, and the diagnostic performance of TVS based on histology as the reference standard was as follows: accuracy, 85.9%; sensitivity, 89.8%; specificity, 75.9%; PPV, 90.4%; NPV, 74.6%; LR+, 3.72; LR-, 0.13. CONCLUSIONS: Using the IDEA consensus methodology provides strong diagnostic accuracy for TVS assessment of DE. We found a higher TVS detection rate of DE overall than that reported by the most recent meta-analysis on the topic (sensitivity, 79%), albeit with a lower specificity. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Female sexuality before and after sacrocolpopexy or vaginal mesh: is vaginal length one of the key factors?

INTRODUCTION AND HYPOTHESIS: We aimed to demonstrate that laparoscopic sacrocolpopexy/cervicopexy (LSC-Cx) versus anterior vaginal mesh (AVM) results in a longer vaginal length without impacting sexual activity or function. METHODS: We performed a secondary analysis of sexual outcomes of a previous randomized control trial comparing LSC-Cx and AVM in 120 women (60/group) with symptomatic POP stage ≥ 3. We evaluated sexually active (SA) and non-sexually active women (NSA) using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA-Revised (PISQ-IR) preoperatively and 1 year postoperatively. Multivariate logistic and linear regression models were built to assess the impact of different variables on sexual activity and function, respectively. RESULTS: Among 120 women included, no statistically significant differences were found between vaginal length and preoperative dyspareunia (20.7% AVM vs. 22,8% LSC-Cx) comparing SA to NSA women and LSC-Cx to AVM. Vaginal length was significantly longer after LSC-Cx versus AVM (p < 0.001). The postoperative dyspareunia rate was 17.2% AVM versus 10.5% LSC-Cx. Partnered women were significantly more likely to be SA than unpartnered women before (OR = 19.04; p = 0.006) and after surgery (OR = 36.28; p = 0.002). Only dyspareunia was independently associated with sexual function pre- (B = -0.431; p = 0.017) and postoperatively (B = -0.3 96; p = 0.007). CONCLUSIONS: Vaginal length was greater following LSC-Cx compared to AVM. While vaginal length has no impact on female sexuality pre- and postoperatively, the most important factors were "having a partner" for sexual activity and dyspareunia for sexual function. Persistence of dyspareunia was higher after AVM. LSC-Cx should be considered in women with POP undergoing mesh surgery with future sexual expectations.

Evaluation of the relationship between homocysteine levels and bone mineral density in postmenopausal women.

OBJECTIVE: The current study aimed to evaluate the relationship between homocysteine (Hcy) levels and bone mineral density (BMD) in postmenopausal women. METHODS: The present, cross-sectional study included 760 postmenopausal women. The following variables were recorded: age, age at menopause, body mass index (BMI), BMD (measured by dual-energy X-ray absorptiometry [DXA] scanning and expressed as lumbar, femoral neck and total hip T-scores), smoking status, biochemical parameters (Hcy, creatinine, calcium, phosphorus, vitamin D and parathormone levels) and vitamin D supplementation. RESULTS: The mean age of the sample population was 56.4 ± 5.77 years and the mean age at menopause was 49.9 ± 3.62 years. The mean BMI was 25.2 ± 4.49 kg/m2. In the current study, a comparison of the subjects with osteoporosis, osteopenia and normal BMD revealed that the subjects in the low BMD group were significantly older (p < 0.001), had a lower age at menopause (p < 0.001) and had lower BMI (p < 0.001). There was no statistically significant difference among the groups with regard to the plasma levels of Hcy (p = 0.946). The levels of Hcy were positively correlated to the creatinine levels (r = 0.21). The present study did not observe any significant correlations between the Hcy levels and other parameters. CONCLUSIONS: In the present study, 15.3% of the subjects had hyperhomocysteinemia and 62.11% had low BMD. The current results obtained from a group of postmenopausal women suggest that the plasma levels of Hcy are not related to BMD in the lumbar spine (L1-L4), femoral neck and total hip. In the current study, age, age at menopause and low BMI were observed to be associated with low BMD.

The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group.

OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates. RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

Short-duration treatment with the novel non-nucleoside inhibitor CDI-31244 plus sofosbuvir/velpatasvir for chronic hepatitis C: An open-label study.

Combination regimens of direct-acting antiviral agents (DAAs) for chronic genotype 1 hepatitis C virus (HCV) infection given for 8 or 12 weeks have high cure rates. Shortened treatment durations that maintain high cure rates may lessen treatment barriers related to affordability and drug adherence. We enrolled 12 treatment-naïve adults with chronic genotype 1 HCV infection without cirrhosis in a single-center, open-label trial to receive 2 weeks of the highly potent and selective non-nucleoside inhibitor (NNI) CDI-31244 concurrent with 6 weeks of sofosbuvir/velpatasvir. The main efficacy endpoints were sustained virologic response at 12 (SVR12) and 24 (SVR24) weeks after treatment completion. In all patients, plasma HCV RNA levels rapidly decreased during the first 2 days of treatment and were below the lower limit of quantification by the end of the 6-week treatment period. Eight of 12 (67%) patients achieved both SVR12 and SVR24. Four patients had virological relapse at Week 10, 4 weeks after end of treatment. The most common adverse event was headache, occurring in five (42%) patients. Pharmacokinetic analysis showed no relevant drug interactions between CDI-31244, sofosbuvir, and velpatasvir. In this pilot study of short-duration combination therapy involving a novel NNI with a fixed-combination DAA, 8 of 12 treatment-naïve patients with chronic genotype 1 HCV infection without cirrhosis achieved virologic cure. Future trials might evaluate whether extending the NNI duration beyond 2 weeks with combination DAAs results in higher cure rates comparable with currently approved longer duration therapy.

Diagnostic accuracy of transvaginal sonography for detecting parametrial involvement in women with deep endometriosis: systematic review and meta-analysis.

OBJECTIVE: To evaluate the accuracy of transvaginal sonography (TVS) for detecting parametrial deep endometriosis, using laparoscopy as the reference standard. METHODS: A search was performed in PubMed/MEDLINE and Web of Science for studies evaluating TVS for detecting parametrial involvement in women with suspected deep endometriosis, as compared with laparoscopy, from January 2000 to December 2020. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of the studies. Pooled sensitivity, specificity and positive and negative likelihood ratios for TVS in the detection of parametrial deep endometriosis were calculated, and the post-test probability of parametrial deep endometriosis following a positive or negative test was determined. RESULTS: The search identified 134 citations. Four studies, comprising 560 patients, were included in the analysis. The mean prevalence of parametrial deep endometriosis at surgery was 18%. Overall, the pooled estimated sensitivity, specificity and positive and negative likelihood ratios of TVS in the detection of parametrial deep endometriosis were 31% (95% CI, 10-64%), 98% (95% CI, 95-99%), 18.5 (95% CI, 8.8-38.9) and 0.70 (95% CI, 0.46-1.06), respectively. The diagnostic odds ratio was 26 (95% CI, 10-68). Heterogeneity was high. Visualization of a lesion suspected to be parametrial deep endometriosis on TVS increased significantly the post-test probability of parametrial deep endometriosis. CONCLUSION: TVS has high specificity but low sensitivity for the detection of parametrial deep endometriosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Vessel morphology depicted by three-dimensional power Doppler ultrasound as second-stage test in adnexal tumors that are difficult to classify: prospective diagnostic accuracy study.

OBJECTIVES: To assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second-stage test in adnexal masses that are difficult to classify. METHODS: This was a prospective observational international multicenter diagnostic accuracy study. Consecutive patients with an adnexal mass underwent standardized transvaginal two-dimensional (2D) grayscale and color or power Doppler and 3D power Doppler ultrasound examination by an experienced examiner, and those with a 'difficult' tumor were included in the current analysis. A difficult tumor was defined as one in which the International Ovarian Tumor Analysis (IOTA) logistic regression model-1 (LR-1) yielded an ambiguous result (risk of malignancy, 8.3% to 25.5%), or as one in which the ultrasound examiner was uncertain regarding classification as benign or malignant when using subjective assessment. Even when the ultrasound examiner was uncertain, he/she was obliged to classify the tumor as most probably benign or most probably malignant. For each difficult tumor, one researcher created a 360° rotating 3D power Doppler image of the vessel tree in the whole tumor and another of the vessel tree in a 5-cm3 spherical volume selected from the most vascularized part of the tumor. Two other researchers, blinded to the patient's history, 2D ultrasound findings and histological diagnosis, independently described the vessel tree using predetermined vessel features. Their agreed classification was used. The reference standard was the histological diagnosis of the mass. The sensitivity of each test for discriminating between benign and malignant difficult tumors was plotted against 1 - specificity on a receiver-operating-characteristics diagram, and the test with the point furthest from the reference line was considered to have the best diagnostic ability. RESULTS: Of 2403 women with an adnexal mass, 376 (16%) had a difficult mass. Ultrasound volumes were available for 138 of these cases. In 79/138 masses, the ultrasound examiner was uncertain about the diagnosis based on subjective assessment, in 87/138, IOTA LR-1 yielded an ambiguous result and, in 28/138, both methods gave an uncertain result. Of the masses, 38/138 (28%) were malignant. Among tumors that were difficult to classify as benign or malignant by subjective assessment, the vessel feature 'densely packed vessels' had the best discriminative ability (sensitivity 67% (18/27), specificity 83% (43/52)) and was slightly superior to subjective assessment (sensitivity 74% (20/27), specificity 60% (31/52)). In tumors in which IOTA LR-1 yielded an ambiguous result, subjective assessment (sensitivity 82% (14/17), specificity 79% (55/70)) was superior to the best vascular feature, i.e. changes in the diameter of vessels in the whole tumor volume (sensitivity 71% (12/17), specificity 69% (48/70)). CONCLUSION: Vessel morphology depicted by 3D power Doppler ultrasound may slightly improve discrimination between benign and malignant adnexal tumors that are difficult to classify by subjective ultrasound assessment. For tumors in which the IOTA LR-1 model yields an ambiguous result, subjective assessment is superior to vessel morphology as a second-stage test. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding.

OBJECTIVE: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. RESULTS: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m2 (range, 16.0-72.1 kg/m2 ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2-1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6-3.4%)) cases with a single vessel without branching on unenhanced ultrasound. CONCLUSIONS: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Sexual activity and function in women with advanced stages of pelvic organ prolapse, before and after laparoscopic or vaginal mesh surgery.

INTRODUCTION AND HYPOTHESIS: The differential impact of specific pelvic organ prolapse (POP) surgery on sexual activity and function is unknown. Our primary aim was to analyse sexual inactivity and function in women with symptomatic advanced stages of POP and the changes incurred after laparoscopic or vaginal mesh surgery. METHODS: We performed a secondary analysis of sexual outcomes of a previously published randomised controlled trial comparing laparoscopic sacrocolpopexy/cervicopexy (LSC-Cx) and anterior vaginal mesh (AVM) in 120 women (60/group) with symptomatic anterior POP stage ≥ 3 and apical ≥ 2. Sexual activity and function were assessed preoperatively and 1 and 2 years postoperatively using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA-Revised (PISQ-IR). RESULTS: Sexual activity was recovered in 42.9% of non-sexually active (NSA) women 1 year postoperatively, mainly in women with higher preoperative POP-related subscale scores of the PISQ-IR, which indicated a negative preoperative sexuality by POP. Recovery of sexual activity was greater after LSC-Cx, albeit not significantly (2 years: 35.5% AVM vs. 45% LSC-Cx). Among sexually active (SA) women preoperatively remaining SA postoperatively, the difference in the mean PISQ-IR summary score significantly improved [mean baseline difference - 2 years; all: 0.3 (95% CI 0.1 to 0.5) p = 0.001; AVM 0.19 (95% CI -0.1 to -0.5) p > 0.05; LSC-Cx 0.37 (95% CI 0.1 to 0.7) p = 0.003]. Preoperative dyspareunia was significantly reduced after LSC-Cx (baseline: 24.6%, 2 years: 9.8%, p = 0.0448), but not after AVM (baseline: 20.7%, 2 years: 18.2%, p = 0.7385). CONCLUSIONS: Most women reported improved sexual activity and function 2 years after LSC-Cx or AVM, mainly because of enhanced POP-related subscales in both NSA and SA women. Recovery of sexual activity and improved sexual function were greater after LSC-Cx compared to AVM, likely related to less postoperative dyspareunia.

Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report.

BACKGROUND: Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown. CASE PRESENTATION: A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation. CONCLUSIONS: We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

"Are changes in breast density during the menstrual cycle relevant? To what?"

PURPOSE: Cancers can be hidden by high breast density (BDen)- the masking effect (ME). BDen is also a modifiable and highly prevalent breast cancer risk (BCR) factor. The purposes of this study were to determine how much glandular volume (GVol), breast volume (BVol) and their ratio: BDen change during the menstrual cycle, and if these changes could affect ME or be relevant to results of interventional studies aiming to diminish BCR using these parameters as surrogates. METHODS: We retrieved GVol, BVol and BDen data values obtained from 39,997 right mammograms performed with photon counting technique of 19,904 premenopausal women who reported their first day of last menses (FDLM). Many women had more than one study included over the years (with a different FDLM) but were not studied longitudinally. We segregated women by age (yearly), divided the menstrual cycle in 4 weeks, and assigned results with respect to the FDLM. RESULTS: All parameters vary cyclically, with higher values in week 4 (GVol and BDen) or week 1 (BVol). Mean inter-week differences were very small for the three parameters, and diminished with age. However, especially in the youngest women, inter-week differences could be more than 10% for BDen, 15% for GVol, and 50% for BVol. CONCLUSION: Small inter-week mean differences almost certainly rule out relevant changes to ME directly attributable to BDen. However, the possibility of large differences during the menstrual cycle in younger women, who are the ideal targets of interventional studies to diminish BCR, might distort results and should be accounted for.

Breast density measured volumetrically in a clinical environment: cross-sectional study with photon counting technology.

OBJECTIVE: Mammographic breast density (BDen), the ratio of glandular volume (GVol) to breast volume (BVol), is the second most prevalent risk factor for breast cancer (BC). Newly developed photon counting technology allows precise and systematic measurements in clinical practice. Our objective is to see how these parameters change with age in women with and without cancer. MATERIALS AND METHODS: This retrospective study analyzed results of BDen, GVol, and BVol in 64,182 mammograms performed with photon counting technology on 32,448 consecutive women from April 2014 to December 2015. Only their first study was included. We excluded women with incomplete data or with breast implants. RESULTS: Mean age of women without BC diagnosed during the study period was 52.1 ± 9.9. BC and was found in 263 women (0.81%). Mean age was 53.0 ± 10.4. BDen, GVol, and BVol were 14%, 24%, and 2% greater in women with BC (P < 0.001 for BDen and GVol and P = 0.02 for BVol). BDen and GVol diminished following similar patterns across age in both groups, with soft slopes before and after a steep drop from 50 to 60, probably due to menopause. CONCLUSION: BDen diminishes with age in women with or without BC, but it is generally higher in women with BC. GVol could be a more robust indicator associated with BC risk than BDen. This technology can ease the way to studies of interventions to diminish BDen (or GVol) in the hope of diminishing BC incidence or predict if longitudinal changes are indicative of impending cancer.