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1.	Jakobsson, J., et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1 2021 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 17:1, s. 1-382 Tidskriftsartikel (refereegranskat)
2.	Goetghebuer, T, et al. (författare) Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand 2018 Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 66:4, s. 594-603 Tidskriftsartikel (refereegranskat)
3.	Shimwell, T. W., et al. (författare) The LOFAR Two-metre Sky Survey: V. Second data release 2022 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659 Tidskriftsartikel (refereegranskat)abstract In this data release from the ongoing LOw-Frequency ARray (LOFAR) Two-metre Sky Survey we present 120a 168 MHz images covering 27% of the northern sky. Our coverage is split into two regions centred at approximately 12h45m +44 30a and 1h00m +28 00a and spanning 4178 and 1457 square degrees respectively. The images were derived from 3451 h (7.6 PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4 396 228 radio sources is derived from our total intensity (Stokes I) maps, where the majority of these have never been detected at radio wavelengths before. At 6a resolution, our full bandwidth Stokes I continuum maps with a central frequency of 144 MHz have: a median rms sensitivity of 83 μJy beama 1; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2a; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8 mJy beama 1. By creating three 16 MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of > a ±a 0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes V) 20a resolution 120a168 MHz continuum images have a median rms sensitivity of 95 μJy beama 1, and we estimate a Stokes I to Stokes V leakage of 0.056%. Our linear polarisation (Stokes Q and Stokes U) image cubes consist of 480a A a 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8 mJy beama 1 at 4a and 2.2 mJy beama 1 at 20a; we estimate the Stokes I to Stokes Q/U leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes I, Q, U and V images in addition to the calibrated uv-data to facilitate the thorough scientific exploitation of this unique dataset.
4.	Collins, IJ, et al. (författare) Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration 2019 Ingår i: The lancet. HIV. - 2352-3018. ; 6:2, s. E105-E115 Tidskriftsartikel (refereegranskat)
5.	Slogrove, AL, et al. (författare) The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis 2018 Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 15:3, s. e1002514- Tidskriftsartikel (refereegranskat)
6.	Di Legge, A., et al. (författare) Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses 2012 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:3, s. 345-354 Tidskriftsartikel (refereegranskat)abstract Objectives To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). Methods We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 49.9 cm; n = 1457) and large tumors (diameter = 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiveroperating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. Results The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (5684% vs 6793% in medium-sized tumors and 7495% in large tumors) while specificity was lowest in large tumors (6087%vs 8395% in medium-sized tumors and 8396% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 711 cm. Conclusion Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
7.	Dierickx, I., et al. (författare) Imaging in gynecological disease (7): clinical and ultrasound features of Brenner tumors of the ovary 2012 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:6, s. 706-713 Tidskriftsartikel (refereegranskat)abstract Objectives To describe clinical and ultrasound features of Brenner tumors of the ovary. Methods In this retrospective study, the databases of the International Ovarian Tumor Analysis (IOTA) studies and one tertiary center were searched to identify patients who had undergone an ultrasound scan before surgery for an adnexal mass that proved to be a Brenner tumor. Twenty-eight patients with 29 Brenner tumors were included, most of which had been collected within the framework of the IOTA studies. An experienced ultrasound examiner reviewed available ultrasound images (available for 14 tumors), searching for a pattern specific to Brenner tumors. Results Most patients were postmenopausal and asymptomatic. Twenty-four (83%) tumors were benign, two (7%) were borderline and three (10%) were malignant. Most benign tumors (17/24, 71%) contained solid components and manifested no or minimal blood flow on Doppler examination (19/24, 79%). Information about calcifications was available for 15 benign tumors, and in 13 (87%) calcifications were present. The five borderline and invasively malignant tumors contained solid components less often than did the benign ones (3/5, 60%) and were more richly vascularized on Doppler examination. Information about calcifications was available for four borderline or invasively malignant tumors, and in three (75%) calcifications were present. Conclusion We failed to demonstrate ultrasound features specific to Brenner tumors. A prospective study is needed to determine if ultrasound features of calcifications can discriminate between Brenner tumors and other types of ovarian tumor. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
8.	Jordans, I. P.M., et al. (författare) Definition and sonographic reporting system for Cesarean scar pregnancy in early gestation : modified Delphi method 2022 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 59:4, s. 437-449 Tidskriftsartikel (refereegranskat)abstract Objective: To develop a standardized sonographic evaluation and reporting system for Cesarean scar pregnancy (CSP) in the first trimester, for use by both general gynecology and expert clinics. Methods: A modified Delphi procedure was carried out, in which 28 international experts in obstetric and gynecological ultrasonography were invited to participate. Extensive experience in the use of ultrasound to evaluate Cesarean section (CS) scars in early pregnancy and/or publications concerning CSP or niche evaluation was required to participate. Relevant items for the detection and evaluation of CSP were determined based on the results of a literature search. Consensus was predefined as a level of agreement of at least 70% for each item, and a minimum of three Delphi rounds were planned (two online questionnaires and one group meeting). Results: Sixteen experts participated in the Delphi study and four Delphi rounds were performed. In total, 58 items were determined to be relevant. We differentiated between basic measurements to be performed in general practice and advanced measurements for expert centers or for research purposes. The panel also formulated advice on indications for referral to an expert clinic. Consensus was reached for all 58 items on the definition, terminology, relevant items for evaluation and reporting of CSP. It was recommended that the first CS scar evaluation to determine the location of the pregnancy should be performed at 6–7 weeks' gestation using transvaginal ultrasound. The use of magnetic resonance imaging was not considered to add value in the diagnosis of CSP. A CSP was defined as a pregnancy with implantation in, or in close contact with, the niche. The experts agreed that a CSP can occur only when a niche is present and not in relation to a healed CS scar. Relevant sonographic items to record included gestational sac (GS) size, vascularity, location in relation to the uterine vessels, thickness of the residual myometrium and location of the pregnancy in relation to the uterine cavity and serosa. According to its location, a CSP can be classified as: (1) CSP in which the largest part of the GS protrudes towards the uterine cavity; (2) CSP in which the largest part of the GS is embedded in the myometrium but does not cross the serosal contour; and (3) CSP in which the GS is partially located beyond the outer contour of the cervix or uterus. The type of CSP may change with advancing gestation. Future studies are needed to validate this reporting system and the value of the different CSP types. Conclusion: Consensus was achieved among experts regarding the sonographic evaluation and reporting of CSP in the first trimester.
9.	Ludovisi, M., et al. (författare) Imaging in gynecological disease (9): clinical and ultrasound characteristics of tubal cancer 2014 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 43:3, s. 328-335 Tidskriftsartikel (refereegranskat)abstract Objectives To describe clinical history and ultrasound findings in patients with tubal carcinoma. Methods Patients with a histological diagnosis of tubal cancer who had undergone preoperative ultrasound examination were identified from the databases of 13 ultrasound centers. The tumors were described by the principal investigator at each contributing center on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, three authors reviewed together all available digital ultrasound images and described them using subjective evaluation of gray-scale and color Doppler ultrasound findings. Results We identified 79 women with a histological diagnosis of primary tubal cancer, 70 of whom (89%) had serous carcinomas and 46 (58%) of whom presented at FIGO stage III. Forty-nine (62%) women were asymptomatic (incidental finding), whilst the remaining 30 complained of abdominal bloating or pain. Fifty-three (67%) tumors were described as solid at ultrasound examination, 14 (18%) as multilocular solid, 10 (13%) as unilocular solid and two (3%) as unilocular. No tumor was described as a multilocular mass. Most tumors (70/79, 89%) were moderately or very well vascularized on color or power Doppler ultrasound. Normal ovarian tissue was identified adjacent to the tumor in 51% (39/77) of cases. Three types of ultrasound appearance were identified as being typical of tubal carcinoma using pattern recognition: a sausage-shaped cystic structure with solid tissue protruding into it like a papillary projection (11/62, 18%); a sausage-shaped cystic structure with a large solid component filling part of the cyst cavity (13/62, 21%); an ovoid or oblong completely solid mass (36/62, 58%). Conclusions A well vascularized ovoid or sausage-shaped structure, either completely solid or with large solid component(s) in the pelvis, should raise the suspicion of tubal cancer, especially if normal ovarian tissue is seen adjacent to it. Copyright (C) 2013 ISUOG. Published by John Wiley & Sons Ltd.
10.	Sokalska, A., et al. (författare) Diagnostic accuracy of transvaginal ultrasound examination for assigning a specific diagnosis to adnexal masses 2009 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 34:4, s. 462-470 Tidskriftsartikel (refereegranskat)abstract Objectives To determine the sensitivity and specificity of subjective evaluation of gray-scale and Doppler ultrasound findings (here called pattern recognition) when used by experienced ultrasound examiners with regard to making a specific diagnosis of adnexal masses. Methods Within the framework of a European multi-center study, the International Ovarian Tumor Analysis study, comprising nine ultrasound centers, women with at least one adnexal mass were examined with gray-scale and color Doppler ultrasonography by experienced ultrasound examiners. A standardized examination technique, and standardized terms and definitions were used. Using pattern recognition the examiners classified each mass as benign or malignant and suggested a specific diagnosis (e.g. dermoid cyst or endometrioma). The reference standard was the histology of the surgically removed adnexal tumors. Results A total of 1066 women were included, of whom 800 bad a benign mass and 266 a malignant mass. A specific diagnosis based on ultrasound findings was suggested in 899 (84%) tumors. The specificity was high for all diagnoses (range, 94-100%). The sensitivity was highest for benign teratoma/dermoid cysts (86%, 100/116), hydrosalpinges (86%, 18/21), peritoneal pseudocysts (80%, 4/5) and endometriomas (77%, 1531199), and lowest for functional cysts (17%, 4124), paraovarian/parasalpingeal cysts (14%, 3121), benign rare tumors (11%, 119), adenofibromas (8%, 3/39), simple cysts (6%, 1/18) and struma ovarii (0%, 0/5). The positive and negative likelihood ratios of pattern recognition with regard to dermoid cysts, hydrosalpinges and endometriomas were 68.2 and 0.14, 38.9 and 0.15, and 33.3 and 0.24, respectively. Dermoid cysts, hydrosalpinges, functional cysts, paraovarian cysts, peritoneal pseudocysts, fibromas/fibrothecomas and simple cysts were never misdiagnosed as malignancies by the ultrasound examiner, whereas more than 10% of inflammatory processes, adenofibromas and rare benign tumors including struma ovarii were misdiagnosed as malignancies. Conclusions Using subjective evaluation of gray-scale and Doppler ultrasound findings it is possible to make an almost conclusive diagnosis of a dermoid cyst, endometrioma and hydrosalpinx. Many other adnexal pathologies can be recognized but not confidently confirmed or excluded. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
11.	Timmerman, D., et al. (författare) Ovarian cancer prediction in adnexal masses using ultrasound-based logistic regression models: a temporal and external validation study by the IOTA group 2010 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 36:2, s. 226-234 Tidskriftsartikel (refereegranskat)abstract Objectives The aims of the study were to temporally and externally validate the diagnostic performance of two logistic regression models containing clinical and ultrasound variables in order to estimate the risk of malignancy in adnexal masses, and to compare the results with the subjective interpretation of ultrasound findings carried out by an experienced ultrasound examiner ('subjective assessment'). Methods Patients with adnexal masses, who were put forward by the 19 centers participating in the study, underwent a standardized transvaginal ultrasound examination by a gynecologist or a radiologist specialized in ultrasonography. The examiner prospectively collected information on clinical and ultrasound variables, and classified each mass as benign or malignant on the basis of subjective evaluation of ultrasound findings. The gold standard was the histology of the mass with local clinicians deciding whether to operate on the basis of ultrasound results and the clinical picture. The models' ability to discriminate between malignant and benign masses was assessed, together with the accuracy of the risk estimates. Results Of the 1938 patients included in the study, 1396 had benign, 373 had primary invasive, 111 had borderline malignant and 58 had metastatic tumors. On external validation (997 patients from 12 centers), the area under the receiver operating characteristics curve (AUC) for a model containing 12 predictors (LR1) was 0.956, for a reduced model with six predictors (LR2) was 0.949 and for subjective assessment was 0.949. Subjective assessment gave a positive likelihood ratio of 11.0 and a negative likelihood ratio of 0.14. The corresponding likelihood ratios for a previously derived probability threshold (0.1) were 6.84 and 0.09 for LR1, and 6.36 and 0.10 for LR2. On temporal validation (941 patients from seven centers), the AUCs were 0.945 (LR1), 0.918 (LR2) and 0.959 (subjective assessment). Conclusions Both models provide excellent discrimination between benign and malignant masses. Because the models provide an objective and reasonably accurate risk estimation, they may improve the management of women with suspected ovarian pathology. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
12.	Van Den Bosch, T., et al. (författare) Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding 2021 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 57:1, s. 164-172 Tidskriftsartikel (refereegranskat)abstract 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.
13.	Van Holsbeke, C., et al. (författare) Endometriomas: their ultrasound characteristics 2010 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 35:6, s. 730-740 Tidskriftsartikel (refereegranskat)abstract Objectives To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas. Methods All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated. Results Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable. Conclusions Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
14.	Ameye, L., et al. (författare) Clinically oriented three-step strategy for assessment of adnexal pathology 2012 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:5, s. 582-591 Tidskriftsartikel (refereegranskat)abstract Objective To determine the diagnostic performance of ultrasound-based simple rules, risk of malignancy index (RMI), two logistic regression models (LR1 and LR2) and real-time subjective assessment by experienced ultrasound examiners following the exclusion of masses likely to be judged as easy and 'instant' to diagnose by an ultrasound examiner, and to develop a new strategy for the assessment of adnexal pathology based on this. Methods 3511 patients with at least one persistent adnexal mass preoperatively underwent transvaginal ultrasonography to assess tumor morphology and vascularity. They were included in two consecutive prospective studies by the International Ovarian Tumor Analysis (IOTA) group: Phase 1 (1999-2005), development of the simple rules and logistic regression models LR1 and LR2, and Phase 2, a validation study (2005-2007). Results Almost half of the cases (43%) were identified as 'instant' to diagnose on the basis of descriptors applied to the database. To assess diagnostic performance in the more difficult 'non-instant' masses, we used only Phase 2 data (n = 1036). The sensitivity of LR2 was 88%, of RMI it was 41% and of subjective assessment it was 87%. The specificity of LR2 was 67%, of RMI it was 90% and of subjective assessment it was 86%. The simple rules yielded a conclusive result in almost 2/3 of the masses, where they resulted in sensitivity and specificity similar to those of real-time subjective assessment by experienced ultrasound examiners: sensitivity 89 vs 89% (P = 0.76), specificity 91 vs 91% (P = 0.65). When a three-step strategy was appliedwith easy 'instant' diagnoses as Step 1, simple rules where conclusive as Step 2 and subjective assessment by an experienced ultrasound examiner in the remaining masses as Step 3, we obtained a sensitivity of 92% and specificity of 92% compared with sensitivity 90% (P = 0.03) and specificity 93% (P = 0.44) when using real-time subjective assessment by experts in all tumors. Conclusion A diagnostic strategy using simple descriptors and ultrasound rules when applied to the variables contained in the IOTA database obtains results that are at least as good as those obtained by subjective assessment of a mass by an expert. Copyright. (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
15.	Biegstraaten, M, et al. (författare) Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease 2018 Ingår i: Blood cells, molecules & diseases. - : Elsevier BV. - 1096-0961 .- 1079-9796. ; 68, s. 203-208 Tidskriftsartikel (refereegranskat)
16.	Daemen, A., et al. (författare) Improving the preoperative classification of adnexal masses as benign or malignant by second-stage tests 2011 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 37:1, s. 100-106 Tidskriftsartikel (refereegranskat)abstract Objective The aim of this study was to establish when a second-stage diagnostic test may be of value in cases where a primary diagnostic test has given an uncertain diagnosis of the benign or malignant nature of an adnexal mass. Methods The diagnostic performance with regard to discrimination between benign and malignant adnexal masses for mathematical models including ultrasound variables and for subjective evaluation of ultrasound findings by an experienced ultrasound examiner was expressed as area under the receiver-operating characteristics curve (AUC), sensitivity and specificity. These were calculated for the total study population of 1938 patients with an adnexal mass as well as for sub-populations defined by the certainty with which the diagnosis of benignity or malignancy was made. The effect of applying a second-stage test to the tumors where risk estimation was uncertain was determined. Results The best mathematical model (LR1) had an AUC of 0.95, sensitivity of 92% and specificity of 84% when applied to all tumors. When model LR1 was applied to the 10% of tumors in which the calculated risk fell closest to the risk cut-off of the model, the AUC was 0.59, sensitivity 90% and specificity 21%. A strategy where subjective evaluation was used to classify these 10% of tumors for which LR1 performed poorly and where LR1 was used in the other 90% of tumors resulted in a sensitivity of 91% and specificity of 90%. Applying subjective evaluation to all tumors yielded an AUC of 0.95, sensitivity of 90% and specificity of 93%. Sensitivity was 81% and specificity 47% for those patients where the ultrasound examiner was uncertain about the diagnosis (n = 115; 5.9%). No mathematical model performed better than did subjective evaluation among the 115 tumors where the ultrasound examiner was uncertain. Conclusion When model LR1 is used as a primary test for discriminating between benign and malignant adnexal masses, the use of subjective evaluation of ultrasound findings by an experienced examiner as a second-stage test in the 10% of cases for which the model yields a risk of malignancy closest to its risk cut-off will improve specificity without substantially decreasing sensitivity. However, none of the models tested proved suitable as a second-stage test in tumors where subjective evaluation yielded an uncertain result. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
17.	Landolfo, C., et al. (författare) Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors : retrospective validation on IOTA 5 multicenter cohort 2023 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 61:2, s. 231-242 Tidskriftsartikel (refereegranskat)abstract Objective: Previous work suggested that the ultrasound-based benign Simple Descriptors can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. We aim to validate a modified version of the Benign Simple Descriptors (BD), and we introduce a two-step strategy to estimate the risk of malignancy: if the BDs do not apply, the ADNEX model is used to estimate the risk of malignancy. Methods: This is a retrospective analysis using the data from the 2-year interim analysis of the IOTA5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during one year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. Results: 8519 patients were recruited at 36 centers between 2012 and 2015. We included all masses that were not already in follow-up at recruitment from 17 centers with good quality surgical and follow-up data, leaving 4905 patients for statistical analysis. 3441 (70%) tumors were benign, 978 (20%) malignant, and 486 (10%) uncertain. The BDs were applicable in 1798/4905 (37%) tumors, and 1786 (99.3%) of these were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI, 0.91-0.95). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). Conclusion: A large proportion of adnexal masses can be classified as benign by the BDs. For the remaining masses the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use.
18.	Sladkevicius, P., et al. (författare) International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm : agreement and reliability study 2018 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 51:2, s. 259-268 Tidskriftsartikel (refereegranskat)abstract Objective: To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. Methods: Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial–myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. Results: Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial–myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial–myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts. Conclusions: Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability.
19.	Sladkevicius, P., et al. (författare) 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 2021 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 57:2, s. 324-334 Tidskriftsartikel (refereegranskat)abstract 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.
20.	Virgilio, B. A., et al. (författare) Imaging in gynecological disease (16) : clinical and ultrasound characteristics of serous cystadenofibromas in adnexa 2019 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 54:6, s. 823-830 Tidskriftsartikel (refereegranskat)abstract Objective: To describe the clinical and ultrasound characteristics of serous cystadenofibromas in the adnexa. Methods: This was a retrospective study of patients identified in the International Ovarian Tumor Analysis (IOTA) database, who had a histological diagnosis of serous cystadenofibroma and had undergone preoperative ultrasound examination by an experienced ultrasound examiner, between 1999 and 2012. In the IOTA database, which contains data collected prospectively, the tumors were described using the terms and definitions of the IOTA group. In addition, three authors reviewed, first independently and then together, ultrasound images of serous cystadenofibromas and described them using pattern recognition. Results: We identified 233 women with a histological diagnosis of serous cystadenofibroma. In the IOTA database, most cystadenofibromas (67.4%; 157/233) were described as containing solid components but 19.3% (45/233) were described as multilocular cysts and 13.3% (31/233) as unilocular cysts. Papillary projections were described in 52.4% (122/233) of the cystadenofibromas. In 79.5% (97/122) of the cysts with papillary projections, color Doppler signals were absent in the papillary projections. Most cystadenofibromas (83.7%; 195/233) manifested no or minimal color Doppler signals. On retrospective analysis of 201 ultrasound images of serous cystadenofibromas, using pattern recognition, 10 major types of ultrasound appearance were identified. The most common pattern was a unilocular solid cyst with one or more papillary projections, but no other solid components (25.9%; 52/201). The second most common pattern was a multilocular solid mass with small solid component(s), but no papillary projections (19.4%; 39/201). The third and fourth most common patterns were multi- or bilocular cyst (16.9%; 34/201) and unilocular cyst (11.9%; 24/201). Using pattern recognition, shadowing was identified in 39.8% (80/201) of the tumors, and microcystic appearance of the papillary projections was observed in 34 (38.6%) of the 88 tumors containing papillary projections. Conclusions: The ultrasound features of serous cystadenofibromas vary. The most common pattern is a unilocular solid cyst with one or more papillary projections but no other solid components, with absent color Doppler signals. Most serous cystadenofibromas were poorly vascularized on color Doppler examination and many manifested acoustic shadowing.
21.	Weihl, CC, et al. (författare) 234th ENMC International Workshop: Chaperone dysfunction in muscle disease Naarden, The Netherlands, 8-10 December 2017 2018 Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 1873-2364 .- 0960-8966. ; 28:12, s. 1022-1030 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
22.	Weiss, M, et al. (författare) 10 clinical tips for advancing patient safety when using syringe pump systems for microinfusion intravenous drug therapy 2023 Ingår i: European journal of anaesthesiology. - 1365-2346. ; 40:6, s. 387-390 Tidskriftsartikel (refereegranskat)
23.	Ciccarone, F., et al. (författare) Imaging in gynecological disease (23) : clinical and ultrasound characteristics of ovarian carcinosarcoma 2022 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 59:2, s. 241-247 Tidskriftsartikel (refereegranskat)abstract Objective: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma. Methods: This was a retrospective multicenter study. Patients with a histological diagnosis of ovarian carcinosarcoma, who had undergone preoperative ultrasound examination between 2010 and 2019, were identified from the International Ovarian Tumor Analysis (IOTA) database. Additional patients who were examined outside of the IOTA study were identified from the databases of the participating centers. The masses were described using the terms and definitions of the IOTA group. Additionally, two experienced ultrasound examiners reviewed all available images to identify typical ultrasound features using pattern recognition. Results: Ninety-one patients with ovarian carcinosarcoma who had undergone ultrasound examination were identified, of whom 24 were examined within the IOTA studies and 67 were examined outside of the IOTA studies. Median age at diagnosis was 66 (range, 33–91) years and 84/91 (92.3%) patients were postmenopausal. Most patients (67/91, 73.6%) were symptomatic, with the most common complaint being pain (51/91, 56.0%). Most tumors (67/91, 73.6%) were International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV. Bilateral lesions were observed on ultrasound in 46/91 (50.5%) patients. Ascites was present in 38/91 (41.8%) patients. The median largest tumor diameter was 100 (range, 18–260) mm. All ovarian carcinosarcomas contained solid components, and most were described as solid (66/91, 72.5%) or multilocular-solid (22/91, 24.2%). The median diameter of the largest solid component was 77.5 (range, 11–238) mm. Moderate or rich vascularization was found in 78/91 (85.7%) cases. Retrospective analysis of ultrasound images and videoclips using pattern recognition in 73 cases revealed that all tumors had irregular margins and inhomogeneous echogenicity of the solid components. Forty-seven of 73 (64.4%) masses appeared as a solid tumor with cystic areas. Cooked appearance of the solid tissue was identified in 28/73 (38.4%) tumors. No pathognomonic ultrasound sign of ovarian carcinosarcoma was found. Conclusions: Ovarian carcinosarcomas are usually diagnosed in postmenopausal women and at an advanced stage. The most common ultrasound appearance is a large solid tumor with irregular margins, inhomogeneous echogenicity of the solid tissue and cystic areas. The second most common pattern is a large multilocular-solid mass with inhomogeneous echogenicity of the solid tissue.
24.	Di Legge, A., et al. (författare) Clinical and ultrasound characteristics of surgically removed adnexal lesions with largest diameter ≤ 2.5 cm : a pictorial essay 2017 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692. ; 50:5, s. 648-656 Tidskriftsartikel (refereegranskat)abstract Objectives: To describe the ultrasound characteristics, indications for surgery and histological diagnoses of surgically removed adnexal masses with a largest diameter of ≤ 2.5 cm (very small tumors), to estimate the sensitivity and specificity of diagnosis of malignancy by subjective assessment of ultrasound images of very small tumors and to present a collection of ultrasound images of surgically removed very small tumors, with emphasis on those causing diagnostic difficulty. Methods: Information on surgically removed adnexal tumors with a largest diameter of ≤ 2.5 cm was retrieved from the ultrasound databases of seven participating centers. The ultrasound images were described using the International Ovarian Tumor Analysis terminology. The original diagnosis, based on subjective assessment of the ultrasound images by the ultrasound examiner, was used to calculate the sensitivity and specificity of diagnosis of malignancy. Results: Of the 129 identified adnexal masses with largest diameter ≤ 2.5 cm, 104 (81%) were benign, 15 (12%) borderline malignant and 10 (8%) invasive tumors. The main indication for performing surgery was suspicion of malignancy in 22% (23/104) of the benign tumors and in all 25 malignant tumors. None of the malignant tumors was a unilocular cyst (vs 50% of the benign tumors), all malignancies contained solid components (vs 43% of the benign tumors), 80% of the borderline tumors had papillary projections (vs 21% of the benign tumors and 20% of the invasive malignancies) and all invasive tumors and 80% of the borderline tumors were vascularized on color/power Doppler examination (vs 44% of the benign tumors). The ovarian crescent sign was present in 85% of the benign tumors, 80% of the borderline tumors and 50% of the invasive malignancies. The sensitivity of diagnosis of malignancy by subjective assessment of ultrasound images was 100% (25/25) and the specificity was 86% (89/104). Excluding unilocular cysts, the specificity was 71% (37/52). Analysis of images illustrated the difficulty in distinguishing benign from borderline very small cysts with papillations and benign from malignant very small well vascularized (color score 3 or 4) solid adnexal tumors. Conclusions: Very small malignant tumors manifest generally accepted ultrasound signs of malignancy. Small unilocular cysts are usually benign, while small non-unilocular masses, particularly ones with solid components, incur a risk of malignancy and pose a clinical dilemma.
25.	Eriksson, L. S.E., et al. (författare) Ultrasound-based risk model for preoperative prediction of lymph-node metastases in women with endometrial cancer : model-development study 2020 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:3, s. 443-452 Tidskriftsartikel (refereegranskat)abstract Objective: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. Methods: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). Results: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68–0.78), the calibration slope was 1.06 (95% CI, 0.79–1.34) and the calibration intercept was 0.06 (95% CI, –0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. Conclusions: Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound.
26.	Guerriero, S., et al. (författare) Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements : A consensus opinion from the International Deep Endometriosis Analysis (IDEA) group 2016 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 0960-7692. ; 48:3, s. 318-332 Tidskriftsartikel (refereegranskat)abstract The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research.
27.	Harmsen, M. J., et al. (författare) Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis : results of modified Delphi procedure 2022 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 60:1, s. 118-131 Tidskriftsartikel (refereegranskat)abstract Objectives: To evaluate whether the Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis need to be better defined and, if deemed necessary, to reach consensus on the updated definitions. Methods: A modified Delphi procedure was performed among European gynecologists with expertise in ultrasound diagnosis of adenomyosis. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings also included three-dimensional (3D) still images) of transvaginal ultrasound (TVS) examinations of the uterus were presented in the first Delphi round (online questionnaire). Experts were asked to confirm or refute the presence of each of the nine MUSA features of adenomyosis (described in the original MUSA consensus statement) in each of the 15 videoclips and to provide comments. In the second Delphi round (online questionnaire), the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVS examinations and to provide feedback on the proposed revisions. A third Delphi round (virtual group meeting) was conducted to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts. Results: Of 18 invited experts, 16 agreed to participate in the Delphi procedure. Eleven experts completed and four experts partly finished the first round. The experts identified a need for more detailed definitions of some MUSA features. They recommended use of 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts participated in the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most of the still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the online meeting, in which they discussed and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct features of adenomyosis, i.e. features indicating presence of ectopic endometrial tissue in the myometrium, and indirect features, i.e. features reflecting changes in the myometrium secondary to presence of endometrial tissue in the myometrium. Myometrial cysts, hyperechogenic islands and echogenic subendometrial lines and buds were classified unanimously as direct features of adenomyosis. Globular uterus, asymmetrical myometrial thickening, fan-shaped shadowing, translesional vascularity, irregular junctional zone and interrupted junctional zone were classified as indirect features of adenomyosis. Conclusion: Consensus between gynecologists with expertise in ultrasound diagnosis of adenomyosis was achieved regarding revised definitions of the MUSA features of adenomyosis and on the classification of MUSA features as direct or indirect signs of adenomyosis.
28.	Heremans, R., et al. (författare) Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA-1 multinomial regression model : validation study 2023 Ingår i: Ultrasound in Obstetrics and Gynecology. - 0960-7692. Tidskriftsartikel (refereegranskat)abstract 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.
29.	Heremans, R., et al. (författare) Imaging in gynecological disease (24) : clinical and ultrasound characteristics of ovarian mature cystic teratomas 2022 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 60:4, s. 549-558 Tidskriftsartikel (refereegranskat)abstract Objective: To describe the clinical and ultrasound features of ovarian mature cystic teratomas (MCTs). Methods: This was a retrospective study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histologically confirmed diagnosis of MCT who had undergone transvaginal ultrasound examination between 1999 and 2016 (IOTA phases 1, 2, 3 and 5) in one of five centers. Ultrasound was performed by an experienced examiner who used the standardized IOTA examination technique and terminology. In addition to extracting data from the IOTA database, available two-dimensional grayscale and color or power Doppler images were reviewed retrospectively to identify typical ultrasound features of MCT described previously and detect possible new features using pattern recognition. All images were reviewed by two independent examiners and further discussed with two ultrasound experts to reach consensus. Results: Included in the study were 454 patients with histologically confirmed MCT. Median age was 33 (range, 8–90) years and 66 (14.5%) patients were postmenopausal. Most MCTs were described by the original ultrasound examiner as unilocular (262/454 (57.7%)) or multilocular (70/454 (15.4%)) cysts with mixed echogenicity of cystic fluid (368/454 (81.1%)), acoustic shadowing (328/454 (72.2%)) and no or little vascularization on color Doppler (color score 1, 240/454 (52.9%); color score 2, 123/454 (27.1%)). The median largest lesion diameter was 66 (range, 15–310) mm. A correct preoperative diagnosis of MCT was suggested by the original ultrasound examiner in 372/454 (81.9%) cases. On retrospective review of ultrasound images of 334 MCTs that had quality sufficient for assessment, ‘dots and/or lines’ and/or ‘echogenic white ball’ (typical features according to the literature) were present in 271/334 (81.1%) masses. We identified four new ultrasound features characteristic of MCT: ‘cotton wool tufts’, ‘mushroom cap sign’, ‘completely hyperechogenic lesion’ and ‘starry sky sign’. At least one classical or novel ultrasound feature was present in 315/334 (94.3%) MCTs. Twenty-nine (8.7%) MCTs manifested vascularized solid tissue, of which seven exhibited no typical features. Conclusion: We provide a comprehensive overview of conventional and newly described ultrasound features of MCTs. Only a small proportion of MCTs did not manifest any of the typical features.
30.	Heremans, R., et al. (författare) Ultrasound features of endometrial pathology in women without abnormal uterine bleeding : results from the International Endometrial Tumor Analysis study (IETA3) 2022 Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 60:2, s. 243-255 Tidskriftsartikel (refereegranskat)abstract 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.
31.	Juneja, M, et al. (författare) PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease 2018 Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 89:8, s. 870-878 Tidskriftsartikel (refereegranskat)abstract Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes.MethodsA proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins. The candidate proteins were validated through real-time quantitative PCR and western blotting on lymphoblast samples of patients and controls, motor neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) and sciatic nerves of CMT2 mouse models.ResultsProteomic profiling of patient lymphoblasts resulted in the identification of profilin 2 (PFN2) and guanidinoacetate methyltransferase (GAMT) as commonly downregulated proteins in different genotypes compared with healthy controls. This decrease was also observed at the transcriptional level on screening 43 CMT2 patients and 22 controls, respectively. A progressive decrease in PFN2 expression with age was observed in patients, while in healthy controls its expression increased with age. Reduced PFN2 expression was also observed in motor neurons differentiated from CMT2 patient-derived iPSCs and sciatic nerves of CMT2 mice when compared with controls. However, no change in GAMT levels was observed in motor neurons and CMT2 mouse-derived sciatic nerves.ConclusionsWe unveil PFN2 and GAMT as molecular determinants of CMT2 with possible indications of the role of PFN2 in the pathogenesis and disease progression. This is the first study describing biomarkers that can boost the development of therapeutic strategies targeting a wider spectrum of CMT2 patients.
32.	Kaijser, J., et al. (författare) Improving strategies for diagnosing ovarian cancer: a summary of the International Ovarian Tumor Analysis (IOTA) studies 2013 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 41:1, s. 9-20 Forskningsöversikt (refereegranskat)abstract In order to ensure that ovarian cancer patients access appropriate treatment to improve the outcome of this disease, accurate characterization before any surgery on ovarian pathology is essential. The International Ovarian Tumor Analysis (IOTA) collaboration has standardized the approach to the ultrasound description of adnexal pathology. A prospectively collected large database enabled previously developed prediction models like the risk of malignancy index (RMI) to be tested and novel prediction models to be developed and externally validated in order to determine the optimal approach to characterize adnexal pathology preoperatively. The main IOTA prediction models (logistic regression model 1 (LR1) and logistic regression model 2 (LR2)) have both shown excellent diagnostic performance (area under the curve (AUC) values of 0.96 and 0.95, respectively) and outperform previous diagnostic algorithms. Their test performance almost matches subjective assessment by experienced examiners, which is accepted to be the best way to classify adnexal masses before surgery. A two-step strategy using the IOTA simple rules supplemented with subjective assessment of ultrasound findings when the rules do not apply, also reached excellent diagnostic performance (sensitivity 90%, specificity 93%) and misclassified fewer malignancies than did the RMI. An evidence-based approach to the preoperative characterization of ovarian and other adnexal masses should include the use of LR1, LR2 or IOTA simple rules and subjective assessment by an experienced examiner. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
33.	Landolfo, C., et al. (författare) Differences in ultrasound features of papillations in unilocular-solid adnexal cysts : a retrospective international multicenter study 2018 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692. ; 52:2, s. 269-278 Tidskriftsartikel (refereegranskat)abstract Objectives: To identify ultrasound features of papillations or of the cyst wall that can discriminate between benign and malignant unilocular-solid cysts with papillations but no other solid components. Methods: From the International Ovarian Tumor Analysis (IOTA) database derived from seven ultrasound centers, we identified patients with an adnexal lesion described at ultrasonography as unilocular-solid with papillations but no other solid components. All patients had undergone transvaginal ultrasound between 1999 and 2007 or 2009 and 2012, by an experienced examiner following the IOTA research protocol. Information on four ultrasound features of papillations had been collected prospectively. Information on a further seven ultrasound features was collected retrospectively from electronic or paper ultrasound images of good quality. The histological diagnosis of the surgically removed adnexal lesion was considered the gold standard. Results: Of 204 masses included, 131 (64.2%) were benign, 42 (20.6%) were borderline tumors, 30 (14.7%) were primary invasive tumors and one (0.5%) was a metastasis. Multivariate logistic regression analysis showed the following ultrasound features to be associated independently with malignancy: height of the largest papillation, presence of blood flow in papillations, papillation confluence or dissemination, and shadows behind papillations. Shadows decreased the odds of malignancy, while the other features increased them. Conclusion: We have identified ultrasound features that can help to discriminate between benign and malignant unilocular-solid cysts with papillations but no other solid components. Our results need to be confirmed in prospective studies.
34.	Lutgendorff, Femke, et al. (författare) Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis. 2009 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2, s. e4512- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and (51)Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r>0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4+/-33.5 vs. placebo 223.7+/-93.7 a.u.; P<0.001), (51)Cr-EDTA flux (16.7+/-10.1 vs. 32.1+/-10.0 cm/s10(-6); P<0.005), apoptosis, lipid peroxidation (0.42+/-0.13 vs. 1.62+/-0.53 pmol MDA/mg protein; P<0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33+/-1.47 vs. 8.82+/-1.30 nmol/mg protein, P<0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33+/-1.47 vs. 10.70+/-1.74 nmol/mg protein, P<0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88+/-1.21 vs. placebo 1.94+/-0.55 nmol/min/mg protein; P<0.05) coinciding with an increase in mRNA expression of glutamate-cysteine-ligase catalytic (GCLc) and modifier (GCLm) subunits. CONCLUSIONS: Probiotic pre-treatment diminished AP-induced intestinal barrier dysfunction and prevented oxidative stress via mechanisms mainly involving mucosal glutathione biosynthesis.
35.	Moro, F., et al. (författare) Imaging in gynecological disease (13) : clinical and ultrasound characteristics of endometrioid ovarian cancer 2018 Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 52:4, s. 535-543 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian pure endometrioid carcinomas.METHODS: This was a retrospective multicenter study of patients with a histological diagnosis of pure endometrioid carcinoma. We identified 161 patients from the International Ovarian Tumor Analysis (IOTA) database who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016, and another 78 patients from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. In addition, one author reviewed all available ultrasound images and described them using pattern recognition.RESULTS: Median age of the 239 patients was 55 years (range, 19-88 years). On ultrasound examination, two (0.8%) endometrioid carcinomas were described as unilocular cysts, three (1.3%) as multilocular cysts, 37 (15.5%) as unilocular-solid cysts, 115 (48.1%) as multilocular-solid cysts and 82 (34.3%) as solid masses. Median largest tumor diameter was 102.5 mm (range, 20-300 mm) and median largest diameter of the largest solid component was 63 mm (range, 9-300 mm). Papillary projections were present in 70 (29.3%) masses. Most cancers (188 (78.7%)) were unilateral. In 49 (20.5%) cases, the cancer was judged by the pathologist to develop from endometriosis. These cancers, compared with those without evidence of tumor developing from endometriosis, more often manifested papillary projections on ultrasound (46.9% (23/49) vs 24.7% (47/190)), were less often bilateral (8.2% (4/49) vs 24.7% (47/190)) and less often associated with ascites (6.1% (3/49) vs 28.4% (54/190)) and fluid in the pouch of Douglas (24.5% (12/49) vs 48.9% (93/190)). Retrospective analysis of available ultrasound images using pattern recognition revealed that many tumors without evidence of tumor developing from endometriosis (36.3% (41/113)) had a large central solid component entrapped within locules, giving the tumor a cockade-like appearance.CONCLUSIONS: Endometrioid cancers are usually large, unilateral, multilocular-solid or solid tumors. The ultrasound characteristics of endometrioid carcinomas developing from endometriosis differ from those without evidence of tumor developing from endometriosis, the former being more often unilateral cysts with papillary projections and no ascites.
36.	Pantazis, CB, et al. (författare) A reference human induced pluripotent stem cell line for large-scale collaborative studies 2022 Ingår i: Cell stem cell. - : Elsevier BV. - 1875-9777 .- 1934-5909. ; 29:12, s. 1685- Tidskriftsartikel (refereegranskat)
37.	Sayasneh, A, et al. (författare) Multicentre external validation of IOTA prediction models and RMI by operators with varied training 2013 Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:12, s. 2448-2454 Tidskriftsartikel (refereegranskat)
38.	Sladkevicius, Povilas, et al. (författare) OC154: Accuracy of transvaginal ultrasound examination for assigning a specific diagnosis to adnexal masses 2007 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 30:4, s. 414-414 Konferensbidrag (refereegranskat)
39.	Strazisar, M, et al. (författare) MIR137 variants identified in psychiatric patients affect synaptogenesis and neuronal transmission gene sets 2015 Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 20:4, s. 472-481 Tidskriftsartikel (refereegranskat)abstract Sequence analysis of 13 microRNA (miRNA) genes expressed in the human brain and located in genomic regions associated with schizophrenia and/or bipolar disorder, in a northern Swedish patient/control population, resulted in the discovery of two functional variants in the MIR137 gene. On the basis of their location and the allele frequency differences between patients and controls, we explored the hypothesis that the discovered variants impact the expression of the mature miRNA and consequently influence global mRNA expression affecting normal brain functioning. Using neuronal-like SH-SY5Y cells, we demonstrated significantly reduced mature miR-137 levels in the cells expressing the variant miRNA gene. Subsequent transcriptome analysis showed that the reduction in miR-137 expression led to the deregulation of gene sets involved in synaptogenesis and neuronal transmission, all implicated in psychiatric disorders. Our functional findings add to the growing data, which implicate that miR-137 has an important role in the etiology of psychiatric disorders and emphasizes its involvement in nervous system development and proper synaptic function.
40.	Testa, A, et al. (författare) Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study. 2014 Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 111:4, s. 680-688 Tidskriftsartikel (refereegranskat)abstract Background:To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3.Methods:This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery.Results:The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5.Conclusions:This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.British Journal of Cancer advance online publication 17 June 2014; doi:10.1038/bjc.2014.333 www.bjcancer.com.
41.	Van Belle, Vanya M. C. A., et al. (författare) A Mathematical Model for Interpretable Clinical Decision Support with Applications in Gynecology 2012 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3 Tidskriftsartikel (refereegranskat)abstract Background: Over time, methods for the development of clinical decision support (CDS) systems have evolved from interpretable and easy-to-use scoring systems to very complex and non-interpretable mathematical models. In order to accomplish effective decision support, CDS systems should provide information on how the model arrives at a certain decision. To address the issue of incompatibility between performance, interpretability and applicability of CDS systems, this paper proposes an innovative model structure, automatically leading to interpretable and easily applicable models. The resulting models can be used to guide clinicians when deciding upon the appropriate treatment, estimating patient-specific risks and to improve communication with patients. Methods and Findings: We propose the interval coded scoring (ICS) system, which imposes that the effect of each variable on the estimated risk is constant within consecutive intervals. The number and position of the intervals are automatically obtained by solving an optimization problem, which additionally performs variable selection. The resulting model can be visualised by means of appealing scoring tables and color bars. ICS models can be used within software packages, in smartphone applications, or on paper, which is particularly useful for bedside medicine and home-monitoring. The ICS approach is illustrated on two gynecological problems: diagnosis of malignancy of ovarian tumors using a dataset containing 3,511 patients, and prediction of first trimester viability of pregnancies using a dataset of 1,435 women. Comparison of the performance of the ICS approach with a range of prediction models proposed in the literature illustrates the ability of ICS to combine optimal performance with the interpretability of simple scoring systems. Conclusions: The ICS approach can improve patient-clinician communication and will provide additional insights in the importance and influence of available variables. Future challenges include extensions of the proposed methodology towards automated detection of interaction effects, multi-class decision support systems, prognosis and high-dimensional data.
42.	van den Bosch, T., et al. (författare) Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group 2015 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 46:3, s. 284-298 Tidskriftsartikel (refereegranskat)abstract The MUSA (Morphological Uterus Sonographic Assessment) statement is a consensus statement on terms, definitions and measurements that may be used to describe and report the sonographic features of the myometrium using gray-scale sonography, color/power Doppler and three-dimensional ultrasound imaging. The terms and definitions described may form the basis for prospective studies to predict the risk of different myometrial pathologies, based on their ultrasound appearance, and thus should be relevant for the clinician in daily practice and for clinical research. The sonographic features and use of terminology for describing the two most common myometrial lesions (fibroids and adenomyosis) and uterine smooth muscle tumors are presented. Copyright (C) 2015 ISUOG. Published by John Wiley & Sons Ltd.
43.	Van Holsbeke, C., et al. (författare) Acoustic streaming cannot discriminate reliably between endometriomas and other types of adnexal lesion: a multicenter study of 633 adnexal masses 2010 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 35:3, s. 349-353 Tidskriftsartikel (refereegranskat)abstract Objective To determine the ability of acoustic streaming to discriminate between endometriomas and other adnexal masses. Methods We used data from 1938 patients with an adnexal mass included in Phase 2 of the International Ovarian Tumor Analysis (IOTA) study. All patients had been examined by transvaginal gray-scale and Doppler ultrasound following a standardized research protocol. Assessment of acoustic streaming was voluntary and was carried out only in lesions containing echogenic cyst fluid. Acoustic streaming was defined as movement of particles inside the cyst fluid during gray-scale and/or color Doppler examination provided that the probe had been held still for two seconds to ensure that the movement of the particles was not caused by movement of the probe or the patient. Only centers where acoustic streaming had been evaluated in > 90% of cases were included. Sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), and positive and negative predictive values (PPV and NPV) of acoustic streaming with regard to endometrioma were calculated. Results 460 (24%) masses were excluded because they were examined in centers where <= 90% of the masses with echogenic cyst fluid had been evaluated for the presence of acoustic streaming. Acoustic streaming was evaluated in 633 of 646 lesions containing echogenic cyst fluid. It was present in 19 (9%) of 209 endometriomas and in 55 (13%) of 424 other lesions. This corresponds to a sensitivity of absent acoustic streaming with regard to endometrioma of 91% (190/209), a specificity of 13% (55/424), LR+ of 1.04, LR- of 0.69, PPV of 34% (190/559) and NPV of 74% (55/74). Conclusions Acoustic streaming cannot discriminate reliably between endometrioinas and other adnexal lesions, and the presence of acoustic streaming does not exclude an endometrioma. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
44.	Van Holsbeke, C., et al. (författare) OC202: Real-time ultrasound versus static image evaluation of adnexal masses 2007 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 30:4, s. 429-429 Konferensbidrag (refereegranskat)
45.	Van Holsbeke, C., et al. (författare) Real-time ultrasound vs. evaluation of static images in the preoperative assessment of adnexal masses 2008 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 32:6, s. 828-831 Tidskriftsartikel (refereegranskat)abstract Objective To determine if the prediction of the Malignancy of all adnexal mass using pattern recognition, i.e. subjective evaluation of gray-scale and Doppler ultrasound findings, is as accurate when based on static images as it is when based on a real-time ultrasound examination. Methods The static images of 166 non-consecutive patients with 'difficult' adnexal masses, who all underwent surgery and for whom a histopathological diagnosis was available, were evaluated by three experts in gynecological ultrasound (image experts'). All ultrasound examinations bad been performed and the static images saved by a fourth expert sonologist ('real-time' sonologist). All four sonologists classified the adnexal masses as benign or malignant based on their subjective impression and stated with what degree of confidence their diagnosis was made. The diagnostic performance of the real-time sonologist was compared with that of each of The three image experts and with that of the 'consensus opinion' of the image experts (i.e. the diagnosis suggested by at least two of the latter). Results The real-time sonologist correctly predicted the diagnosis with an accuracy of 89% (148/166) vs. 85% (141/166) for the consensus opinion of static images (P = 0.0707). Equivalent values for sensitivity and specificity were 80% (56/170) vs. 83%, (58/70) (P = 0.4142) and 96%) (92/96) us. 86%, (83/96) (P = 0.0027), respectively. Conclusions The preoperative diagnosis of all adnexal mass made on the basis of a real-time ultrasound examination is more precise than a diagnosis made on the basis of saved static ultrasound images. Evaluation of static images is associated with lower diagnostic specificity. Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
46.	Van Holsbeke, C., et al. (författare) Ultrasound methods to distinguish between malignant and benign adnexal masses in the hands of examiners with different levels of experience 2009 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 34:4, s. 454-461 Tidskriftsartikel (refereegranskat)abstract Objectives To determine the effect of an ultrasound training course on the performance of pattern recognition when used by less experienced examiners and to compare the performance of pattern recognition, a logistic regression model and a scoring system to estimate the risk of malignancy between examiners with different levels of experience. Methods Using ultrasound images of selected adnexal masses, two trainees classified the masses as benign or malignant by using pattern recognition both before and after they bad attended a theoretical gynecological ultrasound course. They also classified the masses by using a logistic regression model and a scoring system, but only after they bad attended the course. The performance of these three methods when they were used by the trainees was then compared with that when they were used by experts. Results One hundred and sixty-five adnexal masses were included, of which 42% were malignant (21% invasive tumors and 21% borderline tumors). The area under the receiver- operating characteristics curve of pattern recognition when used by the trainees was similar before and after they had attended the course. Training decreased sensitivity (84% vs. 70% for Trainee 1, P = 0.004; 70% vs. 61% for Trainee2, P = 0.08) and increased specificity (77% vs. 92% for Trainee 1, P = 0.001; 89% vs. 95% for Trainee 2, P = 0.058). The performance of pattern recognition was poorer in the hands of the trainees than in the bands of the experts. The sensitivities of the logistic regression model were 70% and 54% for the trainees vs. 83% for an expert (P = 0.020 and < 0.001, respectively) and the specificities were 84% and 94% vs. 89% (P = 0.25 and 0.59, respectively). The sensitivities of the scoring system were 59% and 54% for the trainees vs. 75% for the expert (P = 0.002 and < 0.001, respectively), and the specificities were 90% and 93% vs. 85% (P = 0.103 and 0.008, respectively). Conclusion Theoretical ultrasound teaching did not seem to improve the performance of pattern recognition in the bands of trainees. A logistic regression model and a scoring system to classify adnexal masses as benign or malignant perform less well when they were used by inexperienced examiners than when used by an expert. Before using a model or a scoring system, experience and/or proper training are likely to be of paramount importance if diagnostic performance is to be optimized. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
47.	Verbakel, J. Y., et al. (författare) Validation of ultrasound strategies to assess tumor extension and to predict high-risk endometrial cancer in women from the prospective IETA (International Endometrial Tumor Analysis)-4 cohort 2020 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 55:1, s. 115-124 Tidskriftsartikel (refereegranskat)abstract Objectives: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). Methods: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The ‘subjective prediction model’ included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the ‘objective prediction model’ included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. Results: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver–operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. Conclusions: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%.
48.	Yazbek, J., et al. (författare) OC203: How accurate is ultrasound pattern recognition at predicting the histological diagnosis of an ovarian mass? 2007 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 30:4, s. 429-429 Konferensbidrag (refereegranskat)
49.	Ameye, L., et al. (författare) A scoring system to differentiate malignant from benign masses in specific ultrasound-based subgroups of adnexal tumors 2009 Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 33:1, s. 92-101 Tidskriftsartikel (refereegranskat)abstract Objective To investigate if the prediction of malignant adnexal masses can be improved by considering different ultrasound-based subgroups of tumors and constructing a scoring system for each subgroup instead of using a risk estimation model applicable to all tumors. Methods We used a multicenter database of 1573 patients with at least one persistent adnexal mass. The masses were categorized into four subgroups based on their ultrasound appearance: ( 1) unilocular cyst; ( 2) multilocular cyst; ( 3) presence of a solid component but no papillation; and ( 4) presence of papillation. For each of the four subgroups a scoring system to predict malignancy was developed in a development set consisting of 754 patients in total ( respective numbers of patients: ( 1) 228; ( 2) 143; ( 3) 183; and ( 4) 200). The subgroup scoring system was then tested in 312 patients and prospectively validated in 507 patients. The sensitivity and specificity, with regard to the prediction of malignancy, of the scoring system were compared with that of the subjective evaluation of ultrasound images by an experienced examiner ( pattern recognition) and with that of a published logistic regression (LR) model for the calculation of risk of malignancy in adnexal masses. The gold standard was the pathological classification of the mass as benign or malignant ( borderline, primary invasive, or metastatic). Results In the prospective validation set, the sensitivity of pattern recognition, the LR model and the subgroup scoring system was 90% (129/143), 95% (136/143) and 88% (126/143), respectively, and the specificity was 93% (338/364), 74% (270/364) and 90% (329/364), respectively. Conclusions In the hands of experienced ultrasound examiners, the subgroup scoring system for diagnosing malignancy has a performance that is similar to that of pattern recognition, the latter method being the best diagnostic method currently available. The scoring system is less sensitive but more specific than the LR model. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
50.	Anfelter, P, et al. (författare) Imaging in gynecological disease (17): ultrasound features of malignant ovarian yolk sac tumors (endodermal sinus tumors) 2020 Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 56:2, s. 276-284 Tidskriftsartikel (refereegranskat)

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