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- Landolfo, C., et al.
(författare)
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Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors : retrospective validation on IOTA 5 multicenter cohort
- 2023
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 61:2, s. 231-242
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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.
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| 2. |
- Sladkevicius, P., et al.
(författare)
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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
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 57:2, s. 324-334
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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.
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| 8. |
- Shams, M, et al.
(författare)
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MRI Markers of Small Vessel Disease and the APOE Allele in Cognitive Impairment
- 2022
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Ingår i: Frontiers in aging neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14, s. 897674-
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Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiology of dementia. We aimed to investigate the association between the APOE ε genotype and magnetic resonance imaging (MRI) markers of SVD in a memory clinic population.Material and MethodsThis is a cross-sectional study with a total of 520 patients undergoing dementia investigation, including an MRI brain scan and APOE genotyping in all patients enrolled, and cerebrospinal fluid (CSF) analysis for routine AD biomarkers in 399 patients. MR images were assessed for markers of SVD: cerebral microbleeds (CMBs), cortical superficial siderosis, intracerebral hemorrhage, white matter hyperintensities, lacunar infarcts, and enlarged perivascular spaces.ResultsApolipoprotein E carriers with AD had a higher number of CMBs when looking at all brain regions and lobar brain regions (p < 0.001). A lower number of CMBs were seen in APOE ε2 (p < 0.05), ε3 and ε3/3 carriers (p < 0.001) when looking at all brain regions. A higher number of CMBs in deep and infratentorial regions were seen in APOE ε2 and ε3 (p < 0.05). In APOE ε4/4 carriers, CMBs, cortical superficial siderosis, white matter hyperintensities, and enlarged perivascular spaces were associated with lower levels of CSF amyloid β (Aβ) 42 in the whole cohort, and in individuals with AD and mild cognitive impairment (p < 0.05).ConclusionApolipoprotein E ε4 is associated with MRI markers of SVD related to amyloid pathology, specifically CMBs and Aβ42 plaque formation in the brain, as reflected by decreased CSF Aβ42 levels, whereas APOE ε3 and ε2 are associated with the markers of hypertensive arteriopathy, as reflected by the association with CMBs in deep and infratentorial brain regions.
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| 9. |
- Timmerman, Stefan, et al.
(författare)
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External Validation of the Ovarian-Adnexal Reporting and Data System (O-RADS) Lexicon and the International Ovarian Tumor Analysis 2-Step Strategy to Stratify Ovarian Tumors Into O-RADS Risk Groups
- 2023
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 9:2, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Correct diagnosis of ovarian cancer results in better prognosis. Adnexal lesions can be stratified into the Ovarian-Adnexal Reporting and Data System (O-RADS) risk of malignancy categories with either the O-RADS lexicon, proposed by the American College of Radiology, or the International Ovarian Tumor Analysis (IOTA) 2-step strategy.OBJECTIVE: To investigate the diagnostic performance of the O-RADS lexicon and the IOTA 2-step strategy.DESIGN, SETTING, AND PARTICIPANTS: Retrospective external diagnostic validation study based on interim data of IOTA5, a prospective international multicenter cohort study, in 36 oncology referral centers or other types of centers. A total of 8519 consecutive adult patients presenting with an adnexal mass between January 1, 2012, and March 1, 2015, and treated either with surgery or conservatively were included in this diagnostic study. Twenty-five patients were excluded for withdrawal of consent, 2777 were excluded from 19 centers that did not meet predefined data quality criteria, and 812 were excluded because they were already in follow-up at recruitment. The analysis included 4905 patients with a newly detected adnexal mass in 17 centers that met predefined data quality criteria. Data were analyzed from January 31 to March 1, 2022.EXPOSURES: Stratification into O-RADS categories (malignancy risk <1%, 1% to <10%, 10% to <50%, and ≥50%). For the IOTA 2-step strategy, the stratification is based on the individual risk of malignancy calculated with the IOTA 2-step strategy.MAIN OUTCOMES AND MEASURES: Observed prevalence of malignancy in each O-RADS risk category, as well as sensitivity and specificity. The reference standard was the status of the tumor at inclusion, determined by histology or clinical and ultrasonographic follow-up for 1 year. Multiple imputation was used for uncertain outcomes owing to inconclusive follow-up information.RESULTS: Median age of the 4905 patients was 48 years (IQR, 36-62 years). Data on race and ethnicity were not collected. A total of 3441 tumors (70%) were benign, 978 (20%) were malignant, and 486 (10%) had uncertain classification. Using the O-RADS lexicon resulted in 1.1% (24 of 2196) observed prevalence of malignancy in O-RADS 2, 4% (34 of 857) in O-RADS 3, 27% (246 of 904) in O-RADS 4, and 78% (732 of 939) in O-RADS 5; the corresponding results for the IOTA 2-step strategy were 0.9% (18 of 1984), 4% (58 of 1304), 30% (206 of 690), and 82% (756 of 927). At the 10% risk threshold (O-RADS 4-5), the O-RADS lexicon had 92% sensitivity (95% CI, 87%-96%) and 80% specificity (95% CI, 74%-85%), and the IOTA 2-step strategy had 91% sensitivity (95% CI, 84%-95%) and 85% specificity (95% CI, 80%-88%).CONCLUSIONS AND RELEVANCE: The findings of this external diagnostic validation study suggest that both the O-RADS lexicon and the IOTA 2-step strategy can be used to stratify patients into risk groups. However, the observed malignancy rate in O-RADS 2 was not clearly below 1%.
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| 10. |
- van Amerongen, Suzan, et al.
(författare)
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Severe CTE and TDP-43 pathology in a former professional soccer player with dementia : a clinicopathological case report and review of the literature
- 2023
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Ingår i: Acta Neuropathologica Communications. - 2051-5960. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- In the last decades, numerous post-mortem case series have documented chronic traumatic encephalopathy (CTE) in former contact-sport athletes, though reports of CTE pathology in former soccer players are scarce. This study presents a clinicopathological case of a former professional soccer player with young-onset dementia. The patient experienced early onset progressive cognitive decline and developed dementia in his mid-50 s, after playing soccer for 12 years at a professional level. While the clinical picture mimicked Alzheimer’s disease, amyloid PET imaging did not provide evidence of elevated beta-amyloid plaque density. After he died in his mid-60 s, brain autopsy showed severe phosphorylated tau (p-tau) abnormalities fulfilling the neuropathological criteria for high-stage CTE, as well as astrocytic and oligodendroglial tau pathology in terms of tufted astrocytes, thorn-shaped astrocytes, and coiled bodies. Additionally, there were TAR DNA-binding protein 43 (TDP-43) positive cytoplasmic inclusions in the frontal lobe and hippocampus, and Amyloid Precursor Protein (APP) positivity in the axons of the white matter. A systematic review of the literature revealed only 13 other soccer players with postmortem diagnosis of CTE. Our report illustrates the complex clinicopathological correlation of CTE and the need for disease-specific biomarkers.
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