Accurate and consistent variant classification is imperative for incorporation of rapidly developing sequencing technologies into genomic medicine for improved patient care. An essential requirement for achieving standardized and reliable variant interpretation is data sharing, facilitated by a centralized open-source database. Familial hypercholesterolemia (FH) is an exemplar of the utility of such a resource: it has a high incidence, a favorable prognosis with early intervention and treatment, and cascade screening can be offered to families if a causative variant is identified. ClinVar, an NCBI-funded resource, has become the primary repository for clinically relevant variants in Mendelian disease, including FH. Here, we present the concerted efforts made by the Clinical Genome Resource, through the FH Variant Curation Expert Panel and global FH community, to increase submission of FH-associated variants into ClinVar. Variant-level data was categorized by submitter, variant characteristics, classification method, and available supporting data. To further reform interpretation of FH-associated variants, areas for improvement in variant submissions were identified; these include a need for more detailed submissions and submission of supporting variant-level data, both retrospectively and prospectively. Collaborating to provide thorough, reliable evidence-based variant interpretation will ultimately improve the care of FH patients.
- MeSH
- Databases, Genetic MeSH
- DNA genetics MeSH
- Genetic Variation genetics MeSH
- Genome, Human genetics MeSH
- Genomics MeSH
- Hyperlipoproteinemia Type II genetics MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.
- MeSH
- Databases, Factual * standards MeSH
- Adult MeSH
- Phenotype MeSH
- Internet MeSH
- Cataplexy drug therapy epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Narcolepsy * drug therapy epidemiology MeSH
- Product Surveillance, Postmarketing MeSH
- Prospective Studies MeSH
- Registries * standards MeSH
- Quality Control MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Information Dissemination MeSH
- Rare Diseases drug therapy epidemiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe epidemiology MeSH
OBJECTIVE: To describe the sonographic features of endometrial cancer in relation to tumor stage, grade and histological type, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective multicenter study of 1714 women with biopsy-confirmed endometrial cancer undergoing standardized transvaginal grayscale and Doppler ultrasound examination according to the IETA study protocol, by experienced ultrasound examiners using high-end ultrasound equipment. Clinical and sonographic data were entered into a web-based database. We assessed how strongly sonographic characteristics, according to IETA, were associated with outcome at hysterectomy, i.e. tumor stage, grade and histological type, using univariable logistic regression and the c-statistic. RESULTS: In total, 1538 women were included in the final analysis. Median age was 65 (range, 27-98) years, median body mass index was 28.4 (range 16-67) kg/m2 , 1377 (89.5%) women were postmenopausal and 1296 (84.3%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage of tumor. High-risk tumors, compared with low-risk tumors, were less likely to have regular endometrial-myometrial junction (difference of -23%; 95% CI, -27 to -18%), were larger (mean endometrial thickness; difference of +9%; 95% CI, +8 to +11%), and were more likely to have non-uniform echogenicity (difference of +7%; 95% CI, +1 to +13%), a multiple, multifocal vessel pattern (difference of +21%; 95% CI, +16 to +26%) and a moderate or high color score (difference of +22%; 95% CI, +18 to +27%). CONCLUSION: Grayscale and color Doppler sonographic features are associated with grade and stage of tumor, and differ between high- and low-risk endometrial cancer. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
- MeSH
- Adult MeSH
- Consensus Development Conferences as Topic MeSH
- Middle Aged MeSH
- Humans MeSH
- Endometrial Neoplasms classification diagnostic imaging pathology MeSH
- Prospective Studies MeSH
- Cross-Sectional Studies MeSH
- Reproducibility of Results MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Grading * MeSH
- Terminology as Topic MeSH
- Ultrasonography, Doppler, Color standards MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Multicenter Study MeSH
PURPOSE: Identification of demographic, physical/physiological, lifestyle and genetic factors contributing to the onset of dementia, specifically Alzheimer disease (AD), and implementation of novel methods for early diagnosis are important to alleviate prevalence of dementia globally. The Czech Brain Aging Study (CBAS) is the first large, prospective study to address these issues in Central/Eastern Europe by enrolling non-demented adults aged 55+ years, collecting a variety of personal and biological measures and tracking cognitive function over time. PARTICIPANTS: The CBAS recruitment was initiated in 2011 from memory clinics at Brno and Prague University Hospitals, and by the end of 2018, the study included 1228 participants. Annual follow-ups include collection of socioeconomic, lifestyle and personal history information, neurology, neuropsychology, laboratory, vital sign and brain MRI data. In a subset, biomarker assessment (cerebrospinal fluid (CSF) and amyloid positron emission tomography) and spatial navigation were performed. Participants were 69.7±8.1 years old and had 14.6±3.3 years of education at baseline, and 59% were women. By the end of 2018, 31% finished three and more years of follow-up; 9% converted to dementia. Apolipoprotein E status is available from 95% of the participants. The biological sample bank linked to CBAS database contained CSF, serum and DNA. FINDINGS TO DATE: Overall, the findings, mainly from cross-sectional analyses, indicate that spatial navigation is a promising marker of early AD and that it can be distinguished from other cognitive functions. Specificity of several standard memory tests for early AD pathology was assessed with implications for clinical practice. The relationship of various lifestyle factors to cognition and brain atrophy was reported. FUTURE PLANS: Recruitment is ongoing with secured funding. Longitudinal data analyses are currently being conducted. Proposals for collaboration on specific data from the database or biospecimen, as well as collaborations with similar cohort studies to increase sample size, are welcome. Study details are available online (www.cbas.cz).
- MeSH
- Alzheimer Disease epidemiology MeSH
- Dementia epidemiology MeSH
- Risk Assessment MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Protective Factors MeSH
- Prospective Studies MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.
- MeSH
- Catheter Ablation * adverse effects methods MeSH
- Tachycardia, Ventricular * MeSH
- Humans MeSH
- Prospective Studies MeSH
- Arrhythmias, Cardiac MeSH
- Heart Ventricles MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: Among people receiving current or previous opioid maintenance treatment (OMT), the leading cause of premature death is an opioid overdose. However, other causes of mortality remain high in this group. An understanding of causes of deaths across multiple settings can be useful in informing more comprehensive prevention responses. The aim of this study was to describe all non-overdose causes of death in three national cohorts (Czechia, Denmark, and Norway) among OMT patients and to explore associations of non-overdose mortality with age and gender. METHODS: This prospective comparative cohort study used national mortality registry databases for OMT patients from Czechia (2000-2019), Denmark (2000-2018), and Norway (2010-2019). Crude mortality rates and age-standardized mortality rates (ASMRs) were calculated as deaths per 1,000 person years for cause-specific mortality. RESULTS: In total, 29,486 patients were included, with 5,322 deaths recorded (18%). We found variations in causes of death among the cohorts and within gender and age groups. The leading non-overdose causes of death were accidents in Czechia and Denmark, and neoplasms in Norway. Cardiovascular deaths were highest in Czechia, particularly for women in OMT (ASMR 3.59 vs. 1.24 in Norway and 1.87 in Denmark). CONCLUSION: This study found high rates of preventable death among both genders and all age groups. Different demographic structures, variations in risk exposure, as well as variations in coding practices can explain the differences. The findings support increased efforts towards screening and preventative health initiatives among OMT patients specific to the demographic characteristics in different settings.
- MeSH
- Cohort Studies MeSH
- Humans MeSH
- Opioid-Related Disorders * MeSH
- Drug Overdose * MeSH
- Cause of Death MeSH
- Prospective Studies MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Breast-conserving treatment (BCT) consisting of a lumpectomy followed by radiation is considered the standard of care in early-stage breast cancer, and breast reconstruction using fat transfer has become the standard of care in these patients. Immediately following BCT, patients are theoretically the most prone for cancer recurrence caused by the remaining mass of glandular tissue. Therefore, we conducted a prospective study to evaluate the oncological safety of fat grafting in patients after BCT. METHODS: We analyzed patients who underwent breast reconstruction after BCT between April 2011 and February 2014. The control subjects were matched from a prospective database of women treated for breast cancer who did not undergo fat grafting, and each control was matched for the following variables: date of primary cancer surgery, date of fat grafting, histology, estrogen and progesterone receptors (ER+PR), adjuvant hormone therapy, disease-free interval from primary operation (BCT), and disease-free interval from breast reconstruction involving fat grafting. The primary endpoint of this study was tumor recurrence. RESULTS: The study group consisted of 32 patients, while the control group consisted of 45 patients. Breast tumor recurrence was observed in 2 of 32 cases (6.25%) in the reconstruction group, and distant metastases were detected in both cases. In the control group without reconstruction, we found cancer recurrence in 2 of 41 cases (4.88%), and locoregional recurrence was observed in both cases. The difference in cancer recurrence after BCT was insignificant between groups (p = 0.593). CONCLUSION: The recurrence rate in patients reconstructed with fat grafts after BCT was not significantly different from the recurrence rate of control BCT patients.
- MeSH
- Adult MeSH
- Carcinoma, Ductal, Breast pathology surgery MeSH
- Incidence MeSH
- Neoplasm Invasiveness MeSH
- Middle Aged MeSH
- Humans MeSH
- Carcinoma, Lobular pathology surgery MeSH
- Neoplasm Recurrence, Local diagnosis epidemiology MeSH
- Mammaplasty * MeSH
- Breast Neoplasms pathology surgery MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Prospective Studies MeSH
- Mastectomy, Segmental * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Case-Control Studies MeSH
- Neoplasm Grading MeSH
- Adipose Tissue transplantation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic epidemiology MeSH
BACKGROUND AND AIMS: Radiofrequency ablation (RFA) with/without endoscopic resection (ER) is the standard endoscopic treatment modality for Barrett's esophagus (BE) related neoplasia (BORN). The main aim of this study was to assess the long-term outcomes of RFA in patients with BORN. METHODS: We retrospectively analyzed the prospectively collected data from the Czech national database. Main outcomes were: complete remission of neoplasia (CR-N), complete remission of intestinal metaplasia (CR-IM), recurrence of both neoplasia and IM, and safety. RESULTS: From a total of 170 patients with BORN treated with RFA, 136 patients were analyzed. They were followed up for a median of 27.5 months. Fifty-six patients (41%) had low-grade intraepithelial neoplasia (LGIN), 46 (34%) had high-grade intraepithelial neoplasia (HGIN) and 34 (25%) had early adenocarcinoma (EAC). RFA was combined with previous ER in 65 patients (48%). CR-IM and CR-N were achieved in 77.9% (95% CI 70.0-84.6%) and 98.5% (95% CI 94.8-99.8%). Among 30 patients without CR-IM, 22 (73%) did not have macroscopic signs of BE. Recurrent neoplasia was detected in 4.5% of patients (6/134) and 15% (16/106) experienced a recurrence of IM at the level of the neo-Z-line. Diagnosis of cancer was an independent risk factor for recurrent IM after RFA (OR 7.0, 95% CI 1.6-30.9, p<0.0005). CONCLUSION: RFA is highly effective in achieving remission in patients with BORN. A significant proportion of patients did not achieve CR-IM or had a recurrence of IM despite macroscopically absent BE. Recurrence of neoplasia was infrequent but not negligible, thus, patients after successful RFA still require endoscopic surveillance.
- MeSH
- Barrett Esophagus surgery MeSH
- Databases, Factual MeSH
- Adult MeSH
- Remission Induction MeSH
- Kaplan-Meier Estimate MeSH
- Carcinoma in Situ surgery MeSH
- Catheter Ablation adverse effects methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Young Adult MeSH
- Esophageal Neoplasms surgery MeSH
- Follow-Up Studies MeSH
- Precancerous Conditions surgery MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Elektrokonvulzívna terapia (ECT) má v psychiatrii svoje stále miesto a nezastupiteľnú úlohu v liečbe závažných psychických porúch. Výskyt vážnejších nežiaducich účinkov je zriedkavý, mortalita ECT je nižšia, v porovnaní s inými lekárskymi zákrokmi realizovanými v celkovej anestéze. V súvislosti s ECT sa popisujú rôzne poruchy kognitívnych funkcií, ktoré predstavujú riziko z hľadiska negatívneho vplyvu na kvalitu života pacienta. Obavy z ich výskytu a údajnej vysokej závažnosti dlhodobo pretrvávajú v laickej verejnosti. Jedná sa o tzv. nesystematický prehľad. Literárne zdroje boli čerpané najmä z databázy PubMed (metaanalýzy, systematické prehľadové práce a klinické štúdie, publikované na danú tématiku v priebehu posledných 10 rokov). Podľa nedávnej a pomerne rozsiahlej metaanalýzy bol výskyt subjektívnych kognitívnych nežiaducich účinkov u pacientov po ECT zaznamenaný v 48 % prípadov. Podľa aktuálne dostupných údajov sú však väčšinou prechodné, krátkodobé a týkajú sa len určitých kognitívnych domén (rýchlosť spracovania informácií, exekutívne funkcie, pozornosť, pracovná a verbálna pamäť, autobiografická pamäť). Napriek tomu porucha autobiografickej pamäti môže pretrvávať v niektorých prípadoch aj viac ako 1 rok s parciálnou ireverzibilitou. Na výskyt kognitívnych nežiaducich účinkov má vplyv viacero modifikovateľných faktorov, ktoré je potrebné poznať a rešpektovať. Podstatným z nich je individualizácia množstva aplikovaného elektrického náboja počas ECT prostredníctvom jeho postupnej titrácie, za účelom nájdenia individuálneho záchvatového prahu. Jednoznačne by mali byť uprednostňované ultrakrátke impulzy (0,3ms) pred dlhšími. Ak to klinický stav umožní, je vhodné použiť unilaterálne umiestnenie elektród (nad nedominantnou hemisférou). Neodporúča sa podávanie viac ako 12 aplikácií v jednej sérii v akútnej fáze liečby (pri bitemporálnom umiestnení elektród). Individuálne faktory pacienta, ku ktorým sa radia vyšší vek, ženské pohlavie, prítomnosť organického poškodenia mozgu a nižší intelekt, predstavujú vyššie riziko rozvoja kognitívnych nežiaducich účinkov po ECT, rovnako aj súbežná liečba lítiom počas ECT. Súčasné národné a medzinárodné odporúčania ponúkajú rôzne psychometrické inštrumenty na monitorovanie kognitívnych nežiaducich účinkov ECT. V niektorých krajinách, napríklad v nemecky hovoriacich regiónoch, ale ani na Slovensku, konkrétne odporúčania neboli vypracované. V dnešnej dobe existujú batérie testov hodnotiace relevantné kognitívne domény, ktoré je možné pri ECT použiť v klinickej praxi, pretože nie sú časovo ani odborne náročné na administráciu. Jedná sa napr. o ECCA test (ElectroConvulsive therapy Cognitive Assessment), prípadne o batériu B4ECT-ReCoDe (Battery for ECT Related Cognitive Deficits). Komplikáciou ich využitia v podmienkach Slovenskej i Českej republiky je, že tam nie sú štandardizované. Alternatívou je použitie jednotlivých testov na spomenuté domény. Významné je najmä hodnotenie dĺžky dezorientácie pacienta po ECT zákrokoch, vyhodnocovanie autobiografickej pamäti, schopnosti verbálneho učenia, exekutívnych funkcií a rýchlosti spracovania informácií a pozornosti, resp. pracovnej pamäti. Hodnotenie výskytu a závažnosti kognitívnych nežiaducich účinkov u pacientov podstupujúcich ECT je v praxi potrebné, zníži riziko rozvoja ich závažnejšieho stupňa, prispeje k optimalizácii liečby, ako aj k zlepšeniu spolupráce pacientov pri tejto terapii.
Electroconvulsive therapy (ECT) has a solid place in psychiatry and an irreplaceable role in the treatment of serious mental disorders. The occurrence of serious side effects is rare, the mortality rate of ECT is lower, compared to other medical interventions performed under general anesthesia. In connection with ECT, various disorders of cognitive functions are described, which pose a risk in terms of a negative impact on the patient ́s quality of life. Concerns about their occurrence and alleged high severity persist for a long time in the public. This is the so-called unsystematic review. Literary sources were mainly drawn from the PubMed database (meta-analyses, systematic review works and clinical studies published on the given topic during the last 10 years). According to a recent and fairly extensive meta-analysis, the occurrence of subjective cognitive side effects in patients after ECT was recorded in 48% of cases. However, according to the currently available data, they are mostly transitory, short-term and affect only certain cognitive domains (information processing speed, executive functions, attention, working and verbal memory, autobiographical memory). Nevertheless, the autobiographical memory disorder can persist in some cases for more than 1 year with partial irreversibility. The occurrence of cognitive side effects is influenced by several modifiable factors that need to be known and respected. An essential one is the individualization of the amount of applied electric charge during ECT through its gradual titration, in order to find the individual seizure threshold. Ultrabrief pulses (0.3ms) should clearly be preferred over longer ones. If the clinical condition allows it, it is advisable to use unilateral electrode placement (over the non-dominant hemisphere). It is not recommended to administer more than 12 applications in one series in the acute phase of treatment (with bitemporal placement of electrodes). Individual patient factors such as older age, female gender, presence of organic brain damage, and lower intellect pose a higher risk of developing cognitive adverse effects after ECT. So does concurrent lithium treatment during ECT. Current national and international guidelines offer various psychometric instruments to monitor the cognitive side effects of ECT. In some countries, for example in German-speaking regions, but also in Slovakia, specific recommendations have not been developed. Nowadays, there are batteries of tests evaluating relevant cognitive domains that can be used in clinical practice during ECT, because they are neither time nor expertly hard to administer. It is, for example, the ECCA test (ElectroConvulsive therapy Cognitive Assessment), or the B4ECT-ReCoDe battery (Battery for ECT Related Cognitive Deficits). The complication of their use in the conditions of Slovakia and the Czech Republic is that they are not standardized there. An alternative is to use individual tests for the mentioned domains. It is particularly important to assess the length of the patient ́s disorientation after ECT procedures, the evaluation of autobiographical memory, verbal learning ability, executive functions and information processing speed and attention, or working memory. Assessment of the occurrence and severity of cognitive side effects in patients undergoing ECT is necessary in practice, it will reduce the risk of developing their more severe degree, contribute to the optimization of treatment, as well as to the improvement of patient cooperation in this therapy.
OBJECTIVES: To externally and prospectively validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SRs), Logistic Regression model 2 (LR2) and Assessment of Different NEoplasias in the adneXa (ADNEX) model in a Portuguese population, comparing these approaches with subjective assessment and the risk-of-malignancy index (RMI), as well as with each other. This study also aimed to retrospectively validate the IOTA two-step strategy, using modified benign simple descriptors (MBDs) followed by the ADNEX model in cases in which MBDs were not applicable. METHODS: This was a prospective multicenter diagnostic accuracy study conducted between January 2016 and December 2021 of consecutive patients with an ultrasound diagnosis of at least one adnexal tumor, who underwent surgery at one of three tertiary referral centers in Lisbon, Portugal. All ultrasound assessments were performed by Level-II or -III sonologists with IOTA certification. Patient clinical data and serum CA 125 levels were collected from hospital databases. Each adnexal mass was classified as benign or malignant using subjective assessment, RMI, IOTA SRs, LR2 and the ADNEX model (with and without CA 125). The reference standard was histopathological diagnosis. In the second phase, all adnexal tumors were classified retrospectively using the two-step strategy (MBDs + ADNEX). Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and overall accuracy were determined for all methods. Receiver-operating-characteristics curves were constructed and corresponding areas under the curve (AUC) were determined for RMI, LR2, the ADNEX model and the two-step strategy. The ADNEX model calibration plots were constructed using locally estimated scatterplot smoothing (LOESS). RESULTS: Of the 571 patients included in the study, 428 had benign disease and 143 had malignant disease (prevalence of malignancy, 25.0%), of which 42 had borderline ovarian tumor, 93 had primary invasive adnexal cancer and eight had metastatic tumors in the adnexa. Subjective assessment had an overall sensitivity of 97.9% and a specificity of 83.6% for distinguishing between benign and malignant lesions. RMI showed high specificity (95.6%) but very low sensitivity (58.7%), with an AUC of 0.913. The IOTA SRs were applicable in 80.0% of patients, with a sensitivity of 94.8% and specificity of 98.6%. The IOTA LR2 had a sensitivity of 84.6%, specificity of 86.9% and an AUC of 0.939, at a malignancy risk cut-off of 10%. At the same cut-off, the sensitivity, specificity and AUC for the ADNEX model with vs without CA 125 were 95.8% vs 98.6%, 82.5% vs 79.7% and 0.962 vs 0.960, respectively. The ADNEX model gave heterogeneous results for distinguishing between benign masses and different subtypes of malignancy, with the highest AUC (0.991) for discriminating benign masses from primary invasive adnexal cancer Stages II-IV, and the lowest AUC (0.696) for discriminating primary invasive adnexal cancer Stage I from metastatic lesion in the adnexa. The calibration plot suggested underestimation of the risk by the ADNEX model compared with the observed proportion of malignancy. The MBDs were applicable in 26.3% (150/571) of cases, of which none was malignant. The two-step strategy using the ADNEX model in the second step only, with and without CA 125, had AUCs of 0.964 and 0.961, respectively, which was similar to applying the ADNEX model in all patients. CONCLUSIONS: The IOTA methods showed good-to-excellent performance in the Portuguese population, outperforming RMI. The ADNEX model was superior to other methods in terms of accuracy, but interpretation of its ability to distinguish between malignant subtypes was limited by sample size and large differences in the prevalence of tumor subtypes. The IOTA MBDs are reliable in identifying benign disease. The two-step strategy comprising application of MBDs followed by the ADNEX model if MBDs are not applicable, is suitable for daily clinical practice, circumventing the need to calculate the risk of malignancy in all patients. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
- MeSH
- CA-125 Antigen blood MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Ovarian Neoplasms * diagnostic imaging pathology classification blood MeSH
- Adnexal Diseases * diagnostic imaging MeSH
- Predictive Value of Tests MeSH
- Prospective Studies MeSH
- Reproducibility of Results MeSH
- Retrospective Studies MeSH
- ROC Curve MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Ultrasonography * methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Validation Study MeSH
- Geographicals
- Portugal MeSH
