Noninvasive Diagnosis of Adenomyosis: A Structured Review and Meta-analysis of Diagnostic Accuracy in Imaging.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate imaging methods used to diagnose adenomyosis. DATA SOURCES: A thorough search was completed through the Cochrane Central Register of Controlled Trials, EMBASE, and PubMed or MEDLINE databases from January 2000 to June 2019. METHODS OF STUDY SELECTION: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment of Diagnostic Accuracy Studies 2 tool, studies reporting the diagnostic accuracy of an imaging method and histopathology as a reference standard were selected and prospectively registered in the International Prospective Register of Systematic Reviews. Statistical analysis was performed using the R-package Meta-Analysis of Diagnostic Accuracy. TABULATION, INTEGRATION, AND RESULTS: Of the 1168 records identified, 10 studies were included in the meta-analysis, and these included 827 patients undergoing 2- or 3-dimensional transvaginal ultrasound (TVUS) and 317 patients undergoing magnetic resonance imaging (MRI). The risk of bias was low or unclear for all Quality Assessment of Diagnostic Accuracy Studies domains. The overall prevalence of adenomyosis was 40%. Overall MRI, 2-dimensional TVUS, 3-dimensional TVUS, and TVUS had the following aggregated diagnostic qualities (95% confidence interval): sensitivity of 78% (70%-84%), 74% (68%-79%), 84% (77%-89%), 78% (73%-82%); specificity of 88% (83%-92%), 76% (71%-79%), 84% (77%-89%), 78% (74%-81%); positive likelihood ratio of 6.8 (4.5%-10%), 3 (2.5%-3.7%), 5.2 (3.6%-7.4%), 3.5 (3%-4.2%); negative likelihood ratio of 0.25 (0.18%-0.35%), 0.34 (0.27%-0.43%), 0.19 (0.13%-0.28%), 0.28 (0.23%-0.34%); and pooled area under the operator curve of 0.77, 0.7, 0.83, 0.73, respectively. The pooled area under the operator curve for all modalities was not significantly different (all: p ≥.4). CONCLUSION: As a result of the systemic review and meta-analysis, we identified TVUS and MRI as good and comparable noninvasive imaging methods for diagnosing adenomyosis, leading us to recommend TVUS as the first-line diagnostic imaging method and MRI as a second-line method, if TVUS is inconclusive.

Diagnosing adenomyosis with MRI: a prospective study revisiting the junctional zone thickness cutoff of 12 mm as a diagnostic marker.

OBJECTIVES: To assess the diagnostic accuracy of a junctional zone (JZ) thickness of ≥ 12 mm and morphological features of the JZ in MRI in diagnosing adenomyosis in a premenopausal study population. METHODS: This single-center, prospective observational study consecutively enrolled 93 premenopausal women suffering from a benign gynecological condition, from September 2014 to August 2016. Institutional review board approval and written consent were obtained. All participants underwent MRI and hysterectomy with a histopathological examination. MR images were evaluated in a blinded fashion by two independent readers. The maximum junctional zone thickness (JZmax), presence of JZmax ≥ 12 mm, and any irregular appearance of the JZ (defined as irregular outer or inner borders, focal thickening, presence of high-intensity signal foci, or fingerlike indentations at the inner border) were documented, and the diagnostic performance was evaluated with the AUC, chi-square test, and multiple regression. RESULTS: Adenomyosis was histopathologically confirmed in 57 (61%) of the women. JZmax was not positively correlated with adenomyosis diagnosis (AUC = 0.57, p = 0.26) and did not differ significantly between those with and without adenomyosis (10.3 vs 10.1 mm, p = 0.88), nor was a cutoff of JZmax ≥ 12 mm (n = 30/57 (53%) vs n = 16/36 (44%), p = 0.29). The presence of an irregular JZ showed the best association with adenomyosis among the evaluated signs (sensitivity 74% (95% CI, 60, 85); specificity 83% (95% CI, 67, 94) (p < 0.001)). CONCLUSIONS: JZmax was not correlated with adenomyosis in the present premenopausal study population, but direct signs of adenomyosis such as irregularities of the JZ provided a good diagnostic accuracy. KEY POINTS: • Measuring the junctional zone thickness is of limited value for diagnosing adenomyosis with MRI and should not be used for diagnosing adenomyosis in premenopausal women with moderate disease severity. • An irregular appearance of the junctional zone, the presence of myometrial cysts, and adenomyoma appear to provide the highest specificity for diagnosing adenomyosis. • A consensus for the definition and reading of the junctional zone is needed.

Development of a clinical prediction model for diagnosing adenomyosis.

OBJECTIVE: To develop a multivariate prediction model for diagnosing adenomyosis using predictors available through transvaginal ultrasonography and clinical examinations. DESIGN: Prospective observational single-center study. SETTING: Teaching university hospital. PATIENT(S): One hundred consecutively enrolled premenopausal women aged 30-50 years, undergoing hysterectomy due to a benign condition and not using hormonal treatment. INTERVENTION(S): Preoperative 2-D and 3-D transvaginal ultrasonography investigations were performed, and the results were documented in a standardized form. Clinical information was collected using a questionnaire. Histopathology confirmed the outcome. MAIN OUTCOME MEASURE(S): Diagnostic performance (sensitivity, specificity, area under the curve (AUC)) of a multivariate prediction model for adenomyosis. Independent diagnostic performance of single predictors and their quantitative effect (ß) in the final model. RESULT(S): The final model showed a good test quality (area under the curve [AUC] = 0.86, [95% confidence interval = 0.79-0.94], optimal cutoff 0.56, sensitivity of 85%, specificity 78%). The following nine predictors were included ([sensitivity, specificity, ß] or [AUC, ß]): presence of myometrial cysts (51%, 86%, ß = 0.86), fan-shaped echo (36%, 92%, ß = 0.54), hyperechoic islets (51%, 78%, ß = 0.62), globular uterus (61%, 83%, ß = 0.2), normal uterine shape (83%, 61%, ß = -0.75), thickest/thinnest ratio for uterine wall (0.61, ß = 0.26), maximum width of the junctional zone in sagittal plane (0.71, ß = 0.1), regular appearance of junctional zone (31%, 92%, ß = -1.0), and grade of dysmenorrhea measured on a verbal numerical rating scale (0.61, ß = 0.08). CONCLUSION(S): We have presented a multivariate model for diagnosing adenomyosis that weights predictors based on their diagnostic significance. The reported findings could aid clinicians who are interpreting the heterogeneous appearance of adenomyosis in ultrasonography. CLINICAL TRIAL REGISTRATION NUMBER: NCT02201719.

Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function.

BACKGROUND: Alzheimer's disease (AD) is associated with several antibodies as well as signaling molecules and receptors. These may be detrimental in the presence of a disrupted blood-brain barrier (BBB). OBJECTIVE: To investigate whether the levels of antibodies toward 33 signaling molecules involved in neurotransmitter, vascular, and immune functions were associated with AD and, within the AD group; cognitive function and mood. METHODS: Antibodies in sera from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination ≥ 20 or a Clinical Dementia Rating Scale≤1] and healthy controls (n = 102) were measured with enzyme-linked immunosorbent assays. Levels in AD and controls were compared by Mann-Whitney test. In the AD group, associations between antibodies and psychometric test scores were analyzed by robust regression. The false discovery threshold was set to 0.05. RESULTS: Antibodies to serotonin receptors [5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and 5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1 [VEGFR1 (r = 0.29, p < 0.001)] and immune-receptors (Stabilin-1 (r = 0.23, p = 0.001) and C5aR1 (r = 0.21, p = 0.004) were higher in AD. Psychomotor speed was associated with D1R-abs (ß 0.49, p < 0.001), depression with ETAR-abs (ß 0.31, p < 0.001), and visuospatial function with 5-HT1AR-abs (ß 0.27, p = 0.004) despite similar antibody levels compared to controls. CONCLUSIONS: Antibody levels to VEGFR1, serotonergic receptors, and receptors in the immune system were increased in AD. Antibodies at similar levels as in controls were associated cognitive dysfunction and depression in AD.