Assessment of cyst content using mean gray value for discriminating endometrioma from other unilocular cysts in premenopausal women

Objective To assess whether the analysis of cyst content using mean gray value (MGV) can discriminate ovarian endometriomas from other unilocular ovarian cysts in premenopausal women. Methods Stored three-dimensional (3D) volumes from 54 unilocular ovarian cysts diagnosed in 50 premenopausal women (mean age, 37 (range, 22–50) years) were analyzed to calculate the MGV from cyst content. Cysts with solid components or septations were excluded. MGV was calculated in all cases with the Virtual Organ Computer-aided AnaLysisTM technique. The Bmode presumptive diagnosis based on the examiner’s subjective impression was also recorded. Results Sixteen of the cysts resolved spontaneously and were given a final clinical diagnosis of hemorrhagic functional cyst, while 38 cysts were removed surgically (diagnosed histologically as seven simple cysts, three hemorrhagic cysts, 20 endometriomas, five mucinous cysts and three paraovarian cysts). B-mode diagnoses were as follows: seven simple cysts, 18 hemorrhagic cysts, 24 endometriomas, three mucinous cysts and two paraovarian cysts. MGV was significantly higher in ovarian endometrioma when compared with all other kinds of cyst. The receiver–operating characteristics curve showed that using an MGV cut-off ≥15.560 had a sensitivity of 85% and a specificity of 76.5% for diagnosing ovarian endometrioma (area under the curve, 0.831; 95% CI, 0.718–0.944). These figures were similar to those for B-mode diagnosis (sensitivity, 90%; specificity, 82%) (McNemar test, P = 1.000). Combining B-mode and MGV gave a sensitivity of 80% and a specificity of 91%. Conclusion Cyst content MGV is higher in ovarian endometrioma than it is in other unilocular ovarian cysts. The diagnostic performance of MGV is similar to that of the examiner’s subjective impression. The combination of both criteria achieves the highest specificit

Three-dimensional power Doppler angiography in endometrial cancer: correlation with tumor characteristics

To assess the correlation between intratumoral vascularization using three-dimensional power Doppler angiography (3D-PDA) and several histological tumor characteristics in a series of patients with endometrial carcinoma. METHODS: Ninety-nine women (mean age, 61.7 (range, 31-84) years) diagnosed as having endometrial cancer were assessed by transvaginal 3D-PDA before surgical staging. Endometrial volume (EV) and 3D-PDA vascular indices (vascularization index (VI), flow index (FI) and vascularization flow index (VFI)) were calculated using the Virtual Organ Computer-aided AnaLysis (VOCAL) method. All patients were surgically staged. Individual tumor features such as histological type, tumor grade, myometrial infiltration depth, lymph-vascular space involvement, cervical involvement, lymph node metastases and tumor stage were considered for analysis. Multivariate logistic regression (MLR) analysis was used to determine which 3D-PDA parameters were independently associated with each histological characteristic. RESULTS: MLR analysis showed that only EV and VI were independently associated with myometrial infiltration (EV: odds ratio (OR), 1.119 (95% CI, 1.025-1.221), P = 0.012; VI: OR, 1.127 (95% CI, 1.063-1.195), P = 0.001) and tumor stage (EV: OR, 1.103 (95% CI, 1.012-1.202), P = 0.025; VI: OR, 1.120 (95% CI, 1.057-1.187), P = 0.001), only VI was independently associated with tumor grade (OR, 1.056 (95% CI, 1.023-1.091), P = 0.001) and only EV was independently associated with lymph node metastases (OR, 1.086 (95% CI, 1.017-1.161), P = 0.001). CONCLUSION: 3D-PDA analysis of tumor vascularization in endometrial cancer correlates with some prognostic histological characteristics

Alternative splicing regulates stochastic NLRP3 activity

Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3. exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus reveals unexpected regulatory roles of AS through differential utilization of LRRs modules in vertebrate innate immunity

Imaging in gynecological disease (17): ultrasound features of malignant ovarian yolk sac tumors (endodermal sinus tumors)

Objective To describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs). Methods In this retrospective multicenter study, we included 21 patients with a histological diagnosis of ovarian YST and available transvaginal ultrasound images and/or videoclips and/or a detailed ultrasound report. Ten patients identified from the International Results All cases were pure YSTs, except for one that was a mixed tumor (80% YST and 20% embryonal carcinoma). Median age at diagnosis was 25 (interquartile range (IQR), 19.5–30.5) years. Seventy-six percent (16/21) of women had an International Federation of Gynecology and Obstetrics (FIGO) Stage I–II tumor at diagnosis. Fifty-eight percent (11/19) of women felt pain during the ultrasound examination and one presented with ovarian torsion. Median serum α-fetoprotein (S-AFP) level was 4755 (IQR, 1071–25 303) μg/L and median serum CA 125 level was 126 (IQR, 35–227) kU/L. On ultrasound assessment, 95% (20/21) of tumors were unilateral. The median maximum tumor diameter was 157 (IQR, 107–181) mm and the largest solid component was 110 (IQR, 66–159) mm. Tumors were classified as either multilocular-solid (10/21; 48%) or solid (11/21; 52%). Papillary projections were found in 10% (2/21) of cases. Most (20/21; 95%) tumors were well vascularized (color score, 3–4) and none had acoustic shadowing. Malignancy was suspected in all cases, except in the patient with ovarian torsion, who presented a tumor with a color score of 1, which was classified as probably benign. Image and videoclip quality was considered as adequate in 18/21 cases. On review of the images and videoclips, we found that all tumors contained both solid components and cystic spaces, and that 89% (16/18) had irregular, still fine-textured and slightly hyperechoic solid tissue, giving them a characteristic appearance. Conclusion Malignant ovarian YSTs are often detected at an early stage, in young women usually in the second or third decade of life, presenting with pain and markedly elevated S-AFP. On ultrasound, malignant ovarian YSTs are mostly unilateral, large and multilocular-solid or solid, with fine-textured slightly hyperechoic solid tissue and rich vascularization. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

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

Objective: To evaluate the diagnostic accuracy of different ultrasound signs for diagnosing adnexal torsion, using surgery as the reference standard. Methods: This was a systematic review and meta-analysis of studies published between January 1990 and November 2021 evaluating ovarian edema, adnexal mass, ovarian Doppler flow findings, the whirlpool sign and pelvic fluid as ultrasound signs (index tests) for detecting adnexal torsion, using surgical findings as the reference standard. The search for studies was performed in PubMed/MEDLINE, CINAHL, Scopus, The Cochrane Library, ClinicalTrials.gov and Web of Science databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of the studies. Pooled sensitivity, specificity, and positive and negative likelihood ratios were calculated separately, and the post-test probability of adnexal torsion following a positive or negative test was also determined. Results: The search identified 1267 citations after excluding duplicates. Eighteen studies were ultimately included in the qualitative and quantitative syntheses. Eight studies (809 patients) analyzed the presence of ovarian edema, eight studies (1044 patients) analyzed the presence of an adnexal mass, 14 studies (1742 patients) analyzed ovarian Doppler flow, six studies (545 patients) analyzed the whirlpool sign and seven studies (981 patients) analyzed the presence of pelvic fluid as ultrasound signs of adnexal torsion. Overall, the quality of most studies was considered to be moderate or good. However, there was a high risk of bias in the patient-selection and index-text domains (with the exception of the whirlpool sign) in a significant proportion of studies. Pooled sensitivity, specificity, and positive and negative likelihood ratios of each ultrasound sign were 58%, 86%, 4.0 and 0.49 for ovarian edema, 69%, 46%, 1.3 and 0.67 for adnexal mass, 65%, 91%, 7.6 and 0.38 for the whirlpool sign, 53%, 95%, 11.0 and 0.49 for ovarian Doppler findings and 55%, 69%, 1.7 and 0.66 for pelvic fluid. Heterogeneity was high for all analyses. Conclusions: The presence of an adnexal mass or pelvic fluid have poor diagnostic accuracy as ultrasound signs of adnexal torsion, while the presence of ovarian edema, the whirlpool sign and decreased or absent ovarian Doppler flow have good specificity but moderate sensitivity for detecting adnexal torsion. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.Objetivo.Evaluar la precision diagnostica de diferentes indicios ecograficos para el diagnostico de la torsion anexial,utilizando la cirugia como patron de referencia. Metodos. Se trata de una revision sistematica y un metaanalisis de los estudios publicados entre enero de 1990 y noviembre de 2021 que evaluaron el edema ovarico, la masa anexial, los resultados del flujo Doppler ovarico, el ‘‘signo del remolino’’ (torsion ovarica) y el liquido pelvico como indicios ecograficos (pruebas de referencia) para detectar la torsion anexial, utilizando los resultados quirurgicos como patron de referencia. La busqueda de estudios se realizo en las bases de datos PubMed/MEDLINE, CINAHL, Scopus, The Cochrane Library, ClinicalTrials.gov y Web of Science.Para evaluar la calidad de los estudios se utilizo la herramienta de Evaluacion de Calidad de los Estudios de Precision Diagnostica-2 (QUADAS-2, por sus siglas en ingles). Se calcularon por separado los valores combinados de sensibilidad,especificidad y cocientes de verosimilitud positivos y negativos, y se determino tambien la probabilidad posterior a la prueba de la torsion anexial tras una prueba positiva o negativa. Resultados. La busqueda identifico 1267 citas, una vez excluidas las duplicadas. Se incluyeron dieciocho estudios en las sıntesis cualitativa y cuantitativa. Ocho estudios (809 pacientes) analizaron la presencia de edema ovarico, ocho estudios(1044 pacientes) analizaron la presencia de una masa anexial, 14 estudios (1742 pacientes) analizaron el flujo Doppler ovarico, seis estudios (545 pacientes) analizaron el ‘‘signo del remolino’’ y siete estudios (981 pacientes) analizaron la presencia de lıquido pelvico como indicios ecograficos de torsion anexial. En general, la calidad de la mayorıa de los estudios se considero moderada o buena. Sin embargo, hubo un alto riesgo de sesgo en una proporcion significativa de estudios en las areas de seleccion de pacientes y texto de referencia (con la excepcion del ‘‘signo del remolino’’). Los valores combinados de la sensibilidad, la especificidad y los cocientes de probabilidad positivos y negativos de cada indicio ecografico fueron del 58%, 86%, 4,0 y 0,49 para el edema ovarico, del 69%, 46%, 1,3 y 0,67 para la masa anexial, del 65%, 91%, 7,6 y 0,38 para el ‘‘signo del remolino’’, del 53%, 95%, 11,0 y 0,49 para los resultados del Doppler ovarico y del 55%, 69%, 1,7 y 0,66 para el liquido pelvico. La heterogeneidad fue elevada en todos los analisis. Conclusion. La presencia de una masa anexial o de liquido pelvico apenas tienen precision diagnostica como indicios ecograficos de torsion anexial, mientras que la presencia de edema ovarico, el ‘‘signo del remolino’’ y la disminucion o ausencia de flujo Doppler ovarico tienen una buena especificidad, pero una sensibilidad moderada para detectar la torsion anexial

Tracking the antibody immunome in sporadic colorectal cancer by using antigen self-assembled protein arrays

© 2021 by the authors.Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) “Una manera de hacer Europa” and Junta Castilla-León (COVID19 grant COV20EDU/00187). Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. CNPq-National Council for Scientific and Technological Development (Brazil) (306258/2019-6) and FAPERJ-Foundation for Research Support of Rio de Janeiro State for the financial support (E-26/201.670/2017 and 210.379/2018). M. González-González is supported by MINECOPTA2019-017870-I.A. Landeira-Viñuela is supported by VIII Centenario-USAL PhD Program. P.J.-V. is supported by JCYL PhD Program and scholarship JCYL-EDU/601/2020. P.D. and E.B. are supported by a JCYL-EDU/346/2013 Ph.D. scholarship

Modified Wisconsin Card Sorting Test (M-WCST): Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Modified Wisconsin Card Sorting Test (M-WCST) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the M-WCST as part of a larger neuropsychological battery. Number of categories, perseverative errors, and total error scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models indicated main effects for age on all scores, such that the number of categories correct increased and total number of perseverative errors and total number of errors decrease linearly as a function of age. Age2 had a significant effect in Chile, Cuba, Ecuador, and Spain for numbers of categories; a significant effect for number of perseverative errors in Chile, Cuba, Mexico, and Spain; and a significant effect for number of total errors in Chile, Cuba, Peru, and Spain. Models showed an effect for MLPE in Cuba (total errors), Ecuador (categories and total errors), Mexico (all scores), Paraguay (perseverative errors and total error), and Spain (categories and total errors). Sex affected number of total errors for Ecuador. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate way to interpret the M-WCST with pediatric populations

Trail Making Test: Normative data for the Latin American Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Trail Making Test (TMT) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 3,337 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the TMT as part of a larger neuropsychological battery. The TMT-A and TMT-B scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on both scores, such that as children needed less time to complete the test while they become older. TMT-A scores were affected by age2 for all countries except, Cuba, Guatemala, and Puerto. TMT-B scores were affected by age2 for all countries except, Guatemala and Puerto Rico. Models indicated that children whose parent(s) had a MLPE >12 years of education needed less time to complete the test compared to children whose parent(s) had a MLPE ≤12 years for Mexico and Paraguay in TMT-A scores; and Ecuador, Mexico, Paraguay, and Spain for TMT-B scores. Sex affected TMT-A scores for Chile, Cuba, Mexico, and Peru, in that boys needed less time to complete the test than girls. Sex did not affect TMT-B scores. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the TMT in pediatric populations

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis

Modified Wisconsin Card Sorting Test (M-WCST): Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Modified Wisconsin Card Sorting Test (M-WCST) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the M-WCST as part of a larger neuropsychological battery. Number of categories, perseverative errors, and total error scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models indicated main effects for age on all scores, such that the number of categories correct increased and total number of perseverative errors and total number of errors decrease linearly as a function of age. Age2 had a significant effect in Chile, Cuba, Ecuador, and Spain for numbers of categories; a significant effect for number of perseverative errors in Chile, Cuba, Mexico, and Spain; and a significant effect for number of total errors in Chile, Cuba, Peru, and Spain. Models showed an effect for MLPE in Cuba (total errors), Ecuador (categories and total errors), Mexico (all scores), Paraguay (perseverative errors and total error), and Spain (categories and total errors). Sex affected number of total errors for Ecuador. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate way to interpret the M-WCST with pediatric populations