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Human apolipoprotein E (ApoE) was first identified as a polymorphic gene in the 1970s; however, the genetic association of ApoE genotypes with late-onset sporadic Alzheimer's disease (sAD) was only discovered 20 years later. Since then, intensive research has been undertaken to understand the molecular effects of ApoE in the development of sAD. Despite three decades' worth of effort and over 10,000 papers published, the greatest mystery in the ApoE field remains: human ApoE isoforms differ by only one or two amino acid residues; what is responsible for their significantly distinct roles in the etiology of sAD, with ApoE4 conferring the greatest genetic risk for sAD whereas ApoE2 providing exceptional neuroprotection against sAD. Emerging research starts to point to a novel and compelling hypothesis that the sialoglycans posttranslationally appended to human ApoE may serve as a critical structural modifier that alters the biology of ApoE, leading to the opposing impacts of ApoE isoforms on sAD and likely in the peripheral systems as well. ApoE has been shown to be posttranslationally glycosylated in a species-, tissue-, and cell-specific manner. Human ApoE, particularly in brain tissue and cerebrospinal fluid (CSF), is highly glycosylated, and the glycan chains are exclusively attached via an O-linkage to serine or threonine residues. Moreover, studies have indicated that human ApoE glycans undergo sialic acid modification or sialylation, a structural alteration found to be more prominent in ApoE derived from the brain and CSF than plasma. However, whether the sialylation modification of human ApoE has a biological role is largely unexplored. Our group recently first reported that the three major isoforms of human ApoE in the brain undergo varying degrees of sialylation, with ApoE2 exhibiting the most abundant sialic acid modification, whereas ApoE4 is the least sialylated. Our findings further indicate that the sialic acid moiety on human ApoE glycans may serve as a critical modulator of the interaction of ApoE with amyloid ß (Aß) and downstream Aß pathogenesis, a prominent pathologic feature in AD. In this review, we seek to provide a comprehensive summary of this exciting and rapidly evolving area of ApoE research, including the current state of knowledge and opportunities for future exploration.
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BACKGROUND. Screening mammography has decreased performance in patients with dense breasts. Supplementary screening ultrasound is a recommended option in such patients, although it has yielded mixed results in prior investigations. OBJECTIVE. The purpose of this article is to compare the performance characteristics of screening mammography alone, standalone artificial intelligence (AI), ultrasound alone, and mammography in combination with AI and/or ultrasound in patients with dense breasts. METHODS. This retrospective study included 1325 women (mean age, 53 years) with dense breasts who underwent both screening mammography and supplementary breast ultrasound within a 1-month interval from January 2017 to December 2017; prior mammography and prior ultrasound examinations were available for comparison in 91.2% and 91.8%, respectively. Mammography and ultrasound examinations were interpreted by one of 15 radiologists (five staff; 10 fellows); clinical reports were used for the present analysis. A commercial AI tool was used to retrospectively evaluate mammographic examinations for presence of cancer. Screening performances were compared among mammography, AI, ultrasound, and test combinations, using generalized estimating equations. Benign diagnoses required 24 months or longer of imaging stability. RESULTS. Twelve cancers (six invasive ductal carcinoma; six ductal carcinoma in situ) were diagnosed. Mammography, standalone AI, and ultrasound showed cancer detection rates (per 1000 patients) of 6.0, 6.8, and 6.0 (all p > .05); recall rates of 4.4%, 11.9%, and 9.2% (all p < .05); sensitivity of 66.7%, 75.0%, and 66.7% (all p > .05); specificity of 96.2%, 88.7%, and 91.3% (all p < .05); and accuracy of 95.9%, 88.5%, and 91.1% (all p < .05). Mammography with AI, mammography with ultrasound, and mammography with both ultrasound and AI showed cancer detection rates of 7.5, 9.1, and 9.1 (all p > .05); recall rates of 14.9, 11.7, and 21.4 (all p < .05); sensitivity of 83.3%, 100.0%, and 100.0% (all p > .05); specificity of 85.8%, 89.1%, and 79.4% (all p < .05); and accuracy of 85.7%, 89.2%, and 79.5% (all p < .05). CONCLUSION. Mammography with supplementary ultrasound showed higher accuracy, higher specificity, and lower recall rate in comparison with mammography with AI and in comparison with mammography with both ultrasound and AI. CLINICAL IMPACT. The findings fail to show benefit of AI with respect to screening mammography performed with supplementary breast ultrasound in patients with dense breasts.
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Neoplasias da Mama , Mamografia , Humanos , Feminino , Pessoa de Meia-Idade , Mamografia/métodos , Densidade da Mama , Estudos Retrospectivos , Inteligência Artificial , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodosRESUMO
Monitoring the microenvironment within specific cellular regions is crucial for a comprehensive understanding of life events. Fluorescent probes working in different ranges of pH regions have been developed for the local imaging of different pH environments. Especially, rhodamine-based fluorescent pH probes have been of great interest due to their ON/OFF fluorescence depending on the spirolactam ring's opening/closure. By introducing the N-alkyl-hydroxamic acid instead of the alkyl amines in the spirolactam of rhodamine, we were able to tune the pH range where the ring opening and closing of the spirolactam occurs. This six-membered cyclic hydroxamate spirolactam ring of rhodamine B proved to be highly fluorescent in acidic pH environments. In addition, we could monitor pH changes of lysosomes in live cells and zebrafish.
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Corantes Fluorescentes , Peixe-Zebra , Animais , Concentração de Íons de Hidrogênio , Rodaminas , LisossomosRESUMO
BACKGROUND: Mammography yields inevitable recall for indeterminate findings that need to be confirmed with additional views. PURPOSE: To explore whether the artificial intelligence (AI) algorithm for mammography can reduce false-positive recall in patients who undergo the spot compression view. MATERIAL AND METHODS: From January to December 2017, 236 breasts from 225 women who underwent the spot compression view due to focal asymmetry, mass, or architectural distortion on standard digital mammography were included. Three readers who were blinded to the study purpose, patient information, previous mammograms, following spot compression views, and any clinical or pathologic reports retrospectively reviewed 236 standard mammograms and determined the necessity of patient recall and the probability of malignancy per breast, first without and then with AI assistance. The performances of AI and the readers were evaluated with the recall rate, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. RESULTS: Among 236 examinations, 8 (3.4%) were cancers and 228 (96.6%) were benign. The recall rates of all three readers significantly decreased with AI assistance (P < 0.05). The reader-averaged recall rates significantly decreased with AI assistance regardless of breast composition (fatty breasts: 32.7% to 24.1%m P = 0.002; dense breasts: 33.6% to 21.2%, P < 0.001). The reader-averaged AUC increased with AI assistance and was comparable to that of standalone AI (0.835 vs. 0.895; P = 0.234). The reader-averaged specificity (71.2% to 79.8%, P < 0.001) and accuracy (71.3% to 79.7%, P < 0.001) significantly improved with AI assistance. CONCLUSION: AI assistance significantly reduced false-positive recall without compromising cancer detection in women with focal asymmetry, mass, or architectural distortion on standard digital mammography regardless of mammographic breast density.
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Inteligência Artificial , Neoplasias da Mama , Feminino , Humanos , Estudos Retrospectivos , Mamografia , Mama/diagnóstico por imagem , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de CâncerRESUMO
Lysyl oxidase-2 (LOXL2) is a Cu2+ and lysine tyrosylquinone (LTQ)-dependent amine oxidase that catalyzes the oxidative deamination of peptidyl lysine and hydroxylysine residues to promote crosslinking of extracellular matrix proteins. LTQ is post-translationally derived from Lys653 and Tyr689, but its biogenesis mechanism remains still elusive. A 2.4 Å Zn2+-bound precursor structure lacking LTQ (PDB:5ZE3) has become available, where Lys653 and Tyr689 are 16.6 Å apart, thus a substantial conformational rearrangement is expected to take place for LTQ biogenesis. However, we have recently shown that the overall structures of the precursor (no LTQ) and the mature (LTQ-containing) LOXL2s are very similar and disulfide bonds are conserved. In this study, we aim to gain insights into the spatial arrangement of LTQ and the active site Cu2+ in the mature LOXL2 using a recombinant LOXL2 that is inhibited by 2-hydrazinopyridine (2HP). Comparative UV-vis and resonance Raman spectroscopic studies of the 2HP-inhibited LOXL2 and the corresponding model compounds and an EPR study of the latter support that 2HP-modified LTQ serves as a tridentate ligand to the active site Cu2. We propose that LTQ resides within 2.9 Å of the active site of Cu2+ in the mature LOXL2, and both LTQ and Cu2+ are solvent-exposed.
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Lisina , Proteína-Lisina 6-Oxidase , Lisina/metabolismo , Proteína-Lisina 6-Oxidase/metabolismo , Domínio Catalítico , Quinonas/químicaRESUMO
Lysyl oxidase-like 2 (LOXL2) catalyzes the oxidative deamination of peptidyl lysines and hydroxylysines to promote extracellular matrix remodeling. Aberrant activity of LOXL2 has been associated with organ fibrosis and tumor metastasis. The lysine tyrosylquinone (LTQ) cofactor is derived from Lys653 and Tyr689 in the amine oxidase domain via post-translational modification. Based on the similarity in hydrodynamic radius and radius of gyration, we recently proposed that the overall structures of the mature LOXL2 (containing LTQ) and the precursor LOXL2 (no LTQ) are very similar. In this study, we conducted a mass spectrometry-based disulfide mapping analysis of recombinant LOXL2 in three forms: a full-length LOXL2 (fl-LOXL2) containing a nearly stoichiometric amount of LTQ, Δ1-2SRCR-LOXL2 (SRCR1 and SRCR2 are truncated) in the precursor form, and Δ1-3SRCR-LOXL2 (SRCR1, SRCR2, SRCR3 are truncated) in a mixture of the precursor and the mature forms. We detected a set of five disulfide bonds that is conserved in both the precursor and the mature recombinant LOXL2s. In addition, we detected a set of four alternative disulfide bonds in low abundance that is not associated with the mature LOXL2. These results suggest that the major set of five disulfide bonds is retained post-LTQ formation.
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Dissulfetos , Proteína-Lisina 6-Oxidase , Aminoácido Oxirredutases/metabolismo , Matriz Extracelular/metabolismo , Espectrometria de Massas , Processamento de Proteína Pós-Traducional , Proteína-Lisina 6-Oxidase/metabolismoRESUMO
Background Low nuclear grade ductal carcinoma in situ (DCIS) identified at biopsy can be upgraded to intermediate to high nuclear grade DCIS at surgery. Methods that confirm low nuclear grade are needed to consider nonsurgical approaches for these patients. Purpose To develop a preoperative model to identify low nuclear grade DCIS and to evaluate factors associated with low nuclear grade DCIS at biopsy that was not upgraded to intermediate to high nuclear grade DCIS at surgery. Materials and Methods In this retrospective study, 470 women (median age, 50 years; interquartile range, 44-58 years) with 477 pure DCIS lesions at surgical histopathologic evaluation were included (January 2010 to December 2015). Patients were divided into the training set (n = 330) or validation set (n = 147) to develop a preoperative model to identify low nuclear grade DCIS. Features at US (mass, nonmass) and at mammography (morphologic characteristics, distribution of microcalcification) were reviewed. The upgrade rate of low nuclear grade DCIS was calculated, and multivariable regression was used to evaluate factors for associations with low nuclear grade DCIS that was not upgraded later. Results A preoperative model that included lesions manifesting as a mass at US without microcalcification and no comedonecrosis at biopsy was used to identify low nuclear grade DCIS, with a high area under the receiver operating characteristic curve of 0.97 (95% CI: 0.94, 1.00) in the validation set. The upgrade rate of low nuclear grade DCIS at biopsy was 38.8% (50 of 129). Ki-67 positivity (odds ratio, 0.04; 95% CI: 0.0003, 0.43; P = .005) was inversely associated with constant low nuclear grade DCIS. Conclusion The upgrade rate of low nuclear grade ductal carcinoma in situ (DCIS) at biopsy to intermediate to high nuclear grade DCIS at surgery occurred in more than a third of patients; low nuclear grade DCIS at final histopathologic evaluation could be identified if the mass was viewed at US without microcalcifications and had no comedonecrosis at histopathologic evaluation of biopsy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Rahbar in this issue. An earlier incorrect version appeared online. This article was corrected on April 14, 2022.
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Calcinose , Carcinoma Intraductal não Infiltrante , Calcinose/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Masculino , Mamografia/métodos , Pessoa de Meia-Idade , Curva ROC , Estudos RetrospectivosRESUMO
The APOE genotype is the most prominent genetic risk factor for the development of late-onset Alzheimer''s disease (LOAD); however, the underlying mechanisms remain unclear. In the present study, we found that the sialylation profiles of ApoE protein in the human brain are significantly different among the three isoforms, with ApoE2 exhibiting the most abundant sialic acid modification whereas ApoE4 had the least. We further observed that the sialic acid moiety in ApoE2 significantly affected the interaction between ApoE2 and Aß peptides. The removal of sialic acid in ApoE2 increased the ApoE2 binding affinity for the Aß17-24 region of Aß and promoted Aß fibrillation. These findings provide a plausible explanation for the well-documented differential roles of ApoE isoforms in Aß pathogenesis. Specifically, compared to the other two isotypes, the higher expression of sialic acid in ApoE2 may contribute to the less potent interaction between ApoE2 and Aß and ultimately the slower rate of brain Aß deposition, a mechanism thought to underlie ApoE2-mediated decreased risk for AD. Future studies are warranted to determine whether the differential sialylation in ApoE isoforms may also contribute to some of their other distinct properties, such as their divergent preferences in associations with lipids and lipoproteins, as well as their potential impact on neuroinflammation through modulation of microglial Siglec activity. Overall, our findings lead to the insight that the sialic acid structure is an important posttranslational modification (PTM) that alters ApoE protein functions with relevance for AD.
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Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Apolipoproteínas E/metabolismo , Isoformas de Proteínas/metabolismo , Encéfalo/metabolismo , Humanos , Ácido N-Acetilneuramínico/metabolismoRESUMO
BACKGROUND. Postoperative mammograms present interpretive challenges due to postoperative distortion and hematomas. The application of digital breast tomosyn-thesis (DBT) and artificial intelligence-based computer-aided detection (AI-CAD) after breast-conserving therapy (BCT) has not been widely investigated. OBJECTIVE. The purpose of our study was to assess the impact of additional DBT or AI-CAD on recall rate and diagnostic performance in women undergoing mammographic surveillance after BCT. METHODS. This retrospective study included 314 women (mean age, 53.3 ± 10.6 [SD] years; four with bilateral breast cancer) who underwent BCT followed by DBT (mean interval from surgery to DBT, 15.2 ± 15.4 months). Three breast radiologists independently reviewed images in three sessions: digital mammography (DM), DM with DBT (DM plus DBT), and DM with AI-CAD (DM plus AI-CAD). Recall rates and diagnostic performance were compared between DM, DM plus DBT, and DM plus AI-CAD using the readers' mean results. RESULTS. Of the 314 women, six breast recurrences (three ipsilateral and three contralateral) had developed at the time of surveillance mammography. The ipsilateral breast recall rate was lower for DM plus AI-CAD (1.9%) than for DM (11.2%) or DM plus DBT (4.1%) (p < .001). The contralateral breast recall rate was significantly lower for DM plus AI-CAD (1.5%, p < .001) than for DM (6.6%) but for not DM plus DBT (2.7%, p = .08). In the ipsilateral breast, accuracy was higher for DM plus AI-CAD (97.0%) than for DM (88.5%) or DM plus DBT (94.8%) (p < .05); specificity was higher for DM plus AI-CAD (98.3%) than for DM (89.3%) or DM plus DBT (96.1%) (p < .05); sensitivity was significantly lower for DM plus AI-CAD (22.2%) than for DM (66.7%, p = .03) but not DM plus DBT (22.2%, p > .99). In the contralateral breast, accuracy was significantly higher for DM plus AI-CAD (97.1%) than for DM (92.5%, p < .001) but not DM plus DBT (96.1%, p = .25); specificity was significantly higher for DM plus AI-CAD (98.6%) than for DM (93.7%, p < .001) but not DM plus DBT (97.5%) (p = .09); sensitivity was not different between DM (33.3%), DM plus DBT (22.2%), and DM plus AI-CAD (11.1%) (p > .05). CONCLUSION. After BCT, adjunct DBT or AI-CAD reduced recall rates and improved accuracy in the ipsilateral and contralateral breasts compared with DM. In the ipsilateral breast, the addition of AI-CAD resulted in a lower recall rate and higher accuracy than the addition of DBT. CLINICAL IMPACT. AI-CAD may help address the challenges of interpreting post-BCT surveillance mammograms.
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Inteligência Artificial , Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Mastectomia Segmentar , Recidiva Local de Neoplasia/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Mama/cirurgia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Lysyl oxidase-like 2 (LOXL2) has emerged as a promising therapeutic target against metastatic/invasive tumors and organ and tissue fibrosis. LOXL2 catalyzes the oxidative deamination of lysine and hydroxylysine residues in extracellular matrix (ECM) proteins to promote crosslinking of these proteins, and thereby plays a major role in ECM remodeling. LOXL2 secretes as 100-kDa full-length protein (fl-LOXL2) and then undergoes proteolytic cleavage of the first two scavenger receptor cysteine-rich (SRCR) domains to yield 60-kDa protein (Δ1-2SRCR-LOXL2). This processing does not affect the amine oxidase activity of LOXL2 in vitro. However, the physiological importance of this cleavage still remains elusive. In this study, we focused on characterization of biophysical properties of fl- and Δ1-2SRCR-LOXL2s (e.g., oligomeric states, molecular weights, and hydrodynamic radii in solution) to gain insight into the structural role of the first two SRCR domains. Our study reveals that fl-LOXL2 exists predominantly as monomer but also dimer to the lesser extent when its concentration is <~1 mM. The hydrodynamic radius (Rh) determined by multi-angle light scattering coupled with size exclusion chromatography (SEC-MALS) indicates that fl-LOXL2 is a moderately asymmetric protein. In contrast, Δ1-2SRCR-LOXL2 exists solely as monomer and its Rh is in good agreement with the predicted value. The Rh values calculated from a 3D modeled structure of fl-LOXL2 and the crystal structure of the precursor Δ1-2SRCR-LOXL2 are within a reasonable margin of error of the values determined by SEC-MALS for fl- and Δ1-2SRCR-LOXL2s in mature forms in this study. Based on superimposition of the 3D model and the crystal structure of Δ1-2SRCR-LOXL2 (PDB:5ZE3), we propose a configuration of fl-LOXL2 that explains the difference observed in Rh between fl- and Δ1-2SRCR-LOXL2s in solution.
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Aminoácido Oxirredutases/química , Aminoácido Oxirredutases/metabolismo , Linhagem Celular , Cristalografia por Raios X , Humanos , Hidrodinâmica , Modelos Moleculares , Domínios Proteicos , Multimerização Proteica , Estrutura Terciária de Proteína , ProteóliseRESUMO
BACKGROUND: Because no prior studies have evaluated the chronological trends of ductal carcinoma in situ (DCIS) despite the increasing number of surgeries performed for DCIS, this study analyzed how the clinical, radiologic, and pathologic characteristics of DCIS changed during a 10-year period. METHODS: Of 7123 patients who underwent primary breast cancer surgery at a single institution from 2006 to 2015, 792 patients with pure DCIS were included in this study. The chronological trends of age, symptoms, method for detecting either mammography or ultrasonography, tumor size, nuclear grade, comedonecrosis, and molecular markers were calculated using Poisson regression for all patients and asymptomatic patients. RESULTS: During 10 years, DCIS surgery rates significantly increased (p < 0.001). Despite the high percentage of DCIS detected on mammography, the detection rate for DCIS by mammography significantly decreased (97.3% in 2006 to 67.6% in 2015; p = 0.025), whereas the detection rate by ultrasound significantly increased (2.7% to 31.0%; p < 0.001). Conservation surgery rates (odds ratio [OR], 1.058), low-to-intermediate nuclear grade rates (OR, 1.069), and the absence of comedonecrosis (OR, 1.104) significantly increased over time (all p < 0.05). Estrogen receptor (ER) negativity (OR, 0.935) and human epidermal growth factor receptor 2 (HER2) positivity rates (OR, 0.953) significantly decreased (all p < 0.05). The same trends were observed for the 613 asymptomatic patients. CONCLUSION: The rate of DCIS detected on ultrasound only significantly increased during 10 years. Low-to-intermediate nuclear grade rates significantly increased, whereas ER negativity and HER2 positivity rates significantly decreased during the same period. These findings suggest that DCIS detected on screening ultrasound is less aggressive than DCIS detected on mammography.
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Neoplasias da Mama , Carcinoma in Situ , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mamografia , Estudos RetrospectivosRESUMO
Background In the post-American College of Surgeons Oncology Group Z0011 trial era, radiologists have increasingly focused on excluding high-level or advanced axillary lymph node metastasis (ALNM) by using an additional MRI scan positioned higher than lower axillae; however, the value of these additional scans remains undetermined. Purpose To evaluate whether a standard MRI protocol is sufficient to exclude high-level or advanced ALNM in breast cancer or additional MRI of entire axilla is needed. Materials and Methods This retrospective study evaluated women with invasive breast cancer who underwent breast MRI from April 2015 to December 2016. Some underwent neoadjuvant chemotherapy (NAC) and others underwent upfront surgery. Standard (routine axial scans including the lower axillae) and combined (routine axial scans plus additional scans including the entire axilla) MRI protocols were compared for high-level or advanced ALNM detection. Clinical-pathologic characteristics were analyzed. Uni- and multivariable logistic regression was performed to identify predictors of high-level or advanced ALNM. Results A total of 435 women (mean age ± standard deviation, 52 years ± 11) were evaluated (65 in the NAC group, 370 in the non-NAC group). With the standard MRI protocol, predictors of high-level ALNM were peritumoral edema (odds ratio [OR], 12.3; 95% CI: 3.9, 39.4; P < .001) and positive axilla (OR, 5.9; 95% CI: 2.0, 15.2; P < .001). Only three of 289 women with negative axillae without peritumoral edema had high-level ALNM. Predictors of advanced ALNM were positive axillae (OR, 8.9; 95% CI: 3.7, 21.5; P < .001) and peritumoral edema (OR, 2.8; 95% CI: 1.1, 6.9; P = .03). Only six of 310 women who had negative axillae without peritumoral edema had advanced ALNM. Conclusion The performance of standard MRI was satisfactory in excluding high-level and advanced axillary lymph node metastasis in most patients with breast cancer. However, the presence of peritumoral edema or positive axillae in the MRI findings emphasizes the benefits of a combined MRI protocol. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Abe in this issue.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Mama/diagnóstico por imagem , Mama/patologia , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the diagnostic performances and unnecessary fine-needle aspiration (FNA) rates of two point-scale based TIRADS and compare them with a modified version using the ACR TIRADS' size thresholds. METHODS: Our Institutional Review Board approved this retrospective study and waived the requirement for informed consent. A total of 2106 thyroid nodules 10 mm or larger in size in 2084 patients with definitive cytopathologic findings were included. Ultrasonography categories were assigned according to each guideline. We applied the ACR TIRADS' size thresholds for FNA to the Kwak TIRADS and defined it as the modified Kwak TIRADS (mKwak TIRADS). Diagnostic performances and unnecessary FNA rates were evaluated for both the original and modified guidelines. RESULTS: Of the original guidelines, the ACR TIRADS had higher specificity, accuracy, and area under the receiver operating characteristic curve (AUC) (63.1%, 68.9%, and 0.748, respectively). When the size threshold of the ACR TIRADS was applied to the Kwak TIRADS, the resultant mKwak TIRADS had higher specificity, accuracy, and AUC (64.7%, 70.3%, and 0.765, respectively) than the ACR TIRADS. The mKwak TIRADS also had a lower unnecessary FNA rate than the ACR TIRADS (54.8% and 56.4%, respectively). The false-negative rate of the Kwak TIRADS was the lowest (1.9%) among all TIRADS. CONCLUSION: The modified Kwak TIRADS incorporating the size thresholds of the ACR TIRADS showed higher diagnostic performance and a lower unnecessary FNA rate than the original point-scale based TIRADS. KEY POINTS: ⢠Of the original guidelines, the ACR TIRADS had the highest specificity, accuracy, and area under the receiver operating characteristic curve (AUC) (63.1%, 68.9%, and 0.748, respectively). ⢠When the size threshold of the ACR TIRADS was applied to the Kwak TIRADS, the resultant modified version of Kwak TIRADS had higher specificity, accuracy, and AUC (64.7%, 70.3%, and 0.765, respectively) than the ACR TIRADS. ⢠The false-negative rate of the Kwak TIRADS was the lowest (1.9%) among all TIRADS.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina , Humanos , Curva ROC , Estudos Retrospectivos , UltrassonografiaRESUMO
Sudden cardiac death is an unexpected death originating from the heart that occurs within an hour of the onset of symptoms. The main cause of sudden cardiac death is arrhythmia; however, diagnosing underlying structural heart disease significantly contributes to predicting the long-term risk. Cardiovascular CT and MR provide important information for diagnosing and evaluating structural heart disease, enabling the prediction and preparation of the risk of sudden cardiac death. Therefore, we would like to focus on the various structural heart diseases that increase the risk of clinically-important sudden cardiac death and the importance of imaging findings.
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OBJECTIVE: The aim of this study was to compare the survival rates of Korean females aged 40 to 49 years with breast cancer detected by supplemental screening ultrasound (US) or screening mammography alone. MATERIALS AND METHODS: This single-institution retrospective study included 240 patients with breast cancer (mean age, 45.1 ± 2.8 years) detected by US or mammography who had undergone breast surgery between 2003 and 2008. Medical records were reviewed for clinicopathologic characteristics and detection methods. Disease-free survival (DFS) and overall survival (OS) were compared between patients with breast cancer in the US and mammography groups using the log-rank test. Multivariable cox regression analysis was used to identify independent variables associated with DFS and OS. RESULTS: Among the 240 cases of breast cancer, 43 were detected by supplemental screening US and 197 by screening mammography (mean follow-up: 7.4 years, 93.3% with dense breasts). There were 19 recurrences and 16 deaths, all occurring in the mammography group. While the US group did not differ from the mammography group in tumor stage, the patients in this group were more likely to undergo breast-conserving surgery and radiation therapy than the mammography group. The US group also showed better DFS (p = 0.016); however, OS did not differ between the two groups (p = 0.058). In the multivariable analysis, the US group showed a lower risk of recurrence (hazard ratio, 0.097; 95% confidence interval, 0.001-0.705) compared to the mammography group. CONCLUSION: Our study found that Korean females aged 40-49 years with US-detected breast cancer showed better DFS than those with mammography-detected breast cancer. However, there were no statistically significant differences in OS.
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Neoplasias da Mama/diagnóstico , Mamografia , Ultrassonografia , Adulto , Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVES: To develop a radiomics score using ultrasound images to predict thyroid malignancy and to investigate its potential as a complementary tool to improve the performance of risk stratification systems. METHODS: We retrospectively included consecutive patients who underwent fine-needle aspiration (FNA) for thyroid nodules that were cytopathologically diagnosed as benign or malignant. Nodules were randomly assigned to a training and test set (8:2 ratio). A radiomics score was developed from the training set, and cutoff values based on the maximum Youden index (Rad_maxY) and for 5%, 10%, and 20% predicted malignancy risk (Rad_5%, Rad_10%, Rad_20%, respectively) were applied to the test set. The performances of the American College of Radiology (ACR) and the American Thyroid Association (ATA) guidelines were compared with the combined performances of the guidelines and radiomics score with interpretations from expert and nonexpert readers. RESULTS: A total of 1624 thyroid nodules from 1609 patients (mean age, 50.1 years [range, 18-90 years]) were included. The radiomics score yielded an AUC of 0.85 (95% CI: 0.83, 0.87) in the training set and 0.75 (95% CI: 0.69, 0.81) in the test set (Rad_maxY). When the radiomics score was combined with the ACR or ATA guidelines (Rad_5%), all readers showed increased specificity, accuracy, and PPV and decreased unnecessary FNA rates (all p < .05), with no difference in sensitivity (p > .05). CONCLUSION: Radiomics help predict thyroid malignancy and improve specificity, accuracy, PPV, and unnecessary FNA rate while maintaining the sensitivity of the ACR and ATA guidelines for both expert and nonexpert readers. KEY POINTS: ⢠The radiomics score yielded an AUC of 0.85 and 0.75 in the training and test set, respectively. ⢠For all readers, combining a 5% predicted malignancy risk cutoff for the radiomics score with the ACR and ATA guidelines significantly increased specificity, accuracy, and PPV and decreased unnecessary FNA rates, with no decrease in sensitivity. ⢠Radiomics can help predict malignancy in thyroid nodules in combination with risk stratification systems, by improving specificity, accuracy, and PPV and unnecessary FNA rates while maintaining sensitivity for both expert and nonexpert readers.
Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia , Estados UnidosRESUMO
ABSTRACT: Ductal carcinoma in situ (DCIS) has different prognostic factors according to the detection modality. The purpose of this study was to compare parameters from a radiomic analysis of ultrasonography (US) images for DCIS detected on screening mammography (MMG) and US and detected on screening US only. A total of 154 surgically confirmed DCIS visible on US were included. Regions of interest were drawn onto US images of DCIS, and texture analysis was performed. Lesions were classified into those detected by both US and MMG (the US-MMG group) and those detected by US only (the US group). Analysis parameters were compared between the US-MMG group and the US group. Ninety-six lesions were included in the US-MMG group and 58 lesions in the US group. Energy, entropy, maximum, mean absolute deviation, range, SD, and variance were significantly higher in the US-MMG group than the US group. Kurtosis, skewness, and uniformity were significantly lower in the US-MMG group than the US group. Among the 22 gray-level cooccurrence matrix parameters, 18, 21, 22, 20, and 21 parameters were significantly different between the 2 groups in 0, 45, 90, and 135 degrees and the average value. Among the 11 gray-level run-length matrix parameters, 6, 6, 7, 7, and 6 parameters were significantly different in 0, 45, 90, and 135 degrees and the average value. Inverse variance and gray-level nonuniformity were the most different features between the 2 groups. Screening-detected DCIS showed different radiomic features according to the detection modality.