Infiltrative pattern of invasion is independently associated with shorter survival and desmoplastic stroma markers FAP and THBS2 in mucinous ovarian carcinoma.

AIMS: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer histotype with generally good prognosis when diagnosed at an early stage. However, MOC with the infiltrative pattern of invasion has a worse prognosis, although to date studies have not been large enough to control for covariables. Data on reproducibility of classifying the invasion pattern are limited, as are molecular correlates for infiltrative invasion. We hypothesized that the invasion pattern would be associated with an aberrant tumour microenvironment. METHODS AND RESULTS: Four subspecialty pathologists assessed interobserver reproducibility of the pattern of invasion in 134 MOC. Immunohistochemistry on fibroblast activation protein (FAP) and THBS2 was performed on 98 cases. Association with survival was tested using Cox regression. The average interobserver agreement for the infiltrative pattern was moderate (kappa 0.60, agreement 86.3%). After reproducibility review, 24/134 MOC (18%) were determined to have the infiltrative pattern and this was associated with a higher risk of death, independent of FIGO stage, grade, and patient age in a time-dependent manner (hazard ratio [HR] = 10.2, 95% confidence interval [CI] 3.0-34.5). High stromal expression of FAP and THBS2 was more common in infiltrative MOC (FAP: 60%, THBS2: 58%, both P < 0.001) and associated with survival (multivariate HR for FAP: 1.5 [95% CI 1.1-2.1] and THBS2: 1.91 [95% CI 1.1-3.2]). CONCLUSIONS: The pattern of invasion should be included in reporting for MOC due to the strong prognostic implications. We highlight the histological features that should be considered to improve reproducibility. FAP and THBS2 are associated with infiltrative invasion in MOC.

Community-Engaged Implementation Strategies in Occupational Therapy: A Scoping Review.

IMPORTANCE:  Despite the potential of community-engaged implementation research (CEIR) in developing strategies to accelerate the translation of evidence-based interventions (EBIs), there is a noticeable knowledge gap in the current state of CEIR in occupational therapy. A synthesis of the concept, purpose, and operationalization of CEIR is necessary. OBJECTIVE:  To identify the contexts, purposes, and operationalization of CEIR, focusing on implementation strategies in occupational therapy. DATA SOURCES:  PubMed/MEDLINE, Embase, CINAHL, Scopus, and Web of Science. STUDY SELECTION AND DATA COLLECTION:  We included studies that were explicit and intentional about CEIR and that focused on implementation strategies to support the translation of occupational therapy interventions, clinical guidelines, practice models, theories, or assessments. We extracted the research context (e.g., partners, recruitment), purpose (e.g., why community-engaged research was used), and operationalization (e.g., community engagement [CE] activities, how their findings inform the research) using thematic analysis. FINDINGS:  Of 3,219 records, 6 studies were included. Involved partners were mainly occupational therapy practitioners from existing networks. CEIR that focuses on implementation strategies informs various aspects of research design, ranging from study design to sustainability, by developing community-academia partnerships, building implementation capacity, and creating implementation strategies across diverse research areas. Current research has used various but mostly traditional CE activities (e.g., focus groups). CONCLUSIONS AND RELEVANCE:  We synthesized evidence on CEIR focused on implementation strategies in occupational therapy. Intentional efforts are needed to collaborate with diverse partners, explore innovative CE activities, produce equitable outputs, and develop multilevel implementation strategies to accelerate the translation of EBIs into practice. Plain-Language Summary: In this review, we synthesize evidence on the contexts, purposes, and operationalization of community-engaged implementation research (CEIR), focusing on implementation strategies in occupational therapy research. We found that current implementation efforts mainly rely on occupational therapy practitioners as community partners and use traditional recruitment methods and community engagement activities. In turn, they develop implementation strategies that mainly target practitioners without comprehensive, multilevel implementation support. We suggest more equitable collaboration with diverse partners to effectively promote the implementation and dissemination of evidence-based interventions in occupational therapy practice.

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

BACKGROUND: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC. METHODS: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis. RESULTS: Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant. CONCLUSION: We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

Recurrence is Not Associated with Margin Status in Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial neoplasm of the breast. The proper extent of resection is still under debate. This study aimed to investigate the optimal surgical margin to prevent recurrence after surgery for PT and to evaluate risk factors for local recurrence (LR). METHODS: Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for PT at Seoul National University Bundang Hospital between July 2003 and February 2022 were reviewed. RESULTS: Of the 439 patients included, 285 were benign, 129 were borderline, and 25 were malignant. There was no statistically significant difference in 5-year disease-free survival (DFS) between margin-negative and margin-involved patients (87.3% vs. 85.1%, p = 0.081). When patients were classified into groups, according to margin status, as conventional (≥ 1 cm from tumor), close (< 1 cm from tumor), or involved, 5-year DFS rates were also similar (100% vs. 86.9% vs. 85.1%, p = 0.170). In subgroup analysis for different histologic grades, 5-year DFS was not affected by margin involvement. In univariate analysis, large tumor size (> 5 cm; hazard ratio [HR] 2.857, p = 0.028) and infiltrative tumor border (HR 3.096, p = 0.012) were independent risk factors for LR. Further multivariate analysis found both factors to be prognostic. CONCLUSIONS: Recurrence was not significantly influenced by margin status in all histological grades. In benign and borderline tumors, local excision without wide surgical margins could be sufficient, and watchful waiting could be an option for patients with positive margins after initial surgery.

Multicentre external validation of a commercial artificial intelligence software to analyse chest radiographs in health screening environments with low disease prevalence.

OBJECTIVES: To externally validate the performance of a commercial AI software program for interpreting CXRs in a large, consecutive, real-world cohort from primary healthcare centres. METHODS: A total of 3047 CXRs were collected from two primary healthcare centres, characterised by low disease prevalence, between January and December 2018. All CXRs were labelled as normal or abnormal according to CT findings. Four radiology residents read all CXRs twice with and without AI assistance. The performances of the AI and readers with and without AI assistance were measured in terms of area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. RESULTS: The prevalence of clinically significant lesions was 2.2% (68 of 3047). The AUROC, sensitivity, and specificity of the AI were 0.648 (95% confidence interval [CI] 0.630-0.665), 35.3% (CI, 24.7-47.8), and 94.2% (CI, 93.3-95.0), respectively. AI detected 12 of 41 pneumonia, 3 of 5 tuberculosis, and 9 of 22 tumours. AI-undetected lesions tended to be smaller than true-positive lesions. The readers' AUROCs ranged from 0.534-0.676 without AI and 0.571-0.688 with AI (all p values < 0.05). For all readers, the mean reading time was 2.96-10.27 s longer with AI assistance (all p values < 0.05). CONCLUSIONS: The performance of commercial AI in these high-volume, low-prevalence settings was poorer than expected, although it modestly boosted the performance of less-experienced readers. The technical prowess of AI demonstrated in experimental settings and approved by regulatory bodies may not directly translate to real-world practice, especially where the demand for AI assistance is highest. KEY POINTS: • This study shows the limited applicability of commercial AI software for detecting abnormalities in CXRs in a health screening population. • When using AI software in a specific clinical setting that differs from the training setting, it is necessary to adjust the threshold or perform additional training with such data that reflects this environment well. • Prospective test accuracy studies, randomised controlled trials, or cohort studies are needed to examine AI software to be implemented in real clinical practice.

Evaluation of fully automated commercial software for Agatston calcium scoring on non-ECG-gated low-dose chest CT with different slice thickness.

OBJECTIVES: To evaluate commercial deep learning-based software for fully automated coronary artery calcium (CAC) scoring on non-electrocardiogram (ECG)-gated low-dose CT (LDCT) with different slice thicknesses compared with manual ECG-gated calcium-scoring CT (CSCT). METHODS: This retrospective study included 567 patients who underwent both LDCT and CSCT. All LDCT images were reconstructed with a 2.5-mm slice thickness (LDCT2.5-mm), and 453 LDCT scans were reconstructed with a 1.0-mm slice thickness (LDCT1.0-mm). Automated CAC scoring was performed on CSCT (CSCTauto), LDCT1.0-mm, and LDCT2.5-mm images. The reliability of CSCTauto, LDCT1.0-mm, and LDCT2.5-mm was compared with manual CSCT scoring (CSCTmanual) using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Agreement, in CAC severity category, was analyzed using weighted kappa statistics. Diagnostic performance at various Agatston score cutoffs was also calculated. RESULTS: CSCTauto, LDCT1.0-mm, and LDCT2.5-mm demonstrated excellent agreement with CSCTmanual (ICC [95% confidence interval, CI]: 1.000 [1.000, 1.000], 0.937 [0.917, 0.952], and 0.955 [0.946, 0.963], respectively). The mean difference with 95% limits of agreement was lower with LDCT1.0-mm than with LDCT2.5-mm (19.94 [95% CI, -244.0, 283.9] vs. 45.26 [-248.2, 338.7]). Regarding CAC severity, LDCT1.0-mm achieved almost perfect agreement, and LDCT2.5-mm achieved substantial agreement (kappa [95% CI]: 0.809 [0.776, 0.838], 0.776 [0.740, 0.809], respectively). Diagnostic performance for detecting Agatston score ≥ 400 was also higher with LDCT1.0-mm than with LDCT2.5-mm (F1 score, 0.929 vs. 0.855). CONCLUSIONS: Fully automated CAC-scoring software with both CSCT and LDCT yielded excellent reliability and agreement with CSCTmanual. LDCT1.0-mm yielded more accurate Agatston scoring than LDCT2.5-mm using fully automated commercial software. KEY POINTS: • Total Agatston scores and all vessels of CSCTauto, LDCT1.0-mm, and LDCT2.5-mm demonstrated excellent agreement with CSCTmanual (all ICC > 0.85). • The diagnostic performance for detecting all Agatston score cutoffs was better with LDCT1.0-mm than with LDCT2.5-mm. • This automated software yielded a lower degree of underestimation compared with methods described in previous studies, and the degree of underestimation was lower with LDCT1.0-mm than with LDCT2.5-mm.

Feasibility and Implementation Determinants of a Structured Goal Setting and Goal Management System.

IMPORTANCE: There is no evidence-based system to guide occupational therapists in implementing theory-based, client-engaged goal setting and goal management. A new system is needed to support high-quality goal setting and goal management. OBJECTIVE: To determine the acceptability, appropriateness, feasibility, credibility, and expectancy of a new structured theory-based, client-engaged goal setting and goal management system, called MyGoals, for occupational therapists. We explored MyGoals' implementation determinants, potential positive outcomes, and comparative advantages. DESIGN: This was a mixed-methods feasibility study. SETTING: Community. PARTICIPANTS: Occupational therapists (N = 7). OUTCOMES AND MEASURES: Acceptability, appropriateness, and feasibility were assessed using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Credibility and expectancy were assessed with the Credibility and Expectancy Questionnaire (CEQ). Semistructured 1:1 interviews were conducted to explore occupational therapy perspectives on MyGoals and its implementation-related factors. RESULTS: MyGoals had high AIM (M = 18.1, SD = 1.9), IAM (M = 17.9, SD = 2.2), FIM (M = 17.3, SD = 2.1) scores and high CEQ Credibility (M = 22.1, SD = 5.0) and Expectancy (M = 20.6, SD = 4.3) scores. Interview data revealed suggestions to improve MyGoals, implementation determinants across the individuals involved, inner setting, and intervention characteristic domains, client- and clinician-related potential positive outcomes, and comparative advantages. CONCLUSIONS AND RELEVANCE: MyGoals is an acceptable, appropriate, feasible, credible, and promising system to guide occupational therapists in implementing theory-based, client-engaged goal setting and goal management for adults with chronic conditions in community-based rehabilitation. What This Article Adds: MyGoals is an easy-to-use, appealing, and helpful system to support occupational therapists in delivering theory-based goal setting and goal management components and to enable adults with chronic conditions to actively engage in their rehabilitation. This study supports the usefulness of MyGoals in community-based rehabilitation to improve goal setting and goal management quality and personally meaningful rehabilitation goal achievement in this population.

Endometrial neuroendocrine carcinoma and undifferentiated carcinoma are distinct entities with overlap in neuroendocrine marker expression.

AIMS: Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UDECs) frequently harbour genomic activation of switch/sucrose non-fermentable (SWI/SNF)-complex proteins, and can show histological overlap with neuroendocrine carcinoma (NEC). The aim of this study was to compare the extent of the expression of neuroendocrine markers, SWI/SNF proteins and mismatch repair (MMR) proteins in DDEC/UDEC and NEC. METHODS AND RESULTS: The extent of expression of synaptophysin, chromogranin, CD56, ARID1A, ARID1B, SMARCA4, SMARCB1 and MMR proteins was evaluated by immunohistochemistry on 44 SWI/SNF-deficient DDECs/UDECs and 15 NECs. Thirty-three of 44 (75%) DDECs/UDECs showed expression of at least one neuroendocrine marker, with 18 of 44 (41%) expressing two or more neuroendocrine markers, whereas all 15 NECs showed expression of at least one neuroendocrine marker, with 14 of 15 (93%) expressing two or more neuroendocrine markers. Neuroendocrine marker expression in DDECs/UDECs was typically focal when present, with average extents of 17%, 4% and 8% for synaptophysin, chromogranin and CD56 in the positive cases, respectively, in contrast to 73%, 40% and 62% in the positive NEC cases, respectively. All 15 NECs showed intact expression of SWI/SNF-complex proteins, except for one that showed isolated loss of ARID1A. Thirty-eight of 44 DDECs/UDECs were MMR-abnormal (34 with loss of MLH1 and PMS2, and four with loss of PMS2 alone), whereas all NECs retained MMR protein expression. CONCLUSIONS: Our study demonstrates frequent but typically focal neuroendocrine marker expression in SWI/SNF-deficient DDECs/UDECs, whereas NECs typically express two or more neuroendocrine markers, with diffuse expression of at least one marker. ARID1B, SMARCA4 and SMARCB1 immunohistochemistry can be used to aid in the differentiation between DDEC/UDEC and NEC.

Differentiating pulmonary metastasis from benign lung nodules in thyroid cancer patients using dual-energy CT parameters.

OBJECTIVES: To explore the importance of quantitative characteristics of dual-energy CT (DECT) between pulmonary metastasis and benign lung nodules in thyroid cancer. METHODS: In this retrospective study, we identified 63 patients from our institution's database with pathologically proven thyroid cancer who underwent DECT to assess pulmonary metastasis. Among these patients, 22 had 55 pulmonary metastases, and 41 had 97 benign nodules. If nodules showed increased iodine uptake on I-131 single-photon emission computed tomography-computed tomography or increased size in follow-up CT, they were considered metastatic. We compared the clinical findings and DECT parameters of both groups and performed a receiver operating characteristic analysis to evaluate the optimal cutoff values of the DECT parameters. RESULTS: Patients with metastases were significantly older than patients with benign nodules (p = 0.048). The DECT parameters of the metastatic nodules were significantly higher than those of the benign nodules (iodine concentration [IC], 5.61 ± 2.02 mg/mL vs. 1.61 ± 0.98 mg/mL; normalized IC [NIC], 0.60 ± 0.20 vs. 0.16 ± 0.11; NIC using pulmonary artery [NICPA], 0.60 ± 0.44 vs. 0.15 ± 0.11; slope of the spectral attenuation curves [λHU], 5.18 ± 2.54 vs. 2.12 ± 1.39; and Z-effective value [Zeff], 10.0 ± 0.94 vs. 8.79 ± 0.75; all p < 0.001). In the subgroup analysis according to nodule size, all DECT parameters of the metastatic nodules in all subgroups were significantly higher than those of the benign nodules (all p < 0.05). The cutoff values for IC, NIC, λHU, NICPA, and Zeff for diagnosing metastases were 3.10, 0.29, 3.57, 0.28, and 9.34, respectively (all p < 0.001). CONCLUSIONS: DECT parameters can help to differentiate metastatic and benign lung nodules in thyroid cancer. KEY POINTS: • DECT parameters can help to differentiate metastatic and benign lung nodules in patients with thyroid cancer. • DECT parameters showed a significant difference between benign lung nodules and lung metastases, even for nodules with diameters ≥ 3 mm and < 5 mm. • Among the DECT parameters, the highest diagnostic accuracy for differentiating pulmonary metastases from benign lung nodules was achieved with the NIC and IC, followed by the NICPA and λHU, and their cutoff values were 0.29, 3.10, 0.28, and 3.57, respectively.

Person-Centered Goal Setting: A Systematic Review of Intervention Components and Level of Active Engagement in Rehabilitation Goal-Setting Interventions.

OBJECTIVE: This systematic review aims to examine (1) what components are used in current person-centered goal-setting interventions for adults with health conditions in rehabilitation and (2) the extent to which the engagement of people in their rehabilitation goal setting is encouraged. DATA SOURCES: PubMed/MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, Scopus, and Web of Science from inception to November 2020. STUDY SELECTION: Primary inclusion criteria were peer-reviewed articles that evaluated person-centered goal-setting interventions for adults with health conditions in rehabilitation. Two independent reviewers screened 28,294 records, and 22 articles met inclusion criteria. DATA EXTRACTION: Two reviewers independently completed data extraction and quality assessment using the Physiotherapy Evidence Database (PEDRo) scale based on the original authors' descriptions, reports, and protocol publications. Any discrepancies were resolved by consensus or in consultation with another senior reviewer. DATA SYNTHESIS: Using narrative synthesis, we found that current person-centered goal setting has variability in their inclusion of intervention components. A considerable number of components are underimplemented in current practice, with formulation of coping plan and follow-up being most commonly left out. The active engagement of people does appear to be promoted within the components that are included in the interventions. Nine studies were high-quality defined as a total PEDro scale score of 6 or above. CONCLUSIONS: Although current person-centered goal setting encourages the active engagement of people, many of these interventions lack components considered important for supporting goal achievement and optimal outcomes. Future practice may be improved by incorporating a comprehensive set of goal-setting components and encouraging the active engagement of people throughout the entire goal-setting process. Together, these practices may facilitate the achievement of meaningful rehabilitation goals and improve rehabilitation outcomes for adults with health conditions.

Loss of ARID1B and SMARCB1 expression are specific for the diagnosis of dedifferentiated/undifferentiated carcinoma in tumours of the upper gynaecological tract and cervix.

AIMS: Genomic inactivation of ARID1B in ARID1A-inactivated tumour and genomic inactivation of SMARCB1 represent two recurrent mechanisms, core SWItch/sucrose non-fermentable (SWI/SNF) complex inactivation, that are associated with de-differentiation in endometrial carcinoma. Approximately one-third of dedifferentiated/undifferentiated endometrial carcinomas (DDEC/UEC) show loss of ARID1B expression with a minor subset showing loss of SMARCB1 expression, but little is known regarding the specificity of ARID1B or SMARCB1 loss in gynaecological tract tumours in general. The aim of this study was to examine the frequency of ARID1B and SMARCB1 loss by immunohistochemistry in a series of gynaecological tract epithelial/mesenchymal neoplasms. METHODS AND RESULTS: We evaluated 1849 tumours that included 748 endometrial carcinomas, 101 uterine carcinosarcomas/adenosarcomas, 64 uterine sarcomas, 221 cervical carcinomas and 715 ovarian carcinomas/borderline tumours by tissue microarrays (TMA). We observed ARID1B loss in 35 of 86 (41%) and SMARCB1 loss in three of 86 (3%) DDEC/UEC, but not in any other uterine tumour types examined. ARID1B-deficient DDEC/UEC also showed concurrent loss of ARID1A expression. All SMARCB1-deficient tumours showed loss of MLH1 and PMS2, while 29 of 35 ARID1B-deficient tumours showed loss of MLH1 and PMS2 or loss of MSH6. All ovarian carcinomas/borderline tumours and cervical carcinomas showed intact expression of ARID1B and SMARCB1. CONCLUSION: Our findings indicate that the loss of expression of ARID1B or SMARCB1 by immunohistochemistry is highly specific for undifferentiated carcinoma among tumours of the upper gynaecological tract and cervix, and therefore can be used to identify these highly aggressive malignant tumours.

Nitrates administered by spray versus tablet: comparison of coronary vasodilation on CT angiography.

OBJECTIVES: To compare the coronary vasodilation effects of spray with those induced by tablet administration in coronary CT angiography (CCTA). METHODS: A total of 2024 patients who underwent CCTA were identified for this retrospective study, including 828 patients with spray (spray group) and 1169 with tablets (tablet group). Of these, 93 patients underwent CCTA at least twice using both spray and tablets. The number of measurable segments and diameters of all 18 segments was measured. The number of measurable segments was compared between groups. RESULTS: No statistically significant differences were evident between these two groups in terms of clinical characteristics. All coronary segments except the ramus intermedius (RI) and left posterior descending artery (L-PDA) were significantly larger in the spray group than in the tablet group (all p < 0.001). In peripheral and branch vessels, as well as in central and main coronary arteries, the diameters were significantly larger in the spray group than in the tablet group (all p < 0.001). Although not always statistically significant, all coronary segments tended to be more measurable on CCTA with spray than with tablet. In the subgroup that underwent CCTA twice using both spray and tablets, all coronary segments except the RI, obtuse marginal artery 2 (OM2), and L-PDA were significantly larger in the spray group than in the tablet group (all p < 0.05). CONCLUSION: Lingual isosorbide dinitrate (ISDN) spray was more efficacious than sublingual nitroglycerin (NTG) tablets in coronary vasodilation for CCTA. Therefore, lingual ISDN spray should be preferred over sublingual NTG tablets for CCTA. KEY POINTS: • Lingual ISDN spray was more efficacious than sublingual NTG tablet for coronary vasodilation in coronary CT angiography, even in elderly patients. • The diameters of all coronary segments except RI and L-PDA were significantly larger, and there were significantly more coronary segments greater than 1.5 mm, except RI and L-PDA, in the spray group than in the tablet group in the whole study group. • Even in peripheral and branch vessels, the diameters of coronary arteries were significantly larger in the spray group than in the tablet group, and they were also larger in elderly patients.

Impact of Zr6 Node in a Metal-Organic Framework for Adsorptive Removal of Antibiotics from Water.

Quinolone-based antibiotics commonly detected in surface, ground, and drinking water are difficult to remove and therefore pose a threat as organic contaminants of aqueous environment. We performed adsorptive removal of quinolone antibiotics, nalidixic acid and ofloxacin, using a zirconium-porphyrin-based metal-organic framework (MOF), PCN-224. PCN-224 exhibits the highest adsorption capacities for both nalidixic acid and ofloxacin among those reported for MOFs to date. The accessible metal sites of Zr metal nodes are responsible for efficient adsorptive removal. This study offers a pragmatic approach to design MOFs optimized for adsorptive removal of antibiotics.

Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity.

BACKGROUND: Multiplicity in breast cancer is common. Studies on multiple breast cancers have revealed high concordance in biomarker status among individual lesions. However, genomic differences among multiple lesions are not well-established. We aimed to investigate the potential genomic heterogeneity of multiple breast cancer. METHODS: Twenty-one patients with radiologically and histologically evident multiple breast cancer with similar histology were included. Two lesions from each of the 21 patients were selected, and biomarker status was evaluated for each lesion. Capture-based targeted next-generation sequencing was performed using a cancer gene panel consisting of 170 genes. RESULTS: We identified discordance in intrinsic subtype in 2 (10%) of the 21 patients. Pathogenic mutations were detected in 13 of the 21 patients, of whom 11 shared oncogenic variants in the two lesions. The remaining two patients yielded different mutation results for TP53, ATM, and PIK3CA. Difference in copy number alteration was observed in 7 (33%) of the 21 patients including ERBB2 (n = 2), FGFR1 (n = 2), and FGFR2 (n = 1) genes. CONCLUSION: Despite similar histologic features of the individual lesions, inter-lesional genomic difference was identified in more than one-third of the patients. Inter-lesional genomic heterogeneity needs to be considered when performing a genomic test in multiple breast cancers.

External validation and modification of nomogram for predicting positive resection margins before breast conserving surgery.

PURPOSE: A positive resection margin after breast conserving surgery (BCS) is the most important risk factor for tumor recurrence. In 2012, Seoul National University Hospital (SNUH) breast surgery team developed a nomogram for predicting positive resection margins before BCS to provide individual surgical plans that could reduce local recurrence without increasing re-excision rates. The purpose of this study was to validate this nomogram using an external cohort and to test if addition of surgeon-related factor could improve its use as a predictive model. METHODS: A total of 419 patients with breast cancer who underwent BCS from January to December 2018 were retrospectively reviewed. Using the SNUH BCS nomogram, risk score for positive resection margins was calculated for 343 patients. The predictive accuracy of the nomogram was assessed, and multivariable logistic regression analyses were performed to evaluate the nomogram's predictive variables. RESULTS: The positive resection margin rate of the current external validation cohort was 13.5% (46 out of 343), compared to 14.6% (151 out of 1034) of the original study. The discrimination power of the SNUH BCS nomogram as measure by area under the receiver operating characteristics curve (AUC) was 0.656 [95% confidence interval (CI) 0.576-0.735]. This result is lower than expected value of 0.823 [95% CI 0.785-0.862], the AUC of the original study. Multivariable logistic regression analysis showed that, among the five nomogram variables, presence of tumor size discrepancy greater than 0.5 cm between MRI and ultrasonography (OR 2.445, p = 0.019) and presence of ductal carcinoma in situ on needle biopsy (OR 2.066, p = 0.048) were significantly associated with positive resection margins. Finally, the nomogram score was re-calculated by adding each surgeon's resection margin positive rate as odds ratio and the AUC was increased to 0.733. CONCLUSIONS: Validation of the SNUH BCS nomogram was not successful in the current study as much as its original publication. However, we could improve its predictive power by including surgeon-related factor. Before applying a published nomogram as a preoperative predictive model, we suggest each institution to validate the model and adjust it with surgeon-related factor. Addition of new factors to currently available nomograms holds promise for improving its applicability for breast cancer patients at the actual clinical level.

Identifying germline APOBEC3B deletion and immune phenotype in Korean patients with operable breast cancer.

BACKGROUND: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) is implicated in anti-viral immune response and cancer mutagenesis. Germline APOBEC3B deletion is associated with increased susceptibility to breast cancer. We aimed to evaluate the association between germline APOBEC3B deletion and clinical phenotypes of breast cancer in Korean patients with operable breast cancer. METHODS: Mononuclear blood cell DNA of 103 patients with operable breast cancer was collected at Seoul National University Bundang Hospital in 2009. The DNA was sequenced to analyze APOBEC3B deletion status. Further, tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor cells were measured using immunohistochemistry. RESULTS: Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3Bdel/del), one-one copy deletion (A3Bdel/wt), and no deletion (A3Bwt/wt), respectively. For other cancer susceptibility gene alterations, 9 (8.7%) patients were identified as pathogenic variants: RAD51D (n = 1), GJB2 (n = 1), BRCA1 (n = 1), BRCA2 (n = 2), ATM (n = 1), USH2A (n = 1), RET (n = 1), BARD1 (n = 1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer, such as age, family history of cancer, and bilateral breast cancer. Further, according to follow-up observations, APOBEC3B deletion was not predictive of disease-free survival. In ER+ subtype, a trend toward better survival was observed in patients with A3Bdel/del genotype as compared to patients with A3Bdel/wt and A3Bwt/wt genotype (log-rank, P = 0.25). In patients with sufficient tumor samples for the assessment of TIL (n = 63) and PD-L1 (n = 71), the A3Bdel/del genotype was significantly associated with high TILs (> 10%) than other tumor genotypes (6/7 patients in A3Bdel/del vs. 13/24 in A3Bdel/wt vs. 15/32 in A3Bwt/wt: Fisher's exact test, P = 0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients > 1% PD-L1 in A3Bdel/del vs. 4/26 in A3Bdel/wt vs. 8/38 in A3Bwt/wt: P = 0.901). CONCLUSION: We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3Bdel/del genotype and high TILs suggests that patients carrying this genotype could be potential candidates for immunotherapy.

Benign Breast Papilloma without Atypia: Outcomes of Surgical Excision versus US-guided Directional Vacuum-assisted Removal or US Follow-up.

Background Recent studies suggest that US-guided directional vacuum-assisted removal (DVAR) is a satisfactory alternative to surgery for benign papilloma of the breast and recommend discretionary diagnostic US follow-up without intervention. Purpose To compare the outcomes of benign papilloma without atypia diagnosed with core needle biopsy (CNB) in patients who underwent US-guided DVAR, US follow-up without intervention, or surgery. Materials and Methods This retrospective review included consecutive patients with benign papilloma without atypia diagnosed with US-guided CNB between January 2005 and September 2015. Five hundred female patients who underwent surgical excision (n = 206), US-guided DVAR (n = 233), or more than 2 years of US follow-up without intervention (n = 61) were included. The clinical and radiologic findings and cancer upgrade rate were compared among the three groups. Propensity score matching was performed for comparison of the upgrade rate in the surgery and US-guided DVAR groups. Results The mean patient age (±standard deviation) was 46.4 years ± 9.6. The upgrade rate to malignancy was 1.8% (nine of 500 patients; 95% confidence interval [CI]: 0.9%, 3.4%) in the total study population, 1.9% (four of 206 patients; 95% CI: 0.8%, 4.9%) after surgery, 2.1% (five of 233 patients; 95% CI: 0.9%, 4.9%) after US-guided DVAR, and 0% (0 of 61 patients; 95% CI: 0.0%, 5.9%) after US follow-up without intervention (P = .80); after propensity-score matching, the upgrade rate was 1.9% in the surgery group (three of 151 patients; 95% CI: 0.6%, 5.6%) and 3.3% in the US-guided DVAR group (five of 151 patients; 95% CI: 1.4%, 7.5%; P = .48). The recurrence rate after US-guided DVAR was 3.6% (six of 166 patients) during 24-65 months of follow-up; all recurrences were confirmed as benign at subsequent surgery. Fifty-nine of the 61 lesions in the group with US follow-up without intervention (97%) remained stable in size with no growth during a mean follow-up of 43.3 months (range, 25-130 months). Conclusion Low rates of upgrade, recurrence, and growth after US-guided directional vacuum-assisted removal and US follow-up without intervention suggest that benign papilloma without atypia can be managed more conservatively rather than undergoing surgical excision. © RSNA, 2019 Online supplemental material is available for this article.

Comparison of the Diagnostic Performance of Synthetic Versus Acquired High b-Value (1500 s/mm2 ) Diffusion-Weighted MRI in Women With Breast Cancers.

BACKGROUND: Acquired high b-value (>1000 s/mm2 ) diffusion-weighted imaging (DWI) has its strength in lesion detection. However, it is not easily used, due to a lower signal-to-noise ratio, eddy current distortions, and prolonged acquisition times. Synthetic DWI does not have these disadvantages because it is based on indirect acquisition, calculated in a voxel-wise manner. PURPOSE: To compare the diagnostic performance of synthetic and acquired high b-value (1500 s/mm2 ) DWI in women with breast cancer. STUDY TYPE: Retrospective. POPULATION: A total of 108 patients (median age 49 years [range 32-77]) with 133 breast cancers. FIELD STRENGTH/SEQUENCE: 3T, echo-planar imaging. ASSESSMENT: Three radiologists independently reviewed image sets of both synthetic (S-b1500) and acquired (A-b1500) high b-value DWI. Malignancy confidence of the lesion was scored using a 6-point Likert-type scale. STATISTICAL TEST: Jack-knife alternative free-response receiver-operating characteristic 1 (JAFROC1) analysis was used. Sensitivity and positive predictive value (PPV) were compared using generalized estimating equations. An independent t-test was used to compare the confidence. An intraclass correlation coefficient was calculated to compare interobserver agreement. RESULTS: The JAFROC1 figures of merit values were 0.816 and 0.808 in S-b1500 and A-b1500, respectively, with no statistically significant difference (P = 0.637). Sensitivity was higher in synthetic than in A-b1500 for readers 2 (P = 0.015) and 3 (P = 0.037). Although sensitivity was higher in S-b1500 than in A-b1500 for reader 1, the difference was not significant (P = 0.487). The PPV of S-b1500 was not significantly different from that of A-b1500 (P = 0.397). The malignancy confidence of true-positive tumors was higher in S-b1500 than in A-b1500 (P = 0.013). Interobserver agreement was good for both sequences. DATA CONCLUSIONS: The synthetic high b-value DWI may improve the diagnostic sensitivity for breast cancer detection without affecting PPV compared with acquired high b-value DWI. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:857-863.

Is the epicardial adipose tissue area on non-ECG gated low-dose chest CT useful for predicting coronary atherosclerosis in an asymptomatic population considered for lung cancer screening?

OBJECTS: The purpose was to determine whether the epicardial adipose tissue (EAT) area on low-dose chest CT (LDCT) could be used to predict coronary atherosclerosis in an asymptomatic population considered for lung cancer screening. METHODS: Subjects aged 55-80 years with smoking history who underwent both LDCT and coronary CT angiography (CCTA) were retrospectively enrolled. Correlation between the EAT volume in CCTA and EAT area in LDCT was evaluated. Coronary risk factors including the body surface area (BSA) indexed EAT area were compared between coronary plaque negative and positive groups. Significant factors for predicting coronary atherosclerosis were analyzed with logistic regression analysis. Receiver-operating characteristic curve analysis was performed to determine the cutoff value. RESULTS: A total of 438 subjects were enrolled, including 299 subjects with coronary atherosclerosis. There was a good correlation between the EAT volume in CCTA and EAT area in LDCT (ρ = 0.712, p < 0.001). There were significant differences in age, systolic blood pressure, all BSA indexed EAT area, sex, and hypertension between plaque negative and positive groups. In multivariate logistic regression for the BSA indexed EAT area in LDCT at the RCA level, sex (OR: 11.168, 95% CI: 2.107-59.201, p = 0.005), systolic blood pressure (OR: 1.021, 95% CI: 1.005-1.036, p = 0.009), hypertension (OR: 1.723, 95% CI: 1.103-2.753, p = 0.017), and EAT area (OR: 1.273, 95% CI: 1.154-1.405, p < 0.001) were significant. The area under the curve of the BSA indexed EAT area in LDCT at the RCA level for coronary atherosclerosis was 0.657, and the cut-off value was 7.66 cm2/m2. CONCLUSION: The EAT area in LDCT could be used to predict coronary atherosclerosis in an asymptomatic population considered for lung cancer screening. KEY POINTS: • To quantify EAT, the EAT area in LDCT can be used instead of the EAT volume in CCTA. • The EAT area measured in LDCT can be used as a predictor of coronary artery disease. • The extensive CAD group tended to have a greater EAT area than the non-extensive CAD group.