LI-RADS CT and MRI Ancillary Feature Association with Hepatocellular Carcinoma and Malignancy: An Individual Participant Data Meta-Analysis.

Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Crivellaro in this issue.

Cross-Sectional Evaluation of Open Science Practices at Imaging Journals: A Meta-Research Study.

Objective: To evaluate open science policies of imaging journals, and compliance to these policies in published articles. Methods: From imaging journals listed we extracted open science policy details: protocol registration, reporting guidelines, funding, ethics and conflicts of interest (COI), data sharing, and open access publishing. The 10 most recently published studies from each journal were assessed to determine adherence to these policies. We calculated the proportion of open science policies into an Open Science Score (OSS) for all journals and articles. We evaluated relationships between OSS and journal/article level variables. Results: 82 journals/820 articles were included. The OSS of journals and articles was 58.3% and 31.8%, respectively. Of the journals, 65.9% had registration and 78.1% had reporting guideline policies. 79.3% of journals were members of COPE, 81.7% had plagiarism policies, 100% required disclosure of funding, and 97.6% required disclosure of COI and ethics approval. 81.7% had data sharing policies and 15.9% were fully open access. 7.8% of articles had a registered protocol, 8.4% followed a reporting guideline, 77.4% disclosed funding, 88.7% disclosed COI, and 85.6% reported ethics approval. 12.3% of articles shared their data. 51% of articles were available through open access or as a preprint. OSS was higher for journal with DOAJ membership (80% vs 54.2%; P < .0001). Impact factor was not correlated with journal OSS. Knowledge synthesis articles has a higher OSS scores (44.5%) than prospective/retrospective studies (32.6%, 30.0%, P < .0001). Conclusion: Imaging journals endorsed just over half of open science practices considered; however, the application of these practices at the article level was lower.

Best Practice for MRI Diagnostic Accuracy Research With Lessons and Examples from the LI-RADS Individual Participant Data Group.

Medical imaging diagnostic test accuracy research is strengthened by adhering to best practices for study design, data collection, data documentation, and study reporting. In this review, key elements of such research are discussed, and specific recommendations provided for optimizing diagnostic accuracy study execution to improve uniformity, minimize common sources of bias and avoid potential pitfalls. Examples are provided regarding study methodology and data collection practices based on insights gained by the liver imaging reporting and data system (LI-RADS) individual participant data group, who have evaluated raw data from numerous MRI diagnostic accuracy studies for risk of bias and data integrity. The goal of this review is to outline strategies for investigators to improve research practices, and to help reviewers and readers better contextualize a study's findings while understanding its limitations. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

How to Critically Appraise and Interpret Systematic Reviews and Meta-Analyses of Diagnostic Accuracy: A User Guide.

Systematic reviews of diagnostic accuracy studies can provide the best available evidence to inform decisions regarding the use of a diagnostic test. In this guide, the authors provide a practical approach for clinicians to appraise diagnostic accuracy systematic reviews and apply their results to patient care. The first step is to identify an appropriate systematic review with a research question matching the clinical scenario. The user should evaluate the rigor of the review methods to evaluate its credibility (Did the review use clearly defined eligibility criteria, a comprehensive search strategy, structured data collection, risk of bias and applicability appraisal, and appropriate meta-analysis methods?). If the review is credible, the next step is to decide whether the diagnostic performance is adequate for clinical use (Do sensitivity and specificity estimates exceed the threshold that makes them useful in clinical practice? Are these estimates sufficiently precise? Is variability in the estimates of diagnostic accuracy across studies explained?). Diagnostic accuracy systematic reviews that are judged to be credible and provide diagnostic accuracy estimates with sufficient certainty and relevance are the most useful to inform patient care. This review discusses comparative, noncomparative, and emerging approaches to systematic reviews of diagnostic accuracy using a clinical scenario and examples based on recent publications.

Is There Evidence of P-Hacking in Imaging Research?

BACKGROUND: P-hacking, the tendency to run selective analyses until they become significant, is prevalent in many scientific disciplines. PURPOSE: This study aims to assess if p-hacking exists in imaging research. METHODS: Protocol, data, and code available here https://osf.io/xz9ku/?view_only=a9f7c2d841684cb7a3616f567db273fa. We searched imaging journals Ovid MEDLINE from 1972 to 2021. Text mining using Python script was used to collect metadata: journal, publication year, title, abstract, and P-values from abstracts. One P-value was randomly sampled per abstract. We assessed for evidence of p-hacking using a p-curve, by evaluating for a concentration of P-values just below .05. We conducted a one-tailed binomial test (α = .05 level of significance) to assess whether there were more P-values falling in the upper range (e.g., .045 < P < .05) than in the lower range (e.g., .04 < P < .045). To assess variation in results introduced by our random sampling of a single P-value per abstract, we repeated the random sampling process 1000 times and pooled results across the samples. Analysis was done (divided into 10-year periods) to determine if p-hacking practices evolved over time. RESULTS: Our search of 136 journals identified 967,981 abstracts. Text mining identified 293,687 P-values, and a total of 4105 randomly sampled P-values were included in the p-hacking analysis. The number of journals and abstracts that were included in the analysis as a fraction and percentage of the total number was, respectively, 108/136 (80%) and 4105/967,981 (.4%). P-values did not concentrate just under .05; in fact, there were more P-values falling in the lower range (e.g., .04 < P < .045) than falling just below .05 (e.g., .045 < P < .05), indicating lack of evidence for p-hacking. Time trend analysis did not identify p-hacking in any of the five 10-year periods. CONCLUSION: We did not identify evidence of p-hacking in abstracts published in over 100 imaging journals since 1972. These analyses cannot detect all forms of p-hacking, and other forms of bias may exist in imaging research such as publication bias and selective outcome reporting.

Diagnostic Accuracy of MRI for Solid Renal Masses: A Systematic Review and Meta-analysis.

BACKGROUND: Biparametric (bp)-MRI and multiparametric (mp)-MRI may improve the diagnostic accuracy of renal mass histology. PURPOSE: To evaluate the available evidence on the diagnostic accuracy of bp-MRI and mp-MRI for solid renal masses in differentiating malignant from benign, aggressive from indolent, and clear cell renal cell carcinoma (ccRCC) from other histology. STUDY TYPE: Systematic review. POPULATION: MEDLINE, EMBASE, and CENTRAL up to January 11, 2022 were searched. FIELD STRENGTH/SEQUENCE: 1.5 or 3 Tesla. ASSESSMENT: Eligible studies evaluated the accuracy of MRI (with at least two sequences: T2, T1, dynamic contrast and diffusion-weighted imaging) for diagnosis of solid renal masses in adult patients, using histology as reference standard. Risk of bias and applicability were assessed using QUADAS-2. STATISTICAL TESTS: Meta-analysis using a bivariate logitnormal random effects model. RESULTS: We included 10 studies (1239 masses from approximately 1200 patients). The risk of bias was high in three studies, unclear in five studies and low in two studies. The diagnostic accuracy of malignant (vs. benign) masses was assessed in five studies (64% [179/281] malignant). The summary estimate of sensitivity was 95% (95% confidence interval [CI]: 77%-99%), and specificity was 63% (95% CI: 46%-77%). No study assessed aggressive (vs. indolent) masses. The diagnostic accuracy of ccRCC (vs. other subtypes) was evaluated in six studies (47% [455/971] ccRCC): the summary estimate of sensitivity was 85% (95% CI: 77%-90%) and specificity was 77% (95% CI: 73%-81%). DATA CONCLUSION: Our study reveals deficits in the available evidence on MRI for diagnosis of renal mass histology. The number of studies was limited, at unclear/high risk of bias, with heterogeneous definitions of solid masses, imaging techniques, diagnostic criteria, and outcome measures. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Thoracic imaging tests for the diagnosis of COVID-19.

BACKGROUND: Our March 2021 edition of this review showed thoracic imaging computed tomography (CT) to be sensitive and moderately specific in diagnosing COVID-19 pneumonia. This new edition is an update of the review. OBJECTIVES: Our objectives were to evaluate the diagnostic accuracy of thoracic imaging in people with suspected COVID-19; assess the rate of positive imaging in people who had an initial reverse transcriptase polymerase chain reaction (RT-PCR) negative result and a positive RT-PCR result on follow-up; and evaluate the accuracy of thoracic imaging for screening COVID-19 in asymptomatic individuals. The secondary objective was to assess threshold effects of index test positivity on accuracy. SEARCH METHODS: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 17 February 2021. We did not apply any language restrictions. SELECTION CRITERIA: We included diagnostic accuracy studies of all designs, except for case-control, that recruited participants of any age group suspected to have COVID-19. Studies had to assess chest CT, chest X-ray, or ultrasound of the lungs for the diagnosis of COVID-19, use a reference standard that included RT-PCR, and report estimates of test accuracy or provide data from which we could compute estimates. We excluded studies that used imaging as part of the reference standard and studies that excluded participants with normal index test results. DATA COLLECTION AND ANALYSIS: The review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using QUADAS-2. We presented sensitivity and specificity per study on paired forest plots, and summarized pooled estimates in tables. We used a bivariate meta-analysis model where appropriate. MAIN RESULTS: We included 98 studies in this review. Of these, 94 were included for evaluating the diagnostic accuracy of thoracic imaging in the evaluation of people with suspected COVID-19. Eight studies were included for assessing the rate of positive imaging in individuals with initial RT-PCR negative results and positive RT-PCR results on follow-up, and 10 studies were included for evaluating the accuracy of thoracic imaging for imagining asymptomatic individuals. For all 98 included studies, risk of bias was high or unclear in 52 (53%) studies with respect to participant selection, in 64 (65%) studies with respect to reference standard, in 46 (47%) studies with respect to index test, and in 48 (49%) studies with respect to flow and timing. Concerns about the applicability of the evidence to: participants were high or unclear in eight (8%) studies; index test were high or unclear in seven (7%) studies; and reference standard were high or unclear in seven (7%) studies. Imaging in people with suspected COVID-19 We included 94 studies. Eighty-seven studies evaluated one imaging modality, and seven studies evaluated two imaging modalities. All studies used RT-PCR alone or in combination with other criteria (for example, clinical signs and symptoms, positive contacts) as the reference standard for the diagnosis of COVID-19. For chest CT (69 studies, 28285 participants, 14,342 (51%) cases), sensitivities ranged from 45% to 100%, and specificities from 10% to 99%. The pooled sensitivity of chest CT was 86.9% (95% confidence interval (CI) 83.6 to 89.6), and pooled specificity was 78.3% (95% CI 73.7 to 82.3). Definition for index test positivity was a source of heterogeneity for sensitivity, but not specificity. Reference standard was not a source of heterogeneity. For chest X-ray (17 studies, 8529 participants, 5303 (62%) cases), the sensitivity ranged from 44% to 94% and specificity from 24 to 93%. The pooled sensitivity of chest X-ray was 73.1% (95% CI 64. to -80.5), and pooled specificity was 73.3% (95% CI 61.9 to 82.2). Definition for index test positivity was not found to be a source of heterogeneity. Definition for index test positivity and reference standard were not found to be sources of heterogeneity. For ultrasound of the lungs (15 studies, 2410 participants, 1158 (48%) cases), the sensitivity ranged from 73% to 94% and the specificity ranged from 21% to 98%. The pooled sensitivity of ultrasound was 88.9% (95% CI 84.9 to 92.0), and the pooled specificity was 72.2% (95% CI 58.8 to 82.5). Definition for index test positivity and reference standard were not found to be sources of heterogeneity. Indirect comparisons of modalities evaluated across all 94 studies indicated that chest CT and ultrasound gave higher sensitivity estimates than X-ray (P = 0.0003 and P = 0.001, respectively). Chest CT and ultrasound gave similar sensitivities (P=0.42). All modalities had similar specificities (CT versus X-ray P = 0.36; CT versus ultrasound P = 0.32; X-ray versus ultrasound P = 0.89). Imaging in PCR-negative people who subsequently became positive For rate of positive imaging in individuals with initial RT-PCR negative results, we included 8 studies (7 CT, 1 ultrasound) with a total of 198 participants suspected of having COVID-19, all of whom had a final diagnosis of COVID-19. Most studies (7/8) evaluated CT. Of 177 participants with initially negative RT-PCR who had positive RT-PCR results on follow-up testing, 75.8% (95% CI 45.3 to 92.2) had positive CT findings. Imaging in asymptomatic PCR-positive people For imaging asymptomatic individuals, we included 10 studies (7 CT, 1 X-ray, 2 ultrasound) with a total of 3548 asymptomatic participants, of whom 364 (10%) had a final diagnosis of COVID-19. For chest CT (7 studies, 3134 participants, 315 (10%) cases), the pooled sensitivity was 55.7% (95% CI 35.4 to 74.3) and the pooled specificity was 91.1% (95% CI 82.6 to 95.7). AUTHORS' CONCLUSIONS: Chest CT and ultrasound of the lungs are sensitive and moderately specific in diagnosing COVID-19. Chest X-ray is moderately sensitive and moderately specific in diagnosing COVID-19. Thus, chest CT and ultrasound may have more utility for ruling out COVID-19 than for differentiating SARS-CoV-2 infection from other causes of respiratory illness. The uncertainty resulting from high or unclear risk of bias and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results.

Diagnostic accuracy of thoracic imaging modalities for the detection of COVID-19.

The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to present diagnostic challenges. The use of thoracic radiography has been studied as a method to improve the diagnostic accuracy of COVID-19. The 'Living' Cochrane Systematic Review on the diagnostic accuracy of imaging tests for COVID-19 is continuously updated as new information becomes available for study. In the most recent version, published in March 2021, a meta-analysis was done to determine the pooled sensitivity and specificity of chest X-ray (CXR) and lung ultrasound (LUS) for the diagnosis of COVID-19. CXR gave a sensitivity of 80.6% (95%CI: 69.1-88.6) and a specificity of 71.5% (95%CI: 59.8-80.8). LUS gave a sensitivity rate of 86.4% (95%CI: 72.7-93.9) and specificity of 54.6% (95%CI: 35.3-72.6). These results differed from the findings reported in the recent article in this journal where they cited the previous versions of the study in which a meta-analysis for CXR and LUS could not be performed. Additionally, the article states that COVID-19 could not be distinguished, using chest computed tomography (CT), from other respiratory diseases. However, the latest review version identifies chest CT as having a specificity of 80.0% (95%CI: 74.9-84.3), which is much higher than the previous version which indicated a specificity of 61.1% (95%CI: 42.3-77.1). Therefore, CXR, chest CT and LUS have the potential to be used in conjunction with other methods in the diagnosis of COVID-19.

Sex Differences in Implantation and Outcomes of Cardiac Resynchronization Therapy in Real-World Settings: A Systematic Review of Cohort Studies.

BACKGROUND: Evidence from randomized trials is conflicting on the effects of cardiac resynchronization therapy (CRT) by sex, and differences in access are unknown. We examined sex differences in the implantation rates and outcomes in patients treated with CRT using cohort studies. METHODS: We followed a pre-specified protocol (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42020204804). MEDLINE, Embase, and Web of Science were searched for cohort studies from January 2000 to June 2020 that evaluated the response to CRT in patients ≥ 18 years old and reported sex-specific information in any language. RESULTS: We included 97 studies (1,172,654 men and 486,553 women). Men received CRT more frequently than women (median ratio, 3.16; 25th to 75th interquartile range, 2.48-3.62). In the unadjusted analysis, men had a greater long-term all-cause mortality rate after CRT, compared with women (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.38-1.63; P < 0.001). Adjustment for confounders did not affect the strength or direction of association (HR, 1.45; 95% CI, 1.32-1.59; P < 0.001). Women achieved a greater rate of improvement in left ejection fraction compared with men (HR, 4.66; 95% CI, 4.23-5.13; P < 0.001). Men had a lower risk of a pneumothorax (relative risk, 0.21; 95% CI, 0.13-0.34; P < 0.001]); otherwise, there were no differences in complications. CONCLUSIONS: We found in this large meta-analysis that men were more often implanted with CRT than women, yet men had a higher long-term all-cause mortality following CRT, compared with women, and smaller improvement in left ventricular ejection fraction. Reasons for this difference in implantation rates of CRT in real-world practice need to be investigated.

CONTEXTE: Les données probantes issues des essais randomisés sont contradictoires quant aux effets de la thérapie de resynchronisation cardiaque (TRC) selon le sexe, et les différences en matière d'accès sont inconnues. À l'aide d'études de cohortes, nous avons examiné les différences en fonction du sexe pour les taux d'implantation et les résultats chez les patients recevant une TRC. MÉTHODOLOGIE: Nous avons suivi un protocole prédéterminé (International Prospective Register of Systematic Reviews [PROSPERO] : CRD42020204804). Nous avons recherché dans les bases de données MEDLINE, Embase et Web of Science les études de cohortes réalisées entre janvier 2000 et juin 2020 évaluant la réponse à la TRC chez les patients ≥ 18 ans et faisant état d'informations spécifiques au sexe, peu importe la langue. RÉSULTATS: Nous avons inclus 97 études (1 172 654 hommes et 486 553 femmes). La TRC était plus fréquemment administrée chez les hommes que chez les femmes (rapport médian de 3,16; intervalle interquartile du 25e au 75e centile : 2,48 à 3,62). Lors des analyses non ajustées, le taux de mortalité à long terme toutes causes confondues après une TRC était plus élevé chez les hommes que chez les femmes (rapport de risques instantanés [RRI] : 1,50; intervalle de confiance [IC] à 95 % : 1,38 à 1,63; p < 0,001). L'ajustement en fonction des facteurs de confusion n'affectait pas la force ni le sens de l'association (RRI : 1,45; IC à 95 % : 1,32 à 1,59; p < 0,001). Les femmes affichaient un taux d'amélioration de la fraction d'éjection ventriculaire gauche plus élevé que les hommes (RRI : 4,66; IC à 95 % : 4,23 à 5,13; p < 0,001). Les hommes montraient un risque plus faible de pneumothorax (risque relatif : 0,21; IC à 95 % : 0,13 à 0,34; p < 0,001); il n'y avait aucune autre différence quant aux complications. CONCLUSIONS: Dans le cadre de cette méta-analyse à grande échelle, nous avons constaté que les hommes recevaient plus souvent une TRC que les femmes, mais que, après une TRC, les hommes présentaient une plus grande mortalité à long terme toutes causes confondues, et une amélioration moindre de la fraction d'éjection ventriculaire gauche par rapport aux femmes. Les raisons de cette différence dans les taux d'intégration de la TRC dans la pratique réelle restent à étudier.

PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation.

Protein arginine methyltransferases (PRMTs) are a family of enzymes that modify proteins by methylating the guanidino nitrogen atoms of arginine residues to regulate cellular processes such as chromatin remodeling, pre-mRNA splicing, and signal transduction. PRMT7 is the single type III PRMT solely capable of arginine monomethylation. To date, other than histone proteins, there are very few identified substrates of PRMT7. We therefore performed quantitative mass spectrometry experiments to identify PRMT7's interactome and potential substrates to better characterize the enzyme's biological function(s) in cells. These experiments revealed that PRMT7 interacts with and can methylate eukaryotic translation initiation factor 2 alpha (eIF2α), in vitro and in breast cancer cells. Furthermore, we uncovered a potential regulatory interplay between eIF2α arginine methylation by PRMT7 and stress-induced phosphorylation status of eIF2α at serine 51. Finally, we demonstrated that PRMT7 is required for eIF2α-dependent stress granule formation in the face of various cellular stresses. Altogether, our findings implicate PRMT7 as a novel mediator of eIF2α-dependent cellular stress response pathways.