Assessment of Advanced Diagnostic Bronchoscopy Outcomes for Peripheral Lung Lesions: A Delphi Consensus Definition of Diagnostic Yield and Recommendations for Patient-centered Study Designs. An Official American Thoracic Society/American College of Chest Physicians Research Statement.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Inconsistency Between Pictures on Baby Diaper Packaging in Europe and Safe Infant Sleep Recommendations.

OBJECTIVE: To describe the level of inconsistency between pictures on baby diaper packaging and safe infant sleep recommendations (SISRs) in Europe. STUDY DESIGN: We attempted to identify all packaging of baby diapers sold in 11 European countries for infants weighing less than 5 kg through internet searches from July 2022 through February 2023. For each type of package, we extracted whether there was a picture depicting a baby, whether the baby was sleeping, and whether the picture of the sleeping baby was inconsistent with ≥1 of 3 SISRs: (i) nonsupine sleeping position, (ii) soft objects or loose bedding, or (iii) sharing a sleep surface with another person. Data were aggregated at the country level, and a random-effects meta-analysis of proportions was used to obtain summary estimates. The outcome was the summary estimate of the proportion of pictures that were inconsistent with SISRs. RESULTS: We identified 631 baby diaper packaging types of which 49% (95% CI: 42-57; n = 311) displayed a picture of a sleeping baby. Among those 311 packages, 79% (95% CI 73-84) were inconsistent with ≥1 SISR, including a nonsupine sleeping position, 45% (95% CI 39-51), soft objects or loose bedding such as pillows or blankets, 51% (95% CI 46-57), and sharing a sleep surface with another person, 10% (95% CI 4-18). CONCLUSIONS: Pictures on baby diaper packaging in Europe are often inconsistent with SISRs. The prevention of sudden unexpected death in infancy requires action from manufacturers and legislators to stop parents' exposure to misleading images that may lead to dangerous practices.

Effectiveness of FeNO-guided treatment in adult asthma patients: A systematic review and meta-analysis.

OBJECTIVE: Asthma control is generally monitored by assessing symptoms and lung function. However, optimal treatment is also dependent on the type and extent of airway inflammation. Fraction of exhaled Nitric Oxide (FeNO) is a noninvasive biomarker of type 2 airway inflammation, but its effectiveness in guiding asthma treatment remains disputed. We performed a systematic review and meta-analysis to obtain summary estimates of the effectiveness of FeNO-guided asthma treatment. DESIGN: We updated a Cochrane systematic review from 2016. Cochrane Risk of Bias tool was used to assess risk of bias. Inverse-variance random-effects meta-analysis was performed. Certainty of evidence was assessed using GRADE. Subgroup analyses were performed based on asthma severity, asthma control, allergy/atopy, pregnancy and obesity. DATA SOURCES: The Cochrane Airways Group Trials Register was searched on 9 May 2023. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) comparing the effectiveness of a FeNO-guided treatment versus usual (symptom-guided) treatment in adult asthma patients. RESULTS: We included 12 RCTs (2,116 patients), all showing high or unclear risk of bias in at least one domain. Five RCTs reported support from a FeNO manufacturer. FeNO-guided treatment probably reduces the number of patients having ≥1 exacerbation (OR = 0.61; 95%CI 0.44 to 0.83; six RCTs; GRADE moderate certainty) and exacerbation rate (RR = 0.67; 95%CI 0.54 to 0.82; six RCTs; moderate certainty), and may slightly improve Asthma Control Questionnaire score (MD = -0.10; 95%CI -0.18 to -0.02, six RCTs; low certainty), however, this change is unlikely to be clinically important. An effect on severe exacerbations, quality of life, FEV1, treatment dosage and FeNO values could not be demonstrated. There were no indications that effectiveness is different in subgroups of patients, although evidence for subgroup analysis was limited. CONCLUSIONS: FeNO-guided asthma treatment probably results in fewer exacerbations but may not have clinically important effects on other asthma outcomes.

Proposed quality indicators and recommended standard reporting items in performance of EBUS bronchoscopy: An official World Association for Bronchology and Interventional Pulmonology Expert Panel consensus statement.

BACKGROUND: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. METHODS: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. RESULTS: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. CONCLUSION: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.

European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases.

BACKGROUND: In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD. METHODS: The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied. RESULTS: In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required. CONCLUSIONS: TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low".

Evaluating the Impact of Peer Review on the Completeness of Reporting in Imaging Diagnostic Test Accuracy Research.

BACKGROUND: Despite the nearly ubiquitous reported use of peer review among reputable medical journals, there is limited evidence to support the use of peer review to improve the quality of biomedical research and in particular, imaging diagnostic test accuracy (DTA) research. PURPOSE: To evaluate whether peer review of DTA studies published by imaging journals is associated with changes in completeness of reporting, transparency for risk of bias assessment, and spin. STUDY TYPE: Retrospective cross-sectional study. STUDY SAMPLE: Cross-sectional study of articles published in Journal of Magnetic Resonance Imaging (JMRI), Canadian Association of Radiologists Journal (CARJ), and European Radiology (EuRad) before March 31, 2020. ASSESSMENT: Initial submitted and final versions of manuscripts were evaluated for completeness of reporting using the Standards for Reporting Diagnostic Accuracy Studies (STARD) 2015 and STARD for Abstracts guidelines, transparency of reporting for risk of bias assessment based on Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), and actual and potential spin using modified published criteria. STATISTICAL TESTS: Two-tailed paired t-tests and paired Wilcoxon signed-rank tests were used for comparisons. A P value <0.05 was considered to be statistically significant. RESULTS: We included 84 diagnostic accuracy studies accepted by three journals between 2014 and 2020 (JMRI = 30, CARJ = 23, and EuRad = 31) of the 692 which were screened. Completeness of reporting according to STARD 2015 increased significantly between initial submissions and final accepted versions (average reported items: 16.67 vs. 17.47, change of 0.80 [95% confidence interval 0.25-1.17]). No significant difference was found for the reporting of STARD for Abstracts (5.28 vs. 5.25, change of -0.03 [-0.15 to 0.11], P = 0.74), QUADAS-2 (6.08 vs. 6.11, change of 0.03 [-1.00 to 0.50], P = 0.92), actual "spin" (2.36 vs. 2.40, change of 0.04 [0.00 to 1.00], P = 0.39) or potential "spin" (2.93 vs. 2.81, change of -0.12 [-1.00 to 0.00], P = 0.23) practices. CONCLUSION: Peer review is associated with a marginal improvement in completeness of reporting in published imaging DTA studies, but not with improvement in transparency for risk of bias assessment or reduction in spin. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Association of Accuracy, Conclusions, and Reporting Completeness With Acceptance by Radiology Conferences and Journals.

BACKGROUND: Preferential publication of studies with positive findings can lead to overestimation of diagnostic test accuracy (i.e. publication bias). Understanding the contribution of the editorial process to publication bias could inform interventions to optimize the evidence guiding clinical decisions. PURPOSE/HYPOTHESIS: To evaluate whether accuracy estimates, abstract conclusion positivity, and completeness of abstract reporting are associated with acceptance to radiology conferences and journals. STUDY TYPE: Meta-research. POPULATION: Abstracts submitted to radiology conferences (European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and International Society for Magnetic Resonance in Medicine (ISMRM)) from 2008 to 2018 and manuscripts submitted to radiology journals (Radiology, Journal of Magnetic Resonance Imaging [JMRI]) from 2017 to 2018. Primary clinical studies evaluating sensitivity and specificity of a diagnostic imaging test in humans with available editorial decisions were included. ASSESSMENT: Primary variables (Youden's index [YI > 0.8 vs. <0.8], abstract conclusion positivity [positive vs. neutral/negative], number of reported items on the Standards for Reporting of Diagnostic Accuracy Studies [STARD] for Abstract guideline) and confounding variables (prospective vs. retrospective/unreported, sample size, study duration, interobserver agreement assessment, subspecialty, modality) were extracted. STATISTICAL TESTS: Multivariable logistic regression to obtain adjusted odds ratio (OR) as a measure of the association between the primary variables and acceptance by radiology conferences and journals; 95% confidence intervals (CIs) and P-values were obtained; the threshold for statistical significance was P < 0.05. RESULTS: A total of 1000 conference abstracts (500 ESGAR and 500 ISMRM) and 1000 journal manuscripts (505 Radiology and 495 JMRI) were included. Conference abstract acceptance was not significantly associated with YI (adjusted OR = 0.97 for YI > 0.8; CI = 0.70-1.35), conclusion positivity (OR = 1.21 for positive conclusions; CI = 0.75-1.90) or STARD for Abstracts adherence (OR = 0.96 per unit increase in reported items; CI = 0.82-1.18). Manuscripts with positive abstract conclusions were less likely to be accepted by radiology journals (OR = 0.45; CI = 0.24-0.86), while YI (OR = 0.85; CI = 0.56-1.29) and STARD for Abstracts adherence (OR = 1.06; CI = 0.87-1.30) showed no significant association. Positive conclusions were present in 86.7% of submitted conference abstracts and 90.2% of journal manuscripts. DATA CONCLUSION: Diagnostic test accuracy studies with positive findings were not preferentially accepted by the evaluated radiology conferences or journals. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

EBUS versus EUS-B for diagnosing sarcoidosis: The International Sarcoidosis Assessment (ISA) randomized clinical trial.

BACKGROUND AND OBJECTIVE: Endosonography with intrathoracic nodal sampling is proposed as the single test with the highest granuloma detection rate in suspected sarcoidosis stage I/II. However, most studies have been performed in limited geographical regions. Studies suggest that oesophageal endosonographic nodal sampling has higher diagnostic yield than endobronchial endosonographic nodal sampling, but a head-to-head comparison of both routes has never been performed. METHODS: Global (14 hospitals, nine countries, four continents) randomized clinical trial was conducted in consecutive patients with suspected sarcoidosis stage I/II presenting between May 2015 and August 2017. Using an endobronchial ultrasound (EBUS) scope, patients were randomized to EBUS or endoscopic ultrasound (EUS)-B-guided nodal sampling, and to 22- or 25-G ProCore needle aspiration (2 × 2 factorial design). Granuloma detection rate was the primary study endpoint. Final diagnosis was based on cytology/pathology outcomes and clinical/radiological follow-up at 6 months. RESULTS: A total of 358 patients were randomized: 185 patients to EBUS-transbronchial needle aspiration (EBUS-TBNA) and 173 to EUS-B-fine-needle aspiration (FNA). Final diagnosis was sarcoidosis in 306 patients (86%). Granuloma detection rate was 70% (130/185; 95% CI, 63-76) for EBUS-TBNA and 68% (118/173; 95% CI, 61-75) for EUS-B-FNA (p = 0.67). Sensitivity for diagnosing sarcoidosis was 78% (129/165; 95% CI, 71-84) for EBUS-TBNA and 82% (115/141; 95% CI, 74-87) for EUS-B-FNA (p = 0.46). There was no significant difference between the two needle types in granuloma detection rate or sensitivity. CONCLUSION: Granuloma detection rate of mediastinal/hilar nodes by endosonography in patients with suspected sarcoidosis stage I/II is high and similar for EBUS and EUS-B. These findings imply that both diagnostic tests can be safely and universally used in suspected sarcoidosis patients.

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.

Chest CT in the Emergency Department for Diagnosis of COVID-19 Pneumonia: Dutch Experience.

Background Clinicians need to rapidly and reliably diagnose coronavirus disease 2019 (COVID-19) for proper risk stratification, isolation strategies, and treatment decisions. Purpose To assess the real-life performance of radiologist emergency department chest CT interpretation for diagnosing COVID-19 during the acute phase of the pandemic, using the COVID-19 Reporting and Data System (CO-RADS). Materials and Methods This retrospective multicenter study included consecutive patients who presented to emergency departments in six medical centers between March and April 2020 with moderate to severe upper respiratory symptoms suspicious for COVID-19. As part of clinical practice, chest CT scans were obtained for primary work-up and scored using the five-point CO-RADS scheme for suspicion of COVID-19. CT was compared with severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (RT-PCR) assay and a clinical reference standard established by a multidisciplinary group of clinicians based on RT-PCR, COVID-19 contact history, oxygen therapy, timing of RT-PCR testing, and likely alternative diagnosis. Performance of CT was estimated using area under the receiver operating characteristic curve (AUC) analysis and diagnostic odds ratios against both reference standards. Subgroup analysis was performed on the basis of symptom duration grouped presentations of less than 48 hours, 48 hours through 7 days, and more than 7 days. Results A total of 1070 patients (median age, 66 years; interquartile range, 54-75 years; 626 men) were included, of whom 536 (50%) had a positive RT-PCR result and 137 (13%) of whom were considered to have a possible or probable COVID-19 diagnosis based on the clinical reference standard. Chest CT yielded an AUC of 0.87 (95% CI: 0.84, 0.89) compared with RT-PCR and 0.87 (95% CI: 0.85, 0.89) compared with the clinical reference standard. A CO-RADS score of 4 or greater yielded an odds ratio of 25.9 (95% CI: 18.7, 35.9) for a COVID-19 diagnosis with RT-PCR and an odds ratio of 30.6 (95% CI: 21.1, 44.4) with the clinical reference standard. For symptom duration of less than 48 hours, the AUC fell to 0.71 (95% CI: 0.62, 0.80; P < .001). Conclusion Chest CT analysis using the coronavirus disease 2019 (COVID-19) Reporting and Data System enables rapid and reliable diagnosis of COVID-19, particularly when symptom duration is greater than 48 hours. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Elicker in this issue.

Reporting Bias in Imaging Diagnostic Test Accuracy Studies: Are Studies With Positive Conclusions or Titles Submitted and Published Faster?

OBJECTIVE: The purpose of this study is to evaluate whether imaging diagnostic test accuracy (DTA) studies with positive conclusions or titles have a shorter time to publication than those with nonpositive (i.e., negative or neutral) conclusions or titles. MATERIALS AND METHODS: We included primary imaging DTA studies from systematic reviews published in 2015. The conclusion and title of each study were extracted, and their positivity was classified independently in duplicate. The time from study completion to publication was extracted and calculated. A Cox regression model was used to evaluate associations of conclusion and title positivity with time to publication, with adjustment made for potentially confounding variables. RESULTS: A total of 774 imaging DTA studies were included; time from study completion to publication could be calculated for 516 studies. The median time from completion to publication was 18 months (interquartile range, 13-26 months) for the 413 studies with positive conclusions, 23 months (interquartile range, 16-33 months) for the 63 studies with neutral conclusions, and 25 months (interquartile range, 15-38 months) for the 40 studies with negative conclusions. A positive conclusion was associated with a shorter time from study completion to publication compared with a non-positive conclusion (hazard ratio, 1.31; 95% CI, 1.02-1.68). Of all included studies, 39 (5%) had positive titles, 731 (94%) had neutral titles, and 4 (< 1%) had negative titles. Positive titles were not significantly associated with a shorter time to study publication (hazard ratio, 1.12; 95% CI, 0.75-1.69). CONCLUSION: Positive conclusions (but not titles) were associated with a shorter time from study completion to publication. This finding may contribute to an overrepresentation of positive results in the imaging DTA literature.

Routine screening for pulmonary embolism in COVID-19 patients at the emergency department: impact of D-dimer testing followed by CTPA.

COVID-19 patients have increased risk of pulmonary embolism (PE), but symptoms of both conditions overlap. Because screening algorithms for PE in COVID-19 patients are currently lacking, PE might be underdiagnosed. We evaluated a screening algorithm in which all patients presenting to the ED with suspected or confirmed COVID-19 routinely undergo D-dimer testing, followed by CT pulmonary angiography (CTPA) if D-dimer is ≥ 1.00 mg/L. Consecutive adult patients presenting to the ED of two university hospitals in Amsterdam, The Netherlands, between 01-10-2020 and 31-12-2020, who had a final diagnosis of COVID-19, were retrospectively included. D-dimer and CTPA results were obtained. Of 541 patients with a final diagnosis of COVID-19 presenting to the ED, 25 (4.6%) were excluded because D-dimer was missing, and 71 (13.1%) because they used anticoagulation therapy. Of 445 included patients, 185 (41.6%; 95%CI 37.0-46.3) had a D-dimer ≥ 1.00 mg/L. CTPA was performed in 169 of them, which showed PE in 26 (15.4%; 95%CI 10.3-21.7), resulting in an overall detection rate of 5.8% (95%CI 3.9-8.4) in the complete study group. In patients with and without PE at CTPA, median D-dimer was 9.84 (IQR 3.90-29.38) and 1.64 (IQR 1.17-3.01), respectively (p < 0.001). PE prevalence increased with increasing D-dimer, ranging from 1.2% (95%CI 0.0-6.4) if D-dimer was 1.00-1.99 mg/L, to 48.6% (95%CI 31.4-66.0) if D-dimer was ≥ 5.00 mg/L. In conclusion, by applying this screening algorithm, PE was identified in a considerable proportion of COVID-19 patients. Prospective management studies should assess if this algorithm safely rules-out PE if D-dimer is < 1.00 mg/L.

Thoracic imaging tests for the diagnosis of COVID-19.

BACKGROUND: The respiratory illness caused by SARS-CoV-2 infection continues to present diagnostic challenges. Our 2020 edition of this review showed thoracic (chest) imaging to be sensitive and moderately specific in the diagnosis of coronavirus disease 2019 (COVID-19). In this update, we include new relevant studies, and have removed studies with case-control designs, and those not intended to be diagnostic test accuracy studies. OBJECTIVES: To evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected COVID-19. 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 30 September 2020. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of all designs, except for case-control, that recruited participants of any age group suspected to have COVID-19 and that reported estimates of test accuracy or provided data from which we could compute estimates. DATA COLLECTION AND ANALYSIS: The review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using the QUADAS-2 domain-list. We presented the results of estimated sensitivity and specificity using paired forest plots, and we summarised pooled estimates in tables. We used a bivariate meta-analysis model where appropriate. We presented the uncertainty of accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS: We included 51 studies with 19,775 participants suspected of having COVID-19, of whom 10,155 (51%) had a final diagnosis of COVID-19. Forty-seven studies evaluated one imaging modality each, and four studies evaluated two imaging modalities each. All studies used RT-PCR as the reference standard for the diagnosis of COVID-19, with 47 studies using only RT-PCR and four studies using a combination of RT-PCR and other criteria (such as clinical signs, imaging tests, positive contacts, and follow-up phone calls) as the reference standard. Studies were conducted in Europe (33), Asia (13), North America (3) and South America (2); including only adults (26), all ages (21), children only (1), adults over 70 years (1), and unclear (2); in inpatients (2), outpatients (32), and setting unclear (17). Risk of bias was high or unclear in thirty-two (63%) studies with respect to participant selection, 40 (78%) studies with respect to reference standard, 30 (59%) studies with respect to index test, and 24 (47%) studies with respect to participant flow. For chest CT (41 studies, 16,133 participants, 8110 (50%) cases), the sensitivity ranged from 56.3% to 100%, and specificity ranged from 25.4% to 97.4%. The pooled sensitivity of chest CT was 87.9% (95% CI 84.6 to 90.6) and the pooled specificity was 80.0% (95% CI 74.9 to 84.3). There was no statistical evidence indicating that reference standard conduct and definition for index test positivity were sources of heterogeneity for CT studies. Nine chest CT studies (2807 participants, 1139 (41%) cases) used the COVID-19 Reporting and Data System (CO-RADS) scoring system, which has five thresholds to define index test positivity. At a CO-RADS threshold of 5 (7 studies), the sensitivity ranged from 41.5% to 77.9% and the pooled sensitivity was 67.0% (95% CI 56.4 to 76.2); the specificity ranged from 83.5% to 96.2%; and the pooled specificity was 91.3% (95% CI 87.6 to 94.0). At a CO-RADS threshold of 4 (7 studies), the sensitivity ranged from 56.3% to 92.9% and the pooled sensitivity was 83.5% (95% CI 74.4 to 89.7); the specificity ranged from 77.2% to 90.4% and the pooled specificity was 83.6% (95% CI 80.5 to 86.4). For chest X-ray (9 studies, 3694 participants, 2111 (57%) cases) the sensitivity ranged from 51.9% to 94.4% and specificity ranged from 40.4% to 88.9%. The pooled sensitivity of chest X-ray was 80.6% (95% CI 69.1 to 88.6) and the pooled specificity was 71.5% (95% CI 59.8 to 80.8). For ultrasound of the lungs (5 studies, 446 participants, 211 (47%) cases) the sensitivity ranged from 68.2% to 96.8% and specificity ranged from 21.3% to 78.9%. The pooled sensitivity of ultrasound was 86.4% (95% CI 72.7 to 93.9) and the pooled specificity was 54.6% (95% CI 35.3 to 72.6). Based on an indirect comparison using all included studies, chest CT had a higher specificity than ultrasound. For indirect comparisons of chest CT and chest X-ray, or chest X-ray and ultrasound, the data did not show differences in specificity or sensitivity. AUTHORS' CONCLUSIONS: Our findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID-19. Chest X-ray is moderately sensitive and moderately specific for the diagnosis of COVID-19. Ultrasound is sensitive but not specific for the diagnosis of COVID-19. Thus, chest CT and ultrasound may have more utility for excluding COVID-19 than for differentiating SARS-CoV-2 infection from other causes of respiratory illness. Future diagnostic accuracy studies should pre-define positive imaging findings, include direct comparisons of the various modalities of interest in the same participant population, and implement improved reporting practices.

Overinterpretation of Research Findings: Evaluation of "Spin" in Systematic Reviews of Diagnostic Accuracy Studies in High-Impact Factor Journals.

BACKGROUND: To compare the frequency of "spin" in systematic reviews of diagnostic accuracy studies in high-impact journals with the frequency a previously assessed series of reviews. METHODS: Medline was searched from January 2010 to January 2019. Systematic reviews of diagnostic accuracy studies were included if they reported a meta-analysis and were published in a journal with an impact factor >5. Two investigators independently scored each included systematic review for positivity of conclusions and for actual and potential overinterpretation practices. RESULTS: Of 137 included systematic reviews, actual overinterpretation was present in ≥1 form in the abstract in 63 (46%) and in the full-text report in 52 (38%); 108 (79%) contained a form of potential overinterpretation. Compared with the previously assessed series (reviews published 2015-2016), reviews in this series were less likely to contain ≥1 form of actual overinterpretation in the abstract and full-text report or ≥1 form of potential overinterpretation (P < 0.001 for all comparisons). The significance of these comparisons did not persist for actual overinterpretation in sensitivity analysis in which Cochrane systematic reviews were removed. Reviews published in the Cochrane Database of Systematic Reviews were less likely to contain actual overinterpretation in the abstract or the full-text report than reviews in other high-impact journals (P < 0.001 for both comparisons). CONCLUSIONS: Reviews of diagnostic accuracy studies in high-impact journals are less likely to contain overinterpretation or spin. This difference is largely due to the reviews published in the Cochrane Database of Systematic Reviews, which contain spin less often than reviews published in other high-impact journals.

Publication bias in diagnostic imaging: conference abstracts with positive conclusions are more likely to be published.

OBJECTIVE: To evaluate whether imaging diagnostic test accuracy conference abstracts with positive conclusions or titles are more likely to reach full-text publication than those with negative (or neutral) conclusions or titles. METHODS: Diagnostic accuracy research abstracts were included if they were presented at the 2011 or 2012 Radiological Society of North America conference. Full-text publication status at 5 years post conference abstract submission was determined. Conclusion and title positivity of conference abstracts were extracted, as well as potential confounding factors. The associations of conclusion and title positivity with publication status at 5 years post conference abstract submission were assessed using a multivariable logistic regression model. Conditional odds ratios were calculated to express the strength of associations, adjusting for the confounders. RESULTS: In total, 282/400 (71%) of included conference abstracts reached full-text publication. A total of 246 out of 337 (74%) conference abstracts with positive conclusions resulted in full-text publications, compared with 26/48 (54%) with neutral conclusions and 5/15 (33%) with negative conclusions. In multivariable logistic regression, conclusion positivity was significantly associated with full-text publication (odds ratio 3.6; 95% CI 1.9-6.7 for conference abstracts with positive conclusions, compared with those with non-positive conclusions); this did not apply to title positivity (odds ratio 1.2; 95% CI 0.47-3.0). CONCLUSION: Imaging conference abstracts with positive conclusions were more likely to be published as full-text articles. Title positivity was not associated with publication. This preferential publication pattern may lead to an overrepresentation of positive studies in the literature. An overrepresentation of positive studies may contribute to inflated estimates of test accuracy and has the potential to adversely influence patient care. KEY POINTS: • Imaging diagnostic test accuracy conference abstracts with positive conclusions were more likely to be reported as full-text articles than those with non-positive conclusions. • The majority (75%) of imaging diagnostic test accuracy conference abstracts with positive conclusions were published, compared with only 53% and 33% with neutral and negative conclusions, respectively. • Conclusion positivity remained associated with the full-text publication of conference abstracts when controlling for multiple potential confounding variables.

Thoracic imaging tests for the diagnosis of COVID-19.

BACKGROUND: The diagnosis of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents major challenges. Reverse transcriptase polymerase chain reaction (RT-PCR) testing is used to diagnose a current infection, but its utility as a reference standard is constrained by sampling errors, limited sensitivity (71% to 98%), and dependence on the timing of specimen collection. Chest imaging tests are being used in the diagnosis of COVID-19 disease, or when RT-PCR testing is unavailable. OBJECTIVES: To determine the diagnostic accuracy of chest imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected or confirmed COVID-19. SEARCH METHODS: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, and The Stephen B. Thacker CDC Library. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 5 May 2020. SELECTION CRITERIA: We included studies of all designs that produce estimates of test accuracy or provide data from which estimates can be computed. We included two types of cross-sectional designs: a) where all patients suspected of the target condition enter the study through the same route and b) where it is not clear up front who has and who does not have the target condition, or where the patients with the target condition are recruited in a different way or from a different population from the patients without the target condition. When studies used a variety of reference standards, we included all of them. DATA COLLECTION AND ANALYSIS: We screened studies and extracted data independently, in duplicate. We also assessed the risk of bias and applicability concerns independently, in duplicate, using the QUADAS-2 checklist and presented the results of estimated sensitivity and specificity, using paired forest plots, and summarised in tables. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS: We included 84 studies, falling into two categories: studies with participants with confirmed diagnoses of COVID-19 at the time of recruitment (71 studies with 6331 participants) and studies with participants suspected of COVID-19 (13 studies with 1948 participants, including three case-control studies with 549 cases and controls). Chest CT was evaluated in 78 studies (8105 participants), chest X-ray in nine studies (682 COVID-19 cases), and chest ultrasound in two studies (32 COVID-19 cases). All evaluations of chest X-ray and ultrasound were conducted in studies with confirmed diagnoses only. Twenty-five per cent (21/84) of all studies were available only as preprints, 15/71 studies in the confirmed cases group and 6/13 of the studies in the suspected group. Among 71 studies that included confirmed cases, 41 studies had included symptomatic cases only, 25 studies had included cases regardless of their symptoms, five studies had included asymptomatic cases only, three of which included a combination of confirmed and suspected cases. Seventy studies were conducted in Asia, 2 in Europe, 2 in North America and one in South America. Fifty-one studies included inpatients while the remaining 24 studies were conducted in mixed or unclear settings. Risk of bias was high in most studies, mainly due to concerns about selection of participants and applicability. Among the 13 studies that included suspected cases, nine studies were conducted in Asia, and one in Europe. Seven studies included inpatients while the remaining three studies were conducted in mixed or unclear settings. In studies that included confirmed cases the pooled sensitivity of chest CT was 93.1% (95%CI: 90.2 - 95.0 (65 studies, 5759 cases); and for X-ray 82.1% (95%CI: 62.5 to 92.7 (9 studies, 682 cases). Heterogeneity judged by visual assessment of the ROC plots was considerable. Two studies evaluated the diagnostic accuracy of point-of-care ultrasound and both reported zero false negatives (with 10 and 22 participants having undergone ultrasound, respectively). These studies only reported True Positive and False Negative data, therefore it was not possible to pool and derive estimates of specificity. In studies that included suspected cases, the pooled sensitivity of CT was 86.2% (95%CI: 71.9 to 93.8 (13 studies, 2346 participants) and specificity was 18.1% (95%CI: 3.71 to 55.8). Heterogeneity judged by visual assessment of the forest plots was high. Chest CT may give approximately the same proportion of positive results for patients with and without a SARS-CoV-2 infection: the chances of getting a positive CT result are 86% (95% CI: 72 to 94) in patient with a SARS-CoV-2 infection and 82% (95% CI: 44 to 96) in patients without. AUTHORS' CONCLUSIONS: The uncertainty resulting from the poor study quality and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results. Our findings indicate that chest CT is sensitive but not specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may not be capable of differentiating SARS-CoV-2 infection from other causes of respiratory illness. This low specificity could also be the result of the poor sensitivity of the reference standard (RT-PCR), as CT could potentially be more sensitive than RT-PCR in some cases. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of COVID-19 should be carefully interpreted. Future diagnostic accuracy studies should avoid cases-only studies and pre-define positive imaging findings. Planned updates of this review will aim to: increase precision around the accuracy estimates for CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X rays and ultrasound; and continue to search for studies that fulfil secondary objectives to inform the utility of imaging along different diagnostic pathways.

Thoracic imaging tests for the diagnosis of COVID-19.

BACKGROUND: The respiratory illness caused by SARS-CoV-2 infection continues to present diagnostic challenges. Early research showed thoracic (chest) imaging to be sensitive but not specific in the diagnosis of coronavirus disease 2019 (COVID-19). However, this is a rapidly developing field and these findings need to be re-evaluated in the light of new research. This is the first update of this 'living systematic review'. This update focuses on people suspected of having COVID-19 and excludes studies with only confirmed COVID-19 participants. OBJECTIVES: To evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected COVID-19. 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 22 June 2020. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of all designs that recruited participants of any age group suspected to have COVID-19, and which reported estimates of test accuracy, or provided data from which estimates could be computed. When studies used a variety of reference standards, we retained the classification of participants as COVID-19 positive or negative as used in the study. DATA COLLECTION AND ANALYSIS: We screened studies, extracted data, and assessed the risk of bias and applicability concerns using the QUADAS-2 domain-list independently, in duplicate. We categorised included studies into three groups based on classification of index test results: studies that reported specific criteria for index test positivity (group 1); studies that did not report specific criteria, but had the test reader(s) explicitly classify the imaging test result as either COVID-19 positive or negative (group 2); and studies that reported an overview of index test findings, without explicitly classifying the imaging test as either COVID-19 positive or negative (group 3). We presented the results of estimated sensitivity and specificity using paired forest plots, and summarised in tables. We used a bivariate meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS: We included 34 studies: 30 were cross-sectional studies with 8491 participants suspected of COVID-19, of which 4575 (54%) had a final diagnosis of COVID-19; four were case-control studies with 848 cases and controls in total, of which 464 (55%) had a final diagnosis of COVID-19. Chest CT was evaluated in 31 studies (8014 participants, 4224 (53%) cases), chest X-ray in three studies (1243 participants, 784 (63%) cases), and ultrasound of the lungs in one study (100 participants, 31 (31%) cases). Twenty-six per cent (9/34) of all studies were available only as preprints. Nineteen studies were conducted in Asia, 10 in Europe, four in North America and one in Australia. Sixteen studies included only adults, 15 studies included both adults and children and one included only children. Two studies did not report the ages of participants. Twenty-four studies included inpatients, four studies included outpatients, while the remaining six studies were conducted in unclear settings. The majority of included studies had a high or unclear risk of bias with respect to participant selection, index test, reference standard, and participant flow. For chest CT in suspected COVID-19 participants (31 studies, 8014 participants, 4224 (53%) cases) the sensitivity ranged from 57.4% to 100%, and specificity ranged from 0% to 96.0%. The pooled sensitivity of chest CT in suspected COVID-19 participants was 89.9% (95% CI 85.7 to 92.9) and the pooled specificity was 61.1% (95% CI 42.3 to 77.1). Sensitivity analyses showed that when the studies from China were excluded, the studies from other countries demonstrated higher specificity compared to the overall included studies. When studies that did not classify index tests as positive or negative for COVID-19 (group 3) were excluded, the remaining studies (groups 1 and 2) demonstrated higher specificity compared to the overall included studies. Sensitivity analyses limited to cross-sectional studies, or studies where at least two reverse transcriptase polymerase chain reaction (RT-PCR) tests were conducted if the first was negative, did not substantively alter the accuracy estimates. We did not identify publication status as a source of heterogeneity. For chest X-ray in suspected COVID-19 participants (3 studies, 1243 participants, 784 (63%) cases) the sensitivity ranged from 56.9% to 89.0% and specificity from 11.1% to 88.9%. The sensitivity and specificity of ultrasound of the lungs in suspected COVID-19 participants (1 study, 100 participants, 31 (31%) cases) were 96.8% and 62.3%, respectively. We could not perform a meta-analysis for chest X-ray or ultrasound due to the limited number of included studies. AUTHORS' CONCLUSIONS: Our findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may have limited capability in differentiating SARS-CoV-2 infection from other causes of respiratory illness. However, we are limited in our confidence in these results due to the poor study quality and the heterogeneity of included studies. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of suspected COVID-19 cases should be carefully interpreted. Future diagnostic accuracy studies should pre-define positive imaging findings, include direct comparisons of the various modalities of interest on the same participant population, and implement improved reporting practices. Planned updates of this review will aim to: increase precision around the accuracy estimates for chest CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X-rays and ultrasound; and obtain data to further fulfil secondary objectives (e.g. 'threshold' effects, comparing accuracy estimates across different imaging modalities) to inform the utility of imaging along different diagnostic pathways.

Endobronchial Ultrasound for the Diagnosis of Centrally Located Lung Tumors: A Systematic Review and Meta-Analysis.

INTRODUCTION: Obtaining a tissue diagnosis of centrally located lung tumors in patients presenting without endobronchial abnormalities is challenging, and therefore a considerable diagnostic problem. OBJECTIVE: The objective of this study was to evaluate the performance of linear endobronchial ultrasound guided-transbronchial-needle aspiration (EBUS-TBNA) for the diagnosis of centrally located lung tumors. METHODS: We performed a systematic review (PROSPERO, CRD42017080968) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science till November 18, 2018 for studies that evaluated the yield and/or sensitivity of EBUS-TBNA for diagnosing centrally located lung tumors. We assessed the study quality using QUADAS-2 and performed random-effects meta-analysis. RESULTS: A total of 5,657 manuscripts were identified; of these 14 were considered for the study, including 1,175 patients who underwent EBUS-TBNA for diagnosing an intrapulmonary tumor. All studies had a high risk of bias or applicability concerns, predominately regarding patient selection. The average yield of EBUS-TBNA for diagnosing centrally located lung tumors was 0.89 (95% CI 0.84-0.92) and average sensitivity for diagnosing malignant tumors was 0.91 (95% CI 0.88-0.94). Among studies reporting this information, EBUS-related complications occurred in 5.4% of patients (42/721). CONCLUSION: EBUS-TBNA has a high yield and sensitivity for diagnosing centrally located lung tumors and is safe in selected patients. Prospective studies are recommended to evaluate the routine use of this procedure for diagnosing intrapulmonary tumors.

Publication Bias: Association of Diagnostic Accuracy in Radiology Conference Abstracts with Full-Text Publication.

Background Recent investigations have identified a faster time to publication for imaging studies with higher diagnostic test accuracy (DTA), but it is unknown whether such studies are more likely to be published. A higher probability of full-text publication for studies with higher DTA could have negative consequences on clinical decision making and patient care. Purpose To evaluate the proportion of imaging diagnostic accuracy studies presented as conference abstracts that reach full-text publication and to identify whether there is an association between diagnostic accuracy and full-text publication in peer-reviewed journals within 5 years after abstract submission. Materials and Methods Diagnostic accuracy research abstracts presented at the Radiological Society of North America (RSNA) Annual Meeting in 2011 and 2012 were evaluated between September 1, 2017, and January 11, 2018. Sensitivity and specificity from the abstracts were used to calculate the Youden index (sensitivity + specificity-1); additional abstract characteristics were extracted. To identify full-text publications within 5 years after abstract submission, PubMed and Google Scholar were searched, and authors were contacted. Logistic regression analysis was used to assess for associations between higher diagnostic accuracy and full-text publication. Results A total of 7970 abstracts were evaluated, and 405 were included. Of these, 288 (71%) reached full-text publication within 5 years after abstract submission. Logistic regression analysis accounting for several confounding variables failed to show an association between reported Youden index in the conference abstract and probability of full-text publication (odds ratio, 1.01; 95% confidence interval: 0.99, 1.02; P = .21). Conclusion More than a quarter of abstracts presented at the RSNA Annual Meeting do not reach full-text publication in peer-reviewed journals. The magnitude of reported diagnostic accuracy was not associated with full-text publication, which is consistent with results of diagnostic accuracy studies in other medical specialties. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Fielding in this issue.

Systematic and combined endosonographic staging of lung cancer (SCORE study).

Guidelines recommend endosonography for mediastinal nodal staging in patients with resectable nonsmall cell lung cancer (NSCLC). We hypothesise that a systematic endobronchial ultrasound (EBUS) evaluation combined with an oesophageal investigation using the same EBUS bronchoscope (EUS-B) improves mediastinal nodal staging versus the current practice of targeted positron emission tomography (PET)-computed tomography (CT)-guided EBUS staging alone.A prospective, multicentre, international study (NCT02014324) was conducted in consecutive patients with (suspected) resectable NSCLC. After PET-CT, patients underwent systematic EBUS and EUS-B. Node(s) suspicious on CT, PET, EBUS and/or EUS-B imaging and station 4R, 4L and 7 (short axis ≥8 mm) were sampled. For patients without N2/N3 disease determined on endosonography, surgical-pathological staging was the reference standard.229 patients were included in this study. The prevalence of N2/N3 disease was 103 out of 229 patients (45%). A PET-CT-guided targeted approach by EBUS identified 75 patients with N2/N3 disease (sensitivity 73%, 95% CI 63-81%; negative predictive value (NPV) 81%, 95% CI 74-87%). Four additional patients with N2/N3 disease were found by systematic EBUS (sensitivity 77%, 95% CI 67-84%; NPV 84%, 95% CI 76-89%) and five more by EUS-B (84 patients total; sensitivity 82%, 95% CI 72-88%; NPV 87%, 95% CI 80-91%). Additional clinical relevant staging information was obtained in 23 out of 229 patients (10%).Systematic EBUS followed by EUS-B increased sensitivity for the detection of N2/N3 disease by 9% compared to PET-CT-targeted EBUS alone.