Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy for diagnosing interstitial lung disease (the COLD study): a randomised controlled trial.

BACKGROUND: An adequate diagnosis for interstitial lung disease (ILD) is important for clinical decision making and prognosis. In most patients with ILD, an accurate diagnosis can be made by clinical and radiological data assessment, but in a considerable proportion of patients, a lung biopsy is required. Surgical lung biopsy (SLB) is the most common method to obtain tissue, but it is associated with high morbidity and even mortality. More recently, transbronchial cryobiopsy has been introduced, with fewer adverse events but a lower diagnostic yield than SLB. The aim of this study is to compare two diagnostic strategies: a step-up strategy (transbronchial cryobiopsy, followed by SLB if the cryobiopsy is insufficiently informative) versus immediate SLB. METHODS: The COLD study was a multicentre, randomised controlled trial in six hospitals across the Netherlands. We included patients with ILD with an indication for lung biopsy as assessed by a multidisciplinary team discussion. Patients were randomly assigned in a 1:1 ratio to the step-up or immediate SLB strategy, with follow-up for 12 weeks from the initial procedure. Patients, clinicians, and pathologists were not masked to the study treatment. The primary endpoint was unexpected chest tube drainage, defined as requiring any chest tube after transbronchial cryobiopsy, or prolonged (>24 h) chest tube drainage after SLB. Secondary endpoints were diagnostic yield, in-hospital stay, pain, and serious adverse events. A modified intention-to-treat analysis was performed. This trial is registered with the Dutch Trial Register, NL7634, and is now closed. FINDINGS: Between April 8, 2019, and Oct 24, 2021, 122 patients with ILD were assessed for study participation; and 55 patients were randomly assigned to the step-up strategy (n=28) or immediate SLB (n=27); three patients from the immediate SLB group were excluded. Unexpected chest tube drainage occurred in three of 28 patients (11%; 95% CI 4-27%) in the step-up group, and the number of patients for whom the chest tube could not be removed within 24 h was 11 of 24 patients (46%; 95% CI 2-65%) in the SLB group, with an absolute risk reduction of 35% (11-56%; p=0·0058). In the step-up strategy, the multidisciplinary team diagnostic yield after transbronchial cryobiopsy alone was 82% (64-92%), which increased to 89% (73-96%) when subsequent SLB was performed after inconclusive transbronchial cryobiopsy. In the immediate surgery strategy, the multidisciplinary team diagnostic yield was 88% (69-97%). Total in-hospital stay was 1 day (IQR 1-1) in the step-up group versus 5 days (IQR 4-6) in the SLB group. One (4%) serious adverse event occurred in step-up strategy versus 12 (50%) in the immediate SLB strategy. INTERPRETATION: In ILD diagnosis, if lung tissue assessment is required, a diagnostic strategy starting with transbronchial cryobiopsy, followed by SLB when transbronchial cryobiopsy is inconclusive, appears to result in a significant reduction of patient burden and in-hospital stay with a similar diagnostic yield versus immediate SLB. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW) and Amsterdam University Medical Centers.

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.

Performance of EUS-FNA and EUS-B-FNA for the diagnosis of left adrenal glands metastases in patients with lung cancer: A systematic review and meta-analysis.

OBJECTIVES: For diagnosing left adrenal gland metastasis in lung cancer, clinical guidelines recommend to perform EUS, but EUS-B (EUS using an EBUS-scope) is increasingly being used. We evaluated the diagnostic performance of both procedures. MATERIALS AND METHODS: We did a systematic review (PROSPERO, CRD42023416205) and searched MEDLINE and EMBASE on 04-July-2023 for studies evaluating EUS and/or EUS-B in diagnosing left adrenal gland metastases in adults with (suspected) lung cancer. Outcomes were: (1) ability to visualize the left adrenal gland, (2) ability to sample (in those with successful visualization and in whom sampling was attempted), (3) ability to obtain adequate material (in those with successful sampling), (4) malignancy detection rate (in those with successful sampling), and (5) remaining risk of malignancy (in those with a negative EUS(-B)-FNA and undergoing a reference standard). We performed random-effects meta-analyses. RESULTS: We included 19 studies (EUS: n = 11, EUS-B: n = 6, both: n = 2), covering 1712 patients. All studies had high (n = 18) or unclear (n = 1) risk of bias (QUADAS-2). Average ability to visualize the left adrenal gland was 0.94 (95 %CI 0.82-0.98; n = 7 studies). Average ability to sample was 1.00 (95 %CI 0.99-1.00; n = 9). Average ability to obtain adequate material was 0.96 (95 %CI 0.93-0.98; n = 18). Average malignancy detection rate was 0.42 (95 %CI 0.34-0.49; n = 18). Remaining risk of malignancy was 0.07 (95 %CI 0.04-0.12; n = 8). Ability to visualize was slightly higher for EUS (0.99; 95 %CI 0.90-1.00) than EUS-B (0.84; 95 %CI 0.70-0.92; p = 0.025), but the other performance characteristics were similar. No major complications were reported. CONCLUSION: Both EUS and EUS-B have good performance and are safe for left adrenal gland analysis in patients with lung cancer, but the number of high-quality studies is limited and further well-constructed prospective studies are needed.

Endobronchial ultrasound in diagnosing and staging of lung cancer by Acquire 22G TBNB versus regular 22G TBNA needles: A randomized clinical trial.

OBJECTIVES: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has an important role in the diagnosis and staging of lung cancer. Evaluation of programmed death ligand 1 (PD-L1) expression and molecular profiling has become standard of care but cytological samples frequently contain insufficient tumor cells. The 22G Acquire needle with Franseen needle tip was developed to perform transbronchial needle biopsy (TBNB) with improved tissue specimens. This study evaluated if the 22G Acquire TBNB needle results in enhanced PD-L1 suitability rate compared to the regular Expect 22G TBNA needle. METHODS: in this multi-center randomized clinical trial (Netherlands Trial Register NL7701), patients with suspected (N)SCLC and an indication for mediastinal/hilar staging or lung tumor diagnosis were recruited in five university and general hospitals in the Netherlands, Poland, Italy and Czech Republic. Patients were randomized (1:1) between the two needles. Two blinded reference pathologists evaluated the samples. The primary outcome was PD-L1 suitability rate in patients with a final diagnosis of lung cancer. In case no malignancy was diagnosed, the reference standard was surgical verification or 6 month follow-up. RESULTS: 154 patients were randomized (n = 76 Acquire TBNB; n = 78 Expect TBNA) of which 92.9% (n = 143) had a final malignant diagnosis. Suitability for PD-L1 analysis was 80.0% (n = 56/70; 95 %CI 0.68-0.94) with the Acquire needle and 76.7% (n = 56/73; 95 %CI 0.65-0.85) with the Expect needle (p = 0.633). Acquire TBNB needle specimens provided more frequent superior quality (65.3% (95 %CI 0.57-0.73) vs 49.4% (95 %CI 0.41-0.57, p = 0.005) and contained more tissue cores (72.0% (95 %CI 0.60-0.81) vs 41.0% (95 %CI 0.31-0.54, p < 0.01). There were no statistically significant differences in tissue adequacy, suitability for molecular analysis and sensitivity for malignancy and N2/N3 disease. CONCLUSION: The 22G Acquire TBNB needle procured improved quality tissue specimens compared to the Expect TBNA needle but this did not result in an improved the suitability rate for PD-L1 analysis.

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.

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.

Diagnostic yield and safety of navigation bronchoscopy: A systematic review and meta-analysis.

BACKGROUND: Navigation bronchoscopy has seen rapid development in the past decade in terms of new navigation techniques and multi-modality approaches utilizing different techniques and tools. This systematic review analyses the diagnostic yield and safety of navigation bronchoscopy for the diagnosis of peripheral pulmonary nodules suspected of lung cancer. METHODS: An extensive search was performed in Embase, Medline and Cochrane CENTRAL in May 2022. Eligible studies used cone-beam CT-guided navigation (CBCT), electromagnetic navigation (EMN), robotic navigation (RB) or virtual bronchoscopy (VB) as the primary navigation technique. Primary outcomes were diagnostic yield and adverse events. Quality of studies was assessed using QUADAS-2. Random effects meta-analysis was performed, with subgroup analyses for different navigation techniques, newer versus older techniques, nodule size, publication year, and strictness of diagnostic yield definition. Explorative analyses of subgroups reported by studies was performed for nodule size and bronchus sign. RESULTS: A total of 95 studies (n = 10,381 patients; n = 10,682 nodules) were included. The majority (n = 63; 66.3%) had high risk of bias or applicability concerns in at least one QUADAS-2 domain. Summary diagnostic yield was 70.9% (95%-CI 68.4%-73.2%). Overall pneumothorax rate was 2.5%. Newer navigation techniques using advanced imaging and/or robotics(CBCT, RB, tomosynthesis guided EMN; n = 24 studies) had a statistically significant higher diagnostic yield compared to longer established techniques (EMN, VB; n = 82 studies): 77.5% (95%-CI 74.7%-80.1%) vs 68.8% (95%-CI 65.9%-71.6%) (p < 0.001).Explorative subgroup analyses showed that larger nodule size and bronchus sign presence were associated with a statistically significant higher diagnostic yield. Other subgroup analyses showed no significant differences. CONCLUSION: Navigation bronchoscopy is a safe procedure, with the potential for high diagnostic yield, in particular using newer techniques such as RB, CBCT and tomosynthesis-guided EMN. Studies showed a large amount of heterogeneity, making comparisons difficult. Standardized definitions for outcomes with relevant clinical context will improve future comparability.

High flow nasal cannula for acute respiratory failure due to COVID-19 in patients with a 'do-not-intubate' order: A survival analysis.

INTRODUCTION: High flow nasal cannula (HFNC) reduces the need for intubation in patients with hypoxaemic acute respiratory failure (ARF), but its added value in patients with severe coronavirus disease 2019 (COVID-19) and a do-not-intubate (DNI) order is unknown. We aimed to assess (variables associated with) survival in these patients. MATERIALS AND METHODS: We described a multicentre retrospective observational cohort study in five hospitals in the Netherlands and assessed the survival in COVID-19 patients with severe acute respiratory failure and a DNI order who were treated with high flow nasal cannula. We also studied variables associated with survival. RESULTS AND DISCUSSION: One-third of patients survived after 30 days. Survival was 43.9% in the subgroup of patients with a good WHO performance status and only 16.1% in patients with a poor WHO performance status. Patients who were admitted to the hospital for a longer period prior to HFNC initiation were less likely to survive. HFNC resulted in an increase in ROX values, reflective of improved oxygenation and/or decreased respiratory rate. CONCLUSION: Our data suggest that a trial of HFNC could be considered to increase chances of survival in patients with ARF due to COVID-19 pneumonitis and a DNI order, especially in those with a good WHO performance status.

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".

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.

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.

Endobronchial ultrasound in diagnosing and staging of lung cancer by Acquire 22G TBNB versus regular 22G TBNA needles: study protocol of a randomised clinical trial.

INTRODUCTION: Accurate diagnosis and staging of lung cancer is crucial because it directs treatment and prognosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) are important in this process by sampling hilar/mediastinal lymph nodes and centrally located lung tumours. With the upcoming of immunotherapy and targeted therapies, assessment of programmed death ligand 1 (PD-L1) expression and molecular profiling has become important but is often impossible in cytological samples obtained through standard 22G TBNA needles. Recently, a three-pronged cutting edge 22G needle was developed that allows for transbronchial needle biopsy (TBNB). Our objective is to determine if EBUS/EUS-B-guided nodal/lung tumour sampling with Acquire 22G TBNB needles results in an improved suitability rate for the assessment of PD-L1 expression in comparison to standard 22G TBNA needles in patients with a final diagnosis of lung cancer. METHODS AND ANALYSIS: This is an investigator-initiated, parallel group randomised clinical trial. Patients are recruited at respiratory medicine outpatient clinics of participating university and general hospitals in the Netherlands, Poland and Italy. In total 158 adult patients with (suspected) lung cancer are included if they have an indication for mediastinal/hilar lymph node or lung tumour sampling by EBUS-TBNA and/or EUS-B-FNA based on current clinical guidelines. Web-based randomisation between the two needles will be performed. Samples obtained from mediastinal/hilar lymph nodes and/or primary tumour will be processed for cytology smears and cell block analysis and reviewed by blinded reference pathologists. An intention-to-treat analysis will be applied. Patients with missing data will be excluded from analysis for that specific variable but included in the analysis of other variables. This study is financially supported by Boston Scientific. ETHICS AND DISSEMINATION: The study was approved by the local Ethics Committee (Medisch Ethische Toetsingscommissie Amsterdam Medical Center (AMC)). Dissemination will involve publication in a peer-reviewed biomedical journal. TRIAL REGISTRATION NUMBER: NL7701; Pre-results.

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.

Endobronchial ultrasound for T4 staging in patients with resectable NSCLC.

BACKGROUND: In lung cancer patients, accurate assessment of mediastinal and vascular tumor invasion (stage T4) is crucial for optimal treatment allocation and to prevent unnecessary thoracotomies. We assessed the diagnostic accuracy of linear endobronchial ultrasound (EBUS) for T4-status in patients with centrally located lung cancer. METHODS: This is a retrospective study among consecutive patients who underwent EBUS for diagnosis and staging of lung cancer in four hospitals in The Netherlands (Amsterdam, Leiden), Italy (Bologna) and Poland (Zakopane) between 04-2012 and 04-2019. Patients were included if the primary tumor was detected by EBUS and subsequent surgical-pathological staging was performed, which served as the reference standard. T4-status was extracted from EBUS and pathology reports. Chest CT's were re-reviewed for T4-status. RESULTS: 104 patients with lung cancer in whom EBUS detected the primary tumour, and who underwent subsequent surgical-pathological staging were included. 36 patients (35 %) had T4-status, based on vascular (n = 17), mediastinal (n = 15), both vascular and mediastinal (n = 3), or oesophageal invasion (n = 1). For EBUS, sensitivity, specificity, PPV and NPV for T4-status were (n = 104): 63.9 % (95 %CI 46.2-79.2 %), 92.6 % (83.7-97.6 %), 82.1 % (65.6-91.7 %), and 82.9 % (75.7-88.2 %), respectively. For chest CT (n = 72): 61.5 % (95 %CI 40.6-79.8 %), 37.0 % (23.2-52.5 %), 35.6 % (27.5-44.6 %), and 63.0 % (47.9-75.9 %), respectively. When combining CT and EBUS with concordant T4 status (n = 33): 90.9 % (95 %CI 58.7-99.8 %), 77.3 % (54.6-92.20 %), 66.7 % (47.5-81.6 %), and 94.4 % (721-99.1%), respectively. CONCLUSION: Both EBUS and CT alone are inaccurate for assessing T4-status as standalone test. However, combining a negative EBUS with a negative CT may rule out T4-status with high certainty.