Diagnostic accuracy of ultrasound screening for fetal structural abnormalities during the first and second trimester of pregnancy in low-risk and unselected populations.

BACKGROUND: Prenatal ultrasound is widely used to screen for structural anomalies before birth. While this is traditionally done in the second trimester, there is an increasing use of first-trimester ultrasound for early detection of lethal and certain severe structural anomalies. OBJECTIVES: To evaluate the diagnostic accuracy of ultrasound in detecting fetal structural anomalies before 14 and 24 weeks' gestation in low-risk and unselected pregnant women and to compare the current two main prenatal screening approaches: a single second-trimester scan (single-stage screening) and a first- and second-trimester scan combined (two-stage screening) in terms of anomaly detection before 24 weeks' gestation. SEARCH METHODS: We searched MEDLINE, EMBASE, Science Citation Index Expanded (Web of Science), Social Sciences Citation Index (Web of Science), Arts & Humanities Citation Index and Emerging Sources Citation Index (Web of Science) from 1 January 1997 to 22 July 2022. We limited our search to studies published after 1997 and excluded animal studies, reviews and case reports. No further restrictions were applied. We also screened reference lists and citing articles of each of the included studies. SELECTION CRITERIA: Studies were eligible if they included low-risk or unselected pregnant women undergoing a first- and/or second-trimester fetal anomaly scan, conducted at 11 to 14 or 18 to 24 weeks' gestation, respectively. The reference standard was detection of anomalies at birth or postmortem. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook study selection, quality assessment (QUADAS-2), data extraction and evaluation of the certainty of evidence (GRADE approach). We used univariate random-effects logistic regression models for the meta-analysis of sensitivity and specificity. MAIN RESULTS: Eighty-seven studies covering 7,057,859 fetuses (including 25,202 with structural anomalies) were included. No study was deemed low risk across all QUADAS-2 domains. Main methodological concerns included risk of bias in the reference standard domain and risk of partial verification. Applicability concerns were common in studies evaluating first-trimester scans and two-stage screening in terms of patient selection due to frequent recruitment from single tertiary centres without exclusion of referrals. We reported ultrasound accuracy for fetal structural anomalies overall, by severity, affected organ system and for 46 specific anomalies. Detection rates varied widely across categories, with the highest estimates of sensitivity for thoracic and abdominal wall anomalies and the lowest for gastrointestinal anomalies across all tests. The summary sensitivity of a first-trimester scan was 37.5% for detection of structural anomalies overall (95% confidence interval (CI) 31.1 to 44.3; low-certainty evidence) and 91.3% for lethal anomalies (95% CI 83.9 to 95.5; moderate-certainty evidence), with an overall specificity of 99.9% (95% CI 99.9 to 100; low-certainty evidence). Two-stage screening had a combined sensitivity of 83.8% (95% CI 74.7 to 90.1; low-certainty evidence), while single-stage screening had a sensitivity of 50.5% (95% CI 38.5 to 62.4; very low-certainty evidence). The specificity of two-stage screening was 99.9% (95% CI 99.7 to 100; low-certainty evidence) and for single-stage screening, it was 99.8% (95% CI 99.2 to 100; moderate-certainty evidence). Indirect comparisons suggested superiority of two-stage screening across all analyses regarding sensitivity, with no significant difference in specificity. However, the certainty of the evidence is very low due to the absence of direct comparisons. AUTHORS' CONCLUSIONS: A first-trimester scan has the potential to detect lethal and certain severe anomalies with high accuracy before 14 weeks' gestation, despite its limited overall sensitivity. Conversely, two-stage screening shows high accuracy in detecting most fetal structural anomalies before 24 weeks' gestation with high sensitivity and specificity. In a hypothetical cohort of 100,000 fetuses, the first-trimester scan is expected to correctly identify 113 out of 124 fetuses with lethal anomalies (91.3%) and 665 out of 1776 fetuses with any anomaly (37.5%). However, 79 false-positive diagnoses are anticipated among 98,224 fetuses (0.08%). Two-stage screening is expected to correctly identify 1448 out of 1776 cases of structural anomalies overall (83.8%), with 118 false positives (0.1%). In contrast, single-stage screening is expected to correctly identify 896 out of 1776 cases before 24 weeks' gestation (50.5%), with 205 false-positive diagnoses (0.2%). This represents a difference of 592 fewer correct identifications and 88 more false positives compared to two-stage screening. However, it is crucial to acknowledge the uncertainty surrounding the additional benefits of two-stage versus single-stage screening, as there are no studies directly comparing them. Moreover, the evidence supporting the accuracy of first-trimester ultrasound and two-stage screening approaches primarily originates from studies conducted in single tertiary care facilities, which restricts the generalisability of the results of this meta-analysis to the broader population.

GRADE guidance 37: rating imprecision in a body of evidence on test accuracy.

OBJECTIVES: To provide guidance on rating imprecision in a body of evidence assessing the accuracy of a single test. This guide will clarify when Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down the certainty of evidence by one or more levels for imprecision in test accuracy. STUDY DESIGN AND SETTING: A project group within the GRADE working group conducted iterative discussions and presentations at GRADE working group meetings to produce this guidance. RESULTS: Before rating the certainty of evidence, GRADE users should define the target of their certainty rating. GRADE recommends setting judgment thresholds defining what they consider a very accurate, accurate, inaccurate, and very inaccurate test. These thresholds should be set after considering consequences of testing and effects on people-important outcomes. GRADE's primary criterion for judging imprecision in test accuracy evidence is considering confidence intervals (i.e., CI approach) of absolute test accuracy results (true and false, positive, and negative results in a cohort of people). Based on the CI approach, when a CI appreciably crosses the predefined judgment threshold(s), one should consider rating down certainty of evidence by one or more levels, depending on the number of thresholds crossed. When the CI does not cross judgment threshold(s), GRADE suggests considering the sample size for an adequately powered test accuracy review (optimal or review information size [optimal information size (OIS)/review information size (RIS)]) in rating imprecision. If the combined sample size of the included studies in the review is smaller than the required OIS/RIS, one should consider rating down by one or more levels for imprecision. CONCLUSION: This paper extends previous GRADE guidance for rating imprecision in single test accuracy systematic reviews and guidelines, with a focus on the circumstances in which one should consider rating down one or more levels for imprecision.

Common challenges and suggestions for risk of bias tool development: a systematic review of methodological studies.

OBJECTIVES: To review the findings of studies that have evaluated the design and/or usability of key risk of bias (RoB) tools for the assessment of RoB in primary studies, as categorized by the Library of Assessment Tools and InsTruments Used to assess Data validity in Evidence Synthesis Network (a searchable library of RoB tools for evidence synthesis): Prediction model Risk Of Bias ASessment Tool (PROBAST) , Risk of Bias-2 (RoB2), Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I), Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C), Quality Assessment of Prognostic Accuracy Studies (QUAPAS), Risk Of Bias in Non-randomised Studies of Exposures (ROBINS-E), and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) RoB checklist. STUDY DESIGN AND SETTING: Systematic review of methodological studies. We conducted a forward citation search from the primary report of each tool, to identify primary studies that aimed to evaluate the design and/or usability of the tool. Two reviewers assessed studies for inclusion. We extracted tool features into Microsoft Word and used NVivo for document analysis, comprising a mix of deductive and inductive approaches. We summarized findings within each tool and explored common findings across tools. RESULTS: We identified 13 tool evaluations meeting our inclusion criteria: PROBAST (3), RoB2 (3), ROBINS-I (4), and QUADAS-2 (3). We identified no evaluations for the other tools. Evaluations varied in clinical topic area, methodology, approach to bias assessment, and tool user background. Some had limitations affecting generalizability. We identified common findings across tools for 6/14 themes: (1) challenging items (eg, RoB2/ROBINS-I "deviations from intended interventions" domain), (2) overall RoB judgment (concerns with overall risk calculation in PROBAST/ROBINS-I), (3) tool usability (concerns about complexity), (4) time to complete tool (varying demands on time, eg, depending on number of outcomes assessed), (5) user agreement (varied across tools), and (6) recommendations for future use (eg, piloting) and development (add intermediate domain answer to QUADAS-2/PROBAST; provide clearer guidance for all tools). Of the other eight themes, seven only had findings for the QUADAS-2 tool, limiting comparison across tools, and one ("reorganization of questions") had no findings. CONCLUSION: Evaluations of key RoB tools have posited common challenges and recommendations for tool use and development. These findings may be helpful to people who use or develop RoB tools. Guidance is necessary to support the design and implementation of future RoB tool evaluations.

The impact of cardiovascular diagnostics and treatments on fall risk in older adults: a scoping review and evidence map.

BACKGROUND: We aimed to summarize the published evidence on the fall risk reducing potential of cardiovascular diagnostics and treatments in older adults. METHODS: Design: scoping review and evidence map. DATA SOURCES: Medline and Embase. ELIGIBILITY CRITERIA: all available published evidence; Key search concepts: "older adults," "cardiovascular evaluation," "cardiovascular intervention," and "falls." Studies reporting on fall risk reducing effect of the diagnostic/treatment were included in the evidence map. Studies that investigated cardiovascular diagnostics or treatments within the context of falls, but without reporting a fall-related outcome, were included in the scoping review for qualitative synthesis. RESULTS: Two articles on cardiovascular diagnostics and eight articles on cardiovascular treatments were included in the evidence map. Six out of ten studies concerned pacemaker intervention of which one meta-analyses that included randomized controlled trials with contradictory results. A combined cardiovascular assessment/evaluation (one study) and pharmacotherapy in orthostatic hypotension (one study) showed fall reducing potential. The scoping review contained 40 articles on cardiovascular diagnostics and one on cardiovascular treatments. It provides an extensive overview of several diagnostics (e.g., orthostatic blood pressure measurements, heart rhythm assessment) useful in fall prevention. Also, diagnostics were identified, that could potentially provide added value in fall prevention (e.g., blood pressure variability and head turning). CONCLUSION: Although the majority of studies showed a reduction in falls after the intervention, the total amount of evidence regarding the effect of cardiovascular diagnostics/treatments on falls is small. Our findings can be used to optimize fall prevention strategies and develop an evidence-based fall prevention care pathway. Adhering to the World guidelines on fall prevention recommendations, it is crucial to undertake a standardized assessment of cardiovascular risk factors, followed by supplementary testing and corresponding interventions, as effective components of fall prevention strategies. In addition, accompanying diagnostics such as blood pressure variability and head turning can be of added value.

Benefit-Harm Analysis for Informed Decision Making on Participating in Colorectal Cancer Screening: A Modeling Study.

OBJECTIVES: To facilitate informed decision making on participating in colorectal cancer (CRC) screening, we assessed the benefit-harm balance of CRC screening for a wide range of subgroups over different time horizons. METHODS: The study combined incidence proportions of benefits and harms of (not) participating in CRC screening estimated by the Adenoma and Serrated pathway to CAncer microsimulation model, a preference eliciting survey, and benefit-harm balance modeling combining all outcomes to determine the net health benefit of CRC screening over 10, 20, and 30 years. Probability of net health benefit was estimated for 210 different subgroups based on age, sex, previous participation in CRC screening, and lifestyle. RESULTS: CRC screening was net beneficial in 183 of 210 subgroups over 30 years (median probability [MP] of 0.79, interquartile range [IQR] of 0.69-0.85) across subgroups. Net health benefit was greater for men (MP 0.82; IQR 0.69-0.89) than women (MP 0.76; IQR 0.67-0.83) and for those without history of participation in previous screenings (MP 0.84; IQR 0.80-0.89) compared with those with (MP 0.69; IQR 0.59-0.75). Net health benefit decreased with increasing age, from MP of 0.84 (IQR 0.80-0.86) at age 55 to 0.61 (IQR 0.56-0.71) at age 75. Shorter time horizons led to lower benefit, with MP of 0.70 (IQR 0.62-0.80) over 20 years and 0.54 (IQR 0.48-0.67) over 10 years. CONCLUSIONS: Our benefit-harm analysis provides information about net health benefit of screening participation, based on important characteristics and preferences of individuals, which could assist screening invitees in making informed decisions on screening participation.

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

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

Diagnostic accuracy of qPCR and microscopy for cutaneous leishmaniasis in rural Ecuador: A Bayesian latent class analysis.

BACKGROUND: Clinical and laboratory diagnosis of cutaneous leishmaniasis (CL) is hampered by under-ascertainment of direct microscopy. METHODS: This study compared the diagnostic accuracy of qPCR on DNA extracted from filter paper to the accuracy of direct smear slide microscopy in participants presenting with a cutaneous lesion suspected of leishmaniasis to 16 rural healthcare centers in the Ecuadorian Amazon and Pacific regions, from January 2019 to June 2021. We used Bayesian latent class analysis to estimate test sensitivity, specificity, likelihood ratios (LR), and predictive values (PV) with their 95% credible intervals (95%CrI). The impact of sociodemographic and clinical characteristics on predictive values was assessed as a secondary objective. RESULTS: Of 320 initially included participants, paired valid test results were available and included in the diagnostic accuracy analysis for 129 from the Amazon and 185 from the Pacific region. We estimated sensitivity of 68% (95%CrI 49% to 82%) and 73% (95%CrI 73% to 83%) for qPCR, and 51% (95%CrI 36% to 66%) and 76% (95%CrI 65% to 86%) for microscopy in the Amazon and Pacific region, respectively. In the Amazon, with an estimated disease prevalence among participants of 73%, negative PV for qPCR was 54% (95%CrI 5% to 77%) and 44% (95%CrI 4% to 65%) for microscopy. In the Pacific, (prevalence 88%) the negative PV was 34% (95%CrI 3% to 58%) and 37% (95%CrI 3% to 63%). The addition of qPCR parallel to microscopy in the Amazon increases the observed prevalence from 38% to 64% (+26 (95%CrI 19 to 34) percentage points). CONCLUSION: The accuracy of either qPCR on DNA extracted from filter paper or microscopy for CL diagnosis as a stand-alone test seems to be unsatisfactory and region-dependent. We recommend further studies to confirm the clinically relevant increment found in the diagnostic yield due to the addition of qPCR.

Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies.

Background: This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Methods: Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. Results: A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. Conclusions: We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

Clinical Prediction Models and Predictors for Death or Adverse Neurodevelopmental Outcome in Term Newborns with Hypoxic-Ischemic Encephalopathy: A Systematic Review of the Literature.

BACKGROUND: Although many predictive parameters have been studied, an internationally accepted, validated predictive model to predict the clinical outcome of asphyxiated infants suffering from hypoxic-ischemic encephalopathy is currently lacking. The aim of this study was to identify, appraise and summarize available clinical prediction models, and provide an overview of all investigated predictors for the outcome death or neurodevelopmental impairment in this population. METHODS: A systematic literature search was performed in Medline and Embase. Two reviewers independently included eligible studies and extracted data. The quality was assessed using PROBAST for prediction model studies and QUIPS assessment tools for predictor studies. RESULTS: A total of nine prediction models were included. These models were very heterogeneous in number of predictors assessed, methods of model derivation, and primary outcomes. All studies had a high risk of bias following the PROBAST assessment and low applicability due to complex model presentation. A total of 104 predictor studies were included investigating various predictors, showing tremendous heterogeneity in investigated predictors, timing of predictors, primary outcomes, results, and methodological quality according to QUIPS. Selected high-quality studies with accurate discriminating performance provide clinicians and researchers an evidence map of predictors for prognostication after HIE in newborns. CONCLUSION: Given the low methodological quality of the currently published clinical prediction models, implementation into clinical practice is not yet possible. Therefore, there is an urgent need to develop a prediction model which complies with the PROBAST guideline. An overview of potential predictors to include in a prediction model is presented.

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

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

Over-interpretation of findings in diagnostic accuracy studies of infectious diseases.

OBJECTIVES: To assess the prevalence of overly positive interpretation, also called 'spin',-of results in diagnostic accuracy studies of infectious diseases and to identify suggestions for improvement. METHODS: A PubMed search was performed to identify diagnostic accuracy studies of infectious diseases published between January and March 2019. Each article was assessed by two authors independently to identify study characteristics and forms of actual and potential over-interpretation. 'Actual over-interpretation' was defined as conclusions that were not on the basis of study aims or conclusions that were more favourable than justified by the study findings. There are other practices that may result in the over-interpretation of study findings and these have been described as 'potential over-interpretation'. RESULTS: The final analysis included 120 studies. Favourable or promising recommendations were made in the main text of 101 (84%) of the included studies. Evidence of actual over-interpretation (spin) was found in 30 (25%) articles, with 22 (18%) studies reporting a conclusion that did not match the study aims and 56 (47%) studies with a more positive conclusion in the abstract than the main text. All analysed studies exhibited at least one form of potential over-interpretation, with was most commonly a lack of sample size calculation (n = 109, 91%) and not reporting a null hypothesis (n = 115, 96%). DISCUSSION: Evidence of over-interpretation of results was found in one-third of the included studies. We have proposed possible interventions to prevent overly positive interpretations of results in diagnostic accuracy studies.

Perceived Importance of the Benefits and Harms of Colorectal Cancer Screening: A Best-Worst Scaling Study.

OBJECTIVES: To elicit the relative importance of the benefits and harms of colorectal cancer (CRC) screening among potential screening participants in the Dutch population. METHODS: In a consensus meeting with 11 experts, risk reduction of CRC and CRC deaths (benefits) and complications from colonoscopy, stress of receiving positive fecal immunological test (FIT) results, as well as false-positive and false-negative FIT results (harms) were selected as determinant end points to consider during decision making. We conducted an online best-worst scaling survey among adults aged 55 to 75 years from the Dutch Health Care Consumer Panel of The Netherlands Institute for Health Services Research to elicit preference values for these outcomes. The preference values were estimated using conditional logit regression. RESULTS: Of 265 participants, 234 (89%) had ever participated in CRC screening. Compared with the stress of receiving a positive FIT result, the outcome perceived most important was the risk of CRC death (odds ratio [OR] 4.5; 95% confidence interval [CI] 3.9-5.1), followed by risk of CRC (OR 4.1; 95% CI 3.6-4.7), a false-negative FIT result (OR 3.1; 95% CI 2.7-3.5), colonoscopy complications (OR 1.6; 95% CI 1.4-1.8), and a false-positive FIT result (OR 1.4; 95% CI 1.3-1.6). The magnitude of these differences in perceived importance varied according to age, educational level, ethnic background, and whether the individual had previously participated in CRC screening. CONCLUSION: Dutch men and women eligible for FIT-based CRC screening perceive the benefits of screening to be more important than the harms.

Diagnostic accuracy and added value of blood-based protein biomarkers for pancreatic cancer: A meta-analysis of aggregate and individual participant data.

Background: Novel blood-based protein biomarkers may be of value for efficient, accurate, and non-invasive diagnosis of pancreatic cancer. This study assesses the diagnostic accuracy of newly recognized blood-based protein biomarkers for detecting pancreatic cancer, and investigates their added value to CA19-9, the common blood-based biomarker in clinical use for pancreatic cancer. Methods: PubMed, Embase, Web of Science, and the Wiley/Cochrane Library were systematically searched from inception until June 2022. A meta-analysis of aggregate and individual participant data was conducted using frequentist and Bayesian hierarchical random-effects models. The added clinical utility of protein biomarkers was investigated using bootstrap bias-corrected decision curve analyses. Findings: Aggregate data from 28 primary studies (6127 participants) were included, of which 8 studies (1790 participants) provided individual participant data. CA19-9 was significantly more accurate than MIC-1 for distinguishing pancreatic cancer from benign disease (AUC, 0.83 vs 0.74; relative diagnostic odds ratio [rDOR], 2.10 [95% CI, 0.98-4.48]; p = 0.002), THBS2 (AUC, 0.87 vs 0.69; rDOR, 4.53 [2.16-9.39]; p < 0.0001), TIMP-1 (AUC, 0.91 vs 0.70; rDOR, 8.00 [3.81-16.9]; p < 0.0001), OPN (AUC, 0.89 vs 0.74; rDOR, 4.22 [1.13-15.6]; p < 0.0001), ICAM-1 (AUC, 0.91 vs 0.68; rDOR 9.30 [0.87-99.5]; p < 0.0001), and IGFBP2 (AUC, 0.91 vs 0.68; rDOR, 4.48 [0.78-24.3]; p < 0.0001). The addition of these novel protein biomarkers to CA19-9 did not significantly improve the AUC, and resulted in minor increases or limited decreases in clinical utility. Interpretation: Novel protein biomarkers have moderate diagnostic accuracy, do not outperform CA19-9 in differentiating pancreatic cancer from benign disease, and show limited added clinical value to CA19-9. We propose recommendations to aid the development of minimally invasive diagnostic tests with sufficient clinical utility to improve the management of patients with suspected pancreatic cancer. Funding: Bennink Foundation, Dutch Cancer Foundation (KWF Kankerbestrijding), and AIRC.

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

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