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Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that takes an airway segmentation and CT image as input and systematically parcellates the airway tree into its lobes and generational branches, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent. [ABSTRACT FROM AUTHOR]

Objectives: Head-to-head comparison of ultrasound and CT accuracy in common diagnoses causing acute abdominal pain.Materials and Methods: Consecutive patients with abdominal pain for >2 h and <5 days referred for imaging underwent both US and CT by different radiologists/radiological residents. An expert panel assigned a final diagnosis. Ultrasound and CT sensitivity and predictive values were calculated for frequent final diagnoses. Effect of patient characteristics and observer experience on ultrasound sensitivity was studied.Results: Frequent final diagnoses in the 1,021 patients (mean age 47; 55% female) were appendicitis (284; 28%), diverticulitis (118; 12%) and cholecystitis (52; 5%). The sensitivity of CT in detecting appendicitis and diverticulitis was significantly higher than that of ultrasound: 94% versus 76% (p < 0.01) and 81% versus 61% (p = 0.048), respectively. For cholecystitis, the sensitivity of both was 73% (p = 1.00). Positive predictive values did not differ significantly between ultrasound and CT for these conditions. Ultrasound sensitivity in detecting appendicitis and diverticulitis was not significantly negatively affected by patient characteristics or reader experience.Conclusion: CT misses fewer cases than ultrasound, but both ultrasound and CT can reliably detect common diagnoses causing acute abdominal pain. Ultrasound sensitivity was largely not influenced by patient characteristics and reader experience. [ABSTRACT FROM AUTHOR]

Objectives: To identify and evaluate profiles of US and CT features associated with acute appendicitis.Methods: Consecutive patients presenting with acute abdominal pain at the emergency department were invited to participate in this study. All patients underwent US and CT. Imaging features known to be associated with appendicitis, and an imaging diagnosis were prospectively recorded by two independent radiologists. A final diagnosis was assigned after 6 months. Associations between appendiceal imaging features and a final diagnosis of appendicitis were evaluated with logistic regression analysis.Results: Appendicitis was assigned to 284 of 942 evaluated patients (30%). All evaluated features were associated with appendicitis. Imaging profiles were created after multivariable logistic regression analysis. Of 147 patients with a thickened appendix, local transducer tenderness and peri-appendiceal fat infiltration on US, 139 (95%) had appendicitis. On CT, 119 patients in whom the appendix was completely visualised, thickened, with peri-appendiceal fat infiltration and appendiceal enhancement, 114 had a final diagnosis of appendicitis (96%). When at least two of these essential features were present on US or CT, sensitivity was 92% (95% CI 89-96%) and 96% (95% CI 93-98%), respectively.Conclusion: Most patients with appendicitis can be categorised within a few imaging profiles on US and CT. When two of the essential features are present the diagnosis of appendicitis can be made accurately. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: A prospective single-arm trial. OBJECTIVE.: To investigate whether dynamic isolated resistance training of global lumbar extensor muscles leads to changes in lumbar multifidus (LM) morphology in terms of cross-sectional muscle, and, if so, whether these changes are associated with observed changes in self-experienced functional status of chronic nonspecific low back pain (CNSLBP). SUMMARY OF BACKGROUND DATA.: LM morphology is associated with the recurrence of CNSLBP. METHODS.: Sixteen male patients underwent a dynamic isolated resistance-training program for the lower back muscles of approximately 10 sessions in 12 weeks. In the next 12 weeks, frequency of training was tailored to the patients' need. Participants underwent lumbar magnetic resonance imaging at baseline (T0), after 12 weeks (T12), and after 24 weeks (T24). Functional cross-sectional area was obtained by analyzing the magnetic resonance images. Functional status was assessed using the patient-specific functional scale, Roland-Morris disability questionnaire, and global perceived effect scale. RESULTS.: Roland-Morris disability questionnaire and patient-specific functional scale scores showed significant and clinically relevant improvements between baseline and T12, with 44% and 39%, respectively. Between T12 and T24, these scores did not change significantly. Seven participants (44%) reported clinically relevant improvements in global perceived effect at T12. At T24, 1 more participant reported a relevant global perceived effect improvement, whereas 2 participants (13%) reported worsening of their condition. The magnetic resonance imaging analysis showed minor nonsignificant changes in functional cross-sectional area. CONCLUSION.: Our study shows that 10 weeks of dynamic isolated training of the lumbar extensors, once a week, leads to clinically relevant improvements in functional status of men with CNSLBP, without accompanying improvements in functional cross-sectional area of LM. These findings suggest that improvement in LM morphology is not a critical success factor in restoring functional status of patients with CNSLBP, at least in the short term (6 mo). [ABSTRACT FROM AUTHOR]

Objectives: Screening for obstructive coronary artery disease (CAD) with coronary computed tomography angiography (CCTA) could prevent unnecessary invasive coronary angiography (ICA) procedures during work-up for trans-catheter aortic valve implantation (TAVI). CT-derived fractional flow reserve (CT-FFR) improves CCTA accuracy in chest pain patients. However, its reliability in the TAVI population is unknown. This systematic review and meta-analysis assesses CCTA and CT-FFR in TAVI candidates., Methods: PubMed, Embase and Web of Science were searched for studies regarding CCTA and/or CT-FFR in TAVI candidates. Primary endpoint was correct identification and rule-out of obstructive CAD. Results were pooled in a meta-analysis., Results: Thirty-four articles were part of the meta-analysis, reporting results for CCTA and CT-FFR in 7235 and 1269 patients, respectively. Reference standard was mostly anatomical severity of CAD. At patient level, pooled CCTA sensitivity was 94.0% and specificity 72.4%. CT-FFR sensitivity was 93.2% and specificity 70.3% with substantial variation between studies. However, in studies that compared both, CT-FFR performed better than CCTA. Sensitivity of CCTA versus CT-FFR was 74.9% versus 83.9%, and specificity was 65.5% versus 89.8%., Conclusions: Negative CCTA accurately rules out CAD in the TAVI population. CCTA could lead to significant reduction in pre-TAVI ICA, but false positives remain high. Diagnostic accuracy of CT-FFR was comparable to that of CCTA in our meta-analyses, but in studies performing a direct comparison, CT-FFR performed better than CCTA. However, as most studies were small and used CT-FFR software exclusively available for research, a large study on CT-FFR in TAVI work-up using commercially available CT-FFR software would be appropriate before considering routine implementation., Key Points: Question Coronary artery disease (CAD) screening with invasive coronary angiography before trans-catheter aortic valve implantation (TAVI) is often retrospectively unnecessary, revealing no obstructive CAD. Findings Coronary CTA ruled out CAD in approximately half of TAVI candidates. CT-derived fractional flow reserve (CT-FFR) performed similarly overall but better than coronary CTA in direct comparison. Clinical relevance Addition of coronary CTA to TAVI planning-CT to screen for obstructive CAD could reduce negative invasive coronary angiographies in TAVI work-up. CT-FFR could reduce false-positive coronary CTA results, improving its gatekeeper function in this population, but more data is necessary., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Dr M.J. Swaans. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors has significant statistical expertise (Joyce Peper). Informed consent: Written informed consent was not required for this study because this is a systematic review and meta-analysis on existing literature. Ethical approval: Institutional Review Board approval was not required because this is a systematic review and meta-analysis on existing literature. Study subjects or cohorts overlap: As this is a systematic review and meta-analysis on existing literature, all included subjects have been previously reported in published articles. Methodology: Meta-analysis, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Introduction: Early detection of cardiac sarcoidosis (CS) is crucial due to its association with severe complications such as ventricular arrhythmias, heart failure, and sudden cardiac death. Advanced imaging techniques like cardiac magnetic resonance imaging (CMR) and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) are effective in detecting CS but not easily accessible. The optimal method for selecting patients for advanced screening remains uncertain., Methods: In this retrospective cohort study, all extracardiac sarcoidosis patients screened for CS were reviewed. CS was defined as a multidisciplinary team (MDT) consensus diagnosis. Univariate and multivariate binary logistic regressions were used to identify factors associated with CS, assessing their diagnostic performance, and integrating them into a diagnostic model., Results: Out of 354 patients (average age 51.5 years, 52.5% male), 18.4% were diagnosed with CS. In our cohort, male gender, a QRS duration > 120 ms, and nsVT on Holter monitoring were identified as significant markers associated with CS. Combining age, gender, AV-block or QRS > 120ms on ECG, and nsVT on Holter monitoring provided the highest diagnostic accuracy (AUC of 0.82). Cardiac biomarkers NT-proBNP and troponin T did not improve the diagnostic performance., Conclusion: In our cohort, male gender, a QRS duration > 120 ms, and nsVT on Holter monitoring were identified as significant markers associated with the presence of cardiac sarcoidosis. These clinical markers may aid in selecting sarcoidosis patients for screening with advanced cardiac imaging, potentially leading to earlier detection and management of the disease., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Conflict of interest: None to declared.

Computed tomography-derived fractional flow reserve (CT-FFR) enhances the specificity of coronary computed tomography angiography (CCTA) to that of the most specific non-invasive imaging techniques, while maintaining high sensitivity in stable coronary artery disease (CAD). As gatekeeper for invasive coronary angiography (ICA), use of CT-FFR results in a significant reduction of negative ICA procedures and associated costs and complications, without increasing cardiovascular events. It is expected that CT-FFR algorithms will continue to improve, regarding accuracy and generalisability, and that introduction of new features will allow further treatment guidance and reduced invasive diagnostic testing. Advancements in CCTA quality and artificial intelligence (AI) are starting to unfold the incremental diagnostic and prognostic capabilities of CCTA's attenuation-based images in CAD, with future perspectives promising additional CCTA parameters which will enable non-invasive assessment of myocardial ischaemia as well as CAD activity and future cardiovascular risk. This review discusses practical application, interpretation and impact of CT-FFR on patient care, and how this ties into the CCTA 'one stop shop' for coronary assessment and patient prognosis. In this light, selective adoption of the most promising, objective and reproducible techniques and algorithms will yield maximal diagnostic value of CCTA without overcomplicating patient management and guideline recommendations., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts., Methods: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide ( D LCO ) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups., Results: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations., Conclusion: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients., Competing Interests: Conflict of interest: J. Jacob reports fees from Boehringer Ingelheim, Roche, NHSX, Takeda and GlaxoSmithKline, unrelated to the submitted work, and was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z and the NIHR Biomedical Research Centre at University College London. N. Mogulkoc reports grant TUBITAK (EJP Rare Disease project “COCOS-IPF”), fees from Boehringer Ingelheim, Roche, and Nobel Turkey unrelated to the submitted work, and received support for travel to meetings from Roche and Actelion. T.J. Corte reports unrestricted educational grants from Boehringer Ingelheim, Roche, Biogen and Galapagos, fees from Roche, BMS, Boehringer Ingelheim, Vicore and DevPro, assistance for travel to meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board for Roche, BMS, Boehringer Ingelheim, Vicore, Ad Alta, Bridge Biotherapeutics and DevPro. P. Vasudev reports financial interests from Blackford Analysis. T. Goos is supported by Research Foundation Flanders (1S73921N). L.J. De Sadeleer is supported by Marie Sklodowska-Curie actions postdoctoral fellowship within the European Union's Horizon Europe research and innovation programme. H. Jo reports fees from Boehringer Ingelheim and Roche, and received assistance for travel to meetings from Boehringer Ingelheim and Roche. S. Verleden reports consultancy fees from Boehringer Ingelheim and Sanofi. M. Vermant is supported by an FWO (Research Flanders Foundation) fellowship. S.M. Janes reports fees from AstraZeneca, Bard1 Bioscience, Achilles Therapeutics and Jansen unrelated to the submitted work, received assistance for travel to meetings from AstraZeneca and Takeda, and is the investigator lead on grants from GRAIL Inc., GlaxoSmithKline plc and Owlstone. A.U. Wells reports personal fees and non-financial support from Boehringer Ingelheim, Bayer and Roche Pharmaceuticals, and personal fees from Blade, outside of the submitted work. The remaining authors report no relevant conflicts of interest., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP)., Methods: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change., Results: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045)., Interpretation: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression., Competing Interests: Conflict of interest: J. Jacob reports fees from Boehringer Ingelheim, Roche, NHSX, Takeda and GlaxoSmithKline unrelated to the submitted work. J. Jacob was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z and the NIHR Biomedical Research Centre at University College London. S.M. Janes reports fees from AstraZeneca, Bard1 Bioscience, Achilles Therapeutics and Janssen unrelated to the submitted work. S.M. Janes received assistance for travel to meetings from AstraZeneca to American Thoracic Conference 2018 and from Takeda to World Conference Lung Cancer 2019, and is the Investigator Lead on grants from GRAIL Inc, GlaxoSmithKline plc and Owlstone. A.U. Wells reports personal fees and nonfinancial support from Boehringer Ingelheim, Bayer and Roche Pharmaceuticals; and personal fees from Blade, outside of the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Connective tissue diseases-associated interstitial lung disease (CTD-ILD) is a heterogeneous condition that impairs quality of life and is associated with premature death. Progressive pulmonary fibrosis (PPF) has been identified as an important risk factor for poor prognosis. However, different criteria for PPF are used in clinical studies, which may complicate comparison between trials and translation of study findings into clinical practice., Methods: This is a retrospective single center study in patients with CTD-ILD. The prognostic relevance of PPF definitions, including INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified progressive fibrosing (simplified PF) criteria, were examined in this cohort and validated in the other reported Dutch CTD-ILD cohort., Results: A total of 230 patients with CTD-ILD were included and the median follow-up period was six (3-9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p  < 0.001), smoking history (adjusted HR 1.90, p  = 0.045), extent of fibrosis on high-resolution computed tomography (HRCT) at baseline (adjusted HR 1.05, p  = 0.018) and baseline DLCO (adjusted HR 0.97, p  = 0.013). Patients with regular pulmonary function tests in the first 2 years (adjusted HR 0.42, p  = 0.002) had a better survival. The prognostic relevance for survival was similar between the three PPF criteria in the two cohorts., Conclusion: Higher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis, while regular pulmonary function evaluation was associated with better survival. The INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified PF criteria revealed similar prognostication., Competing Interests: JS and JL have received an unrestricted grant from Boehringer, JL has received honoraria from Abbvie, Arxx Tx, Galapagos, Gesyntha, Leadiant, Roche, and research grants from Astra Zeneca, MSD, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chiu, Koops, Voortman, van Es, Langezaal, Welsing, Jamnitski, Wind, van Laar, Grutters and Spierings.)

Background: Idiopathic pulmonary fibrosis (IPF) often has significant diagnostic delay. At present it is not well-known what factors associate with time to diagnosis and if this is associated with survival after the diagnosis. There has also been increasing attention for interstitial lung abnormalities on chest CT-scans. In this study we assessed what factors associate with time to diagnosis in patients with IPF, and whether early stages of pulmonary fibrosis can be seen on chest X-rays prior to the start of symptoms., Methods: In this retrospective study, 409 Dutch patients with IPF were included. Clinical characteristics, including patient demographics, medical history, time of start of symptoms, time of first visit to pulmonologist, and any previous radiographic imaging reports were collected from patient records., Results: In 96 patients (23%) a chest X-ray was available that had been made prior to the start of symptoms (median of 50.5 months (IQR 26.3-83.3 months)), and this showed potential interstitial lung abnormalities in 56 patients (58%). The median time from the start of symptoms to the final diagnosis was 24.0 months (interquartile range 9.0-48.0 months). In a multivariate model that corrected for diffusion capacity of the lung for carbon monoxide, forced vital capacity, sex, and age at diagnosis, time to diagnosis did not associate with survival (hazard ratio 1.051 (95% CI 0.800-1.380; p = 0.72))., Conclusions: There is a significant diagnostic delay for patients with IPF, but longer time to diagnosis did not associate with survival. Interstitial lung abnormalities were seen in more than half of the patients in whom a chest X-ray had been made prior to the start of symptoms. This illustrates that a computed tomography scan should be strongly considered for analysis of unexplained abnormalities on a chest X-ray. This could facilitate early detection and possibly prevention of disease progression for patients with pulmonary fibrosis., (© 2022. The Author(s).)

Background: Cardiac sarcoidosis (CS) is associated with an increased risk for sudden cardiac death. An implantable cardiac defibrillator (ICD) is recommended in a subgroup of CS patients. However, the recommendations for primary prevention differ between guidelines. The purpose of the study was to evaluate the efficacy and safety of ICDs in CS and to identify predictors of appropriate therapy., Methods: A retrospective cohort study was performed in CS patients with an ICD implantation between 2010 and 2019. Primary outcome was appropriate ICD therapy. Independent predictors were calculated using Cox proportional hazard analysis., Results: 105 patients were included. An ICD was implanted for primary prevention in 79%. During a median follow-up of 2.8 years, 34 patients (32.4%) received appropriate ICD therapy of whom 24 (22.9%) received an appropriate shock. Three patients (2.9%) received an inappropriate shock due to atrial fibrillation. Independent predictors of appropriate therapy included prior ventricular arrhythmias (hazard ratio [HR]: 10.5 [95% confidence interval (CI): 5.0-21.9]) and right ventricular late gadolinium enhancement (LGE) (HR: 3.6 [95% CI: 1.7-7.6]). Within the primary prevention group, right ventricular LGE (HR: 5.7 [95% CI: 1.6-20.7]) was the only independent predictor of appropriate therapy. Left ventricular ejection fraction did not differ between patients with and without appropriate therapy (44.4% vs. 45.6%, p = .70)., Conclusion: In CS patients with an ICD, a high rate of appropriate therapy was observed and a low rate of inappropriate shocks. Prior ventricular arrhythmias and right ventricular LGE were independent predictors of appropriate therapy., (© 2022 Wiley Periodicals LLC.)

Right ventricular (RV) dysfunction in sarcoidosis is associated with adverse outcomes. Assessment of RV function by conventional transthoracic echocardiography (TTE) is challenging due to the complex RV geometry. Knowledge-based reconstruction (KBR) combines TTE measurements with three-dimensional coordinates to determine RV volumes. The aim of this study was to investigate the accuracy of TTE-KBR compared to the gold standard cardiac magnetic resonance imaging (CMR) in determining RV dimensions in pulmonary sarcoidosis. Pulmonary sarcoidosis patients prospectively received same-day TTE and TTE-KBR. If performed, CMR within 90 days after TTE-KBR was used as reference standard. Outcome parameters included RV end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (RVSV) and ejection fraction (RVEF). 281 patients underwent same day TTE and TTE-KBR. In total, 122 patients received a CMR within 90 days of TTE and were included. TTE-KBR measured RVEDV and RVESV showed strong correlation with CMR measurements (R = 0.73, R = 0.76), while RVSV and RVEF correlated weakly (R = 0.46, R = 0.46). Bland-Altman analyses (mean bias ± 95% limits of agreement), showed good agreement for RVEDV (ΔRVEDV KBR-CMR , 5.67 ± 55.4 mL), while RVESV, RVSV and RVEF showed poor agreement (ΔRVESV KBR-CMR , 21.6 ± 34.1 mL; ΔRVSV KBR-CMR , - 16.1 ± 42.9 mL; ΔRVEF KBR-CMR , - 12.9 ± 16.4%). The image quality and time between CMR and TTE-KBR showed no impact on intermodality differences and there was no sign of a possible learning curve. TTE-KBR is convenient and shows good agreement with CMR for RVEDV. However, there is poor agreement for RVESV, RVSV and RVEF. The use of TTE-KBR does not seem to provide additional value in the determination of RV dimensions in pulmonary sarcoidosis patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cardiac sarcoidosis (CS) diagnosis is usually based on advanced imaging techniques and multidisciplinary evaluation. Diagnosis is classified as definite, probable, possible or unlikely. If diagnostic confidence remains uncertain, cardiac imaging can be repeated. The objective is to evaluate the usefulness of repeated cardiac magnetic resonance imaging (CMR) and fluorodeoxyglucose positron emission tomography (FDG PET/CT) for CS diagnosis in patients with an initial "possible" CS diagnosis., Methods: We performed a retrospective cohort study in 35 patients diagnosed with possible CS by our multidisciplinary team (MDT), who received repeated CMR and FDG PET/CT within 12 months after diagnosis. Imaging modalities were scored on abnormalities suggestive for CS and classified as CMR+/PET+, CMR+/PET-, CMR-/PET+ and CMR-/PET-. Primary endpoint was final MDT diagnosis of CS., Results: After re-evaluation, nine patients (25.7%) were reclassified as probable CS and 16 patients (45.7%) as unlikely CS. Two patients started immunosuppressive treatment after re-evaluation. At baseline, eleven patients (31.4%) showed late gadolinium enhancement (LGE) on CMR (CMR+) and 26 (74.3%) patients showed myocardial FDG-uptake (PET+). At re-evaluation, nine patients (25.7%) showed LGE (CMR+), while 16 patients (45.7%) showed myocardial FDG-uptake (PET+). When considering both imaging modalities together, 82.6% of patients with CMR-/PET+ at baseline were reclassified as possible or unlikely CS, while 36.4% of patients with CMR+ at baseline were reclassified as probable CS. Three patients with initial CMR-/PET+ showed LGE at re-evaluation., Conclusion: Repeated CMR and FDG PET/CT may be useful in establishing or rejecting CS diagnosis, when initial diagnosis is uncertain. However, clinical relevance has to be further determined., (© 2021. The Author(s).)

Background and Objective: Diagnostic and predictive genetic testing for disease cause and risk estimation is common in many countries. For genetic diseases, predictive test results are commonly straightforward: presence of the mutation involves increased risk for disease and absence of the mutation involves no inherit risk for disease. Germline mutations in telomere-related genes (TRGs) can lead to telomere shortening and are associated with short telomere syndrome (STS). Telomere length is heritable, and in families with STS due to a TRG mutation, progeny with and without the TRG mutation is known to have shorter than average telomeres. We hypothesize that progeny of TRG mutation carriers who did not inherit the TRG mutation may still develop pulmonary fibrosis., Methods: A genetic screen of 99 unrelated families with familial pulmonary fibrosis revealed five patients with features of pulmonary fibrosis but without carrying the familial disease-causing TRG mutation., Results: Features of STS were present in each family, including short telomeres in blood and tissue of the non-mutation carrying patients. Additional genetic, clinical or environmental risk factors for pulmonary fibrosis were present in each non-mutation carrying patient., Conclusion: Our study shows that non-mutation carrying first-degree relatives in families with STS are at increased risk for pulmonary fibrosis. Disease development may be triggered by inherited short telomeres and additional risk factors for disease. This observation has profound consequences for genetic counselling. Unlike any other genetic syndrome, absence of the mutation does not imply absence of disease risk. Therefore, clinical follow-up is still urged for non-mutation carrying first-degree family members., (© 2021 Asian Pacific Society of Respirology.)

In patients with combined pulmonary fibrosis and emphysema, emphysema and fibrosis do not have a synergistic effect that results in worsened survival when compared to IPF patients without emphysema https://bit.ly/35EJMo6., Competing Interests: Conflict of interest: A. Zhao has nothing to disclose. Conflict of interest: E. Gudmundsson has nothing to disclose. Conflict of interest: N. Mogulkoc has nothing to disclose. Conflict of interest: M.G. Jones has nothing to disclose. Conflict of interest: C. van Moorsel has nothing to disclose. Conflict of interest: T.J. Corte reports personal fees from Ad Alta, grants and personal fees from Boehringer Ingelheim and Bristol Myers Squibb, personal fees from Promedior, grants and personal fees from Roche, and grants from Actelion, Avalyn Pharma, Biogen and Galapagos, outside the submitted work. Conflict of interest: C. Romei has nothing to disclose. Conflict of interest: R. Savas has nothing to disclose. Conflict of interest: C.J. Brereton has nothing to disclose. Conflict of interest: H.W. van Es has nothing to disclose. Conflict of interest: H. Jo has nothing to disclose. Conflict of interest: A. De Liperi has nothing to disclose. Conflict of interest: O. Unat has nothing to disclose. Conflict of interest: K. Pontoppidan has nothing to disclose. Conflict of interest: F. van Beek has nothing to disclose. Conflict of interest: M. Veltkamp has nothing to disclose. Conflict of interest: P. Hopkins has nothing to disclose. Conflict of interest: Y. Moodley has nothing to disclose. Conflict of interest: A. Taliani has nothing to disclose. Conflict of interest: L. Tavanti has nothing to disclose. Conflict of interest: B. Gholipour has nothing to disclose. Conflict of interest: A. Nair reports a proportion of their permanent employment at UCL Hospital is funded by the Biomedical Research Centre, and nonfinancial support for an advisory board from Aidence BV, the Netherlands, outside the submitted work. Conflict of interest: S. Janes reports personal fees and nonfinancial support from AstraZeneca, personal fees from Bard1 Bioscience, Achilles Therapeutics and Jansen, nonfinancial support from Takeda, and grants from GRAIL Inc., GlaxoSmithKline plc and from Owlstone, outside the submitted work. Conflict of interest: I. Stewart has nothing to disclose. Conflict of interest: D. Barber has nothing to disclose. Conflict of interest: D.C. Alexander has nothing to disclose. Conflict of interest: A.U. Wells reports personal fees and nonfinancial support from Boehringer Ingelheim, Bayer and Roche Pharmaceuticals, and personal fees from Blade, outside the submitted work. Conflict of interest: J. Jacob reports personal fees from Boehringer Ingelheim and Roche, grants and personal fees from GlaxoSmithKline, personal fees from NHSX, and grants from the Wellcome Trust, outside the submitted work., (Copyright ©The authors 2021.)

Background: Idiopathic pulmonary fibrosis (IPF) and pleuroparenchymal fibroelastosis (PPFE) are known to have poor outcomes but detailed examinations of prognostic significance of an association between these morphologic processes are lacking., Methods: Retrospective observational study of independent derivation and validation cohorts of IPF populations. Upper-lobe PPFE extent was scored visually (vPPFE) as categories of absent, moderate, marked. Computerised upper-zone PPFE extent (cPPFE) was examined continuously and using a threshold of 2·5% pleural surface area. vPPFE and cPPFE were evaluated against 1-year FVC decline (estimated using mixed-effects models) and mortality. Multivariable models were adjusted for age, gender, smoking history, antifibrotic treatment and diffusion capacity for carbon monoxide., Findings: PPFE prevalence was 49% (derivation cohort, n  = 142) and 72% (validation cohort, n  = 145). vPPFE marginally contributed 3-14% to variance in interstitial lung disease (ILD) severity across both cohorts.In multivariable models, marked vPPFE was independently associated with 1-year FVC decline (derivation: regression coefficient 18·3, 95 CI 8·47-28·2%; validation: 7·51, 1·85-13·2%) and mortality (derivation: hazard ratio [HR] 7·70, 95% CI 3·50-16·9; validation: HR 3·01, 1·33-6·81). Similarly, continuous and dichotomised cPPFE were associated with 1-year FVC decline and mortality (cPPFE ≥ 2·5% derivation: HR 5·26, 3·00-9·22; validation: HR 2·06, 1·28-3·31). Individuals with cPPFE ≥ 2·5% or marked vPPFE had the lowest median survival, the cPPFE threshold demonstrated greater discrimination of poor outcomes at two and three years than marked vPPFE., Interpretation: PPFE quantification supports distinction of IPF patients with a worse outcome independent of established ILD severity measures. This has the potential to improve prognostic management and elucidate separate pathways of disease progression., Funding: This research was funded in whole or in part by the Wellcome Trust [209,553/Z/17/Z] and the NIHR UCLH Biomedical Research Centre, UK., Competing Interests: JJ reports fees from Boehringer Ingelheim, Roche, NHSX and GlaxoSmithKline unrelated to the submitted work. JJ was supported by Wellcome Trust Clinical Research Career Development Fellowship 209,553/Z/17/Z. SMJ reports fees from Astra-Zeneca, Bard1 Bioscience, Achilles Therapeutics, and Jansen unrelated to the submitted work. SMJ received assistance for travel to meetings from Astra Zeneca to American Thoracic Conference 2018 and from Takeda to World Conference Lung Cancer 2019 and is the Investigator Lead on grants from GRAIL Inc, GlaxoSmithKline plc and Owlstone. AUW personal fees and non-financial support from Boehringer Ingelheim, Bayer and Roche Pharmaceuticals; and personal fees from Blade, outside of the submitted work. EG, AZ, NM, IS, MGJ, CvM, RS, CJB, HWvE, OU, KP, FvB, MV, BG, AN, DA report no relevant conflicts of interest., (© 2021 The Author(s).)

Objective: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms., Summary of Background Data: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown., Methods: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia., Results: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence., Conclusions: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures.

Background: Computed tomography (CT) is considered the imaging modality of choice to diagnose pulmonary arteriovenous malformations PAVMs. The drawback of this technique is that it requires ionizing radiation. Magnetic resonance (MR) imaging does not have the limitation, but little is known about the performance of MR compared to CT for the detection of PAVMs. The aim of this study is to investigate the sensitivity of contrast-enhanced MR angiography (CE-MRA) in the detection of PAVMs with feeding artery diameters (FAD) > 2 mm., Methods: Patients with a grade 2 or 3 shunt on screening transthoracic contrast echocardiography (TTCE) were asked to participate. Included patients underwent chest CT and CE-MRA. CT was considered the reference standard. CT and CE-MRA scans were anonymized and assessed for the presence of PAVMs with FAD > 2 mm by one and two readers respectively. Data analysis was performed on per patient and per PAVM basis., Results: Fifty-three patients were included. 105 PAVMs were detected on CT, 45 with a FAD ≥ 2 mm. In per patient analysis, sensitivity and specificity of CE-MRA were 92% and 97% respectively for reader 1 and 92% and 62% for reader 2. Negative and positive predictive value (NPV/PPV) were 93% and 96% for R1 and 90% and 67% for R2. In per PAVM analysis, sensitivity, specificity, NPV and PPV were 96%, 99%, 100% and 86% for R1 and 93%, 96%, 100% and 56% for R2, respectively., Conclusions: CE-MRA has excellent sensitivity and NPV for detection of PAVMs with FAD ≥ 2 mm and can therefore be used to detect these PAVMs. We are hopeful that future advancements in CE-MRA technology will reduce false positive rates and allow for more broad use of CE-MRA in PAVM diagnosis and management.

Background: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG., Methods: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death., Results: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P =0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05])., Conclusions: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.

Rationale: A subset of patients with idiopathic pulmonary fibrosis (IPF) contains short leukocyte telomeres or telomere related mutations. We previously showed that alveolar type 2 cells have short telomeres in fibrotic lesions. Our objectives were to better understand how telomere shortening associates with fibrosis in IPF lung and identify a subset of patients with telomere-related disease., Methods: Average telomere length was determined in multiple organs, basal and apical lung, and diagnostic and end-stage fibrotic lung biopsies. Alveolar type 2 cells telomere length was determined in different areas of IPF lungs., Results: In IPF but not in controls, telomere length in lung was shorter than in other organs, providing rationale to focus on telomere length in lung. Telomere length did not correlate with age and no difference in telomere length was found between diagnostic and explant lung or between basal and apical lung, irrespective of the presence of a radiological apicobasal gradient or fibrosis. Fifteen out of 28 IPF patients had average lung telomere length in the range of patients with a telomerase (TERT) mutation, and formed the IPFshort group. Only in this IPFshort and TERT group telomeres of alveolar type 2 cells were extremely short in fibrotic areas. Additionally, whole exome sequencing of IPF patients revealed two genetic variations in RTEL1 and one in PARN in the IPFshort group., Conclusions: Average lung tissue telomere shortening does not associated with fibrotic patterns in IPF, however, approximately half of IPF patients show excessive lung telomere shortening that is associated with pulmonary fibrosis driven by telomere attrition., Competing Interests: The authors have declared that no competing interests exist.

A diagnosis of silicosis is made on the basis of exposure and typical radiological findings, according to the ILO's International Classification of Radiographs of Pneumoconiosis. Radiological patterns of silicosis can, however, resemble sarcoidosis. Sarcoidosis is a multi-systemic disorder of unknown etiology, although a role for initiating inorganic triggers such as metals or silica has been suggested. In this case report, we illustrate a patient previously diagnosed with silicosis based on exposure and radiological features, progressive under immunosuppressive treatment. In view of these findings, an open lung biopsy was performed and revealed sarcoidosis. The patient was effectively treated with infliximab. Further analysis showed the presence of silica in the granulomas. Sensitization to silica was also demonstrated, suggesting an association between silica exposure and sarcoidosis in this patient.

Objectives: This meta-analysis determined the diagnostic performance of coronary computed tomography (CT) angiography (CTA), CT myocardial perfusion (CTP), fractional flow reserve CT (FFR CT ), the transluminal attenuation gradient (TAG), and their combined use with CTA versus FFR as a reference standard for detection of hemodynamically significant coronary artery disease (CAD)., Background: CTA provides excellent anatomic, albeit limited functional information for the evaluation of CAD. Recently, various functional CT techniques emerged to assess the hemodynamic consequences of CAD., Methods: This meta-analysis was performed in adherence to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, EMBASE, and Web of Science were searched from inception until September 7, 2017. Bayesian random effects analysis was used to compute pooled sensitivity, specificity, and the summary receiver-operating characteristic curve of the index tests and compare them with the FFR as a reference standard. Analyses were performed on vessel and patient levels. Because CTA has excellent sensitivity, specificity was considered most relevant. Individual FFR CT values were collected., Results: Overall, 54 articles and 5,330 patients were included. At vessel level, pooled specificity of CTP (0.86; 95% confidence interval [CI]: 0.76 to 0.93), FFR CT (0.78; 95% CI: 0.72 to 0.83) and TAG (0.77; 95% CI: 0.61 to 0.89) were substantially higher than that of CTA (0.61; 95% CI: 0.54 to 0.68). The addition of FFR CT, CTP, and TAG to CTA resulted in high to excellent specificities (0.80 to 0.92). The summary receiver-operating characteristic curve at vessel level yielded superior diagnostic accuracy for CTP, FFR CT , and combined CTA and CTP, compared with CTA. A subanalysis of on-site versus off-site FFR CT revealed no substantial differences between the sensitivity (0.84 vs. 0.85) and specificity (0.80 vs. 0.73) of the 2 techniques. In a second subanalysis, dynamic CTP showed higher sensitivity (0.85 vs. 0.72), but had a lower specificity (0.81 vs. 0.90) than static CTP., Conclusions: CTP and FFR CT demonstrated a substantial improvement in the identification of hemodynamically significant CAD compared with CTA; therefore, their integration to clinical workflow before revascularization is recommended., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RAILD) to identify patients with a progressive fibrosis phenotype.RAILD patients had computed tomography (CT) scans scored visually and using CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques, as follows. 1) Scleroderma system evaluating visual interstitial lung disease extent and FVC values; 2) Fleischner Society idiopathic pulmonary fibrosis (IPF) diagnostic guidelines applied to RAILD; and 3) CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.On univariable Cox analysis, all three staging systems strongly predicted outcome (scleroderma system hazard ratio (HR) 3.78, p=9×10 -5 ; Fleischner system HR 1.98, p=2×10 -3 ; and 4.4% VRS threshold HR 3.10, p=4×10 -4 ). When the scleroderma and Fleischner systems were combined, termed the progressive fibrotic system (C-statistic 0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF. On multivariable analysis, with adjustment for patient age, sex and smoking status, when analysed alongside the progressive fibrotic system, the VRS threshold of 4.4% independently predicted outcome (model C-statistic 0.77).The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent., Competing Interests: Conflict of interest: J. Jacob reports advisory board fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: N. Hirani reports personal fees from Boehringer Ingelheim, Intermune, Roche, Galecto and UCB, outside the submitted work. Conflict of interest: C.H.M. van Moorsel has nothing to disclose. Conflict of interest: S. Rajagopalan reports grants (provided to Mayo Clinic for supporting the handling and processing of the CT datasets used in the study) from Royal Brompton Hospital, during the conduct of the study; and that Mayo Clinic has received royalties from Imbio, LCC towards licensing CALIPER, outside the submitted work; in addition, S. Rajagopalan has a patent Systems And Methods For Analysing In Vivo Tissue Volumes Using Medical Imaging Data licensed to Imbio, LLC. Conflict of interest: J.T. Murchison has nothing to disclose. Conflict of interest: H.W. van Es has nothing to disclose. Conflict of interest: B.J. Bartholmai reports grants (provided to Mayo Clinic for supporting the handling and processing of CT datasets used in the study) from Royal Brompton Hospital, during the conduct of the study; and that Mayo Clinic has received royalties from Imbio, LCC towards licensing CALIPER, outside the submitted work; in addition, B.J. Bartholmai has a patent Systems And Methods For Analysing In Vivo Tissue Volumes Using Medical Imaging Data licensed to Imbio, LLC. Conflict of interest: F.T. van Beek has nothing to disclose. Conflict of interest: M.H.L. Struik has nothing to disclose. Conflict of interest: G.A. Stewart has nothing to disclose. Conflict of interest: M. Kokosi has nothing to disclose. Conflict of interest: R. Egashira has nothing to disclose. Conflict of interest: A.L. Brun has nothing to disclose. Conflict of interest: G. Cross has nothing to disclose. Conflict of interest: J. Barnett has nothing to disclose. Conflict of interest: A. Devaraj reports personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: G. Margaritopoulos has nothing to disclose. Conflict of interest: R. Karwoski reports grants (provided to Mayo Clinic for supporting the handling and processing of CT datasets used in the study) from Royal Brompton Hospital, during the conduct of the study; and that Mayo Clinic has received royalties from Imbio, LCC towards licensing CALIPER, outside the submitted work; in addition, R. Karwoski has a patent Systems And Methods For Analysing In Vivo Tissue Volumes Using Medical Imaging Data licensed to Imbio, LLC. Conflict of interest: E. Renzoni reports lecture fees from Roche and Takeda, and lecture fees and advisory board fees from Boehringer, outside the submitted work. Conflict of interest: T.M. Maher has, via his institution, received industry-academic funding from GlaxoSmithKline R&D, UCB and Novartis and has received consultancy or speakers fees from Apellis, Astra Zeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, GlaxoSmithKline R&D, Lanthio, InterMune, ProMetic, Roche, Sanofi-Aventis, Takeda and UCB. Conflict of interest: A.U. Wells reports advisory board and speaker fees from Intermune, Boehringer Ingelheim, Roche and Bayer, advisory board fees from Gilead and MSD, and speaker fees from Chiesi, outside the submitted work., (Copyright ©ERS 2019.)

Rationale: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials., Objectives: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations., Methods: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria., Measurements and Main Results: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%., Conclusions: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.

Objectives: This study sought to document the closure rate, safety, and stroke rate after thoracoscopic left atrial appendage (LAA) clipping., Background: The LAA is the main source of stroke in patients with atrial fibrillation, and thoracoscopic clipping may provide a durable and safe closure technique., Methods: The investigators studied consecutive patients undergoing clipping as part of a thoracoscopic maze procedure in 4 referral centers (the Netherlands and the United States) from 2012 to 2016. Completeness of LAA closure was assessed by either computed tomography (n = 100) or transesophageal echocardiography (n = 122). The primary outcome was complete LAA closure (absence of residual LAA flow and pouch <10 mm). The secondary outcomes were 30-day complications; the composite of ischemic stroke, hemorrhagic stroke, or transient ischemic attack; and all-cause mortality., Results: A total of 222 patients were included, with a mean age of 66 ± 9 years, and 68.5% were male. The mean CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65 to 74 years, sex category [female]) score was 2.3 ± 1.0. Complete LAA closure was achieved in 95.0% of patients. There were no intraoperative or clip-related complications, and the overall 30-day freedom from any complication rate was 96.4%. The freedom from cerebrovascular events after surgery was 99.1% after median follow-up of 20 months (interquartile range: 14 to 25 months; 369 patient-years of follow-up), and overall survival was 98.6%. The observed rate of cerebrovascular events after LAA clipping was low (0.5 per 100 patient-years)., Conclusions: LAA clipping during thoracoscopic ablation is a feasible and safe technique for closure of the LAA in patients with atrial fibrillation. The lower than expected rate of cerebrovascular events after deployment was likely multifactorial, including not only LAA closure, but also the effect of oral anticoagulation and rhythm control., (Copyright © 2018 American College of Cardiology Foundation. All rights reserved.)

Background and Objective: The diagnostic classification of 'possible idiopathic pulmonary fibrosis (posIPF)' is characterized by a radiological pattern of inconsistent usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT) scan and a UIP pattern in surgical lung biopsy (SLB). The evidence base to guide treatment for patients with posIPF is lacking; the clinician must choose between observation, treatment with immunomodulatory agents or anti-fibrotic agents., Methods: To evaluate outcomes of immunomodulatory treatment, a multicentre cohort of 59 posIPF patients treated with prednisone was analysed retrospectively. Prednisone starting dose was 0.5 mg/kg/day and tapered to 0.15 mg/day/kg over 6 months. Outcome measures were forced vital capacity (FVC) and serious adverse events (SAE), defined as death or hospital admissions., Results: The majority of prednisone-treated posIPF patients were non-responders (68%) with a decrease in FVC >5% or death within 6 months from baseline; 90% of patients with radiographical presence of honeycombing were non-responders. In contrast, six out of seven patients with focal desquamative interstitial pneumonia-like reaction in the SLB who had stopped smoking for <5 years ago were responders to prednisone, demonstrating <5% FVC decline. The mean decline of FVC was 8.7% (95% CI: 3.1-14.3%) before treatment and 20% (95% CI: 9.4-31.1%) after treatment (P = 0.018) in the 32 patients with available FVC data. Twelve SAE occurred within the first 3 months on prednisone (at dosage >0.3 mg/kg/day), including five deaths., Conclusion: Patients with posIPF demonstrated an accelerated FVC decline and a substantial number of SAE on steroid therapy., (© 2017 Asian Pacific Society of Respirology.)

Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) is a new technique for the diagnosis of ischemic coronary artery stenoses. The aim of this prospective study was to evaluate the diagnostic performance of a novel on-site computed tomography-based fractional flow reserve algorithm (CT-FFR) compared with invasive FFR as the gold standard, and to determine whether its diagnostic performance is affected by interobserver variations in lumen segmentation. We enrolled 44 consecutive patients (64.6 ± 8.9 years, 34% female) with 60 coronary atherosclerotic lesions who underwent coronary CTA and invasive coronary angiography in 2 centers. An FFR value ≤0.8 was considered significant. Coronary CTA scans were evaluated by 2 expert readers, who manually adjusted the semiautomated coronary lumen segmentations for effective diameter stenosis (EDS) assessment and on-site CT-FFR simulation. The mean CT-FFR value was 0.77 ± 0.15, whereas the mean EDS was 43.6 ± 16.9%. The sensitivity, specificity, positive predictive value, and negative predictive value of CT-FFR versus EDS with a cutoff of 50% were the following: 91%, 72%, 63%, and 93% versus 52%, 87%, 69%, and 77%, respectively. The on-site CT-FFR demonstrated significantly better diagnostic performance compared with EDS (area under the curve 0.89 vs 0.74, respectively, p <0.001). The CT-FFR areas under the curve of the 2 readers did not show any significant difference (0.89 vs 0.88, p = 0.74). In conclusion, on-site CT-FFR simulation is feasible and has better diagnostic performance than anatomic stenosis assessment. Furthermore, the diagnostic performance of the on-site CT-FFR simulation algorithm does not depend on the readers' semiautomated lumen segmentation adjustments., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Modern pacemakers are designed to allow patients to undergo magnetic resonance imaging (MRI) under a set of specific conditions. Aim of this study is to provide confirmatory evidence of safety and performance of a new pacing system (ImageReady™, Boston Scientific) in patients undergoing 1.5 and 3T MRI., Methods and Results: Two prospective, nonrandomized, single-arm studies were designed to provide confirmatory data of no impact of MRI on device function, lead parameters, and patient conditions in subjects implanted with the system undergoing a clinically non-indicated 1.5T and 3T MRI, respectively. Device measurements were done within 1 hour before and after the scan and at 1 month follow-up. Thirty-two subjects underwent MRI visit (17 subjects with 1.5T MRI and 15 subjects with 3T MRI). There were no unanticipated adverse effects related to the pacemaker. Device measurements taken pre- and post-MRI scan did not show any clinical relevant change that could indicate an effect of the MRI on the device or at the lead-tissue interface (RV threshold change: 0.01 ± 0.13 V, P = 0.60; RA threshold change: 0.01 ± 0.11 V, P = 0.53; R wave change: -0.44 ± 1.73 mV, P = 0.36; R wave change: 0.12 ± 1.67 mV, P = 0.73), with data confirmed at 1-month follow-up visit., Conclusion: The study documented safety of the pacing system in the 1.5T and 3T MRI environment by showing no adverse events related to device or MRI scan. Additional data are required to cover the more complex scenarios involving different diagnostic needs, conditions of use, clinical conditions, and new emerging technologies., (© 2017 Wiley Periodicals, Inc.)

Competing Interests: Conflict of interestF.A.A. Mohamed Hoesein, M.J. Swaans, L.S. Jiwa, C.A. Seldenrijk and H.W. van Es declare that they have no competing interests.

Background: Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease., Methods: We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis., Findings: 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (κ=0·50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (κw=0·71 [IQR 0·64-0·77]) and connective tissue disease-related interstitial lung disease (κw=0·73 [0·68-0·78]); moderate for non-specific interstitial pneumonia (NSIP; κw=0·42 [0·37-0·49]); and fair for hypersensitivity pneumonitis (κw=0·29 [0·24-0·40]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinician's diagnosis of this disease in five of seven MDTMs, and radiologist's diagnosis of IPF in four of seven MDTMs., Interpretation: Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease., Funding: National Institute of Health Research, Imperial College London., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Pulmonary fibrosis is a frequent manifestation of telomere syndromes. Telomere gene mutations are found in up to 25% and 3% of patients with familial disease and sporadic disease, respectively. The telomere gene TINF2 encodes an eponymous protein that is part of the shelterin complex, a complex involved in telomere protection and maintenance. A TINF2 gene mutation was recently reported in a family with pulmonary fibrosis. We identified a heterozygous Ser245Tyr mutation in the TINF2 gene of previously healthy female patient that presented with progressive cough due to pulmonary fibrosis as well as panhypogammaglobulinemia at age 52. Retrospective multidisciplinary evaluation classified her as a case of possible idiopathic pulmonary fibrosis. Telomere length-measurement indicated normal telomere length in the peripheral blood compartment. This is the first report of a TINF2 mutation in a patient with sporadic pulmonary fibrosis, which represents another association between TINF2 mutations and this disease. Furthermore, this case underlines the importance of telomere dysfunction and not telomere length alone in telomere syndromes and draws attention to hypogammaglobulinemia as a manifestation of telomere syndromes.

Purpose: To determine inter-rater reliability of sarcoidosis-related computed tomography (CT) findings that can be used for scoring of thoracic sarcoidosis., Materials and Methods: CT images of 51 patients with sarcoidosis were scored by five chest radiologists for various abnormal CT findings (22 in total) encountered in thoracic sarcoidosis. Using intra-class correlation coefficient (ICC) analysis, inter-rater reliability was analysed and reported according to the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) criteria. A pre-specified sub-analysis was performed to investigate the effect of training. Scoring was trained in a distinct set of 15 scans in which all abnormal CT findings were represented., Results: Median age of the 51 patients (36 men, 70%) was 43 years (range 26 - 64 years). All radiographic stages were present in this group. ICC ranged from 0.91 for honeycombing to 0.11 for nodular margin (sharp versus ill-defined). The ICC was above 0.60 in 13 of the 22 abnormal findings. Sub-analysis for the best-trained observers demonstrated an ICC improvement for all abnormal findings and values above 0.60 for 16 of the 22 abnormalities., Conclusions: In our cohort, reliability between raters was acceptable for 16 thoracic sarcoidosis-related abnormal CT findings., Key Points: • Thoracic sarcoidosis is common; knowledge on reliability of CT scoring is limited. • Scoring CT abnormalities in pulmonary sarcoidosis can achieve good inter-rater agreement. • CT scoring validation in thoracic sarcoidosis is important for diagnostic and prognostic studies.

Objectives: To compare the diagnostic accuracy of conditional computed tomography (CT), i.e. CT when initial ultrasound findings are negative or inconclusive, and immediate CT for patients with suspected appendicitis., Methods: Data were collected within a prospective diagnostic accuracy study on imaging in adults with acute abdominal pain. All patients underwent ultrasound and CT, read by different observers who were blinded from the other modality. Only patients with clinical suspicion of appendicitis were included. An expert panel assigned a final diagnosis to each patient after 6 months of follow-up (clinical reference standard)., Results: A total of 422 patients were included with final diagnosis appendicitis in 251 (60 %). For 199 patients (47 %), ultrasound findings were inconclusive or negative. Conditional CT imaging correctly identified 241 of 251 (96 %) appendicitis cases (95 %CI, 92 % to 98 %), versus 238 (95 %) with immediate CT (95 %CI, 91 % to 97 %). The specificity of conditional CT imaging was lower: 77 % (95 %CI, 70 % to 83 %) versus 87 % for immediate CT (95 %CI, 81 % to 91 %)., Conclusion: A conditional CT strategy correctly identifies as many patients with appendicitis as an immediate CT strategy, and can halve the number of CTs needed. However, conditional CT imaging results in more false positives., Key Points: • Conditional CT (CT after negative/inconclusive ultrasound findings) can be used for suspected appendicitis. • Half the number of CT examinations is needed with a conditional strategy. • Conditional CT correctly identifies as many patients with appendicitis as immediate CT. • Conditional imaging results in more false positive appendicitis cases.

Objective: To compare the diagnostic accuracy of conditional CT strategy, i.e. CT if ultrasound findings are negative or inconclusive, with immediate CT strategy for patients with suspected appendicitis., Design: Subanalysis of a prospective multicenter diagnostic accuracy study., Method: Only data of patients with signs of appendicitis based on medical history, physical examination, and laboratory tests were analyzed. All patients underwent both ultrasound and CT. Images of each were read by different observers who were blinded to the results of the other imaging modality. The observer then selected the most likely diagnosis. These diagnoses were compared with the reference standard, i.e. final diagnoses as assigned by an expert panel based on all available data and at least 6 months of follow-up., Results: A total of 422 patients with suspected appendicitis were included. In 251 patients the final diagnosis was acute appendicitis (59%). In 199 patients (47%), ultrasound findings were inconclusive or negative. Use of conditional CT strategy resulted in correctly identified number of correctly identified patients with appendicitis, i.e. 96% (95% CI 93-98), versus 95% identified by immediate CT (95% CI 91-97). However, conditional CT strategy resulted in more false positive diagnoses compared with immediate CT (39 versus 22), had an accompanying lower specificity of 77% (95% CI 70-83) versus 87% (95% CI 81-91), and a lower positive predictive value of 86% (95% CI 81-90) versus 92% (95% CI 87-95)., Conclusion: Use of a conditional CT strategy results in exactly the same number of patients with correctly identified acute appendicitis while halving the number of CTs needed. However, conditional strategy results in more false positive diagnoses.

Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

Objective: To compare accuracy and interobserver agreement between radiologists with limited experience in the evaluation of abdominal MRI (non-experts), and radiologists with longer MR reading experience (experts), in reading MRI in patients with suspected appendicitis., Methods: MR imaging was performed in 223 adult patients with suspected appendicitis and read independently by two members of a team of eight MR-inexperienced radiologists, who were trained with 100 MR examinations previous to this study (non-expert reading). Expert reading was performed by two radiologists with a larger abdominal MR experience (>500 examinations) in consensus. A final diagnosis was assigned after three months based on all available information, except MRI findings. We estimated MRI sensitivity and specificity for appendicitis and for all urgent diagnoses separately. Interobserver agreement was evaluated using kappa statistics., Results: Urgent diagnoses were assigned to 147 of 223 patients; 117 had appendicitis. Sensitivity for appendicitis was 0.89 by MR-non-expert radiologists and 0.97 in MR-expert reading (p=0.01). Specificity was 0.83 for MR-non-experts versus 0.93 for MR-expert reading (p=0.002). MR-experts and MR-non-experts agreed on appendicitis in 89% of cases (kappa 0.78). Accuracy in detecting urgent diagnoses was significantly lower in MR-non-experts compared to MR-expert reading: sensitivity 0.84 versus 0.95 (p<0.001) and specificity 0.71 versus 0.82 (p=0.03), respectively. Agreement on urgent diagnoses was 83% (kappa 0.63)., Conclusion: MR-non-experts have sufficient sensitivity in reading MRI in patients with suspected appendicitis, with good agreement with MR-expert reading, but accuracy of MR-expert reading was higher., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

An 84-year-old man was admitted with 4 days of postprandial emesis. Gastroscopy revealed the presence of a large gallstone in the duodenal bulb causing gastric outlet obstruction. The patient was diagnosed with Bouveret's syndrome. Treatment consisted of gastrotomy with removal of the gallstone.

Objectives: To identify MRI features associated with appendicitis., Methods: Features expected to be associated with appendicitis were recorded in consensus by two expert radiologists on 223 abdominal MRIs in patients with suspected appendicitis. Nine MRI features were studied: appendix diameter >7 mm, appendicolith, peri-appendiceal fat infiltration, peri-appendiceal fluid, absence of gas in the appendix, appendiceal wall destruction, restricted diffusion of the appendiceal wall, lumen or focal fluid collections. Appendicitis was assigned as the final diagnosis in 117/223 patients. Associations between imaging features and appendicitis were evaluated with logistic regression analysis., Results: All investigated features were significantly associated with appendicitis in univariate analysis. Combinations of two and three features were associated with a probability of appendicitis of 88 % and 92 %, respectively. In patients without any of the nine features, appendicitis was present in 2 % of cases. After multivariate analysis, only an appendix diameter >7 mm, peri-appendiceal fat infiltration and restricted diffusion of the appendiceal wall were significantly associated with appendicitis. The probability of appendicitis was 96 % in their presence and 2 % in their absence., Conclusions: An appendix diameter >7 mm, peri-appendiceal fat infiltration and restricted diffusion of the appendiceal wall have the strongest association with appendicitis on MRI., Key Points: • An enlarged appendix, fat infiltration and restricted diffusion are associated with appendicitis. • One such feature on MRI gives an 88 % probability of appendicitis. • Two features in combination give a probability of appendicitis of 94 %. • Combinations of three features give a probability of appendicitis of 96 %. • The absence of these features almost rules out appendicitis (2 %).