ESR Essentials: imaging in fibrotic lung diseases-practice recommendations by the European Society of Thoracic Imaging.

Fibrotic lung diseases (FLDs) represent a subgroup of interstitial lung diseases (ILDs), which can progress over time and carry a poor prognosis. Imaging has increased diagnostic discrimination in the evaluation of FLDs. International guidelines have stated the role of radiologists in the diagnosis and management of FLDs, in the context of the interdisciplinary discussion. Chest computed tomography (CT) with high-resolution technique is recommended to correctly recognise signs, patterns, and distribution of individual FLDs. Radiologists may be the first to recognise the presence of previously unknown interstitial lung abnormalities (ILAs) in various settings. A systematic approach to CT images may lead to a non-invasive diagnosis of FLDs. Careful comparison of serial CT exams is crucial in determining either disease progression or supervening complications. This 'Essentials' aims to provide radiologists a concise and practical approach to FLDs, focusing on CT technical requirements, pattern recognition, and assessment of disease progression and complications. Hot topics such as ILAs and progressive pulmonary fibrosis (PPF) are also discussed. KEY POINTS: Chest CT with high-resolution technique is the recommended imaging modality to diagnose pulmonary fibrosis. CT pattern recognition is central for an accurate diagnosis of fibrotic lung diseases (FLDs) by interdisciplinary discussion. Radiologists are to evaluate disease behaviour by accurately comparing serial CT scans.

Diagnostic performance of radiologists in distinguishing post-COVID-19 residual abnormalities from interstitial lung abnormalities.

OBJECTIVE: Distinguishing post-COVID-19 residual abnormalities from interstitial lung abnormalities (ILA) on CT can be challenging if clinical information is limited. This study aimed to evaluate the diagnostic performance of radiologists in distinguishing post-COVID-19 residual abnormalities from ILA. METHODS: This multi-reader, multi-case study included 60 age- and sex-matched subjects with chest CT scans. There were 40 cases of ILA (20 fibrotic and 20 non-fibrotic) and 20 cases of post-COVID-19 residual abnormalities. Fifteen radiologists from multiple nations with varying levels of experience independently rated suspicion scores on a 5-point scale to distinguish post-COVID-19 residual abnormalities from fibrotic ILA or non-fibrotic ILA. Interobserver agreement was assessed using the weighted κ value, and the scores of individual readers were compared with the consensus of all readers. Receiver operating characteristic curve analysis was conducted to evaluate the diagnostic performance of suspicion scores for distinguishing post-COVID-19 residual abnormalities from ILA and for differentiating post-COVID-19 residual abnormalities from both fibrotic and non-fibrotic ILA. RESULTS: Radiologists' diagnostic performance for distinguishing post-COVID-19 residual abnormalities from ILA was good (area under the receiver operating characteristic curve (AUC) range, 0.67-0.92; median AUC, 0.85) with moderate agreement (κ = 0.56). The diagnostic performance for distinguishing post-COVID-19 residual abnormalities from non-fibrotic ILA was lower than that from fibrotic ILA (median AUC = 0.89 vs. AUC = 0.80, p = 0.003). CONCLUSION: Radiologists demonstrated good diagnostic performance and moderate agreement in distinguishing post-COVID-19 residual abnormalities from ILA, but careful attention is needed to avoid misdiagnosing them as non-fibrotic ILA. KEY POINTS: Question How good are radiologists at differentiating interstitial lung abnormalities (ILA) from changes related to COVID-19 infection? Findings Radiologists had a median AUC of 0.85 in distinguishing post-COVID-19 abnormalities from ILA with moderate agreement (κ = 0.56). Clinical relevance Radiologists showed good diagnostic performance and moderate agreement in distinguishing post-COVID-19 residual abnormalities from ILA; nonetheless, caution is needed in distinguishing residual abnormalities from non-fibrotic ILA.

Lung and Liver Stereotactic Body Radiation Therapy During Mechanically Assisted Deep Inspiration Breath-Holds: A Prospective Feasibility Trial.

Purpose: Radiation therapy for tumors subject to breathing-related motion during breath-holds (BHs) has the potential to substantially reduce the irradiated volume. Mechanically assisted and noninvasive ventilation (MANIV) could ensure the target repositioning accuracy during each BH while facilitating treatment feasibility through oxygen supplementation and a perfectly replicated mechanical support. However, there is currently no clinical evidence substantiating the use of MANIV-induced BH for moving tumors. The aim of this work was, therefore, to evaluate the technique's performance under real treatment conditions. Methods and Materials: Patients eligible for lung or liver stereotactic body radiation therapy were prospectively included in a single-arm trial. The primary endpoint corresponded to the treatment feasibility with MANIV. Secondary outcomes comprised intrafraction geometric uncertainties extracted from real-time imaging, tolerance to BH, and treatment time. Results: Treatment was successfully delivered in 92.9% (13/14) of patients: 1 patient with a liver tumor was excluded because of a mechanically induced gastric insufflation displacing the liver cranially by more than 1 cm. In the left-right/anteroposterior/craniocaudal directions, the recalculated safety margins based on intrafraction positional data were 4.6 mm/5.1 mm/5.6 mm and 4.7 mm/7.3 mm/5.9 mm for lung and liver lesions, respectively. Compared with the free-breathing internal target volume and midposition approaches, the average reduction in the planning target volume with MANIV reached -47.2% ± 15.3%, P < .001, and -29.4% ± 19.2%, P = .007, for intrathoracic tumors and -23.3% ± 12.4%, P < .001, and -9.3% ± 15.3%, P = .073, for upper abdominal tumors, respectively. For 1 liver lesion, large caudal drifts of occasionally more than 1 cm were measured. The total slot time was 53.1 ± 10.6 minutes with a BH comfort level of 80.1% ± 10.6%. Conclusions: MANIV enables high treatment feasibility within a nonselected population. Accurate intrafraction tumor repositioning is achieved for lung tumors. Because of occasional intra-BH caudal drifts, pretreatment assessment of BH stability for liver lesions is, however, recommended.

Radiomics and Delta-Radiomics Signatures to Predict Response and Survival in Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

The aim of our study was to determine the potential role of CT-based radiomics in predicting treatment response and survival in patients with advanced NSCLC treated with immune checkpoint inhibitors. We retrospectively included 188 patients with NSCLC treated with PD-1/PD-L1 inhibitors from two independent centers. Radiomics analysis was performed on pre-treatment contrast-enhanced CT. A delta-radiomics analysis was also conducted on a subset of 160 patients who underwent a follow-up contrast-enhanced CT after 2 to 4 treatment cycles. Linear and random forest (RF) models were tested to predict response at 6 months and overall survival. Models based on clinical parameters only and combined clinical and radiomics models were also tested and compared to the radiomics and delta-radiomics models. The RF delta-radiomics model showed the best performance for response prediction with an AUC of 0.8 (95% CI: 0.65-0.95) on the external test dataset. The Cox regression delta-radiomics model was the most accurate at predicting survival with a concordance index of 0.68 (95% CI: 0.56-0.80) (p = 0.02). The baseline CT radiomics signatures did not show any significant results for treatment response prediction or survival. In conclusion, our results demonstrated the ability of a CT-based delta-radiomics signature to identify early on patients with NSCLC who were more likely to benefit from immunotherapy.

Implementation of artificial intelligence in thoracic imaging-a what, how, and why guide from the European Society of Thoracic Imaging (ESTI).

This statement from the European Society of Thoracic imaging (ESTI) explains and summarises the essentials for understanding and implementing Artificial intelligence (AI) in clinical practice in thoracic radiology departments. This document discusses the current AI scientific evidence in thoracic imaging, its potential clinical utility, implementation and costs, training requirements and validation, its' effect on the training of new radiologists, post-implementation issues, and medico-legal and ethical issues. All these issues have to be addressed and overcome, for AI to become implemented clinically in thoracic radiology. KEY POINTS: • Assessing the datasets used for training and validation of the AI system is essential. • A departmental strategy and business plan which includes continuing quality assurance of AI system and a sustainable financial plan is important for successful implementation. • Awareness of the negative effect on training of new radiologists is vital.

Strategies to safely rule out pulmonary embolism in COVID-19 outpatients: a multicenter retrospective study.

OBJECTIVES: The objective was to define a safe strategy to exclude pulmonary embolism (PE) in COVID-19 outpatients, without performing CT pulmonary angiogram (CTPA). METHODS: COVID-19 outpatients from 15 university hospitals who underwent a CTPA were retrospectively evaluated. D-Dimers, variables of the revised Geneva and Wells scores, as well as laboratory findings and clinical characteristics related to COVID-19 pneumonia, were collected. CTPA reports were reviewed for the presence of PE and the extent of COVID-19 disease. PE rule-out strategies were based solely on D-Dimer tests using different thresholds, the revised Geneva and Wells scores, and a COVID-19 PE prediction model built on our dataset were compared. The area under the receiver operating characteristics curve (AUC), failure rate, and efficiency were calculated. RESULTS: In total, 1369 patients were included of whom 124 were PE positive (9.1%). Failure rate and efficiency of D-Dimer > 500 µg/l were 0.9% (95%CI, 0.2-4.8%) and 10.1% (8.5-11.9%), respectively, increasing to 1.0% (0.2-5.3%) and 16.4% (14.4-18.7%), respectively, for an age-adjusted D-Dimer level. D-dimer > 1000 µg/l led to an unacceptable failure rate to 8.1% (4.4-14.5%). The best performances of the revised Geneva and Wells scores were obtained using the age-adjusted D-Dimer level. They had the same failure rate of 1.0% (0.2-5.3%) for efficiency of 16.8% (14.7-19.1%), and 16.9% (14.8-19.2%) respectively. The developed COVID-19 PE prediction model had an AUC of 0.609 (0.594-0.623) with an efficiency of 20.5% (18.4-22.8%) when its failure was set to 0.8%. CONCLUSIONS: The strategy to safely exclude PE in COVID-19 outpatients should not differ from that used in non-COVID-19 patients. The added value of the COVID-19 PE prediction model is minor. KEY POINTS: • D-dimer level remains the most important predictor of pulmonary embolism in COVID-19 patients. • The AUCs of the revised Geneva and Wells scores using an age-adjusted D-dimer threshold were 0.587 (95%CI, 0.572 to 0.603) and 0.588 (95%CI, 0.572 to 0.603). • The AUC of COVID-19-specific strategy to rule out pulmonary embolism ranged from 0.513 (95%CI: 0.503 to 0.522) to 0.609 (95%CI: 0.594 to 0.623).

Platypnea-orthodeoxia syndrome in a postoperative patient: a case report.

BACKGROUND: We report a case of platypnea-orthodeoxia syndrome observed in a complex clinical situation associating a bilateral pleural effusion, lobar pulmonary embolism, and a partial anomalous pulmonary venous return. CASE PRESENTATION: A 57-year-old Caucasian woman developed acute dyspnea in the postoperative course of an elective gynecological surgery for advanced stage ovarian cancer. Preoperative evaluation had failed to reveal any respiratory or cardiac problem. After evidence of a low arterial oxygen saturation, blood gas analysis from the central venous line correctly inserted in the right internal jugular vein revealed a higher oxygen saturation than in the arterial compartment. A thoracic computed tomography showed bilateral pleural effusion, lobar pulmonary embolism, and a drainage of a left pulmonary vein into the left innominate vein. This unique combination resulted in an uncommon cause of platypnea-orthodeoxia syndrome. CONCLUSION: Often associated with right-to-left shunting, platypnea-orthodeoxia syndrome may be observed in complex clinical conditions with several factors influencing the ventilation/perfusion ratio. The paradoxical finding of a higher oxygen saturation in a central venous line than in an arterial line should prompt the clinician to look at the possibility of partial anomalous pulmonary venous return. No specific treatment is required in asymptomatic adults, except for an echocardiographic follow-up to detect the onset of pulmonary hypertension.

Real-life prevalence of progressive fibrosing interstitial lung diseases.

The concept of progressive fibrosing interstitial lung disease (PF-ILD) has recently emerged. However, real-life proportion of PF-ILDs outside IPF is still hard to evaluate. Therefore, we sought to estimate the proportion of PF-ILD in our ILD cohort. We also determined the proportion of ILD subtypes within PF-ILD and investigated factors associated with PF-ILDs. Finally, we quantified interobserver agreement between radiologists for the assessment of fibrosis. We reviewed the files of ILD patients discussed in multidisciplinary discussion between January 1st 2017 and December 31st 2019. Clinical data, pulmonary function tests (PFTs) and high-resolution computed tomography (HRCTs) were centrally reviewed. Fibrosis was defined as the presence of traction bronchiectasis, reticulations with/out honeycombing. Progression was defined as a relative forced vital capacity (FVC) decline of ≥ 10% in ≤ 24 months or 5% < FVC decline < 10% and progression of fibrosis on HRCT in ≤ 24 months. 464 consecutive ILD patients were included. 105 had a diagnosis of IPF (23%). Most frequent non-IPF ILD were connective tissue disease (CTD)-associated ILD (22%), hypersensitivity pneumonitis (13%), unclassifiable ILD (10%) and sarcoidosis (8%). Features of fibrosis were common (82% of CTD-ILD, 81% of HP, 95% of uILD). After review of HRCTs and PFTs, 68 patients (19% of non-IPF ILD) had a PF-ILD according to our criteria. Interobserver agreement for fibrosis between radiologists was excellent (Cohen's kappa 0.86). The main diagnosis among PF-ILD were CTD-ILD (36%), HP (22%) and uILD (20%). PF-ILD patients were significantly older than non-F-ILD (P = 0.0005). PF-ILDs represent about 20% of ILDs outside IPF. This provides an estimation of the proportion of patients who might benefit from antifibrotics. Interobserver agreement between radiologists for the diagnosis of fibrotic ILD is excellent.

Tumor response to EGFR/BRAF/MEK co-inhibition in a patient with EGFR mutated lung adenocarcinoma developing a BRAFV600 mutation as an acquired resistance mechanism.

EGFR-mutant adenocarcinomas represent 12% of unselected lung adenocarcinomas and 44% of never smoker adenocarcinomas in the Caucasian population. Activating mutations like exon19 deletion or exon21 Leu858Arg point mutations are predictive of tumor response to EGFR tyrosine kinase inhibitors. Unfortunately, acquired resistance inevitably occurs by the development of novel EGFR mutations, mutations in other genes, gene amplification, gene fusion or tumor transformation. The management of tumors presenting multiple targetable mutations is unclear. We present the case of a patient developing a BRAFV600 mutation as acquired resistance mechanism to osimertinib, who responded favorably to the combination of dabrafenib, trametinib and osimertinib.

Integrative respiratory follow-up of severe COVID-19 reveals common functional and lung imaging sequelae.

BACKGROUND: COVID-19 pandemic resulted in an unprecedented number of hospitalizations in general wards and intensive care units (ICU). Severe and critical COVID-19 patients suffer from extensive pneumonia; therefore, long-term respiratory sequelae may be expected. RESEARCH QUESTION: We conducted a cohort study to determine respiratory sequelae in patients with severe and critical COVID-19. We aimed at evaluating the proportion of patients with persisting respiratory symptoms and/or abnormalities in pulmonary function tests (PFT) or in lung imaging. STUDY DESIGN: and methods: This is a single center cohort study including COVID-19 survivors who underwent a three-month follow-up with clinical evaluation, PFT and lung high-resolution computed tomography (HRCT). All clinical, functional, and radiological data were centrally reviewed. Multiple linear regression analysis was performed to identify factors associated with residual lesions on HRCT. RESULTS: Full clinical evaluation, PFT and lung HRCT were available for central review in 126, 122 and 107 patients, respectively. At follow-up, 25% of patients complained from dyspnea and 35% from fatigue, lung diffusion capacity (DLCO) was decreased in 45%, 17% had HRCT abnormalities affecting more than 5% of their lung parenchyma while signs of fibrosis were found in 21%. In multiple linear regression model, number of days in ICU were related to the extent of persisting lesions on HRCT, while intubation was associated with signs of fibrosis at follow-up (P = 0.0005, Fisher's exact test). In contrast, the severity of lung imaging or PFT changes were not predictive of fatigue and dyspnea. INTERPRETATION: Although most hospitalized COVID-19 patients recover, a substantial proportion complains from persisting dyspnea and fatigue. Impairment of DLCO and signs suggestive of fibrosis are common but are not strictly related to long-lasting symptoms.

Pulmonary tumor thrombotic microangiopathy in a patient with a metastatic urothelial carcinoma.

A 78-year-old woman was admitted for acute dyspnoea. One year before, she had been treated with cisplatin and gemcitabine for a high grade urothelial carcinoma. Immunotherapy was discussed 9 months later due the progression of bone metastases but could not be administered before this episode of respiratory distress. There was a major discrepancy between the findings of a limited pulmonary embolism at thoracic tomodensitometry and the severity of a recently developed pulmonary hypertension at echocardiography. The patient presented cardiac arrest on day 6 and post-mortem findings were consistent with diffuse pulmonary tumor thrombotic microangiopathy, a rare complication of urothelial carcinoma.

Vertebral uptake of 99mTc-macroaggregated albumin during lung perfusion scanning.

A 53-year-old female underwent a lung ventilation/perfusion scintigraphy (V/Q scan) in the workup of extensive thrombosis of the left subclavian and internal jugular veins. The perfusion lung scan visualized an atypical uptake in the thoracic vertebrae. A chest Computed Tomography (CT) scan demonstrated unusual tortuous and opacified thoracic superficial veins, collaterals of the lateral thoracic vein. Many venous collateral pathways can be developed in the case of superior vena cava syndrome. 99mTc-macroaggregated albumin particles may pass through the lateral thoracic vein and eventually through the vertebral venous plexus before being finally trapped by the vertebral capillaries. Besides right-to-left shunting, extrapulmonary uptake in the lung perfusion scintigraphy is very rare and may be used by collateral venous pathways.

Short telomeres increase the risk of severe COVID-19.

Telomeres are non-coding DNA sequences that protect chromosome ends and shorten with age. Short telomere length (TL) is associated with chronic diseases and immunosenescence. The main risk factor for mortality of coronavirus disease 2019 (COVID-19) is older age, but outcome is very heterogeneous among individuals of the same age group. Therefore, we hypothesized that TL influences COVID-19-related outcomes. In a prospective study, we measured TL by Flow-FISH in 70 hospitalized COVID-19 patients and compared TL distribution with our reference cohort of 491 healthy volunteers. We also correlated TL with baseline clinical and biological parameters. We stained autopsy lung tissue from six non-survivor COVID-19 patients to detect senescence-associated ß-galactosidase activity, a marker of cellular aging. We found a significantly higher proportion of patients with short telomeres (<10th percentile) in the COVID-19 patients as compared to the reference cohort (P<0.001). Short telomeres were associated with a higher risk of critical disease, defined as admission to intensive care unit (ICU) or death without ICU. TL was negatively correlated with C-reactive protein and neutrophil-to-lymphocyte ratio. Finally, lung tissue from patients with very short telomeres exhibit signs of senescence in structural and immune cells. Our results suggest that TL influences the severity of the disease.

Carcinoid Heart Disease on Computed Tomography.

Teaching Point: Carcinoid tumors can release hormones responsible of cardiac valves fibrosis known as carcinoid heart disease.

Familial hypersensitivity pneumonitis triggered by Cladosporium herbarum exposure during carpooling.

This series reports cases of Cladosporium herbarum-related HP due to an uncommon exposure source, illustrating the genetic background underlying HP, and highlighting the role of environmental home inquiry and serum precipitins in diagnosis and follow-up https://bit.ly/3hzvE4w.

Hazardous Removal of a Misplaced Nasogastric Tube.

Teaching point: Careful analysis of tubes positioning on chest X-ray not only reveals misplacement but also helps to plan a safe removal.

COVID-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 22 Cases From Belgium.

RATIONALE & OBJECTIVE: The world is facing a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although kidney transplant recipients are at increased risk for viral infections, the impact of their chronic immunosuppressed status on the risk for acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown. STUDY DESIGN: All cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients. SETTING & PARTICIPANTS: 22 COVID-19 infections were diagnosed in our cohort of 1,200 kidney transplant recipients. RESULTS: Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n = 3), moderate (n = 8), extensive (n = 1), severe (n = 2), and critical (n = 1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died. LIMITATIONS: Small sample size and short follow-up. CONCLUSIONS: The clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.