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Non-cystic fibrosis bronchiectasis represents a heterogenous spectrum of disorders characterised by an abnormal and permanent dilatation of the bronchial tree associated with respiratory symptoms. To date, diagnosis relies on computed tomography (CT) evidence of dilated airways. Nevertheless, definite radiological criteria and standardised CT protocols are still to be defined. Although largely used, current radiological scoring systems have shown substantial drawbacks, mostly failing to correlate morphological abnormalities with clinical and prognostic data. In limited cases, bronchiectasis morphology and distribution, along with associated CT features, enable radiologists to confidently suggest an underlying cause. Quantitative imaging analyses have shown a potential to overcome the limitations of the current radiological criteria, but their application is still limited to a research setting. In the present review, we discuss the role of imaging and its current limitations in non-cystic fibrosis bronchiectasis. The potential of automatic quantitative approaches and artificial intelligence in such a context will be also mentioned., (© 2021 The Authors. Published by the British Institute of Radiology.)

Lung nodules are frequent findings in chest computed tomography (CT) in patients with metastatic melanoma. In this study, we assessed the frequency and compared morphologic differences of metastases and benign nodules. We retrospectively evaluated 85 patients with melanoma (AJCC stage III or IV). Inclusion criteria were ≤20 lung nodules and follow-up using CT ≥183 days after baseline. Lung nodules were evaluated for size and morphology. Nodules with significant growth, nodule regression in line with RECIST assessment or histologic confirmation were judged to be metastases. A total of 438 lung nodules were evaluated, of which 68% were metastases. At least one metastasis was found in 78% of patients. A 10 mm diameter cut-off (used for RECIST) showed a specificity of 95% and a sensitivity of 20% for diagnosing metastases. Central location ( n = 122) was more common in metastatic nodules ( p = 0.009). Subsolid morphology ( n = 53) was more frequent ( p < 0.001), and calcifications ( n = 13) were solely found in non-metastatic lung nodules ( p < 0.001). Our data show that lung nodules are prevalent in about two-thirds of melanoma patients (AJCC stage III/IV) and the majority are metastases. Even though we found a few morphologic indicators for metastatic or non-metastatic lung nodules, morphology has limited value to predict the presence of lung metastases.

Lung cancer screening (LCS) is gaining some interest worldwide after positive results from International trials. Unlike other screening practices, LCS is performed by an extremely sensitive test, namely low-dose computed tomography (LDCT) that can detect the smallest nodules in lung parenchyma. Up-to-date detection approaches, such as computer aided detection systems, have been increasingly employed for lung nodule automatic identification and are largely used in most LCS programs as a complementary tool to visual reading. Solid nodules of any size are represented in the vast majority of subjects undergoing LDCT. However, less than 1% of solid nodules will be diagnosed lung cancer. This fact calls for specific characterization of nodules to avoid false positives, overinvestigation, and reduce the risks associated with nodule work up. Recent research has been exploring the potential of artificial intelligence, including deep learning techniques, to enhance the accuracy of both detection and characterisation of lung nodule. Computer aided detection and diagnosis algorithms based on artificial intelligence approaches have demonstrated the ability to accurately detect and characterize parenchymal nodules, reducing the number of false positives, and to outperform some of the currently used risk models for prediction of lung cancer risk, potentially reducing the proportion of surveillance CT scans. These forthcoming approaches will eventually integrate a new reasoning for development of future guidelines, which are expected to evolve into precision and personalized stratification of lung cancer risk stratification by continuous fashion, as opposed to the current format with a limited number of risk classes within fixed thresholds of nodule size. This review aims to detail the standard of reference for optimal management of solid nodules by low-dose computed and its projection into the fine selection of candidates for work up., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-296). The series “Lung cancer screening” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Aims: This study aims to investigate whether HS-when associated with an excessive amount of epicardial adipose tissue-correlates with CAD in subjects with symptoms suggestive of CVD., Methods and Results: CCTA images, demographic and clinical variables of 1.182 individuals were retrieved: semi-automated measurements for EFV, CAC, and MLD were obtained. Individuals were grouped into three categories according to the presence of CAD, resulting in absent (CAD 0 ), non-obstructive (CAD 1 ) or obstructive (CAD 2 ) disease-groups, and into two categories based on the presence of HS (with no HS, named HS - , and with HS, named HS + ). EFV was significantly higher in HS + than in HS - group (p < 0.001), whereas MLD was lower in CAD + than in CAD - subjects (p < 0.001). Two predictive models for CAD were tested: the former included clinical risk factors for CAD along with age, gender, EFV and MLD, whereas the latter did not include clinical variables. The logistic regression analysis of the second proposed model reliably discriminated CAD 0 from CAD 1 and CAD 2 (AUC of 0.712, range 0.682-0.742)., Conclusion: Lower MLD was associated with increased EFV, and MLD-as a marker of HS-discriminate symptomatic patients with CAD from whom without.

Objectives: To evaluate the inter-rater agreement of chest X-ray (CXR) findings in coronavirus disease 2019 (COVID-19) and to determine the value of initial CXR along with demographic, clinical, and laboratory data at emergency department (ED) presentation for predicting mortality and the need for ventilatory support., Methods: A total of 340 COVID-19 patients who underwent CXR in the ED setting (March 1-13, 2020) were retrospectively included. Two reviewers independently assessed CXR abnormalities, including ground-glass opacities (GGOs) and consolidation. Two scoring systems (Brixia score and percentage of lung involvement) were applied. Inter-rater agreement was assessed by weighted Cohen's kappa (κ) or intraclass correlation coefficient (ICC). Predictors of death and respiratory support were identified by logistic or Poisson regression., Results: GGO admixed with consolidation (n = 235, 69%) was the most common CXR finding. The inter-rater agreement was almost perfect for type of parenchymal opacity (κ = 0.90), Brixia score (ICC = 0.91), and percentage of lung involvement (ICC = 0.95). The Brixia score (OR: 1.19; 95% CI: 1.06, 1.34; p = 0.003), age (OR: 1.16; 95% CI: 1.11, 1.22; p < 0.001), PaO 2 /FiO 2 ratio (OR: 0.99; 95% CI: 0.98, 1; p = 0.002), and cardiovascular diseases (OR: 3.21; 95% CI: 1.28, 8.39; p = 0.014) predicted death. Percentage of lung involvement (OR: 1.02; 95% CI: 1.01, 1.03; p = 0.001) and PaO 2 /FiO 2 ratio (OR: 0.99; 95% CI: 0.99, 1.00; p < 0.001) were significant predictors of the need for ventilatory support., Conclusions: CXR is a reproducible tool for assessing COVID-19 and integrates with patient history, PaO 2 /FiO 2 ratio, and SpO 2 values to early predict mortality and the need for ventilatory support., Key Points: • Chest X-ray is a reproducible tool for assessing COVID-19 pneumonia. • The Brixia score and percentage of lung involvement on chest X-ray integrate with patient history, PaO 2 /FIO 2 ratio, and SpO 2 values to early predict mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.

Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine leiomyoma. Currently, there are no specific criteria to predict the metastasizing ability of the uterine leiomyoma and the risk of malignant degeneration of pulmonary BML, and these are the aims of this study. We analyzed 10 uterine (three leiomyomas, four leiomyomas that gave rise to lung BML, three healthy tissues) and 11 pulmonary tissue samples (eight lung BML, three healthy tissues). Interestingly, one of the BML lesions exceptionally evolved into a leiomyosarcoma (case 2). Uterine leiomyoma microvascular density (MVD) was higher in the patients with uterine leiomyomas that gave rise to lung BML, reaching a peak in case 2. Strong positivity for the estrogen (ER) and progesterone (PR) receptors and a low proliferation index (Ki67 < 1%) were discovered both in patients with uterine leiomyoma and in patients with BML. Interestingly, in case 2, the last dedifferentiated leiomyosarcoma showed a weaker ER and PR positivity with a higher proliferation index (Ki67:30%). Regarding the uterine miRNA-126, a trend toward a hypo-expression between uterine leiomyoma and uterine leiomyoma that gave rise to lung BML was discovered, reaching the lowest level in case 2. Considering the pulmonary samples, we observed a higher miRNA-221 and a lower miRNA-126 expression in the leiomyosarcoma. We tried to better elucidate the biological behaviour of this rare disease. The analysis of the miRNA-221 and miRNA-126 could offer new diagnostic, prognostic and therapeutic perspectives.

Objectives: The 2019 Lung CT Screening Reporting & Data System version 1.1 (Lung-RADS v1.1) introduced volumetric categories for nodule management. The aims of this study were to report the distribution of Lung-RADS v1.1 volumetric categories and to analyse lung cancer (LC) outcomes within 3 years for exploring personalized algorithm for lung cancer screening (LCS)., Methods: Subjects from the Multicentric Italian Lung Detection (MILD) trial were retrospectively selected by National Lung Screening Trial (NLST) criteria. Baseline characteristics included selected pre-test metrics and nodule characterization according to the volume-based categories of Lung-RADS v1.1. Nodule volume was obtained by segmentation with dedicated semi-automatic software. Primary outcome was diagnosis of LC, tested by univariate and multivariable models. Secondary outcome was stage of LC. Increased interval algorithms were simulated for testing rate of delayed diagnosis (RDD) and reduction of low-dose computed tomography (LDCT) burden., Results: In 1248 NLST-eligible subjects, LC frequency was 1.2% at 1 year, 1.8% at 2 years and 2.6% at 3 years. Nodule volume in Lung-RADS v1.1 was a strong predictor of LC: positive LDCT showed an odds ratio (OR) of 75.60 at 1 year (p < 0.0001), and indeterminate LDCT showed an OR of 9.16 at 2 years (p = 0.0068) and an OR of 6.35 at 3 years (p = 0.0042). In the first 2 years after negative LDCT, 100% of resected LC was stage I. The simulations of low-frequency screening showed a RDD of 13.6-21.9% and a potential reduction of LDCT burden of 25.5-41%., Conclusions: Nodule volume by semi-automatic software allowed stratification of LC risk across Lung-RADS v1.1 categories. Personalized screening algorithm by increased interval seems feasible in 80% of NLST eligible., Key Points: • Using semi-automatic segmentation of nodule volume, Lung-RADS v1.1 selected 10.8% of subjects with positive CT and 96.87 relative risk of lung cancer at 1 year, compared to negative CT. • Negative low-dose CT by Lung-RADS v1.1 was found in 80.6% of NLST eligible and yielded 40 times lower relative risk of lung cancer at 2 years, compared to positive low-dose CT; annual screening could be preference sensitive in this group. • Semi-automatic segmentation of nodule volume and increased screening interval by volumetric Lung-RADS v1.1 could retrospectively suggest a 25.5-41% reduction of LDCT burden, at the cost of 13.6-21.9% rate of delayed diagnosis.

Introduction: According to the Urology guidelines, in selected cases of distal upper tract urothelial carcinoma (UTUC) segmental ureterectomy (SU) can be offered. There is no consensus in the surgical technique of preference. Robot-assisted SU could be an option to overcome all the limitations of open and laparoscopic techniques. We describe our first experience of robot assisted SU with psoas hitch ureteral reimplantation (RAPHUR)., Materials and Methods: 11 patients underwent RAPHUR for distal UTUC between 2013 and 2017 in a single centre. Pre-, intra-, and postoperative outcomes were assessed. Conventional imaging was performed after 1, 3, 6 months and 1 year from surgery as follow up protocol. We retrospectively evaluated the technical feasibility, oncological and functional outcomes., Results: Median age was 71 years (57-91). The median length of the ureteral defect was 23 mm (10-40). Median preoperative creatinine level was 1.22 mg/dl (0.7-1.85) and median eGFR was 57.5 ml/min/1.73m2 (31-80). Five (45.5%) patients were symptomatic and 7 (63.6%) had hydronephrosis. Median operative time was 185 min (120-240), with a median blood loss of 100 ml (50-300). No case required conversion to open surgery. Overall, only 1 (9%) patient developed Clavien Dindo ≥ 3 postoperative complications. Average hospital stay was 7 (2-9) days. Mean postoperative creatinine was 1.05 mg/dl (0.8-1.85) and mean postoperative eGFR was 72 (36-83). During a median follow up time of 25.5 months (12-53), 4 (36.4%) patients experienced recurrence of urothelial cancer at conventional imaging follow up and 2 (18.2%) died due to its progression., Conclusions: In our initial experience RAPHUR can be proposed to selected cases of distal ureteral carcinoma with optimal perioperative and functional outcomes. However, cancer control may be undermined compared to nephroureterectomy. Thus, further prospective studies are needed to confirm our findings.

This collection includes some unusual cases and how they were diagnosed and treated. Case 1: A case of a patient with primary hyperthyroidism presenting with a submucosal ureteral stone after endoscopic lithotripsy was described. After multiple endoscopic treatment, the stone was successfully removed by open ureterolithotomy recovering ureteral patency and normal renal function. Case 2: A case of burned-out testicular cancer with atypical lymphatic spread (stage II A) was presented. After right orchiectomy and complete remission of tumor markers, due to atypical metastases location and uncertain histology, the patient was treated with systemic therapy based on bleomycin, etoposide and cisplatin (PEB). At re-staging after chemotherapy computed tomography showed reduction of all node metastases and an observation protocol was proposed. Case 3: A patient was readmitted to hospital after 12 days from an uneventful Robot-Assisted Radical Prostatectomy (RARP) for prostate cancer due to lower abdominal pain plus abdominal distension, nausea and constipation not responsive to medical therapy. Computed Tomography showed colon and small bowel dilatation without any evidence of anatomical or mechanical obstruction. Laparoscopic abdominal exploration confirmed bowel distension without evidence of obstructing lesions. Ogilvie's Syndrome or acute colonic pseudo-obstruction (ACPO) was diagnosed. The patient fully recovered and was discharged six days after the procedure. Case 4: A case of recurrent Acute Idiopathic Scrotal Edema (AISE) was diagnosed on clinical signs together with the decisive help of pathognomonic ultrasound findings as the "fountain sign". Case 5: Small bilateral testicular nodules were diagnosed in a 30-years old patient undergoing scrotal ultrasound in follow up of acute lymphoblastic leukemia. Ultrasound guided testis sparing surgery was performed demonstrating Leydig cell tumors.

Objectives: Ground-glass opacity and consolidation are recognized typical features of Coronavirus disease-19 (COVID-19) pneumonia on Chest CT, yet ancillary findings have not been fully described. We aimed to describe ancillary findings of COVID-19 pneumonia on CT, to define their prevalence, and investigate their association with clinical data., Methods: We retrospectively reviewed our CT chest cases with coupled reverse transcriptase polymerase chain reaction (rt-PCR). Patients with negative rt-PCR or without admission chest CT were excluded. Ancillary findings included: vessel enlargement, subpleural curvilinear lines, dependent subpleural atelectasis, centrilobular solid nodules, pleural and/or pericardial effusions, enlarged mediastinal lymph nodes. Continuous data were expressed as median and 95% confidence interval (95% CI) and tested by Mann-Whitney U test., Results: Ancillary findings were represented by 106/252 (42.1%, 36.1 to 48.2) vessel enlargement, 50/252 (19.8%, 15.4 to 25.2) subpleural curvilinear lines, 26/252 (10.1%, 7.1 to 14.7) dependent subpleural atelectasis, 15/252 (5.9%, 3.6 to 9.6) pleural effusion, 15/252 (5.9%, 3.6 to 9.6) mediastinal lymph nodes enlargement, 13/252 (5.2%, 3 to 8.6) centrilobular solid nodules, and 6/252 (2.4%, 1.1 to 5.1) pericardial effusion. Air space disease was more extensive in patients with vessel enlargement or centrilobular solid nodules ( p < 0.001). Vessel enlargement was associated with longer history of fever ( p = 0.035) and lower admission oxygen saturation ( p = 0.014); dependent subpleural atelectasis with lower oxygen saturation ( p < 0.001) and higher respiratory rate ( p < 0.001); mediastinal lymph nodes with shorter history of cough ( p = 0.046); centrilobular solid nodules with lower prevalence of cough ( p = 0.023), lower oxygen saturation ( p < 0.001), and higher respiratory rate ( p = 0.032), and pericardial effusion with shorter history of cough ( p = 0.015). Ancillary findings associated with longer hospital stay were subpleural curvilinear lines ( p = 0.02), whereas centrilobular solid nodules were associated with higher rate of intensive care unit admission ( p = 0.01)., Conclusion: Typical high-resolution CT findings of COVID-19 pneumonia are frequently associated with ancillary findings that variably associate with disease extent, clinical parameters, and disease severity., Advances in Knowledge: Ancillary findings might reflect the broad range of heterogeneous mechanisms in severe acute respiratory syndrome from viral pneumonia, and potentially help disease phenotyping.

The prevalence of heart failure (HF) is approximately 1-2% of the adult population in developed countries, rising to  ≥ 10% among people over 70. The common symptoms of HF include shortness of breath, ankle swelling and fatigue, determined by a reduced cardiac output. Multimodality imaging is crucial to define HF etiology, determine prognosis and guiding tailored treatments. Echocardiography is the most widely used imaging modality and maintains a pivotal role in the initial diagnostic work-up and in the follow-up of HF patients. Cardiac magnetic resonance (CMR) may support the morpho-functional assessment provided by echocardiography when the acoustic window is limited or a gold standard evaluation is required. Furthermore, CMR is frequently used due to the unmatched capability to characterize myocardial structure. Coronary computed tomography angiography has become the non-invasive imaging of choice to diagnose or rule-out coronary artery disease, acquiring remarkable importance in the management of HF patients. Moreover, emerging capabilities of CT-based tissue characterization may be useful, especially when CMR is contraindicated. Finally, chest CT may contribute to precisely define the framework of HF patients, revealing new insight about cardiopulmonary pathophysiological interactions with potential high prognostic value.

Objectives: To evaluate the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after CT-guided lung biopsy (CT-LB). To test correlations of PTX and chest tube insertion (CTI) with PH and other imaging and procedural parameters., Methods: Pre-procedural CT and CT-LB scans of 904 patients were examined. Incidence of PTX and PH and PH location (type-1 along needle track; type-2 perilesional) and severity according to its thickness (low grade < 6 mm; high grade > 6 mm) were recorded. PTX was considered clinically significant if treated with CTI, PH if treated with endoscopic/endovascular procedure. Binary logistic regression analyses were used to determine the effects of different imaging and procedural parameters on the likelihood to develop PTX, CTI and PH and to define their correlation., Results: PTX occurred in 306/904 cases (33.8%); CTI was required in 18/306 (5.9%). PH occurred in 296/904 cases (32.7%), and no case required treatment. Nodule-to-pleura distance (OR PTX  = 1.052; OR CTI  = 1.046; OR PH 1.077), emphysema (OR PTX  = 1.287; OR PH  = 0.573), procedure time (OR PTX  = 1.019; OR CTI  = 1.039; OR PH  = 1.019), target size (OR PTX  = 0.982; OR PH  = 0.968) and needle gauge (OR PTX  = 0.487; OR CTI  = 4.311; OR PH  = 2.070) showed statistically significant correlation to PTX, CTI and PH. Type-1 PH showed a protective effect against PTX and CTI (OR PTX  = 0.503; OR CTI  = 0.416)., Conclusion: PTX and PH have similar incidence after CT-guided lung biopsy. PH along needle track may represent a protective factor against development of PTX and against PTX requiring CTI.

We present three patients affected by pulmonary squamous cell carcinoma, metastatic esophageal cancer and advanced non-Hodgkin lymphoma, who incurred in coronavirus 2019 (COVID-19) infection during the early phase of epidemic wave in Italy. All patients presented with fever. Social contact with subject positive for COVID-19 was declared in only one of the three cases. In all cases, laboratory findings showed lymphopenia and elevated C-reactive protein (CRP). Chest x-ray and computed tomography showed bilateral ground-glass opacities, shadowing, interstitial abnormalities, and "crazy paving" pattern which evolved with superimposition of consolidations in one patient. All patients received antiviral therapy based on ritonavir and lopinavir, associated with hydroxychloroquine. Despite treatment, two patients with advanced cancers died after 39 and 17 days of hospitalization, while the patient with lung cancer was dismissed at home, in good conditions., Competing Interests: Declaration of competing interest The Authors declared no conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 90-year-old woman received a dual chamber pacemaker (PM) for a sick sinus syndrome. The PM was programmed with SafeR AAI-DD pacing mode at 60 bpm. During a standard follow up, some memorized electrograms (EGMs) were found in SafeR diagnostics, with atrial pacing (Ap) not followed by any ventricular sensing/pacing event, due to simultaneous junctional activity falling into ventricular blanking period during Ap and, for this reason, unsensed by the PM. Blanking periods can affect PM functioning if not revealed and adjusted., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.)

The objective of this study was to determine the correlation between functional and radiological longitudinal change in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), and to test the OMERACT definition of clinically meaningful progression of pulmonary function tests (PFTs) for the prediction of ILD radiological evolution. We retrospectively retrieved high-resolution computed tomography (HRCT) studies and PFTs including DLco, both available at two time-points and performed within 6 months of each other, in SSc patients. A subset of patients was selected using a 12-24-month clinically oriented interval (n = 58). The extent of ILD at HRCT was scored according to a visual semi-quantitative method (SQCT). The correlation of absolute change (Δ) in the SQCT score with change in FVC and DLco was examined using Pearson's correlation coefficient. The concordance between the OMERACT criteria (≥ 10% FVC relative decline; or 5-10% FVC and ≥ 15% DLco relative decline) and SQCT categorical change (5% and 10%) was investigated. A total of 129 patients were enrolled. During 12-24-month follow-up, ΔSQCT was negatively correlated with ΔFVC (r = - 0.487, p = 0.0001) and ΔDLco (r = - 0.298, p = 0.023). Ten patients demonstrated CT progression ΔSQCT > 5%, among whom 5 with ΔSQCT > 10%. OMERACT criteria identified 25 patients with progressive SSc-ILD, of whom only 5 presented ΔSQCT > 5 and 3 presented ΔSQCT > 10%. In conclusion, change in radiological extent of SSc-ILD was correlated to functional decline in a limited time-frame. Repeated HRCT after 12-24 months may be useful for the longitudinal characterization of ILD evolution in patients with stable pulmonary function. Conversely, functional changes are suggestive of a concurrent radiological progression only after this interval. Key Points • In SSc patients, chest HRCT performed every 12-24 months can detect minimal but significant changes in ILD extent, even in subjects with stable pulmonary function. • PFT changes in 12-24 months are related to the radiological ILD progression. • OMERACT criteria might overlook patients with radiological progression. • Repeated chest HRCT may be useful for monitoring SSc-ILD when performed within 12 to 24 months from baseline in order to promptly detect progression and possibly impact on prognosis.

Purpose: To test the association between death and both qualitative and quantitative CT parameters obtained visually and by software in coronavirus disease (COVID-19) early outbreak., Methods: The study analyzed retrospectively patients underwent chest CT at hospital admission for COVID-19 pneumonia suspicion, between February 21 and March 6, 2020. CT was performed in case of hypoxemia or moderate-to-severe dyspnea. CT scans were analyzed for quantitative and qualitative features obtained visually and by software. Cox proportional hazards regression analysis examined the association between variables and overall survival (OS). Three models were built for stratification of mortality risk: clinical, clinical/visual CT evaluation, and clinical/software-based CT assessment. AUC for each model was used to assess performance in predicting death., Results: The study included 248 patients (70% males, median age 68 years). Death occurred in 78/248 (32%) patients. Visual pneumonia extent > 40% (HR 2.15, 95% CI 1.2-3.85, P = 0.01), %high attenuation area - 700 HU > 35% (HR 2.17, 95% CI 1.2-3.94, P = 0.01), exudative consolidations (HR 2.85-2.93, 95% CI 1.61-5.05/1.66-5.16, P < 0.001), visual CAC score > 1 (HR 2.76-3.32, 95% CI 1.4-5.45/1.71-6.46, P < 0.01/P < 0.001), and CT classified as COVID-19 and other disease (HR 1.92-2.03, 95% CI 1.01-3.67/1.06-3.9, P = 0.04/P = 0.03) were significantly associated with shorter OS. Models including CT parameters (AUC 0.911-0.913, 95% CI 0.873-0.95/0.875-0.952) were better predictors of death as compared to clinical model (AUC 0.869, 95% CI 0.816-0.922; P = 0.04 for both models)., Conclusions: In COVID-19 patients, qualitative and quantitative chest CT parameters obtained visually or by software are predictors of mortality. Predictive models including CT metrics were better predictors of death in comparison to clinical model.

Purpose: Chest computed tomography (CT) is considered a reliable imaging tool for COVID-19 pneumonia diagnosis, while lung ultrasound (LUS) has emerged as a potential alternative to characterize lung involvement. The aim of the study was to compare diagnostic performance of admission chest CT and LUS for the diagnosis of COVID-19., Methods: We included patients admitted to emergency department between February 21-March 6, 2020 (high prevalence group, HP) and between March 30-April 13, 2020 (moderate prevalence group, MP) undergoing LUS and chest CT within 12 h. Chest CT was considered positive in case of "indeterminate"/"typical" pattern for COVID-19 by RSNA classification system. At LUS, thickened pleural line with ≥ three B-lines at least in one zone of the 12 explored was considered positive. Sensitivity, specificity, PPV, NPV, and AUC were calculated for CT and LUS against real-time reverse transcriptase polymerase chain reaction (RT-PCR) and serology as reference standard., Results: The study included 486 patients (males 61 %; median age, 70 years): 247 patients in HP (COVID-19 prevalence 94 %) and 239 patients in MP (COVID-19 prevalence 45 %). In HP and MP respectively, sensitivity, specificity, PPV, and NPV were 90-95 %, 43-69 %, 96-72 %, 20-95 % for CT and 94-93 %, 7-31 %, 94-52 %, 7-83 % for LUS. CT demonstrated better performance than LUS in diagnosis of COVID-19, both in HP (AUC 0.75 vs 0.51; P < 0.001) and MP (AUC 0.85 vs 0.62; P < 0.001)., Conclusions: Admission chest CT shows better performance than LUS for COVID-19 diagnosis, at varying disease prevalence. LUS is highly sensitive, but not specific for COVID-19., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 μm long, which includes 35-40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase-3 and caspase-9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo-mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8-13%) and undifferentiated (4-13%) cells reminiscent of STCs suggests a non-negligible cell turnover., (© 2020 American Association for Anatomy.)

Background: To determine if an increased epicardial fat volume (EFV) is associated with coronary artery disease (CAD) in individuals with symptoms of cardiovascular (CV) disease., Methods: Coronary Computed Tomographic Angiography (CCTA), demographic and clinical variables of 1344 individuals were retrieved: semi-automated measurements for EFV and coronary artery calcifications (CAC) were obtained. Individuals were grouped into three categories according to the presence of CAD, resulting in absent (CAD 0 ), non-obstructive (CAD 1 ) or obstructive (CAD 2 ) disease-groups. Relation of EFV with CAD was assessed with two approaches: 1) presence of any CAD; 2) each individual CAD category., Results: Median EFV was 90.52 ml (range 11.27-442.21 ml); median CAC was 56.5 (range 0-10,144); 848 individuals (63.1%) were categorized as CAD 0 , 326 (24.3%) as CAD 1 , 170 (12.6%) as CAD 2 . EFV was lower in subjects without CAC (EFV median  = 66.5 ml), as compared to those with CAC 0.1-100 (EFV median  = 91.47), CAC 100.1-400 (EFV median  = 97.46) and CAC >400 (EFV median  = 109.48) (p < 0.001). EFV was lower in CAD 0 (EFV median  = 87.21 ml), as compared to CAD 1 (EFV median  = 93.89 ml) and CAD 2 (EFV median  = 102.98 ml) individuals (p < 0.001). A logistic regression model built by including demographic and clinical variables showed inconsistent predictive value of EFV for either CAD 1 or CAD 2 (p > 0.05)., Conclusions: In the setting of symptomatic individuals, an increased amount of epicardial fat was associated with larger amount of coronary artery calcifications and was observed in individuals with obstructive CAD, however without predictive value to confidently determine CAD presence and severity., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background CT of patients with severe acute respiratory syndrome coronavirus 2 disease depicts the extent of lung involvement in coronavirus disease 2019 (COVID-19) pneumonia. Purpose To determine the value of quantification of the well-aerated lung (WAL) obtained at admission chest CT to determine prognosis in patients with COVID-19 pneumonia. Materials and Methods Imaging of patients admitted at the emergency department between February 17 and March 10, 2020 who underwent chest CT were retrospectively analyzed. Patients with negative results of reverse-transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 at nasal-pharyngeal swabbing, negative chest CT findings, and incomplete clinical data were excluded. CT images were analyzed for quantification of WAL visually (%V-WAL), with open-source software (%S-WAL), and with absolute volume (VOL-WAL). Clinical parameters included patient characteristics, comorbidities, symptom type and duration, oxygen saturation, and laboratory values. Logistic regression was used to evaluate the relationship between clinical parameters and CT metrics versus patient outcome (intensive care unit [ICU] admission or death vs no ICU admission or death). The area under the receiver operating characteristic curve (AUC) was calculated to determine model performance. Results The study included 236 patients (59 of 123 [25%] were female; median age, 68 years). A %V-WAL less than 73% (odds ratio [OR], 5.4; 95% confidence interval [CI]: 2.7, 10.8; P < .001), %S-WAL less than 71% (OR, 3.8; 95% CI: 1.9, 7.5; P < .001), and VOL-WAL less than 2.9 L (OR, 2.6; 95% CI: 1.2, 5.8; P < .01) were predictors of ICU admission or death. In comparison with clinical models containing only clinical parameters (AUC = 0.83), all three quantitative models showed better diagnostic performance (AUC = 0.86 for all models). The models containing %V-WAL less than 73% and VOL-WAL less than 2.9 L were superior in terms of performance as compared with the models containing only clinical parameters ( P = .04 for both models). Conclusion In patients with confirmed coronavirus disease 2019 pneumonia, visual or software quantification of the extent of CT lung abnormality were predictors of intensive care unit admission or death. ©  RSNA, 2020 Online supplemental material is available for this article.

The immune regulation of cancer growth and regression has been underscored by the recent success of immunotherapy. The possibility that immune microenvironmental factors may impact on clinical outcome and treatment response still requires intense investigations. Hereby, supporting data of the research article "Integrated CT Imaging and Tissue Immune Features Disclose a Radio-Immune Signature with High Prognostic Impact on Surgically Resected NSCLC" [1], are presented. With the ultimate aim to provide non-invasive prognostic scores, we report on our approach to correlate different Tumor Immune Microenvironment (TIME) profiles with CT imaging-derived qualitative (semantic, CT-SFs) and quantitative (radiomic, CT-RFs) features in a cohort of 60 surgically resected NSCLC. The renowned characterization of TIME, essentially based on the score evaluation of Programme Death Ligand-1 (PD-L1) and Tumor Infiltrating Lymphocytes (TILs), was implemented here by the assessment of effector and suppressor phenotypes including the analysis of Programme Death receptor 1 (PD-1). Thus, we defined two main TIME categories: hot inflamed (PD-L1 high , CD8/CD3 high and PD-1/CD8 low ) as opposed to cold inactive (PD-L1 low , CD8/CD3 low and PD-1/CD8 high ). Importantly, as reported in the extended publication [1], these distinctive immune contextures identified different prognostic classes and were decoded by radiomics. To corroborate our radiomic approach, a comparative estimation of CT-RFs extracted from 60 NSCLC and 13 non neoplastic tissues was undertaken, documenting high discrimination ability. Moreover, we tested the potential association of qualitative radiologic features with clinico-pathological and TIME parameters. Taken together, our findings suggest that CT-SFs and CT-RFs may underlay specific patterns of lung cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 Published by Elsevier Inc.)

Objectives: Qualitative and quantitative CT imaging features might intercept the multifaceted tumor immune microenvironment (TIME), providing a non-invasive approach to design new prognostic models in NSCLC patients., Materials and Methods: Our study population consisted of 100 surgically resected NSCLC patients among which 31 served as a validation cohort for quantitative image analysis. TIME was classified according to PD-L1 expression and the magnitude of Tumor Infiltrating Lymphocytes (TILs) and further defined as hot or cold by the tissue analysis of effector (CD8-to-CD3 high /PD-1-to-CD8 low ) or inert (CD8-to-CD3 low /PD-1-to-CD8 high ) phenotypes. CT datasets acted as source for qualitative (semantic, CT-SFs) and quantitative (radiomic, CT-RFs) features which were correlated with clinico-pathological and TIME profiles to determine their impact on survival outcome., Results: Specific CT-SFs (texture [TXT], effect [EFC] and margins [MRG]) strongly correlated to PD-L1 and TILs status and showed significant impact on survival outcome (TXT, HR:3.39, 95 % CI 1.12-10-27, P < 0.05; EFC, HR:0.41, 95 % CI 0.18-0.93, P < 0.05; MRG, HR:1.93, 95 % CI 0.88-4.25, P = 0.09). Seven CT derived radiomic features were able to sharply discriminate cases with hot (inflamed) vs cold (desert) TIME, which also exhibited opposite OS (long vs short, HR:0.09, 95 % CI 0.04-0.23, P < 0.001) and DFS (long vs short, HR:0.31, 95 % CI 0.16-0.58, P < 0.001). Moreover, we identified 6 prognostic radiomic features among which ClusterProminence displayed the highest statistical significance (HR:0.13, 95 % CI 0.06-0.31, P < 0.001). These findings were independently validated in an additional cohort of NSCLC (HR:0.11, 95 % CI 0.03-0.40, P = 0.001). Finally, in our training cohort we developed a multiparametric prognostic model, interlacing TIME and clinico-pathological characteristics with CT-SFs (ROC curve AUC:0.83, 95 % CI 0.71-0.92, P < 0.001) or CT-RFs (AUC: 0.91, 95 % CI 0.83-0.99, P < 0.001), which appeared to outperform pTNM staging (AUC: 0.66, 95 % CI 0.51-0.80, P < 0.05) in the risk assessment of NSCLC., Conclusion: Higher order CT extracted features associated with specific TIME profiles may reveal a radio-immune signature with prognostic impact on resected NSCLC., Competing Interests: Declaration of Competing Interest All Authors have declared no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the coronavirus disease 2019 (COVID-19), a respiratory disease that ranges from an asymptomatic or mild flu-like illness to severe pneumonia, multiorgan failure, and death. Imaging might play an important role in clinical decision making by supporting rapid triage of patients with suspected COVID-19 and assessing supervening complications, such as super-added bacterial infection and thrombosis. Further studies will clarify the real impact of imaging on COVID-19 patients' management and the potential role of radiology in future outbreaks.

The goal of the current study was to identify potential roles of paraoxonase-2 in bladder carcinogenesis. T24 bladder cancer cells were transfected with plasmids inducing paraoxonase-2 silencing or overexpression. Upon the selection of clones stably down- or upregulating paraoxonase-2, cell proliferation, migration, and the production of reactive oxygen species were evaluated, before and after treatment with cisplatin and gemcitabine, used alone or in combination. The activity levels of both caspase-3 and caspase-8 were also analyzed. shRNA-mediated gene silencing and the overexpression of paraoxonase-2 revealed that the enzyme was able to promote both the proliferation and migration of T24 cells. Moreover, the knockdown of paraoxonase-2 was significantly associated with a reduced cell viability of T24 cells treated with chemotherapeutic drugs and led to both an increase of reactive oxygen species production and caspase-3 and caspase-8 activation. Conversely, under treatment with anti-neoplastic compounds, a higher proliferative capacity was found in T24 cells overexpressing paraoxonase-2 compared with controls. In addition, upon enzyme upregulation, both the production of reactive oxygen species and activation of caspase-3 and caspase-8 were reduced. Although further analyses will be required to fully understand the involvement of paraoxonase-2 in bladder tumorigenesis and in mechanisms leading to the development of chemoresistance, the data reported in this study seem to demonstrate that the enzyme could exert a great impact on tumor progression and susceptibility to chemotherapy, thus suggesting paraoxonase-2 as a novel and interesting molecular target for effective bladder cancer treatment., Competing Interests: The authors declare no conflicts of interest.

Objectives: To retrospectively compare semi-qualitative and quantitative CT pulmonary angiography (CTPAs) image metrics testing diagnostic performance between protocols performed by 20 or 40 ml of contrast medium (CM) in patients with suspected pulmonary embolism (PE)., Methods: A total of 102 CTPAs performed by 20 ml (ultra-low volume: ULV) and 74 CTPAs performed by 40 ml (low volume: LV) protocol for the diagnosis of clinically suspected PE performed between October 2012 and September 2013 were retrieved. High-concentration CM (Iomeprol 400 mgI/ml) was injected at 3 ml/s (iodine delivery rate 1.2 mgI/s). Two radiologists (blinded and independent) semi-qualitatively scored vascular enhancement and image noise according to a five-point visual scoring system. Quantitative analysis was performed by regions of interest quantifying densitometric parameters, such as central and peripheral pulmonary arteries vascular contrast enhancement (CE, threshold for diagnostic CE ≥ 250 HU), and metrics for image noise. Continuous variables were compared by the Student's t test between groups if normally distributed while categorical variables were analyzed with the Chi-squared test. Interobserver agreement was calculated by the weighted kappa test; correlation coefficients were calculated using Pearson's correlation tests., Results: The semi-qualitative scores for central and peripheral pulmonary arteries vascular CE were sufficient by ULV, yet inferior than LV (p < 0.001). Semi-qualitative image noise was comparable between ULV and LV, and the interobserver agreement was only fair for quality of peripheral vessels. Agreement on nondiagnostic semi-qualitative parameters was seen in 9/102 (8.8%) ULV CTPAs, in particular associated with massive PE (2/9), pleuro-pulmonary abnormalities (5/9) or without major abnormalities (2/9). Quantitative analysis showed that mean CE was lower in ULV group (p < 0.001), though greater than the diagnostic threshold of 250 HU in both groups., Conclusions: Diagnostic vascular CE (> 250 HU) was obtained in both 20 ml and 40 ml CTPAs. CTPA by 20 ml of CM rendered diagnostic CE for the assessment of pulmonary arteries in patients with clinical suspicion of acute PE. Decreased image quality was mostly associated with massive PE or concomitant pleuro-parenchymal abnormalities.

Background: Lung ultrasound (LUS) is an accurate, safe, and cheap tool assisting in the diagnosis of several acute respiratory diseases. The diagnostic value of LUS in the workup of coronavirus disease-19 (COVID-19) in the hospital setting is still uncertain., Objectives: The aim of this observational study was to explore correlations of the LUS appearance of COVID-19-related pneumonia with CT findings., Methods: Twenty-six patients (14 males, age 64 ± 16 years) urgently hospitalized for COVID-19 pneumonia, who underwent chest CT and bedside LUS on the day of admission, were enrolled in this observational study. CT images were reviewed by expert chest radiologists, who calculated a visual CT score based on extension and distribution of ground-glass opacities and consolidations. LUS was performed by clinicians with certified competency in thoracic ultrasonography, blind to CT findings, following a systematic approach recommended by ultrasound guidelines. LUS score was calculated according to presence, distribution, and severity of abnormalities., Results: All participants had CT findings suggestive of bilateral COVID-19 pneumonia, with an average visual scoring of 43 ± 24%. LUS identified 4 different possible -abnormalities, with bilateral distribution (average LUS score 15 ± 5): focal areas of nonconfluent B lines, diffuse confluent B lines, small subpleural microconsolidations with pleural line irregularities, and large parenchymal consolidations with air bronchograms. LUS score was significantly correlated with CT visual scoring (r = 0.65, p < 0.001) and oxygen saturation in room air (r = -0.66, p < 0.001)., Conclusion: When integrated with clinical data, LUS could represent a valid diagnostic aid in patients with suspect COVID-19 pneumonia, which reflects CT findings., (© 2020 S. Karger AG, Basel.)

Purpose: To test ultra-low-dose computed tomography (ULDCT) scanning protocols for the detection of pulmonary nodules (PN)., Methods: A chest phantom containing 19 solid and 11 subsolid PNs was scanned on a third-generation dual-source computed tomography (CT) scanner. Five ULDCT scans (Sn100kVp and 120, 70, 50, 30, and 20 reference mAs, using tube current modulation), reconstructed with iterative reconstruction (IR) algorithm at strength levels 2, 3, 4, and 5, were compared with standard CT (120kVp, 150 reference mAs, using tube current modulation). PNs were subjectively assessed according to a 4-point scale: 0, nondetectable nodule; 1, detectable nodule, very unlikely to be correctly measured; 2, detectable nodule, likely to be correctly measured; 3, PN quality equal to standard of reference. PN scores were analysed according to the Lung Imaging Reporting and Data System (Lung-RADS), simulating detection of nodules at baseline and incidence screening round., Results: For the baseline round, there were 17 Lung-RADS 2, 4 Lung-RADS 3, 8 Lung-RADS 4A, and 1 Lung-RADS 4B PNs. They were detectable in any ULDCT protocol, with the exception of 1 nondetectable part-solid nodule in 1 scanning protocol (120 reference mAs; IR strength: 3). For the incidence round, there were 4 Lung-RADS 2, 14 Lung-RADS 3, 2 Lung-RADS 4A, and 10 Lung-RADS 4B PNs. Ten were nondetectable in at least one ULDCT dataset; however, they were at least detectable in ULDCT with 70 reference mAs (IR strength: 4 and 5)., Conclusions: ULDCT scanning protocols allowing the detection of PNs can be proposed for the purpose of lung cancer screening.

Purpose: The aim of this study was to assess computed-tomography histogram analysis (CTHA) as prognostic and predictive factor in platinum-refractory non-small cell lung carcinoma (NSCLC) treated with immune checkpoint inhibitor Nivolumab., Method: One hundred and four patients were enrolled from 3 different centers. CT was performed using similar parameters among different scanners. CTHA was performed with the proprietary software TexRAD, which extracts histogram features at different spatial scale (spatial scale filters, SSF) producing 30 CTHA features per patients. Cross-validated Least Absolute Shrinkage and Selection Operator LASSO was used to select those features which were related to overall and progression-free survival (OS and PFS, respectively). High- and low-risk subgroups were identified using the best cutoff., Results: Median follow-up was 13.8 weeks. Median OS and PFS were 7.3 and 3 months, respectively. LASSO selected kurtosis obtained by SSF = 4 mm as the single feature related to OS, leading to an hazard ratio (HR) of 0.476 (95%CI 0.29-0.77). PFS was related with kurtosis SSF = 6 mm, with HR of 0.556 (95%CI 0.36-0.86)., Conclusion: Despite its limitations, this study is the first which suggests that CTHA could play a role in stratifying prognosis and treatment response in patients with NSCLC treated with Nivolumab., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To reduce the radiation exposure from chest computed tomography (CT), ultralow-dose CT (ULDCT) protocols performed at sub-millisievert levels were previously tested for the evaluation of pulmonary nodules (PNs). The purpose of our study was to investigate the effect of ULDCT and iterative image reconstruction on volumetric measurements of solid PNs., Methods: CT datasets of an anthropomorphic chest phantom containing solid microspheres were obtained with a third-generation dual-source CT at standard dose, 1/8th, 1/20th and 1/70th of standard dose [CT volume dose index (CTDI vol ): 0.03-2.03 mGy]. Semi-automated volumetric measurements were performed on CT datasets reconstructed with filtered back projection (FBP) and advanced modelled iterative reconstruction (ADMIRE), at strength level 3 and 5. Absolute percentage error (APE) evaluated measurement accuracy related to the effective volume. Scan repetition differences were evaluated using Bland-Altman analysis. Two-way analysis of variance (ANOVA) assessed influence of different scan parameters on APE. Proportional differences (PDs) tested the effect of dose settings and reconstruction algorithms on volumetric measurements, as compared to the standard protocol (standard dose-FBP)., Results: Bland-Altman analysis revealed small mean interscan differences of APE with narrow limits of agreement (-0.1%±4.3% to -0.3%±3.8%). Dose settings (P<0.001), reconstruction algorithms (P<0.001), nodule diameters (P<0.001) and nodule density (P=0.011) had statistically significant influence on APE. Post-hoc Bonferroni tests showed slightly higher APE when scanning with 1/70th of standard dose [mean difference: 3.4%, 95% confidence interval (CI): 2.5-4.3%; P<0.001], and for image reconstruction with ADMIRE5 (mean difference: 1.8%, 95% CI: 1.0-2.5%; P<0.001). No significant differences for scanning with 1/20th of standard dose (P=0.42), and image reconstruction with ADMIRE3 (P=0.19) were found. Scanning with 1/70th of standard dose and image reconstruction with FBP showed the widest range of PDs (-16.8% to 23.4%) compared to standard dose-FBP., Conclusions: Our phantom study showed no significant difference between nodule volume measurements on standard dose CT (CTDI vol : 2 mGy) and ULDCT with 1/20th of standard dose (CTDI vol : 0.10 mGy)., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

To test whether texture analysis (TA) can discriminate between Systemic Sclerosis (SSc) and non-SSc patients in computed tomography (CT) with different radiation doses and reconstruction algorithms.In this IRB-approved retrospective study, 85 CT scans at different radiation doses [49 standard dose CT (SDCT) with a volume CT dose index (CTDIvol) of 4.86 ± 2.1 mGy and 36 low-dose (LDCT) with a CTDIvol of 2.5 ± 1.5 mGy] were selected; 61 patients had Ssc ("cases"), and 24 patients had no SSc ("controls"). CT scans were reconstructed with filtered-back projection (FBP) and with sinogram-affirmed iterative reconstruction (SAFIRE) algorithms. 304 TA features were extracted from each manually drawn region-of-interest at 6 pre-defined levels: at the midpoint between lung apices and tracheal carina, at the level of the tracheal carina, and 4 between the carina and pleural recesses. Each TA feature was averaged between these 6 pre-defined levels and was used as input in the machine learning algorithm artificial neural network (ANN) with backpropagation (MultilayerPerceptron) for differentiating between SSc and non-SSc patients.Results were compared regarding correctly/incorrectly classified instances and ROC-AUCs.ANN correctly classified individuals in 93.8% (AUC = 0.981) of FBP-LDCT, in 78.5% (AUC = 0.859) of FBP-SDCT, in 91.1% (AUC = 0.922) of SAFIRE3-LDCT and 75.7% (AUC = 0.815) of SAFIRE3-SDCT, in 88.1% (AUC = 0.929) of SAFIRE5-LDCT and 74% (AUC = 0.815) of SAFIRE5-SDCT.Quantitative TA-based discrimination of CT of SSc patients is possible showing highest discriminatory power in FBP-LDCT images.

Objectives: We hypothesize a significant correlation between parameters of preoperative dynamic magnetic resonance imaging (MRI) and postoperative outcomes measured by pulmonary function tests., Methods: Dynamic MRI of the lungs was prospectively performed during 2 breath cycles 1 day before and 3 months after surgery, herein termed as pre- and post-lung-volume reduction surgery (LVRS) MRI. Quantitative measurements were performed on sagittal planes for the left lung and right lung: lung height, anteroposterior diameter, hemidiaphragm height and area as well as perimeter. Additionally, dynamic changes in hemidiaphragmatic area and height were measured. Parameters were normalized by patients' height. Pulmonary function test pre-LVRS and post-LVRS was performed. The cut-off value for treatment benefit was defined as a 30% increase in forced expiratory volume in 1 s., Results: Thirty-nine consecutive patients (15 women, median age 61 years) were included. On expiration, the mean lung area on both sides (Pright = 0.001 and Pleft = 0.016) and anteroposterior diameter of the right lung (Pright = 0.003) improved post-LVRS. Dynamic measurements showed differences pre- and post-LVRS on the right lung but not on the left lung (Pright < 0.001 and Pleft = 0.090). There were no significant changes in lung height for both sides, in hemidiaphragmatic height on the right as well as diaphragmatic area pre- and post-LVRS (P > 0.05). Except for hemidiaphragmatic height on the left lung (P = 0.039), no significant differences were found on inspiration. Considering the 30% cut-off for treatment benefit, the receiver operating curves analysis indicated a height-normalized expiratory lung area ≥35 793 mm2 as the most sensitive preoperative outcome predictor (sensitivity = 86%; specificity = 61%)., Conclusions: Preoperative dynamic MRI can be used as an additional outcome predictor for patient selection in LVRS. A height-normalized total lung area in expiration ≥35 793 mm2 correlates with a 30% increase in forced expiratory volume in 1 s., Clinical Trial Registration Number: SNCTP000000480., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Implantable cardioverter-defibrillator (ICD) alarm systems are an important means of monitoring device functioning. The aim of this study was to compare the ability of patients with sense two types of device alert systems: an audible alert and a vibratory alarm., Methods: The ability to recognize the alarms was assessed in three alarm tests performed in a series of consecutive ICD patients enrolled during routine outpatient device follow-up. To avoid overestimating the rate of patients able to sense the alarm, the first test was performed without forewarning. Subsequently, the second test was performed after the patients had been forewarned. Finally, to assess the learning effect of a demonstration test, a third test was performed, again without forewarning., Results: A total of 528 patients (65.4 ± 14.4 years, 74.6% male) were enrolled: 347 (65.7%) with an audible alert-endowed device and 181 (34.3%) with a vibratory alarm-endowed device. When emitted without warning, the alarms were sensed by 72.4% of patients. When patients were forewarned, the probability of sensing the alarms rose to 92.5% (P < 0.001). In both cases, the vibratory alarm was more likely to be sensed than the audible alert (77.3 vs. 67.7% in the first case; 96.1 vs. 87.9% in the second case; all P < 0.05)., Conclusion: ICD alarms emitted in an outpatient setting are sensed by a large proportion of patients, but not by all. Training patients by means of demonstration tests significantly increases the rate of patients who recognize the alarm. Vibratory alarm seems to be more effective than audible alert.

Objective: To evaluate the radiation dose for pregnant women and fetuses undergoing commonly used computed tomography of the pulmonary arteries (CTPA) scan protocols and subsequently evaluate the simulated effect of an optimized scan length., Materials and Methods: A total of 120 CTPA datasets were acquired using four distinctive scan protocols, with 30 patients per protocol. These datasets were mapped to Cristy phantoms in order to simulate pregnancy and to assess the effect of an effective radiation dose (in mSv) in the first, second, or third trimester of pregnancy, including a simulation of fetal dose in second and third trimesters. The investigated scan protocols involved a 64-slice helical scan at 120 kVp, a high-pitch dual source acquisition at 100 kVp, a dual-energy acquisition at 80/140 kVp, and an automated-kV-selection, high pitch helical scan at a reference kV of 100 kV ref . The effective dose for women and fetuses was simulated before and after scan length adaptation. The original images were interpreted before and after scan length adaptations to evaluate potentially missed diagnoses., Results: Large inter-scanner and inter-protocol variations were found; application of the latest technology decreased the dose for non-pregnant women by 69% (7.0-2.2 mSv). Individual scan length optimization proved safe and effective, decreasing the fetal dose by 76-83%. Nineteen (16%) cases of pulmonary embolism were diagnosed and, after scan length optimization, none were missed., Conclusion: Careful CTPA scan protocol selection and additional optimization of scan length may result in significant radiation dose reduction for a pregnant patient and her fetus, whilst maintaining diagnostic confidence., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2019 The Korean Society of Radiology.)

Objectives: To assess the value of pre-procedural computed tomography angiography (CTA) measurements of the suprahepatic inferior vena cava (IVC) to detect elevated central venous pressure (CVP) assessed by right heart catheterisation (RHC), and to predict post-procedural 1-year mortality in a cohort of patients undergoing transcatheter aortic valve implantation (TAVI)., Methods: We retrospectively evaluated 408 consecutive patients undergoing CTA before TAVI between January 2011 and December 2014. Two hundred and five patients were included in the RHC cohort, who underwent RHC and CTA within ≤1 day prior to TAVI. Two hundred and three patients not fulfilling this requirement were included in the validation cohort. Measurements of the IVC were performed between diaphragm and right atrium on axial slices. Receiver operating characteristic (ROC) analyses, Kaplan-Meier analyses and Cox regression analyses were performed., Results: In the RHC cohort, ROC curve analyses for IVC area measurements indicated an AUC of 0.77 (p < 0.001) to detect CVP ≥10mmHg and an area under the ROC curve (AUC) of 0.72 (p < 0.001) to predict 1-year mortality. An IVC area cut-off of ≥665 mm 2 predicted 1-year mortality with a specificity of 84% and a sensitivity of 63%. Kaplan-Meier analysis showed that patients with an IVC area ≥665 mm 2 had a significantly higher post-procedural 1-year mortality (38% versus 7%, log-rank p < 0.001) with a hazard ratio of 5.5 (95% CI, 2.2-13.6; p < 0.001). Applying this cut-off value to the validation cohort confirmed a significantly higher 1-year mortality after TAVI (34% versus 11%; log-rank p = 0.004) for patients with an IVC area ≥665 mm 2 ., Conclusions: Pre-procedural enlargement of the suprahepatic IVC is a predictor of post-procedural 1-year mortality in patients evaluated for TAVI., Key Points: • IVC measurements are moderate predictors of an elevated CVP in TAVI patients. • Pre-procedural IVC enlargement is a predictor of 1-year mortality after TAVI. • IVC enlargement is associated with right heart dysfunction in TAVI patients.

Purpose: We aimed to assess the association between features of epicardial adipose tissue and demographic, morphometric and clinical data, in a large population of symptomatic patients with clinical indication to cardiac computed tomography (CT) angiography., Methods: Epicardial fat volume (EFV) and adipose CT density of 1379 patients undergoing cardiac CT angiography (918 men, 66.6%; age range, 18-93 years; median age, 64 years) were semi-automatically quantified. Clinical variables were compared between diabetic and nondiabetic patients to assess potential differences in EFV and adipose CT density. Multiple regression models were calculated to find the clinical variables with a significant association with EFV and adipose CT density., Results: The median EFV in diabetic patients (112.87 mL) was higher compared with nondiabetic patients (82.62 mL; P < 0.001). The explanatory model of the multivariable analysis showed the strongest associations between EFV and BMI (β=0.442) and age (β=0.365). Significant yet minor association was found with sex (β=0.203), arterial hypertension (β=0.072), active smoking (β=0.068), diabetes (β=0.068), hypercholesterolemia (β=0.046) and cardiac height (β=0.118). The mean density of epicardial adipose tissue was associated with BMI (β=0.384), age (β=0.105), smoking (β=0.088), and diabetes (β=0.085)., Conclusion: In a large population of symptomatic patients, EFV is higher in diabetic patients compared with nondiabetic patients. Clinical variables are associated with quantitative features of epicardial fat.

Purpose: The ALARA principle is not only relevant for effective dose (ED) reduction, but also applicable for contrast media (CM) management. Therefore, the aim was to evaluate the feasibility of an ultra-low CM protocol in the assessment of peripheral artery disease (PAD)., Materials and Methods: Fifty PAD patients were scanned on third-generation dual-source computed tomography, from diaphragm to the forefoot, as follows: tube voltage: 70 kV, reference effective tube current: 90 mAs, collimation: 192 × 2 × 0.6 mm, with individualized acquisition timing. The protocol ED (mSv) was quantified with dedicated software. CM protocol consisted of 15 ml test bolus and 30 ml main bolus (300 mgI/ml) injected at 5 ml/s, followed by a 40 ml saline chaser at the same flow rate. Aorto-popliteal bolus transit time was used to calculate the overall acquisition time and delay. Objective (hounsfield units-HU; contrast-to-noise ratio-CNR) and subjective image quality (four-point Likert score) were assessed at different anatomical regions from the aorta down to the forefoot., Results: Mean attenuation values were exceeding 250 HU from aorta down to the anterior tibial artery with CNR < 13. However, decline in attenuation was observed in more distal region with mean values of 165 and 199 HU, in left and right dorsalis pedis artery, respectively. Mode subjective image quality from the level of aorta down to the popliteal segment was excellent; below the knee mode score was good. The mean ED per protocol was 1.1 ± 0.5 mSv., Conclusion: Use of an ultra-low CM volume protocol at 70 kV is feasible in the evaluation of PAD, resulting in good to excellent image quality with mean ED of 1.1 ± 0.5 mSv., Level of Evidence: Level 3, Local non-random sample.

Purpose of Review: The purpose of this review is to provide the radiological description of interstitial lung abnormalities (ILA) as an increasingly reported entity on high-resolution computed tomography (HRCT), and to discuss their prospective interpretation., Recent Findings: Elementary findings consistent with ILA are described on HRCT, yet the diagnostic confidence for the interpretation of these subtle features might be challenging and further hampered by interobserver variability. Quantitative analysis is expected to provide standardized and reproducible description of ILA. There is affinity between ILA morphology and histopathological pattern, either fibrosis or atypical adenomatous hyperplasia. Beyond radiology, there are predictors of risk of ILA, such as: age, smoking habit, circulating biomarkers, and genetic sequencing. ILA with fibrotic morphology show prognostic impact including progression to interstitial lung disease, mortality from respiratory disease, and all-cause mortality. The association between ILA and susceptibility to lung damage further includes the interlacing connection between interstitial findings and lung cancer, both as a risk factor for diagnosis and as a predictor of survival., Summary: ILA are a (minor) finding on HRCT and they should be reported by radiologists for optimal management within the specific clinic-functional scenario. ILA encompass a number of semiological characteristics associated with either fibrotic or nonfibrotic disease.

Objectives: To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer-specific mortality-free survival after surgery in pN1 prostate cancer patients through an external validation., Methods: We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram-derived probability cut-off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice., Results: External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer-specific mortality-free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none., Conclusions: In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery., (© 2018 The Japanese Urological Association.)

Renal cell carcinoma (RCC) is the most common tumor of the kidney and its major histologic subtype is clear cell RCC (ccRCC). About 30% of diagnosed ccRCCs already have metastasis. Traditionally, localized ccRCC is treated with nephrectomy but the relapse rate is 30%. Thus, the discovery of effective biomarkers for early detection, as well as the identification of new targets for molecular-based therapy of ccRCC are urgently required. In this study, we focused on molecules that could modulate the trascription of the enzyme nicotinamide N-methyltransferase (NNMT) that is known to be up-regulated in ccRCC. Signal transducer and activator of transcription 3 (STAT3), interleukin 6 (IL-6), hepatocyte nuclear factor 1 beta (HNF-1β) and transforming growth factor beta 1 (TGF-β1) expression levels were determined in tumor and non tumor samples obtained from 30 patients with ccRCC, using Real-Time PCR. Results obtained showed that TGF-β1 is significantly (p&lt;0.05) overexpressed in tumor compared with normal tissue samples of ccRCC patients. Conversely, we did not find any statistically significant difference concerning STAT3, IL-6, HNF-1β gene expression levels. TGF-β1 up-regulation could be responsible for the high levels of NNMT observed in ccRCC. Targeting TGF-β1 could improve the outcome of ccRCC patients due to its role in epithelial-mesenchymal transition (EMT), that is known to be associated with a worse overall survival (OS) in this neoplasm.

Objective: To evaluate whether vessel-suppressed computed tomography (VSCT) can be reliably used for semi-automated volumetric measurements of solid pulmonary nodules, as compared to standard CT (SCT) MATERIAL AND METHODS: Ninety-three SCT were elaborated by dedicated software (ClearRead CT, Riverain Technologies, Miamisburg, OH, USA), that allows subtracting vessels from lung parenchyma. Semi-automated volumetric measurements of 65 solid nodules were compared between SCT and VSCT. The measurements were repeated by two readers. For each solid nodule, volume measured on SCT by Reader 1 and Reader 2 was averaged and the average volume between readers acted as standard of reference value. Concordance between measurements was assessed using Lin's Concordance Correlation Coefficient (CCC). Limits of agreement (LoA) between readers and CT datasets were evaluated., Results: Standard of reference nodule volume ranged from 13 to 366 mm 3 . The mean overestimation between readers was 3 mm 3 and 2.9 mm 3 on SCT and VSCT, respectively. Semi-automated volumetric measurements on VSCT showed substantial agreement with the standard of reference (Lin's CCC = 0.990 for Reader 1; 0.985 for Reader 2). The upper and lower LoA between readers' measurements were (16.3, -22.4 mm 3 ) and (15.5, -21.4 mm 3 ) for SCT and VSCT, respectively., Conclusions: VSCT datasets are feasible for the measurements of solid nodules, showing an almost perfect concordance between readers and with measurements on SCT., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The frenetic development of imaging technology-both hardware and software-provides exceptional potential for investigation of the lung. In the last two decades, CT was exploited for detailed characterization of pulmonary structures and description of respiratory disease. The introduction of volumetric acquisition allowed increasingly sophisticated analysis of CT data by means of computerized algorithm, namely quantitative CT (QCT). Hundreds of thousands of CTs have been analysed for characterization of focal and diffuse disease of the lung. Several QCT metrics were developed and tested against clinical, functional and prognostic descriptors. Computer-aided detection of nodules, textural analysis of focal lesions, densitometric analysis and airway segmentation in obstructive pulmonary disease and textural analysis in interstitial lung disease are the major chapters of this discipline. The validation of QCT metrics for specific clinical and investigational needs prompted the translation of such metrics from research field to patient care. The present review summarizes the state of the art of QCT in both focal and diffuse lung disease, including a dedicated discussion about application of QCT metrics as parameters for clinical care and outcomes in clinical trials.

Background: Bladder cancer (BC) represents the most common neoplasm of the urinary tract. Although cystoscopy and urine cytology represent the gold standard methods to monitor BC, both procedures have limitations. Therefore, the identification of reliable biomarkers for early and noninvasive detection of BC is urgently required., Methods: In this study, we analyzed nicotinamide N-methyltransferase (NNMT) expression in urine samples from 55 BC patients and 107 controls, using real-time polymerase chain reaction (PCR). Receiver operating characteristic (ROC) analysis was used to identify the best cutoff value to discriminate BC patients from healthy donors, and to evaluate the diagnostic accuracy of a urine-based NNMT test., Results: The results demonstrated that urinary NNMT expression was significantly (p<0.05) higher in BC patients. Moreover, a significant (p<0.05) inverse correlation was found between NNMT expression and histological grade. The ROC analysis revealed that a ΔCq of 13.3 was the best cutoff value, since it was associated with the highest combination of sensitivity and specificity. Moreover, the area under the curve (AUC) value was 0.913 (p<0.05), indicating the excellent diagnostic accuracy of a urine-based NNMT test., Conclusions: Our data indicate that NNMT is a promising biomarker that could be used to support the early and noninvasive diagnosis of BC.